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Role of natural antioxidants and potential use of bergamot in treating rheumatoid arthritis
... As a result, antioxidants have been widely explored for the RHA treatment. Flavonoids, isolated from the citrus fruits especially bergamot juice, are of paramount importance, for their potential applications, in the RHA treatment (Marino et al., 2015;Newman & Cragg, 2007). Flavonoids interact with RHA receptors and modulate cellular and intracellular activities. ...
... dulce, has been proven to show antioxidant activity, by preventing cellular damage and inflammation caused by oxidative stress. These effects of Luteolin were consequential to significant suppression of phosphorylation of extracellular signal-regulated kinase and mitogen-activated protein kinase-1 (Marino et al., 2015). A study investigated the combined effect of luteolin and endocannabinoid N-palmitoylethanolamine (PEA) in RHA using mouse model. ...
... Evidences suggested that phenolic compounds of olive oil reduce the aggregation of platelets and the formation of pro-inflammatory cytokines, leukotriene B4, and thromboxane-2 and also inhibit lipoxygenase and COX (cyclooxygenase) (Tripoli et al., 2005). Oleuropein present in olive oil, exhibits antioxidant activity via superoxide anions and hydroxyl radical scavenging and inhibiting the respiratory burst of neutrophils and hypochlorous acid-derived radicals (Kremastinos, 2008;Marino et al., 2015;Menendez et al., 2007). A study performed to understand the inflammatory response and its possible amelioration with oleuropein treatment, in a mouse model with arthritis, induced by injection of collagen type II concluded that aglycone part of oleuropein ameliorates RHA inflammation by downregulating the poly-ADP-ribosyl polymerase enzyme and ROS. ...
Rheumatoid arthritis (RHA) is one of the most prevalent complex, chronic, inflammatory diseases, manifested by elevated oxidative stress and inflammatory biomarkers. Prolonged administration of NSAIDs, steroids, and DMARDs, used in the treatment of RHA, is associated with deleterious side effects. This necessitates the urge of new and safe approaches for RHA management, based on the complementary and alternative system of medicine. Documented evidences have suggested that supplementation with nutritional, dietary, and herbal components; can play a crucial role as an adjuvant, in the alleviation of the RHA symptoms, through their influence on the pathological inflammatory processes. Dietary phenolic compounds, flavonoids, carotenoids, and alkaloids with their ability to modulate prooxidant and pro‐inflammatory pathways, have been effective in delaying the arthritic disease progression. Moreover, in scientific explorations, herbs containing phenolic compounds, alkaloids, carotenoids flavonoids, spices such as ginger, turmeric, Ayurvedic formulations, different diets such as Mediterranean diet, vegan diet, beverages, and oils such as sesame oil, rice bran oil, vitamins, and probiotics are proven to modulate the action of inflammatory molecules, involved in RHA pathology. Subsequently, the purpose of this review article is to summarize various in vitro, in vivo, and clinical studies in RHA, which have documented remarkable insights into the anti‐inflammatory, antioxidant, analgesic, and immunomodulatory, bone erosion preventing properties of dietary, nutritional, and herbal components with the focus on their molecular level mechanisms involved in RHA. Even though major findings were derived from in vitro studies, several in vivo and clinical studies have established the use of diet, herbal, and nutritional management in RHA treatment.
Practical applications
Thickening of the synovial membrane, bone erosion, and cartilage destruction is known to trigger rheumatoid arthritis causing inflammation and pain in bone joints. Continuous intake of NSAIDs, steroids, and DMARD therapy are associated with detrimental side effects. These side effects can be overcome by the use of dietary, nutritional, and herbal interventions based on the complementary and alternative therapy. This concept portrays the food components and other natural components having the potential to promote health, improve general well‐being, and reduce the risk of RHA.
... IL-6 plays an active role in the production of VEGF, which is responsible for pannus formation. IL-1β is produced in the inflamed synovium by macrophages and monocytes, and has the same activities as TNF-α [21]. These inflammatory cytokines induce inflammation by activating various pathways such as mitogen-activated protein kinase (MAPks), c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), p38, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), and NF-κB, responses that are not antigen-specific, adaptive, or associated with immunologic memory. ...
... IL-6 plays an active role in the production of VEGF, which is responsible for pannus formation. IL-1β is produced in the inflamed synovium by macrophages and monocytes, and has the same activities as TNF-α [21]. These inflammatory cytokines induce inflammation by activating various pathways such as mitogen-activated protein kinase (MAPks), c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), p38, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), and NF-κB, responses that are not antigenspecific, adaptive, or associated with immunologic memory. ...
Polyphenols have gained widespread attention as they are effective in the prevention and management of various diseases, including cancer diseases (CD) and rheumatoid arthritis (RA). They are natural organic substances present in fruits, vegetables, and spices. Polyphenols interact with various kinds of receptors and membranes. They modulate different signal cascades and interact with the enzymes responsible for CD and RA. These interactions involve cellular machinery, from cell membranes to major nuclear components, and provide information on their beneficial effects on health. These actions provide evidence for their pharmaceutical exploitation in the treatment of CD and RA. In this review, we discuss different pathways, modulated by polyphenols, which are involved in CD and RA. A search of the most recent relevant publications was carried out with the following criteria: publication date, 2012–2022; language, English; study design, in vitro; and the investigation of polyphenols present in extra virgin olive, grapes, and spices in the context of RA and CD, including, when available, the underlying molecular mechanisms. This review is valuable for clarifying the mechanisms of polyphenols targeting the pathways of senescence and leading to the development of CD and RA treatments. Herein, we focus on research reports that emphasize antioxidant properties.
... Besides usage in cosmetology [43], these properties have been essentially investigated with reference to multiple favorable effects on health and ensuing pharmaceutical relevance. This refers to possible applications in the treatment of neurological [44] and vascular disorders [45], and as antioxidant [12,[46][47][48][49][50], anticholesterolemic [51], antidiabetic [12] and antitumor agents [43,52]. The latter effects have been also studied with reference to purified products, such as citral [53,54], bergamottin and 5-geranyloxy-7-methoxycoumarin [13]. ...
... The above-mentioned antioxidant properties of EOs, documented in the case of extracts from several citrus species [12,[46][47][48][49][50], should also be considered with reference to their preservative action on fruit in postharvest. EOs and other volatile organic compounds (VOCs) have been proposed and routinely used as biofumigants for the treatment of several food commodities, including fruit where postharvest deterioration caused by molds is a general problem affecting trade and storage [134]. ...
Citrus essential oils (EOs) are widely used as flavoring agents in food, pharmaceutical, cosmetical and chemical industries. For this reason, their demand is constantly increasing all over the world. Besides industrial applications, the abundance of EOs in the epicarp is particularly relevant for the quality of citrus fruit. In fact, these compounds represent a natural protection against postharvest deteriorations due to their remarkable antimicrobial, insecticidal and antioxidant activities. Several factors, including genotype, climatic conditions and cultural practices, can influence the assortment and accumulation of EOs in citrus peels. This review is focused on factors influencing variation of the EOs’ composition during ripening and on the implications on postharvest quality of the fruit.
... A chemoprevention approach in patients with high risk of PCa can be proposed in order to reduce the disease progression rate. It is known that natural product can be used to prevent and/or alleviate several health disorders (2)(3)(4), including those affecting the urinary tract (5). Moreover, regular dietary habits coupled with a healthy lifestyle may protect against certain types of cancer (6,7), including PCa. ...
... In recent decades, natural drugs gained particular attention mainly because of their antioxidant and anti-inflammatory activities exploitable in the prevention of certain chronic degenerative pathologies (4,(33)(34)(35). However, the increased employment of alternative and complementary medicines requires a lot of attention from the scientific community in order to evaluate the effectiveness and safety of herbal preparations since studies have cast some doubts on whether their use is really producing an alternative to synthetic drugs (5,36,37). ...
Background and study objective:
Several studies suggest a protective role of green tea catechins against prostate cancer (PCa). In order to evaluate the efficacy of green tea catechins for chemoprevention of PCa in patients with high-grade prostate intraepithelial neoplasia (HG-PIN) we performed a phase II clinical trial.
Methods:
Sixty volunteers with HG-PIN were enrolled to carry out a double-blind randomized placebo-controlled phase II clinical trial. Treated group took daily 600 mg of green tea catechins (Categ Plus®) for 1 year. Patients were screened at 6 and 12 months through prostatic biopsy and measurements of prostate-specific antigen (PSA).
Results:
Despite the statistically significant reduction of PSA observed in subjects who received green tea catechins for 6 and 12 months, we did not find any statistical difference in PCa incidence between the experimental groups neither after 6 nor after 12 months. However, throughout the one-year follow- up we observed very limited adverse effects induced by green tea catechins and a not significant improvement in lower urinary tract symptoms and quality of life.
Conclusions:
Although the small number of patients enrolled in our study and the relatively short duration of intervention, our findings seems to deny the efficacy of green tea catechins. However, results of our clinical study, mainly for its low statistical strength, suggest that the effectiveness of green tea catechins should be evaluated in both a larger cohort of men and longer trial.
... Luteolin reduces inflammation and cellular damage caused by OS [82]. RA was conducted using a mouse model, investigating the combined effects of luteolin and PEA. ...
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic involvement, inflammation , and the destruction of synovial joints. RA can be categorized as anti-citrullinated protein antibodies-positive or negative based on genetic risk factors and autoantibodies. This review systematically sourced articles related to RA, phytocompounds, signaling pathways, and clinical insights from primary medical databases, including Scopus, PubMed, and Web of Science. This review explores the therapeutic potential of phytocompounds in treating RA by targeting key inflammation and immunological response signaling pathways. Phytocompounds such as curcumin, resveratrol, and flavonoids alter essential molecular pathways in RA pathophysiology, including nuclear factor kappa-light-chain-enhancer of activated B cells, mitogen-activated protein kinases, janus ki-nase-signal transducer and activator of transcription, and the inflammasome. These substances possess pro-resolving, anti-apoptotic, and antioxidant properties, which enhance their therapeutic efficacy. Alternative medicine , including dietary, herbal, and nutritional supplements, may help reduce RA symptoms. In vitro, in vivo, and clinical studies have demonstrated the effectiveness of these treatments. Phytocompounds have potential as a treatment for RA by altering signaling pathways, reducing oxidative stress, and protecting cartilage and bone. However, few clinical trials confirm its long-term safety, bioavailability, and effectiveness. Further clinical trials and translational research are needed to validate the effectiveness, safety, and pharmacokinetics of phytocompounds, while identifying novel plant-derived bioactive chemicals could improve patient outcomes.
... The delicate balance between inflammation and tolerance is disrupted in RA due to the modulation of innate and acquired immune responses by gut and oral microbiota. Diet, probiotics, prebiotics, antibiotics, exogenous enzymes, fecal microbiota transplantation, and other environmental factors can all have a positive impact on the gut microbiota (18). This microbe is essential for maintaining immunological homeostasis in RA because it forms the intestinal barrier. ...
Rheumatoid arthritis (RA) is a chronic autoimmune systemic inflammatory disease, which has serious physical, psychological, and social consequences. Many RA patients continue to experience intolerable side effects from their treatments or an inadequate response, which leads to the disease progressing despite advancements in targeted biological and pharmacologic interventions. Examining the multi-modular, drugless approach of yoga and naturopathy to this autoimmune disease is equally important as it enables physicians to provide better care. Hence, the current review was undertaken to present an overview of the available scientific evidence on the mechanism of naturopathy and yoga therapeutic modalities in the management of RA. We searched PubMed and PubMed Central for pertinent English-language articles about the impact of yoga and naturopathy on RA. The results in this review are presented based on the therapeutic effect of yoga and various naturopathy treatment modalities with their mechanisms on RA. It shows naturopathy and yoga was effective in the management of RA due to its analgesic, anti-inflammatory, immunomodulatory and antioxidant effect.
... The renewed interest of the scientific community towards natural products dramatically enhanced in the last two decades and resulted in the discovery of new plant sources and their byproducts for the prevention and treatment of several diseases, including inflammatory-based ones [2]. This is the case for Citrus bergamia Risso (bergamot), an endemic plant of the southern coast of the Calabria region (Italy), to which we have focused our studies for over a decade, thus documenting relevant pharmacological activities [3][4][5]. ...
Chronic inflammation is the result of an acute inflammatory response that fails to eliminate the pathogenic agent or heal the tissue injury. The consequence of this failure lays the foundations to the onset of several chronic ailments, including skin disorders, respiratory and neurodegenerative diseases, metabolic syndrome, and, eventually, cancer. In this context, the long-term use of synthetic anti-inflammatory drugs to treat chronic illnesses cannot be tolerated by patients owing to the severe side effects. Based on this, the need for novel agents endowed with anti-inflammatory effects prompted to search potential candidates also within the plant kingdom, being recognized as a source of molecules currently employed in several therapeutical areas. Indeed, the ever-growing evidence on the anti-inflammatory properties of dietary polyphenols traced the route towards the study of flavonoid-rich sources, such as Citrus bergamia (bergamot) and its derivatives. Interestingly, the recent paradigm of the circular economy has promoted the valorization of Citrus fruit waste and, in regard to bergamot, it brought to light new evidence corroborating the anti-inflammatory potential of bergamot byproducts, thus increasing the scientific knowledge in this field. Therefore, this review aims to gather the latest literature supporting the beneficial role of both bergamot derivatives and waste products in different models of inflammatory-based diseases, thus highlighting the great potentiality of a waste re-evaluation perspective.
... IL-1β and chemokines. The role of flavonoids in RHA treatment has also been discussed (65,66). Pomegranate extract has been proven to be a potent for RHA treatment in a clinical trial showing the successful results by reduction in joint swelling, pain severity, rate, and level of erythrocyte sedimentation, etc. (67). ...
Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting primarily the joints, producing discomfort, inflammation, and potentially damaging joint destruction. Rheumatoid arthritis affects people all around the world, and its prevalence and impact differ by place. The World Health Organisation (WHO) estimates that 0.5% to 1% of the global population has rheumatoid arthritis. To decrease the progression of rheumatoid arthritis, disease-modifying anti-rheumatic medications (DMARDs) such as methotrexate and sulfasalazine are used. TNF inhibitors and IL-6 inhibitors are two examples of biologic DMARDs that target specific immune system components. Nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesics help manage pain and inflammation while corticosteroids provide short-term relief during flares. Treatment strategies are tailored to the individual, and talking with a healthcare expert is essential for effective management. Herbal therapies are regarded to offer an advantage over synthetic pharmaceuticals for the treatment of rheumatoid arthritis due to their natural approach, potential symptom relief, holistic approach to health, and individualised therapy possibilities. However, scientific data supporting their effectiveness is sparse and variable, and their quality and safety can vary. Before adopting herbal therapies as part of a treatment plan, it is critical to check with a healthcare expert. Because of their natural chemicals with anti-inflammatory and analgesic characteristics, medicinal herbs may aid rheumatoid arthritis. However, further research is required to determine their efficacy, safety, and appropriate application.
... Many natural products have been claimed to possess anti-arthritic properties [94]. ...
Natural products have dominated our lives since ancient times. Today, they are an inexhaustible source of new medications for disease treatment. The practice of evaluating bioactive compounds extracted from natural sources has also advanced significantly, prompting a need to understand current methods to identify and evaluate them.
This book covers basic scientific aspects of preclinical research on natural products for specific conditions and diseases. These include aging, gynecological disorders, inflammatory disorders, renal disorders and cardiovascular disorders. Each of the 10 book chapters give a structured overview on preclinical methods on the etiology of diseases, natural products as the materials for the bioassays, extract types, concentration of the extracts/compounds for in vitro and in vivo assays, preparation of the test materials, application of the test materials, step-by-step methods and related calculations.
The book is intended as a quick reference for natural product researchers, pharmacists and postgraduate students in pharmacognosy. Medical doctors working in preclinical research on natural products will also benefit from the information provided.
