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A Critical Review on Pear Fruit’s Polyphenols and its Chlorogenic acid: Composition, Bioavailability, and Pharmacological Potential
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To make full use of young pear fruit thinned from the trees for optimal fruit load during cultivation, this study explored the nutritional diversity in young fruit of seventy-nine different pear varieties, focusing on their bioactive compounds. Our results showed significant variability in total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activity of pear varieties. The TPC values ranged from 0.317 ± 0.051 mg GAE/g to 0.0054 ± 0.021 mg GAE/g FW; the highest TPC value has been found in Lixian new bapan, mulberry pear, and red pear varieties, while the lowest value has found in yaqing, weining fragrant pear and apple pear varieties. Similarly, the TFC values demonstrated substantial differences, with Lijiang sesame pear (0.16 ± 0.01), Lixian new bapan (0.13 ± 0.04), and Xiangyuan (0.13 ± 0.02) pear exhibiting the highest flavonoid content. Antioxidant activity, assessed using the Ferric Reducing Antioxidant Power (FRAP) assay, varied significantly, indicating diverse phytochemical profiles across the varieties. HPLC analysis showed that the high value of bioactive compounds is chlorogenic acid (17.86 ± 4.5), arbutin (2.57 ± 0.3), Epicatechin (1.57 ± 0.27), rutin (0.04 ± 0.03) and ferulic acid (0.30 ± 0.04) found in the mulberry pear variety. Molecular docking studies revealed that chlorogenic acid, Epi-catechin, Rutin, and Ferulic acid showed strong affinity towards proteins such as Nrf2, NF-κB, and iNOS, suggesting potential health benefits. These findings provide valuable insights for breeders, nutritionists, and the food industry, emphasizing the importance of the nutritional quality of pear fruits, and their recycling utilization in the production practice.
Coffee bean extract (Chlorogenic Acid), Disease Modifying Anti-Rheumatoid Drug (DMARD) agent in the treatment of Rheumatoid Arthritis is believed to inhibit the production of TNF-α by blocking the cell associated conversion of TNF Precursor to mature proteins this, halting the proliferation of synovitis.CGA inhibit the proliferation of the fibroblast‑like synoviocyte cell line (RSC‑364), stimulated by interleukin (IL)‑6, through inducing apoptosis. CGA inhibit the inflammatory proliferation of RSC‑364 cells mediated by IL‑6 through inducing apoptosis. CGA was also able to suppress the expression levels of key molecules in the JAK/STAT and NF‑κB signaling pathways, and inhibit the activation of these signaling pathways in the inflammatory response through IL‑6‑mediated signaling, thereby resulting in the inhibition of the inflammatory proliferation of synoviocytes. The aim of the present study was to formulate and evaluate coffee bean extract (chlorogenic acid) solid lipid nanoparticles using a positive charge on it by means of enabling lymphatic uptake. Coffee bean extract (chlorogenic acid) solid lipid nanoparticles were prepared by melt emulsification-high pressure homogenization method and the particle size, PDI and % entrapment efficiency was found to be 210nm, 0.455 and 91.18% .ex vivo endocytic uptake studies revealed engrossment of endocytic pathways in the uptake of solid lipid nanoparticles from intestine. Keywords: Coffee bean extract (Chlorogenic Acid), Glyceryl monostearate, Solid Lipid Nanoparticles, Lymphatic Uptake
Cardiovascular diseases (CVDs) are a global health problem. The mortality associated with them is one of the highest. Essentially, CVDs occur when the heart or blood vessels are damaged. Oxidative stress is an imbalance between the production of reactive oxygen species (free radicals) and antioxidant defenses. Increased production of reactive oxygen species can cause cardiac and vascular injuries, leading to CVDs. Antioxidant therapy has been shown to have beneficial effects on CVDs. Plants are a rich source of bioactive antioxidants on our planet. Several classes of these compounds have been identified. Among them, carotenoids and phenolic compounds are the most potent antiox-idants. This review summarizes the role of some carotenoids (a/β-carotene, lycopene and lutein), polyphenols such as phenolic acids (caffeic, p-coumaric, ferulic and chlorogenic acids), flavonoids (quercetin, kaempferol and epigallocatechin gallate), and hydroxytyrosol in mitigating CVDs by studying their biological antioxidant mechanisms. Through detailed analysis, we aim to provide a deeper understanding of how these natural compounds can be integrated into cardiovascular health strategies to help reduce the overall burden of CVD.
Phenolic compounds, present in plants, provide substantial health advantages, such as antioxidant and anti-inflammatory properties, which enhance cardiovascular and cognitive well-being. Australia is enriched with a wide range of plants with phytopharmacological potential, which needs to be fully elucidated. In this context, we analyzed leaves of aniseed myrtle (Syzygium anisatum), lemon myrtle (Backhousia citriodora), and cinnamon myrtle (Backhousia myrtifolia) for their complex phytochemical profile and antioxidant potential. LC-ESI-QTOF-MS/MS was applied for screening and characterizing these Australian myrtles' phenolic compounds and the structure-function relation of phenolic compounds. This study identified 145 and quantified/semi-quantified 27 phenolic compounds in these Australian myrtles. Furthermore, phenolic contents (total phenolic content (TPC), total condensed tannins (TCT), and total flavonoids (TFC)) and antioxidant potential of phenolic extracts from the leaves of Australian myrtles were quantified. Aniseed myrtle was quantified with the highest TPC (52.49 ± 3.55 mg GAE/g) and total antioxidant potential than other selected myrtles. Catechin, epicatechin, isovitexin, cinnamic acid, and quercetin were quantified as Australian myrtles' most abundant phenolic compounds. Moreover, chemometric analysis further validated the results. This study provides a new insight into the novel potent bioactive phenolic compounds from Australian myrtles that could be potentially useful for functional, nutraceutical, and therapeutic applications.
Chlorogenic acid (CGA) is a type of polyphenol compound found in rich concentrations in many plants such as green coffee beans. As an active natural substance, CGA exerts diverse therapeutic effects in response to a variety of pathological challenges, particularly conditions associated with chronic metabolic diseases and age-related disorders. It shows multidimensional functions, including neuroprotection for neurodegenerative disorders and diabetic peripheral neuropathy, anti-inflammation, anti-oxidation, anti-pathogens, mitigation of cardiovascular disorders, skin diseases, diabetes mellitus, liver and kidney injuries, and anti-tumor activities. Mechanistically, its integrative functions act through the modulation of anti-inflammation/oxidation and metabolic homeostasis. It can thwart inflammatory constituents at multiple levels such as curtailing NF-kB pathways to neutralize primitive inflammatory factors, hindering inflammatory propagation, and alleviating inflammation-related tissue injury. It concurrently raises pivotal antioxidants by activating the Nrf2 pathway, thus scavenging excessive cellular free radicals. It elevates AMPK pathways for the maintenance and restoration of metabolic homeostasis of glucose and lipids. Additionally, CGA shows functions of neuromodulation by targeting neuroreceptors and ion channels. In this review, we systematically recapitulate CGA’s pharmacological activities, medicinal properties, and mechanistic actions as a potential therapeutic agent. Further studies for defining its specific targeting molecules, improving its bioavailability, and validating its clinical efficacy are required to corroborate the therapeutic effects of CGA.
Chlorogenic acid (CGA), a polyphenol found mainly in coffee and tea, exerts antioxidant, anti-inflammatory and anti-apoptotic effects at the gastrointestinal level. However, although CGA is known to cross the blood–brain barrier (BBB), its effects on the CNS are still unknown. Oligodendrocytes (OLs), the myelin-forming cells in the CNS, are the main target in demyelinating neuroinflammatory diseases such as multiple sclerosis (MS). We evaluated the antioxidant, anti-inflammatory and anti-apoptotic roles of CGA in M03-13, an immortalized human OL cell line. We found that CGA reduces intracellular superoxide ions, mitochondrial reactive oxygen species (ROS) and NADPH oxidases (NOXs) /dual oxidase 2 (DUOX2) protein levels. The stimulation of M03-13 cells with TNFα activates the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kB) pathway, leading to an increase in superoxide ion, NOXs/DUOX2 and phosphorylated extracellular regulated protein kinase (pERK) levels. In addition, tumor necrosis factor alpha (TNF-α) stimulation induces caspase 8 activation and the cleavage of poly-ADP-ribose polymerase (PARP). All these TNFα-induced effects are reversed by CGA. Furthermore, CGA induces a blockade of proliferation, driving cells to differentiation, resulting in increased mRNA levels of myelin basic protein (MBP) and proteolipid protein (PLP), which are major markers of mature OLs. Overall, these data suggest that dietary supplementation with this polyphenol could play an important beneficial role in autoimmune neuroinflammatory diseases such as MS.
