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Inhibition of estrogen sulfation by Xian-Ling-Gu-Bao capsule

文献类型：期刊论文

作者He, Liangliang5; Chen, Chanjuan5; Duan, Shuyi4; Li, Yang5; Li, Chuan3; Yao, Xinsheng2,5; Gonzalez, Frank J.1; Qin, Zifei4,5; Yao, Zhihong2,3,4,5
刊名JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
出版日期2023
卷号225页码:12
关键词Xian-Ling-Gu-Bao capsule Estrogens Sulfotransferase enzymes Inhibitory effects Molecular docking
ISSN号0960-0760
DOI10.1016/j.jsbmb.2022.106182
通讯作者Qin, Zifei() ; Yao, Zhihong(yaozhihong_jnu@163.com)
英文摘要Xian-Ling-Gu-Bao capsule (XLGB) is a widely prescribed traditional Chinese medicine used for the treatment of osteoporosis. However, it significantly elevates levels of serum estrogens. Here we aimed to assess the dominant contributors of sulfotransferase (SULT) enzymes to the sulfation of estrogens and identify the effective inhibitors of this pathway in XLGB. First, estrone, 170-estradiol, and estriol underwent sulfation in human liver S9 extracts. Phenotyping reactions and enzyme kinetics assays revealed that SULT1A1, 1A2, 1A3, 1C4, 1E1, and 2A1 all participated in estrogen sulfation, with SULT1E1 and 1A1 as the most important contributors. The incubation system for these two active enzymes were optimized with Tris-HCl buffer, DL-Dithiothreitol (DTT), MgCl2, adenosine 3'-phosphate 5'-phosphosulfate (PAPS), protein concentration, and incubation time. Then, 29 compounds in XLGB were selected to investigate their inhibitory effects and mechanisms against SULT1E1 and 1A1 through kinetic modelling. Moreover, in silico molecular docking was used to validate the obtained results. And finally, the prenylated flavonoids (isobavachin, neobavaisoflavone, etc.) from Psoralea corylifolia L., prenylated flavanols (icariside II) from Epimedium brevicornu Maxim., tanshinones (dihydrotanshinone, tanshinone II-A,) from Salvia miltiorrhiza Bge., and others (corylifol A, corylin) were identified as the most potent inhibitors of estrogen sulfation. Taken together, these findings provide insights into the understanding regioselectivity of estrogen sulfation and identify the effective components of XLGB responsible for the promotion of estrogen levels.
WOS关键词UDP-GLUCURONOSYLTRANSFERASE ENZYMES ; PSORALEA-CORYLIFOLIA ; 1ST MULTICENTER ; HERBAL FUFANG ; IDENTIFICATION ; METABOLITES ; PHARMACOKINETICS ; GLUCURONIDATION ; HEPATOTOXICITY ; DETERMINANTS
资助项目National Natural Science Foundation of China ; Young Elite Scientists Sponsorship Program by Henan Association for Science and Technology ; Guangdong Basic and Applied Basic Research Foundation ; State Key Laboratory of Drug Research ; [81903704] ; [2022HYTP045] ; [2019A1515011285] ; [SIMM1903KF-07]
WOS研究方向Biochemistry & Molecular Biology ; Endocrinology & Metabolism
语种英语
WOS记录号WOS:000863945600001
出版者PERGAMON-ELSEVIER SCIENCE LTD
源URL[http://119.78.100.183/handle/2S10ELR8/302772]  
专题新药研究国家重点实验室
通讯作者Qin, Zifei; Yao, Zhihong
作者单位1.NCI, NIH, Ctr Canc Res, Lab Metab, Bethesda, MD USA
2.Jinan Univ, Int Cooperat Lab Tradit Chinese Med Modernizat Inn, Minist PR China, Guangzhou 510632, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, State key Lab Drug Res, Shanghai 201203, Peoples R China
4.Zhengzhou Univ, Affiliated Hosp 1, Dept Pharmacol, Zhengzhou 450052, Peoples R China
5.Jinan Univ, Coll Pharm, Guangzhou 510632, Peoples R China
推荐引用方式
GB/T 7714		 He, Liangliang,Chen, Chanjuan,Duan, Shuyi,et al. Inhibition of estrogen sulfation by Xian-Ling-Gu-Bao capsule[J]. JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY,2023,225:12.
APA He, Liangliang.,Chen, Chanjuan.,Duan, Shuyi.,Li, Yang.,Li, Chuan.,...&Yao, Zhihong.(2023).Inhibition of estrogen sulfation by Xian-Ling-Gu-Bao capsule.JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY,225,12.
MLA He, Liangliang,et al."Inhibition of estrogen sulfation by Xian-Ling-Gu-Bao capsule".JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY 225(2023):12.

入库方式： OAI收割

来源：上海药物研究所

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