Curcumin analog JM-2 alleviates diabetic cardiomyopathy inflammation and remodeling by inhibiting the NF-κB pathway.

Abstract

Cardiac inflammation is an important pathological process in diabetic cardiomyopathy (DCM). Curcumin is a natural compound found in the rhizome of Curcuma longa and has been shown to possess multifunctional bioactivities. In the present study, we identified a new curcumin-derived compound, JM-2, and investigated its therapeutic effects against DCM in mouse models of streptozotocin-induced type 1 diabetes mellitus (T1DM) and HFD-induced type 2 diabetes (T2DM). Treatment with JM-2 (10 mg/kg) prevented cardiac functional and structural deficits effectively and reduced cardiac inflammation and fibrosis. JM-2 administration attenuated DCM by inhibiting nuclear factor kappa-B (NF-κB) activation in the heart of both models. In addition, treatment with JM-2 completely prevented the increase in proinflammatory factors and macrophage infiltration in T1DM and T2DM mice. RNA-seq analysis showed that the anti-inflammatory activity of JM-2 was associated with the inhibition of NF-κB activation. In vitro, JM-2 suppressed high glucose (HG)-induced myocardial hypertrophy and fibrosis in H9c2 cells, accompanied by inhibition of HG-induced NF-κB activation. Collectively, our results showed that JM-2, a new curcumin analog, provides strong protection against DCM via inhibition of the NF-κB-mediated inflammation. In summary, our data suggest that the curcumin analog JM-2 may be a potential therapeutic agent for DCM.

• Authors: Minxiu Wang, Leiming Jin, Qianhui Zhang, Weiwei Zhu, Hanghui He, Shuaijie Lou, Wu Luo, Xue Han, Guang Liang
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 154 Pg. 113590 (Oct 2022) ISSN: 1950-6007 [Electronic] France
• PMID: 36057221 (Publication Type: Journal Article)
• Copyright: Copyright © 2022. Published by Elsevier Masson SAS.

Chemical References

• NF-kappa B
• Curcumin

Topics

• Animals
• Curcumin (metabolism, pharmacology, therapeutic use)
• Diabetes Mellitus, Type 1 (complications, drug therapy, metabolism)
• Diabetes Mellitus, Type 2 (drug therapy)
• Diabetic Cardiomyopathies (metabolism)
• Fibrosis
• Inflammation (metabolism)
• Mice
• Myocytes, Cardiac
• NF-kappa B (metabolism)