Alzheimer’s disease (AD) is a prevalent neurodegenerative disease account for 60–80% of the total number of people with dementia, but its treatment and prevention strategies are still in a long process of exploration. It has been reported that a healthy lifestyle may be an effective non-pharmacological intervention for the prevention and treatment of AD, including increased physical activity and the consumption of polyphenol-rich foods. This study, therefore, investigated the effects of 8 weeks of moderate-intensity aerobic exercise (EX), administration of chlorogenic acid administration (GCA), and a combination of both (EX+GCA) on β-amyloid (Aβ) deposition, inflammatory factors, oxidative stress markers, neuronal damage, and cognitive performance in the brains of AD model mice (APP/PS1) and which signaling pathways may be responsible for these effects. The study used Western blot to detect the expression of signaling pathway-related proteins, enzyme-linked immunosorbent assay to detect the expression of inflammatory factors, hematoxylin–eosin staining to detect hippocampal neuronal morphology, immunohistochemistry to detect changes in Aβ deposition in the hippocampus, an oxidative stress marker kit to detect oxidative stress status and the Morris water maze to detect changes in cognitive performance. This study showed that an 8-week intervention (EX/GCA/EX+GCA) activating the SIRT1/PGC-1α signaling pathway improved oxidative stress, neuroinflammation, Aβ deposition, and cognitive performance in mice. However, there was no obvious difference between the EX and GCA groups. In contrast, the combined EX+GCA intervention was significantly better than phase EX or GCA. Our study suggests that although relief of Aβ deposition, neuroinflammation, oxidative stress, neuronal damage, and cognitive decline could also be achieved with EX or GCA, the combined EX+GCA intervention showed better results. These relief effects on AD-related conditions may be obtained by mediating the activation of the SIRT1/PGC-1α signaling pathway. This study is the first to explore the improvement of AD-related conditions with a combined lifestyle of EX+GCA. This healthy lifestyle could be a candidate option for the treatment of AD.
Chlorogenic acid is a bioactive compound ubiquitously present in the natural realm, lauded for its salient anti-inflammatory and antioxidant attributes. It executes its anti-inflammatory function by moderating the synthesis and secretion of inflammatory mediators, namely, TNF-α, IL-1β, IL-6, IL-8, NO, and PGE2. Concurrently, it modulates key signaling pathways and associated factors, including NF-κB, MAPK, Nrf2, and others, bestowing protection upon cells and tissues against afflictions such as cardio-cerebrovascular and diabetes mellitus. Nevertheless, the inherent low bioavailability of chlorogenic acid poses challenges in practical deployments. To surmount this limitation, sophisticated delivery systems, encompassing liposomes, micelles, and nanoparticles, have been devised, accentuating their stability, release mechanisms, and bioactivity. Given its innate anti-inflammatory prowess and safety profile, chlorogenic acid stands as a promising contender for advanced biomedical investigations and translational clinical endeavors.
Document Reviewers
Luis Alcocer (Mexico), Christina Antza (Greece), Mustafa Arici (Turkey), Eduardo Barbosa (Brazil), Adel Berbari (Lebanon), Luís Bronze (Portugal), John Chalmers (Australia), Tine De Backer (Belgium), Alejandro de la Sierra (Spain), Kyriakos Dimitriadis (Greece), Dorota Drozdz (Poland), Béatrice Duly-Bouhanick (France), Brent M. Egan (USA), Serap Erdine (Turkey), Claudio Ferri (Italy), Slavomira Filipova (Slovak Republic), Anthony Heagerty (UK), Michael Hecht Olsen (Denmark), Dagmara Hering (Poland), Sang Hyun Ihm (South Korea), Uday Jadhav (India), Manolis Kallistratos (Greece), Kazuomi Kario (Japan), Vasilios Kotsis (Greece), Adi Leiba (Israel), Patricio López-Jaramillo (Colombia), Hans-Peter Marti (Norway), Terry McCormack (UK), Paolo Mulatero (Italy), Dike B. Ojji (Nigeria), Sungha Park (South Korea), Priit Pauklin (Estonia), Sabine Perl (Austria), Arman Postadzhian (Bulgaria), Aleksander Prejbisz (Poland), Venkata Ram (India), Ramiro Sanchez (Argentina), Markus Schlaich (Australia), Alta Schutte (Australia), Cristina Sierra (Spain), Sekib Sokolovic (Bosnia and Herzegovina), Jonas Spaak (Sweden), Dimitrios Terentes-Printzios (Greece), Bruno Trimarco (Italy), Thomas Unger (The Netherlands), Bert-Jan van den Born (The Netherlands), Anna Vachulova (Slovak Republic), Agostino Virdis (Italy), Jiguang Wang (China), Ulrich Wenzel (Germany), Paul Whelton (USA), Jiri Widimsky (Czech Republic), Jacek Wolf (Poland), Grégoire Wuerzner (Switzerland), Eugene Yang (USA), Yuqing Zhang (China).
Ischemic stroke causes severe brain damage and high mortality. Chlorogenic acid is a phenolic compound that has neuroprotective properties. B-cell lymphoma-2 (Bcl-2) family proteins are important for apoptosis regulation. Bcl-2 and Bcl-xL are proteins that inhibit apoptosis, and Bax and Bad induce apoptosis. In this study, we investigated whether chlorogenic acid exerts a neuroprotective effect against ischemic stroke damage by regulating Bcl-2 family proteins. We performed middle cerebral artery occlusion (MCAO) to induce ischemic stroke in adult male rats. The animals were intraperitoneally injected with normal saline as a vehicle or chlorogenic acid (30 mg/kg) 2 hr after MCAO. Cerebral cortex tissue was collected 24 hr after MCAO damage. MCAO damage caused histopathological changes and increased the number of terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling-positive cells, while chlorogenic acid attenuated these changes. RT-qPCR and Western blot results showed decreases in Bcl-2 and Bcl-xL expression and an increase in Bax and Bad expression in MCAO animals. However, chlorogenic acid treatment attenuated these changes due to MCAO damage. The interaction of Bax with Bcl-2 or Bcl-xL decreased in MCAO animals, and the binding of Bad with Bcl-2 or Bcl-xL increased. However, chlorogenic acid treatment reduced these changes. Chlorogenic acid also prevented MCAO-induced increases in caspase-3 and caspase-9 expression. This study provides evidence that chlorogenic acid has neuroprotective effects against MCAO damage by modulating Bcl-2 family proteins including Bcl-2, Bcl-xL, Bax, and Bad. Furthermore, chlorogenic acid regulates the interaction between Bcl-2 family proteins. In conclusion, chlorogenic acid contributes to neuroprotection against ischemic stroke damage by controlling Bcl-2 family proteins.
Background:
Cerebral ischemia is a serious neurological disorder that can lead to high morbidity and mortality. Chlorogenic acid is a polyphenol compound with antioxidant that can regulate proteins in cerebral ischemia. Middle cerebral artery occlusion (MCAO) surgery was performed to induce ischemic brain injury and was maintained for 24 h. Chlorogenic acid (30 mg/kg) or vehicle was administrated into the peritoneal cavity 2 h after MCAO surgery. The cerebral cortical tissues were collected for further study and a proteomic approach was performed to identify the proteins changed by chlorogenic acid in the MCAO animals.
Results:
We found that chlorogenic acid alleviated in changes in adenosylhomocysteinase, glycerol-3-phosphate dehydrogenase, eukaryotic translation initiation factor 4A-II, apolipoprotein A-I, and mu-crystallin. These proteins were reduced in MCAO animals with vehicle, and these reductions were attenuated by chlorogenic acid treatment. The mitigation of this reduction by chlorogenic acid was confirmed by the reverse transcription PCR technique. These proteins are associated with energy metabolism, protein synthesis, inflammation, and physiological metabolism. They are involved in the neuroprotective effect of chlorogenic acid. These results showed that chlorogenic acid alleviates the neurological disorders caused by MCAO and regulates the expression of proteins involved in neuroprotection.
Conclusions:
Therefore, our findings provide evidence that chlorogenic acid plays a neuroprotective role in stroke animal models by controlling specific proteins.
Introduction
Dietary medicinal plants are among the most sought-after topics in alternative medicine today due to their preventive and healing properties against many diseases.
Aim
This study aimed to extract and determine the polyphenols from indigenous plants extracts, i.e., Mentha longifolia, M. arvensis, Tinospora cordifolia, Cymbopogon citratus, Foeniculum vulgare, Cassia absus, Camellia sinensis, Trachyspermum ammi, C. sinensis and M. arvensis, then evaluate the antioxidant, cytotoxicity, and antimicrobial properties, besides enzyme inhibition of isolated polyphenols.
