Azouz Asmaa A, Ali Sara E, Abd-Elsalam Reham M, Emam Shimaa R, Galal Mona K, Elmosalamy Sherif H, Alsherbiny Muhammed A, Hassan Bardes B, Li Chun Guang, El Badawy Shymaa A
Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.
Department of Physiology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.
Chin Med. 2021 Apr 29;16(1):36. doi: 10.1186/s13020-021-00444-z.
Complementary remedies such as the Chinese herb 'Sheng Ma' (Black cohosh; Actaea racemosa 'AR') are being sought to overcome the shortcomings of conventional hormonal and surgical therapies developed for the treatment of polycystic ovary syndrome (PCOS). However, AR-induced hepatotoxicity necessitates a cautionary warning to be labeled on its products as recommended by the United States Pharmacopeia, where four out of seven hepatotoxic cases in Sweden were possibly associated with black cohosh products.
We investigated the effects, safety, and molecular targets of black cohosh ethanolic extract and/or vitamin C on ovarian functionality and oxidative response in hyperandrogenism-induced PCOS rats. A well-established rat model using oral letrozole, daily, for 21 days was employed. The rats then received the AR extract with and without vitamin C for 28 days. The hormonal evaluation, antioxidant status, histopathological examination, immunohistochemical analysis, cell proliferation, and the expression ratio of the aromatase (Cyp19α1) gene were evaluated. Additionally, holistic profiling of the AR arsenal of secondary metabolites was performed using ultra-high-performance liquid chromatography (UHPLC) coupled with quadrupole high-resolution time of flight mass spectrometry (QTOF-MS).
Beneficial effects were exerted by AR in PCOS rats as antioxidant status, hormonal profile, lipid profile, glucose level, liver functions, and the induced Ki-67 expression in the granulosa, theca cell layers and interstitial stromal cells were all improved. Notably, the combination of AR with vitamin C was not only more effective in reversing the dysregulated levels of testosterone, luteinizing hormone, and mRNA level of Cyp19α1 gene in the PCOS rat, but also safer. The combination regulated both ovarian and hepatic malondialdehyde (MDA) and glutathione (GSH) levels with histological improvement observed in the liver and ovaries. In addition, the untargeted metabolomic profiling enabled the identification of 61 metabolites allocated in five major chemical classes.
This study demonstrated the benefit of the combinatorial effects of AR and vitamin C in mitigating the reproductive and metabolic disorders associated with PCOS with the elimination of AR hepatotoxic risk.
人们正在寻求诸如中药“升麻”（黑升麻；总状升麻“AR”）等补充疗法，以克服为治疗多囊卵巢综合征（PCOS）而开发的传统激素和手术疗法的缺点。然而，AR引起的肝毒性使得必须按照美国药典的建议在其产品上贴上警示标签，在瑞典的七例肝毒性病例中，有四例可能与黑升麻产品有关。
我们研究了黑升麻乙醇提取物和/或维生素C对高雄激素血症诱导的PCOS大鼠卵巢功能和氧化反应的影响、安全性及分子靶点。采用一种成熟的大鼠模型，每天口服来曲唑，持续21天。然后，大鼠接受含或不含维生素C的AR提取物，持续28天。评估激素水平、抗氧化状态、组织病理学检查、免疫组化分析、细胞增殖以及芳香化酶（Cyp19α1）基因的表达率。此外，使用超高效液相色谱（UHPLC）结合四极杆高分辨率飞行时间质谱（QTOF-MS）对AR次生代谢产物库进行整体分析。
AR对PCOS大鼠产生了有益作用，如抗氧化状态、激素水平、血脂水平、血糖水平、肝功能以及颗粒细胞、卵泡膜细胞层和间质基质细胞中诱导的Ki-67表达均得到改善。值得注意的是，AR与维生素C联合使用不仅在逆转PCOS大鼠睾酮、促黄体生成素水平失调以及Cyp19α1基因mRNA水平方面更有效，而且更安全。该联合用药调节了卵巢和肝脏的丙二醛（MDA）和谷胱甘肽（GSH）水平，肝脏和卵巢的组织学得到改善。此外，非靶向代谢组学分析鉴定出61种代谢产物，分属于五个主要化学类别。
本研究证明了AR和维生素C联合使用在减轻与PCOS相关的生殖和代谢紊乱方面的益处，同时消除了AR的肝毒性风险。
