Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Phytomedicine. 2021 Oct;91:153654. doi: 10.1016/j.phymed.2021.153654. Epub 2021 Jul 12.
Polycystic ovary syndrome (PCOS) is a clinical syndrome with reproductive and endocrine disorders. Berberine is a monomer from Chinese herbs such as Coptis chinensis, whose effect on improving ovulation and endometrial receptivity of PCOS is uncertain.
To evaluate the effect of berberine on improving PCOS and explore the mechanism.
The rat model of PCOS was induced by intraperitoneal injection of testosterone propionate. Then they was divided into model (Mod) group, low-dose of berberine (BL) group, high-dose of berberine (BH) group and metformin (Met) group as well as a control (Con) group was established. Ovary morphology, hormone level, glucolipid metabolism were measured. UID-mRNA-seq of ovary tissue was conducted to seek the mechanism of berberine on improving ovulation. Three biomarkers of endometrial receptivity were also examined in endometrium by immunohistochemistry.
The number of cystic follicles was increased while the number of corpus luteum was decreased in the rats of Mod group. These changes could be reversed by high-dose of berberine intervention. Berberine could also decrease the levels of serum luteinizing hormone (LH) and total cholesterol (TC) in PCOS rats. Meanwhile, berberine improved the impairment of abnormal oral glucose tolerance without affecting fasting insulin level and Homeostasis model assessment-insulin resistance (HOMA-IR). Luteinizing hormone/ choriogonadotropin receptor (LHCGR) and cytochrome P450 Family 19 Subfamily A Member 1 (CYP19A1) were focused via RNA-seq of ovary. Protein expression in ovary and mRNA expression in granulosa cell of LHCGR and CYP19A1 were decreased in Mod group and rescued by the intervention of berberine. A decrease of endometrial thickness and an increase of integrin αvβ3 and lysophosphatidic acid receptor 3 (LPAR3) protein expression were observed in Mod group, which could be also reversed by berberbine.
Berberine could improve ovulation in PCOS and the mechanism might be associated with up-regulating LHCGR and CYP19A1. Berberine could also improve endometrial receptivity through down-regualting αvβ3 and LPAR3.
多囊卵巢综合征（PCOS）是一种生殖和内分泌紊乱的临床综合征。小檗碱是黄连等中草药中的一种单体，其改善 PCOS 排卵和子宫内膜容受性的效果尚不确定。
评价小檗碱改善 PCOS 的作用并探讨其机制。
采用睾酮丙酸酯腹腔注射诱导 PCOS 大鼠模型，分为模型（Mod）组、小檗碱低剂量（BL）组、小檗碱高剂量（BH）组和二甲双胍（Met）组，并设立对照组（Con）。检测卵巢形态、激素水平、糖脂代谢，进行卵巢组织 UID-mRNA-seq 以寻找小檗碱改善排卵的机制，通过免疫组化检测子宫内膜容受性的三个生物标志物。
Mod 组大鼠囊状卵泡数增加，黄体数减少，小檗碱高剂量干预可逆转上述改变。小檗碱还可降低 PCOS 大鼠血清促黄体生成素（LH）和总胆固醇（TC）水平。同时，小檗碱改善了异常口服葡萄糖耐量损伤，而不影响空腹胰岛素水平和稳态模型评估-胰岛素抵抗（HOMA-IR）。通过卵巢 RNA-seq 聚焦黄体生成素/绒毛膜促性腺激素受体（LHCGR）和细胞色素 P450 家族 19 亚家族 A 成员 1（CYP19A1）。Mod 组卵巢中 LHCGR 和 CYP19A1 的蛋白表达以及颗粒细胞中 mRNA 表达降低，小檗碱干预可恢复其表达。Mod 组子宫内膜厚度减少，整合素αvβ3 和溶血磷脂酸受体 3（LPAR3）蛋白表达增加，小檗碱也可逆转这种情况。
小檗碱可改善 PCOS 排卵，其机制可能与上调 LHCGR 和 CYP19A1 有关。小檗碱还可通过下调αvβ3 和 LPAR3 改善子宫内膜容受性。
