Pien Tze Huang accelerated wound healing by inhibition of abnormal fibroblast apoptosis in Streptozotocin induced diabetic mice

J Ethnopharmacol. 2020 Oct 28:261:113203. doi: 10.1016/j.jep.2020.113203. Epub 2020 Jul 25.

Abstract

Ethnopharmacological relevance: Diabetic foot ulcer is one of the most serious complications of diabetes. Effective medical treatment regarding improvement of ulcer healing in patients is essential. Pien Tze Huang (PZH), a valuable Chinese traditional medicine, has been found significant efficacy on the curing of diabetic wound in clinic recently.

Aim of the study: This work was conducted to confirm the efficacy, and compare the therapeutic effect through the oral administration and local delivery route, providing a rationale for the new PZH form development; besides, the mechanisms through which PZH promoted the wound healing was also discussed.

Materials and methods: First, the chemical composition of PZH was characterized by 1H-NMR and HPLC. The anti-apoptosis effects of PZH on high concentration glucose injured epidermal fibroblast (HFF-1) was investigated in a dose dependent way. Then, the effects of the systematical administration of PZH, and the topical used route on excisional wounds of Streptozotocin (STZ) induced diabetic mice were compared.

Results: The results illustrated that PZH decreased the reactive oxygen species (ROS) levels in cells, preventing cell damage/apoptosis through an ROS/Bcl-2/Bax/Caspase-3 pathway. The in vivo study proved that topical use of PZH exceeded the systematical route both in accelerating the wound closure and improving the healing quality. Meanwhile, PZH promoted wound closure through stimulating the secretion of Col-I, decreasing fibroblast apoptosis, and enhancing myo-fibroblast differentiation, in consistent with the mechanism study in vitro.

Conclusions: Local used PZH improves wound healing by inhibiting the abnormal HFF-1 apoptosis and senescence. The study held a great promise for development of a topical dosage form of PZH for diabetic wound healing.

Keywords: Diabetic foot; Epidermal fibroblast apoptosis; Pien Tze Huang; Wound healing.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Cutaneous
  • Administration, Oral
  • Animals
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Blood Glucose / metabolism
  • Cell Differentiation / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / chemically induced
  • Drugs, Chinese Herbal / administration & dosage
  • Drugs, Chinese Herbal / pharmacology*
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Male
  • Mice, Inbred C57BL
  • Myofibroblasts / drug effects*
  • Myofibroblasts / metabolism
  • Myofibroblasts / pathology
  • Reactive Oxygen Species / metabolism
  • Skin / drug effects*
  • Skin / injuries
  • Skin / metabolism
  • Skin / pathology
  • Streptozocin
  • Time Factors
  • Wound Healing / drug effects*
  • Wounds and Injuries / complications
  • Wounds and Injuries / drug therapy*
  • Wounds and Injuries / metabolism
  • Wounds and Injuries / pathology

Substances

  • Apoptosis Regulatory Proteins
  • Blood Glucose
  • Drugs, Chinese Herbal
  • Reactive Oxygen Species
  • pien tze huang
  • Streptozocin