... ROS also function as secondary messengers and stimulate other inflammatory mediators [66]. By modulating cell signalling and gene expression, these components (CNC-g-PAA/CaO) reduce the formation of inflammatory mediators and oxidants [67]. ...
The combination treatment is considered an approach to attaining synergistic impact while minimizing applied dosage. Hydrogels are analogous to the tissue environment attributed to hydrophilic and porous structure. Despite extensive study in biological and biotechnological domains, their restricted mechanical strength and limited functionalities impede their potential uses. Emerging strategies are centred on research and developing nanocomposite hydrogels to combat these issues. Herein, we prepared copolymerized hydrogel by grafting poly-acrylic acid P(AA) onto cellulose nanocrystals (CNC) and adding CNC-g-PAA as dopant (2 and 4 wt%) in calcium oxide (CaO) nanoparticles to generate an effective hydrogel doped nanocomposite (NCH) (CNC-g-PAA/CaO) for biomedical applications such as anti-arthritic, anti-cancer, and antibacterial investigations alongside their comprehensive characterization. CNC-g-PAA/CaO (4 %), compared to other samples, had a substantially higher antioxidant potential (72.21 %). Doxorubicin, a potential chemotherapeutic drug, was then effectively loaded into NCH (99 %) via electrostatic interaction, and pH-triggered based release was found to be >57.9 % in 24 h. Furthermore, molecular docking investigation against targeted protein Cyclin-dependent kinase 2 and in vitro cytotoxicity study verified the improved antitumor effectiveness of CNC-g-PAA and CNC-g-PAA/CaO. These outcomes indicated that hydrogels might serve as potential delivery vehicles for innovative multifunctional biomedical applications.
... Among the richest food sources of flavonoids, citrus juices, and their derivatives are in the lead, with their acknowledged antioxidant and anti-inflammatory effects [84,85] potentially exploited to counteract inflammation-based diseases such as obesity [86]. In this regard, a flavonoid-rich extract of orange juice (OJe) has been shown to significantly reduce body weight and BMI values in overfed zebrafish. ...
A Mediterranean-style diet is highly encouraged thanks to its healthy food pattern, which includes valuable nutraceuticals such as polyphenols. Among these, flavonoids are associated with relevant biological properties through which they prevent or fight the onset of several human pathologies. Globally, the enhanced incidence of overweight and obese people has caused a dramatic increase in comorbidities, raising the need to provide better therapies. Therefore, the development of sophisticated animal models of metabolic dysregulation has allowed for a deepening of knowledge on this subject. Recent advances in using zebrafish (Danio rerio) as model for metabolic disease have yielded fundamental insights into the potential anti-obesity effects of flavonoids. Chronic low-grade inflammation and immune system activation seem to characterize the pathogenesis of obesity; thus, their reduction might improve the lipid profile of obese patients or prevent the development of associated metabolic illnesses. In this review, we highlight the beneficial role of flavonoids on obesity and related diseases linked to their anti-inflammatory properties. In light of the summarized studies, we suggest that anti-inflammatory therapies could have a relevant place in the prevention and treatment of obesity and metabolic disorders.
... Noteworthy, flavonoids are definitely the polyphenols that sparked among the others and proved to possess undoubted anti-oxidant, anti-inflammatory, anti-cancer, anti-rheumatic, anti-microbial and neuroprotective activities (Cirmi et al. 2016(Cirmi et al. , 2018Mannucci et al. 2021;Marino et al. 2015;Maugeri et al. 2019;Musumeci et al. 2020), exploited also in clinical settings (Mannucci et al. 2018(Mannucci et al. , 2017. Furthermore, coumarins, anthocyanins and lignans represent well-studied plant secondary metabolites, arising from the same biosynthetic pathway as flavonoids, which are known for their anticancer, vasoprotective and neuroprotective activities (Bruni et al. 2019;Smeriglio et al. 2016;Talarek et al. 2017). ...
Tannins are an interesting class of polyphenols, characterized, in almost all cases, by a different degree of polymerization, which, inevitably, markedly influences their bioavailability, as well as biochemical and pharmacological activities. They have been used for the process of tanning to transform hides into leather, from which their name derives. For several time, they have not been accurately evaluated, but now researchers have started to unravel their potential, highlighting anti-inflammatory, antimicrobial, antioxidant and anticancer activities, as well as their involvement in cardiovascular, neuroprotective and in general metabolic diseases prevention. The mechanisms underlying their activity are often complex, but the main targets of their action (such as key enzymes modulation, activation of metabolic pathways and changes in the metabolic fluxes) are highlighted in this review, without losing sight of their toxicity. This aspect still needs further and better-designed study to be thoroughly understood and allow a more conscious use of tannins for human health.
... Citrus fruits, tea, and red wine are among their primary nutritional sources. Numerous studies have revealed that eating polyphenol-rich foods on a daily basis may benefit a wide range of human pathologies, including those characterized by an abnormal inflammatory and oxidant status, such as infections, autoimmune and neurodegenerative diseases, along with cancer [96][97][98][99][100][101][102]. These interesting properties are also exploited in clinical settings, mainly in the aromatherapy [103,104]. ...
The role of environmental factors in influencing health status is well documented. Heavy metals, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls, dioxins, pesticides, ultrafine particles, produced by human activities put a strain on the body’s entire defense system. Therefore, together with public health measures, evidence-based individual resilience measures are necessary to mitigate cancer risk under environmental stress and to prevent reproductive dysfunction and non-communicable diseases; this is especially relevant for workers occupationally exposed to pollutants and/or populations residing in highly polluted areas. The Mediterranean diet is characterized by a high intake of fruits and vegetables rich in flavonoids, that can promote the elimination of pollutants in tissues and fluids and/or mitigate their effects through different mechanisms. In this review, we collected evidence from pre-clinical and clinical studies showing that the impairment of male fertility and gonadal development, as well as cancers of reproductive system, due to the exposure of organic and inorganic pollutants, may be counteracted by flavonoids.
... Recently, bergamot juice (BJ) has also been evaluated for its great pharmacological value. Indeed, it has been reported its antimicrobial activity against Helicobacter pylori [119], and its anticancer activity both in in vitro and in vivo models [120][121][122][123][124]. Given the high polyphenolic content of BJ [125], its flavonoid-rich fraction (BJe) was further studied for the hypolipemic and hypoglycemic activities [126], neuroprotective [127] as well as the anti-inflammatory potential [128]. In this field, BJe prevented both LPS-and β-amyloid-induced inflammatory response in THP-1 monocytes, by modulating NF-κB pathway via the AMPK/SIRT1 [129,130] axis and the MAPK/AP-1 pathways, respectively [131]. ...
Citrus fruits (CF) are among the most widely cultivated fruit crops throughout the world and their production is constantly increasing along with consumers’ demand. Therefore, huge amounts of waste are annually generated through CF processing, causing high costs for their disposal, as well as environmental and human health damage, if inappropriately performed. According to the most recent indications of an economic, environmental and pharmaceutical nature, CF processing residues must be transformed from a waste to be disposed to a valuable resource to be reused. Based on a circular economy model, CF residues (i.e., seeds, exhausted peel, pressed pulp, secondary juice and leaves) have increasingly been re-evaluated to also obtain, but not limited to, valuable compounds to be employed in the food, packaging, cosmetic and pharmaceutical industries. However, the use of CF by-products is still limited because of their underestimated nutritional and economic value, hence more awareness and knowledge are needed to overcome traditional approaches for their disposal. This review summarizes recent evidence on the pharmacological potential of CF waste to support the switch towards a more environmentally sustainable society.
... The capability of these natural compounds to improve health status was attributed especially to their antioxidant activity, being able to prevent and scavenge the formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), representing important hallmarks of inflammation [20][21][22]. Furthermore, they can influence cellular function by direct interaction with several receptors, as well as modulate intracellular signaling and transcription of gene involved in different pro-inflammatory pathways [23,24]. Flavonoids act as antioxidants through different mechanisms: (i) by scavenging free radicals; (ii) by chelating metallic ions that in turn could have catalyzed the generation of free radicals; (iii) by the donation of a proton from the phenolic compounds to the radicals; (iv) by inhibiting pro-oxidant enzymes, such as lipoxygenases, cyclooxygenases and xanthine oxidases, that generate free radicals; (v) by interfering with the oxidative/antioxidative potential of the cell [25]. ...
The zebrafish is considered one of the most versatile experimental animal models. The transparency of the embryos, the small size, the rapid development and the homology with higher vertebrates have made the zebrafish a valuable model also for drug screening. Its use is closely related for the determination of bioactivity, toxicity and off-target side effects of novel drug candidates, which also allows a thorough evaluation of new targets; thus, it may represent a suitable model for drug screening and the optimization of novel candidates. Flavonoids are polyphenolic compounds widely present in fruits, vegetables and cereals. Polyphenols are important for both plants and humans, considering their involvement in defense mechanisms, particularly against oxidative stress. They protect plants from biotic and abiotic stressors and prevent or treat oxidative-based human diseases. For these reasons, polyphenols are used as nutraceuticals, functional foods and supplements by the pharmaceutical industry. Therefore, the most relevant findings on zebrafish as a useful experimental model to study oxidative stress-linked disorders, focusing on the biological activities of flavonoids, are here summarized and reviewed.
... Citrus fruits are one of the most eaten fruits in the world and a great source of dietary flavonoids is well-known for their beneficial effects [55][56][57]. In this study, we demonstrated the protective effect of BJe, alone (40 mg/kg), or in combination (at the lowest dose of 20 mg/kg) to Cur and Re, against Cd-induced testicular injury. ...
It is known that cadmium damages testis structure and functionality. We examined the effects of nutraceuticals such as a flavonoid-rich extract of bergamot juice (BJe), alone or in association with curcumin (Cur) and resveratrol (Re), on mice testicular dysfunction caused by cadmium chloride (CdCl2). Controversial data on the protective effects of Cur and Re are available, while no evidence on the possible role of BJe exists. Adult male C57 BL/6J mice were administered with CdCl2 and treated with Cur, Re, or BJe alone or in combination for 14 days. Then, testes were removed and processed for molecular, structural, and immunohistochemical analyses. CdCl2 increased the mRNA of IL-1β, TNF-α, p53, and BAX while reduced that of Bcl-2 and induced tubular lesions and apoptosis of germinal cells. Cur, Re, and BJe at 40 mg/kg significantly improved all of these parameters and events, although BJe at 20 mg/kg showed a lower protective effect. The association of Cur, Re, and BJe at both doses of 50/20/20 and 100/20/40 mg/kg brought each parameter close to those of the control. Our results indicate that the nutraceuticals employed in this study and their associations exert a positive action against Cd-induced testicular injury, suggesting a possible protection of testis functionality in subjects exposed to environmental toxicants.
... It has been claimed that BJe possesses antioxidant activity [26,27] and is able to hinder inflammation, both in vitro [28,29] and in vivo [30][31][32]. BJe interacted also with the AMPK/SIRT1 axis [33], indicating its potential role as a remedy for inflammation-based illnesses [34]. BEO, the most important product obtained by bergamot fruits and used mostly in perfume industry, is a phytocomplex composed by a volatile fraction, (almost the 95% of the total) that consists of monoterpenes like limonene, linalool, linalyl acetate, α-pinene, β-pinene, and γ-terpinene, and a non-volatile one, that consists mostly of coumarins and psoralens, like bergapten, bergamottin and citropten [35]. ...
The plant kingdom has always been a treasure trove for valuable bioactive compounds, and Citrus fruits stand out among the others. Bergamottin (BRG) and 5-geranyloxy-7-methoxycoumarin (5-G-7-MOC) are two coumarins found in different Citrus species with well-acknowledged pharmacological properties. Previously, they have been claimed to be relevant in the anti-proliferative effects exerted by bergamot essential oil (BEO) in the SH-SY5Y human neuroblastoma cells. This study was designed to verify this assumption and to assess the mechanisms underlying the anti-proliferative effect of both compounds. Our results demonstrate that BRG and 5-G-7-MOC are able to reduce the proliferation of SH-SY5Y cells, inducing apoptosis and increasing cell population in sub-G0/G1 phase. Moreover, we demonstrated the pro-oxidant activity of the two coumarins that increased reactive oxygen species and impaired mitochondrial membrane potential. From a molecular point of view, BRG and 5-G-7-MOC were able to modulate apoptosis related factors at both protein and gene levels. Lastly, we evaluated the synergistic effect of their combination, finding that the highest synergy was observed at a concentration ratio similar to that occurring in the BEO, supporting our initial hypothesis. Taken together, our results deepen the knowledge regarding the effect of BRG and 5-G-7-MOC in SH-SY5Y cells, emphasizing the relevance of their cooperation in achieving this effect.
... Here, we found that MJe was able to restore both SOD and CAT activity, two fundamental enzymes that act together to quench oxygen radicals, as well as GSH levels. Interestingly, MJe proved to also be a great antioxidant in abiotic models, where it was able to quench both oxygen (ORAC) and nitrogen (DPPH) radicals along with reducing ferric ions into ferrous ones, effects likely ascribed to the high polyphenol content, as assessed by Folin-Ciocalteu assay and in line with previous reports on Citrus extracts [39,40]. ...
Parkinson’s disease (PD) is a degenerative disorder of the nervous system due to unceasing impairment of dopaminergic neurons situated in the substantia nigra. At present, anti-PD drugs acting on dopamine receptors are mainly symptomatic and have only very limited neuroprotective effects, whereas drugs slowing down neurodegeneration of dopaminergic neurons and deterioration of clinical symptoms are not yet available. Given that, the development of more valuable pharmacological strategies is highly demanded. Comprehensive research on innovative neuroprotective drugs has proven that anti-inflammatory and antioxidant molecules from food sources may prevent and/or counteract neurodegenerative diseases, such as PD. The present study was aimed at the evaluation the protective effect of mandarin juice extract (MJe) against 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y human neuroblastoma cell death. Treatment of differentiated SH-SY5Y cells with 6-OHDA brought cell death, and specifically, apoptosis, which was significantly inhibited by the preincubation with MJe through caspase 3 blockage and the modulation of p53, Bax, and Bcl-2 genes. In addition, it showed antioxidant properties in abiotic models as well as in vitro, where it reduced both reactive oxygen and nitrogen species induced by 6-OHDA, along with restored mitochondrial membrane potential, and prevented the oxidative DNA damage evoked by 6-OHDA. Furthermore, MJe restored the impaired balance of SNCA, LRRK2, PINK1, parkin, and DJ-1 gene levels, PD-related factors, caused by 6-OHDA oxidative stress. Overall, these results indicate that MJe exerts neuroprotective effects against 6-OHDA-induced cell death in SH-SY5Y cells by mechanisms involving both the specific interaction with intracellular pathways and its antioxidant capability. Our study suggests a novel possible strategy to prevent and/or ameliorate neurodegenerative diseases, such as PD.
... Rheumatoid arthritis (RA) is a chronic autoimmune disease, characterised by synovial hyperplasia, inammatory cell inltration, pannus formation and destruction of articular cartilage and bone matrix. 1 It is one of the most common and disabling forms of osteoarthritis. It is mainly manifested by redness, swelling, a hot sensation, pain, and other symptoms of the Dr Feng Guan majored in chemical constituents and pharmacological effects of traditional Chinese medicine and medicinal plant and received her PhD degree in 2008 at Heilongjiang University of Chinese medicine, China. ...
