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

作　　者：Lu-Sha Cen Yi Cao Yi-Mai Zhou Jing Guo Jing-Wen Xue 

机构地区：[1]Department of Ophthalmology,The First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine),Hangzhou 310006,Zhejiang Province,China [2]Department of Dermatology,The First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine),Hangzhou 310006,Zhejiang Province,China [3]The First School of Clinical Medicine,Zhejiang Chinese Medical University,Hangzhou 310006,Zhejiang Province,China [4]School of Biological and Chemical Engineering,Zhejiang University of Science and Technology,Hangzhou 310023,Zhejiang Province,China

出　　处：《World Journal of Diabetes》2024年第12期2338-2352,共15页世界糖尿病杂志（英文）

基　　金：Supported by National Natural Science Foundation of China,No.82104862;Zhejiang Provincial Natural Science Foundation of China,No.LTY22E030003;Scientific Research Project Foundation of Zhejiang Chinese Medical University,No.2023FSYYZZ01.

摘　　要：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 essen-tial for wound healing.However,the relationship among Shikonin,NFAT5,and mitochondrial function has not been thoroughly studied.Here,we offer new per-spectives on the advantages of shikonin for managing diabetes.AIM To assess the therapeutic mechanism of shikonin in diabetic wounds,its rela-tionship 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.

关 键 词：SHIKONIN Diabetic wounds NFAT5 Mitochondrial function AMPK Wound healing 

分 类 号：R587.1[医药卫生—内分泌]