Methods
The antioxidant activity was evaluated by DPPH, Superoxide radical, Hydroxyl radical (OH.), and Nitric oxide (NO.) scavenging activity; the antidiabetic activity was evaluated by enzymatic methods, and anticancer activity using MTT assay, while the antibacterial activity.
Results
The results showed that tested medicinal plants’ polyphenolic extracts (MPPE) exhibited the most significant antioxidant activity in DPPH, hydroxyl, nitric oxide, and superoxide radical scavenging methods because of the considerable amounts of total polyphenol and flavonoid contents. UHPLC profile showed twenty-five polyphenol complexes in eight medicinal plant extracts, categorized into phenolic acids, flavonoids, and alkaloids. The main polyphenol was 3-Feroylquinic acid (1,302 mg/L), also found in M. longifolia, C. absus, and C. sinensis, has a higher phenolic content, i.e., rosmarinic acid, vanillic acid, chlorogenic acid, p-coumaric acid, ferulic acid, gallic acid, catechin, luteolin, 7-O-neohesperideside, quercetin 3,7-O-glucoside, hesperidin, rutin, quercetin, and caffeine in the range of (560–780 mg/L). At the same time, other compounds are of medium content (99–312 mg/L). The phenolics in C. sinensis were 20–116% more abundant than those in M. longifolia, C. absus, and other medicinal plants. While T. cordifolia is rich in alkaloids, T. ammi has a lower content. The MTT assay against Caco-2 cells showed that polyphenolic extracts of T. ammi and C. citratus had maximum cytotoxicity. While M. arvensis, C. sinensis, and F. vulgare extracts showed significant enzyme inhibition activity, C. sinensis showed minor inhibition activity against α-amylase. Furthermore, F. vulgare and C. sinensis polyphenolic extracts showed considerable antibacterial activity against S. aureus, B. cereus, E. coli, and S. enterica.
Discussion
The principal component analysis demonstrated clear separation among medicinal plants’ extracts based on their functional properties. These findings prove the therapeutic effectiveness of indigenous plants and highlight their importance as natural reserves of phytogenic compounds with untapped potential that needs to be discovered through advanced analytical methods.
Cancer is a leading cause of death worldwide and involves an oxidative stress mechanism. The transcription factor Nrf2 has a crucial role in cytoprotective response against oxidative stress, including cancer growth and progression and therapy resistance. For this reason, inhibitors of Nrf2 are new targets to be studied. Traditional plant-based remedies rich in phytochemicals have been used against human cancers and phenolic compounds are known for their chemopreventive properties. This comprehensive review offers an updated review of the role of phenolic compounds as anticancer agents due to their action on Nrf2 inhibition. In addition, the role of naturally-occurring bioactive anticancer agents are covered in the clinical applications of polyphenols as Nrf2 inhibitors.
Background: The genetic diversity of Sardinian pear germplasm has received limited attention regarding its chemical composition. Understanding this composition can aid in the setting up of resilient, extensive groves that offer multiple products and ecosystem services. This research aimed at investigating the antioxidant properties and phenolic compounds of ancient pear cultivars grown extensively in Sardinia (Italy); Methods: the cultivars Buttiru, Camusina, Spadona, and Coscia (as a reference) were compared. Fruit samples were manually peeled and cut. Their flesh, peel, core, and peduncle were frozen separately, lyophilized, and milled before being analysed; Results: The content of total phenolics (TotP), total flavonoids (TotF), condensed tannins (CT), and antioxidant capacity in each fruit part varied significantly among the cultivars. The TotP content was high in the peduncle (42.2-58.8 g GAE kg −1 DM) and low in flesh (6.4-17.7 g GAE kg −1 DM); Conclusions: the highest values of antioxidant capacity, TotP, NTP, TotF, and CT were found in the flesh of the cultivar Buttiru and in the peel of the cultivar Camusina. Chlorogenic acid was the major individual phenolic compound in peel, flesh and core, whereas arbutin was mostly present in the peduncle. Results can contribute to revise target exploitations of underutilized ancient pear cultivars.
Coffee is one of the most widely consumed beverages, which has several effects on the human body. In particular, current evidence suggests that coffee consumption is associated with a reduced risk of inflammation, various types of cancers, and certain neurodegenerative diseases. Among the various constituents of coffee, phenolic phytochemicals, more specifically chlorogenic acids, are the most abundant, and there have been many attempts to utilize coffee chlorogenic acid for cancer prevention and therapy. Due to its beneficial biological effect on the human body, coffee is regarded as a functional food. In this review article, we summarize the recent advances and knowledge on the association of phytochemicals contained in coffee as nutraceuticals, with a particular focus on phenolic compounds, their intake, and nutritional biomarkers, with the reduction of disease risk, including inflammation, cancer, and neurological diseases.
Polycystic ovary syndrome (PCOS) is a heterogeneous clinical syndrome. Recent studies examine different strategies to modulate its related complications. Chlorogenic acid, as a bioactive component of green coffee (GC), is known to have great health benefits. The present study aimed to determine the effect of GC on lipid profile, glycemic indices, and inflammatory biomarkers. Forty-four PCOS patients were enrolled in this randomized clinical trial of whom 34 have completed the study protocol. The intervention group (n = 17) received 400 mg of GC supplements, while the placebo group (n = 17) received the same amount of starch for six weeks. Then, glycemic indices, lipid profiles, and inflammatory parameters were measured. After the intervention period, no significant difference was shown in fasting blood sugar, insulin level, Homeostasis model assessment of insulin resistance index, low-density lipoprotein, high-density lipoprotein, Interleukin 6 or 10 between supplementation and placebo groups. However, cholesterol and triglyceride serum levels decreased significantly in the intervention group (p < 0.05). This research confirmed that GC supplements might improve some lipid profiles in women with PCOS. However, more detailed studies with larger sample sizes are required to prove the effectiveness of this supplement.
Chlorogenic acid (CGA), also known as coffee tannic acid and 3-caffeoylquinic acid, is a water-soluble polyphenolic phenylacrylate compound produced by plants through the shikimic acid pathway during aerobic respiration. CGA is widely found in higher dicotyledonous plants, ferns, and many Chinese medicine plants, which enjoy the reputation of “plant gold.” We have summarized the biological activities of CGA, which are mainly shown as anti-oxidant, liver and kidney protection, anti-bacterial, anti-tumor, regulation of glucose metabolism and lipid metabolism, anti-inflammatory, protection of the nervous system, and action on blood vessels. We further determined the main applications of CGA in the food industry, including food additives, food storage, food composition modification, food packaging materials, functional food materials, and prebiotics. With a view to the theoretical improvement of CGA, biological activity mechanism, and subsequent development and utilization provide reference and scientific basis.
The cardiovascular complications contribute to a majority of diabetes associated morbidity and mortality, accounting for 44% of death in those patients with type 1 diabetes mellitus (DM) and 52% of deaths in type 2 DM. Diabetes elicits cardiovascular dysfunction through 2 major mechanisms: ischemic and non-ischemic. Non-ischemic injury is usually under-recognized although common in DM patients, and also a pathogenic factor of heart failure in those diabetic individuals complicated with ischemic heart disease. Diabetic cardiomyopathy (DCM) is defined as a heart disease in which the myocardium is structurally and functionally abnormal in the absence of coronary artery disease, hypertensive, valvular, or congenital heart disorders in diabetic patients, theoretically caused by non-ischemic injury solely. Current therapeutic strategies targeting DCM mainly address the increased blood glucose levels, however, the effects on heart function are disappointed. Accumulating data indicate endothelial dysfunction plays a critical role in the initiation and development of DCM. Hyperglycemia, hyperinsulinemia, and insulin resistance cause the damages of endothelial function, including barrier dysfunction, impaired nitric oxide (NO) activity, excessive reactive oxygen species (ROS) production, oxidative stress, and inflammatory dysregulation. In turn, endothelial dysfunction promotes impaired myocardial metabolism, intracellular Ca²⁺ mishandling, endoplasmic reticulum (ER) stress, mitochondrial defect, accumulation of advanced glycation end products, and extracellular matrix (ECM) deposit, leads to cardiac stiffness, fibrosis, and remodeling, eventually results in cardiac diastolic dysfunction, systolic dysfunction, and heart failure. While endothelial dysfunction is closely related to cardiac dysfunction and heart failure seen in DCM, clinical strategies for restoring endothelial function are still missing. This review summarizes the timely findings related to the effects of endothelial dysfunction on the disorder of myocardium as well as cardiac function, provides mechanical insights in pathogenesis and pathophysiology of DCM developing, and highlights potential therapeutic targets.
