Therapeutic potential of icariin in rats with letrozole and high-fat diet-induced polycystic ovary syndrome

作者全名："Zuo, Ling; Hai, Yang; Zhang, Ruoyu; Zuo, Biao; Tian, Jiayu; Li, Pan; Ke, Xiumei; Wang, Meng; Ren, Li; Li, Xuezhi; Huang, Xuekuan; Wang, Jianwei"

作者地址："[Zuo, Ling; Hai, Yang; Zhang, Ruoyu; Zuo, Biao; Tian, Jiayu; Wang, Meng; Ren, Li; Li, Xuezhi; Huang, Xuekuan; Wang, Jianwei] Chongqing Med Univ, Coll Tradit Chinese Med, Chongqing Key Lab Tradit Chinese Med Prevent & Cur, Chongqing 400016, Peoples R China; [Hai, Yang] Chongqing Med Univ, Coll Basic Med, Chongqing 400016, Peoples R China; [Li, Pan; Ke, Xiumei] Chongqing Med Univ, Coll Pharm, Chongqing 400016, Peoples R China; [Huang, Xuekuan; Wang, Jianwei] Chongqing Key Lab Tradit Chinese Med Prevent & Cur, Chongqing 400016, Peoples R China"

通信作者："Huang, XK; Wang, JW (通讯作者)，Chongqing Key Lab Tradit Chinese Med Prevent & Cur, Chongqing 400016, Peoples R China."

来源：EUROPEAN JOURNAL OF PHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001024615800001

JCR分区：Q1

影响因子：4.2

年份：2023

卷号：953

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Polycystic ovary syndrome; Icariin; Apoptosis; Transcriptome; JAK2; STAT

摘要："Polycystic ovary syndrome (PCOS) is characterized by reproductive, endocrine, and metabolic disorders. Icariin has been shown to regulate endocrine and metabolic imbalances. This study aimed to determine the therapeutic effect and pharmacological mechanism of icariin in PCOS rats. Rats were fed a high-fat diet and gavaged with letrozole to induce PCOS. Thirty-six female rats were randomly divided into four groups: control, model, low dose, and high-dose icariin. After 30 days of treatment, we evaluated the therapeutic effects on weight and diet, sex hormone levels, ovarian morphology, estrous cycle, inflammatory factors, and indicators of glucolipid metabolism. Combined with the ovarian transcriptome, we verified the key markers of apoptosis and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway by RT-qPCR for mRNA level, western blot, and immunohistochemistry for protein expression. Icariin significantly improved ovarian function and reproductive endocrine disorders by regulating sex hormones, restoring the estrous cycle, and reducing ovarian morphological damage in PCOS rats. Icariin-treated rats had lower weight gain and reduced triglycerides, fasting insulin, HOMA-IR, TNF-& alpha;, and interleukin-6 with higher high-density lipoprotein cholesterol levels than PCOS rats. TUNEL staining showed icariin improved apoptosis in the ovaries. This was supported by an increase in Bcl2 and a decrease in Bad and Bax. Icariin decreased the ratios of p-JAK2/JAK2, pSTAT1/STAT1, p-STAT3/STAT3, and p-STAT5a/STAT5a, decreased IL-6, gp130 expression, and increased cytokine-inducible SH2-containing protein (CISH) and suppressor of cytokine signaling 1 (SOCS1) expression. The pharmacological mechanism may be related to the reduction in ovarian apoptosis and inhibition of the IL-6/ gp130/JAK2/STATs pathway."

基金机构："National Natural Science Founda-tion of China [81973653, 81374033]"

基金资助正文：Funding This study was supported by the National Natural Science Founda-tion of China (No. 81973653 and No. 81374033) .