Ascorbate formulation improves healing efficacy in excisional wound mice model through interplay between pro and anti-inflammatory cytokines and angiogenic markers

Cytokine. 2023 Apr:164:156158. doi: 10.1016/j.cyto.2023.156158. Epub 2023 Feb 22.

Abstract

Background and objective: Biomedical research in regenerative medicine prompts researchers to formulate cost-effective therapeutics for wound healing. The present study was conducted to characterize the ascorbate based formulation vis-a-vis investigating the molecular dynamics of the formulation.

Materials and methods: To characterize the formulation, particle size, zeta potential, thermal stability, compatibility, anti-oxidant, and permeation prospective were measured using standard protocols. The in-vitro healing potential and safety formulae were evaluated using the L929 cell line. For molecular unravelling of the pharmacodynamics of formulation, an excision wound model was used, and 54 mice were randomly and equally divided into three groups, i.e., untreated, betadine-treated, and formulation-treated, to ascertain the interplay between cytokines and chemokines and their culminative role in the release of growth factors.

Results: The ascorbate formulae were found to be amorphous, biocompatible, safe, and long-lasting, with particle sizes and zeta potentials of 389.7 ± 0.69 nm and -38.1 ± 0.65 mV, respectively, and anti-oxidative potential. An in-vitro study revealed that the formulation has a significant (p<0.05) migration potential and is non-toxic. Expression profiling of TGF-β, FGF-2, VEGF, and collagen III & I showed significant (p<0.05) up-regulation, whereas significant (p<0.05) down-regulation of pro-inflammatory genes like IL-1α, IL-1β, TNF-α, IL-6, and temporal change in CCR-5 was observed in formulae-treated animals as compared to other groups.

Conclusion: By up-regulating angiogenic and collagen-promoting growth factor gene expression while down-regulating pro-inflammatory gene expression, ascorbate formulation promotes wound healing via extracellular matrix and granulation tissue deposition with significant improvement in tensile strength.

Keywords: Anti-inflammation; Ascorbic acid; Cytokines; Gene expression; Tensile strength.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents
  • Collagen
  • Collagen Type I / genetics
  • Cytokines*
  • Disease Models, Animal
  • Mice
  • Prospective Studies
  • Wound Healing* / physiology

Substances

  • Cytokines
  • Collagen
  • Collagen Type I
  • Anti-Inflammatory Agents