Full
Outline
To investigate the potential mechanism by which dihydromyricetin (DHM) ameliorates diabetic nephropathy (DN), and to screen and validate its possible key molecular targets.
A DN model was established using db/db mice, and 100 mg/(kg·d) DHM was administered via gavage 5 d per week for totally 10 weeks. Renal morphological changes were observed after staining to evaluate the effects of DHM. GSE161885 and GSE270526 datasets were obtained from the Gene Expression Omnibus (GEO) database and analyzed in combination with the GeneCards database to screen for DN-related differentially expressed genes (DEGs). Protein-protein interaction (PPI) network and molecular docking were employed to predict potential DHM targets. Western blotting and immunofluorescence staining were performed to detect the effects of DHM on pyroptosis-related pathways in the renal tissues of db/db mice and in high glucose (HG)-induced human renal tubular epithelial cells (HK-2). The specific NLR family pyrin domain containing protein 3 (NLRP3) inhibitor MCC950 was also used to validate the predicted mechanism.
In vivo experiments showed that DHM significantly ameliorated renal pathological damage in db/db mice, alleviated glomerular hypertrophy and mesangial expansion, and markedly reduced Paller scores (P<0.001). Immunofluorescence staining revealed significantly weakened fluorescence signals for α-smooth muscle actin (α-SMA), fibronectin, and collagen Ⅰ in renal tissues. Western blot results showed that the expression levels of collagen Ⅰ, collagen Ⅲ, α-SMA, and transforming growth factor beta 1 (TGF-β1) were significantly decreased (P<0.05). A total of 16 DN-related DEGs were identified. Enrichment analysis revealed that these genes were primarily enriched in pathways such as viral protein interactions, cytokine-cytokine receptor interaction, and the AGE-RAGE signaling pathway in diabetic complications, and were primarily involved in gene functions such as the positive regulation of lymphocyte-mediated immunity, positive regulation of adaptive immune response, and chemokine activity. Molecular docking confirmed NLRP3 as a potential target of DHM. In vivo validation showed that DHM significantly down-regulated gasdermin-D (GSDMD) fluorescence signals and inhibited the expression of pyroptosis-related proteins including NLRP3, Caspase 1, Cleaved-Caspase 1, interleukin 18 (IL-18), and GSDMD (P<0.05). In vitro studies further confirmed that both DHM and the specific NLRP3 inhibitor MCC950 alleviate high glucose-induced fibrosis and pyroptosis in HIC-2 cells.
DHM can ameliorate the progression of DN, and its mechanism is related to inhibiting NLRP3 inflammasome-mediated pyroptosis, thereby alleviating renal inflammation and fibrosis.
11
3
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
关闭全屏
No. 86 Xueyuan South Road, Haidian District, Beijing
010-62662699(Operation and Technical Support)
qkjq@cast.org.cn
Copyright © 2025 China Association for Science and Technology. All rights reserved. For all open access content, the relevant licensing terms apply.
Sponsored by the Office of the Leading Group for Cybersecurity and Informatization of CAST, and supported by Science and Technology Review Publishing House
