药学学报, 2019, 54(2): 308-312
引用本文:
赵莹莹, 陈燕, 韩杜菀, 单增福, 李孟, 冯卫生, 郑晓珂. 地黄苦苷元的雌激素样活性筛选研究[J]. 药学学报, 2019, 54(2): 308-312.
ZHAO Ying-ying, CHEN Yan, HAN Du-wan, SHAN Zeng-fu, LI Meng, FENG Wei-sheng, ZHENG Xiao-ke. Evaluation of the estrogenic effects of rehmapicrogenin[J]. Acta Pharmaceutica Sinica, 2019, 54(2): 308-312.

地黄苦苷元的雌激素样活性筛选研究
赵莹莹1, 陈燕1, 韩杜菀1, 单增福1, 李孟1, 冯卫生1,2, 郑晓珂1,2
1. 河南中医药大学药学院, 河南 郑州 450046;
2. 河南中医药大学呼吸疾病诊疗与新药研发河南省协同创新中心, 河南 郑州 450046
摘要:
探讨地黄苦苷元(rehmapicrogenin)的植物雌激素活性及其作用机制。采用小鼠子宫增重实验和MCF-7细胞增殖实验对地黄苦苷元进行雌激素样活性筛选。动物实验操作符合中华人民共和国“实验动物管理条例”。Western blot法检测子宫组织雌激素受体表达量,ELISA法检测小鼠血清雌二醇(E2)、黄体生成素(LH)、卵泡刺激素(FSH)水平的变化。采用特异性雌激素受体拮抗剂(ICI182,780)、雌激素受体α阻断剂(MPP)、雌激素受体β阻断剂(THC)、雌激素膜受体GPR30阻断剂(G15)进行MCF-7细胞增殖拮抗实验探讨其作用机制。结果表明,地黄苦苷元(50 mg·kg-1)显著提高性未成熟小鼠子宫指数(P<0.05),显著降低血清卵泡刺激素(FSH)、黄体生成素(LH)的水平(P<0.01);地黄苦苷元(6和8 μmol·L-1)能极显著促进MCF-7细胞增殖(P<0.01),且其对MCF-7细胞的促增殖作用可被ICI182,780、MPP、G15拮抗;Western blot结果显示,地黄苦苷元能显著增加小鼠子宫ERα、GPR30表达。本研究结果表明地黄苦苷元具有雌激素样活性,且通过ERα、GPR30共同介导。
关键词:   
Evaluation of the estrogenic effects of rehmapicrogenin
ZHAO Ying-ying1, CHEN Yan1, HAN Du-wan1, SHAN Zeng-fu1, LI Meng1, FENG Wei-sheng1,2, ZHENG Xiao-ke1,2
1. School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China;
2. Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment and Chinese Medicine Development of Henan Province, Henan University of Chinese Medicine, Zhengzhou 450046, China
Abstract:
This study offers preliminary insight into the phytoestrogen activity and mechanism of rehmapicrogenin. In this study, we characterized the estrogenic activity of rehmapicrogenin using immature female mice in vivo and MCF-7 cell proliferation assay in vitro. All the procedures for the care of the mice were conducted in accordance with the Regulations of Experimental Animal Administration issued by the State Committee of Science and Technology of the People's Republic of China. Uterine wet weight/body mass ratios, Western blot assay for estrogen receptor, and serum estrogen levels of estradiol (E2), luteinizing hormone (LH) and follicle stimulating hormone (FSH) were investigated. The effects of rehmapicrogenin, and the estrogen receptor antagonist ICI182,780, the estrogen receptor alpha antagonist MPP, the estrogen receptor beta antagonist THC, the G-protein coupled receptor 30 antagonist G15 combined with rehmapicrogenin on cell proliferation were examined in MCF-7 cells. Rehmapicrogenin (50 mg·kg-1) treatments demonstrated significant estrogenic activity by promoting the development of uterus in immature female mice, as well as increasing the expression of estrogen receptor alpha (ERα) and G-protein coupled receptor 30 (GPR30) at the protein level in uterus, and decreasing FSH and LH compared with the control group. Meanwhile, rehmapicrogenin (6 and 8 μmol·L-1) promoted the proliferation of MCF-7 cells, which were significantly antagonized by ICI182,780, MPP and G15. This study demonstrates rehmapicrogenin exerts estrogenic effects through ERα and GPR30.
Key words:   
收稿日期: 2018-10-23
DOI: 10.16438/j.0513-4870.2018-0962
基金项目: 河南省重大科技专项(171100310500);国家重点研发计划:中医药现代化研究重点专项(2017YFC1702800).
