Topical Digitoxigenin for Wound Healing: A Feasibility Study.

Xinchi Feng,Jinsong Hao,Cuifen Wang,Joel Turley,Zijian Xie,Yunhui Xu,Sandrine Pierre

doi:10.3390/bioengineering5010021

Xinchi Feng, Jinsong Hao + Show 5 more

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https://doi.org/10.3390/bioengineering5010021

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Abstract

(1) Background: Cardiotonic steroids have been found to stimulate collagen synthesis and might be potential wound healing therapeutics. The objective of this study was to evaluate the feasibility of digitoxigenin and its topical formulation for wound healing; (2) Methods: In the in vitro study, the human dermal fibroblast cells were treated with digitoxigenin and collagen synthesis was assessed. In the in vivo study, digitoxigenin was applied to excisional full-thickness wounds in rats immediately after wounding and remained for three days, and wound open was evaluated over 10 days. A digitoxigenin formulation for topical administration was prepared, and the in vitro release and in vivo wound healing effect were investigated; (3) Results: The expression of procollagen in human dermal fibroblast was significantly increased with the exposure to 0.1 nM digitoxigenin. Topical application of digitoxigenin in olive oil or alginate solution for three days significantly decreased the wound open in rats. Similarly, topical administration of the developed digitoxigenin formulation for three days also significantly increased wound healing. No wound healing effects were observed at days 7 and 10 after wounding when digitoxigenin was not applied; and, (4) Conclusions: It was possible to deliver digitoxigenin using the developed formulation. However, the wound healing effect of digitoxigenin and its mechanisms need to be further investigated in future studies.

Highlights

Chronic wounds are one of the major clinical challenges in the world
Researchers found that a signal cascade involving EGFR and PLC could be initiated by Cardiotonic steroids (CTSs) via their binding to Na/K-ATPase, resulting in an increase in collagen expression [4,5,6]. These findings suggest that CTSs may be potential wound healing therapeutics by stimulating collagen synthesis, which is one of the most important mechanisms in wound healing [7]
Digitoxigenin as a promising wound healing candidate warrants future studies to validate the efficacy and better understand the mechanisms. This was the first investigation of using digitoxigenin in wound healing, and would present a new direction to explore novel therapeutics for wound healing. This was a pilot feasibility study to determine (1) if digitoxigenin, a cardiac aglycone, had effects on collagen synthesis in vitro and wound closure in vivo as previously reported for digoxin, a cardiac glycoside; and, (2) if a formulation could be developed for topical application

Summary

Introduction

Chronic wounds are one of the major clinical challenges in the world. It is estimated that the annual cost on the treatment of chronic wounds is over $25 billion [1]. Due to aging population and increased number of people with diabetes and obesity worldwide, the financial burden of treating chronic wounds is increasing. Current treatment options of chronic wounds are less effective. There is an urgent need for the development of novel wound healing therapeutics. Herbal medicines have been used over 5000 years and their enduring popularity may be attributed to the perception that they cause minimal unwanted side effects. Discovering novel therapeutics from herbal medicines remains a promising approach for drug development [2]

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