A comprehensive study on mechanisms of action of fibroin, aloe vera, and ginger extracts through histochemical, inflammation biomarkers, and matrix metalloproteinases analysis against diabetic wounds

Diabetes causes complications like delayed wound healing for a long time. Fibroin, aloe vera, and ginger extracts along with their combinations are used for diabetic wound healing. After induction of diabetes, The wound healing effects of fibroin (50 mg/ml), aloe vera gel (50 mg/ml), and ginger extract (30 mg/ml), individually and in combination, were assessed. The pro-inflammatory cytokines including tumor narcosis factor-α (TNF-α) interleukin (IL-6, IL-8, IL-1β), matrix metalloproteinases (MMP 2, MMP7, MMP 9), vascular endothelial growth factor (VEGF) and tissue inhibitors of metalloproteinases (TIMPs) levels were analyzed in the serum. A combination of fibroin + aloe vera gel + ginger extract (Fi + Al + Gi) healed the wounds in 11 days via wound contraction of 98.5 ± 0.9 % as compared to diabetic control (58.2 ± 0.7 %) and positive control (73.3 ± 0.6 %) groups. However, the wounds of the Polyfax and the diabetic control groups were healed in 17 and 19 days, corresponding to a contraction of: 96.7 ± 1.4 % and 96.3 ± 1.1 %. The histological assay showed that the Fi + Al + Gi group indicated an increased growth of collagen fibers, fibroblasts, keratinocytes and blood vessels with lessened inflammation. The Fi + Al + Gi group alleviated the serum level of TNF-α (12.7 ± 0.9 pg/ml), IL-6 (9.6 ± 0.9 pg/ml), IL-8 (19.6 ± 1.0 pg/ml), MMP2 (217.0 ± 9.2 pg/ml), MMP7 (279.0 ± 9.8 pg/ml), and MMP9 (156.0 ± 11.6 pg/ml) significantly as compared to the diabetic control (P ≤ 0.05). TIMP serum level (202.0 ± 6.9 pg/ml) was significantly elevated as compared to the diabetes control group. The present study concludes that the biomaterials in their combinations possess high regenerative and healing abilities. •Three biomaterials fibroin, aloe vera, and ginger were used either individually or in combination form to enhance the diabetic wound healing process•Quantification analysis of four inflammatory markers (TNF-α, IL-6 IL-1β and IL-8), was performed to understand the healing process.•Histopathological examinations of wounded skin demonstrated the elevated number of keratinocytes, fibroblasts, collagen fibers, and blood vessels.•Quantification values of five markers (MMP 2, MMP7, MMP 9), TIMPs), and VEGF evaluate new blood vessel formation and healing process were analyzed