Shikonin protects mitochondria through the NFAT5/AMPK pathway for the treatment of diabetic wounds.

IF 4.2 3区医学 Q1 ENDOCRINOLOGY & METABOLISM

World Journal of Diabetes Pub Date : 2024-12-15 DOI:10.4239/wjd.v15.i12.2338

Lu-Sha Cen, Yi Cao, Yi-Mai Zhou, Jing Guo, Jing-Wen Xue

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引用次数: 0

Abstract

Background: Shikonin is a natural remedy that is effective at treating diabetic wounds. NFAT5 is a potential therapeutic target for diabetes, and mitochondrial function is essential for wound healing. However, the relationship among Shikonin, NFAT5, and mitochondrial function has not been thoroughly studied. Here, we offer new perspectives on the advantages of shikonin for managing diabetes.

Aim: To assess the therapeutic mechanism of shikonin in diabetic wounds, its relationship with NFAT5, and its protection of mitochondrial function.

Methods: Hypertonic cell and diabetic wound mouse models were established. NFAT5 expression was measured through western blotting and immunofluorescence, in vivo and in vitro. Mitochondrial function was evaluated using reactive oxygen species (ROS) detection and JC-1 and Calcein AM dyes. Mitochondrial structures were observed using transmission electron microscopy. The NFAT5/AMPK pathway was analyzed using a transfection vector and an inhibitor. The effect of shikonin on cells under hypertonic conditions via the NFAT5/AMPK pathway was assessed using western blotting.

Results: Shikonin treatment preserved HaCaT cell viability, while significantly reducing cyclooxygenase-2 expression levels in a high-glucose environment (P < 0.05). Additionally, shikonin maintained mitochondrial morphology, enhanced membrane potential, reduced membrane permeability, and decreased ROS levels in HaCaT cells under hyperosmolar stress. Furthermore, shikonin promoted wound healing in diabetic mice (P < 0.05). Shikonin also inhibited NFAT5, in vivo and in vitro (P < 0.05). Shikonin treatment reduced NFAT5 expression levels, subsequently inhibiting AMPK expression in vitro (P < 0.05). Finally, shikonin inhibited several key downstream molecules of the NFAT5/AMPK pathway, including mammalian target of rapamycin, protein kinase B, nuclear factor kappa-light-chain-enhancer of activated B cells, and inducible nitric oxide synthase (P < 0.05).

Conclusion: Shikonin protects mitochondria via the NFAT5/AMPK-related pathway and enhances wound healing in diabetes.

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来源期刊

World Journal of Diabetes ENDOCRINOLOGY & METABOLISM-

自引率

2.40%

发文量

909

期刊介绍： The WJD is a high-quality, peer reviewed, open-access journal. The primary task of WJD is to rapidly publish high-quality original articles, reviews, editorials, and case reports in the field of diabetes. In order to promote productive academic communication, the peer review process for the WJD is transparent; to this end, all published manuscripts are accompanied by the anonymized reviewers’ comments as well as the authors’ responses. The primary aims of the WJD are to improve diagnostic, therapeutic and preventive modalities and the skills of clinicians and to guide clinical practice in diabetes. Scope: Diabetes Complications, Experimental Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus, Diabetes, Gestational, Diabetic Angiopathies, Diabetic Cardiomyopathies, Diabetic Coma, Diabetic Ketoacidosis, Diabetic Nephropathies, Diabetic Neuropathies, Donohue Syndrome, Fetal Macrosomia, and Prediabetic State.