Luteolin Alleviates Diabetic Nephropathy Fibrosis Involving AMPK/NLRP3/TGF-(3 Pathway

被引:0
作者
Huang, Rong [1 ,2 ]
Zeng, Jun [1 ,2 ]
Yu, Xiaoze [1 ,2 ]
Shi, Yunke [3 ]
Song, Na [1 ,2 ]
Zhang, Jie [1 ,2 ]
Wang, Peng [1 ,2 ]
Luo, Min [1 ,2 ]
Ma, Yiming [3 ]
Xiao, Chuang [1 ,2 ]
Wang, Lueli [1 ,2 ]
Du, Guanhua [4 ]
Cai, Hongyan [5 ]
Yang, Weimin [1 ,2 ]
机构
[1] Kunming Med Univ, Sch Pharmaceut Sci, Kunming 650500, Yunnan, Peoples R China
[2] Kunming Med Univ, Yunnan Key Lab Pharmacol Nat Prod, Kunming 650500, Yunnan, Peoples R China
[3] Kunming Med Univ, Affiliated Hosp 1, Cardiol Dept, Kunming, Yunnan, Peoples R China
[4] Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, Key Lab Drug Target Res & Drug Screen, Beijing 100050, Peoples R China
[5] Kunming Med Univ, Dept Cardiol 2, Affiliated Hosp 1, Kunming 650032, Yunnan, Peoples R China
来源
DIABETES METABOLIC SYNDROME AND OBESITY | 2024年 / 17卷
基金
中国国家自然科学基金;
关键词
diabetic nephropathy; network pharmacology; inflammation; TGF-(3; fibrosis; ACTIVATION; MECHANISMS;
D O I
10.2147/DMSO.S450094
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Purpose: Luteolin is a promising candidate for diabetic nephropathy due to its potential anti-inflammatory and anti-fibrotic properties. This study explored the molecular mechanisms through which luteolin combats fibrosis in DN. Methods: Potential targets affected by luteolin and genes associated with DN were collected from databases. Overlapping targets between luteolin and diabetic nephropathy were identified through Venn analysis. A protein-protein interaction network was constructed using these common targets, and critical pathways and targets were elucidated through GO and KEGG analysis. These pathways and targets were confirmed using a streptozotocin-induced mouse model. Luteolin was administered at 45 mg/kg and 90 mg/ kg. Various parameters were evaluated, including body weight, blood glucose levels, and histopathological examinations. Protein levels related to energy metabolism, inflammation, and fibrosis were quantified. Results: Fifty-three targets associated with luteolin and 36 genes related to diabetic nephropathy were extracted. The AGE-RAGE signaling pathway was the key pathway impacted by luteolin in diabetic nephropathy. Key molecular targets include TGF-(3, IL-1(3, and PPARG. Luteolin reduced body weight and blood glucose levels, lowered the left kidney index, and improved insulin and glucose tolerance. Furthermore, luteolin mitigated inflammatory cell infiltration, basement membrane thickening, and collagen deposition in the kidney. Luteolin up-regulated the protein expression of p-AMPK alpha (Th172) while simultaneously down-regulated the protein expression of p-NF-& kgreen;B (p65), NLRP3, TGF-(31, alpha-SMA, and Collagen I. Conclusion: Luteolin mitigated renal fibrosis by alleviating energy metabolism disruptions and inflammation by modulating the AMPK/NLRP3/TGF-(3 signaling pathway.
引用
收藏
页码:2855 / 2867
页数:13
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