IL1β/TNFα/COX-2/VEGF axis responsible for effective healing potential of C-glucoside xanthone (mangiferin) based ointment in immunocompromised rats

Present study was conducted to undermine the wound healing potential of mangiferin vis a vis its molecular dynamics in immunocompromised excisional rat model. 120 rats were randomly and equally divided into five groups viz. group I (Healthy control), group II (Immunocompromised control), group III (Immunocompromised group treated with silver sulphadiazine), group IV (Immunocompromised group treated with 2.5 %Mangiferin) and group V (Immunocompromised group treated with 5 %Mangiferin). Immuno compromised state was achieved following intramuscular injection of Hydrocortisone @ 80 mg/kg body weight. Study was conducted for a period of 28 days. Six animals from each group were humanely sacrificed at weekly interval till day 28th of study. Planimetric analysis, biochemical studies viz. hydroxyproline assay, total protein and DNA content, antioxidative potential through LPO assay was done along with molecular studies involving expression profiling of IL18, TNF alpha and COX-2 and Immunohistochemistry of angiogenic marker i.e. VEGF was performed to undermine the pharmacodynamics of mangiferin. Histopathological studies including H&E and Masson's Trichome was also performed to study histoarchitectural changes in wound healing and reparative process following application of mangiferin ointment. Study revealed significant (P <= 0.05) reduction in wound area measurement and significant (P <= 0.05) increase in wound contraction (%) following mangiferin administration in immunocompromised rats. Hydroxyproline, DNA and total protein showed significant (P <= 0.05) increase in skin tissues of mangiferin treated immunocompromised rats. LPO assay revealed significant (P <= 0.05) reduction in mangiferin treated animals. Histopathological studies of skin tissues revealed complete restoration advocating grade III of healing in 2.5% mangiferin treated group. Higher expression and strong signal intensity of VEGF was noticed in 2.5% mangiferin treatment group along with significant (P <= 0.05) upregulation IL18 and TNF alpha on day 7 in 2.5% mangiferin treatment group with significant (P <= 0.05) down regulation of COX-2 in mangiferin treatment group as compared to other groups i.e. group II and III. It is concluded from our study that mangiferin facilitates wound healing through improved wound closure, organized deposition of collagen deposition and granulation matrix formation.

Automated summary

This study investigated the potential of mangiferin in promoting wound healing in an immunocompromised rat model. The results showed that mangiferin treatment significantly reduced wound area and increased wound contraction in immunocompromised rats. It also increased levels of hydroxyproline, DNA, and total protein in the skin tissues of treated rats. Additionally, mangiferin exhibited antioxidative effects and modulated the expression of IL18, TNF alpha, and COX-2. Histopathological studies further revealed improved wound healing and tissue restoration in the mangiferin-treated group. Overall, mangiferin was found to enhance wound closure, collagen deposition, and granulation matrix formation.