Melanoma is one of the most common malignant tumors. The anti-PD-1 antibody is used for the treatment of metastatic melanoma. Treatment success is only 35–40% and a range of immune-related adverse reactions can occur. Combination of anti-PD1 antibody therapy with other oncology therapies has been attempted. Herein, we assessed whether chlorogenic acid liposomes modified with sialic acid (CA-SAL) combined with anti-PD1 antibody treatment was efficacious as immunotherapy for melanoma. CA-SAL liposomes were prepared and characterized. In a mouse model of B16F10 tumor, mice were treated with an anti-PD1 antibody, CA-SAL, or combination of CA-SAL + anti-PD1 antibody, and compared with no treatment controls. The tumor inhibition rate, tumor-associated macrophages (TAMs) phenotype, T-cell activity, and safety were investigated. We observed a significant decrease in the proportion of M2-TAMs and CD4⁺Fop3⁺ T cells, while there was a significant increase in the proportion of M1-TAMs and CD8⁺ T cells, and in the activity of T cells, and thus in the tumor inhibition rate. No significant toxicity was observed in major organs. CA-SAL and anti-PD1 Ab combination therapy presented synergistic anti-tumor activity, which enhanced the efficacy of the PD-1 checkpoint blocker in a mouse model of melanoma. In summary, combination immunotherapy of CA-SAL and anti-PD1 Ab has broad prospects in improving the therapeutic effect of melanoma, and may provide a new strategy for clinical treatment.
Background
Pears have been world-widely used as a sweet and nutritious food and a folk medicine for more than two millennia.
Methods
We conducted a review from ancient literatures to current reports to extract evidence-based functions of pears.
Results
We found that pears have many active compounds, e.g., flavonoids, triterpenoids, and phenolic acids including arbutin, chlorogenic acid, malaxinic acid, etc. Most of researchers agree that the beneficial compounds are concentrated in the peels. From various in vitro , in vivo , and human studies, the medicinal functions of pears can be summarized as anti-diabetic,-obese, −hyperlipidemic, −inflammatory, −mutagenic, and -carcinogenic effects, detoxification of xenobiotics, respiratory and cardio-protective effects, and skin whitening effects. Therefore, pears seem to be even effective for prevention from Covid-19 or PM 2.5 among high susceptible people with multiple underlying diseases.
Conclusion
For the current or post Covid-19 era, pears have potential for functional food or medicine for both of communicable and non-communicable disease.
In the present study, the inhibitory effect of chlorogenic acid (CGA), a phenolic compound with potential antitumor effects, on circulating microRNA 31 (miR-31), was evaluated in RKO colon cancer cells. The capacity of gold nanoparticles (AuNPs) to enhance miR-31 quantification after treatment with CGA was assessed. RKO cells were treated with different concentrations of CGA for 24, 48 and 72 h, after which AuNPs coupled to CD81 were added to the supernatants. Total RNA was extracted, and miR-31 was quantified by reverse transcription-quantitative PCR. The results revealed an 85% decrease in miR-31 level following treatment with 1,000 µM CGA for 72 h, and the highest capacity to detect miR-31 (after treatment and isolation with AuNPs + CD81) was observed at 24 h. Furthermore, CGA decreased the expression of the miR-31 oncogene in an in vitro colon cancer model, and the use of AuNPs enhanced the levels of miRNA detection. The results suggest that miR-31 inhibition is one mechanism by which CGA decreases colon cancer cell proliferation. Moreover, AuNPs can increase the capacity of miR-31 quantification, representing a new strategy to develop non-invasive tools for the molecular diagnosis and monitoring of colon cancer.
The effect of a mainly polyunsaturated oil (soybean oil) and a mainly medium chain triglyceride oil (coconut oil) on the absorption of the phenolic antioxidant chlorogenic acid (5-caffeoylquinic acid) was investigated using 90 healthy volunteers. Serum concentrations and the absorbed percentages of chlorogenic acid of volunteers who received chlorogenic acid without oils (0.006 ± 0.001 mg/ml, 5.7 ± 0.2%), chlorogenic acid with soybean oil (0.012 ± 0.001 mg/ml, 11.8 ± 1.3%), and chlorogenic acid with coconut oil (0.067 ± 0.014 mg/ml, 65.6 ± 18.1%) were significantly different from each other (p < .05). There was a strong positive correlation between the increase in serum and plasma antioxidant capacity and the absorption of chlorogenic acid. The major fatty acid of each of soybean oil and coconut oil also improved the permeability of chlorogenic acid in Caco-2 cell monolayers. The results suggest that the tested edible oils may improve the nutritional value of chlorogenic acid-containing foods by improving the absorption of chlorogenic acid.
Practical applications
Small polar antioxidants such as phenolic acids and flavonoids are poorly absorbed through the intestinal epithelium. Chlorogenic acid was used in the present study as a model for small polar phenolic antioxidants. According to the present study, soybean oil with mainly polyunsaturated fatty acids and coconut oil with mainly medium chain fatty acids improve the absorption of these antioxidants. These findings suggest that proper planning of diets or food supplements containing phenolic antioxidants with medium chain or polyunsaturated fatty acid-rich edible oils may enhance the nutritional benefits expected from phenolic antioxidants.
Pear ( Pyrus communis L.) is consumed as fresh fruit, in numerous food products, and also used as a traditional remedy in various countries, including Serbia. In search of bioactive compounds, six traditional pear varieties (‘Vidovača’, ‘Lubeničarka’, ‘Karamanka’, ‘Jeribasma’, ‘Lončara’, ‘Takiša’) and wild pear from Serbia were investigated and compared with a commercial variety (‘Williams Bartlett’). The aim of this study was to determine the total phenolic and flavonoid contents, phenolic composition, antioxidant capacity, and antineurodegenerative activities of methanolic extracts of peel, flesh, and mixed peel and flesh of pear fruits. Phenolic composition of extracts was determined with HPLC-DAD, while the antioxidant activity of extracts was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and ferric-reducing antioxidant power (FRAP) assays. Bearing in mind that oxidative stress is closely linked to neurodegeneration, the antineurodegenerative potential of the extracts was assessed by the inhibition of acetycholineserase (AChE) and tyrosinase (TYR) activities. The extracts of traditional varieties, particularly peel extracts, had a high content of phenolics, as well as significant antioxidant and moderate antineurodegenerative potential, compared to the commercial variety. The highest contents of total flavonoids and individual compounds, such as arbutin and chlorogenic acid, as well as the strongest antioxidant and TYR inhibitory activities were reported for the ‘Takiša’ peel extract. The performed analyses have revealed that fruits of traditional Serbian pear varieties are rich in bioactive components and could be used as functional food and for possible nutraceutical applications, to prevent diseases induced by oxidative stress.
The increased healthspan afforded by coffee intake provides novel opportunities to identify new therapeutic strategies. Caffeine has been proposed to afford benefits through adenosine A 2A receptors, which can control synaptic dysfunction underlying some brain disease. However, decaffeinated coffee and other main components of coffee such as chlorogenic acids, also attenuate brain dysfunction, although it is unknown if they control synaptic function. We now used electrophysiological recordings in mouse hippocampal slices to test if realistic concentrations of chlorogenic acids directly affect synaptic transmission and plasticity. 3-(3,4-dihydroxycinnamoyl)quinic acid (CA, 1–10 μM) and 5-O-(trans-3,4-dihydroxycinnamoyl)-D-quinic acid (NCA, 1–10 μM) were devoid of effect on synaptic transmission, paired-pulse facilitation or long-term potentiation (LTP) and long-term depression (LTD) in Schaffer collaterals-CA1 pyramidal synapses. However, CA and NCA increased the recovery of synaptic transmission upon re-oxygenation following 7 min of oxygen/glucose deprivation, an in vitro ischemia model. Also, CA and NCA attenuated the shift of LTD into LTP observed in hippocampal slices from animals with hippocampal-dependent memory deterioration after exposure to β-amyloid 1–42 (2 nmol, icv), in the context of Alzheimer’s disease. These findings show that chlorogenic acids do not directly affect synaptic transmission and plasticity but can indirectly affect other cellular targets to correct synaptic dysfunction. Unraveling the molecular mechanisms of action of chlorogenic acids will allow the design of hitherto unrecognized novel neuroprotective strategies.
