Santa Cirmi

University of Messina | UNIME · Dipartimento di Scienze Chimiche Biologiche Farmaceutiche ed Ambientali

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 o...

Objective: To quantify the relationship between Citrus intake and risk of cancer of the oral cavity and pharynx. Design: Systematic review and meta-analysis. Data sources: Ovid MEDLINE, EMBASE, and Web of Science were searched until September 2017. Search terms included Citrus, Citrus aurantifolia, Citrus sinensis, Citrus paradisi, Citrus frui...

Tyrosine kinase inhibitors (TKIs), the treatment of choice for chronic myeloid leukemia (CML), can be associated to cardiovascular (CV) adverse events (AEs). A case/non-case study was performed using AE reports registered in the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database to compare the risk of CV event report...

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...

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...

Red blood cells (RBCs) are the main cells of the blood, perform numerous functions within the body and are in continuous contact with endogenous and exogenous molecules. In this context, the study aims to investigate the effect of epicatechin (EC) (flavan-3-ols) on the erythrocytes, analyzing the protective effect of the molecule and the action exe...

Over the last ten years, researchers’ efforts have aimed to replace the classic linear economy model with the circular economy model, favoring green chemical and industrial processes. From this point of view, biologically active molecules, coming from plants, flowers and biomass, are gaining considerable value. In this study, firstly we focus on th...

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...

Human exposure to bisphenol A (BPA) occurs through the ingestion of contaminated food and water, thus leading to endothelial dysfunction, the first signal of atherosclerosis. Vitis vinifera L. (grape) juice is well known for its health-promoting properties, due to its numerous bioactive compounds among which are polyphenols. The aim of this study w...

Introduction Growth hormone secretagogues (GHSs) exert multiple actions, being able to activate GHS-receptor 1a, control inflammation and metabolism, to enhance GH/insulin-like growth factor-1 (IGF-1)-mediated myogenesis, and to inhibit angiotensin-converting enzyme. These mechanisms are of interest for potentially targeting multiple steps of patho...

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 obes...

Phytochemicals have long been effective partners in the fight against several diseases, including cancer. Among these, flavonoids are valuable allies for both cancer prevention and therapy since they are known to influence a large panel of tumor-related processes. Particularly, it was revealed that quercetin, one of the most common flavonoids, cont...

In age-related sarcopenia, the gradual loss of skeletal muscle mass, function and strength is underpinned by an imbalanced rate of protein synthesis/breakdown. Hence, an adequate protein intake is considered a valuable strategy to mitigate sarcopenia. Here, we investigated the effects of a 12-week oral supplementation with branched-chain amino acid...

Novel targets are constantly sought to fight hematologic malignancies. In this regard, high levels of SIRT2 expression are associated with unfavorable prognosis of acute myeloid leukemia. The interest in the plant kingdom has allowed the identification of ever-new anti-leukemic agents. Citrus × bergamia (bergamot) was proved to possess anticancer p...

The absence of protein dystrophin in Duchenne muscular dystrophy leads to progressive muscle weakness and wasting, paralleled by failing regeneration. Recently, a key role of deregulated nitric oxide production in epigenetic control of regeneration program has been demonstrated. We focused on the potential interest of the amino acid L-citrulline (L...

In skeletal muscle, several ion channels interact with the dystrophin complex, which is disrupted in Duchenne muscular dystrophy (DMD). However, little is known about their involvement in myogenesis in DMD. Here, we performed a pilot study to characterize the electrophysiological asset of myoblasts and myocytes at day 2/4/6/11 by using two immortal...

Growth hormone secretagogues (GHSs) exert multiple actions of interest in Duchenne muscular dystrophy (DMD), such as controlling inflammation and metabolism via GHS-R1a activation, enhancing GH/IGF-1 mediated myogenesis, and inhibiting angiotensin-converting enzyme (ACE). Our study aims to provide preclinical evidence for potential benefits of GHSs...

Acute myeloid leukemia (AML) represents the most alarming hematological disease for adults. Several genetic modifications are known to be pivotal in AML; however, SIRT2 over-expression has attracted the scientific community’s attention as an unfavorable prognostic marker. The plant kingdom is a treasure trove of bioactive principles, with flavonoid...

The veterinary visit is necessary for safeguarding the health of dogs, but it can be stressful and threaten both the welfare of the patient and the accuracy of the examination. This randomized, triple-blind, placebo-controlled, crossover study aims at evaluating how dog appeasing pheromone (DAP) in a novel gel formulation influences the behavioral...

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...

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 deriv...

