Mode of pancreatic lipase inhibition activity in vitro by some flavonoids and non-flavonoid polyphenols

Abu Torab M A Rahim; Yoko Takahashi; Kohji Yamaki

doi:10.1016/j.foodres.2015.05.017

Mode of pancreatic lipase inhibition activity in vitro by some flavonoids and non-flavonoid polyphenols

Food Res Int. 2015 Sep:75:289-294. doi: 10.1016/j.foodres.2015.05.017. Epub 2015 May 12.

Authors

Abu Torab M A Rahim¹, Yoko Takahashi², Kohji Yamaki³

Affiliations

¹ National Food Research Institute, National Agricultural and Food Research Organization, 2-1-12 Kannondai, Tsukuba, Ibaraki 305-8642, Japan; Institute of Nutrition and Food Science, University of Dhaka, Dhaka 1000, Bangladesh.
² National Food Research Institute, National Agricultural and Food Research Organization, 2-1-12 Kannondai, Tsukuba, Ibaraki 305-8642, Japan.
³ National Food Research Institute, National Agricultural and Food Research Organization, 2-1-12 Kannondai, Tsukuba, Ibaraki 305-8642, Japan. Electronic address: kyamaki@affrc.go.jp.

PMID: 28454959
DOI: 10.1016/j.foodres.2015.05.017

Abstract

Numerous reports have shown plant metabolites as potential inhibitors of pancreatic lipase (PL). The most notable group is plant polyphenols. However, a limited number of reports diagnosed their mode of inhibition delineating conflicting results. To elucidate the kinetic mode of PL inhibition, some selected flavonoid and non-flavonoid polyphenol standards were first screened for their lipase inhibition potency by their half maximal inhibitory concentration (IC₅₀) followed by inhibition kinetic analysis. Of the phenolics tested, only gallic acid (GA) and galloyl moiety containing epicatechin, viz., epigallocatechin (EGC) and epigallocatechin gallate (EGCG) showed, comparative to others, higher PL inhibitions (IC₅₀, 387.2, 237.3, and 391.2μM respectively). Analysis of enzyme inhibition modalities at various substrate concentrations revealed a dose-dependent inhibition of reaction velocity. Inhibitory rates decreased by the order of EGCG>EGC>GA (Ki, 13.29>35.0>44.61μM respectively). The results, when verified by visual inspection of Lineweaver-Burk as well as Dixon plots, showed inhibitions of PL by GA, EGC, and EGCG that were best fit to competitive inhibitions. A role of the galloyl moiety in enzyme-inhibitor binding has been evident from their structural resemblance. Depicting it further, ethyl gallate (EG), showed a similar competitive inhibition, therefore, indicating a galloyl moiety driven competitive inhibition of PL.

Keywords: Double-reciprocal plot; IC(50) value; Inhibition mode; Ki; Lipase.