Search

A Mediterranean-style diet is highly encouraged thanks to its healthy food pattern, which includes valuable nutraceuticals such as polyphenols. Among these, flavonoids are associated with relevant biological properties through which they prevent or fight the onset of several human pathologies. Globally, the enhanced incidence of overweight and obese people has caused a dramatic increase in comorbidities, raising the need to provide better therapies. Therefore, the development of sophisticated animal models of metabolic dysregulation has allowed for a deepening of knowledge on this subject. Recent advances in using zebrafish ( Danio rerio ) as model for metabolic disease have yielded fundamental insights into the potential anti-obesity effects of flavonoids. Chronic low-grade inflammation and immune system activation seem to characterize the pathogenesis of obesity; thus, their reduction might improve the lipid profile of obese patients or prevent the development of associated metabolic illnesses. In this review, we highlight the beneficial role of flavonoids on obesity and related diseases linked to their anti-inflammatory properties. In light of the summarized studies, we suggest that anti-inflammatory therapies could have a relevant place in the prevention and treatment of obesity and metabolic disorders.

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-Apc am1137 ), mutated in Apc, the key gene in CRC, were treated with two different doses of BJe (35 mg/kg or 70 mg/kg body weight, respectively) mixed in the diet for 12 weeks. Then, the entire intestine was surgically removed and dissected for histological, immunohistochemical and molecular analyses., Results: Rats treated with BJe showed a significant dose-related reduction in the colon preneoplastic lesions mucin-depleted foci (MDF). Colon and small intestinal tumours were also significantly reduced in rats supplemented with 70 mg/kg of BJe. To elucidate the involved mechanisms, markers of inflammation and apoptosis were determined. Compared to controls, colon tumours from BJe 70 mg/kg-supplemented rats showed a significant down-regulation of inflammation-related genes (COX-2, iNOS, IL-1β, IL-6 and IL-10 and Arginase 1). Moreover, in colon tumours from rats fed with 70 mg/kg BJe, apoptosis was significantly higher than in controls. Up-regulation of p53 and down-regulation of survivin and p21 genes was also observed., Conclusions: These data indicate a strong chemopreventive activity of BJe that, at least in part, is due to its pro-apoptotic and anti-inflammatory actions. This effect could be exploited as a strategy to prevent CRC in high-risk patients.

Inflammatory bowel disease (IBD), with its major manifestations being Crohn's disease and ulcerative colitis, belongs to the gastrointestinal inflammatory disorders, whose main therapeutic approach is represented by synthetic anti-inflammatory drugs. However, they are often accompanied by many side effects that shifted the interest of the scientific community towards natural products. In this context, several studies asserted the anti-IBD effects of Citrus fruits and their flavonoids, thus the aim of the present review is to provide robust evidence favouring their role in the prevention and treatment of IBD. Key mechanisms relate to their anti-inflammatory and antioxidant properties, as well as their ability to modulate gut microbiota. All the findings collected in this review, lay the foundations for further studies in human with the aim of evaluating the concrete applicability as a novel preventive and therapeutic approach of Citrus fruits and their flavonoids.[Figure: see text].

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 effective treatment for ND, and the drugs currently marketed are symptom-oriented, albeit with several side effects. Within the past decades, several natural remedies have gained attention as potential neuroprotective drugs. Moreover, an increasing number of studies have suggested that dietary intake of vegetables and fruits can prevent or delay the onset of ND. These properties are mainly due to the presence of polyphenols, an important group of phytochemicals that are abundantly present in fruits, vegetables, cereals and beverages. The main class of polyphenols is flavonoids, abundant in Citrus fruits. Our review is an overview on the scientific literature concerning the neuroprotective effects of the Citrus flavonoids in the prevention or treatment of ND. This review may be used as scientific basis for the development of nutraceuticals, food supplements or complementary and alternative drugs to maintain and improve the neurophysiological status.

Plant polyphenols exert anti-inflammatory activity through both anti-oxidant effects and modulation of pivotal pro-inflammatory genes. Recently, Citrus bergamia has been studied as a natural source of bioactive molecules with antioxidant activity, but few studies have focused on molecular mechanisms underlying their potential beneficial effects. Several findings have suggested that polyphenols could influence cellular function by acting as activators of SIRT1, a nuclear histone deacetylase, involved in the inhibition of NF-κB signaling. On the basis of these observations we studied the anti-inflammatory effects produced by the flavonoid fraction of the bergamot juice (BJe) in a model of LPS-stimulated THP-1 cell line, focusing on SIRT1-mediated NF-κB inhibition. We demonstrated that BJe inhibited both gene expression and secretion of LPS-induced pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) by a mechanism involving the inhibition of NF-κB activation. In addition, we showed that BJe treatment reversed the LPS-enhanced acetylation of p65 in THP-1 cells. Interestingly, increasing concentrations of Sirtinol were able to suppress the inhibitory effect of BJe via p65 acetylation, underscoring that NF-κB-mediated inflammatory cytokine production may be directly linked to SIRT1 activity. These results suggest that BJe may be useful for the development of alternative pharmacological strategies aimed at reducing the inflammatory process.

Colorectal cancer (CRC) is a leading cause of cancer mortality in the industrialized world, second to lung cancer. A lot of evidences highlight that a diet rich in fruits and vegetables may reduce the risk of some types of cancer including CRC. In this study we demonstrate that Citrus bergamia juice extracts (BJe) reduces CRC cell growth by multiple mechanisms. Low BJe concentrations inhibit MAPKs pathway and alter apoptosis-related proteins, that in turn induce cell cycle arrest and apoptosis in HT-29 cells. Instead, high concentrations of BJe induce oxidative stress causing DNA damage. Our study highlights the role of BJe as modulator of cell apoptosis in CRC cells and strengthens our previous hypothesis that the flavonoid fraction of bergamot juice may play a role as anti-cancer drug.