Therapeutic potential of selected South African macrofungi in diabetic wound healing: An in vitro evaluation

Abstract

Diabetic wounds frequently undergo impaired and prolonged wound healing due to cellular dysfunction. Treatment options, however, remain limited, non-specific, and generally unsuccessful. The potential of medicinal mushrooms in treating several diseases have been exploited by traditional folk medicines for centuries yet very little scientific evidence to support these practices exists. To explore natural products as potential therapeutics to treat diabetic wounds and encourage more research on this topic, this study sought out to screen the potential of four wild mushroom species (Pisolithus tinctorius, Russula capensis, Imleria badia and Pleurotus ostreatus) as suitable diabetic wound healing therapies. This was achieved using various in vitro models characteristic of the diabetic state including LPS and glycated gelatin to mimic bacterial infection and protein glycation, respectively. Activities screened include antioxidant (FRAP and DPPH), collagenase inhibition, immune modulatory capacity in RAW 264.7 macrophages (NO production, NO scavenging, COX-2, M1/M2 polarisation and phagocytosis) as well as MRHF fibroblast migration. In vitro toxicity screening revealed negligible toxicity for all of the tested aqueous and ethanolic extracts with a mildly cytostatic response recorded for P. tinctorius. P. tinctorius also demonstrated strong pro-inflammatory activity in RAW 264.7 macrophages (NO production and COX-2) however, in the presence of LPS the opposite effect was observed owing to strong NO scavenging capabilities while the pro-inflammatory nature of R. capensis aqueous extract was found to be due to the presence of bacterial endotoxins. Overall, different mushroom species presented divergent macrophage responses with the ethanol extract of R. capensis producing the most favourable effects with respect to established diabetic wounds due to its capacity to attenuate inflammation, promote macrophage transition from a pro-inflammatory to a wound healing phenotype, re-establish the phagocytic activity of macrophages and stimulate dermal fibroblast cell migration.