Cen Lu-Sha, Cao Yi, Zhou Yi-Mai, Guo Jing, Xue Jing-Wen
Department of Ophthalmology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 310006, Zhejiang Province, China.
Department of Dermatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 310006, Zhejiang Province, China.
World J Diabetes. 2024 Dec 15;15(12):2338-2352. doi: 10.4239/wjd.v15.i12.2338.
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.
To assess the therapeutic mechanism of shikonin in diabetic wounds, its relationship with NFAT5, and its protection of mitochondrial function.
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.
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).
Shikonin protects mitochondria the NFAT5/AMPK-related pathway and enhances wound healing in diabetes.
紫草素是一种对治疗糖尿病伤口有效的天然药物。核因子活化T细胞5（NFAT5）是糖尿病的一个潜在治疗靶点，而线粒体功能对伤口愈合至关重要。然而，紫草素、NFAT5和线粒体功能之间的关系尚未得到充分研究。在此，我们为紫草素在糖尿病治疗方面的优势提供了新的见解。
评估紫草素在糖尿病伤口中的治疗机制、其与NFAT5的关系以及对线粒体功能的保护作用。
建立高渗细胞和糖尿病伤口小鼠模型。通过蛋白质免疫印迹法和免疫荧光法检测NFAT5表达， 并 。使用活性氧（ROS）检测以及JC-1和钙黄绿素-AM染料评估线粒体功能。用透射电子显微镜观察线粒体结构。使用转染载体和抑制剂分析NFAT5/AMPK途径。通过蛋白质免疫印迹法评估紫草素在高渗条件下对细胞中NFAT5/AMPK途径的影响。
紫草素处理可维持人永生化角质形成细胞（HaCaT细胞）的活力，同时在高糖环境中显著降低环氧合酶-2的表达水平（P<0.05）。此外，在高渗应激下，紫草素可维持HaCaT细胞的线粒体形态，增强膜电位，降低膜通透性，并降低ROS水平。此外，紫草素可促进糖尿病小鼠伤口愈合（P<0.05）。紫草素还抑制NFAT5， 以及 （P<0.05）。紫草素处理降低了NFAT5表达水平，随后抑制了AMPK表达 （P<0.05）。最后，紫草素抑制了NFAT5/AMPK途径的几个关键下游分子，包括雷帕霉素靶蛋白、蛋白激酶B、活化B细胞核因子κB轻链增强子和诱导型一氧化氮合酶（P<0.05）。
紫草素通过NFAT5/AMPK相关途径保护线粒体，并增强糖尿病伤口愈合。
