Investigation of synergistic potential of green tea polyphenols and orlistat combinations using pancreatic lipase assay-based synergy directed fractionation strategy

Abstract

The present study investigated the synergistic potential of methanol extract/fractions of Camellia sinensis (L.) Kuntze (CSM) leaves and orlistat on inhibition of Pancreatic Lipase (PL). Since PL is responsible for 50–70% of dietary fats digestion, its inhibition is considered as a promising target for the management of obesity. A synergy guided fractionation strategy has been incorporated with the help of combination index (CI) and isobologram methods. CSM exhibited a potential synergistic activity in combination with orlistat (CI value: 0.66). Amongst the subfractions of CSM, polyphenol-rich fraction exhibited a greater synergistic potential (CI-0.35) than remaining fractions. HPLC analysis identified epicatechin gallate (ECG) and epigallocatechin gallate (EGCG) as major phytochemicals in polyphenol-rich fraction and the most active subfractions (F6 and F7). Two drug and three-drug combinations of these phytochemicals were investigated by partnering with orlistat. The three-drug combination (orlistat-EGCG-ECG) exhibited a greater synergistic potential (CI value-0.17) than the two-drug combinations of EGCG-orlistat and ECG-orlistat (CI values of 0.40 & 0.71, respectively). The resultant orlistat-EGCG-ECG combination resulted in a 12.11-fold dose reduction index for orlistat. Thus, synergistic drug combinations of polyphenol-rich fraction along with orlistat offers the prospect to enhance the orlistat anti-obesity efficacy in a decreased dose level, that will help to reduce its associated toxicities while maintaining its efficacy.