期刊
BIOMEDICINE & PHARMACOTHERAPY
卷 154, 期 -, 页码 -出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2022.113590
关键词
Diabetic cardiomyopathy; JM-2; Inflammation; NF-kappa B; Curcumin
资金
- National Natural Science Foundation of China [21961142009]
- Zhejiang Provincial Key Scientific Project [2021C03041]
- Natural Science Foundation of Zhejiang Province [LGJ18H310002]
The curcumin analog JM-2 was found to effectively prevent and reduce cardiac functional and structural deficits in diabetic cardiomyopathy (DCM) through inhibition of NF-kappa B-mediated inflammation. JM-2 exhibited anti-inflammatory and anti-fibrotic activities both in vivo and in vitro.
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 bio-activities. 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-kappa B) 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-kappa B activation. In vitro, JM-2 suppressed high glucose (HG)-induced myocardial hypertrophy and fibrosis in H9c2 cells, accompanied by inhibition of HG-induced NF-kappa B activation. Collectively, our results showed that JM-2, a new curcumin analog, provides strong protection against DCM via inhibition of the NF-kappa B-mediated inflammation. In summary, our data suggest that the curcumin analog JM-2 may be a potential therapeutic agent for DCM.
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