Evaluation of the Biological Effects of Lyophilized Hydrophilic Extract of Rhus coriaria on Myeloperoxidase (MPO) Activity, Wound Healing, and Microbial Infections of Skin Wound Tissues

Abstract

Impaired wound healing was mainly associated with severe microbial infections which significantly affect diagnostic and therapeutic strategies. Thus, in this study, the potential wound healing activity, anti-inflammatory, and antimicrobial activity of an aqueous extract of Rhus coriaria extract (AERc) were evaluated by wound contraction, scar formation, period of epithelization, MPO enzyme activity, collagenase-2 (MMP-8), hydroxyproline (HPX), and collagen deposition as markers of wound healing at different days of postwound. Phytoconstituents, microbial activity, and fibrogenic markers were screened by HPLC, disc-diffusion, and colorimetric assays. The animals were treated with Rhus coriaria extract (AERc) concentrations at doses of 5 mg.kg^-1and 10 mg.kg^-1, respectively. On days 6 and 9, the AERc-treated animals at doses of 5 mg.mL^-1 and 10 mg.mL^-1 exhibited a significant reduction in the wound area, increased deposition of collagen, HPX, and reduction in MMP-8, and MPO enzyme activity when compared with controls. Scar formation and epithelization were completed in 10 days compared to controls. In addition, in wounds infected separately with Staph. aureus or P. aeruginosa, the AERc extract significantly improved wound contraction, deposition of collagen, and HPx and reduced MMP-8 and MPO concentrations, with complete epithelization of wounds in 10-13 days compared to the saline-treated group. Hydrolyzable tannins, gallic acid, quercetin, and myricetin were the most common active components of AERc. In vitro, the AERc and its components were effective against a set of microbes especially Staph. aureus, P. aeruginosa, and Staph. aureus (MRSA). In conclusion, the results showed that antimicrobial, anti-inflammatory, and antioxidant activity of Rhus coriaria extract suggested its importance as a target for formulation of novel drugs against many microbial infections with minimal side effects and could play a good potential role in accelerating wound healing activity via promoting myofibroblast activity, increase of hydroxyproline and collagen deposition, and regulation of MMP-8 and MPO enzyme activities.

Figure 1

Screening of active Phytochemical contents present in aqueous extract of Rhus coriaria fruits.

Figure 2

Photographs represent the percentage of wound closer rates on different postexcision days (3^th - -15^th).

Figure 3

Effect of aqueous extract of Rhus coriaria fruits on myeloperoxidase (MPO) activity at a dose of 5 mg.mL⁻¹ of AERc (a) and at adose of 10 mg.mL⁻¹ of AERc (b) and hydroxyproline (HPX) in noninfected (c) and infected wounds (d) treated at 3, 6, 9, 15, and 21 postoperative days. In wounds infected with gram positive (S. aureus) and gram negative (P. aeruginosa), there was significant decrease (p=0.001) in the level of MPO activity and increase (p<0.05) in the levels of HPX at days 15th, 18^th, and 21^st following treatment with AERc at doses of 5 mg.mL⁻¹, 10 mg.mL⁻¹, and compared with control treatments, respectively.

Figure 4

Mean values and standard errors of the percentage of MMP-8 (a) in noninfected, (b) infected wounds, and collagen in noninfected (c), and infected wounds (d). Wounds are infected separately with 10 μL of S. aureus (ATCC 25923) and P. aeruginosa at 108 Colony Forming Unit (CFU). The data showed significant depletion in the activity of MMP-8 and increase in the level of collagen deposition in wounds of control and treated animals at 3, 6, 9, 15, and 21 postoperative days.