Therapeutic effects of pomegranate hot-water extract via inhibition of apoptosis and oxidative stress in a DHEA-induced mouse model of PCOS

IF 4.9 4区医学 Q2 INTEGRATIVE & COMPLEMENTARY MEDICINE

Integrative Medicine Research Pub Date : 2026-06-01 Epub Date: 2025-10-11 DOI:10.1016/j.imr.2025.101264

Sohee Moon , Yena Oh , Hajin Noh , Soo Dong Kim , Jae Youl Cho

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引用次数: 0

Abstract

Background

Polycystic ovarian syndrome (PCOS), which affects approximately 10 % of women of reproductive age worldwide, is closely associated with metabolic disturbances such as obesity and insulin resistance. Despite its high prevalence, the pathophysiology of PCOS is still not fully understood, underscoring the need for appropriate animal models and effective therapeutic strategies.

Methods

In this study, we established a PCOS mouse model through subcutaneous administration of dehydroepiandrosterone (DHEA) and investigated the therapeutic potential of a pomegranate (Punica granatum L.) hot water extract (Pg-hWE) (also called ESTROBAL®), administered orally.

Results

Histological analysis of ovarian tissue sections of mice showed that Pg-hWE improved ovulation function and suppressed cell death of follicles by promoting maintenance and regeneration of corpus luteum and reducing the number of atretic follicles. Furthermore, Pg-hWE showed inhibitory effects on gene and protein levels of apoptosis factors such as BAX, cleaved caspase-3, and cleaved caspase-9 in ovarian and uterine tissues. In addition, in ovarian tissues, it promoted apoptosis such as BAX and inhibited the expression of inflammation-related genes such as IL-6, TNF-α, and IFN-γ, while increasing the expression of Bcl-2, an anti-apoptosis factor. Plus, Pg-hWE demonstrated the ability to modulate hormonal balance by regulating the expression of CYP11A1 and CYP17A1, key genes encoding enzymes involved in androgen biosynthesis. Supporting these findings, studies using CHO-K1 cells confirmed that Pg-hWE exerts both anti-apoptotic and antioxidant effects, thereby linking its roles in mitigating PCOS, suppressing cell death, and controlling oxidative stress.

Conclusion

Collectively, these results indicate that Pg-hWE ameliorates PCOS-related pathology by reducing oxidative stress, suppressing apoptosis, and supporting hormonal balance, highlighting its promise as a natural therapeutic candidate.

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石榴热水提取物对dhea诱导的PCOS小鼠模型细胞凋亡和氧化应激的抑制作用

多囊卵巢综合征（PCOS）影响全球约10%的育龄妇女，与代谢紊乱（如肥胖和胰岛素抵抗）密切相关。尽管多囊卵巢综合征的发病率很高，但其病理生理机制仍未完全了解，因此需要适当的动物模型和有效的治疗策略。方法本研究通过皮下注射脱氢表雄酮（DHEA）建立PCOS小鼠模型，并研究口服石榴（Punica granatum L.）热水提取物（Pg-hWE）（也称为ESTROBAL®）的治疗作用。结果小鼠卵巢组织切片组织学分析显示，Pg-hWE通过促进黄体维持和再生，减少闭锁卵泡数量，改善排卵功能，抑制卵泡细胞死亡。此外，Pg-hWE对卵巢和子宫组织中BAX、cleaved caspase-3、cleaved caspase-9等凋亡因子的基因和蛋白水平均有抑制作用。此外，在卵巢组织中，它促进BAX等细胞凋亡，抑制IL-6、TNF-α、IFN-γ等炎症相关基因的表达，同时增加抗凋亡因子Bcl-2的表达。此外，Pg-hWE通过调节CYP11A1和CYP17A1的表达来调节激素平衡，CYP11A1和CYP17A1是编码雄激素生物合成酶的关键基因。使用CHO-K1细胞的研究证实，Pg-hWE具有抗凋亡和抗氧化作用，从而将其与减轻PCOS，抑制细胞死亡和控制氧化应激的作用联系起来，支持这些发现。总之，这些结果表明，Pg-hWE通过减少氧化应激、抑制细胞凋亡和支持激素平衡来改善pcos相关病理，突出了其作为天然治疗候选药物的前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Integrative Medicine Research Medicine-Complementary and Alternative Medicine

CiteScore

6.50

自引率

2.90%

发文量

审稿时长

12 weeks

期刊介绍： Integrative Medicine Research (IMR) is a quarterly, peer-reviewed journal focused on scientific research for integrative medicine including traditional medicine (emphasis on acupuncture and herbal medicine), complementary and alternative medicine, and systems medicine. The journal includes papers on basic research, clinical research, methodology, theory, computational analysis and modelling, topical reviews, medical history, education and policy based on physiology, pathology, diagnosis and the systems approach in the field of integrative medicine.