Protective effects of petroleum ether extracts of Herpetospermum caudigerum against α-naphthylisothiocyanate-induced acute cholestasis of rats

Cao, Wen-rui; Ge, Jingqiu; Xie, Xin‐Bao; Fan, Menglin; Fan, Xu-dong; Wang, Hong; Dong, Zhaoyue; Liao, Zhihua; Lan, Xiaozhong; Chen, Min

doi:10.1016/j.jep.2017.01.003

Cited by 20 publications

(10 citation statements)

References 49 publications

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“…To date, evaluation of the effects of lignans on bile acids has only been conducted in animal models, mainly in the context of cholestasis [ 42 , 43 , 44 , 45 , 46 ] or hepatocarcinogenesis [ 47 , 48 ]. In vitro, ENL has been shown to inhibit cholesterol 7α hydroxylase (CYP7A1) activity, the enzyme involved in catalyzing the rate-limiting step in the conversion of cholesterol to primary bile acids, [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of a Flaxseed Lignan Intervention on Circulating Bile Acids in a Placebo-Controlled Randomized, Crossover Trial

et al. 2020

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Plant lignans and their microbial metabolites, e.g., enterolactone (ENL), may affect bile acid (BA) metabolism through interaction with hepatic receptors. We evaluated the effects of a flaxseed lignan extract (50 mg/day secoisolariciresinol diglucoside) compared to a placebo for 60 days each on plasma BA concentrations in 46 healthy men and women (20–45 years) using samples from a completed randomized, crossover intervention. Twenty BA species were measured in fasting plasma using LC-MS. ENL was measured in 24-h urines by GC-MS. We tested for (a) effects of the intervention on BA concentrations overall and stratified by ENL excretion; and (b) cross-sectional associations between plasma BA and ENL. We also explored the overlap in bacterial metabolism at the genus level and conducted in vitro anaerobic incubations of stool with lignan substrate to identify genes that are enriched in response to lignan metabolism. There were no intervention effects, overall or stratified by ENL at FDR < 0.05. In the cross-sectional analysis, irrespective of treatment, five secondary BAs were associated with ENL excretion (FDR < 0.05). In vitro analyses showed positive associations between ENL production and bacterial gene expression of the bile acid-inducible gene cluster and hydroxysteroid dehydrogenases. These data suggest overlap in community bacterial metabolism of secondary BA and ENL.

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Section: Discussionmentioning

confidence: 99%

Effect of a Flaxseed Lignan Intervention on Circulating Bile Acids in a Placebo-Controlled Randomized, Crossover Trial

et al. 2020

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“…In untreated cases, hepatic cholestasis can cause itchy skin, hyperlipidemia, and jaundice, which progresses to liver cirrhosis, fibrosis, and liver failure. Ursodeoxycholic acid is currently the only Food and Drug Administration (FDA) approved drug for the treatment of cholestasis that has not seen improvement in cholestasis symptoms in some patients after taking this drug [ 4 ]. Despite liver disorders being a global problem with high mortality and morbidity, there is no effective treatment to control their progression.…”

Section: Introductionmentioning

confidence: 99%

Antioxidant and Anti-Inflammatory Effects of Origanum majorana L. Methanolic Extract on Bile Duct Ligation in Male Rats

Gheitasi

Motaghi

Sadeghi

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Introduction. Cholestasis is caused by malfunction of the hepatobiliary system. This disorder is the result of the accumulation of bile fatty acids and other toxins in the liver. The aim of the current study was to investigate the antioxidative and hepatoprotective effects of methanolic extract of Origanum majorana L. (OM) on hepatic disorder and tissue damage induced by bile duct ligation (BDL) in rats. Materials and methods. Twenty-eight male Wistar rats were randomly divided into 4 groups including sham control group received vehicle (SC-V), bile duct ligation received vehicle (BDL-V), bile duct ligation group received OM extract (BDL + OM), and sham control group received OM extract (SC + OM). One day after surgery, the animals received vehicle or methanolic extract of OM 300 mg/kg/day for 7 consecutive days by oral gavage. Finally, the animals were anesthetized and the blood samples were collected from each animal. After sacrificing of animals, liver tissue from each rat was removed and divided into three parts: one part was used for preparing of homogenized tissue, one part was fixed in 10% neutral formalin for histopathology examination, and the third part was kept in liquid nitrogen for gene expression analysis. Biomarkers of oxidative stress in the liver tissue and serum, as well as histopathological changes of the liver, were assessed. Also, the gene expression of IL-1, TNF-α, TGF-β, and α-SMA has been measured. Results. The results showed that BDL-V significantly increased the activity of ALT, AST, ALP, and total bilirubin compared to the SC-V group. The oxidative stress markers such as MDA and FRAP significantly increased due to BDL, while the CAT activity reduced in the BDL-V group compared to SC-V group. Oral treatment with OM reduced ALT and AST activity, although it was not statistically significant. OM treatment considerably increased the activity of CAT compared to BDL group. BDL-V induced a significant histological change in the liver, while treatment with OM at a dose of 300 mg/kg showed a minor effect on histopathological changes. In addition, the mRNA of IL-1, TNF-α, TGF-β, and α-SMA significantly increased in the BDL-V group, while treatment with OM only significantly reduced TGF-β in comparison with BDL-V rats. Conclusions. The results of the present study showed that oral administration of OM extract had a moderate protective effect on cholestasis due to BDL. Indeed, more studies with different doses of extract are needed to confirm this finding.