Pear (Pyrus communis L.) is widely spread throughout the temperate regions of the world, such as China, America and Australia. This fruit is popular among consumers due to its excellent taste and perceived health benefits. Various bioactive compounds, which contribute to these health benefits, have been detected in the pear fruits, including a range of phenolic compounds. Five Australian grown pear varieties, which include Packham’s Triumph, Josephine de Malines, Beurre Bosc, Winter Nelis and Rico were selected for this study to examine the phenolic compounds in pears. Beurre Bosc exhibited the highest total polyphenol content (TPC) (3.14 ± 0.02 mg GAE/g), total tannin content (TTC) (1.43 ± 0.04 mg CE/g) and 2,2′-diphenyl-1-picrylhydrazyl (DPPH) (5.72 ± 0.11 mg AAE/g), while the Josephine de Malines variety was high in total flavonoid content (TFC) (1.53 ± 0.09 mg QE/g), ferric reducing antioxidant power (FRAP) (4.37 ± 0.04 mg AAE/g), 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) (4.44 ± 0.01 mg AAE/g) and total antioxidant capacity (TAC) (5.29 ± 0.09 mg AAE/g). The liquid chromatography coupled with electrospray-ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS/MS) data indicate that a total of 73 phenolic compounds were detected in Beurre Bosc (37 compounds), Josephine de Malines (34), Rico (22), Packham’s Triumph (15) and Winter Nelis (9), respectively. From HPLC-PDA quantification, the Beurre Bosc pear variety showed significantly higher in phenolic acids (chlorogenic acid; 17.58 ± 0.88 mg/g) and while flavonoids were significantly higher in Josephine de Malines (catechin; 17.45 ± 1.39 mg/g), as compared to other pear varieties. The analyses suggest that the Australian grown pears might contain an ideal source of phenolic compounds which benefit human health. The information provided by the present work can serve as practical supporting data for the use of pears in the nutraceutical, pharmaceutical and food industries.
Background:
Currently, obesity is a global health challenge due to its increasing prevalence and associated health risk. It is associated with various metabolic diseases, including diabetes, hypertension, cardiovascular disease, stroke, certain forms of cancer, and non-alcoholic liver diseases (NAFLD).
Objective:
The aim of this study to evaluate the effects of polyphenol enriched herbal complex (Rubus crataegifolius/ellagic acid, Crataegus pinnatifida Bunge/vitexin, chlorogenic acid, Cinnamomum cassiaa/cinnamic acid) on obesity and obesity induced NAFLD in the high-fat diet (HFD)-induced obese mouse model.
Methods:
Obesity was induced in male C57BL/6 mice using HFD. After 8 weeks, the mice were treated with HFD+ plants extract for 8 weeks. Body weight, food intake weekly, and blood sugar level were measured. After sacrifice, changes in the treated group's liver weight, fat weight, serum biochemical parameters, hormone levels, and enzyme levels were measured. For histological analysis, tissues were stained with hematoxylin-eosin (H&E) and Oil Red-O.
Results:
Our results showed that the herbal complex ameliorated body weight and liver weight gain, and decreased total body fat in HFD-fed animals. Post prandial blood glucose (PBG) and fasting blood glucose (FBG) were lower in the herbal complex-treated group than in the HFD control group. Additionally, herbal formulation treatment significantly increased HDL levels in serum and decreased TC, TG, AST, ALT, deposition of fat droplets in the liver, and intima media thickness (IMT) in the aorta. Herbal complex increased serum adiponectin and decreased serum leptin. Herbal complex also increased carnitine palmityl transferase (CPT) activity and significantly decreased enzyme activity of beta-hydroxy beta methyl glutamyl-CoA (HMG-CoA) reductase, and fatty acid synthase (FAS).
Conclusions:
The results of this study demonstrated that the herbal complex is an effective herbal formulation in the attenuation of obesity and obesity-induced metabolic dysfunction including NAFLD in HFD-induced mouse model.
Background
Epidemiological studies have reported lower risk of cardiovascular disease with moderate coffee consumption. In addition, emerging evidence indicates that consumption of coffee beverages enriched in chlorogenic acids (CGAs) may influence blood pressure and endothelial function, suggesting that the beneficial cardiovascular effect of coffee may relate to its CGA content.
Objectives
We conducted a double-blind randomized crossover trial to test the effect of acute consumption of a decaffeinated green coffee extract (DGCE), rich in CGAs, on endothelial function in healthy subjects.
Methods
We compared 3 different doses of DGCE (302, 604, and 906 mg, respectively) with a placebo. Endothelial function was defined as the percentage change in the internal diameter of the brachial artery in response to flow-mediated dilation (%FMD). In addition, we followed the plasma concentration-time profiles of 25 systemic CGA metabolites over 24 h after DGCE consumption and we explored the relation between systemic concentrations of CGAs and the effect on %FMD.
Results
The DGCE formulations containing different amounts of CGAs resulted in dose-proportional increases in overall total polyphenol concentrations. The systemic appearance of total CGAs was biphasic, in agreement with previous results suggesting 2 sites of absorption in the gastrointestinal tract. Compared with the placebo group, a significant FMD increase (>1%) was observed 8.5, 10, and 24 h after consumption of 302 mg DGCE (∼156.4 mg CGAs). The differences with placebo observed in the other 2 groups were not statistically significant. Evaluation of the relation between phenolic exposure and %FMD showed a positive tendency toward a larger effect at higher concentrations and different behavior of CGA metabolites depending on the conjugated chemical position.
Conclusions
We demonstrated an acute improvement in %FMD over time after ingestion of a DGCE, explained at least partly by the presence in the blood circulation of CGAs and their metabolites. This trial was registered at clinicaltrials.gov as NCT03520452.
Breast cancer which is the most common type of diagnosed cancer among women worldwide possesses metastatic potential, multi‑drug resistance, and high mortality. The NF‑κB signaling pathway has been revealed to be abnormally activated in breast cancer cells and closely associated with high metastasis and poor prognosis. In the present study, it was reported that chlorogenic acid (CGA), a potent NF‑κB inhibitor derived from coffee, exerted antitumor activity in breast cancer. MTT and colony formation assays were conducted and it was revealed that CGA inhibited viability and proliferation in breast cancer cells. Additionally, CGA significantly induced apoptosis and suppressed migration and invasion in breast cancer cells. Notably, immunofluorescence analysis confirmed that CGA could efficiently suppress nuclear transcription of NF‑κB p65. In addition, results of western blotting demonstrated that CGA markedly impaired the NF‑κB and EMT signaling pathways. The antitumor effect of CGA was evaluated in a subcutaneous tumor mouse model of 4T1 cells, and the results revealed that CGA markedly retarded tumor growth and prolonged the survival rate of tumor‑bearing mice. Notably, CGA inhibited pulmonary metastasis of 4T1 cells by enhancing the proportion of CD4+ and CD8+ T cells in spleens of mice, which indicated an improvement of antitumor immunity. In conclusion, the present present study demonstrated that CGA improved antitumor immunity, exerting antitumor and anti‑metastatic effects by impairing the NF‑κB/EMT signaling pathway, suggesting that CGA may serve as a potential candidate for therapy of breast cancer.
A static magnetic field (SMF) or the bioactive compounds that are found in foods are potential agents that can be used to support cancer therapy. Therefore, the aim of our study was to assess the impact of the SMF that are induced by neodymium magnets on the culture growth and antioxidant status of melanoma cells that had been treated with chlorogenic acid (CGA). The melanoma cells, the control and those that had been treated with CGA, were put in special magnetic test chambers that generated a 0.7 T magnetic field. The mRNA levels of the antioxidant enzymes were analyzed using RT‐qPCR. The activity of SOD, GPx, and CAT was measured in the cell lysates. While the expression and activity of the antioxidant enzymes was inhibited relative to the untreated cells as a result of the CGA treatment (1 mmol/L), it was not after the CGA treatment in combination with an SMF. The demonstrated cytotoxicity of CGA (1 mmol/L) and its inhibition of the antioxidant enzymes suggests the usefulness of phenolic compounds as a supporting pharmacological treatment for melanoma.
Practical applications
Phenolic acids and their derivatives, which are the bioactive components of the human diet, are signal molecules that transfer information from the external environment that affects the level of gene expression in cells. This study suggests the usefulness of phenolic compounds as a supporting pharmacological treatment for melanoma and seems to be important for the development of experimental oncology.
Chlorogenic acids (CGAs), a group of hydroxycinnamates, are generally abundant in everyday foods and beverages, most prominently in certain coffee drinks. Among them, the chlorogenic acid (CGA), also termed as 5‐O‐caffeoylquinic acid (5‐CQA), is one of the most abundant, highly functional polyphenolic compounds in the human diet. The evidence of its health benefits obtained from clinical studies, as well as basic research, indicates an inverse correlation between 5‐CQA consumption and a lower risk of metabolic syndromes and chronic diseases. This review focuses on the beneficial properties for health and mechanisms of action of 5‐CQA, starting with its history, isomers, dietary sources, processing effects, preparation methods, pharmacological safety evaluation, and bioavailability. It also provides the possible molecular mechanistic bases to explain the health beneficial effects of 5‐CQA including neuroprotective, cardiovascular protective, gastrointestinal protective, renoprotective, hepatoprotective, glucose and lipid metabolism regulatory, and anticarcinogenic effects. The information summarized here could aid in the basic and clinical research on 5‐CQA as a natural dietary additive, potential drug candidate, as well as a natural health promoter.