Rheumatoid arthritis (RA) is a common worldwide chronic autoimmune disease, characterised by synovial hyperplasia, inflammatory cell infiltration, pannus formation and destruction of articular cartilage and bone matrix. It is one of the most common forms of osteoarthritis bestowing high rates of both disability and death. Increasing attention has been paid to the use of natural medicines and natural products in the treatment of RA and patients' acceptance has increased year by year because of their high efficacy and safety. Flavonoids are a group of important secondary metabolites occurring in many plants which have rich biological activities such as anti-rheumatic, vasodilator, and anti-tumor effects. Many successful medical treatments of RA appear to be attributable to the application of flavonoids. Quercetin, a representative active member of the flavonoid family, is found abundantly in many plants, e.g. apples, berries, cabbages, onions, and ginkgo. In recent years, progress has been made in the research of its anti-rheumatoid effects which indicate that it is potentially a noteworthy prodrug for the treatment of RA. However, the poor solubility of quercetin affects its bioavailability and clinical efficacy. This review aims to provide an up to date summary of the biological effects and mechanism of action of quercetin for the treatment of RA, and the research progress made towards nano formulations of quercetin to improve its solubility and efficacy.
... The results indicate that stevioside exhibits anti-oxidant properties by scavenging free radicals. The role played by lipid peroxidation-induced injury in encouraging the progression of rheumatoid arthritis has been previously reported (Marino et al. 2015). Stevioside treatment was observed to considerably diminish the lipid peroxidation levels in mice. ...
Adjuvant arthritis is a chronic, autoimmune and inflammatory disorder of the joints. The occurrence of disorder causes a severe damage to the connective tissue eventually leading to progressive physical disability and eventual death. The recent years of evidence suggests the anti-inflammatory properties of stevioside, a diterpene glycoside. However, the effect of stevioside against adjuvant arthritis, a chronic inflammatory disorder is not known. Hence, the present study was designed to study the effect of stevioside against Freund's complete adjuvant induced arthritis model in rats. The acute anti-inflammatory effect of stevioside also studied by employing carrageenan-induced paw oedema model in rats. The biochemical markers, haematological parameters, lipid peroxidation, myeloperoxidase activity, lipoxygenase activity, the levels of PGE2 and pro-inflammatory (TNF-α, IL-6 & IL-1β) and anti-inflammatory cytokine (IL-10) were analysed. The protein expression of NF-κB (p65) COX-2 and iNOS in paw tissues were estimated by western blotting. Stevioside treatment significantly ameliorates the adjuvant induced arthritic scoring, histological alterations, paw volume, elevation of biochemical (AST, ALT, ALP and glucose levels) and haematological (haemoglobin, differential and platelet count) parameters and restored the endogenous anti-oxidant (SOD, CAT, GSH and GST) activities. Treatment with stevioside also significantly prevented the adjuvant induced elevation of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), pro-inflammatory protein expressions (iNOS, COX-2, NF-κB (p65) and pIκB/IκB ratio), prevented the increase in myeloperoxidase activity and significantly restored the anti-inflammatory (IL-10) cytokine level in paw tissues. Collectively, our findings suggest that stevioside may serve as anti-inflammatory agent and could serve as a potential adjunct therapeutic option in treating adjuvant arthritis.
... Black rice is well known for its high content of phenolic compounds, such as flavonoids, that are reported to have beneficial impacts on human health for their role as natural antioxidants [17][18][19][20], together with recognized effects on several diseases [21][22][23][24][25]. Anthocyanins are a flavonoid sub-class commonly known, among others, for their potential antidiabetic effect [26][27][28]. ...
Aim: The present study aimed to assess the efficacy of a nutraceutical ingredient, SelectSIEVE ® Rainbow, based on botanical extracts, in ameliorating cellulite-derived skin imperfections and microcirculation. The nutritional supplement contained a mixture of Oryza sativa (L.), Citrus sinensis (L.) Osbeck, Ananas comosus (L.) Merr, and Actinidia chinensis Planch; all ingredients were botanicals that can be used in food supplements. Results: In vitro studies showed the high capacity of the supplement to have an anti-inflammatory, antioxidant, and hypolipidemic effect, accompanied by an interesting proteolytic activity. The randomized double-blind placebo-controlled clinical trial, carried out on 60 women during an 8-week treatment period, confirmed the in vitro study results. SelectSIEVE ® Rainbow showed a whole-body shaping activity, with a reduction of the waist, hip, and tight circumference of 0.8, 0.65 and 0.72 cm, respectively. It also showed a reduction of subcutaneous fat mass of 1.24 mm and body weight, with an average of 0.7 kg and positive peaks of −2.9 kg. Skin health and appearance were also improved: +5.4% skin elasticity, +5.5% skin tonicity and +5.7% skin draining. Finally, the dermatological evaluation of the cellulite score and microcirculation showed an improvement in 57% and 60% of the subjects enrolled in the studies. Conclusions: This first study provides interesting inputs on the effectiveness of the nutraceutical complex standardized in polyphenols, anthocyanins and proteolytic enzymes to counteract cellulite blemishes and improve local microcirculation. The positive response encourages deeper studies and further investigation.
... Citrus fruits are typically consumed during winter in the Mediterranean diet and, together with their derivatives, have been extensively studied for their health properties, such as anti-inflammatory, antimicrobial, anti-aging, neuroprotective, and anticancer effects [1][2][3][4][5][6][7][8][9][10]. Amongst Citrus fruits, Citrus bergamia Risso et Poiteau (bergamot), a small tree belonging to the family of Rutaceae, has stimulated an ever-growing interest of the scientific community. ...
Renewed interest in natural products as potential source of drugs led us to investigate on both the anti-inflammatory and anti-nociceptive activity of Citrus bergamia Risso et Poiteau (bergamot) essential oil (BEO). Carrageenan-induced paw edema in rats was used as an experimental model of inflammation. Because of the toxicity of furocoumarins, we performed our study by using the BEO fraction deprived of these compounds (BEO-FF). Treatment with BEO-FF led to a significant inhibition of paw edema induced by a sub-plantar injection of carrageenan. Moreover, histological examination of BEO-FF-treated rat paw biopsies showed a reduction of pathological changes typical of edema. Pre-treatment with BEO-FF significantly reduced interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α levels in the paw homogenates, as well as nitrite/nitrate and prostaglandin E2 (PGE2) content in exudates. In addition, BEO-FF possesses antioxidant properties, as determined by cell-free assays. Furthermore, results of the writhing test showed that BEO-FF elicited a pronounced analgesic response, as demonstrated by a significant inhibition of constrictions in mice receiving acetic acid, with respect to control animals, whereas the results of the hot plate test suggested that the supra-spinal analgesia participates in the anti-nociceptive effect of BEO-FF. Our study indicates that BEO-FF exerts anti-inflammatory and anti-nociceptive effects, and suggests its potential role as an anti-edemigen and analgesic drug.
... Similarly, immunobiological agents such as rituximab, abatacept, and tocilizumab also have several adverse effects (29). Therefore, the development of safer effective therapeutic agents for the treatment of RA is warranted (30). In this study, we tested rhoifolin for acute toxicity as well as hepatic and kidney toxicity. ...
Rheumatoid arthritis (RA) is an autoimmune disease of knee joints involving pain and inflammation. Rhoifolin is a plant flavonoid known to have antioxidant and anti-inflammatory properties. This study was taken to identify the effect of rhoifolin on complete Freund’s adjuvant (CFA)-induced arthritis in the rat model. Treatment with rhoifolin (10 and 20 mg/kg) showed a significant improvement in the overall health parameters such as paw edema and weight loss. This improvement in morphological parameters corroborated the findings with gross morphological changes observed in the histopathological analysis. Rhoifolin treatment also caused a significant decrease in oxidative stress, evident from changes in intracellular levels of glutathione, glutathione peroxidase, malondialdehyde, and superoxide dismutase in the articular cartilage tissue. Moreover, proinflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin(IL)-1β, and IL-6 showed a significant downregulation of gene expression and intracellular protein concentration levels. The NF-κB pathway showed a significant attenuation as evident in the significant reduction in the levels of NF-κB p65 and p-IκB-α. These results indicated that rhoifolin can be a natural therapeutic alternative to the extant regimens, which include non-steroidal anti-inflammatory drugs and immunosuppressants. Additionally, the antioxidant and anti-inflammatory action of rhoifolin was probably mediated by the NF-κB pathway. However, the exact target molecules of this pathway need to be determined in further studies.
... 48 Nevertheless, occasionally, it can be appropriate to take nutraceuticals, food supplements, and natural remedies in order to improve the natural defences. 27,49,50 The results of our study support the use of dietary compounds to maintain the health status, especially with regards to cancer prevention. ...
Several studies published in the last decade, suggest that the beneficial role of extra-virgin olive oil (EVOO) in human health is mostly attributable to the main secoiridoid derivatives (oleuropein, oleocanthal and oleacein). Anti-cancer properties have also been demonstrated for certain compounds present in small quantities in the EVOO, including oleuropein and hydroxytyrosol, that have been extensively studied, while minor attention has been addressed to the most abundant secoiridoid oleacein. Aim of our research was to study the molecular mechanisms underlying the anti-proliferative and the anti-metastatic capacity of oleacein in the SH-SY5Y human neuroblastoma cell line. Our results demonstrate that oleacein is able to reduce the proliferation of SH-SY5Y cells by blocking the cell cycle in S phase and inducing apoptotic cell death, through the increase of both Bax and p53, as well as a reduction of Bcl2 expression and STAT3 phosphorilation. Moreover, oleacein determined a reduction of SH-SY5Y cell adhesion and migration. Overall, these findings indicate that oleacein exerts anticancer effects against neuroblastoma cells, suggesting a promising role as candidate against this type of cancer.
... In the last 30 years, an ever-increasing number of people have employed natural remedies to maintain good health as well as to treat several diseases [11,12], and there has been growing interest in Citrus derivatives as weapons to fight different chronic illnesses [13,14]. In this line, several natural products used as nutraceuticals or dietary supplements are taken to combat excessive adiposity and promote weight loss [15][16][17], including Citrus extracts [18,19]. ...
Background: Obesity is a pathological condition that has reached epidemic proportions; hence, it is necessary to find novel strategies aimed at fighting this disease. The present study was designed to evaluate the effect of a flavonoid-rich extract of orange (Citrus sinensis) juice (OJe) in diet-induced obese zebrafish. Methods: Adult zebrafish were divided into four diet groups: (i) normally fed (NF); (ii) overfed (OF); (iii) NF supplemented with OJe (5 mL/L in fish water; NF + OJe); and (iv) OF supplemented with OJe (OF + OJe). Each week, body weight (BW) and body mass index (BMI) were measured, and, at the end of the fifth week, euthanized zebrafish were processed for both microscopic evaluations and qPCR analyses. Results: In OF zebrafish, OJe significantly decreased both BW and BMI values and lowered the visceral adipose tissue, while it had little effect in the NF group. Moreover, it significantly reduced adipocyte cell size in both NF and OF groups in both visceral and subcutaneous adipose tissues, as well as their number in OF fish. Finally, OJe modulated some obesity-related genes, such as leptin A, ghrelin, orexin, pro-opiomelanocortin (POMC), and neuropeptide Y (NPY), in both gut and brain. Conclusion: This study adds new insights into the anti-obesity properties of orange juice and its flavonoids, suggesting their role as weight management agents through a lipolytic action linked to a restoration of metabolism-regulating gene expression.
... In addition, a flavonoid-rich extract of BJ (BJe) was shown to possess antioxidant activity and to counteract inflammatory response (Curro et al. 2016;Risitano et al. 2014), through a mechanism involving the AMPK/SIRT1 axis . The anti-inflammatory action of both BJe (Gugliandolo et al. 2019;Impellizzeri et al. 2015Impellizzeri et al. , 2016 as well as that of orange juice extract (Fusco et al. 2017) was also demonstrated in vivo, indicating its possible role in the treatment of inflammatory processes (Marino et al. 2015). Finally, Citrus derivatives are employed in aromatherapy (Mannucci et al. 2017(Mannucci et al. , 2018 and clinically used as hypolipidemic supplement (Mollace et al. 2011). ...
Inflammaging is a low-grade, chronic, asymptomatic, controlled and systemic pro-inflammatory status that appears during the aging process and is linked to many age-related diseases. Growing evidence indicates that Mediterranean diet is a reliable instrument to counteract inflammaging, due to its high content of flavonoids, whose main source are Citrus fruits. Our objective was to summarize and critically discuss the rich clinical evidence on the properties of Citrus fruits and their derivatives focusing on a series of age-related diseases and their potential use to maintain health in aging populations. A systematic review of articles using MEDLINE, Web of Sciences and Scopus was performed independently by two reviewers. Search terms included keywords related to Citrus fruits or their derivatives and inflammation. No language restriction was applied. The last search was performed on November 15th, 2018. The study selection and systematic review were carried out in accordance with the PRISMA statement. Prior to the beginning of the review, Authors defined a checklist for inclusion criteria. Three reviewers independently performed the extraction of articles. Eighty-five papers met our inclusion criteria and were eligible for inclusion in the final review. Citrus fruits seem to possess capabilities in counteracting inflammation-based age-related diseases, thus representing a possible weapon to fight inflammaging. This review may be used as a scientific basis for further studies on the role of Citrus fruits consumption and inflammaging.
... Here we show that daily intake of BJe up to 70 mg/kg for 3 months displays no apparent signs of toxicity in Pirc rats. In this line, several studies performed in both animals and humans revealed that BJ or its polyphenol extracts did not exert any sign of systemic toxicity, suggesting their valuable efficacy and safety ratio [1,37]. ...
Purpose
To determine the potential of a flavonoid-rich extract from bergamot juice (BJe) to prevent colorectal carcinogenesis (CRC) in vivo.
Main methods
Pirc rats (F344/NTac-Apcam1137), mutated in Apc, the key gene in CRC, were treated with two different doses of BJe (35 mg/kg or 70 mg/kg body weight, respectively) mixed in the diet for 12 weeks. Then, the entire intestine was surgically removed and dissected for histological, immunohistochemical and molecular analyses.
Results
Rats treated with BJe showed a significant dose-related reduction in the colon preneoplastic lesions mucin-depleted foci (MDF). Colon and small intestinal tumours were also significantly reduced in rats supplemented with 70 mg/kg of BJe. To elucidate the involved mechanisms, markers of inflammation and apoptosis were determined. Compared to controls, colon tumours from BJe 70 mg/kg-supplemented rats showed a significant down-regulation of inflammation-related genes (COX-2, iNOS, IL-1β, IL-6 and IL-10 and Arginase 1). Moreover, in colon tumours from rats fed with 70 mg/kg BJe, apoptosis was significantly higher than in controls. Up-regulation of p53 and down-regulation of survivin and p21 genes was also observed.
Conclusions
These data indicate a strong chemopreventive activity of BJe that, at least in part, is due to its pro-apoptotic and anti-inflammatory actions. This effect could be exploited as a strategy to prevent CRC in high-risk patients.
... Staudte et al. (2005) suggested that 2 weeks intake of grapefruit leads to increased plasma levels of vitamin C and improves sulcus bleeding scores in patients with chronic periodontitis, especially in smokers. These findings, together with the previous reports on the antioxidant properties of BJe (Marino et al., 2015;Ferlazzo et al., 2016a), led us to investigate its effects in an experimental model of periodontitis in order to evaluate its potentiality and to discover the mechanism of action. To our best knowledge, this is the first study demonstrating the antioxidant and anti-inflammatory activity of a Citrus derivative against periodontal disease. ...
Objective: In this study, we investigated the effects of a flavonoid-rich fraction of Bergamot juice (BJe) in rats subjected to experimental periodontitis induced by a single intragingival injection of lipopolysaccharides (LPS).
Main Methods: Periodontitis was induced by a single intragingival injection of 1 μl LPS (10 μg/μl) derived from Salmonella typhimurium in sterile saline solution. The injection was made in the mesolateral side at the interdental papilla between the first and the second molar. Fourteen days after LPS injection, we performed radiographic analyses and then we surgically removed the gingivomucosal tissue surrounding the mandibular first molar for histological, immunohistochemical and molecular analysis.
