Evaluation of hepatotoxicity and cholestasis in rats treated with EtOH extract of Fructus Psoraleae

Wang, Jiaying; Jiang, Zhenzhou; Ji, Jin-Zi; Li, Yanyan; Chen, I‐Ming; Wang, Yurong; Zhang, Yun; Tai, Ting; Wang, Tao; Zhang, Luyong

doi:10.1016/j.jep.2012.08.028

Cited by 51 publications

(29 citation statements)

References 32 publications

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“…Notably, herbal medicines-drug interactions were significant clinical safety concerns, especially the reports of liver and renal injury induced by Psoralea corylifolia (Cheung et al, 2009;Teschke and Bahre 2009;Wang et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Metabolism and disposition of corylifol A from Psoralea corylifolia: metabolite mapping, isozyme contribution, species differences and identification of efflux transporters for corylifol A-O-glucuronide in HeLa1A1 cells

Yang

et al. 2020

Xenobiotica

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2020): Metabolism and disposition of corylifol A from Psoralea corylifolia: metabolite mapping, isozyme contribution, species differences, and identification of efflux transporters for corylifol A-O-glucuronide in HeLa1A1 cells, Xenobiotica, Abstract 1. Corylifol A (CA), a phenolic compound from Psoralea corylifolia, possessed several biological properties but poor bioavailability. Here we aimed to investigate the roles of cytochromes P450s (CYPs), UDP-glucuronosyltransferases (UGTs) and efflux transporters in metabolism and disposition of CA. 2. Metabolism of CA were evaluated in HLM, expressed CYPs and UGTs. Chemical inhibitors and shRNA-mediated gene siliencing of multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP) were performed to assess the roles of transporters in CA disposition. 3. Three oxidated metabolites (M1-M3) and two glucuronides (M4-M5) were detected. The intrinsic clearances (CL int ) values of M1 and M4 in HLM were 48.10 and 184.03 μL/min/mg, respectively. Additionally, CYP1A1, 2C8 and 2C19 were identified as main contributors with CL int values of 13.01~49.36 μL/min/mg, while UGT1A1, 1A7, 1A8 and 1A9 were with CL int values ranging form 85.01 to 284.07 μL/min/mg. Furthermore, activity correlation analysis proved CYP2C8, UGT1A1 and 1A9 were main active hepatic isozymes. Besides, rats and monkeys were appropriate model animals. Moreover, dipyridamole and MK571 both could significantly inhibit M4 efflux. Gene silencing results also indicated MRP4 and BCRP were major contributors in HeLa1A1 cells. 4. Taken together, CYPs, UGTs, MRP4 and BCRP were important determinants of CA A c c e p t e d M a n u s c r i p t pharmacokinetics.

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Section: Discussionmentioning

confidence: 99%

Metabolism and disposition of corylifol A from Psoralea corylifolia: metabolite mapping, isozyme contribution, species differences and identification of efflux transporters for corylifol A-O-glucuronide in HeLa1A1 cells

Yang

et al. 2020

Xenobiotica

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“…MRP2 is a multispecific organic anion transporter of the hepatocellular canalicular membrane and mediates the efflux of a variety of organic anions, including bilirubin, GSH, glucuronides, glutathione conjugates, and sulfated and glucuronidated BA (Konig et al, 1999;Kullak-Ublick et al, 2000;Shoda et al, 2004). During cholestasis, MRP2 exhibits a reduced expression that may contribute to impaired hepatic excretion of BA and other biliary constituents (Brandoni et al, 2012;Dietrich et al, 2004;Wang et al, 2012). During their enterohepatic circulation, approximately 95% of BA are efficiently reabsorbed in intestine and return to liver where they are taken up by hepatocytes and undergo a further cycle of biliary excretion and subsequent enterohepatic circulation.…”

Section: Discussionmentioning

confidence: 99%

Investigations of the total flavonoids extracted from flowers of Abelmoschus manihot (L.) Medic against α-naphthylisothiocyanate-induced cholestatic liver injury in rats

Yan

Zhang

et al. 2015

Journal of Ethnopharmacology

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“…Samples were assessed for β-actin content as an internal control. The relative expression of target proteins was calculated as the grayscale ratio of the target protein to that of β-actin [19] . Each experimental group was tested three times.…”

Section: Western Blot Analysismentioning

confidence: 99%

Resveratrol effectively attenuates α-naphthyl-isothiocyanate-induced acute cholestasis and liver injury through choleretic and anti-inflammatory mechanisms

et al. 2014

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Aim: α-Naphthylisothiocyanate (ANIT) is a well-characterized cholestatic agent for rats. The aim of this study was to examine whether resveratrol could attenuate ANIT-induced acute cholestasis and liver injury in rats. Methods: SD rats were treated with resveratrol (15 or 30 mg/kg, ip) or a positive control drug ursodeoxycholic acid (100 mg/kg, po) for 5 consecutive days followed by a single dose of ANIT (60 mg/kg, po). Bile flow, and serum biochemical markers and bile constituents were measured 48 h after ANIT administration. Hepatic levels of oxidative repair enzymes (glutathione peroxidase, catalase and MnSOD), myeloperoxidase activity, TNF-α, IL-6, and ATP content, as well as the expression of liver transporter genes and proteins were assayed. Results: ANIT exposure resulted in serious cholestasis and liver injury, as shown by marked neutrophil infiltration in liver, dramatically increased serum levels of ALT, AST, GGT, ALP, TBA, TBIL, IBIL, and DBIL, and significantly decreased bile excretion and biliary output of GSH and HCO 3 -. ANIT significantly increased TNF-α and IL-6 release and myeloperoxidase activity, decreased mitochondrial biogenesis in liver, but had little effect on hepatic oxidative repair enzymes and ATP content. Furthermore, ANIT significantly decreased the expression of Mrp2, FXR, and Cyp7a1, markedly increased Mrp3 expression in liver. Pretreatment with resveratrol attenuated ANITinduced acute cholestasis and liver injury, and other pathological changes. Pretreatment with ursodeoxycholic acid was less effective. Conclusion: Resveratrol effectively attenuates ANIT-induced acute cholestasis and liver injury in rats, possibly through suppression of neutrophil infiltration, as well as upregulation of expression of hepatic transporters and enzymes, thus decreasing accumulation of bile acids.

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Evaluation of hepatotoxicity and cholestasis in rats treated with EtOH extract of Fructus Psoraleae

Cited by 51 publications

References 32 publications

Metabolism and disposition of corylifol A from Psoralea corylifolia: metabolite mapping, isozyme contribution, species differences and identification of efflux transporters for corylifol A-O-glucuronide in HeLa1A1 cells

Metabolism and disposition of corylifol A from Psoralea corylifolia: metabolite mapping, isozyme contribution, species differences and identification of efflux transporters for corylifol A-O-glucuronide in HeLa1A1 cells

Investigations of the total flavonoids extracted from flowers of Abelmoschus manihot (L.) Medic against α-naphthylisothiocyanate-induced cholestatic liver injury in rats

Resveratrol effectively attenuates α-naphthyl-isothiocyanate-induced acute cholestasis and liver injury through choleretic and anti-inflammatory mechanisms

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