Shikonin Protects Mitochondria Through the NFAT5/AMPK Pathway for the Treatment of Diabetic Wounds

Overview

Journal World J Diabetes

Publisher Baishideng Publishing Group

Specialty Endocrinology

Date 2024 Dec 16

PMID 39676806

Authors

Lu-Sha Cen

Yi Cao

Yi-Mai Zhou

Jing Guo

Jing-Wen Xue

Affiliations

Soon will be listed here.

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, and . 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 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 ( < 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 ( < 0.05). Shikonin also inhibited NFAT5, and ( < 0.05). Shikonin treatment reduced NFAT5 expression levels, subsequently inhibiting AMPK expression ( < 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 ( < 0.05).

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

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