Sheng-ji Hua-yu ointment ameliorates cutaneous wound healing in diabetes via up-regulating CCN1.
Sheng-ji Hua-yu ointment ameliorates cutaneous wound healing in diabetes via up-regulating CCN1.
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DOI：
10.2139/ssrn.4243464
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发表时间：
2022-11
影响因子：
5.4
通讯作者：
Dan-Zhou Yang;Yilun Tan;Ying Zhang;Jiankun Song;Yue Luo;Ying Luo;Xiao-ya Fei;Y. Ru;Bin Li-B
中科院分区：
文献类型：
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作者：
Dan-Zhou Yang;Yilun Tan;Ying Zhang;Jiankun Song;Yue Luo;Ying Luo;Xiao-ya Fei;Y. Ru;Bin Li-B
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。生肌化瘀膏是一种能明显改善DU缺陷的经典中药方剂，但其具体作用机制尚未完全阐明。研究目的：探讨四味地黄膏促进溃疡愈合的作用机制。材料与方法利用模块药理学和分子对接技术预测中药复方软膏对DU的治疗作用靶点。雄性db/db糖尿病小鼠和由甲基乙二醛诱导的HaCaT细胞模型用于验证发现。结果：CCN 1是参参三黄膏治疗DU的核心靶点。在创伤后第9天检测到通过SJHY处理（0.5g/cm 2/天）在mRNA和蛋白水平上上调的CCN 1。当CCN 1敲低时，SJHY处理（10 mg/L）的加速细胞增殖、迁移和抗炎作用被逆转。结论：四君子愈伤膏通过上调CCN 1的表达促进皮肤创面愈合。
ETHNOPHARMACOLOGICAL RELEVANCE 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. AIM OF THE STUDY In order to verify the underlying mechanism of SJHY ointment in accelerating the closure of DUs. MATERIALS AND METHODS 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. RESULTS CCN1 was proven to be the core target of SJHY ointment involved in DUs treatment. CCN1 up-regulated by SJHY treatment (0.5 g/cm2/day) at the mRNA and protein levels were detected on Day 9 after wounding. When CCN1 knockdown, accelerated cell proliferation, migration, and anti-inflammatory effect of SJHY treatment (10 mg/L) were reversed. CONCLUSIONS SJHY ointment ameliorates cutaneous wound healing by up-regulating CCN1.