临床传统医学和药理学（英文）2025，Vol.6Issue(4)：46-56,11.DOI:10.1016/j.ctmp.2025.200245
三七总皂苷通过调节TXNIP/NLRP3信号通路治疗小鼠糖尿病肾病
Total Panax notoginseng saponins treats diabetic kidney disease in mice by regulating the TXNIP/NLRP3 signaling pathway
摘要
Abstract
Background:The escalating diabetes pandemic presents a critical worldwide healthcare burden,with diabetic kidney disease(DKD)emerging as a predominant microvascular complication that frequently progresses to renal functional impairment.Current clinical interventions lack effective therapeutics to halt DKD progression. Objective:This study examined the nephroprotective mechanisms of total Panax Notoginseng saponins(TPNS)against DKD using cellular and animal models. Methods:In vitro,MPC-5 mouse renal podocytes were treated with 30 mM high glucose(HG)and co-treated with 20 μg/mL TPNS.Assessments included MTT assay for cell viability,flow cytometry for intracel-lular/mitochondrial reactive oxygen species(ROS)detection,Western blotting for key proteins involved in the PI3K/AKT/NRF2 and TXNIP/NLRP3 signaling pathways,and confocal microscopy for mitochondrial membrane potential analysis and immunofluorescence imaging of TXNIP/NLRP3.In vivo,the C57BLKs/J db/db mice(type 2 DKD model)were orally administered TPNS(50 mg/(kg·d)and 100 mg/(kg-d))for 8 weeks.Biochemical anal-yses(blood glucose,urinary protein,serum blood urea nitrogen(BUN),creatinine),ELISA for renal interleukin-6(IL-6),8-OHdG,and malondialdehyde(MDA)were performed,with hematoxylin-eosin(H&E)staining for renal histopathological evaluation. Results:In vitro,TPNS effectively counteracted HG-induced oxidative stress by inhibiting the PI3K/AKT signaling cascade,promoting nuclear translocation of NRF2,and upregulating downstream antioxidant enzymes(HO-1,NQO1).This intervention significantly reduced both cytoplasmic and mitochondrial ROS levels(P<0.001)and downregulated components of the TXNIP/NLRP3 pathway(P<0.01).In vivo,TPNS significantly reduced blood glucose,urinary protein,BUN,and creatinine(P<0.01),decreased the renal IL-6 and oxidative markers(8-OHdG,MDA),and ameliorated glomerular hypertrophy and tubular injury. Conclusion:TPNS mitigates DKD progression through dual modulation of the PI3K/AKT/NRF2 axis and the TXNIP/NLRP3 pathway.These findings support TPNS as a multi-target therapeutic candidate for DKD.关键词
三七总皂苷/糖尿病肾病/NLRP3/NRF2/PI3K/AKT/TXNIPKey words
Total Panax notoginseng saponins/Diabetic kidney disease/NLRP3/NRF2/PI3K/AKT/TXNIP引用本文复制引用
高翔,陈凌云,张春婷,高红伟,杨世林,黄国栋,刘秋霞,吕建珍..三七总皂苷通过调节TXNIP/NLRP3信号通路治疗小鼠糖尿病肾病[J].临床传统医学和药理学（英文）,2025,6(4):46-56,11.基金项目
Financial backing for this research was provided through the Guangxi Provincial Natural Science Research Fund[2022GXNS-FAA035608,2020GXNSFAA159070]along with the Guangxi Univer-sity Student Innovation and Entrepreneurship Development Initiative[S202413643003]. （）
