Ponicidin alleviates atherosclerosis by inhibiting inflammation and oxidative stress through the SIRT1 and PI3K/Akt pathway

Articles in Press

Document Type : Original Article

Authors

1 Department of Internal Medicine-Cardiovascular, Guangming Traditional Chinese Medicine Hospital of Pudong New Area, Shanghai 201399, China

2 Department of Internal Medicine-Cardiovascular, Guangming Traditional Chinese Medicine Hospital of Pudong New Area, Shanghai 201321, China

10.22038/ijbms.2026.91294.19693

Abstract

Objective(s): Atherosclerosis (AS) is caused by dyslipidemia, chronic inflammation, and oxidative stress. Ponicidin, a diterpenoid from Isodon species, has reported anti-inflammatory and antioxidant effects, but its role in AS remains unclear.  In this study, we evaluated the therapeutic potential and safety of ponicidin in an experimental AS model.
Materials and Methods: ApoE-/- mice were fed a Western diet and treated with ponicidin (10 mg/kg/day, intraperitoneally) for 12 weeks. Hepatic and renal safety were assessed using histological and serum biochemical markers. Aortic plaque burden was quantified using hematoxylin  and eosin and Oil Red O staining. Plasma lipids, cytokines, oxidative stress markers, and antioxidant enzymes were measured using biochemical assays and ELISA. The effects on SIRT1 and PI3K/Akt/eNOS signaling were analyzed using immunohistochemistry, RT-qPCR, ELISA, and Western blotting.
Results: Ponicidin showed no liver or kidney toxicity and moderately altered the body weight. Treatment significantly reduced aortic root plaque coverage and lesion area while improving plasma lipid profiles (↓TG, ↓TC, ↓LDL-C, and ↑HDL-C). Serum cytokine analysis revealed decreased TNF-α, IL-1β, IL-6, MCP-1, and TGF-β1 levels, with elevated IL-10. Oxidative stress was attenuated, as evidenced by reduced malondialdehyde and myeloperoxidase levels, increased superoxide dismutase, catalase, and glutathione levels, and restored nitric oxide levels. Mechanistically, ponicidin up-regulated SIRT1 expression and enhanced the phosphorylation of PI3K, Akt, and eNOS, suggesting improved endothelial function.
Conclusion: Ponicidin protects against AS by improving lipid metabolism, reducing vascular inflammation and oxidative stress, and enhancing endothelial signaling.

Keywords

Main Subjects

References

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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 17 June 2026

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