Results: LPS significantly induced oedema, tissue damage and increased neutrophil infiltration. At molecular level, we found increased NF-κB translocation as well as raised both TNF-α and IL-1β expression, other than modulation of apoptosis-associated proteins. Moreover, the increased myeloperoxidase activity was associated with up-regulation of adhesion molecules. Immunohistochemical analysis for nitrotyrosine and poly ADP-ribose displayed an intense staining in the gingivomucosal tissue. Oral administration of BJe for 14 consecutive days reduced tissue injury and several markers of gingival inflammation including nuclear NF-κB translocation, cytokines expression, myeloperoxidase activity and the expression of some adhesion molecules such as ICAM and P-selectin. BJe also decreased both nitrosative stress and PARP positive staining. Moreover, it caused down-regulation of Bax and up-regulation of Bcl-2 expression.
Conclusion: Our findings demonstrate that BJe improves LPS-induced periodontitis in rats by reducing the typical markers of inflammation, thus suggesting its potential in the treatment of periodontal diseases.
... It helps to lower down the levels of uric acid and thus it is very helpful for patients suffering from arthritis and gout. 37 High doses of limonene increase the production and activation of a protein called TGF-beta, which programs the cancer cells to self-destruct 38 and thus helps in fighting breast cancer and pancreatic cancer. ...
Citrus medica (Citron) is an underutilized fruit plant having various bioactive components in all parts of the plant. The major bioactive compounds present are iso-limonene, citral, limonene, phenolics, flavonones, Vitamin C, pectin, linalool, decanal, and nonanal, accounting for several health benefits. Pectin and heteropolysachharides also play a major role as dietary fibers. The potential impact of citron and its bioactive components to prevent or reverse destructive deregulated processes responsible for certain diseases has attracted different researchers' attention. The fruit has numerous nutraceutical benefits, proven by pharmacological studies; for example, anti-catarrhal, capillary protector, anti-hypertensive, diuretic, antibacterial, antifungal, anthelmintic, antimicrobial, analgesic, strong antioxidant, anticancerous, antidiabetic, estrogenic, antiulcer, cardioprotective, and antihyperglycemic. The present review explores new insights into the benefits of citron in various body parts. Throughout the world, citron has been used in making carbonated drinks, alcoholic beverages, syrup, candied peels, jams, marmalade, cordials, and many other value added products, which suggests it is an appropriate raw material to develop healthy processed food. In the present review, the fruit taxonomical classification, beneficial phytochemicals, antioxidant activities, and health benefits are discussed.
... It helps to lower down the levels of uric acid and thus it is very helpful for patients suffering from arthritis and gout. 37 High doses of limonene increase the production and activation of a protein called TGF-beta, which programs the cancer cells to self-destruct 38 and thus helps in fighting breast cancer and pancreatic cancer. ...
Citrus medica (Citron) is an underutilized fruit plant having various bioactive components in all parts of the plant. Major bioactive compounds present are iso-limonene, citral, limonene, phenolics, flavonones, vitamin C, pectin, linalool, decanal and nonanal, accounting for several health benefits. Pectin and heteropolysachharides also play a major role as dietary fibers. The potential impact of citron and its bioactive components to prevent or reverse destructive deregulated processes responsible for the disease has attracted different researchers’ attention. The fruit has numerous nutraceutical benefits proven with pharmacological study, for example, anti-catarrhal, capillary protector, anti–hypertensive, diuretic, antibacterial, antifungal, anthelmintic, antimicrobial, analgesic, strong antioxidant, anticancerous, antidiabetic, estrogenic, antiulcer, cardioprotective and antihyperglycemic. The review explores new insights on the benefits of citron in various body parts. Throughout the world citron has been used in making carbonated drinks, alcoholic beverages, syrup, candied peels, jams, marmalade, cordials and many other value added products which makes it an appropriate raw material to develop healthy processed food. In present review fruit taxonomical classification, beneficial phytochemicals, antioxidant activities and health benefits have been discussed.
... For example higher omega 3 & vitamin D intake in the year proceeding diseasemodifying anti rheumatic drugs (DMARD) initiation produced better outcomes in RA patients [5]. Similarly the review of Marino et al. [6] highlights the potential of various dietary compounds including natural antioxidants such as flavanoids to reduce inflammatory mediators, pro inflammatory gene expression and damaging oxidant production. ...
... Dentro de esta riqueza vegetal, resaltan muchas especies cuyos frutos contienen alta calidad, de vitaminas (A, B, C, E, etc.) carotenoides y pigmentos antociánicos que sumados a sustancias fenólicas como los flavonoides; les confieren a estas frutas y vegetales el hecho de poseer una alta capacidad antioxidante (Bhat et al., 2016;Jatinder et al., 2016). Muchos estudios dan a conocer los beneficios que aportan las frutas para la salud: Reducen las enfermedades cardiovasculares (Mostacero et al., 2011;Boeing et al., 2012;Cárdenas et al., 2015;Gan et al., 2015;Goszcz et al., 2015), la diabetes (Boeing et al., 2012;Wang et al.,2016), hipercolesterolemia (Mannarino et al., 2014), resistencia a la insulina (Parikh et al.,2014); e incluso ayudan considerablemente a prevenir y combatir varios tipos de cáncer (Freedman et al., 2014;Shigihara et al., 2014;Magadi et al., 2015), artritis y arterosclerosis (Lü et al., 2015;Marino et al., 2015), disfunción cerebral, y también se ha demostrado que disminuyen los procesos de aceleración del envejecimiento (Goszcz et al., 2015;Bhat et al., 2016). La capacidad que tienen estas frutas por sus vitaminas, sales minerales y antioxidantes (Zielinska y Michalska, 2016), está orientado actualmente a investigaciones que aporten al conocimiento taxonómico, fitogeográfico, etnobotánico; determinando las características organolépticas, fitoquímicas, y bromatológicas de estas especies para validar su consumo local y regional y así mejorar los beneficios que aportan a la salud y nutrición de la población; y así ampliar su cultivo y el uso masivo por la población; utilizando en todo momento sistemas de producción ambientalmente sostenible (Kahane et al., 2013). ...
La megafitodiversidad del Perú presenta especies nativas de toda índole; entre ellas frutales, los que a pesar de ser consumidos desde hace cientos de años, aún no han sido atendidos por la investigación para validar su uso, con la seguridad de que estamos consumiendo recursos que pueden superar en cantidad y calidad de vitaminas, sales minerales y pigmentos antociánicos. Así, el objetivo del presente estudio fue realizar un Inventario Taxonómico, Fitogeográfico y Etnobotánico de los frutales nativos del Norte del Perú. Se realizaron colectas a través de exploraciones botánicas programadas a varias localidades del Norte del Perú. Luego se llevó a cabo una revisión crítica de la bibliografía especializada y reforzando esta información con la obtenida por la experiencia personal tanto de los investigadores como de los pobladores locales y regionales. Se reportan 45 especies, distribuidas en 18 familias; donde destacan por su número las: Ericaceae (7), Myrtaceae (6), Cactaceae (4), Solanaceae (4), Caricaceae (3), Passifloraceae (3) y Rosaceae (3). Así mismo 29 especies (64%) son consumidas en estado fresco y/o natural, mientras que 16 especies (36%) tanto al estado fresco como procesadas (jaleas, mermeladas, helados, vinos, jugos, natilla, mazamorra, etc.).
... Accordingly, it has received much interest as a potential therapeutic agent for the prevention and/or treatment of various malignant diseases, allergies, arthritis, Alzheimer's disease, and other inflammatory illnesses. Because most chronic diseases are mediated through dysregulated inflammation, [38][39][40] curcumin has potential use in the treatment of numerous diseases. However, its use in an unmodified form is limited due to its poor bioavailability, 27 and enhancing the bioavailability of curcumin greatly increases its potential usefulness for the prevention and treatment of human diseases. ...
Rheumatoid arthritis (RA) is an autoimmune, chronic systemic inflammatory disorder. The long-term use of currently available drugs for the treatment of RA has many potential side effects. Natural phytonutrients may serve as alternative strategies for the safe and effective treatment of RA, and curcuminoids have been used in Ayurvedic medicine for the treatment of inflammatory conditions for centuries. In this study, a novel, highly bioavailable form of curcumin in a completely natural turmeric matrix was evaluated for its ability to improve the clinical symptoms of RA. A randomized, double-blind, placebo-controlled, three-arm, parallel-group study was conducted to evaluate the comparative efficacy of two different doses of curcumin with that of a placebo in active RA patients. Twelve patients in each group received placebo, 250 or 500 mg of the curcumin product twice daily for 90 days. The responses of the patients were assessed using the American College of Rheumatology (ACR) response, visual analog scale (VAS), C-reactive protein (CRP), Disease Activity Score 28 (DAS28), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF) values. RA patients who received the curcumin product at both low and high doses reported statistically significant changes in their clinical symptoms at the end of the study. These observations were confirmed by significant changes in ESR, CPR, and RF values in patients receiving the study product compared to baseline and placebo. The results indicate that this novel curcumin in a turmeric matrix acts as an analgesic and anti-inflammatory agent for the management of RA at a dose as low as 250 mg twice daily as evidenced by significant improvement in the ESR, CRP, VAS, RF, DAS28, and ACR responses compared to placebo. Both doses of the study product were well tolerated and without side effects.
... In addition, it exerts antimicrobial effects (Filocamo et al., 2015;Mandalari et al., 2017). Evidence that BJ, BJe or other polyphenol extracts from BJ did not exhibit noticeably signs of systemic toxicity either in animals or in human suggests their valuable risk/benefit ratio (Marino et al., 2015). Four studies focused on the anticancer activity of BJ and BJe, in particular three performed in vitro (Delle Monache et al., 2013;Visalli et al., 2014;Ferlazzo et al., 2016b) and one in vivo , and met the inclusion criteria of our systematic review. ...
Background: During the last decades, a huge body of evidence has been accumulated suggesting that Citrus fruits and their juices might have a role in preventing many diseases including cancer.
Objective: To summarize the numerous evidences on the potential of Citrus juices and their extracts as anticancer agents.
Data sources: A systematic review of articles written in English using MEDLINE (1946-present), EMBASE (1974-present) and Web of Sciences (1970-present) was performed independently by two reviewers. Search terms included Citrus, Citrus aurantifolia, Citrus sinensis, Citrus paradisi, Citrus fruits, Citrus fruits extract, cancer, neoplasm, neoplasia, tumor, metastasis, carcinogenesis, proliferation. The last search was performed on March 16th, 2017.
Study selection: Study selection and systematic review were carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Prior to the beginning of the review, Authors defined a checklist for inclusion criteria, thus including articles which meet the following: (i) published on peer-reviewed scientific journals; (ii) Citrus juice used alone; (iii) extracts derived from Citrus juice; (iii) for preclinical studies, an exposure time to Citrus juices and their extracts more than 24 h. Reviews, meta-analyses, conference abstracts and book chapters were excluded.
Data extraction: Three reviewers independently performed the extraction of articles.
Data synthesis: 22 papers met our inclusion criteria and were eligible for inclusion in the final review. According to the kind of study, the selected ones were further divided in preclinical (n = 20) and observational (n = 2) studies.
Conclusion: The studies discussed in this review strongly corroborate the role of Citrus juices and their derivatives as potential resource against cancer.
Agapanthus is derived from Greek and means “flower of love”. Lily of the Nile, it is a bulbous exotic ornamental plant, characterized by being tall and erect (30–60 cm height) with blue or white flowers formed in late spring, early summer. Agapanthus is a monocotyledon that belongs to the family Amaryllidaceae, and, originating in South Africa, is cultivated all over the world. Agapanthus is used in South Africa, in folk medicine, for various purposes, but other studies show that it presents toxicity as well. In addition, it has several anthocyanins and anthocyanidins, responsible for the blue color observed. When considering breeding programs and new studies, it is imperative to taking into account current advances Agapanthus culture. It is also important to consider the understanding of the reproductive biology of the species as a source for the advance of genetic improvement programs, under an ecological, chemical and phytochemical overview. It is evident that it is still possible to perform chemical and phytochemical studies, analyzing uses and applications of the plant with the objective of understanding its metabolic action, as well as employing vegetable dyes in new materials in order to develop intelligent materials, contributing to the sustainability and environment and meeting the principles of Sustainable Development Goals proposed by the United Nations, directed at Green Chemistry.
Inflammatory Bowel Disease [IBD] is a chronic inflammatory disorder that affects the digestive system. As a disorder of the Gastro inflammatory condition, IBD symptoms could be alleviated by nutritional factors. Polyphenols are the secondary plant metabolites exclusively present in plants, vegetables and fruits and are known to be beneficial due to their wide range of biological effects. Increased intake of polyphenols appears to protect against disease in virtue of their anti‐inflammatory properties. There is growing evidence showing that polyphenols isolated from plants have great therapeutic potential in the prevention and treatment of different chronic diseases, including inflammatory disorders as well as gastrointestinal diseases. Present study proposal is designed to evaluate the possible effect of three major polyphenols: Ellagic Acid, Gallic acid and Quercetin for their therapeutic potential in inhibiting adherence and cytokines release in rat intestinal cells exposed to bacterial infection in-vitro. In the current study, the E.coli strain HM 95 which has 1.51 ± 3.75 invasion capacity and 5.75 ± 9.36 adhesion capacity was used in the study to co-culture with Normal Rat Epithelium Cell Line [IEC-6] to study the Genotoxicity. Exposure to Gallic acid prevented DNA damage which was studied by Comet assay. However, Ellagic acid and Quercetin did not exhibit significant prevention of DNA damage.
Medicinal plants are promptly used in this era for the treatment of various human disorders among which one is autoimmune disorder. This is characterized by pathological changes such as (structural or functional) in tissues/organs as a result of autoreactive cells and it affects 5% of the worldwide population. Autoimmune disorders are characterized by the presence of antibodies, inflammations, mononuclear phagocytes, and autoreactive cells. Various plant-based herbal medicines are effective for the management of autoimmune disorders, and the most of the active constituents of the plant products are investigated for their immunosuppressive properties such as Emblica officinalis, Tinosopra cordifolia, Curcuma longa, Tripterygium wilfordii, Withania somnifera, berberine, Quercetin, Glycyrrhiza glabra, and baicalein, etc. Thus, the purpose of this chapter is to emphasize the importance of natural compounds for the management of autoimmune disorders and put into the limelight of the scientific community several health-promoting effects of natural compounds that could be beneficial for the development of novel and effective drug compounds from natural products.
The impact of food on immune functions is recognized since centuries and is now being increasingly explored for therapeutic applications. Rice, in addition to being the staple food in most...
Background:
Autoimmune diseases are chronic disorders in which the immune system does not recognize and attacks one self's healthy components. In this context, although natural remedies might represent a promising therapeutic strategy, evidence regarding Citrus flavonoids is still controversial.
Objective:
To summarize and critically discuss the clinical evidence on the effects of Citrus flavonoids for the management of autoimmune diseases.
Method:
A systematic review of articles has been carried out independently by two Authors using MEDLINE, Scopus and ISI Web of Science databases. Search terms comprised keywords related to Citrus flavonoids and autoimmune diseases. The last search was performed on March 16, 2021. No language restrictions were applied. Systematic review and study selection were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Before starting the review, Authors defined the types of articles to be included. Three reviewers independently carried out the extraction of papers.
Results:
Ten clinical studies fulfilled the eligibility criteria and were included in the final review.
Conclusion:
The studies discussed in this review are heterogeneous. Indeed, some studies suggest the use of Citrus flavonoids in the frame of autoimmune disorders, whereas others discourage it. Hence, this systematic review highlights the need of further large-scale clinical studies to define the exact role of Citrus flavonoids in the management of autoimmune diseases (PROSPERO number CRD42021234903).
