Sanqi oral solution ameliorates renal fibrosis by suppressing fibroblast activation via HIF-1α/PKM2/glycolysis pathway in chronic kidney disease

作者：Dongmei Hu, Lixin Wang, Yuanyuan Zhang, Xusheng Liu, Zhaoyu Lu, H. Li · 发表于：Journal of Ethnopharmacology · 年份：2024 · DOI：10.1016/j.jep.2024.118679 · 被引用次数：17 · 研究领域：Chronic Kidney Disease and Diabetes、Chemotherapy-induced organ toxicity mitigation、Kidney Stones and Urolithiasis Treatments

ETHNOPHARMACOLOGICAL RELEVANCE: Sanqi oral solution (SQ) is a traditional Chinese patent medicine, widely used to treat chronic kidney diseases (CKD) in the clinic in China. Previous studies have confirmed its anti-renal fibrosis effect, but the specific pharmacological mechanism is still unclear. AIM OF THE STUDY: Focusing on energy metabolism in fibroblasts, the renoprotective mechanism of SQ was investigated in vitro and in vivo. METHODS: Firstly, the fingerprint of SQ was constructed and its elementary chemical composition was analyzed. In the 5/6Nx rats experiment, the efficacy of SQ on the kidney was evaluated by detecting serum and urine biochemical indexes and pathological staining of renal tissues. Lactic acid and pyruvic acid levels in serum and renal tissues were detected. PCNA protein expression in kidney tissue was detected by immunofluorescence assay and Western blot. Expression levels of HIF-1α, PKM2 and HK2 were determined by immunohistochemistry, Western blot or RT-qPCR assay. In addition, the effect of SQ intervention on cell proliferation and glycolysis was evaluated in TGF-β1-induced NRK-49F cells, and the role of SQ exposure and HIF-1α/PKM2/glycolysis pathway were further investigated by silencing and overexpressing HIF-1α gene in NRK-49F cells. RESULTS: In 5/6 Nx rats, SQ effectively improved renal function and treated renal injury. It reduced the levels of lactic acid and pyruvic acid in kidney homogenates from CKD rats and decreased the expression leve...