flavan-3-ol and Inflammation

Obesity has major adverse consequences on human health contributing to the development of, among others, insulin resistance and type 2 diabetes, cardiovascular disease, non-alcoholic fatty liver disease, altered behavior and cognition, and cancer. Changes in dietary habits and lifestyle could contribute to mitigate the development and/or progression of these pathologies. This review will discuss current evidence on the beneficial actions of the flavan-3-ol (-)-epicatechin (EC) on obesity-associated comorbidities. These benefits can be in part explained through EC's capacity to mitigate several common events underlying the development of these pathologies, including: i) high circulating levels of glucose, lipids and endotoxins; ii) chronic systemic inflammation; iii) tissue endoplasmic reticulum and oxidative stress; iv) insulin resistance; v) mitochondria dysfunction and vi) dysbiosis. The currently known underlying mechanisms and cellular targets of EC's beneficial effects are discussed. While, there is limited evidence from human studies supplementing with pure EC, other studies involving cocoa supplementation in humans, pure EC in rodents and in vitro studies, support a potential beneficial action of EC on obesity-associated comorbidities. This evidence also stresses the need of further research in the field, which would contribute to the development of human dietary strategies to mitigate the adverse consequences of obesity.

Topics: Animals; Blood Glucose; Cardiovascular Diseases; Catechin; Comorbidity; Diabetes Mellitus, Type 2; Dysbiosis; Dyslipidemias; Endoplasmic Reticulum; Endotoxins; Flavonoids; Humans; Inflammation; Insulin Resistance; Lipid Metabolism; Mental Disorders; Mitochondria; Non-alcoholic Fatty Liver Disease; Obesity; Oxidative Stress

The process of inflammation constitutes a reactive response of the organism to tissue damage and is an important factor making part of a number of degenerative pathologies as insulin resistance, dyslipidemia, and hypertension, all of them comprised in the metabolic syndrome. There is an increasing interest in plant products rich in flavan-3-ols and anthocyanins because of their potential beneficial effects observed in epidemiological studies against inflammatory-related diseases. Their anti-inflammatory effects are exerted by modulation of cell redox status and inhibition of signaling pathways as NF-κB activation. The effects depend on their concentrations in target tissues and hence the bioavailability pathways followed by each particular compound. In this sense, in vitro studies performed with parental compounds at doses exceeding to those found in vivo may be drawing erroneous conclusions about their real efficacy. Contradictory results have been observed in human intervention trials, which may be ascribed to the type of population studied, length of study, source of flavan-3-ol/anthocyanin, and dose provided. Human studies are required to confirm the positive effects found in vitro and in animal models. Future research should be focused on the understanding of dose/flavonoid intake-response relationship with pharmacokinetic studies, evaluating proper biomarkers of intake. Long-term dietary interventions are necessary to observe effects on markers of late activation as well as the possible preventive effects of these compounds on long-term inflammation-related diseases.

Topics: Anthocyanins; Anti-Inflammatory Agents; Dose-Response Relationship, Drug; Flavonoids; Humans; Inflammation; NF-kappa B; Phytotherapy; Signal Transduction

Inflammation and pain underlies several pathological conditions. Synthetic drugs used for the management of these conditions carry severe toxic effects. Globally efforts are ongoing to introduce novel medicinal plants to develop effective, economic and innocuous drugs. The current study was aimed at investigating the antipyretic, anti-inflammatory and analgesic activity of methanol extract of A. hydaspica aerial parts (AHM) and its active fraction. Furthermore identification and isolation of polyphenolic compounds was carried out to identify the active principles.. Yeast induced pyrexia, Paw edema, acetic acid-induced writhing and hot plate test were carried out in vivo. HPLC-DAD analysis and combination of different chromatographic techniques, involving vacuum liquid chromatography (VLC) and flash chromatography (FC) were carried out for chemical characterization. The structural heterogeneity of flavanols was characterized by ESI- MS, (1)H NMR, (13)C NMR and (2)D NMR spectroscopic analyses, and also by comparison with reported literature.. Oral administration of A. hydaspica methanol extract (AHM) and A. hydaspica ethyl acetate fraction (AHE), showed dose and time dependent decrease in body temperature in yeast induced pyrexia, comparable to standard, Paracetamol. AHM and AHE (150 mg/kg) significantly (p < 0.001) inhibit pain sensation in various pain models, i.e. acetic acid induced writhing and hot plate test. Similarly AHM and AHE demonstrated an anti-inflammatory effect in carrageenan-induced paw edema in rats and 150 mg/kg dose being distinctly more effective (91.92% inhibition). When studied on prostaglandin E2 (PGE2) induced edema in rats, AHM and AHE showed maximum inhibition of edema at 150 mg/kg after 4 h. HPLC chromatogram of AHM revealed the presence of gallic acid, catechin, rutin and caffeic acid. Chromatographic separation and structure characterization of AHE, has led to the identification of three flavan-3-ol derivative including 7-O-galloyl catechin, +catechin and methyl gallate, which have been reported for the first time in A. hydaspica.. These results revealed that the presence of bioactive compounds in A. hydaspica might be responsible for the pharmacological activities, confirming the indigenous utility of A. hydaspica against inflammatory disorders.

Topics: Acacia; Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Antipyretics; Carrageenan; Edema; Female; Fever; Flavonoids; Hot Temperature; Inflammation; Male; Pain; Phytotherapy; Plant Extracts; Rats, Sprague-Dawley; Yeasts