Bone is a highly vascularized tissue that relies on a close spatial and temporal interaction between blood vessels and bone cells. As a result, angiogenesis is critical for bone formation and healing. The vascular system supports bone regeneration by delivering oxygen, nutrients, and growth factors, as well as facilitating efficient cell–cell contact. Most clinical applications of engineered bone grafts are hampered by insufficient vascularization after implantation. Over the last decade, a number of flavonoids have been reported to have osteogenic–angiogenic potential in bone regeneration because of their excellent bioactivity, low cost, availability, and minimal in vivo toxicity. During new bone formation, the osteoinductive nature of certain flavonoids is involved in regulating multiple signaling pathways contributing toward the osteogenic–angiogenic coupling. This review briefly outlines the osteogenic–angiogenic potential of those flavonoids and the mechanisms of their action in promoting bone regeneration. However, further studies are needed to investigate their delivery strategies and establish their clinical efficacy.
Antioxidants are substances that fight free radicals produced in the body due to several intrinsic as well as extrinsic factors such as pollution, smoking, UV radiation, etc. They play a preventive as well as scavenging role in removing the excess free radicals thereby preventing oxidative stress. Oxidative stress is capable of disturbing the normal body physiology and may cause lethal diseases such as cancer, Alzheimer’s, diabetes, etc. The antioxidants have an important role to play with the rapid increase in the external forces causing uncontrolled generation of free radicals. The human body produces its own antioxidants, called endogenous antioxidants. However, some antioxidants are obtained from external sources; these exogenous antioxidants fulfill the dietary requirements of the body. In the present chapter, natural as well as synthetic antioxidants have been discussed with special emphasis on plant-derived antioxidants and their potential applications in the treatment and management of life-threatening diseases. Plants being an all-natural hub for antioxidants have been discussed for their safer use, variety, and dosage. In addition to this, the role of antioxidants in the food, packaging, and cosmetics industry has also been highlighted. This chapter sums up the potential applications as well as working of antioxidants while underscoring its future prospects for further study.
Cadmium (Cd) represents a public health risk due to its non-biodegradability and long biological half-life. The main target of Cd is considered the kidney, where it accumulates. No effective treatment for Cd poisoning is available so that several therapeutic approaches were proposed to prevent damages after Cd exposure. We evaluated the effects of a flavonoid-rich extract of bergamot juice (BJe), alone or in association with curcumin (Cur) and resveratrol (Re), in the kidney of mice exposed to cadmium chloride (CdCl2). Male mice were administered with CdCl2 and treated with Cur, Re, or BJe alone or in combination for 14 days. The kidneys were processed for biochemical, structural and morphometric evaluation. Cd treatment significantly increased urea nitrogen and creatinine levels, along with tp53, Bax, Nos2 and Il1b mRNA, while reduced that of Bcl2, as well as glutathione (GSH) content and glutathione peroxidase (GPx) activity. Moreover, Cd caused damages to glomeruli and tubules, and increased Nrf2, Nqo1 and Hmox1 gene expression. Cur, Re and BJe at 40 mg/kg significantly improved all parameters, while BJe at 20 mg/kg showed a lower protective effect. After treatment with the associations of the three nutraceuticals, all parameters were close to normal, thus suggesting a new potential strategy in the protection of renal functions in subjects exposed to environmental toxicants.
Este libro está diseñado como un texto de apoyo para los estudiantes de pregrado en química y carreras relacionadas, para introducirse en el campo extenso de la química de los productos naturales, específicamente en lo relacionado al conocimiento químico de los denominados metabolitos secundarios como: Compuestos aromáticos como los flavonoides, compuestos no-aromáticos como los terpenoides, compuestos nitrogenados como los alcaloides, compuestos azufrados, etc. Además del enfoque químico se menciona el uso o potencial farmacéutico de estas sustancias. Se describen las técnicas experimentales que se utilizan para la obtención, el aislamiento, la identificación y la caracterización química de estas sustancias. Se plantean problemas para retar a los estudiantes en la caracterización de los metabolitos secundarios, especialmente mediante la Espectrometría de Resonancia Magnética Nuclear.
Rheumatoid arthritis is an autoimmune disease characterized by chronic inflammation in the joints, leukocyte infiltration in the synovium, and joint and bone degradation. It affects about 1% of the world’s population, mostly women and elderly, but has no medical cure. Patients are recommended to manage their conditions through lifestyle changes and medications. Mounting evidence from clinical trials, animal models, and cell culture studies suggested that dietary polyphenols have a beneficial effect on the development and symptoms of rheumatoid arthritis. In RA patients, phenolic compounds have been found to reduce early morning stiffness, morning pain, and after activity pain, and decrease plasma levels of inflammatory mediators. In rodents with RA, polyphenols were shown to delay the onset, alleviate the symptoms, and reduce inflammation. The major mechanisms of RA prevention and symptom alleviation were the reduction of inflammatory mediators and inhibition of specific signaling pathways involved in the inflammatory response in rheumatoid arthritis. Future research is needed to assess the bioactivity of phase-2 and microbial metabolites of polyphenols and explore how interactions between polyphenols and gut microbiome affect RA development.
Inflammation-related pathologies remain a serious health problem with high costs for the community. Citrus flavonoids are known to possess important pharmacological properties, including anti-inflammatory activity. In this study we evaluated the effects of a flavonoid-rich extract of orange juice (OJe) in an experimental model of enteritis induced by Vibrio anguillarum in adult zebrafish (Danio rerio). Administration of V. anguillarum through live feed (Artemia nauplii) for three consecutive days caused evident signs of enteritis in zebrafish. Three days of treatment with OJe before the pathogenic insult resulted in a remarkable reduction of tissue inflammatory events as well as a molecular down-regulation of the inflammatory genes such as IL-1β, IL-6 and TNFα. Our data suggest that OJe counteracts the inflammation of zebrafish intestinal mucosa, indicating that the pool of flavonoids present in orange juice could be useful for the prevention of enteritis.
Inflammatory bowel disease (IBD), with its major manifestations being Crohn’s disease and ulcerative colitis, belongs to the gastrointestinal inflammatory disorders, whose main therapeutic approach is represented by synthetic anti-inflammatory drugs. However, they are often accompanied by many side effects that shifted the interest of the scientific community towards natural products. In this context, several studies asserted the anti-IBD effects of Citrus fruits and their flavonoids, thus the aim of the present review is to provide robust evidence favouring their role in the prevention and treatment of IBD. Key mechanisms relate to their anti-inflammatory and antioxidant properties, as well as their ability to modulate gut microbiota. All the findings collected in this review, lay the foundations for further studies in human with the aim of evaluating the concrete applicability as a novel preventive and therapeutic approach of Citrus fruits and their flavonoids.
The use of natural compounds for treating chronic bone diseases holds remarkable potential. Among these therapeutics, naringin, a flavanone glycoside, represents one of the most promising candidates owing to its multifaceted effect on bone tissues. This review provides an up-to-date overview on naringin applications in the treatment of bone disorders, such as osteoporosis and osteoarthritis, and further highlights its potential for stem cell pro-osteogenic differentiation therapies. A critical perspective on naringin clinical translation is also provided. The topic is discussed in light of recently developed biomaterial-based approaches that potentiate its bioavailability and bioactivity. Overall, the reported pro-osteogenic, antiresorptive and antiadipogenic properties establish this flavanone as an exciting candidate for application in bone tissue engineering and regenerative medicine.
Bergapten (BG) is a cumarine-derivate compound in many medicinal plants. Here, in vitro and in vivo experimental results indicated that BG possesses anti-inflammatory properties, Based on this, we further investigated the precise molecular mechanisms of BG in LPS-stimulated inflammation response. Studies revealed that BG inhibited LPS-stimulated productions of TNF-α, IL-1β, IL-6, PGE2 and NO as well as the expression of iNOS and COX-2, and at the same time, it increased LPS-induced release of IL-10 in a dose-dependent manner in RAW264.7 cells. Mechanistically, BG suppressed the activations of JAK/STAT, but not that of MAPKs and NF-κB. In addition, BG, as an antioxidant, prevented the accumulation of ROS, which further exerted its anti-inflammatory function. In vivo researches revealed that BG decreased LPS-induced mortality in mice. In conclusions, BG may be a potential candidate for inflammation therapy via inhibiting JAK/STAT activation and ROS production in RAW264.7 cells.
Citrus bergamia Risso et Poiteau, also known as “Bergamot,” is a plant belonging to the Rutaceae family, defined as a hybrid of bitter orange and lemon. It is an endemic plant of the Calabria region (Italy). Bergamot fruit is primarily used for the extraction of its essential oil (bergamot essential oil: BEO), employed in perfume, cosmetics, food, and confections. The aim of this review was to collect recent data from the literature on C. bergamia essential oil and, through a critical analysis, focus on safety and the beneficial effects on human health. Clinical studies on the therapeutic applications of BEO exclusively focus on the field of aromatherapy, suggesting that its use can be useful for reducing anxiety and stress.
Diabetes mellitus is a serious world health problem and one of the most studied diseases; a major concern about its treatment is that β-cell mass and functionality is hard to restore. In addition, it is frequently associated with severe complications, such as diabetic nephropathy and cardiomyopathy. The anti-inflammatory, anti-oxidative and anti-apoptotic properties of curcumin have made it a promising molecule for the treatment of this pathology; however, its solubility and bioavailability problems are still the subject of multiple studies. To cope with those difficulties, several approaches have been evaluated, such as the development of pharmaceutical formulations and curcumin analogues. This review discusses some of the studied therapeutic targets for curcumin in diabetes as well as the structural characteristics and targets of its analogues. The shortening of the central seven-carbon chain of curcumin has given rise to compounds without glucose-lowering effects but potentially useful for the treatment of diabetes complications; whereas preserving this chain retains the glucose-lowering properties. Most of the analogues discussed here have been recently synthesized and tested in animal models of type 1 diabetes; more studies in models of type 2 diabetes are needed.
Copyright © 2015. Published by Elsevier B.V.
Plant polyphenols exert anti-inflammatory activity through both anti-oxidant effects and modulation of pivotal pro-inflammatory genes. Recently, Citrus bergamia has been studied as a natural source of bioactive molecules with antioxidant activity, but few studies have focused on molecular mechanisms underlying their potential beneficial effects. Several findings have suggested that polyphenols could influence cellular function by acting as activators of SIRT1, a nuclear histone deacetylase, involved in the inhibition of NF-κB signaling. On the basis of these observations we studied the anti-inflammatory effects produced by the flavonoid fraction of the bergamot juice (BJe) in a model of LPS-stimulated THP-1 cell line, focusing on SIRT1-mediated NF-κB inhibition. We demonstrated that BJe inhibited both gene expression and secretion of LPS-induced pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) by a mechanism involving the inhibition of NF-κB activation. In addition, we showed that BJe treatment reversed the LPS-enhanced acetylation of p65 in THP-1 cells. Interestingly, increasing concentrations of Sirtinol were able to suppress the inhibitory effect of BJe via p65 acetylation, underscoring that NF-κB-mediated inflammatory cytokine production may be directly linked to SIRT1 activity. These results suggest that BJe may be useful for the development of alternative pharmacological strategies aimed at reducing the inflammatory process.
Neuroblastoma is the most common extracranial pediatric solid tumour with poor prognosis in children with disseminated stage of disease. A number of studies show that molecules largely distributed in commonly consumed fruits and vegetables may have anti-tumour activity. In this study we evaluate the effect of Citrus bergamia (bergamot) juice (BJ) in vitro and in a spontaneous metastatic neuroblastoma SCID mouse model. Qualitative and quantitative characterization of BJ flavonoid fractions were performed by RP-HPLC/PDA/MS. We show that BJ significantly affects SK-N-SH and LAN-1 cells proliferation in vitro, but fails to reduce primary tumour weight in vivo. Moreover, BJ reduced cell adhesiveness and invasion of LAN-1 and SK-N-SH cells in vitro and the number of pulmonary metastases under consideration of number of tumour cells in the blood in mice inoculated with LAN-1 cells in vivo. These effects without any apparent sign of systemic toxicity confirm the potential clinical interest of BJ and lay the basis for further investigation in cancer.
N-palmitoylethanolamine (PEA) is an endogenous fatty acid amide belonging to the family of the N-acylethanolamines (NAEs). Recently, several studies demonstrated that PEA is an important analgesic, anti-inflammatory and neuroprotective mediator. The aim of this study was to investigate the effect of co-ultramicronized PEA + luteolin formulation on the modulation of the inflammatory response in mice subjected to collagen-induced arthritis (CIA).
CIA was induced by an intradermally injection of 100 mul of the emulsion (containing 100 mug of bovine type II collagen (CII)) and complete Freund's adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. Mice subjected to CIA were administered with PEA (10 mg/kg 10% ethanol, intraperitoneally (i.p.)) or with co-ultramicronized PEA + luteolin (1mg/kg, i.p.) every 24 hours, starting from day 25 to 35.
Mice developed erosive hind paw arthritis when immunized with CII in CFA. Macroscopic clinical evidence of CIA first appeared as peri-articular erythema and edema in the hind paws. The incidence of CIA was 100% by day 28 in the CII challenged mice and the severity of CIA progressed over a 35-day period with a resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint. Treatment with PEA or PEA + luteolin ameliorated the clinical signs at days 26 to 35 and improved histological status in the joint and paw. The degree of oxidative and nitrosative damage was significantly reduced in PEA + luteolin treated mice as indicated by nitrotyrosine and malondialdehyde (MDA) levels. Plasma levels of the pro-inflammatory cytokines and chemokines were significantly reduced by PEA + luteolin treatment.
We demonstrated PEA co-ultramicronized with luteolin exerts an anti-inflammatory effect during chronic inflammation and ameliorates CIA.
Rheumatoid arthritis (RA) is the rheumatism mainly manifested as disabling joint disease and mainly involves hands, wrists, feet and other small joints. Recurrent arthritis attacks, synovial cell hypertrophy and hyperplasia and bone and cartilage damages eventually lead to joint dysfunction and other complications, and there is no cure. Quercetin (QU) is a kind of natural flavonoids, with lipid-lowering, anti-inflammatory and other pharmacological activities, and minor toxic side effects. Thus, we assume that QU may be an adjuvant natural drug for treatment of RA. The possible mechanism is through regulation of NF-κB, to inhibit the transcription of joint synovitis factors, hinder the generation of inflammatory factors, and inhibit the inflammatory reaction; through inhibiting the activities of VEGF, bFGF, MMP-2 and other cytokines, to inhibit angiogenesis in multiple links and inhibit synovial pannus formation. QU may be an adjuvant natural drug for treatment of RA.
Rheumatoid arthritis (RA) is a chronic inflammatory disease in which the progressive destruction of joint causes morbidity. It is also associated with an increased risk of atherosclerosis, which can result in cardiovascular disease and mortality. The therapeutic goal is to control the systemic inflammation to obtain not only the remission of symptoms, but also improve general state of health. Although recent biologic immunosuppressive therapies targeting pro-inflammatory cytokines have spawned a paradigm shift regarding the prognosis of RA, these therapies possess inherent side effects. Also, early diagnosis of the disease remains confounded by uncertainty. While the mechanisms responsible for the onset of RA remain unclear, reactive oxygen species (ROS) play a significant role in the pathogenesis of RA. ROS play a central role both upstream and downstream of NF-κB and TNFa pathways, which are located at the center of the inflammatory response. Among the ROS, the hydroxyl radical is the most harmful, and molecular hydrogen (H2) is a selective scavenger for this species. Recently, it has been shown that H2 is useful when administered along with the conventional therapy in RA as it acts to reduce oxidative stress in the patients. Especially in the early stage, H2 showed significant therapeutic potential, which also seemed to assist diagnosis and treatment decisions of RA. The possible expectations regarding the potential benefits of H2 by reducing the oxidative stress, resulting from inflammatory factors, are raised and discussed here. They include prevention of RA and related atherosclerosis, as well as therapeutic validity for RA.
