Molecular updates on berberine in liver diseases: Bench to bedside

Abstract

Liver diseases are life-threatening illnesses and are the major cause of mortality and morbidity worldwide. These may include liver fibrosis, liver cirrhosis, and druginduced liver toxicity. Liver diseases have a wide prevalence globally and the fifth most common cause of death among all gastrointestinal disorders. Several novel therapeutic approaches have emerged for the therapy of liver diseases that may provide better clinical outcomes with improved safety. The use of phytochemicals for the amelioration of liver diseases has gained considerable popularity. Berberine (BBR), an isoquinoline alkaloid of the protoberberine type, has emerged as a promising molecule for the treatment of gastrointestinal disorders. Accumulating studies have proved the hepatoprotective effects of BBR. BBR has been shown to modulate multiple signaling pathways implicated in the pathogenesis of liver diseases including Akt/FoxO2, PPAR-γ, Nrf2, insulin, AMPK, mTOR, and epigenetic pathways. In the present review, we have emphasized the important pharmacological activities and mechanisms of BBR in liver diseases. Further, we have reviewed various pharmacokinetic and toxicological barriers of this promising phytoconstituent. Finally, formulation-based novel approaches are also summarized to overcome the clinical hurdles for BBR.

Therapeutic Effects of Berberine on Liver Fibrosis are associated With Lipid Metabolism and Intestinal Flora

“…(Zhang BJ. et al, 2008;Bansod et al, 2021). BBR-mediated normalization of liver function, suppression of inflammation, amelioration of ECM deposition and prevention of fibrosis correlate with NF-κB-and PPARγ-regulation.…”

“…Several studies have demonstrated the efficacy of BBR against fibrotic diseases in vivo , including pulmonary fibrosis, ( Chitra et al, 2015 ) myocardial fibrosis, ( Zhang et al, 2014 ) renal fibrosis, ( Wang et al, 2014 ) and adipose tissue fibrosis, ( Xu X. et al, 2021 ) and multifaceted causal relationships illustrate the efficacy of BBR against liver fibrosis. ( Wang et al, 2016 ; Bansod et al, 2021 ). As a multifunctional drug used in traditional Chinese medicine, berberine (BBR) can be used to treat various liver diseases.…”

“…Similar effects of BBR in carbon tetrachloride (CCl 4 )-induced liver fibrosis models were also demonstrated by other team recently. ( Bansod et al, 2021 ). The activity of BBR against these multifactorial chronic diseases may be attributable to its multi-targeted mode of action.…”

“…The fundamental feature of liver fibrosis is the abnormal activation of HSCs, and BBR has been shown to be a potential treatment for thioacetamide (TAA)-, CCl 4 -, ethanol- and high cholesterol-induced liver fibrosis models; in these contexts, it likely acts by suppressing HSC activation and downregulating alpha-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1) levels. ( Sun et al, 2009 ; Domitrovic et al, 2013 ; Eissa et al, 2018 ; Bansod et al, 2021 ). Previous studies have indicated that the direct beneficial effects of BBR involving modulation of the expression of multiple genes involved in HSC activation, cholangiocyte proliferation and liver fibrosis are linked to the downregulation of two important ribonucleotide molecules that promote liver fibrosis progression: microRNA34a and long noncoding RNA H19.…”

The Traditional Uses, Phytochemistry, Pharmacokinetics, Pharmacology, Toxicity, and Applications of Corydalis saxicola Bunting: A Review

“…Toxicological studies of other constituents in CSBTA also seem to provide some insight into the safety of the drug. The study found that berberine, a constituent of CSBTA, generally was considered safe at clinical doses ( Bansod et al, 2021 ). However, gastrointestinal discomfort, reduced blood pressure, heart damage, shortness of breath and flu-like symptoms might occur at high doses.…”