1-Deoxynojirimycin attenuates diabetic cardiomyopathy via PI3K/AKT-mediated mitochondrial protection and anti-apoptosis.
DNJ shows promise in reducing diabetic cardiomyopathy markers in preclinical models, potentially through the PI3K/AKT pathway, but human studies are needed to confirm its therapeutic potential.
Where it sits
this study against the rest of the mots-c corpusSummary and findings
The study investigated the effects of 1-Deoxynojirimycin (DNJ) on diabetic cardiomyopathy using a high glucose-induced model in H9C2 cells and db/db mice. DNJ was found to potentially lower body weight and fasting blood glucose, enhance glucose tolerance, and improve cardiac performance. The effects were associated with the PI3K/AKT pathway, suggesting a mechanism for mitochondrial protection and anti-apoptosis.
Abstract
<h4>Ethnopharmacological relevance</h4>1-Deoxynojirimycin (DNJ), a naturally occurring alkaloid derived from mulberry leaves (Morus alba L.), is a powerful α-glucosidase inhibitor that has notable hypoglycemic effects. Nonetheless, the fundamental molecular mechanisms-especially diabetic cardiomyopathy (DCM)-are still not fully understood.<h4>Purpose</h4>This study sought to determine the cardioprotective effect of DNJ in diabetic cardiomyopathy and to elucidate the associated molecular mechanism.<h4>Methods</h4>A high glucose-induced DCM model was established in H9C2 cells and db/db mice. DNJ was administered by gavage or coculture with cells. The molecular mechanism of DNJ activity and changes in the activity of the PI3K/AKT pathway were evaluated by echocardiography, tissue staining, transmission electron microscopy, fluorescence probes, biochemical kits, Western blotting, and transcriptome sequencing, and the pathway was verified by the use of inhibitors.<h4>Results</h4>In vivo tests initially demonstrated that DNJ may lower body weight and fasting blood glucose levels; enhance glucose tolerance and cardiac performance; diminish myocardial fibrosis, myocardial hypertrophy, and lipid accumulation; and reduce myocardial cell death in db/db mice. DNJ therapy improved the HG-induced reduction in H9C2 cell viability, reduced ROS levels, mitigated oxidative damage, and inhibited cell death. DNJ can restore HG-mediated suppression of ATP5B expression and ATP levels, potentially enhancing mitochondrial energy utilization. The therapeutic efficacy of DNJ may be contingent upon the PI3K/AKT pathway, underscoring its regulatory significance, particularly in mediating cellular responses to oxidative stress and promoting cell survival in H9C2 cells.<h4>Conclusions</h4>Our preliminary findings suggest that DNJ may alleviate diabetic myocardial injury, possibly by triggering the PI3K/AKT pathway. This work offers a preliminary rationale for DNJ as a prospective treatment agent for DCM.
Background
Diabetic cardiomyopathy (DCM) is a complication of diabetes characterized by structural and functional changes in the heart muscle. Current treatments are limited, and understanding the molecular mechanisms involved is crucial for developing new therapies. This study explores the potential of 1-Deoxynojirimycin (DNJ), an α-glucosidase inhibitor, in mitigating DCM through mitochondrial protection and anti-apoptosis.
Methods
The study used a high glucose-induced DCM model in H9C2 cells and db/db mice. DNJ was administered via gavage in mice and cocultured with cells. Various techniques, including echocardiography, tissue staining, and Western blotting, were employed to assess the effects of DNJ and the involvement of the PI3K/AKT pathway.
Results
DNJ administration in db/db mice led to reductions in body weight and fasting blood glucose, improved glucose tolerance, and enhanced cardiac performance. It also decreased myocardial fibrosis, hypertrophy, and lipid accumulation. In H9C2 cells, DNJ improved cell viability, reduced ROS levels, and mitigated oxidative damage. The PI3K/AKT pathway was implicated in these effects, suggesting a role in mitochondrial protection and anti-apoptosis.
Interpretation
The findings suggest that DNJ may have a protective role in DCM by activating the PI3K/AKT pathway, which is known to mediate cellular responses to oxidative stress. However, the clinical significance of these findings is uncertain due to the preclinical nature of the study. Further research in humans is needed to confirm these effects and determine their therapeutic potential.
Key findings
- DNJ lowered body weight and fasting blood glucose in db/db mice.
- DNJ enhanced glucose tolerance and cardiac performance.
- DNJ reduced myocardial fibrosis, hypertrophy, and lipid accumulation.
- DNJ improved H9C2 cell viability and reduced ROS levels.
- DNJ's effects may involve the PI3K/AKT pathway.
Limitations
- Animal and cell model study only, no human data.
- No specific quantitative results or statistical significance reported.
- Potential confounding factors not addressed.