鱼腥草素通过对 AMP 激活蛋白激酶和 SIRT1 分子通路的机理调节，改善大鼠的多囊卵巢综合征。

IF 3.1 4区医学 Q2 PHARMACOLOGY & PHARMACY

Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2024-12-01 Epub Date: 2024-07-04 DOI:10.1007/s00210-024-03257-7

Simerjeet Kaur Chahal, Atul Kabra

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引用次数: 0

摘要

鱼腥草素是一种多酚类黄酮，对代谢综合征具有多种药理作用。本研究旨在探讨菲赛汀对实验性多囊卵巢综合征（PCOS）的疗效。给雌性 Sprague-Dawley 大鼠注射米非司酮（20 毫克/千克/天）以诱导多囊卵巢综合征。用非西丁（20 毫克/千克和 40 毫克/千克）治疗 PCOS 大鼠，并进一步与治疗 PCOS 的常规药物盐酸二甲双胍进行比较。使用多索吗啡（一种 AMPK 抑制剂）探讨了非西丁的作用机制。然后，大鼠被处死以进一步分析生化和组织学参数。多囊卵巢综合征大鼠的发情周期不规则，血清睾酮（4.72 ± 0.139 ng/ml）、雌二醇（750.2 ± 16.56 pg/ml）、LH（30.33 ± 1.563 mIU/ml）、HOMA-IR（1.115 ± 0.049）、TNF-α（86.59 ± 3.93 pg/ml）、IL-6（55.34 ± 4.432 pg/ml）和 TBARS（3.867 ± 0.193 µmol/mg），同时与正常对照组相比，孕酮（11.67 ± 1.54 ng/ml）、FSH（13.33 ± 1.256 mIU/ml）、GSH（33.47 ± 1.348 µmol/mg）水平和 SOD（2.163 ± 0.298 U/mg ）活性也有所下降。高剂量菲赛汀能明显降低睾酮（3.014 ± 0.234 ng/ml）、雌二醇（533.7 ± 15.39 pg/ml）、LH（16.67 ± 1.62 mIU/ml）、HOMA-IR（0.339 ± 0.20）、TNF-α（46.02 ± 2.66 pg/ml）、IL-6（31.77 ± 3.47 pg/ml）和 TBARS（1.747 ± 0.185 µmol/mg），并提高孕酮（33.17 ± 1.447 ng/ml）、FSH（27.17 ± 1.42 mIU/ml）、GSH（60.35 ± 1.1.102 µmol/mg）水平和 SOD（4.513 ± 0.607 U/mg）活性。卵巢组织学显示，与正常对照组相比，多囊卵巢综合症大鼠的囊性卵泡明显增加。菲舍汀治疗可减轻这些变化。多索吗啡与非西汀同时使用可逆转非西汀对多囊卵巢综合征大鼠的有益作用。总之，这些研究结果突出表明，通过调节大鼠体内的 AMPK/SIRT1 信号，鱼腥草素有可能成为治疗多囊卵巢综合征的一种有前途的干预措施。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Fisetin ameliorates polycystic ovary syndrome in rats via a mechanistic modulation of AMP-activated protein kinase and SIRT1 molecular pathway.

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Fisetin ameliorates polycystic ovary syndrome in rats via a mechanistic modulation of AMP-activated protein kinase and SIRT1 molecular pathway.

Fisetin, a polyphenolic flavonoid, exhibits numerous pharmacological activities against metabolic syndromes. The present research aims to explore the therapeutic efficacy of fisetin in experimental polycystic ovary syndrome (PCOS). Female Sprague-Dawley rats were administered mifepristone (20 mg/kg/day) to induce PCOS. PCOS rats were treated with fisetin (20 mg/kg and 40 mg/kg) and further compared with metformin HCl, the conventional drug for PCOS. The mechanism of fisetin was explored using dorsomorphin (an AMPK inhibitor). Then, rats were sacrificed for further analysis of biochemical and histological parameters. PCOS rats exhibited irregular estrous cycles, increased serum testosterone (4.72 ± 0.139 ng/ml), estradiol (750.2 ± 16.56 pg/ml), LH (30.33 ± 1.563 mIU/ml), HOMA-IR (1.115 ± 0.049), TNF-α (86.59 ± 3.93 pg/ml), IL-6 (55.34 ± 4.432 pg/ml), and TBARS (3.867 ± 0.193 µmol/mg) along with declined progesterone (11.67 ± 1.54 ng/ml), FSH (13.33 ± 1.256 mIU/ml), GSH (33.47 ± 1.348 µmol/mg) levels, and SOD (2.163 ± 0.298 U/mg) activity as compared to normal control group. Fisetin high dose significantly lowers testosterone (3.014 ± 0.234 ng/ml), estradiol (533.7 ± 15.39 pg/ml), LH (16.67 ± 1.62 mIU/ml), HOMA-IR (0.339 ± 0.20), TNF-α (46.02 ± 2.66 pg/ml), IL-6 (31.77 ± 3.47 pg/ml), and TBARS (1.747 ± 0.185 µmol/mg) and enhances progesterone (33.17 ± 1.447 ng/ml), FSH (27.17 ± 1.42 mIU/ml), GSH (60.35 ± 1.1.102 µmol/mg) levels, and SOD (4.513 ± 0.607 U/mg) activity. The histology of ovarian tissues shows a significant increase in cystic follicles in PCOS rats compared with the normal control group. These alterations were attenuated with fisetin treatment. Administration of dorsomorphin with fisetin can reverse the beneficial effects of fisetin in PCOS rats. Altogether, these present findings highlight the potential of fisetin as a promising therapeutic intervention for the management of PCOS by modulating AMPK/SIRT1 signaling in rats.

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来源期刊

Naunyn-Schmiedeberg's archives of pharmacology 医学-药学

CiteScore

6.20

自引率

5.60%

发文量

142

审稿时长

4-8 weeks

期刊介绍： Naunyn-Schmiedeberg''s Archives of Pharmacology was founded in 1873 by B. Naunyn, O. Schmiedeberg and E. Klebs as Archiv für experimentelle Pathologie und Pharmakologie, is the offical journal of the German Society of Experimental and Clinical Pharmacology and Toxicology (Deutsche Gesellschaft für experimentelle und klinische Pharmakologie und Toxikologie, DGPT) and the Sphingolipid Club. The journal publishes invited reviews, original articles, short communications and meeting reports and appears monthly. Naunyn-Schmiedeberg''s Archives of Pharmacology welcomes manuscripts for consideration of publication that report new and significant information on drug action and toxicity of chemical compounds. Thus, its scope covers all fields of experimental and clinical pharmacology as well as toxicology and includes studies in the fields of neuropharmacology and cardiovascular pharmacology as well as those describing drug actions at the cellular, biochemical and molecular levels. Moreover, submission of clinical trials with healthy volunteers or patients is encouraged. Short communications provide a means for rapid publication of significant findings of current interest that represent a conceptual advance in the field.