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“…The rats in groups 4, 5, and 6 were intragastrically administered YCHD every 24 h for 10 consecutive days. The rats in group 3 were orally administered UDCA at a dose of 100 mg/kg every 24 h for 10 consecutive days, which is well-documented to treat induced liver injury and cholestasis ( Chen et al, 2016 ; Cao et al, 2017 ). Moreover, groups 1 and 2 were intragastrically treated with physiological saline (0.9%) at a dose of 1 mL/100 g. On the eighth day, all the groups, except for group 1, were treated with ANIT at a dose of 50 mg/kg to induce cholestatic liver injury.…”

Section: Methodsmentioning

confidence: 99%

Yinchenhao Decoction Ameliorates Alpha-Naphthylisothiocyanate Induced Intrahepatic Cholestasis in Rats by Regulating Phase II Metabolic Enzymes and Transporters

Ding

Zhang

et al. 2018

Front. Pharmacol.

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Yinchenhao Decoction (YCHD), a famous traditional Chinese formula, has been used for treating cholestasis for 1000s of years. The cholagogic effect of YCHD has been widely reported, but its pharmacodynamic material and underlying therapeutic mechanism remain unclear. By using ultra-high-performance liquid chromatography (UHPLC)-quadrupole time-of-flight mass spectrometry, 11 original active components and eight phase II metabolites were detected in rats after oral administration of YCHD, including three new phase II metabolites. And it indicated that phase II metabolism was one of the major metabolic pathway for most active components in YCHD, which was similar to the metabolism process of bilirubin. It arouses our curiosity that whether the metabolism process of YCHD has any relationship with its cholagogic effects. So, a new method for simultaneous quantitation of eight active components and four phase II metabolites of rhein, emodin, genipin, and capillarisin has been developed and applied for their pharmacokinetic study in both normal and alpha-naphthylisothiocyanate (ANIT)-induced intrahepatic cholestasis rats. The results indicated the pharmacokinetic behaviors of most components of YCHD were inhibited, which was hypothesized to be related to different levels of metabolic enzymes and transporters in rat liver. So dynamic changes of intrahepatic enzyme expression in cholestasis and YCHD treated rats have been monitored by an UHPLC-tandem mass spectrometry method. The results showed expression levels of UDP-glucuronosyltransferase 1-1 (UGT1A1), organic anion-transporting polypeptide 1A4 (OATP1A4), multidrug resistance-associated protein 2 (MRP2), multidrug resistance protein 1, sodium-dependent taurocholate cotransporter, and organic anion-transporting polypeptide 1A2 were significantly inhibited in cholestasis rats, which would account for reducing the drug absorption and the metabolic process of YCHD in cholestatic rats. A high dose (12 g/kg) of YCHD remarkably increased the expression of UGT1A1, bile salt export pump, MRP2, OATP1A4 in cholestasis rats presented it exhibited the greatest ameliorative effect on cholestasis, also particularly in histopathological examination and reducing levels of alanine transaminase, aspartate transaminase, total bilirubin, direct bilirubin, and total bile acid. Considering the metabolic process of bilirubin in vivo, the choleretic effect of YCHD is proven to be related to its regulatory action on expression of metabolic enzymes and transporters in cholestatic liver.

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Protective effects of petroleum ether extracts of Herpetospermum caudigerum against α-naphthylisothiocyanate-induced acute cholestasis of rats

Cited by 20 publications

References 49 publications

Effect of a Flaxseed Lignan Intervention on Circulating Bile Acids in a Placebo-Controlled Randomized, Crossover Trial

Effect of a Flaxseed Lignan Intervention on Circulating Bile Acids in a Placebo-Controlled Randomized, Crossover Trial

Antioxidant and Anti-Inflammatory Effects of Origanum majorana L. Methanolic Extract on Bile Duct Ligation in Male Rats

Yinchenhao Decoction Ameliorates Alpha-Naphthylisothiocyanate Induced Intrahepatic Cholestasis in Rats by Regulating Phase II Metabolic Enzymes and Transporters

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