Journal of ethnopharmacology · 2026
Xiaozheng Anshen Formula alleviates podocyte injury in diabetic kidney disease by restoring autophagy flux via inhibiting TRPC6-mediated calcium signaling.
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.
Yan Ziming, Bai Jiajia, Liang Yingnan, Du Yiran, Wu Ruifei, Chen Zhenjie, Wang Ying, Zhou Jingwei
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: Emerging evidence implicates podocyte autophagy and calcium channels in diabetic kidney disease (DKD). Xiaozheng Anshen Formula (XZASF) is a contemporary clinical empirical prescription that exerts prominent therapeutic effects against DKD.
AIM OF STUDY: This study investigated the mechanisms underlying XZASF-mediated reduction of proteinuria in DKD, identified its bioactive constituents, and pinpointed its principal therapeutic targets.
MATERIALS AND METHODS: A rat model of DKD was established by streptozotocin/high-fat diet (STZ/HFD). After 12 weeks of oral XZASF administration, urinary protein levels, renal function and histopathology were assessed. Immunofluorescence staining was performed to detect the podocyte markers. To predict potential therapeutic targets, network pharmacology was applied to integrate the screened bioactive components of XZASF with two sets of differentially expressed genes (DEGs). Finally, Western blot and immunofluorescence staining were employed to evaluate the effects of XZASF on the TRPC6-calcium signaling pathway and autophagy flux in both DKD rat kidneys and high-glucose (HG)-induced Mpc-5 cells.
RESULTS: Treatment with XZASF significantly reduced proteinuria and protected renal function in the DKD rat model. Network pharmacology and bioinformatic analysis revealed connections between XZASF and the TRPC6 calcium channel in podocytes, as well as the calcium signaling pathway, in DKD. Further validation confirmed that XZASF downregulated TRPC6 expression both in vivo and in vitro, suppressed cytosolic Ca2+ overload and calpain activation, preserved ATG5 and Beclin1, restored autophagic flux, and ultimately protected against podocyte injury and loss.
CONCLUSION: XZASF protects podocytes in DKD by restoring impaired autophagy through inhibition of the TRPC6-mediated calcium signaling pathway.
AIM OF STUDY: This study investigated the mechanisms underlying XZASF-mediated reduction of proteinuria in DKD, identified its bioactive constituents, and pinpointed its principal therapeutic targets.
MATERIALS AND METHODS: A rat model of DKD was established by streptozotocin/high-fat diet (STZ/HFD). After 12 weeks of oral XZASF administration, urinary protein levels, renal function and histopathology were assessed. Immunofluorescence staining was performed to detect the podocyte markers. To predict potential therapeutic targets, network pharmacology was applied to integrate the screened bioactive components of XZASF with two sets of differentially expressed genes (DEGs). Finally, Western blot and immunofluorescence staining were employed to evaluate the effects of XZASF on the TRPC6-calcium signaling pathway and autophagy flux in both DKD rat kidneys and high-glucose (HG)-induced Mpc-5 cells.
RESULTS: Treatment with XZASF significantly reduced proteinuria and protected renal function in the DKD rat model. Network pharmacology and bioinformatic analysis revealed connections between XZASF and the TRPC6 calcium channel in podocytes, as well as the calcium signaling pathway, in DKD. Further validation confirmed that XZASF downregulated TRPC6 expression both in vivo and in vitro, suppressed cytosolic Ca2+ overload and calpain activation, preserved ATG5 and Beclin1, restored autophagic flux, and ultimately protected against podocyte injury and loss.
CONCLUSION: XZASF protects podocytes in DKD by restoring impaired autophagy through inhibition of the TRPC6-mediated calcium signaling pathway.