Sheng-Ji Hua-Yu Ointment Ameliorates Cutaneous Wound Healing in Diabetes Via Up-Regulating CCN1

Abstract

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. Moreover, we validated the findings from the predictions with in vivo and in vitro experiments.

Results: (1) CCN1 proved to be the core target of SJHY ointment involved in DUs treatment. (2) Topical application of SJHY ointment up-regulated CCN1 expression in db/db diabetic mice wounds. (3) Accelerated HaCaT keratinocytes proliferation, migration, and anti-inflammatory effect of SJHY treatment were reversed when CCN1 knockdown.

Conclusions: CCN1 represents a critical therapeutic target for SJHY ointment treatment of DUs.

Note:

Funding Information: This work was supported by the National Natural Science Foundation of China (No. 81904214, 82174383, 81973860, 82004235); the National Key Research and Development Program of China (No. 2018YFC1705305); Xinglin Youth Scholar of Shanghai University of Traditional Chinese Medicine (No. RY411.33.10); Shanghai Sailing Program (No. 21YF1448100, 22YF1450000, 22YF1441300); Three-Year Action Plan of Shanghai Municipality for further acceleration of the development of Chinese medicine (No. ZY(2021-2023)-0302); Three-Year Action Plan of Shanghai Municipality for the development of Chinese medicine (No. ZY(2018-2020)-FWTX 1008); Shanghai Clinical Key Specialty Construction Project (No. shslczdzk05001); Clinical Transformation Incubation Program in Hospital (No. lczh2021-05); Young Elite Scientists Sponsorship Program of China Association of Chinese Medicine (No. 2021-QNRC2-A10).

Declaration of Interests: The authors state no conflict of interest.

Ethics Approval Statement: The animal study was reviewed and approved by the Animal Ethics Committee of Yueyang Hospital (YYLAC-2020-078-2).

Keywords: Keywords: Diabetic ulcers, Wound healing, Sheng-ji Hua-yu ointment, Modular pharmacology, CCN1