Baicalin Protects Against 17α-Ethinylestradiol-Induced Cholestasis via the Sirtuin 1/Hepatic Nuclear Receptor-1α/Farnesoid X Receptor Pathway

Abstract

Estrogen-induced cholestasis (EIC) is characterized by impairment of bile flow and accumulated bile acids (BAs) in the liver, always along with the liver damage. Baicalin is a major flavonoid component of Scutellaria baicalensis, and has been used in the treatment of liver diseases for many years. However, the role of baicalin in EIC remains to be elucidated. In this study, we demonstrated that baicalin showed obvious hepatoprotective effects in EIC rats by reducing serum biomarkers and increasing the bile flow rate, as well as by alleviating liver histology and restoring the abnormal composition of hepatic BAs. In addition, baicalin protected against estrogen-induced liver injury by up-regulation of the expression of hepatic efflux transporters and down-regulation of hepatic uptake transporters. Furthermore, baicalin increased the expression of hepatic BA synthase (CYP27A1) and metabolic enzymes (Bal, Baat, Sult2a1) in EIC rats. We showed that baicalin significantly inhibited hepatic inflammatory responses in EIC rats through reducing elevated levels of TNF-a, IL-1b, IL-6, and NF-kB. Finally, we confirmed that baicalin maintains hepatic BA homeostasis and alleviates inflammation through sirtuin 1 (Sirt1)/hepatic nuclear receptor-1a (HNF-1a)/ farnesoid X receptor (FXR) signaling pathway. Thus, baicalin protects against estrogeninduced cholestatic liver injury, and the underlying mechanism involved is related to activation of the Sirt1/HNF-1a/FXR signaling pathway.

Alcohol and Liver Clock Disruption Increase Small Droplet Macrosteatosis, Alter Lipid Metabolism and Clock Gene mRNA Rhythms, and Remodel the Triglyceride Lipidome in Mouse Liver

“…Moreover, alcohol impacts lipid metabolism at the transcriptional level by affecting SREBP-1c (You et al, 2002), PPARα and γ (Abdelmegeed et al, 2011;Zhang et al, 2016bZhang et al, , 2018, and LXR-mediated pathways (Sengupta et al, 2018). Alcohol also impairs lipid droplet turnover and lipophagy, which contribute to the development of hepatic steatosis (Orlicky et al, 2011;Carr et al, 2013;Yang et al, 2019). Steatosis is recognized as a crucial first step in the initiation and progression of ALD by sensitizing hepatocytes to additional metabolic stressors, leading to cell death and disease (Spach et al, 1991;Jou et al, 2008;Zelickson et al, 2011).…”

Paeoniflorin Protects against ANIT-Induced Cholestatic Liver Injury in Rats via the Activation of SIRT1-FXR Signaling Pathway

“…Bile acid metabolism disorder and inflammation are known to be the common feature of cholestatic liver injury. The accumulation of bile acids may cause hepatocyte toxicity and liver injury-induced inflammatory response [ 24 – 26 ]. It is believed that inflammation and bile acid metabolism disorder are the decisive generating factors in the pathogenesis of cholestatic liver injury, and anti-inflammatory and regulating bile acid metabolism therapy will be the recommended therapeutic strategy.…”

“…The protein levels of NF- κ B p65 (380172, ZEN BIO) and Nrf2 (380773, ZEN BIO) were analyzed by immunohistochemistry as previously described [ 24 ]. In brief, the liver tissues sections were incubated with primary antibodies directed against NF- κ B p65 and Nrf2 overnight at 4°C, then treated with corresponding peroxidase-coupled secondary antibodies for 50 min at room temperature and then developed by diaminobenzidine (DAB).…”

Chinese herbal medicine: Fighting SARS-CoV-2 infection on all fronts

“…Due to a successful clinical trial, it is now listed officially in the 2020 Chinese Pharmacopoeia, 2020 British Pharmacopoeia, and European Pharmacopoeia v10.0. Huangqin's major chemical constituents are flavonoids, which contribute to its therapeutic effects, including anti-viral ( Lin et al, 2016 ), lung injury ( Yang et al, 2019a ), hepatoprotective ( Yang et al, 2019a ), and neuroprotective activities ( Li et al, 2019 ). A total of 100 flavonoids (56 free flavonoids and 44 flavonoid glycosides) have been isolated from Scutellaria baicalensis ( Wang et al, 2018 ), among which baicalein, baicalin, wogonin, and wogonoside ( Fig.…”