Based on the growing deal of data concerning the biological activity of flavonoid-rich natural products, the aim of the present study was to explore in vitro the potential anti-tumoral activity of Citrus Bergamia (bergamot) juice (BJ), determining its molecular interaction with cancer cells. Here we show that BJ reduced growth rate of different cancer cell lines, with the maximal growth inhibition observed in neuroblastoma cells (SH-SY5Y) after 72 hs of exposure to 5% BJ. The SH-SY5Y antiproliferative effect elicited by BJ was not due to a cytotoxic action and it did not induce apoptosis. Instead, BJ stimulated the arrest in the G1 phase of cell cycle and determined a modification in cellular morphology, causing a marked increase of detached cells. The inhibition of adhesive capacity on different physiologic substrates and on endothelial cells monolayer were correlated with an impairment of actin filaments, a reduction in the expression of the active form of focal adhesion kinase (FAK) that in turn caused inhibition of cell migration. In parallel, BJ seemed to hinder the association between the neural cell adhesion molecule (NCAM) and FAK. Our data suggest a mechanisms through which BJ can inhibit important molecular pathways related to cancer-associated aggressive phenotype and offer new suggestions for further studies on the role of BJ in cancer treatment.
The aim of this study was to investigate the effect of oleuropein aglycone, an olive oil compound, on the modulation of the inflammatory response in mice subjected to collagen-induced arthritis (CIA). CIA was induced in mice by an intradermal injection of 100 μl of an emulsion containing 100 μg of bovine type II collagen (CII) and complete Freund's adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. Mice developed erosive hind paw arthritis when immunized with CII in CFA. Macroscopic clinical evidence of CIA first appeared as periarticular erythema and edema in the hind paws. The incidence of CIA was 100% by day 28 in the CII-challenged mice and the severity of CIA progressed over a 35-day period with resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint. Treatment with oleuropein aglycone starting at the onset of arthritis (day 25) ameliorated the clinical signs at days 26 to 35 and improved histological status in the joint and paw. The degree of oxidative and nitrosative damage was also significantly reduced in oleuropein aglycone-treated mice. Plasma levels of the proinflammatory cytokines were also significantly reduced by oleuropein aglycone. In addition, we have confirmed the beneficial effects of oleuropein aglycone on an experimental model of CIA in a therapeutic regimen of post-treatment, with treatment started at day 28, demonstrating that oleuropein aglycone exerts an anti-inflammatory effect during chronic inflammation and ameliorates the tissue damage associated with CIA.
Mouse models of rheumatoid arthritis (RA) have proven critical for identifying genetic and cellular mechanisms of the disease. Upon discovering mice in our breeding colony that had spontaneously developed inflamed joints reminiscent of RA, we established the novel IIJ (inherited inflamed joints) strain. The purpose of this study was to characterize the histopathological, clinical, genetic and immunological properties of the disease.
To begin the IIJ strain, an arthritic male mouse was crossed with SJL/J females. Inheritance of the phenotype was then tracked by intercrossing, backcrossing and outcrossing to other inbred strains. The histopathology of the joints and extraarticular organ systems was examined. Serum cytokines and immunoglobulins (Igs) were measured by ELISA and cytometric bead array. Transfer experiments tested whether disease could be mediated by serum alone. Finally, the cellular joint infiltrate and the composition of secondary lymphoid organs were examined by immunohistochemistry and flow cytometry.
After nine generations of intercrossing, the total incidence of arthritis was 33% (304 of 932 mice), with females being affected more than males (38% vs. 28%; P < 0.001). Swelling, most notably in the large distal joints, typically became evident at an early age (mean age of 52 days). In addition to the joint pathology, which included bone and cartilage erosion, synovial hyperproliferation and a robust cellular infiltration of mostly Gr-1(+) neutrophils, there was also evidence of systemic inflammation. IL-6 was elevated in the sera of recently arthritic mice, and extraarticular inflammation was observed histologically in multiple organs. Total serum Ig and IgG1 levels were significantly elevated in arthritic mice, and autoantibodies such as rheumatoid factor and Ig reactive to joint components (collagen type II and joint homogenate) were also detected. Nevertheless, serum failed to transfer disease. A high percentage of double-negative (CD4(-)CD8(-)) CD3(+) TCRα/β(+) T cells in the lymphoid organs of arthritic IIJ mice suggested significant disruption in the T-cell compartment.
Overall, these data identify the IIJ strain as a new murine model of inflammatory, possibly autoimmune, arthritis. The IIJ strain is similar, both histologically and serologically, to RA and other murine models of autoimmune arthritis. It may prove particularly useful for understanding the female bias in autoimmune diseases.
Oxidative stress is believed to be a cause of aging and cardiovascular disorders. In response to inflam-mation or endothelial cell injury, production of reactive oxygen species (ROS) is enhanced in vascular cells. These changes contribute to the initiation of atherosclerosis. Vascular cells possess anti-oxidant systems to protect against oxidative stress, in addition to the redox system. The redox status of pro-tein thiols is important for cellular functions. The Akt signaling pathway exerts effects on survival and apoptosis, and is regulated by the glutathione (GSH)/glutaredoxin (GRX)-dependent redox sys-tem. Sex hormones such as estrogens protect against oxidative stress by protecting the Akt signaling pathway but the physiological role of the extracellular GSH/GRX system has not been clarified, although found an increase in the levels of S-glutathionylated serum proteins in patients with athero-sclerosis obliterans. The results suggested that impaired serum redox potential is a marker of the development vascular dysfunction and estrogen has a possible role in the prevention of atherosclerosis.
Inflammation is a stereotypical physiological response to infections and tissue injury; it initiates pathogen killing as well as tissue repair processes and helps to restore homeostasis at infected or damaged sites. Acute inflammatory reactions are usually self-limiting and resolve rapidly, due to the involvement of negative feedback mechanisms. Thus, regulated inflammatory responses are essential to remain healthy and maintain homeostasis. However, inflammatory responses that fail to regulate themselves can become chronic and contribute to the perpetuation and progression of disease. Characteristics typical of chronic inflammatory responses underlying the pathophysiology of several disorders include loss of barrier function, responsiveness to a normally benign stimulus, infiltration of inflammatory cells into compartments where they are not normally found in such high numbers, and overproduction of oxidants, cytokines, chemokines, eicosanoids and matrix metalloproteinases. The levels of these mediators amplify the inflammatory response, are destructive and contribute to the clinical symptoms. Various dietary components including long chain omega-3 fatty acids, antioxidant vitamins, plant flavonoids, prebiotics and probiotics have the potential to modulate predisposition to chronic inflammatory conditions and may have a role in their therapy. These components act through a variety of mechanisms including decreasing inflammatory mediator production through effects on cell signaling and gene expression (omega-3 fatty acids, vitamin E, plant flavonoids), reducing the production of damaging oxidants (vitamin E and other antioxidants), and promoting gut barrier function and anti-inflammatory responses (prebiotics and probiotics). However, in general really strong evidence of benefit to human health through anti-inflammatory actions is lacking for most of these dietary components. Thus, further studies addressing efficacy in humans linked to studies providing greater understanding of the mechanisms of action involved are required.
Wine has been part of human culture for 6,000 years, serving dietary and socioreligious functions. Its production takes place on every continent, and its chemical composition is profoundly influenced by enological techniques, the grape cultivar from which it originates, and climatic factors. In addition to ethanol, which in moderate consumption can reduce mortality from coronary heart disease by increasing high‐density lipoprotein cholesterol and inhibiting platelet aggregation, wine (especially red wine) contains a range of polyphenols that have desirable biological properties. These include the phenolic acids (p‐coumaric, cinnamic, caffeic, gentisic, ferulic, and vanillic acids), trihydroxy stilbenes (resveratrol and polydatin), and flavonoids (catechin, epicatechin, and quercetin). They are synthesized by a common pathway from phenylalanine involving polyketide condensation reactions. Metabolic regulation is provided by competition between resveratrol synthase and chalcone synthase for a common precursor pool of acyl‐CoA derivatives. Polymeric aggregation gives rise, in turn, to the viniferins (potent antifungal agents) and procyanidins (strong antioxidants that also inhibit platelet aggregation). The antioxidant effects of red wine and of its major polyphenols have been demonstrated in many experimental systems spanning the range from in vitro studies (human low‐density lipoprotein, liposomes, macrophages, cultured cells) to investigations in healthy human subjects. Several of these compounds (notably catechin, quercetin, and resveratrol) promote nitric oxide production by vascular endothelium; inhibit the synthesis of thromboxane in platelets and leukotriene in neutrophils, modulate the synthesis and secretion of lipoproteins in whole animals and human cell lines, and arrest tumour growth as well as inhibit carcinogenesis in different experimental models. Target mechanisms to account for these effects include inhibition of phospholipase A2 and cyclo‐oxygenase, inhibition of phosphodiesterase with increase in cyclic nucleotide concentrations, and inhibition of several protein kinases involved in cell signaling. Although their bioavailability remains to be fully established, red wine provides a more favourable milieu than fruits and vegetables, their other dietary source in humans. J. Clin. Lab. Anal. 11:287–313, 1997. © 1997 Wiley‐Liss, Inc.
Introduction:
Previous studies suggest that people with arthritis have high rates of using complementary and alternative medicine (CAM) approaches for managing their arthritis, in addition to conventional treatments such as prescription medications. However, little is known about the use of CAM by diagnosis, or which forms of CAM are most frequently used by people with arthritis. This study was designed to provide detailed information about use of CAM for symptoms associated with arthritis in patients followed in primary care and specialty clinics in North Carolina.
Methods:
Using a cross-sectional design, we drew our sample from primary care (n = 1,077) and specialist (n = 1,063) physician offices. Summary statistics were used to calculate differences within and between diagnostic groups, practice settings, and other characteristics. Logistic regression models clustered at the site level were used to determine the effect of patient characteristics on ever and current use of 9 CAM categories and an overall category of "any use."
Results:
Most of the participants followed by specialists (90.5%) and a slightly smaller percentage of those in the primary care sample (82.8%) had tried at least 1 complementary therapy for arthritis symptoms. Participants with fibromyalgia used complementary therapies more often than those with rheumatoid arthritis, osteoarthritis, or chronic joint symptoms. More than 50% of patients in both samples used over-the-counter topical pain relievers, more than 25% used meditation or drew on religious or spiritual beliefs, and more than 19% used a chiropractor. Women and participants with higher levels of education were more likely to report current use of alternative therapies.
Conclusion:
Most arthritis patients in both primary care and specialty settings have used CAM for their arthritis symptoms. Health care providers (especially musculoskeletal specialists) should discuss these therapies with all arthritis patients.
RA, a chronic inflammatory disorder of unknown etiology, affects about 1% of the population. Aging is associated with increased free radical production, decreased lean body mass, and increased fat mass; however, these changes are more accelerated with RA. Since resistance training may modulate the production of hormones and mediators that affect body composition and free radical production, the effect of 12 wk of PRT on urinary excretion of 8-hydroxy-2-deoxyguanosine (8 OHdG), a DNA breakdown product which is a marker of free radical production, and oxidative stress was studied in 8 healthy elderly (65-80 y), 8 subjects (25-65 y) with RA, and 8 young (22-30 y) healthy controls Urine from all groups was collected over 48 h at baseline and after training in the elderly and RA groups. Urinary 8-OHdG was measured by ELISA. At baseline, elderly subjects tended (p=0.08) to excrete more 8-OHdG than young subjects (6.3±1.5 vs. 1.8±0.9 ug/24h). Subjects with RA excreted more than Twice as much 8-OHdG (11.6±1.5 ug/24 h) as elderly (p=0.02) and 5 times more than young subjects (p=0.002). Following PRT , there was a trend (p=0.09) toward overall reduction of 8-OHdG production in both the elderly (37%) and RA (34%) subjects. While production of urinary 8-OHdG in the RA group remained higher than in the young group, training diminished the difference between RA and elderly groups. We conclude that subjects with RA have higher oxidative stress as measured by 8-OHdG, but these levels can be reduced with PRT.
AIM: To explore the role of the adaptor molecule in liver regeneration after partial hepatectomy (PH).
METHODS: We used transgenic mice expressing an N-terminal truncated form of MORT1/FADD under the control of the albumin promoter. As previously shown, this transgenic protein abrogated CD95- and CD120a-mediated apoptosis in the liver. Cyclin A expression was detected using Western blotting. ELISA and RT-PCR were used to detect IL-6 and IL-6 mRNA, respectively. DNA synthesis in liver tissue was measured by BrdU staining.
RESULTS: Resection of 70% of the liver was followed by a reduced early regenerative response in the transgenic group at 36 h. Accordingly, 36 h after hepatectomy, cyclin A expression was only detectable in wild-type animals. Consequently, the onset of liver mass restoration was retarded as measured by MRI volumetry and mortality was significantly higher in the transgenic group.
CONCLUSION: Our data demonstrate for the first time an involvement of the death receptor molecule MORT1/FADD in liver regeneration, beyond its well described role as part of the intracellular death signaling pathway.
Background
Bergamot essential oil (BEO) is obtained from the fruit peel of Citrus bergamia (bergamot), a small tree cultivated almost exclusively along the southern coast of the Calabria region of Italy. BEO is appreciated for its organoleptic properties and is widely used in the manufacture of perfumes. The goals of our study were to investigate the mechanisms underlying the antiproliferative effects of BEO and to identify the compounds mainly responsible for its inhibition of SH-SY5Y cell growth.
Methods
Five BEO extractive fractions (BEOs) differing in chemical composition were used. Cell proliferation was determined by MTT and cell count assays. The trypan blue exclusion test and annexin V/PI staining were done to assess their cytotoxic activity. Genotoxic effects were detected by the comet assay. The cell cycle was also analysed cytofluorimetrically. Reactive oxygen species and Δψm were measured fluorimetrically. Western blotting analyses for some apoptosis-related proteins were carried out.
Findings
Treatment of SH-SY5Y cells with some types of BEOs decreased rate of cell growth by a mechanism correlated to both apoptotic and necrotic cell death. Coloured BEOs act by increasing generation of reactive oxygen species, responsible for the drop in m, and modulating p38 and ERK1/2 MAPKs, p53, Bcl-2 and Bax signalling pathways. Finally, we identified bergamottin and 5-geranyloxy-7-methoxycoumarin as the bioactive molecules that play a pivotal part in the antiproliferative effects exerted by coloured BEOs.
Interpretation
Our study provides novel insights into the antiproliferative effects of BEO, which could be exploited in the context of multitarget pharmacological strategies.
The goals were to investigate the mechanisms underlying the antiproliferative effects of bergamot essential oil (BEO) and to identify the compounds mainly responsible for its SH-SY5Y cells growth rate inhibition.
Five BEO extractive fractions (BEOs) differing in their chemical composition were used. Cell proliferation was determined by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and cell count assays. Trypan blue exclusion test and Annexin V/PI staining were performed to assess their cytotoxic activity. Genotoxicity was detected by comet assay. The cell cycle was checked cytofluorimetrically. Reactive oxygen species (ROS) and Δψm were measured fluorimetrically. Western blotting analyses for some apoptosis-related proteins were carried out.
Treatment of SH-SY5Y cells with some types of BEOs decreased cell growth rate by a mechanism correlated to both apoptotic and necrotic cell death. Coloured BEOs act by increasing ROS generation, responsible for the drop in Δψm, and modulate p38 and extracellular signal-regulated kinases (ERK ½) mitogen-activated protein kinases, p53, Bcl-2 and Bax signalling pathways. Finally, we identify bergamottin and 5-geranyloxy-7-methoxycoumarin as the bioactive molecules that could play a pivotal role in the antiproliferative effects exerted by coloured BEOs.
Our study provides novel insights into the field of the antiproliferative effects of BEO, which could be exploited in the context of a multitarget pharmacological strategy.
© 2015 Royal Pharmaceutical Society.
