Pharmacokinetic Characteristics of Baicalin in Rats with 17α-ethynyl-estradiol-induced Intrahepatic Cholestasis

Abstract

Baicalin is one of the main active ingredients of choleretic traditional Chinese medicine drug Radix Scutellariae. The aim of this study was to explore the pharmacokinetic characteristics of baicalin in rats with 17α-ethynylestradiol (EE)-induced intrahepatic cholestasis (IC) based on its choleretic effects. Firstly, rats were subcutaneously injected with EE solution (5 mg/kg, 0.25 mL/100 g) for 5 consecutive days to construct an IC model. Then the bile excretion rate, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bile acid (TBA) and pathological changes of the liver were detected. Secondly, after successfully modeling, the rats were intragastrically given baicalin solution (200 mg/kg) (n=6). Blood samples were collected from the tail vein at different time points after intragastric administration. The protective effects of low- (50 mg/kg), medium- (100 mg/kg) and high-dose (200 mg/kg) baicalin on the liver in IC rats were evaluated. The content of baicalin in plasma was detected by liquid chromatography-mass spectrometry/mass spectrometry and pharmacokinetics parameters were calculated. Pharmacodynamic results showed that low-, medium- and high-dose baicalin all significantly increased the average excretion rate of bile (P<0.05), and significantly decreased serum levels of ALT, AST and ALP and TBA (P<0.05). Meanwhile, HE staining showed that baicalin significantly relieved EE-induced hepatocyte edema and necrosis. Pharmacokinetic results exhibited that the absorption of baicalin in both IC and normal control rats showed bimodal phenomenon. C, AU and AUC of baicalin in IC rats were significantly higher than those of the normal control group (P<0.01). T of plasma baicalin in the model group was significantly extended to (11.09±1.84) h, with clearance dropping to 61.78% of that of the normal control group (P<0.01). The above results suggested that baicalin had protective effects on the liver of IC rats, accompanied by significantly increased in vivo exposure, delayed in vivo clearance and markedly alterative pharmacokinetic characteristics. This study provides a theoretical basis for further development of baicalin as a feasible drug for treating IC.

Probiotic Lactobacillus rhamnosus GG Prevents Liver Fibrosis Through Inhibiting Hepatic Bile Acid Synthesis and Enhancing Bile Acid Excretion in Mice

“…Hepatic activation of FXR induces elevation of SHP, which inhibits CYP7A1 expression . Previous studies have shown that systemic activation of FXR by specific synthetic FXR ligands such as GW4064 and 6α‐ethyl‐CDCA (INT‐747) protected animals from BDL‐induced, α‐naphthyl isothiocyanate–induced, and ethinyl estradiol–induced cholestasis . The observed protective effects were ascribed, in part, to the induction of BSEP, MDR2, and MRP2 to enhance excretion of BAs and phospholipids from the liver into the small intestine and, in part, to the repression of CYP7A1 through hepatic SHP to reduce BA synthesis .…”

Pharmacological properties of baicalin on liver diseases: a narrative review

“…Shen et al found that baicalin administration in mice significantly alleviates intrahepatic cholestasis and fibrosis after bile duct ligation [ 86 ]. Moreover, our previous work demonstrated that baicalin exerts a protective effect on estrogen-induced cholestatic liver injury via the induction of the sirtuin 1/hepatic nuclear receptor-1a/FXR signaling pathway, consequently maintaining hepatic bile acid homeostasis and alleviating hepatic inflammation [ 87 , 88 ]. However, the protective effect of baicalin on cholestatic liver injury needs further investigation in the future due to the complex pathogenesis of this injury, and multi-omics technology might be used to improve our knowledge on this protective effect.…”

Natural products for the prevention and treatment of cholestasis: A review

“…Zhang reported that baicalin at doses ranging from 50 mg/kg to 200 mg/kg significantly reversed 17α‐ethynylestradiol (EE)‐induced intrahepatic cholestasis. Baicalin has pharmacokinetic characteristics of increased in vivo exposure and delayed in vivo clearance that might contribute to its protective effect (Zhang et al, ).…”