Objective Systemic sclerosis (SSc) mortality is extremely variable in its internal organ involvement. Pulmonary fibrosis occurs in up to 30% of the cases. Animal models provide evidence that IL-33 is able to induce both cutaneous and pulmonary fibrosis via increased IL-13 and in SSc patients the levels of IL-33 correlate with skin fibrosis. Our aim...

It is known that plant phenolic compounds exert anti-inflammatory activity through both anti-oxidant effects and modulation of pivotal pro-inflammatory factors. Recently, Olea europaea has been studied as a natural source of bioactive molecules; however, few studies have focused on the biological effect of oleacein (OLC), the most abundant secoirid...

The chorioallantoic membrane (CAM) of the chicken embryo is a highly vascularized extra-embryonic structure that has been widely used as an in vivo model for the evaluation of angiogenesis. This study was designed to optimize data extrapolation from the most exploited experimental protocol to improve its efficiency and the reliability of the obtain...

ROS-activated cSrc tyrosine kinase (TK) promotes the degradation of β-dystroglycan (β-DG), a dystrophin-glycoprotein complex component, which may reinforce damaging signals in Duchenne muscular dystrophy (DMD). Therefore, cSrc-TK represents a promising therapeutic target. In mdx mice, a 4-week subcutaneous treatment with dasatinib (DAS), a pan-Src-...

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 inappropriatel...

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 s...

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...

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 i...

A caloric surplus and a sedentary lifestyle are undoubtedly known to be the leading causes of obesity. Natural products represent valuable allies to face this problematic issue. This study was planned to assess the effect of a white grape (Vitis vinifera) juice extract (WGJe) in diet-induced obese zebrafish (Danio rerio). Fish were divided into fou...

Callus, suspension and bioreactor cultures of Verbena officinalis were established, and optimized for biomass growth and production of phenylpropanoid glycosides, phenolic acids, flavonoids and iridoids. All types of cultures were maintained on/in the Murashige and Skoog (MS) media with 1 mg/L BAP and 1 mg/L NAA. The inoculum sizes were optimized i...

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...

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...

Much evidence suggests that both oxidative stress and apoptosis play a key role in the pathogenesis of Parkinson’s disease (PD). The present study aims to evaluate the protective effect of bergamot juice (BJ) against 6-hydroxydopamine (6-OHDA)- or H2O2-induced cell death. Treatment of differentiated SH-SY5Y human neuroblastoma cells with 6-OHDA or...

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....

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...

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 Cit...

In the last decades, glucosinolates (GLs), precursors of isothiocyanates (ITCs), have been studied mostly for their chemopreventive and chemotherapeutic properties. The aim of our research was to study the antiproliferative effect of 4-(α-L-rhamnopyranosyloxy) benzyl glucosinolate (glucomoringin; GMG) bioactivated by myrosinase enzyme to form the c...

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 scientifi...

Introduction: Colorectal cancer (CRC) is the second leading cause of cancer death in Europe. During past decades, polyphenolic-rich extracts have attracted attention as potential chemopreventive agents. Citrus bergamia Risso et Poiteau (Bergamot) is a typical tree of Calabria region (Italy). Its fruits are mainly used for the extraction of its esse...

Flavonoids may be effective in preventing chronic degenerative diseases linked to oxidative stress, which in turn is involved in the etiopathogenesis of inflammatory bowel disease. This study was designed to assess the effects of a flavonoid-rich extract of orange juice (OJe) in mice exposed to experimental colitis. Four days of intracolonic inject...

Due to the pivotal role of mitochondria in cell physiology and pathology, recently, a great deal of data has been acquired on mitochondrial dysfunction in aging and in age-related diseases. This stimulated the search for compounds able to promote mitochondrial functionality. Our study was designed to evaluate the antioxidant property of a white gra...

It is known that Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer, and gastric carcinoma. Due to the increased side effects of the treatment regimens and the development of antimicrobial resistance, a number of natural compounds have been tested as potential alternatives. In this review, we will examine the current k...

Flavonoids may be effective in preventing chronic degenerative diseases linked to oxidative stress, which in turn is involved in the etiopathogenesis of inflammatory bowel disease. This study was designed to assess the effects of a flavonoid-rich extract of orange juice (OJe) in mice exposed to experimental colitis. Four days of intracolonic inject...

A series of spiro[isoindole-1,5-isoxazolidin]-3(2H)-ones has been synthesized by 1,3-dipolar cycloaddition of N-benzylnitrone with isoindolin-3-methylene-1-ones. The regio-and stereoselectivity of the process have been rationalized by computational methods. The obtained compounds show cytotoxic properties and antiproliferative activity in the range...

Biological tests, 1H and 13C NMR spectra of all new compounds, computational methods and X-ray data.

