Topical combined Phyllanthus emblica Linn. and simvastatin improves wound healing in diabetic mice by enhancing angiogenesis and reducing neutrophil infiltration

The present study aimed to investigate the effects of combined Phyllanthus emblica Linn. (PE) and simvastatin (SIM) on diabetic wounds in male BALB/C mice. Bilateral full thickness wound excisions were performed in the control and diabetic groups (45 mg/kg streptozotocin, intraperitoneally injected daily for 5 days). The diabetic mice received daily treatment with four different types of cream: Vehicle [diabetes mellitus (DM) + Vehicle group], 100% PE (DM + PE group), 5% SIM (DM + SIM group) and combined 100% PE + 5% SIM (DM + Combination group) for 4, 7 and 14 days. The tissue malondialdehyde (MDA) and IL-6 protein levels, the number of infiltrated neutrophils, and the percentages of wound closure (%WC), capillary vascularity (%CV) and re-epithelialization (%RE) were subsequently measured. The results indicated that in the DM + Combination group, %CV and %WC were significantly increased when compared with the DM + Vehicle group on days 7 and 14. The tissue MDA content on day 14, and the number of infiltrated neutrophils on days 4 and 7 were significantly reduced in the DM + Combination group compared with those in the DM + Vehicle group. Furthermore, a strong positive correlation was revealed between %CV and %WC in the five groups on day 7 (r=0.736; P=0.0003). These findings indicated that topical application of combined PE and SIM could enhance wound healing by upregulating angiogenesis and reducing neutrophil infiltration in mice with diabetic wounds.