Chlorogenic acid, an important active component of coffee with anti-tumor activities, has been found for a hundred years. However, the lack of understanding about its target proteins greatly limits the exploration of its anti-tumor molecular mechanisms and clinical applications. Here, in vitro and animal experiments showed that chlorogenic acid had a significant inhibitory effect on the proliferation of A549 cells. The ability of chlorogenic acid to naturally emit fluorescence was exploited to screen its target proteins while avoiding false positives brought about by chemical modifications when using fluorescent tags. Consequently, we identified and verified annexin A2 as a covalent binding target of chlorogenic acid in A549 cells. We also discovered that chlorogenic acid inhibits the binding of annexin A2 to p50 subunit thereby inhibiting the expression of downstream anti-apoptotic genes cIAP1 and cIAP2 of the NF-κB signaling pathway in A549 cells in vitro and in vivo. Moreover, we found that chlorogenic acid hindered the binding of annexin A2 to actin possibly causing inhibition of tumor cell cycle and migration. Thus, this work demonstrates that chlorogenic acid binds annexin A2, causing a decrease in the expression of NF-κB downstream anti-apoptotic genes, and inhibiting the proliferation of A549 cells in vivo and in vitro.
The demand for plant‐derived antidiabetic nutraceuticals is increasing. In this study, the effects of three common caffeoylquinic acids (CQAs) (chlorogenic acid, isochlorogenic acid A, and cynarin) on α‐glucosidase activity and glucose consumption in HepG2 cells were systematically compared. Their α‐glucosidase inhibitory activities followed the order of isochlorogenic acid A > chlorogenic acid > cynarin. The fluorescence analysis indicated that they exerted the inhibitory role by forming the complex with α‐glucosidase at the molar ratio of 1:1. Isochlorogenic acid A possessed the highest binding capacity, followed by chlorogenic acid and cynarin. The effect of caffeoyl group distribution on the α‐glucosidase inhibitory activity was clarified by the molecular docking results. In the HepG2 cells, isochlorogenic acid A also showed the best glucose consumption with negligible cytotoxicity, which might be related to its reactive oxygen species scavenging capacity in cells. Our results confirm its potential application as the antidiabetic nutraceutical.
Practical applications
The hypoglycemic activities of three common CQAs (chlorogenic acid, isochlorogenic acid A, and cynarin) were systemically evaluated in this study. Isochlorogenic acid A exhibited the strongest α‐glucosidase inhibitory activity and highest glucose consumption in HepG2 cells with low cytotoxicity. The results suggest that isochlorogenic acid A can be used as the potential hypoglycemic nutraceutical in functional foods.
Mitochondrial dysfunction and oxidative stress characterize major factors involved in the activation of complex processes corresponding to apoptosis-mediated neuronal senescence of dopaminergic neurons (DA) in Parkinson’s disease (PD). Here, we evaluated the molecular mechanisms participating in the treatment of a 1-methyl-4-phenyl-1,2,3,6-tetrahydopyridine- (MPTP-) intoxicated PD mouse model in response to chlorogenic acid (CGA). The results indicate that CGA treatment significantly improved the motor coordination of the MPTP-intoxicated mice. CGA also alleviated the fall in activity of mitochondrial complexes I, IV, and V in accordance with ameliorating the level of superoxide dismutase and mitochondrial glutathione in the midbrain of MPTP-induced mice. CGA inhibited the activation of proapoptotic proteins including Bax and caspase-3, while elevating the expression of antiapoptotic protein like Bcl-2 consequently preventing the MPTP-mediated apoptotic cascade. The study also revealed the improved phosphorylation state of Akt, ERK1/2, and GSK3β which was downregulated as an effect of MPTP toxicity. Our findings signify that CGA may possess pharmacological properties and contribute to neuroprotection against MPTP induced toxicity in a PD mouse model associated with phosphorylation of GSK3β via activating Akt/ERK signalling in the mitochondrial intrinsic apoptotic pathway. Thus, CGA treatment may arise as a potential therapeutic candidate for mitochondrial-mediated apoptotic senescence of DA neurons in PD.
Importance
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in December 2019 and has spread globally with sustained human-to-human transmission outside China.
Objective
To report the initial experience in Singapore with the epidemiologic investigation of this outbreak, clinical features, and management.
Design, Setting, and Participants
Descriptive case series of the first 18 patients diagnosed with polymerase chain reaction (PCR)–confirmed SARS-CoV-2 infection at 4 hospitals in Singapore from January 23 to February 3, 2020; final follow-up date was February 25, 2020.
Exposures
Confirmed SARS-CoV-2 infection.
Main Outcomes and Measures
Clinical, laboratory, and radiologic data were collected, including PCR cycle threshold values from nasopharyngeal swabs and viral shedding in blood, urine, and stool. Clinical course was summarized, including requirement for supplemental oxygen and intensive care and use of empirical treatment with lopinavir-ritonavir.
Results
Among the 18 hospitalized patients with PCR-confirmed SARS-CoV-2 infection (median age, 47 years; 9 [50%] women), clinical presentation was an upper respiratory tract infection in 12 (67%), and viral shedding from the nasopharynx was prolonged for 7 days or longer among 15 (83%). Six individuals (33%) required supplemental oxygen; of these, 2 required intensive care. There were no deaths. Virus was detectable in the stool (4/8 [50%]) and blood (1/12 [8%]) by PCR but not in urine. Five individuals requiring supplemental oxygen were treated with lopinavir-ritonavir. For 3 of the 5 patients, fever resolved and supplemental oxygen requirement was reduced within 3 days, whereas 2 deteriorated with progressive respiratory failure. Four of the 5 patients treated with lopinavir-ritonavir developed nausea, vomiting, and/or diarrhea, and 3 developed abnormal liver function test results.
Conclusions and Relevance
Among the first 18 patients diagnosed with SARS-CoV-2 infection in Singapore, clinical presentation was frequently a mild respiratory tract infection. Some patients required supplemental oxygen and had variable clinical outcomes following treatment with an antiretroviral agent.
Background:
Liver diseases have a negative impact on global health and are a leading cause of death worldwide. Chlorogenic acids (CGAs), a family of esters formed between certain trans-cinnamic acids and quinic acid, are natural polyphenols abundant in coffee, tea, and a variety of traditional Chinese medicines (TCMs). They are reported to have good hepatoprotective effects against various liver diseases.
Purpose:
This review aims to analyze the available literature on the hepatoprotective effect of CGAs, with particular emphasis on their mechanisms.
Methods:
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. PubMed and Web of Science databases were adopted to retrieve all relevant literature on CGAs for liver disease from 2013 to March 2023.
Results:
Research has indicated that CGAs play a crucial role in improving different types of liver diseases, including drug-induced liver injury (DILI), alcoholic liver disease (ALD), metabolic (dysfunction)-associated fatty liver disease (MAFLD), cholestatic liver disease (CLD), liver fibrosis, and liver cancer. CGAs display remarkable antioxidant and anti-inflammatory effects by activating erythroid 2-related factor 2 (Nrf2) and inhibiting toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathways. Some important molecules such as AMP-activated protein kinase (AMPK) and extracellular signal-regulated kinases 1 and 2 (ERK1/2), and other key physiological processes like intestinal barrier and gut microbiota have also been discovered to participate in CGAs-provided amelioration on various liver diseases.
Conclusion:
In this review, different studies indicate that CGAs have an excellent protective effect against various liver diseases associated with various signaling pathways.
Objective: To explore the anti-aging effects of chlorogenic acid (CGA) and the underlying mechanisms based on a Caenorhabditis elegans (C. elegans) model. Methods: The anti-aging activity of CGA was studied based on the body length, exercise behavior, lipofuscin content, antioxidative stress ability, swallowing frequency, body-bending frequency, and head-swinging ability of C. elegans. Through DAF-16 nuclear translocation and SOD-3-GFP fluorescence experiments, the effects of CGA on ROS levels, antioxidant enzyme activities, MDA content, mutant-strain lifespan, and anti-aging molecular signaling pathways were explored, as well as the underlying mechanisms. Results: CGA improved multiple indices of the nematode: body length was increased (all P
Background:
Respiratory syncytial virus (RSV) is an important cause of acute respiratory infection, lower respiratory tract disease, clinical complications, and death in older adults. There is currently no licensed vaccine against RSV infection.
