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Calculus Bovis Sativus up-regulates hepatic protein 2(Mrp2) and Mrp4 in 17α-ethynylestradiol-induced cholestasis via a regulatory effect on ER signaling

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Journal of Traditional Chinese Medicine 2019年第3期39卷 402-409页

作者： Wu Tao Liu Dong Song Hongping Department of Pharmacy Wuhan Fourth Hospital/Puai Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China Department of Pharmacy Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430000 China

OBJECTIVE:To investigate the pathway through which Calculus Bovis Sativus (CBS) up-regulates hepatic multidrug resistance-associated protein 2 (Mrp2) and Mrp4 in 17α-ethynylestradiol (EE)-induced ***:Five groups of rats were designed:control group,EE+ICI182780 group,EE group,EE+CBS 50 mg/kg group and EE + CBS 150 mg/kg *** (50 and 150 ***-1· d-1) was orally given to rats by gavage for five consecutive days in coadministration with *** levels of cholestasis biomarkers,alanine aminotransferase (ALT),aspartate aminotransferase (AST),alkaline phosphatase (ALP) and total bilirubin (TBIL) were determined by biochemical *** bile flow was *** histopathology of the liver tissue was *** expression of Mrp2,Mrp3,Mrp4,estrogen receptor α(ERα) and ERβ was determined by Western ***:CBS markedly improved EE-induced *** exposure significantly reduced hepatic Mrp2 and Mrp4 expression compared with the control *** also dramatically up-regulated the expression of *** to the EE group,CBS notably up-regulated hepatic Mrp2 and Mrp4 but failed to influence the Mrp3 level ***182780,an ER antagonist,showed similar beneficial effects as *** expression of Mrp2 and Mrp4 caused by EE was also restored by ***,EE significantly induced hepatic ERα expression,which was reversed by ICI182780 or CBS (150 mg/kg) treatment,suggesting that CB5 exerted a moderate regulatory effect on ER ***:CBS up-regulated hepatic Mrp2 and Mrp4 expression in EE-induced cholestasis,which might be associated with its regulation of ER signaling.

关键词： Calculus Bovis Ethynylestradiol receptors,estrogen Multidrug resistance-associated proteins ICI182780

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Liuwei Dihuang formula(六味地黄方)protect endothelial cells from apoptosis by up-regulating expression of estrogen receptor-α

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Journal of Traditional Chinese Medicine 2021年第2期41卷 227-235页

作者： CHEN Qi QI Xu FU Yu JI Tingting CHAO Ying LI Jun MENG Qinghai BIAN Huimin LI Yu Collage of Pharmacy Nanjing University of Chinese MedicineNanjing 210023China Department of Respiratory Medicine The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica collage of PharmacyNanjing University of Chinese MedicineNanjing 210023China School of Medicine and Life Sciences Nanjing University of Chinese MedicineNanjing 210023China

OBJECTIVE:To evaluate the efficacy of Liuwei Dihuang formula(六味地黄方,LWDHF)on endothelial cells,and to study the mechanism behind the action of modulating expression of estrogen ***:Hydrogen peroxide(H_(2)O_(2))was applied to induce the apoptosis of human umbilical vein endothelial cells(HUVECs).The concentration of nitric oxide(NO),endothelial nitric oxide synthase(eNOS)and inducible NOS(iNOS)were measured by assay *** blot and real-time polymerase chain reaction(RT-PCR)were used to detect the expression of iNOS,eNOS,b-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),estrogen receptor(ER)αand ERβ.Also,small interfering RNA(siRNA)was involved to confirm whether the protective effects of LWDHF was medicated by *** vivo,the female rats were ovariectomized to establish postmenopausal vascular injury *** the model rats were divided into three groups and treated with saline,estradiol and LWDHF *** concentration of NO and NOS in serum were measured by assay kits,and the expression of Bax,Bcl-2,ERαand ERβwere detected by western blot and ***:In vitro study,LWDHF significantly protected HUVECs from H_(2)O_(2)-induced apoptosis,with the increase of Bcl-2 and the decrease of *** treatment with LWDHF inhibited concentration of NO and iNOS,and upregulated the expression of eNOS,ERαand ERβ.In addition,ERαsiRNA could block the protective effects of LWDHF,while ERβsiRNA showed little *** vivo,the treatment with LWDHF suppressed the vascular injury and reduced the level of NO and *** increased the expression of Bcl-2,ERαand ERβ,as well as inhibiting the Bax ***:LWDHF could improve endothelial function and protect HUVECs from apoptosis via increasing the expression of ERα.

关键词： human umbilical vein endothelial cells receptors,estrogen apoptosis Liuwei Dihuang

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