Dandekar Manoj P, Tadas Manasi, Satthi Srilakshmi, Jangli Aditi, Shaikh Arbaz Sujat, Rao Gajula Siva Nageswara, Kaki Venkata Rao, Sonti Rajesh
Department of Biological Sciences, Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India.
Department of Biological Sciences, Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India.
Eur J Pharmacol. 2025 Jun 15;997:177613. doi: 10.1016/j.ejphar.2025.177613. Epub 2025 Apr 8.
Polycystic ovarian syndrome (PCOS) is a prevalent endocrine disorder in reproductive-age women, which also negatively perturbs person's psychiatric health. Herein, we investigated the effect of oxyberberine on PCOS- and depression-like phenotypes in female Sprague-Dawley rats. To generate PCOS- and depression-like phenotypes, rats were injected with letrozole (1 mg/kg/day for 21 days) and exposed to 14 days of chronic-unpredictable mild stress (CUMS). We synthesized oxyberberine from its natural parent phytoconstituent i.e., berberine. Rats underwent letrozole + CUMS exposure displayed an increased number of neutrophils in a vaginal smear test indicating a PCOS-like phenotype (i.e., disrupted estrus cycle). Moreover, these rats also showed anhedonia-, depression-, and anxiety-like behaviors in the sucrose-preference test, forced-swimming test, and elevated plus-maze test. Peroral administration of oxyberberine for 21 days, at 50 and 100 mg/kg doses, reversed letrozole + CUMS generated perturbations in rats. The total exploratory behavior in the open field test remained unaffected across the treatment groups. Oxyberberine treatment also restored the organ-weight index of the ovary and uterus and follicular development of the ovary. Systemic and uterine levels of oxyberberine were found to be 0.17-0.80 ng/mL and 1.03-3.62 ng/mL, respectively measured using a liquid chromatography-mass spectrometry assay. Oxyberberine also positively modulated the levels of catalase and malondialdehyde in intestine and spleen, and testosterone and luteinizing hormones in the systematic circulation and CYP17A1, CYP19A1, and SHBG expression in the ovary. These results suggest that oxyberberine improves PCOS- and depression-like phenotypes in rats by modulating testosterone hormone, CYP17A1, CYP19A1, and SHBG enzyme expression in the ovary.
多囊卵巢综合征（PCOS）是育龄女性中一种常见的内分泌紊乱疾病，它也会对人的心理健康产生负面影响。在此，我们研究了氧化小檗碱对雌性Sprague-Dawley大鼠的PCOS样和抑郁样表型的影响。为了产生PCOS样和抑郁样表型，给大鼠注射来曲唑（1mg/kg/天，共21天），并使其暴露于14天的慢性不可预测轻度应激（CUMS）中。我们从其天然母体植物成分即小檗碱合成了氧化小檗碱。接受来曲唑+CUMS暴露的大鼠在阴道涂片试验中显示中性粒细胞数量增加，表明存在PCOS样表型（即发情周期紊乱）。此外，这些大鼠在蔗糖偏好试验、强迫游泳试验和高架十字迷宫试验中还表现出快感缺失、抑郁和焦虑样行为。以50和100mg/kg剂量口服氧化小檗碱21天，可逆转来曲唑+CUMS对大鼠产生的干扰。在旷场试验中，各治疗组的总探索行为未受影响。氧化小檗碱治疗还恢复了卵巢和子宫的器官重量指数以及卵巢的卵泡发育。使用液相色谱-质谱分析法测定，发现氧化小檗碱的全身水平和子宫水平分别为0.17-0.80ng/mL和1.03-3.62ng/mL。氧化小檗碱还正向调节肠道和脾脏中的过氧化氢酶和丙二醛水平，以及全身循环中的睾酮和黄体生成素水平，以及卵巢中CYP17A1、CYP19A1和SHBG的表达。这些结果表明，氧化小檗碱通过调节卵巢中的睾酮激素、CYP十七烷酸1、CYP十九烷酸1和SHBG酶表达来改善大鼠的PCOS样和抑郁样表型。