通讯作者: 郑晓珂,Tel:86-371-60190296,E-mail:zhengxk.2006@163.com
Email: zhengxk.2006@163.com
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参考文献:
[1] Zhu Y, Huang XP. Pharmacology and clinical application of estrogen[J]. Chin J New Drugs Clin Rem (中国新药与临床杂志), 2018, 37:S3-S8.
[2] Chen Q, Li WL, Ding ZD, et al. Study on two-way adjustment mechanism of traditional Chinese medicine phytoestrogens[J]. J Harbin Univ Commerce (哈尔滨商业大学学报(自然科学版)), 2014, 30:138-141.
[3] Ma Q, Wang DM. Application of epimedium in gynecological diseases[J]. Jilin J Tradit Chin Med (吉林中医药), 2017, 37:78-81.
[4] Su YF, Tian ZT, Ge SS, et al. Salvia application status and formulations in the treatment of gynecological diseases in the country[J]. Pract Pharm Clin Remed (实用医学志), 2014, 31:453-455.
[5] Guo ZK, Li LL, Wei J. Discussion on the compatibility of Astragalus and Rhizoma in the treatment of gynecological tumors[J]. Liaoning J Tradit Chin Med (辽宁中志), 2014, 41:1376-1377.
[6] Li HW, Meng XL. Research progress on chemical constituents and pharmacological activities of Rehmannia glutinosa[J]. Drug Eva Res (药物评价研究), 2015, 38:218-228.
[7] LI HF. Summary on pharmacological action and clinical usage of Rehmanniae radix[J]. J Pharm Res (药学研究), 2014, 36:345-347.
[8] Luo YX, Li XR, Yang JL, et al. Effect of Liuwei Dihuang Pills on ovarian function in natural aging SD rats[J]. J Ningxia Med Univ (宁夏医科大学学报), 2018, 40:512-516.
[9] Zheng XK, Liu ZY, Jiang Y, et al. Evaluation of the estrogenic effects of Rehmannia glutinosa Libosch[J]. Chin Pharm J (中国药学杂志), 2013, 48:1813-1836.
[10] Feng WS, Li M, Zheng XK, et al. Study on chemical of immunosuppressive parts from the roots of Rehmannia glutinasa[J]. Acta Pharm Sin (药学学报), 2014, 49:1496-1502.
[11] Evans RM. The steroid and thyroid hormone superfamily[J]. Science, 1988, 240:889-895.
[12] Beato M, Herrlich P, Schutz G. Steroid hormone receptors:many actors in search of a plot[J]. Cell, 1995, 83:851-857.
[13] Maggiolini M, Picard D. The unfolding stories of GPR30, a new membrane-bound estrogen receptor[J]. J Endocrinol, 2010, 2014:105-114.
[14] Andersen HR, Andersen AM, Aronold SF, et al. Comparison of short-term estrogenicity tests for identification of hormone-disrupting chemicals[J]. Environ Health Perspect, 1999, 107:89-108.
[15] Thigpen JE, Haseman JK, Saunders H, et al. Dietary factors affecting uterine weights of immature CD-1 mice used in uterotrophic bioassays[J]. Cancer Detect Prev, 2002, 26:381-393.
[16] Hall JM, McDonnell DP. The estrogen receptor beta-isoform (ER beta) of the human estrogen receptor modulates ER alpha transcriptional activity and is a key regulator of the cellular response to estrogens and antiestrogens[J]. Endocrinology, 1999, 140:5566-5578.
[17] Soto AM, Sonnenschein C, Chung KL, et al. The E-screen assay as a tool to identify estrogens:an update on estrogenic environmental pollutants[J]. Environ Health Perspect, 1995, 103:113-122.
[18] Sawada M, Alkayed NJ, Goto S, et al. Estrogen receptor antagonist ICI182,780 exacerbates ischemic injury in female mouse[J]. J Cereb Blood Flow Metab, 2000, 20:112-118.
[19] Chen Y, Hong DY, Wang J, et al. Baicalein, unlike 4-hydroxytamoxifen but similar to G15, suppresses 17β-estradiol-induced cell invasion, and matrix metalloproteinase-9 expressionand activation in MCF-7 human breast cancer cells[J]. Oncol Lett, 2017, 14:1823-1830.
[20] David S, Jean T. Estrogen regulation and ion dependence of taurine uptake by MCF-7 human breast cancer cells[J]. Cell Mol Biol Lett, 2007, 12:2177-2183.
[21] Watanabe K, Motoya E, Matsuzawa N. Marijuana extracts possess the effects like the endocrine disrupting chemicals[J]. Toxicology, 2004, 206:471-478.
[22] Li JM, Yang L, Wang YQ, et al. Study on the estrogen-like effects of glycyrrhetinic acid and glycyrrhizin[J]. Chin Prev Med (中国预防医学杂志), 2017, 18:168-172.