Investigation of the effect of Centella asiatica extract on wound healing in burn model in streptozotocin-induced diabetic ratsusing pathological and molecular methods

In this study, the effects of Centella asiatica extract-containing cream and pomade formulations on wound healing were investigated at the pathological and molecular levels in a burn model created in streptozotocin-induced diabetic rats. In the study, a total of 92 female Wistar-Albino rats aged 12 weeks were divided into 6 main groups: Control (K), burn (Y), diabetes (D), diabetes+burn (DY), diabetes+burn+cream (DYK), and diabetes+burn+pomade (DYP). The control group consisted of 12 rats, while the experimental groups consisted of 16 rats each. Each main group was divided into two subgroups; 7-day treatment (First Group) and 14-day treatment (Second Group) groups were created. A single dose of 55 mg/kg streptozotocin was injected intraperitoneally (ip) into the rats in which diabetes was to be induced. Fasting blood glucose levels were measured 2 days after the injection, and those above 200 mg/dl were considered to have established a diabetes model. Second-degree thermal burns with a diameter of 1 cm were inflicted on the back skin of rats in the burn groups (Y, DY, DYK, DYP) under general anesthesia. The DYK group received a cream containing 2,5% Centella asiatica daily after the burn, while the DYP group received an pomade applied topically. The area of skin lesions was measured on days 0, 3, 7, 10, and 14 according to the groups and evaluated macroscopically. Necropsies were performed on rats in first group on the 7th day and on rats in second group on the 14th day after the formation of burns. Half of the excised control and lesion skin areas were stored at -80°C for molecular analysis, and the other half were fixed in 10% formalin for histopathological examination. In the macroscopic evaluation, it was observed that the wound areas were significantly larger in the DY group, while they decreased significantly on days 7 and 14 in the DYK and DYP groups that received treatment. Histopathological examination revealed a decrease in PMNL and MNH infiltration in the treatment groups, while there was a significant increase in fibroblast/fibrocyte density, angiogenesis, and epithelialization parameters. It was determined that cellular infiltration decreased in the early period compared to the DY group, while fibroblast proliferation and epithelialization increased in the late period (p<0,05). In molecular analyses, a significant decrease in TNF-α levels and a significant increase in FGF-2, EGF, VEGF, and IGF-1 levels were observed in the treatment groups (p<0,05). When comparing cream and pomade formulations, it was determined that pomade showed a slightly higher healing effect, although not statistically significant. In conclusion, Centella asiatica extract has been shown to support healing in a diabetic burn model through its anti-inflammatory, regenerative, angiogenic, and epithelializing effects, and to play a partial role in the treatment efficacy of the formulation. In light of the findings, it has been concluded that plant-based topical agents containing Centella asiatica may be a promising alternative for the treatment of diabetic burns, and that more detailed elucidation of the mechanisms of this effect may guide future translational studies.