Wound healing activity of the leaves of Artocarpus heterophyllus Lam. (Moraceae) on ex-vivo porcine skin wound healing model

ABSTRACT Objective: To prescreen the ex- vivo wound healing activity of flavonoid rich fraction of ethyl acetate extract of the leaves of Artocarpus heterophyllus Lam. Family Moraceae using porcine skin wound healing model (PSWHM) along with  phytochemical, XRF, HPTLC analysis. The aim of this present study is to provide pharmacological validation to the traditional claim for wound healing activity of Artocarpus heterophyllus leaves. Method: Total phenolic content by UV spectral methods and ursolic acid content by HPTLC, trace elements by X-ray fluorescence were determined.  The wound healing effect of the ethyl acetate extract of the leaves of A.heterophyllus (EAAH) was evaluated using ex- vivo porcine skin wound healing model - a novel organ culture model system for evaluation of drugs in cell-cell junction in the wound healing process. Results: Total phenolic content by UV method, HPTLC determination of ursolic acid content of EAAH was found to be 376.5mg/g GAE, 134mg/g respectively. XRF study showed the presence of calcium (39.4%), potassium (29.6%), magnesium (2.06%), Iron (0.99%), sulphur (1.83%), zinc (0.083%), strontium (0.23%), manganese (0.13%) and aluminium (0.005%).  Histopathological evaluation showed all treated wounds were sound with no signs of apoptosis, necrosis or bacterial contamination and no toxicity of the tested concentrations of EAAH of the leaves. Morphology of the wound margins, epidermis and dermis layer were found to be normal. Epidermal migration or keratinocyte migration distances from the edges of each wound were measured, normalized with the PBS control group and expressed as mean%. The result clearly showed EAAH (1.5%) promoted statistically significant wound healing effect is comparable to the standard drug Mupirocin. Conclusion: This study indicates that the ethyl acetate extract of the leaves of A.heterophyllus possesses potential wound healing activity on ex-vivo porcine skin wound healing model. Wound healing activity of EAAH (leaves) may be due to its phenolic content (flavonoids), triterpenoids constituents especially ursolic acid. Both of them known to have astringent property which is responsible for wound contraction and increased rate of epithelialisation along with the supportive anti-microbial activity. More over trace elements like Zinc (Zn), Copper (Cu), Manganese (Mn), Iron (Fe) supports wound healing property as essential trace mineral are required for cellular growth and replication. This present investigation provides scientific evidence to ethnomedical use of A.heterophyllus leaves in wound healing activity. Our study showed significant enhancement of wound repair and therefore can be beneficially, safely used as auxiliary therapy in diabetic patient with foot ulcers in addition to the other available treatment as the leaves possesses scientifically validated traditional use in diabete