NMR-based metabolomic analysis for the effects of Huiyang Shengji extract on rat diabetic skin ulcers

Tong Zhang; Feng Huang; Bin Li; Caihua Huang; Chang Xu; Kejiang Lin; Donghai Lin

doi:10.1016/j.jep.2020.112978

NMR-based metabolomic analysis for the effects of Huiyang Shengji extract on rat diabetic skin ulcers

J Ethnopharmacol. 2020 Oct 28:261:112978. doi: 10.1016/j.jep.2020.112978. Epub 2020 May 19.

Authors

Tong Zhang¹, Feng Huang², Bin Li³, Caihua Huang⁴, Chang Xu⁵, Kejiang Lin⁶, Donghai Lin⁷

Affiliations

¹ Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, 210009, China; College of Chemistry and Chemical Engineering, Key Laboratory for Chemical Biology of Fujian Province, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Xiamen University, Xiamen, 361005, China.
² Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China; Acupuncture and Moxibustion, China Academy of Chinese Medical Science, Beijing, 100700, China. Electronic address: hf2061043@ccmu.edu.cn.
³ Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China.
⁴ Research and Communication Center of Exercise and Health, Xiamen University of Technology, Xiamen, 361024, China.
⁵ Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.
⁶ Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, 210009, China. Electronic address: link@cpu.edu.cn.
⁷ College of Chemistry and Chemical Engineering, Key Laboratory for Chemical Biology of Fujian Province, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Xiamen University, Xiamen, 361005, China. Electronic address: dhlin@xmu.edu.cn.

PMID: 32442586
DOI: 10.1016/j.jep.2020.112978

Abstract

Ethnopharmacological relevance: Huiyang Shengji formula (HSF) is a compound Chinese herbal medicine prescription, and has long been used for treating chronic non-healing wounds.

Aim of the study: The purpose of this study was to provide new insight into molecular mechanisms of healing effects of the HSF treatments.

Materials and methods: We established a rat diabetic skin ulcer (DSU) model, and assessed healing effects of four HSF treatments on DSUs by calculating wound healing rates and immunohistochemical detection of the expressions of angiogenesis-related factors in the model rats (Mod) relative to normal rats (Nor), including Huiyang extract (HE), Shengji extract (SE), Huiyang Shengji extract (HSE) and HSE associated with acupuncture (Ac-HSE). We then performed NMR-based metabolomic analyses on skin tissues of the Nor, Mod, HSE-treated, Ac-HSE-treated rats to address metabolic mechanisms underlying these effects.

Results: These treatments up-regulated expressions of two angiogenesis-related factors VEGF and CD31, and improved efficacy of healing DSUs, in which HSE and Ac-HSE exhibited the most significant effects. Compared with Mod, HSE and Ac-HSE groups shared four characteristic metabolites (lactate, histidine, succinate and acetate) and four significantly altered metabolic pathways with Nor. Both HSE and Ac-HSE treatments could partly reverse the metabolically disordered pathological state of DSUs to the normal state. They might improve wound healing through promoting glucose metabolism, BCAAs metabolism, and enhancing antioxidant capacity and angiogenesis in DSU tissues. Ac-HSE significantly enhanced wound healing rates compared to HSE, potentially owing to significant capacities of enhancing anti-oxidation and angiogenesis and interfering three more metabolic pathways.

Conclusions: This work provides a mechanistic understanding of the healing effects of the HSE and Ac-HSE treatments on DSUs, is of benefit to improvements of the HSF treatments for clinically healing chronic non-healing wounds.

Keywords: Acupuncture; Diabetic skin ulcer model; Huiyang Shengji formula; NMR-Based metabolomics; Rat.

Publication types

Comparative Study

MeSH terms

Acupuncture Therapy*
Animals
Diabetes Mellitus, Experimental / chemically induced
Diabetic Angiopathies / metabolism
Diabetic Angiopathies / pathology
Diabetic Angiopathies / therapy*
Disease Models, Animal
Drugs, Chinese Herbal / pharmacology*
Energy Metabolism / drug effects
Magnetic Resonance Spectroscopy*
Male
Metabolomics*
Neovascularization, Physiologic / drug effects
Rats, Sprague-Dawley
Signal Transduction
Skin / drug effects*
Skin / injuries
Skin / metabolism
Skin / pathology
Skin Ulcer / metabolism
Skin Ulcer / pathology
Skin Ulcer / therapy*
Streptozocin
Wound Healing / drug effects*
Wounds and Injuries / metabolism
Wounds and Injuries / pathology
Wounds and Injuries / therapy*

Substances

Drugs, Chinese Herbal
Streptozocin