The Identification of the Biomarkers of Sheng-Ji Hua-Yu Formula Treated Diabetic Wound Healing Using Modular Pharmacology

Jing-Si Jiang; Jing-Si Jiang; Ying Zhang; Ying Zhang; Ying Luo; Ying Luo; Yi Ru; Yue Luo; Xiao-Ya Fei; Jian-Kun Song; Xiao-Jie Ding; Xiao-Jie Ding; Zhan Zhang; Dan Yang; Shuang-Yi Yin; Hui-Ping Zhang; Tai-Yi Liu; Bin Li; Bin Li; Bin Li; Le Kuai; Le Kuai

doi:10.3389/fphar.2021.726158

Frontiers in Pharmacology (Nov 2021)

The Identification of the Biomarkers of Sheng-Ji Hua-Yu Formula Treated Diabetic Wound Healing Using Modular Pharmacology

Jing-Si Jiang,
Jing-Si Jiang,
Ying Zhang,
Ying Zhang,
Ying Luo,
Ying Luo,
Yi Ru,
Yue Luo,
Xiao-Ya Fei,
Jian-Kun Song,
Xiao-Jie Ding,
Xiao-Jie Ding,
Zhan Zhang,
Dan Yang,
Shuang-Yi Yin,
Hui-Ping Zhang,
Tai-Yi Liu,
Bin Li,
Bin Li,
Bin Li,
Le Kuai,
Le Kuai

Affiliations

Jing-Si Jiang: Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Jing-Si Jiang: Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
Ying Zhang: Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Ying Zhang: Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
Ying Luo: Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Ying Luo: Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
Yi Ru: Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
Yue Luo: Shanghai Skin Disease Hospital of Tongji University, Shanghai, China
Xiao-Ya Fei: Shanghai Skin Disease Hospital of Tongji University, Shanghai, China
Jian-Kun Song: Shanghai Skin Disease Hospital of Tongji University, Shanghai, China
Xiao-Jie Ding: Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Xiao-Jie Ding: Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
Zhan Zhang: Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
Dan Yang: Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
Shuang-Yi Yin: Center for Translational Medicine, Huaihe Hospital of Henan University, Kaifeng, China
Hui-Ping Zhang: Shanghai Applied Protein Technology Co., Ltd., Shanghai, China
Tai-Yi Liu: Shanghai Applied Protein Technology Co., Ltd., Shanghai, China
Bin Li: Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Bin Li: Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
Bin Li: Shanghai Skin Disease Hospital of Tongji University, Shanghai, China
Le Kuai: Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Le Kuai: Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China

DOI: https://doi.org/10.3389/fphar.2021.726158
Journal volume & issue: Vol. 12

Abstract

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Sheng-Ji Hua-Yu (SJHY) formula has been proved to reduce the severity of diabetic wound healing without significant adverse events in our previous clinical trials. However, based on multi-target characteristics, the regulatory network among herbs, ingredients, and hub genes remains to be elucidated. The current study aims to identify the biomarkers of the SJHY formula for the treatment of diabetic wound healing. First, a network of components and targets for the SJHY formula was constructed using network pharmacology. Second, the ClusterONE algorithm was used to build a modular network and identify hub genes along with kernel pathways. Third, we verified the kernel targets by molecular docking to select hub genes. In addition, the biomarkers of the SJHY formula were validated by animal experiments in a diabetic wound healing mice model. The results revealed that the SJHY formula downregulated the mRNA expression of Cxcr4, Oprd1, and Htr2a, while upregulated Adrb2, Drd, Drd4, and Hrh1. Besides, the SJHY formula upregulated the kernel pathways, neuroactive ligand–receptor interaction, and cAMP signaling pathway in the skin tissue homogenate of the diabetic wound healing mice model. In summary, this study identified the potential targets and kernel pathways, providing additional evidence for the clinical application of the SJHY formula for the treatment of diabetic wound healing.

Published in Frontiers in Pharmacology

ISSN: 1663-9812 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://journal.frontiersin.org/journals/pharmacology

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