Resveratrol (3, 5, 4'-trihydroxystilbene) is a phytoalexin contained in a variety of plants, such as grapes, berries and especially in the dried roots of Polygonum cuspidatum Sieb. et Zucc. It has been shown to exhibit anti-oxidative and anti-inflammation activity, and to reverse the effects of aging. Its ability to suppress cell proliferation, induce apoptosis and suppress the metastasis and invasion in a number of cell lines has prompted a large interest from people for its use as an anti-tumor component. In this review, evidence of resveratrol's anti-tumor effects and molecular mechanisms are recapitulated. First, we present the anti-apoptosis, anti-invasion/metastasis and anti-inflammation effect of resveratrol; second, the main signaling pathways involved in these activities are described and summarized with the studies of different tumors involved. Resveratrol not only induces apoptosis of tumor cells through intrinsic/extrinsic pathways and cell cycle arrest, but also inhibits the invasion and metastasis abilities of tumors via modulating collagen degradation-related molecular targets. Altogether, the present findings suggest the anti-tumor potential of resveratrol against various types of cancers.
Research on antioxidants proceeds at full speed after a partial decline of public interest, when claims on effectiveness of mega doses of vitamin C proved unfounded. The main role of antioxidants is to liquidate the uncontrolled production of reactive oxygen species (ROS) that is being linked to pathogenesis of cardiovascular disease (CVD), malignancy, diabetes type 2, mechanism of infection, fibrogenesis and some neurological disorders. This review summarizes the most recent reports on antioxidants, published since 2010. Follow up data on vitamins C and E focus on their potential for immune modulation and on endothelial nitric oxide bioavailability. Previously well established antioxidants carotenoids and polyphenols are still much in scientific interest. Interestingly, several antioxidants (for example rasveratrol and feruloylnoradrenaline) are generated in infected or injured plants. An intensive attention is directed to resveratrol. This compound, in addition to antioxidation, stimulates nitric oxid production, protects endothelial cells from oxidative functional damage, lowers platelet aggregation and directly inhibits cyclic adenosine monophosphate-specific phosphodiesterases. Recently discovered feruloylnoradrenaline in microbially infected tomatoes is reported to have 14 times the antioxidant power of resveratrol. With all this new information, it is important to point out the prevailing opinion that additional supplements of antioxidants are not needed, as long as the organism has adequate stores of antioxidants and the diet is normal in composition and in quantity (Fig. 3, Ref. 34).
reactive oxygen species (ROS), antioxidants, vitamin C and E, carotenoids, polyphenols, immune modulation, nitric oxide (NO), bioavailability, resveratrol, feruloylnoradrenaline.
The beneficial properties of the flavonoid fraction of bergamot juice (BJe) have been raising interest and have been the subject of recent studies, considering the potentiality of its health promoting substances. Flavonoids have demonstrated radical-scavenging and anti-inflammatory activities. The aim of the present study was to examine the effects of BJe in mice subjected to experimental colitis.
Colitis was induced in mice by intracolonic instillation of dinitrobenzene sulfonic acid (DNBS). BJe was administered daily orally (at 5, 10 and 20 mg/kg).
Four days after DNBS administration, colon nuclear factor NF-κB translocation and MAP kinase phospho-JNK activation were increased as well as cytokine production such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β. Neutrophil infiltration, by myeloperoxidase (MPO) activity, in the mucosa was associated with up-regulation of adhesion molecules (ICAM-1 and P-selectin). Immunohistochemistry for nitrotyrosine and poly ADP-ribose (PAR) also showed an intense staining in the inflamed colon. Treatment with BJe decreased the appearance of diarrhea and body weight loss. This was associated with a reduction in colonic MPO activity. BJe reduced nuclear NF-κB translocation, p-JNK activation, the pro-inflammatory cytokines release, the appearance of nitrotyrosine and PAR in the colon and reduced the up-regulation of ICAM-1 and P-selectin. In addition, colon inflammation was also associated with apoptotic damage. Treatment with BJe caused a decrease of pro-apoptotic Bax expression and an increase of anti-apoptotic Bcl-2 expression.
The results of this study suggested that administration of BJe induced, partly specified, anti-inflammatory mechanisms, which potentially may be beneficial for the treatment of IBD in humans.
Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Rheumatoid Arthritis (RA) is a chronic inflammatory disease affecting synovial joints. Tumor necrosis factor (TNF) α is a key component of RA pathogenesis and blocking this cytokine is the most common strategy to treat the disease. Though TNFα blockers are very efficient, one third of the RA patients are unresponsive or present side effects. Therefore, the development of novel therapeutic approaches is required. RA pathogenesis is characterized by the hyperplasia of the synovium, closely associated to the pseudo-tumoral expansion of fibroblast-like synoviocytes (FLS), which invade and destroy the joint structure. Hence, depletion of RA FLS has been proposed as an alternative therapeutic strategy. The TNF family member Fas ligand (FasL) was reported to trigger apoptosis in FLS of arthritic joints by binding to its receptor Fas and therefore suggested as a promising candidate for targeting the hyperplastic synovial tissue. However, this cytokine is pleiotropic and recent data from the literature indicate that Fas activation might have a disease-promoting role in RA by promoting cell proliferation. Therefore, a FasL-based therapy for RA requires careful evaluation before being applied. In this review we aim to overview what is known about the apoptotic and non-apoptotic effects of Fas/FasL system and discuss its relevance in RA.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Rheumatoid arthritis (RA) remains a formidable clinical challenge. This is despite remarkable recent advances in our understanding of pathogenesis and the introduction of a variety of novel agents, particularly biologic therapeutics that are potent inhibitors of extracellular immune pathways. Whereas the latter have brought substantial improvements in efficacy and thus outcomes, there remain significant numbers of non- or partial responders to current standard of care. The discovery of key intracellular pathways, particularly kinases that subserve the function of these pivotal cytokine and immune cell receptors implicated in RA pathogenesis, has facilitated the advent of a new phase of RA drug development. Thus, a range of kinase inhibitors has entered clinical trials and one agent has been licenced for use in some regions. Herein we summarise the chequered history of kinase inhibitor development in RA, describing successes and failures alike, and thereafter examine future trends in this exciting field.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Colorectal cancer (CRC) is a leading cause of cancer mortality in the industrialized world, second to lung cancer. A lot of evidences underline that a diet rich in fruits and vegetables may reduce the risk of some types of cancer among CRC. In this study we demonstrate that Citrus bergamia juice extracts (BJe) reduces CRC cell growth by multiple mechanisms. Lower BJe concentrations inhibit MAPKs pathway and altering apoptosis-related proteins, that in turn induced cell cycle arrest and apoptosis in HT-29 cells. Instead, high concentration of BJe induced oxidative stress causing DNA damage. Our study highlights the role of BJe as modulator of cell apoptosis in CRC cells and strengthen our previous hypothesis that the flavonoid fraction of bergamot juice may play a role as anti-cancer drug.
Background:
This study aims to investigate the effect of antioxidants supplement on clinical outcomes and antioxidant parameters in rheumatoid arthritis (RA).
Methods:
The pre-post study was conducted on 40 female patients with RA in 12 weeks that taken daily one Selenplus capsule contained 50 μg selenium, 8 mg zinc, 400 μg vitamin A, 125 mg vitamin C, and 40 mg vitamin E. About 5 mL venous blood sample was taken from all participants and disease activity score (DAS) was determined by DAS-28 formula and high-sensitive C-reactive protein (hs-CRP). Glutathione peroxidase (GPX) and superoxide dismutase (SOD) were measured by spectrophotometric kit and catalase (CAT) was measured by Abei method. Total antioxidant capacity (TAC) was determined by spectrophotometric kit. Distribution of the variables was assessed using histogram with normal curve as well as Kolmogorov-Smirnov test and data were analyzed with paired t-test for differences between pre-post data using SPSS software version 13.5.
Conclusions:
Our findings showed that antioxidants may improve disease activity significantly, but it did not affect the number of painful and swollen joints and increased erythrocyte antioxidant levels. Antioxidants may be useful for controlling of clinical outcomes and oxidative stress in RA.
Aim of the studyAlstonia scholaris (Family: Apocynaceae) is a medicinal plant which is indicated for the treatment of various diseases including arthritis in folklore medicine. The purpose of this study is to investigate the antiarthritic activity and in vivo antioxidant role of A. scholaris leaves in animal models.Materials and methodsThe ethanol extract of A. scholaris leaves (EEAS) was tested against Freund's Complete Adjuvant (FCA) induced arthritic rats. Arthritis assessment and body weight were measured daily till day 28 whereas nociceptive threshold was measured once in 2 days. On day 28, the animals were anaesthetized, synovial fluid withdrawn and leukocyte concentration was determined. The animals were sacrificed, synovial tissue was extracted and estimated for the myeloperoxide, malonaldehyde, glutathione, glutathione peroxidase and superoxide dismutase. Effect of EEAS on ethanol and sodium salicylate induced gastropathy was also studied.ResultsEEAS significantly decreased the arthritis which was evident with arthritis index, body weight and leukocyte infiltration. EEAS significantly reduced gastric lesion indices and gastric juice secretion. It also significantly decreased the levels of lipid peroxidation and myeloperoxide in the articular tissue, whereas it significantly increased the antioxidant enzymes glutathione, glutathione peroxidase and superoxide dismutase.Conclusion
The present study is suggestive that EEAS has prominent antiarthritic activity which may be attributed to its analgesic, anti-inflammatory, immunosuppressant and antioxidant activities.
Citrus extracts, particularly bergamot essential oil (BEO) and its fractions, have been found to exhibit anticancer efficacy. However, the poor water solubility, low stability and limited bioavailability have prevented the use of BEO in cancer therapy. To overcome such drawbacks, we formulated BEO liposomes that improved the water solubility of the phytocomponents and increased their anticancer activity in vitro against human SH-SY5Y neuroblastoma cells. The results warrant further investigation of BEO liposomes for in vivo applications.
The effect of Semecarpus anacardium Linn. nut extract (SA) on the level of Lipid peroxides (LPO) and activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH) in the lymphocytes and lymphoid organs, namely spleen and thymus of adjuvant induced arthritic rats, were investigated. The results were compared with normal and untreated arthritic rats. The levels of reactive oxygen species (ROS), namely Hydroxy radical, Superoxide radical, and H2O2 were also measured in spleen, thymus, and lymphocytes of control and experimental animals. Biochemical markers of inflammation namely C-reactive protein (CRP) level and Erythrocyte sedimentation rate (ESR) were determined. Anti-arthritic profile was evaluated from the changes in the paw edema and arthritic scores of arthritic and drug-treated rats. A significant increase in the level of LPO, ROS and decreased levels of antioxidant enzymes in arthritic rats were observed. On treatment with the drug, the above changes were reverted back to near normal levels. The increment in CRP level and ESR observed in arthritic animals were found to be significantly restored in SA treated rats. There were no significant changes in sole drug-administered normal rats. Semecarpus anacardium Linn. nut extract significantly decreased the paw edema and arthritic score in arthritic rats on administration, whereas in untreated arthritic rats, there was a significant edema in the hind paw.
The aim of this study was to explore the effect of the essential oil of Citrus bergamia Risso (bergamot) on mouse blood vessels and to analyse the mechanism of this effect from a pharmacological perspective.
We investigated the effect of bergamot essential oil (BEO) on vascular tonus during contraction of mouse aorta induced by prostaglandin F2α (PGF2α ) or noradrenaline (norepinephrine).
In mouse aortic rings, BEO (0.01, 0.1 and 0.2% v/v) reduced contraction in a dose-dependent manner, and relaxed the vascular tonus induced by PGF2α . No significant difference in the extent of vasorelaxation induced by 0.1% (v/v) BEO was evident when rings with intact endothelium and endothelium-denuded rings were compared. When aortic rings were suspended in a medium that was Ca(2+) -free but contained 80 mm KCl, addition of CaCl2 (1, 2.5 or 5 mm) induced contraction in a dose-dependent manner. However, addition of Ca(2+) after incubation of the rings with BEO strongly suppressed CaCl2 -induced contraction. Further, the K(+) -channel blocker tetraethylammonium chloride partially blocked BEO-induced vasorelaxation.
Our findings suggest that BEO may induce endothelium-independent vasorelaxation by regulating the vascular tone of smooth muscle. Activation of K(+) channels and inhibition of Ca(2+) influx may be involved in vasorelaxation of mouse aorta elicited by BEO.
Resveratrol (trans-3,4'-trihydroxystilbene), a natural phytoalexin, possesses anti-inflammatory, anti-proliferative, and immunomodulatory properties and has the potential for treating inflammatory disorders. The present study was designed to investigate the effects of resveratrol on TNF-α-induced inflammatory cytokines production of IL-1β and MMP3 in Rheumatoid arthritis (RA) Fibroblast-like synoviocytes (FLS) and further to explore the role of PI3K/Akt signaling pathway by which resveratrol modulates those cytokines production. The levels of IL-1β, MMP-3 in cultural supernatants among groups were measured by enzyme-linked immunosorbent assay. Messenger RNA expression of IL-1β and MMP-3 in RA FLS was analyzed using a reverse transcription-polymerase chain reaction. Western blot analysis was used to detect proteins expression in RA FLS intervened by resveratrol. Resveratrol inhibited both mRNA and proteins expressions of IL-1β and MMP-3 on RA FLS in a dose-dependent manner. Resveratrol also decreased significantly the expression of phosphorylated Akt dose dependently. Activation of PI3K/Akt signaling pathway exists in TNF-α-induced production of IL-1β and MMP3 on RA FLS, which is hampered by PI3K inhibitor LY294002. Immunofluorescence staining showed that TNF-α alone increased the production of P-Akt, whereas LY294002 and 50 μM resveratrol suppressed the TNF-α-stimulated expression of P-Akt. Resveratrol attenuates TNF-α-induced production of IL-1β and MMP-3 via inhibition of PI3K-Akt signaling pathway in RA FLS, suggesting that resveratrol plays an anti-inflammatory role and might have beneficial effects in preventing and treating RA.
Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder that may affect many tissues and organs. Without treatment, inflammation leads to cartilage damage, bone erosions, joint destruction, and impaired movement. Because of the limited success of disease-modifying anti-rheumatic drugs, the exploration of new anti-rheumatic drugs with high efficacy and less toxicity is eagerly needed. Genistein, the major active compound from soybean, has received much attention due to its potential beneficial effects on some of the degenerative diseases. It has been found that genistein has anti-inflammatory, antiangiogenesis, antiproliferative, antioxidant, immunomodulatory, pain relief, and joint protection properties. Hence, significant advances have been made, both by in vitro and in vivo studies showing that genistein is a promising agent for RA treatment.
Bergamot oil (Citrus bergamia) is mainly employed in the perfumery and cosmetic industries and also, in a smaller amount, in the pharmaceutical and food industries, for its fragrant notes, fixative and antimicrobial properties. Due to the presence of some phototoxic compounds in its composition, it has become a common practice to reduce or sometimes completely eliminate these substances before using the oil. Samples of treated bergamot oils have been investigated in this study (terpeneless, furocoumarin- and bergapten-free) by means of GC–FID, GC–MS, enantio-GC–FID and HPLC. The results are reported in terms of either peak areas or g/100 g. Some considerations are made in order to discuss the technologies used for treating bergamot oil. Copyright © 2009 John Wiley & Sons, Ltd.
Objective
The continuous presence of bacteria or their degraded antigens in the synovium may be involved in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to determine the presence of bacterial nucleic acids and bacterial cell wall constituents in the joints of patients with RA and other forms of arthritis.Methods
Joint samples were obtained from patients with RA (n = 26), septic arthritis (n = 2), inflammatory osteoarthritis (n = 5), and gout (n = 6), and joint trauma (n = 1). Universal 16S-ribosomal RNA primers were used to detect the presence of bacterial DNA in these samples, using stringent regimens for sample collection and molecular microbiologic analysis. Automated sequencing and comparative data analysis were performed to identify the species. The presence of bacterial peptidoglycan–polysaccharide complexes in synovial tissue was detected by immunohistologic analysis with a specific antibody.ResultsThe bacterial species cultured from the synovium could be identified in both of the patients with septic arthritis. DNA amplicons were also detected in the synovial fluid and/or tissue samples from 5 patients with RA and 2 patients with crystal-induced arthritis; these originated from multiple bacterial species. Staining for peptidoglycan–polysaccharide complexes was positive in the synovial tissue of both patients with septic arthritis, 16 with RA, 4 with inflammatory osteoarthritis, 4 with crystal-induced arthropathy, and 1 with joint trauma. The staining was mainly found in cells in the synovial sublining, including macrophages.Conclusion
The results indicate that bacterial DNA and bacterial cell wall constituents are retained in the joints of some patients with arthritis, where they might enhance synovial inflammation.
