基于网络药理学的牛蒡子和枸杞子生精功能障碍有效成分及潜在靶点预测策略

Jianxiong Ma , Siqi Guan , Yutian Zhu , Lei Dong , Xiting Wang , Wangqiang Chen , Caifei Ding , Bodong Lv , Hongxuan Tong
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引用次数: 1

摘要

中药Cuscutae semen (SC, Tusizi from Cuscuta chinensis Lam.)和Lycii fructus (FL,枸杞from Lycium barbarum L.)也被用作草药对(SC-FL)来治疗各种疾病,包括生精功能障碍(SD),一种导致男性低生育能力的疾病。目的进一步确定该中药对治疗SD的生物活性成分、作用靶点及部分分子机制。方法采用中药系统药理学数据库,结合超高效液相色谱(UHPLC)分析,对SC-FL中药对的有效成分进行分析,探讨其治疗生精功能障碍(SD)的可能靶点和作用机制。此外,我们使用雷公藤(雷公藤)的葡萄糖苷建立了Sprague-Dawley大鼠模型,以评估SC-FL对SD的作用及其潜在机制,以及药理学分析得出的某些关键靶点和通路的可靠性。结果我们在SC-LF中鉴定出56种有效成分,影响41种影响SD治疗结果的重叠基因信号。通过对基因本体、京都基因和基因组通路百科全书的分析,获得262个基因本体(GO)术语和170个通路,预测SC-LF治疗SD的主要生物学过程是细胞增殖和细胞凋亡。结果表明,SC-FL处理显著提高SD模型大鼠睾丸脏器系数、精子数量和活力,减少睾丸损伤和睾丸组织细胞凋亡。机制上,SC-FL显著上调抗凋亡蛋白AR和BCL2的表达水平,下调促凋亡蛋白BAD、BAX、cleaved caspase 3和CASP3的表达水平。综上所述,SC-FL可能通过调控细胞凋亡而发挥保护作用,是一种治疗男性不育症的有效试剂。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Network Pharmacology-based Strategy for Predicting Active Ingredients and Potential Targets of Cuscutae semen and Lycii fructus in Spermatogenic Dysfunction

Network Pharmacology-based Strategy for Predicting Active Ingredients and Potential Targets of Cuscutae semen and Lycii fructus in Spermatogenic Dysfunction

Background

Traditional Chinese Medicine (TCM) Cuscutae semen (SC, Tusizi from Cuscuta chinensis Lam.) and Lycii fructus (FL, Gouqi from Lycium barbarum L.), are also used as a herb pair (SC-FL) to treat various ailments, including spermatogenic dysfunction (SD), a disease responsible for low fertility in males.

Objective

Herein, we will further determine the bioactive components, component targets and partial molecular mechanisms of the herb pair for the treatment of SD.

Methods

We employed the traditional Chinese medicine systems pharmacology database in combination with Ultra high performance liquid chromatography (UHPLC) analysis to analyze the active ingredients of the SC-FL herbal pair and explore its possible targets and underlying mechanism in treatment of spermatogenic dysfunction (SD). Moreover, we used a Sprague-Dawley rat model, generated by using glucosides of Tripterygium wilfordii (GTW), to evaluate the effect of SC-FL and the underlying mechanism on SD and reliability of certain key targets and pathways obtained from the pharmacology analysis.

Results

We identified 56 active ingredients in SC-LF affecting 41 overlapping gene signals that influenced SD treatment outcomes. 262 Gene Ontology (GO) terms and 170 pathways were yielded under analyses of Gene Ontology, Kyoto Encyclopedia of Gene and Genome pathway from which we predicted that cell proliferation and apoptosis were the primary biological processes (BP) involved in the treatment of SD by SC-LF. The results showed that SC-FL treatment significantly improved the testicular organ coefficient along with sperm count and motility, while reduced testicular damage and testicular tissue cell apoptosis in SD model. Mechanistically, SC-FL significantly upregulated the expression levels of anti-apoptotic proteins AR and BCL2 and downregulated those of pro-apoptotic proteins BAD, BAX, cleaved caspase 3, and CASP3.

Conclusion

Collectively, these results indicated that SC-FL elicited a protective effect by potentially regulating apoptosis, thus suggesting that it will represent an effective reagent for male infertility.

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来源期刊
Clinical complementary medicine and pharmacology
Clinical complementary medicine and pharmacology Complementary and Alternative Medicine
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