Diabetes & Metabolism Journal

Original Article

Basic and Translational Research
Shionone Inhibits Glomerular Fibirosis by Suppressing NLRP3 Related Inflammasome though SESN2-NRF2/ HO-1 Pathway: Tian Xiao, Hanzhen Zhao, Yucong Wang, Mengyin Chen, Cong Wang, Chen Qiao; Diabetes Metab J. 2025;49(1):34-48. Published online August 28, 2024; DOI: https://doi.org/10.4093/dmj.2024.0024

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Background
Diabetic nephropathy (DN) is the most common and serious complication of diabetes mellitus. Shionone (SH), an important triterpenoid compound in the root extract of Aster, might exert a protective effect in DN mice and high glucose cultivated glomerular podocytes. The current study aimed to unravel the underlying mechanism by which SH mitigates DN. We postulate that SH stimulates the expression of sestrin-2 (SESN2), a pivotal stress-inducible protein in the anti-inflammasome machinery.
Methods
We utilized high-fat diet combined with streptozotocin (55 mg/kg intraperitoneal) for DN mice model, and high glucose (30 mM, 48 hours) cultured glomerular podocytes for DN cell model to evaluate the effect of SH. We also preformed experimentation on SESN2 deficiency models (SESN2 knockout mice and SESN2 siRNA in cells) to further prove our hypothesis.
Results
The results demonstrated that SH effectively suppressed glomerular fibrosis, induced adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, and inhibited NLR family pyrin domain containing 3 (NLRP3) activation. Furthermore, our findings revealed that SH exerted its anti-inflammatory effect through Sesn2-dependent nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation and subsequent activation of its downstream target heme oxygenase-1 (HO-1).
Conclusion
In summary, our findings suggest that SH serves as a promising therapeutic agent for the treatment of DN-related glomerular fibrosis. SH enhances the expression of SESN2, attenuates α-smooth muscle actin accumulation, and suppresses NLRP3-related inflammation through the Nrf2/HO-1 signaling pathway.

Citations

Citations to this article as recorded by

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Hereditas.2026;[Epub] CrossRef
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International Immunopharmacology.2026; 180: 116703. CrossRef
Advances in understanding the NLRP3 inflammasome‑mediated mechanisms and therapeutic targets in diabetic nephropathy (Review)
Xiwei Wang, Shuang Li, Xiaotian Ge, Tao Xie, Sainan Li, Ruiqi Yuan, Tianxi Li, Hui Yuan
International Journal of Molecular Medicine.2026; 58(1): 1. CrossRef
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Jing Feng, Zifei Wang, Xiyu Li, Chongyun Bao, Yu Xiao
ACS Applied Materials & Interfaces.2025; 17(4): 6144. CrossRef

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