Two pH and temperature controlled drug delivery systems for cancer therapy are here reported by using vapour phase and liquid phase functionalized multiwalled carbon nanotubes (MWCNT). Both oxidized MWCNT were functionalized at the carboxyl groups with a short hydrophilic polyethylene glycol (PEG) chain. The nanosystems were loaded with doxorubicin...

Background Systemic sclerosis (SSc) is a complex autoimmune disease characterized by vascular alterations and autoimmune activation leading to widespread organ fibrosis. At the early stage of disease when organ involvement and extent of disease are emerging, mast cells may have some role, as implied by both symptoms and histologic evidence. Case pr...

Fruits and vegetables have long been recognized as potentially important in the prevention of cancer risk. Thus, scientific interest in nutrition and cancer has grown over time, as shown by increasing number of experimental studies about the relationship between diet and cancer development. This review attempts to provide an insight into the anti-c...

Neurodegenerative diseases (ND) result from the gradual and progressive degeneration of the structure and function of the central nervous system or the peripheral nervous system or both. They are characterized by deterioration of neurons and/or myelin sheath, disruption of sensory information transmission and loss of movement control. There is no e...

Inflammatory diseases affect a large portion of the worldwide population, and chronic inflammation is a major risk factor for several dangerous pathologies. To limit the side effects of both synthetic and biological anti-inflammatory drugs, the use of herbal medicines, nutraceuticals and food supplements has increased tremendously as alternative an...

Infectious diseases remain among the leading causes of morbidity and mortality worldwide, mainly because of the increase of resistance to chemotherapeutic drugs. Nature is the major source of anti-infective drugs and could represent a font of medicines that may help overcome antibiotic resistance. Recently, the potential antimicrobial effect of cer...

Exogenous iron in particulate matter and imbalanced iron homeostasis cause deleterious effects on health. Natural and synthetic iron chelators may be of therapeutic benefit, therefore we evaluated the protective effect of Citrus flavonoids-rich extracts from bergamot and orange juices in iron overloaded human lung epithelial cells. Cytofluorimetric...

Flavonoids have been shown to be effective in protecting against age-related cognitive and motor decline in both in vitro and in vivo models. Recently, a flavonoid-rich extract of Citrus bergamia juice (BJe) has been shown to display anti-oxidant and anti-inflammatory properties against LPS-induced activation of human THP-1 monocytes. In the light...

Helicobacter pylori infection has been associated with chronic gastritis, peptic ulcer and gastric carcinoma as over half of the world's population is colonized with this gram-negative bacterium. Due to the increasing antibiotic resistance, its eradication rates fails in a great portion of patients. A number of studies showed that molecules largely...

Background Increasing interest in the antitumour activity of several fruit juices and vegetable extracts led us to investigate the antitumour effects of bergamot juice in in vitro models. Citrus bergamia Risso et Poiteau (bergamot) is a small tree cultivated almost exclusively along the southern coast of the Calabria region of Italy. Bergamot fruit...

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 t...

Effects of flavonoids extracted from Citrus reticulata (mandarin) juice on proliferation and migration of 3 human anaplastic thyroid carcinoma (ATC) cell lines were evaluated. Flavonoid components of Mandarin juice extract (MJe) were analyzed by uHPLC. Proliferation of CAL-62, C-643, and 8505C cells, measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-dip...

It has been reported that oxidant/antioxidant imbalance triggers cell damage that in turn causes a number of lung diseases. Flavonoids are known for their health benefits, and Citrus fruits juices are one of the main food sources of these secondary plant metabolites. The present study was designed to evaluate the effect of the flavonoid fraction of...

Schematic illustration of the protection mechanism provided by FFBJ and FFOJ against H2O2-induced oxidative stress in human lung epithelial A549 cells.

A novel series of C-nucleosides, featuring the presence of a 1,2,3-triazole ring linked to an isoxazolidine system, has been designed as mimetics of the pyrimidine nucleobases. An antiproliferative effect was observed for compounds 17a and 17b: the growth inhibitory effect reaches the 50% in HepG2 and HT-29 cells and increases up to 56% in the SH-S...

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-dimet...

A straightforward and efficient method for the synthesis of novel highly substituted and diversely functionalized indazolone derivatives has been developed. The transformation consists of a cyclocondensation of selected [Formula: see text]-tricarbonyls with monosubstituted hydrazines. The starting [Formula: see text]-triketones were prepared by an...

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. Se...

1,2,3-Triazole-appended N,O-nucleosides have been synthesized by an approach combining a 1,3-dipolar cycloaddition process and an alkyne–azide click chemistry reaction. Biological assays, performed on six tumor cell lines, revealed the antiproliferative activity of the synthesized compounds. The effect was more evident in the U87MG human glioblasto...