Modulation of Human Cytochrome P450 by Momordica charantia (Bitter Melon)

Abstract

Momordica charantia (bitter melon, BM) is traditionally used to treat diabetes and its complications. However, the safety and interaction of BM with other therapeutic drugs is unknown. The cytochrome (CYP) P450 enzymes metabolize variety of xenobiotics. Since BM modulates CYP in diabetic rats, we hypothesized that BM will also differentially modulate human P450 enzymes. Our aim was to investigate the effects of BM on CYP1A2 and CYP3A4, using cDNA‐expressed human CYP450, human hepatoma cells, HepG2 and primary human hepatocytes. BMJ had no effect on cDNA‐expressed human CYP1A2 but significantly inhibited CYP3A4 activity, up to 85%. BMJ was non‐toxic to both, HepG2 and primary human hepatocytes as measured by cellular ATP levels and had no effect on CYP1A2 induction in HepG2 cells, for up to 72 h, but significantly inhibited the 3‐methylcholanthrene induced CYP1A2 activity by 48%. BMJ exhibited a dose‐ and time‐dependent inhibition of CYP3A4 activity by 64%. BMJ for 4 h demonstrated a significant reduction of CYP1A2 activity by 30% and CYP3A4 by 20% respectively in primary human hepatocytes. CYP3A4 is an important drug metabolizer for majority of clinically relevant therapeutic drugs. Identifying the BMJ‐associated modulation of P450 is important to determine its safety for future clinical trials and to minimize drug‐drug interactions. [NCCAM (R21AT003719) and NCMHD (P20MD000173), NIH].