Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.
Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China; Professional Technical Service Platform for Clinical Evaluation of Skin Health Related Products, Shanghai Science and Technology Commission, Shanghai, 200443, China; NMPA Key Laboratory for Monitoring and Evaluation of Cosmetics, Shanghai, 200443, China; Human Phenome Institute, Fudan University, Shanghai, 200433, China.
J Ethnopharmacol. 2023 Mar 1;303:115954. doi: 10.1016/j.jep.2022.115954. Epub 2022 Nov 24.
Diabetic ulcers (DUs) are one of the most severe complications of diabetes, and efficacious therapeutic means are currently lacking. Sheng-ji Hua-yu (SJHY) ointment is a classical Chinese traditional prescription that can significantly attenuate DU defects, but the specific mechanism remains to be fully elucidated.
In order to verify the underlying mechanism of SJHY ointment in accelerating the closure of DUs.
Modular pharmacology and molecular docking were utilized to predict the therapeutic targets of SJHY ointment against DUs. Male db/db diabetic mice and HaCaT cell models induced by methylglyoxal were used to validate the findings.
CCN1 was proven to be the core target of SJHY ointment involved in DUs treatment. CCN1 up-regulated by SJHY treatment (0.5 g/cm/day) at the mRNA and protein levels was detected on Day9 after wounding. With CCN1 knockdown, accelerated cell proliferation, migration, and anti-inflammatory effect of SJHY treatment (10 mg/L) were reversed.
SJHY ointment ameliorates cutaneous wound healing by up-regulating CCN1.
糖尿病溃疡(DU)是糖尿病最严重的并发症之一,目前缺乏有效的治疗手段。生肌化瘀(SJHY)软膏是一种经典的中药方剂,能显著减轻 DU 缺陷,但具体机制仍有待充分阐明。
为了验证 SJHY 软膏在加速 DU 愈合中的潜在机制。
采用模块药理学和分子对接技术预测 SJHY 软膏治疗 DU 的治疗靶点。利用甲基乙二醛诱导的雄性 db/db 糖尿病小鼠和 HaCaT 细胞模型进行验证。
证明 CCN1 是 SJHY 软膏治疗 DU 的核心靶点。在创伤后第 9 天,SJHY 治疗(0.5 g/cm/天)可检测到 CCN1 在 mRNA 和蛋白水平上调。CCN1 敲低后,SJHY 治疗(10 mg/L)促进细胞增殖、迁移和抗炎作用被逆转。
SJHY 软膏通过上调 CCN1 改善皮肤伤口愈合。