Key result
Luteolin administration prevented cardiac hypertrophy, fibrosis, and dysfunction in diabetic mice by upregulating AMPK and AKT/GSK-3 pathways and decreasing proteasome activity.
Why the study?
The mechanism of luteolin in diabetic myocardial hypertrophy remains uncertain, prompting evaluation of whether it improves diabetic cardiomyopathy by inhibiting proteasome activity.
Does luteolin prevent diabetic myocardial hypertrophy and dysfunction in diabetic mice and cardiomyocyte models?
Does luteolin prevent diabetic myocardial hypertrophy and dysfunction in diabetic mice and cardiomyocyte models?
Luteolin protects against diabetic cardiomyopathy in preclinical models by inhibiting proteasome activity and modulating AMPK and AKT/GSK-3 pathways.
Luteolin effects on diabetic cardiomyopathy remain preclinical; leaves open any clinical role pending trials.
INTRODUCTION: Luteolin is a flavonoid polyphenolic compound exerting broad pharmacological and medicinal properties. Diabetes-related obesity increases the total blood volume and cardiac output and may increase the myocardial hypertrophy progression. However, the mechanism of luteolin in diabetic myocardial hypertrophy remains uncertain. Therefore, this study aimed to evaluate whether luteolin improved diabetic cardiomyopathy (DCM) by inhibiting the proteasome activity. METHODS: Cardiomyopathy was induced in streptozotocin-treated diabetes mellitus (DM) and db/db mice. Luteolin (20 mg kg-1·day-1) was administrated via gavage for 12 weeks. In vitro, high glucose and high insulin (HGI, glucose at 25.5 mM and insulin at 0.1 µM) inducing primary neonatal rat cardiomyocytes (NRCMs) were treated with or without luteolin for 48 h. Echocardiography, reverse transcription quantitative polymerase chain reaction, histology, immunofluorescence, and Western blotting were conducted. Proteasome activities were also detected using a fluorescent peptide substrate. RESULTS: Luteolin administration significantly prevented the onset of cardiac hypertrophy, fibrosis, and dysfunction in type 1 DM (T1DM) and type 2 DM (T2DM). Compared with DCM mice, luteolin groups showed lower serum triglyceride and total cholesterol levels. Furthermore, luteolin attenuated HGI-induced myocardial hypertrophy and reduced atrial natriuretic factor mRNA level in NRCMs. Proteasome activities were inhibited by luteolin in vitro. Luteolin also reduces the proteasome subunit levels (PSMB) 1, PSMB2, and PSMB5 of the 20S proteasome, as well as proteasome-regulated particles (Rpt) 1 and Rpt4 levels of 19S proteasome. Furthermore, luteolin treatment increased protein kinase B (AKT) and GSK-3α/β (inactivation of GSK-3) phosphorylation. The phosphorylation level of AMPK activity was also reversed after the treatment with luteolin in comparison with the HGI-treated group. CONCLUSION: This study indicates that luteolin protected against DCM in mice, including T1DM and T2DM, by upregulating phosphorylated protein AMPK and AKT/GSK-3 pathways while decreasing the proteasome activity. These findings suggest that luteolin may be a potential therapeutic agent for DCM.
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Li et al. (2022) studied Diabetic cardiomyopathy. Luteolin vs. Untreated diabetic mice / HGI-treated cells was evaluated on Cardiac hypertrophy, fibrosis, dysfunction, and proteasome activity. Luteolin administration prevented cardiac hypertrophy, fibrosis, and dysfunction in diabetic mice by upregulating AMPK and AKT/GSK-3 pathways and decreasing proteasome activity.
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