Berberine: New Insights from Pharmacological Aspects to Clinical Evidences in the Management of Metabolic Disorders

Abstract

Berberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids found in such plants as gender Berberis. Berberine is recognised to improve glucose and lipid metabolism disorders and preliminary clinical evidences suggest the ability of berberine to reduce endothelial inflammation improving vascular health, even in patients already affected by cardiovascular diseases, suggesting a possible interesting role of berberine and its metabolites in clinical practice. However, its physicochemical properties, pharmacokinetic, and metabolism are not fully elucidated and contradictory data have been reported. This review provides a summary regarding the pharmacological and biological features of berberine, with a focus on berberine as well as their pharmacologically active metabolites and the different mechanisms underlying their activities in order to clarify the correct use of berberine supplementation, alone or in association with other nutraceuticals, for the management of metabolic disorders associated to increased cardiovascular disease risk. A particular attention has also been given to the available clinical trials assessing its short- and middle- term use tolerability, safety and efficacy in various conditions, such as dyslipidaemia, impaired fasting glucose, metabolic syndrome and type 2 diabetes.

Berberine ameliorates lipopolysaccharide‐induced acute lung injury via the PERK‐mediated Nrf2/HO‐1 signaling axis

“…Berberine, the principal isoquinoline alkaloid constituent of many popular medicinal plants (e.g., the Berberis , Coptis , and Hydrastis , among others; Figure a), has historically been used in traditional Chinese medicine due to its various biological activities, including antidiarrheal, anticancer, antidiabetic, antihyperlipidemic, and cardioprotective effects (Menees, Saad, & Chey, ; Pirillo & Catapano, ; H. L. Tan et al, ; W. Tan, Li, Chen, & Wang, ). Notably, berberine has attracted considerable attention because of its anti‐inflammatory activity in vitro and in vivo (Caliceti, Franco, Spinozzi, Roda, & Cicero, ; Seo, Fischer, & Efferth, ; Xie & Du, ). However, considering the extensive pharmacological effects of berberine and the complex molecular mechanisms of ALI, the protective effect of berberine against LPS‐induced ALI requires further study.…”

Involvement of P-glycoprotein and multidrug and toxin extrusion protein 1 in hepatic and renal berberine efflux in mice

“…Clinical studies have reported the effectiveness of BBR in treating conditions such as chronic congestive heart failure, hypercholesterolemia, type 2 diabetes, polycystic ovary syndrome, and irritable bowel syndrome. 7 However, oral BBR has been reported to cause extrapyramidal system reactions, arrhythmia, liver dysfunction, and even death in clinics in China, 8 as well as acute toxicity in animals. 9 To guide rational clinical drug therapy, it is necessary to elucidate the pharmacokinetic properties of BBR.…”

The Use of Nutraceuticals to Counteract Atherosclerosis: The Role of the Notch Pathway

“…Berberine. Berberine (BBR), a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids (5,6-dihydrodibenzoquinolizinium derivative) found in Berberis species plants (Berberidaceae), exhibits many different types of biological activities, including its effectiveness in lipid disorders and hyperglycemia [166]. The poor intestinal absorption and bioavailability of BBR are the main drawback when orally administered even though its metabolites maintain higher concentration in plasma, behaving like the pharmacologically active forms of BBR; its main metabolite berberrubine (M1) tautomerizes to a highly conjugated, electroneutral quinoid structure [167] reaching a high plasma concentration as a consequence of a more efficient intestinal absorption [167].…”