Methods:
In an ongoing, international, placebo-controlled, phase 3 trial, we randomly assigned, in a 1:1 ratio, adults 60 years of age or older to receive a single dose of an AS01E-adjuvanted RSV prefusion F protein-based candidate vaccine (RSVPreF3 OA) or placebo before the RSV season. The primary objective was to show vaccine efficacy of one dose of the RSVPreF3 OA vaccine against RSV-related lower respiratory tract disease, confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR), during one RSV season. The criterion for meeting the primary objective was a lower limit of the confidence interval around the efficacy estimate of more than 20%. Efficacy against severe RSV-related lower respiratory tract disease and RSV-related acute respiratory infection was assessed, and analyses according to RSV subtype (A and B) were performed. Safety was evaluated.
Results:
A total of 24,966 participants received one dose of the RSVPreF3 OA vaccine (12,467 participants) or placebo (12,499). Over a median follow-up of 6.7 months, vaccine efficacy against RT-PCR-confirmed RSV-related lower respiratory tract disease was 82.6% (96.95% confidence interval [CI], 57.9 to 94.1), with 7 cases (1.0 per 1000 participant-years) in the vaccine group and 40 cases (5.8 per 1000 participant-years) in the placebo group. Vaccine efficacy was 94.1% (95% CI, 62.4 to 99.9) against severe RSV-related lower respiratory tract disease (assessed on the basis of clinical signs or by the investigator) and 71.7% (95% CI, 56.2 to 82.3) against RSV-related acute respiratory infection. Vaccine efficacy was similar against the RSV A and B subtypes (for RSV-related lower respiratory tract disease: 84.6% and 80.9%, respectively; for RSV-related acute respiratory infection: 71.9% and 70.6%, respectively). High vaccine efficacy was observed in various age groups and in participants with coexisting conditions. The RSVPreF3 OA vaccine was more reactogenic than placebo, but most adverse events for which reports were solicited were transient, with mild-to-moderate severity. The incidences of serious adverse events and potential immune-mediated diseases were similar in the two groups.
Conclusions:
A single dose of the RSVPreF3 OA vaccine had an acceptable safety profile and prevented RSV-related acute respiratory infection and lower respiratory tract disease and severe RSV-related lower respiratory tract disease in adults 60 years of age or older, regardless of RSV subtype and the presence of underlying coexisting conditions. (Funded by GlaxoSmithKline Biologicals; AReSVi-006 ClinicalTrials.gov number, NCT04886596.).
Lychnophora is a genus of South American flowering plants in the daisy family, popularly known as "Brazilian arnica". It is used in traditional medicine as an anti-inflammatory and analgesic agent, whose active components are derived from chlorogenic acid (CGA) and C-flavonoids. Since the drugs currently used are ineffective to treat glaucoma, agents with antioxidant and anti-inflammatory properties may represent new alternatives in preventing cellular lesions in retinal ischemia. In this study, we report the neuroprotective effects of CGA and 4,5-di-O-[E]-caffeoylquinic (CQA) acid, isolated from Lychnophora plants, in a rodent glaucoma model. Wistar rats were administered intravitreally with 10 µg CGA or CGA, and then subjected to acute retinal ischemia (ISC) by increasing intraocular pressure (IPO) for 45 minutes followed (or not) by 15 minutes of reperfusion (I/R). Qualitative and quantitative analyses of neurodegeneration were performed using hematoxylin-eosin or Fluoro-Jade C staining protocols. All retinas submitted to ISC or I/R exhibited matrix disorganization, pyknotic nuclei, and pronounced vacuolization of the cytoplasm in the ganglion cell layer (GCL) and inner nuclear layer (INL). Pretreatment with CGA or CQA resulted in the protection of the retinal layers against matrix disorganization and a reduction in the number of vacuolized cells and pyknotic nuclei. Also, pretreatment with CGA or CQA resulted in a significant reduction in neuronal death in the GCL, the INL, and the outer nuclear layer (ONL) after ischemic insult. Our study demonstrated that CGA and CQA exhibit neuroprotective activities in retinas subjected to ISC and I/R induced by IPO in Wistar rats.
Chlorogenic acid (CA), also known as 5-O-caffeoylquinic acid, is a dietary phenolic acid produced by various plant species. CA, is the most ubiquitous compound among the phenolic acid group, is also present in tea and green coffee extracts. Its consumption reduces the risk of numerous diseases as validated by preclinical and clinical studies. CA possesses a wide range of pharmacological properties, such as hepatoprotective, antimicrobial, immunomodulatory, antioxidant, antidiabetic, and anticancer activities. It has been extensively used in the food, chemical, medicine, and health care industries. Available reports revealed that CA can exert anticancer activity by inhibiting the cell cycle, triggering apoptosis, and suppressing the proliferation of cancer cells. It upregulates the expression of nuclear factor of activated T cells 2 (NFATC2) and NFATC3 genes involved in immune pathway and downregulates B cell-specific moloney murine leukemia virus integration site 1 protein and SRY-box transcription factor 2 gene expression to facilitate tumor cell destruction. It promotes intracellular DNA impairment and topoisomerase I- and topoisomerase-II-DNA complex formation that perform a key function in apoptosis. In addition, CA has been documented to be an effective natural anticancer drug and was approved by the China Food and Drug Administration. Several previously published reports have provided fragmented summary of various anticancer activities of CA. Therefore, this review aims to deliver up-to-date and comprehensive assessment about the natural sources of CA, its bioavailability, metabolism, and anticancer property with an emphasis on the molecular mechanisms associated with several signaling pathways in tumor cells.
Background: Immunologic characterization of tumors and their microenvironments had been proposed based on the combination of PD-L1 expression and the presence of tumor-infiltrating lymphocytes (TILs). This study aims to investigate in metastatic samples from patients with cancer, the distribution of TILs and expression of PD-L1 using Combined Positive Score (CPS), Tumor Proportion Score (TPS), as well as TILs. These variables were further evaluated in paired primary and metastatic samples and correlated with clinical outcome.
Patients and methods: 550 pan-cancer patients of SHIVA01 trial (NCT01771458) with available contributive FFPE sample from a metastatic biopsy and 111 paired primary and metastatic samples were evaluated for TILs. The 550 metastatic specimens were biopsies from different anatomical sites subdivided into 7 groups: liver biopsies (n=179; 33%), visceral organ biopsies (n=92; 17%), lung biopsies (n=89; 16%), lymph node biopsies (n= 88; 16%), cutaneous biopsies (n=53; 10%), soft tissue biopsies (n=48; 9%) and brain biopsy (n=1; 0.2%). PD-L1 expression was assessed by Immunohistochemistry using the 22C3 antibody clone (Merck & Co) and quantified using two scores: CPS and TPS, in 494 metastatic tumors and in 77 paired primary and metastatic tumors patients with contributive immunohistochemistry. The correlations of TILs and PD-L1 expression with clinical outcomes are ongoing.
Results: In metastatic samples, we found no difference in TILs distribution according to histological subtype, primary system or biopsy site with a median of 10% [range: 0%-70%]. A significant decrease in the median percentage of TILs was found in metastases in comparison to their paired primary lesions (20% [5%-60%] versus 10% [0%-40%], p<0.0001). PD-L1 expression was homogenous in all metastatic tumors independently of primary system or biopsy site (median TPS = 2% ; CPS = 0 n=218, CPS≥1 n=265 ; p=0.056). There was a strong association between TPS count and histological subtypes (p=0.015) that was not observed with CPS (p=0.23). In paired primary/metastatic samples, we did not observe any changes in the CPS and TPS scores (p>0.3 for both).
Conclusion: We show that metastatic sites are less infiltrated with lymphocytes as compared to their paired primary lesions independently of the initial primary tumor site, histological type or biopsy site. PD-L1 expression was similar in paired primary and metastatic samples.
Citation Format: Zakhia El Beaino, Célia Dupain, Grégoire Marret, Xavier Paoletti, Laëtitia Fuhrmann, Charlotte Martinat, Ivan Bièche, Christophe Le Tourneau, Maud Kamal, Anne Vincent-Salomon. Pancancer evaluation of tumor infiltrating lymphocytes (TILs) and PD-L1 in SHIVA-01 trial patients with different biopsy sites and histological types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1724.