Plants in the Mediterranean basin, such as vine and olive trees, have developed an array of antioxidant defences to protect themselves from environmental stress. Accordingly, the incidence of coronary heart disease and certain cancers is lower in the Mediterranean area, where olive oil is the dietary fat of choice. As opposed to other vegetable oils, extra virgin olive oil, which is obtained by physical pressure from a whole fruit, is rich in phenolic components that are responsible for the particular stability of the oil. We have investigated the scavenging actions of some olive oil phenolics, namely hydroxytyrosol and oleuropein, with respect to superoxide anion generation, neutrophils respiratory burst, and hypochlorous acid. The low EC50s indicate that both compounds are potent scavengers of superoxide radicals and inhibitors of neutrophils respiratory burst: whenever demonstratedin vivo,these properties may partially explain the observed lower incidence of CHD and cancer associated with the Mediterranean diet.
Rheumatoid arthritis (RA) is characterized as a chronic inflammatory disease in joints and concomitant destruction of cartilage and bone. Cartilage extracellular matrix components, such as type II collagen and aggrecan are enzymatically degraded by matrix metalloproteinases (MMPs) and aggrecanases in RA. Currently, treatments targeting cytokines, including anti-tumor necrosis factor (TNF) α antibodies, soluble TNF receptor, anti-interleukin (IL)-6 receptor antibody, and IL-1 receptor antagonist, are widely used for treating RA in addition to antiantiinflammatory agents and disease-modifying antirheumatic drugs (DMARDs), such as inflmethotrexate, but these treatments have some problems, especially in terms of cost and the increased susceptibility of patients to infection in addition to the existence of low-responders to these treatments. Therefore, therapeutics that can be safely used for an extended period of time would be preferable. Complementary and alternative medicines including traditional Chinese medicines (TCM) have been used for the arthritic diseases through the ages. Recently, there are many reports concerning the anti-arthritic action mechanisms of TCM-based herbal formulas and crude herbal extracts or isolated ingredients. These natural herbal medicines are thought to moderately improve RA, but they exert various actions for the treatment of RA. In this review, the current status of the mechanism exploration of natural compounds and TCM-based herbal formulas are summarized, focusing on the protection of cartilage destruction in arthritic diseases including RA and osteoarthritis.
The effects of bergamot essential oil (BEO; Citrus bergamia, Risso) on excitotoxic neuronal damage was investigated in vitro.
The study was performed in human SH-SY5Y neuroblastoma cells exposed to N-methyl-D-aspartate (NMDA). Cell viability was measured by dye exclusion. Reactive oxygen species (ROS) and caspase-3 activity were measured fluorimetrically. Calpain I activity and the activation (phosphorylation) of Akt and glycogen synthase kinase-3beta (GSK-3beta) were assayed by Western blotting.
NMDA induced concentration-dependent, receptor-mediated, death of SH-SY5Y cells, ranging from 11 to 25% (0.25-5 mM). Cell death induced by 1 mM NMDA (21%) was preceded by a significant accumulation of intracellular ROS and by a rapid activation of the calcium-activated protease calpain I. In addition, NMDA caused a rapid deactivation of Akt kinase and this preceded the detrimental activation of the downstream kinase, GSK-3beta. BEO (0.0005-0.01%) concentration dependently reduced death of SH-SY5Y cells caused by 1 mM NMDA. In addition to preventing ROS accumulation and activation of calpain, BEO (0.01%) counteracted the deactivation of Akt and the consequent activation of GSK-3beta, induced by NMDA. Results obtained by using specific fractions of BEO, suggested that monoterpene hydrocarbons were responsible for neuroprotection afforded by BEO against NMDA-induced cell death.
Our data demonstrate that BEO reduces neuronal damage caused in vitro by excitotoxic stimuli and that this neuroprotection was associated with prevention of injury-induced engagement of critical death pathways.
Oxygen metabolism has an important role in the pathogenesis of rheumatoid arthritis. Reactive oxygen species (ROS) produced in the course of cellular oxidative phosphorylation, and by activated phagocytic cells during oxidative bursts, exceed the physiological buffering capacity and result in oxidative stress. The excessive production of ROS can damage protein, lipids, nucleic acids, and matrix components. They also serve as important intracellular signaling molecules that amplify the synovial inflammatory-proliferative response. Repetitive cycles of hypoxia and reoxygenation associated with changes in synovial perfusion are postulated to activate hypoxia-inducible factor-1alpha and nuclear factor-kappaB, two key transcription factors that are regulated by changes in cellular oxygenation and cytokine stimulation, and that in turn orchestrate the expression of a spectrum of genes critical to the persistence of synovitis. An understanding of the complex interactions involved in these pathways might allow the development of novel therapeutic strategies for rheumatoid arthritis.
Puerarin is a major active ingredient extracted from the root of P. lobata, a traditional Chinese herb, and possesses anti-oxidative and anti-inflammatory activities. However, the low oral bioavailability of puerarin limits its further application. Therefore, we synthesized tetraacetyl puerarin (4AC) through acetylation to improve its liposolubility and bioavailability. In the present investigations, we tested the anti-oxidative and TNF-α suppressive activity of 4AC in lipopolysaccharide (LPS)-induced RAW264.7 macrophages and bovine type II collagen-induced arthritic (CIA) rats. The results showed that 4AC retained the bioactivity of puerarin. And 4AC significantly increased the activity of SOD and reduced the level of MDA both in vitro and in vivo. It also improved the level of GSH-PX and the total antioxidant capacity in vivo. Furthermore, it dramatically decreased TNF-α level in the cultured supernatant of RAW264.7 cells treated with LPS and in the serum of CIA rats. These initial results indicated that 4AC had a potential therapeutic effect on CIA rats through an anti-oxidative and TNF-α suppressive activity. In addition, the molecular mechanism of anti-oxidation of 4AC was explored by testing the MAPKs/NF-κB signaling pathway. The results showed that 4AC significantly inhibited NF-κB expression and down-regulated the levels of p-ERK and p-JNK in LPS-activated RAW264.7 cells. These results indicated that 4AC had bioactive anti-oxidative effects and suggest the potential value of 4AC for the treatment of rheumatoid arthritis.
Hepatocellular carcinoma (HCC), one of the most common cancers in the world, is a leading cause of cancerrelated mortality. HCC develops most frequently in the background of oxidative stress and chronic hepatic inflammation due to viral infections, alcohol abuse as well as exposure to environmental and dietary carcinogens. As the prognosis of HCC is extremely poor and mostly unresponsive to current chemotherapeutic treatment regimens, novel preventive approaches like chemoprevention are urgently needed. We have recently found that resveratrol, a dietary polyphenol present in grapes, berries, peanuts as well as red wine, prevents diethylnitrosamine (DENA)-initiated hepatocarcinogenesis in rats through suppression of inflammation and oxidative stress. As cytokines are considered to be important mediators of inflammation, the objective of the present study was to investigate the effects of resveratrol on hepatic cytokines during DENA-initiated hepatocarcinogenesis in rats. Liver samples were harvested from our previous study in which resveratrol (50, 100 and 300 mg/kg) was found to exert a chemopreventive action against rat liver tumorigenesis induced by DENA. The levels of proinflammatory cytokines, namely tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin- 6 (IL-6), were measured using enzyme-linked immunosorbent assays. The mRNA expression of these cytokines was studied by reverse transcriptase-polymerase chain reaction for comparison. Resveratrol treatment reversed the DENAinduced alteration of the level and expression of hepatic TNF-α, IL-1β and IL-6. From the current results in conjunction with our previous findings, it can be concluded that resveratrol-mediated chemoprevention of rat liver carcinogenesis is related to alteration of proinflammatory cytokines.
Bergamot essential oil (BEO), Citrus aurantium subsp. bergamia (Risso) Wright & Arn. (Rutaceae), is used widely in aromatherapy to reduce stress and anxiety despite limited scientific evidence. A previous study showed that BEO significantly increased gamma-aminobutyric acid levels in rat hippocampus, suggesting potential anxiolytic properties. The aim of this study was to investigate the effect of BEO (1.0%, 2.5% and 5.0% w/w) administered to rats on both anxiety-related behaviours (the elevated plus-maze (EPM) and hole-board tests) and stress-induced levels of plasma corticosterone in comparison with the effects of diazepam. Inhalation of BEO (1% and 2.5%) and injection of diazepam (1 mg/kg, i.p.) significantly increased the percentage of open arm entries on the EPM. The percentage time spent in the open arms was also significantly enhanced following administration of either BEO (2.5% and 5%) or diazepam. Total arm entries were significantly increased with the highest dose (5%), suggesting an increase in locomotor activity. In the hole-board test, 2.5% BEO and diazepam significantly increased the number of head dips. 2.5% BEO and diazepam attenuated the corticosterone response to acute stress caused by exposure to the EPM. In conclusion, both BEO and diazepam exhibited anxiolytic-like behaviours and attenuated HPA axis activity by reducing the corticosterone response to stress.
Green tea's active ingredient, epigallocatechin 3-gallate (EGCG), has gained significant attention among scientists and has been one of the leading plant-derived molecules studied for its potential health benefits. In the present review I summarize the findings from some of the most significant preclinical studies with EGCG in arthritic diseases. The review also addresses the limitations of the dose, pharmacokinetics, and bioavailability of EGCG in experimental animals and findings related to the EGCG-drug interaction. Although these findings provide scientific evidence of the anti-rheumatic activity of EGCG, further preclinical studies are warranted before phase clinical trials could be initiated with confidence for patients with joint diseases.
To review efficacy studies of antioxidant and antiinflammatory dietary supplements used to manage osteoarthritis (OA) and rheumatoid arthritis (RA) and make conclusions about their place in therapy. Glucosamine, chondroitin, and methyl sulfonyl methane were excluded.
A literature search was conducted using MEDLINE (1996 through January 2009), EMBASE, Cochrane Library, Natural Medicines Comprehensive Database, and Natural Standard, with bibliographic review of relevant articles. Cited studies from before our search range were included if they represented the only published human data available. Search words included "antioxidant," "antiinflammatory," "cat's claw," "ginger," "fish oil," "omega-3," "turmeric," "vitamin E," "vitamin C," "Baikal skullcap," "barberry," "Chinese goldthread," "green tea," "Indian holy basil," "hu zhang,"oregano," and"rosemary."
Efficacy studies published in English were included provided they evaluated the dietary supplements in patients with OA or RA.
Our search strategy yielded 16 clinical studies (11 randomized, placebo-controlled clinical trials, three crossover trials, one case-controlled study, and one open-label study) in addition to one meta-analysis and one review article.
Three studies support cat's claw alone or in combination for OA, and two studies support omega-3 fatty acids for the treatment of RA. We cannot recommend use of vitamin E alone; vitamins A, C, and E in combination; ginger; turmeric; or Zyflamend (New Chapter, Brattleboro, Vermont) for the treatment of OA or RA or omega-3 fatty acids for OA. Whether any of these supplements can be effectively and safely recommended to reduce nonsteroidal antiinflammatory drug or steroid usage is unclear and requires more high-quality research.
Glycopeptide-resistant Enterococcus (GRE) is an important healthcare-acquired infection (HCAI) which costs the healthcare service many millions of pounds worldwide. In this study, lemon (Citrus limon), sweet orange (Citrus sinensis) or bergamot (Citrus bergamia) essential oils (EO) and their vapours, alone and in combination, are tested for their antimicrobial activity against vancomycin-resistant and vancomycin-sensitive strains of E. faecium and E. faecalis. A blend of 1:1 (v/v) orange and bergamot EO was the most effective of the oils and/or blends tested with a minimum inhibitory concentration (MIC), at 25 degrees C and pH 5.5, of 0.25-0.5% (v/v) and a minimum inhibitory dose (MID) of 50 mg/L, at 50 degrees C at pH 7.5, when viable counts reduced by 5.5-10 log10 colony forming units (cfu)/mL, suggesting that this blend of citrus oils is effective under a range of conditions for inhibiting the growth and survival of E. faecalis, E. faecium and VRE.
Numerous dietary compounds, ubiquitous in fruits, vegetables and spices have been isolated and evaluated during recent years for their therapeutic potential. These compounds include flavonoid and non-flavonoid polyphenols, which describe beneficial effects against a variety of ailments. The notion that these plant products have health promoting effects emerged because their intake was related to a reduced incidence of cancer, cardiovascular, neurological, respiratory, and age-related diseases. Exposure of the body to a stressful environment challenges cell survival and increases the risk of chronic disease developing. The polyphenols afford protection against various stress-induced toxicities through modulating intercellular cascades which inhibit inflammatory molecule synthesis, the formation of free radicals, nuclear damage and induce antioxidant enzyme expression. These responses have the potential to increase life expectancy. The present review article focuses on curcumin, resveratrol, and flavonoids and seeks to summarize their anti-inflammatory, cytoprotective and DNA-protective properties.
Chronic inflammation is being shown to be increasingly involved in the onset and development of several pathological disturbances such as arteriosclerosis, obesity, diabetes, neurodegenerative diseases and even cancer. Treatment for chronic inflammatory disorders has not been solved, and there is an urgent need to find new and safe anti-inflammatory compounds. Flavonoids belong to a group of natural substances occurring normally in the diet that exhibit a variety of beneficial effects on health. The anti-inflammatory properties of flavonoids have been studied recently, in order to establish and characterize their potential utility as therapeutic agents in the treatment of inflammatory diseases. Several mechanisms of action have been proposed to explain in vivo flavonoid anti-inflammatory actions, such as antioxidant activity, inhibition of eicosanoid generating enzymes or the modulation of the production of proinflammatory molecules. Recent studies have also shown that some flavonoids are modulators of proinflammatory gene expression, thus leading to the attenuation of the inflammatory response. However, much work remains to be done in order to achieve definitive conclusions about their potential usefulness. This review summarizes the known mechanisms involved in the anti-inflammatory activity of flavonoids and the implications of these effects on the protection against cancer and cardiovascular disease.
Previous studies suggest that people with arthritis have high rates of using complementary and alternative medicine (CAM) approaches for managing their arthritis, in addition to conventional treatments such as prescription medications. However, little is known about the use of CAM by diagnosis, or which forms of CAM are most frequently used by people with arthritis. This study was designed to provide detailed information about use of CAM for symptoms associated with arthritis in patients followed in primary care and specialty clinics in North Carolina.
Using a cross-sectional design, we drew our sample from primary care (n = 1,077) and specialist (n = 1,063) physician offices. Summary statistics were used to calculate differences within and between diagnostic groups, practice settings, and other characteristics. Logistic regression models clustered at the site level were used to determine the effect of patient characteristics on ever and current use of 9 CAM categories and an overall category of "any use."
Most of the participants followed by specialists (90.5%) and a slightly smaller percentage of those in the primary care sample (82.8%) had tried at least 1 complementary therapy for arthritis symptoms. Participants with fibromyalgia used complementary therapies more often than those with rheumatoid arthritis, osteoarthritis, or chronic joint symptoms. More than 50% of patients in both samples used over-the-counter topical pain relievers, more than 25% used meditation or drew on religious or spiritual beliefs, and more than 19% used a chiropractor. Women and participants with higher levels of education were more likely to report current use of alternative therapies.
Most arthritis patients in both primary care and specialty settings have used CAM for their arthritis symptoms. Health care providers (especially musculoskeletal specialists) should discuss these therapies with all arthritis patients.