Biphasic Effect of Phyllanthus emblica L. Extract on NSAID-Induced Ulcer: An Antioxidative Trail Weaved with Immunomodulatory Effect

Amla (Phyllanthus emblica L.), apart from its food value, can be used as a gastroprotective agent in non steroidal anti-inflammatory drug (NSAID)-induced gastropathy. It has been suggested that the antioxidative property of amla is the key to its therapeutic effect. Hence, on the basis of in vitro antioxidative potential, the ethanolic extract of amla (eAE) was selected for in vivo study in NSAID-induced ulcer. Intriguingly, eAE showed biphasic activity in ulcerated mice, with healing effect observed at 60 mg/kg and an adverse effect at 120 mg/kg.The dose-dependent study revealed that switching from anti-oxidant to pro-oxidant shift and immunomodulatory property could be the major cause for its biphasic effect, as evident from the total antioxidant status, thiol concentration, lipid peroxidation, protein carbonyl content followed by mucin content, PGE(2) synthesis and cytokine status. Further, Buthionine sulfoxamine (BSO) pretreatment established the potential impact of antioxidative property in the healing action of eAE. However, eAE efficiently reduced pro-inflammatory cytokine (TNF-α and IL-1β) levels and appreciably upregulate anti-inflammatory cytokine (IL-10) concentration. In conclusion, gastric ulcer healing induced by eAE was driven in a dose-specific manner through the harmonization of the antioxidative property and modulation of anti-inflammatory cytokine level.