Trimethyltin chloride (TMT) is acknowledged to have potent neurotoxicity. Chlorogenic acid (CGA), the most abundant polyphenol in the human diet, is well-known for its neuroprotective activity. This investigation was performed to determine the effects and mechanisms of CGA on TMT-induced neurobehavioral dysfunctions. Mice received oral administrations of CGA (30 mg kg-1) for 11 days, in which they were intraperitoneally injected with TMT (2.7 mg kg-1) once on the 8th day. The daily intake of CGA significantly alleviated TMT-induced epilepsy-like seizure and cognition impairment, ameliorating hippocampal neuronal degeneration and neuroinflammation. Oral gavage of CGA potentially exerted neuroprotective effects through JNK/c-Jun and TLR4/NFκB pathways. Microbiome analysis revealed that daily consumption of CGA raised the relative abundance of Lactobacillus in TMT-treated mice. SCFAs, the gut microbial metabolites associated with neuroprotection, were increased in the mouse hippocampus following CGA treatment. TMT-induced neurotransmitter disorders were regulated by oral gavage of CGA, especially DL-kynurenine and acetylcholine chloride. Additionally, neurotransmitters in the mouse hippocampus were found to be highly associated with the gut microbiota. Our findings provided research evidence for the neuroprotective effect of CGA on TMT-induced neurobehavioral dysfunctions.
Pyrus ussuriensis is the most important cultivated pear in the northeastern, cold areas of China. However, studies on the biological activity of Pyrus ussuriensis fruit are rare in the public domain. The present study compared antioxidant, anti-inflammatory, and antimicrobial activities and chemical composition in tissues from the peel and flesh of nine Pyrus ussuriensis cultivars. The chemical composition differed among cultivars and tissue sources. Phenolics were predominant in peel samples, whereas sugars were predominant in flesh samples. Twenty-one phenolic compounds were identified and quantified, including hydroxycinnamic acids, hydroquinones, flavanols, flavonols, flavones, and anthocyanins (only in peel samples). The total phenolic content ranged between 363.0 and 1734.0 mg kg− 1 FW in the peel and from 28.5 to 182.3 mg kg− 1 FW in the flesh. In addition, cultivars with high total phenolic and flavonoid contents had significantly higher antioxidant activities. The in vitro anti-inflammatory study, performed using an egg albumin denaturation assay, demonstrated that both peel and flesh samples had strong activity, which was comparable with that of the standard anti-inflammatory drug diclofenac sodium. The antimicrobial results showed that ‘Jianba’ and ‘Balixiang’ cultivars exhibited strong activity against bacteria strains in the peel and flesh, respectively. The present study provided information for selecting promising Pyrus ussuriensis cultivars with improved health benefits.
Scope:
Chlorogenic acid (5-caffeoylquinic acid), the most prominent polyphenolic compound in coffee, has been attributed multiple health-promoting effects such as anti-inflammatory, antidiabetic and antioxidative effects. These effects are dependent on the bioavailability of chlorogenic acid, which is determined by the pharmacokinetic properties: absorption, distribution, metabolism and excretion (ADME). In order to have a better understanding of the biological properties of chlorogenic acid and to optimize formulation and dosing of chlorogenic acid-containing food supplements, information on the absorption of chlorogenic acid and its microbial biotransformation products is of essence.
Methods and results:
In the present work, the intestinal absorption of chlorogenic acid and quinic acid, one of its most prominent intestinal biotransformation products, was studied by an in vitro permeability assay using a human Caco-2 cell line model. For both chlorogenic acid and quinic acid, the involvement of an active efflux mechanism was demonstrated, suggesting an overall low intestinal absorption.
Conclusions:
An overall low intestinal absorption for chlorogenic acid and quinic acid was reported given the involvement of an active efflux mechanism. These findings could aid in the development of optimal formulation and dosing strategies of chlorogenic acid in food supplements in order to obtain beneficial health effects.
(Poly)Phenolic compounds or polyphenols are the most common and ubiquitous groups of secondary metabolites widely distributed in the plant kingdom. These metabolites are involved in important roles in plants, such as pigmentation, growth and reproduction functions, protection against ultraviolet (UV) radiation, resistance to pathogens and herbivores, as well as contributing substantially to the organoleptic characteristics of flowers, leaves, fruits, and vegetables. Apart from beneficial effects on plants, many of these nonnutrient metabolites have been attributed as the molecules potentially responsible for health effects in humans. In this chapter, the classification and chemistry of polyphenols, their dietary intake and food sources, and their bioavailability, metabolism, and bioactivity are reviewed and discussed.
The crude extract of Sonchus oleraceus Linn (CE) and its main phenolic acids (PA), chlorogenic acid and caffeic acid have anti-diabetic activity, but the mechanisms for their effects on glucose intake remain largely unknown. Aim of this study was to examine the synergistic effect of chlorogenic and caffeic acid from S. oleraceus Linn attenuate insulin resistance and modulate glucose uptake in HepG2 cells. Major phenolic acids in SOL were isolated and identified by HPLC. Insulin-resistance HepG2 cell model was used to elucidate the effect of CE on glucose metabolism. Pre-treatment of HepG2 cells with CE or PA enhanced levels of glucose production and avoided the decrease total levels of IRS-1 triggered by high insulin concentration. CE or PA pre-treatment also could prevent the inactivation of the PI3K/AKT pathway, as well as the diminution of GLUT4 levels induced by high glucose. These findings suggested that CE and its main phenolic acids improved insulin sensitivity of HepG2 cells treated with insulin, preventing or delaying a potential hepatic dysfunction through the attenuation of the insulin signaling blockade and the modulation of glucose consumption.
Despite all the new treatments, metastatic breast cancer (BC) causes many deaths. Chlorogenic acid (CGA) is a polyphenol compound with various pharmacological traits, such as anticancer properties. Targeting apoptotic death pathways has been propounded as the most effective therapeutic method in various cancers. In the current study, apoptotic agents such as p53, Bax, Bcl‐2, and caspase‐3 have been investigated. The experimental groups included saline, BC, CGA, protective (PR), and treatment (TM) groups. First, 4T1 mouse BC was established and then the effects of treatment with CGA were investigated through measurement of tumor weight and volume, metastatic nodules, liver biochemical tests, hematoxylin and eosin (H&E), immunohistochemistry (IHC) staining, and real‐time reverse transcription‐polymerase chain reaction (RT‐PCR) in experimental groups. The findings showed that CGA reduced tumor weight and volume in the PR group (P < .05) and in the TM group (P < .001). Surprisingly, it eliminated the tumors in the TM group. Metastatic nodules in the PR and TM groups were significantly reduced as compared with the BC group (P < .001). The evaluation by H&E staining showed cell apoptosis in both the PR and TM groups. The results of real‐time RT‐PCR showed that CGA therapy increased the expression ratio of Bax/Bcl‐2 (P < .001 and P < .05, respectively) and the expression of p53 (P < .001 and P < .05, respectively) and caspase‐3 genes (P < .01) in the PR and TM groups. The IHC data regarding the Bax/Bcl‐2 ratio confirmed the other results (P < .001). The findings demonstrate that CGA plays a significant role in the induction of apoptosis and the treatment of 4T1 BC tumors in BALB/c mice.
Chlorogenic acids (CGAs) have gained considerable attention as pervasive human dietary constituents with potential cardiovascular-preserving effects. The main sources include coffee, yerba mate, Eucommia ulmodies leaves, and Lonicerae Japonicae Flos. CGAs consumption can reduce the risks of hypertension, atherosclerosis, heart failure, myocardial infarction, and other factors associated with cardiovascular risk, such as obesity and type 2 diabetes. This review recapitulates recent advances of CGAs in the cardiovascular-preserving effects, pharmacokinetics, sources and safety. Emerging evidence indicates that CGAs exhibit circulatory guarding properties through the suppression of oxidative stress, leukocyte infiltration, platelet aggregation, platelet-leukocyte interactions, vascular remodeling, and apoptosis as well as the regulation of glucose and lipid metabolism, and vasodilatory action in the cardiovascular system. CGAs exert these effects by acting on complex signaling networks, but the global mechanisms are still not clear. The oral bioavailability of CGA is poor and there is a potential sensitization concern about CGA. The bioactive metabolites, systematic toxicity, and optimized structure are needed to further identify.
To investigate the mechanism of combinational effects of chlorogenic acid (CGA) and caffeine on lipid metabolism in high-fat diet-induced obese mice, eighty female ICR mice were randomly divided into eight groups and fed with high-fat diet containing/without CGA and/or caffeine for 14 weeks. CGA and caffeine combination effectively decreased body weight gain, intraperitoneal adipose tissues weight, serum LDL-c, FFA, TC, TG, leptin, IL-6 concentrations, hepatic TG and TC levels, while increased serum adiponectin level. CGA and caffeine combination promoted the phosphorylation of AMPKα, inhibited the expressions of transcriptional regulators (SREBP-1c and LXRα), and decreased the expressions of FAS and HMGR. Besides, the expressions of ACO, ATGL and HSL were increased by CGA and caffeine combinations. The results indicated that CGA and caffeine combinations exhibited anti-obesity and regulation of lipid metabolism in high-fat diet-induced obese mice, via the AMPKα-LXRα/SREBP-1c signaling pathway. Thus, chronic CGA and caffeine intakes may be potent for preventing obesity.