Journal of ethnopharmacology · 2025
Research on the mechanism of Zuogui Wan in ameliorating oligoasthenozoospermia in rats via modulating cuproptosis-related pathways.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zha Yarong, Li Hongwei, Jiang Shan, Wang Zhuo, Liu Yang, Wei Zhitao, Yang Yong
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: Zuogui Wan (ZGW), a classic traditional Chinese medicine formula first recorded in Jingyue Quanshu by Zhang Jingyue in the Ming Dynasty, has a long history of use in nourishing kidney yin, replenishing essence, and treating male infertility related to kidney essence deficiency. Clinical practices and previous studies have supported its efficacy in improving oligoasthenozoospermia.
AIM OF THE STUDY: This study aims to utilize transcriptomic sequencing to predict the therapeutic targets and potential biological mechanisms of ZGW in treating Tripterygium Wilfordii Glycosides (GTW)-induced oligoasthenozoospermia in rats.
MATERIALS AND METHODS: A rat model of oligoasthenospermia was induced using GTW. A total of 66 SD rats were randomly divided into a control group, model group, L-carnitine group (LEV), and low(0.8 g/kg)-, medium(1.5 g/kg)-, and high(2.3 g/kg)-dose groups of ZGW. Each treatment group received consecutive gavage for 28 days. Sperm concentration and motility, sex hormone levels (T, FSH, LH, PRL, E2), and levels of SOD, GSH-PX, CAT, GSH, MDA, and ROS in testicular tissue were measured, along with morphological assessment of the testes using H&E staining. Differentially expressed genes were analyzed by RNA-Seq and subjected to functional enrichment analysis. Key pathways were verified using qPCR, Western blot, immunohistochemistry, immunofluorescence, and copper content measurement, including Nrf2/HO-1/GPX4/ACSL4, PGC-1α/TFAM, PRM1/PRM2, Bax/Bcl-2, and copper death-related genes FDX1, LIAS, DLAT, SLC31A1, ATP7A, and ATP7B.
RESULTS: Transcriptome analysis identified a total of 78 key genes related to both disease and treatment. Further validation showed that ZGW upregulates Nrf2, HO-1, and GPX4, downregulates ACSL4, and improves oxidative stress and lipid peroxidation; ZGW restores PGC-1α and TFAM expression, suggesting an improvement in mitochondrial biogenesis and energy metabolism; GW upregulates PRM1/PRM2, improving sperm nuclear protein replacement and DNA integrity; ZGW alters Bax/Bcl-2 expression, inhibiting germ cell apoptosis; ZGW significantly downregulates key proteins and genes related to cuproptosis, including FDX1, LIAS, DLAT, and SLC31A1, while upregulating ATP7A and ATP7B, and simultaneously reducing copper ion content in the testes.
CONCLUSION: This study, for the first time, confirms from multiple dimensions that ZGW alleviates GTW-induced testicular tissue damage and improves sperm quality by regulating the 'antioxidant-mitochondrial function-cuproptosis' interaction network. The research not only reveals the systemic mechanism of ZGW in treating oligoasthenoteratozoospermia but also provides an important basis for the modernization of classical Chinese medicine prescriptions.
AIM OF THE STUDY: This study aims to utilize transcriptomic sequencing to predict the therapeutic targets and potential biological mechanisms of ZGW in treating Tripterygium Wilfordii Glycosides (GTW)-induced oligoasthenozoospermia in rats.
MATERIALS AND METHODS: A rat model of oligoasthenospermia was induced using GTW. A total of 66 SD rats were randomly divided into a control group, model group, L-carnitine group (LEV), and low(0.8 g/kg)-, medium(1.5 g/kg)-, and high(2.3 g/kg)-dose groups of ZGW. Each treatment group received consecutive gavage for 28 days. Sperm concentration and motility, sex hormone levels (T, FSH, LH, PRL, E2), and levels of SOD, GSH-PX, CAT, GSH, MDA, and ROS in testicular tissue were measured, along with morphological assessment of the testes using H&E staining. Differentially expressed genes were analyzed by RNA-Seq and subjected to functional enrichment analysis. Key pathways were verified using qPCR, Western blot, immunohistochemistry, immunofluorescence, and copper content measurement, including Nrf2/HO-1/GPX4/ACSL4, PGC-1α/TFAM, PRM1/PRM2, Bax/Bcl-2, and copper death-related genes FDX1, LIAS, DLAT, SLC31A1, ATP7A, and ATP7B.
RESULTS: Transcriptome analysis identified a total of 78 key genes related to both disease and treatment. Further validation showed that ZGW upregulates Nrf2, HO-1, and GPX4, downregulates ACSL4, and improves oxidative stress and lipid peroxidation; ZGW restores PGC-1α and TFAM expression, suggesting an improvement in mitochondrial biogenesis and energy metabolism; GW upregulates PRM1/PRM2, improving sperm nuclear protein replacement and DNA integrity; ZGW alters Bax/Bcl-2 expression, inhibiting germ cell apoptosis; ZGW significantly downregulates key proteins and genes related to cuproptosis, including FDX1, LIAS, DLAT, and SLC31A1, while upregulating ATP7A and ATP7B, and simultaneously reducing copper ion content in the testes.
CONCLUSION: This study, for the first time, confirms from multiple dimensions that ZGW alleviates GTW-induced testicular tissue damage and improves sperm quality by regulating the 'antioxidant-mitochondrial function-cuproptosis' interaction network. The research not only reveals the systemic mechanism of ZGW in treating oligoasthenoteratozoospermia but also provides an important basis for the modernization of classical Chinese medicine prescriptions.