文献类型：期刊文献

英文题名：Mechanisms of Traditional Chinese Medicine in regulating Nrf2-related signaling pathways for the treatment of Oligoasthenozoospermia: A review

作者：Li, Shenglong[1];Jing, Shuaishuai[1];Zhou, Jiuyun[2];Li, Hui[1];Yin, Pengdong[1];Su, Lining[1];Gong, Meisheng[3];Zhao, Yongqiang[2];Lu, Ganggang[1];Jin, Guangwei[1]

第一作者：李淑玲

通信作者：Zhao, YQ[1]

机构：[1]Gansu Univ Chinese Med, Lanzhou, Peoples R China;[2]Gansu Prov Hosp Tradit Chinese Med, Lanzhou, Peoples R China;[3]Heilongjiang Acad Tradit Chinese Med, Harbin, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Prov Hosp Tradit Chinese Med, Lanzhou, Peoples R China.

年份：2026

卷号：360

外文期刊名：JOURNAL OF ETHNOPHARMACOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001662867900001)】；

基金：The project is funded by the Regional Science Fund of the National Natural Science Foundation of China (No. 82460897) , the Project of Enhancement of Traditional Chinese Medicine Innovation Capability of the Science and Technology Department of the State Administration ofTraditional Chinese Medicine (No. Gan Cai She [2023] No. 53) , the Project of Central Guided Local Science and Technology Development Funds (No. 24ZYQA037) , and the Project funded by Key Research and Development Funds of the Gansu Science and Technology Department (No. 22YF7FA101) ; the Gansu Provincial Natural Science Foundation (No. 22JR5RA638) ; Gansu Provincial Joint Research Fund Project (No. 25JRRA1227) .

语种：英文

外文关键词：Oligoasthenozoospermia; Nrf2; Signaling pathway; Traditional Chinese medicine (TCM); Oxidative stress; Ferroptosis

摘要：Ethnopharmacological relevance: Oligoasthenozoospermia (OAS) is among the leading causes of male infertility and is characterized by a complex pathogenesis. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a central transcription factor by which cellular redox homeostasis is maintained, chiefly through the Keap1-Nrf2-antioxidant response element (ARE) signaling pathway. Emerging evidence indicates that Traditional Chinese Medicine (TCM) has therapeutic potential to modulate Nrf2-related mechanisms and thereby ameliorate OAS. Aim of the study: This review is intended to summarize the role of the Nrf2 pathway in OAS pathogenesis and to evaluate therapeutic advances in TCM interventions, with emphasis on mechanistic features and potential applications in OAS management. Materials and methods: Relevant literature was systematically retrieved from PubMed, Web of Science, EMBASE, the Cochrane Library, Wanfang, and the China National Knowledge Infrastructure (CNKI). The following keywords were used: "oligoasthenozoospermia," "Nrf2," "oxidative stress," "ferroptosis," "traditional Chinese medicine," "Chinese herbal medicine," and "herbal compounds." Both experimental and clinical studies were included to comprehensively evaluate TCM-mediated regulation of Nrf2 in OAS. Inclusion criteria were as follows: (1) In vivo and in vitro studies relevant to the topic, as well as systematic reviews and meta-analyses. (2) Articles published in the past 10 years in peer-reviewed journals, in Chinese or English. (3) Studies evaluating Chinese medicine interventions-including classical formulae, single herbs, extracts, purified active constituents, and modern preparations-and acupuncture for OAS or related phenotypes. (4) Evidence implicating the Nrf2/ Keap1/ARE axis and its upstream or downstream nodes. (5) Reporting at least one quantitative outcome with sufficient statistics; experimental studies were required to specify the disease or injury model and dosing, route, and regimen. Exclusion criteria were as follows: (1) Abstracts, conference papers, theses/dissertations, editorials/ opinions, preprints, and non-systematic narrative reviews. (2) Absence of a control group or missing key dosing/ model details; missing primary outcomes or statistical results that precluded effect estimation. (3) Not related to OAS or lacking involvement of the Nrf2-related pathway; studies confined to nonreproductive models that could not be extrapolated to OAS. (4) Overlapping datasets; only the most complete or the most recent report was retained. Results: Activation of Nrf2 is associated with scavenging of reactive oxygen species, suppression of lipid peroxidation and ferroptosis, stabilization of mitochondrial function, mitigation of apoptosis and endoplasmic reticulum stress, repair of the blood-testis barrier, and preservation of testicular microenvironmental homeostasis. In this review, approximately 25 active compounds, 6 single-herb interventions, 20 multi-herb formulas, and several acupuncture modalities were identified; collectively, these TCM approaches target Nrf2-related pathways-modulating oxidative stress, ferroptosis, inflammation, and apoptosis-to promote spermatogenesis and improve reproductive function. Accumulating preclinical and clinical evidence indicates that TCM formulas and their active constituents protect against testicular injury and improve semen quality, thereby providing mechanistic underpinnings and practical strategies for OAS treatment. Conclusions: The Nrf2 signaling pathway is central to OAS pathogenesis through the regulation of oxidative stress, ferroptosis, autophagy, apoptosis, and endocrine homeostasis. TCM interventions, characterized by multi-component and multi-target actions, show promise and provide mechanistic insights and theoretical support for OAS prevention, treatment, and clinical translation. Integration of mechanistic research with clinical validation may facilitate precise targeting of Nrf2 and advance TCM modernization, thereby offering potentially safer and more effective therapeutic strategies for patients with OAS.