The effect of Bu Shen Huo Xue Tang on autoimmune premature ovarian insufficiency via Modulation of the Nrf2/Keap1 signaling pathway in mice
The effect of Bu Shen Huo Xue Tang on autoimmune premature ovarian insufficiency via Modulation of the Nrf2/Keap1 signaling pathway in mice
复制标题
补肾活血汤通过调节Nrf2/Keap1信号通路对小鼠自身免疫性卵巢早衰的影响
DOI：
10.1016/j.jep.2021.113996
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发表时间：
2021-03-16
影响因子：
5.4
通讯作者：
Wang, Peijuan
中科院分区：
文献类型：
--
作者：
Chen, Si;Lu, Yan;Wang, Peijuan
民族药理学相关性：补肾活血汤（BSHXT）是一种传统的中药配方，临床上用于治疗卵巢功能不全（POI）。然而，其治疗mechanism.Aim of the study：本研究旨在探讨BSHXT的药理活性的潜在分子机制，通过Nrf 2/Keap 1信号通路，在治疗自身免疫性POI.材料和方法：BSHXT的化学成分进行了分析，采用超高效液相色谱四极杆飞行时间串联质谱。用透明质酸（ZP）糖蛋白3抗原免疫小鼠两次，诱导自身免疫性POI小鼠模型。连续给自身免疫性POI小鼠施用BSHXT 28天。记录体重和器官指数。观察卵巢病理形态学变化。记录每只小鼠的发情周期。免疫荧光法检测小鼠卵巢中ZP抗体的水平。ZP抗体、卵泡刺激素（FSH）、抗M？测定血清中的勒氏管激素（AMH）、雌二醇（E2）、黄体生成素（LH）、超氧化物歧化酶（SOD）和丙二醛（MDA）。采用Q-PCR和免疫组化技术检测BSHXT水提物中Nrf 2/Keap 1信号通路相关基因和蛋白的表达。结果表明，补肾活血片能增加体重，提高卵巢指数，改善卵巢功能，减少发情周期紊乱。它还降低了POI小鼠卵巢和血清中ZP抗体的表达。BSHXT显著升高E2和AMH水平，降低FSH和LH水平。提高SOD水平，降低MDA水平。结论：补肾泻心汤对自身免疫性POI小鼠具有治疗作用，其机制可能与增强抗氧化能力和激活Nrf 2/Keap 1信号通路有关。BSHXT是一种很好的候选药物，可用作POI的保护剂，并可用于临床实践。
Ethnopharmacological relevance: Bu Shen Huo Xue Tang (BSHXT) is a traditional Chinese medicine formula that is clinically used in the treatment of premature ovarian insufficiency (POI). However, its therapeutic mechanism remains unclear.Aim of the study: This study aimed to investigate the underlying molecular mechanism of pharmacological activity of BSHXT, via the Nrf2/Keap1 signaling pathway, in the treatment of autoimmune POI.Materials and methods: The chemical composition of BSHXT was analyzed using ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry. The autoimmune POI mouse model was induced by immunizing mice twice, with zona pellucida (ZP) glycoprotein 3 antigen. The autoimmune POI mice were continuously administered BSHXT for 28 days. Body weight and organ indices were recorded. The pathological morphology of the ovaries was observed. The estrous cycle of each mouse was recorded. Immunofluorescence assay was used to detect the levels of ZP antibodies in the mouse ovaries. The levels of ZP antibodies, follicle-stimulating hormone (FSH), anti-M?llerian hormone (AMH), estradiol (E2), luteinizing hormone (LH), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured. The expression of genes and proteins involved in the Nrf2/Keap1 signaling pathway were measured by Q-PCR and IHC, respectively.Results: Twenty-one compounds were identified in the BSHXT water extract. BSHXT was found to increase the body weight and ovarian index, improve ovarian function, and reduce disorders in the estrus cycle. It also reduced the expression of ZP antibodies in the ovaries and serum of POI mice. BSHXT significantly increased E2 and AMH levels and decreased FSH and LH levels. It also increased the levels of SOD, and reduced MDA levels. The levels of Nrf2 and Keap1 were also increased, and the expression of Nrf2, HO-1 and NQO1 genes was upregulated.Conclusions: BSHXT has a therapeutic effect on autoimmune POI in mice, which may be a result of the enhanced antioxidant capacity and activation of the Nrf2/Keap1 signaling pathway. BSHXT is a good drug candidate for use as a protective agent for POI and may be used in clinical practice.