Dr. Vikram Sarabhai Institute of Cell and Molecular Biology, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, 390 002, India.
Nova IVI Fertility, Behind Xavier's Ladies Hostel, 108, Swastik Society Rd, Navrangpura, Ahmedabad, 390009, Gujarat, India.
J Ovarian Res. 2023 Mar 18;16(1):55. doi: 10.1186/s13048-023-01126-0.
Conventional drugs have limitations due to prevalence of contraindications in PCOS patients. To explore the potential effects of swertiamarin, on abrupted insulin and steroidogenic signaling in human luteinized granulosa cells from PCOS patients with or without insulin resistance.
hLGCs from 8 controls and 16 PCOS patients were classified for insulin resistance based on down regulation of protein expression of insulin receptor-β (INSR- β) as shown in our previous paper. Cells were grouped as control, PCOS-IR and PCOS-NIR, treated with swertiamarin (66 µM) and metformin (1 mM). Expression of key molecules involved in insulin signaling, fat metabolism, IGF system and steroidogenesis were compared between groups.
Swertiamarin significantly (P < 0.05) reversed the expression of INSR-β, PI(3)K, p-Akt, PKC-ζ, PPARγ, (P < 0.01) IRS (Ser 307) and IGF system in PCOS-IR group and was equally potent to metformin. In the same group, candidate genes viz SREBP1c, FAS, ACC-1 and CPT-1 were down regulated by swertiamarin (P < 0.001) and metformin (P < 0.001). Significant upregulation was demonstrated in expression of StAR, CYP19A1, 17β-HSD and 3β-HSD when treated with swertiamarin (P < 0.01) and metformin (P < 0.01) in PCOS-IR followed by increase in 17β-HSD and 3β-HSD enzyme activity along with estradiol and progesterone secretions. However, swertiamarin did not reveal any effect on PCOS-NIR group as compared to metformin that significantly (P < 0.01) reversed all the parameters related to steroidogenesis and down regulated basal expression of insulin signaling genes.
Swertiamarin, presents itself as a potential fertility drug in hLGCs from PCOS-IR patients.
由于多囊卵巢综合征（PCOS）患者普遍存在禁忌症，常规药物存在局限性。本研究旨在探讨裂环烯醚萜苷（swertiamarin）对胰岛素和类固醇生成信号通路的潜在影响，以观察其对胰岛素抵抗和非胰岛素抵抗的 PCOS 患者黄素化颗粒细胞的作用。
根据我们之前的研究结果，根据胰岛素受体-β（INSR-β）蛋白表达下调，将来自 8 名对照者和 16 名 PCOS 患者的 hLGC 分为胰岛素抵抗组。将细胞分为对照组、PCOS-IR 组和 PCOS-NIR 组，分别用裂环烯醚萜苷（66μM）和二甲双胍（1mM）处理。比较各组间胰岛素信号、脂肪代谢、IGF 系统和类固醇生成相关关键分子的表达。
裂环烯醚萜苷可显著（P<0.05）逆转 PCOS-IR 组 INSR-β、PI(3)K、p-Akt、PKC-ζ、PPARγ、（P<0.01）IRS（Ser307）和 IGF 系统的表达，其作用与二甲双胍相当。在同一组中，候选基因 SREBP1c、FAS、ACC-1 和 CPT-1 的表达被裂环烯醚萜苷（P<0.001）和二甲双胍（P<0.001）下调。裂环烯醚萜苷（P<0.01）和二甲双胍（P<0.01）可显著上调 PCOS-IR 组 StAR、CYP19A1、17β-HSD 和 3β-HSD 的表达，同时增加 17β-HSD 和 3β-HSD 酶活性以及雌二醇和孕酮的分泌。然而，与二甲双胍相比，裂环烯醚萜苷对 PCOS-NIR 组无明显作用，二甲双胍可显著（P<0.01）逆转与类固醇生成相关的所有参数，并下调胰岛素信号基因的基础表达。
裂环烯醚萜苷可能成为胰岛素抵抗的 PCOS 患者 hLGC 中潜在的生育药物。
