In Vivo Antimicrobial and Wound-Healing Activity of Resveratrol, Dihydroquercetin, and Dihydromyricetin against Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans.

Alexei B Shevelev,Alexander S Belous,Dmitrii A Sivokhin,Nicola La Porta,Elena V Trubnikova,Marina V Zylkova,Stefan Martens,Maria S Smirnova,Alla V Belyakova,Yulia K Biryukova,Yulia I Deryabina,Elena P Isakova

doi:10.3390/pathogens9040296

Abstract

An increase in the spread of antibiotic-resistant opportunistic microorganisms causes serious problems in the treatment of purulent infections, burns, and trophic ulcers. We tested the antimicrobial activity in vivo of three polyphenols, Resveratrol, Dihydroquercetin (Taxifolin), and Dihydromyricetin (Ampelopsin) from Norway spruce bark to promote the elimination of Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans from wounds. Purulent infection was modelled on wounds in rats infected with suspensions containing 109 CFU (colony-forming unit)/mL of pathogens. The wound area was treated daily with solutions of the polyphenols or placebo for 14 days after the beginning of the treatment. The animals were examined daily, and each stage of the wound healing (inflammation, granulation, and maturation (marginal epithelialisation) was documented. The planimetric analysis of the wound recovery percentage was performed on the 3rd, 10th, and 14th day after the start of curing. Then, one echelon (three or four animals from each subgroup) was withdrawn from the experiment on days 3 (three animals), 10 (three animals), and 14 (four animals) for microscopy analysis of cytological composition of their wound defects by microscopy and microbiological analysis of their contamination with pathogens. Our results show that they are also able to suppress mast cell infiltration and stimulate lymphocyte and macrophage (monocyte) infiltration into the wound. Resveratrol stimulated the replacement of the scar with normal tissue (with a clear boundary between the dermis and epidermis) and the restoration of hair follicles. Resveratrol turned out to be significantly better than some commercial antimicrobial (Levomecol) and antifungal (Clotrimazole) ointments and can be proposed as a promising drug for topical use for the treatment of trophic ulcers and burns.

Highlights

Due to the broad use of antibiotics, drug resistance of microbial pathogens has become one of the greatest problems of modern medicine
We showed the effectiveness of Resveratrol and Dihydroquercetin and Dihydromyricetin against S. aureus
The data for the visual examination and planimetric assay of the compounds studied using sterile wounds (Tables 1–3) showed an evident acceleration of uninfected wound healing following treatment with Resveratrol, which is unachievable for Dihydroquercetin and Dihydromyricetin during the early stages of treatment

Summary

Introduction

Due to the broad use of antibiotics, drug resistance of microbial pathogens has become one of the greatest problems of modern medicine. It is of particular importance under complicated chronic conditions such as in trophic ulcers in patients with diabetes mellitus where long-term antimicrobial therapy is mandatory [1]. Resveratrol and Dihydroquercetin were isolated from grape juice and peanut and coniferous tree bark extracts [4] as agents responsible for the response to a fungus Botrytis cinereae infection in plants. These compounds were supposed to be responsible for the so-called French paradox [5]

Methods

Results

Conclusion