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Exp Clin Endocrinol Diabetes 2024; 132(10): 536-544
DOI: 10.1055/a-2322-7438
Article

Oridonin Attenuates Diabetes‑induced Renal Fibrosis via the Inhibition of TXNIP/NLRP3 and NF‑κB Pathways by Activating PPARγ in Rats

Gengzhen Huang‡
1   Chengdu University of Traditional Chinese Medicine, Chengdu, China
2   Chengdu Second people's Hospital, Chengdu, China
,
Yaodan Zhang‡
3   Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
,
Yingying Zhang‡
1   Chengdu University of Traditional Chinese Medicine, Chengdu, China
,
Xiaotao Zhou
1   Chengdu University of Traditional Chinese Medicine, Chengdu, China
,
Yuan Xu
1   Chengdu University of Traditional Chinese Medicine, Chengdu, China
,
Huiting Wei
1   Chengdu University of Traditional Chinese Medicine, Chengdu, China
,
Xian Chen
3   Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
,
Yuerong Ma
1   Chengdu University of Traditional Chinese Medicine, Chengdu, China
› Institutsangaben Funding Information the Science and Technology Strategic Cooperation Project of Nanchong City — 19SXHZ0181 the National Natural Science Foundation of China — 81973732 the Project of Sichuan Administration of Traditional Chinese Medicine — 2020JC0040 This study was supported by the National Natural Science Foundation of China (Grant No. 81973732), the Science and Technology Strategic Cooperation Project of Nanchong City (No. 19SXHZ0181), and the Project of Sichuan Administration of Traditional Chinese Medicine (No.2020JC0040).
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Abstract

Introduction Oridonin possesses remarkable anti-inflammatory, immunoregulatory properties. However, the renoprotective effects of oridonin and the underlying molecular mechanisms in diabetic nephropathy (DN). We hypothesized that oridonin could ameliorate diabetes‑induced renal fibrosis.

Methods Streptozocin (STZ)-induced diabetic rats were provided with a high-fat diet to establish a type 2 diabetes mellitus (T2DM) animal model, and then treated with Oridonin (10, 20 mg/kg/day) for two weeks. Kidney function and renal fibrosis were assessed. High glucose-induced human renal proximal tubule epithelial cells (HK-2) were also treated with oridonin. The expression of inflammatory factors and fibrotic markers were analyzed.

Results Oridonin treatment preserved kidney function and markedly limited the renal fibrosis size in diabetic rats. The renal fibrotic markers were inhibited in the oridonin 10 mg/kg/day and 20 mg/kg/day groups compared to the T2DM group. The expression of thioredoxin-interacting proteins/ nod-like receptor protein-3 (TXNIP/NLRP3) and nuclear factor (NF)‑κB pathway decreased, while that of peroxisome proliferator-activated receptor-gamma (PPARγ) increased in the oridonin treatment group compared to the non-treated group. In vitro, PPARγ intervention could significantly regulate the effect of oridonin on the high glucose-induced inflammatory changes in HK-2 cells.

Conclusion Oridonin reduces renal fibrosis and preserves kidney function via the inhibition of TXNIP/NLRP3 and NF‑κB pathways by activating PPARγ in rat T2DM model, which indicates potential effect of oridonin in the treatment of DN.

Keywords

oridonin - diabetes - renal fibrosis - NLRP3 - PPARγ


Publikationsverlauf

Eingereicht: 09. Juni 2023
Eingereicht: 29. März 2024

Angenommen: 08. Mai 2024

Accepted Manuscript online:
08. Mai 2024

Artikel online veröffentlicht:
02. September 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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