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Constituents of Indonesian medicinal plant averrhoa bilimbi and Their Cytochrome P450 3A4 and 2D6 Inhibitory Activities
Auw L.a, Subehanb, Sukrasnoc, Kadota S.a, Tezuka Y.d
a Institute of Natural Medicine, University of Toyama, Toyama, 930-0194, Japan
b Biofarmaka Research Center, Faculty of Pharmacy, Hasanuddin University, Makassar, 90245, Indonesia
c School of Pharmacy, Institut Teknologi Bandung, Bandung, 40132, Indonesia
d Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, 920-1181, Japan
[vc_row][vc_column][vc_row_inner][vc_column_inner][vc_separator css=”.vc_custom_1624529070653{padding-top: 30px !important;padding-bottom: 30px !important;}”][/vc_column_inner][/vc_row_inner][vc_row_inner layout=”boxed”][vc_column_inner width=”3/4″ css=”.vc_custom_1624695412187{border-right-width: 1px !important;border-right-color: #dddddd !important;border-right-style: solid !important;border-radius: 1px !important;}”][vc_empty_space][megatron_heading title=”Abstract” size=”size-sm” text_align=”text-left”][vc_column_text]As constituents of Averrhoa bilimbi leaves we identified three new compounds (1-3) together with 12 known ones (4-15); their inhibitory activities on cytochrome P450 3A4 (CYP3A4) and 2D6 (CYP2D6) were examined. Among the isolated compounds, the mixture of 1 and 2, and compounds 4 and 9 showed strong inhibition on CYP3A4, but mild or no inhibition on CYP2D6. These compounds revealed the characteristics of 1) time-and concentrationdependent inhibition, 2) requirement of NADPH for the inhibition, 3) no protection by nucleophiles, and 4) suppression of the inhibition by competitive inhibitor. Thus, they are suggested to be mechanism-based inactivators of CYP3A4 and CYP2D6. The kinetic parameters for the inactivation (kinact and KI) were 0.19 min-1 and 36.7 μM for the mixture of 1 and 2, 0.126 min-1 and 10.5 μM for 4, and 0.29 min-1 and 23.4 μM for 9.[/vc_column_text][vc_empty_space][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][vc_empty_space][megatron_heading title=”Author keywords” size=”size-sm” text_align=”text-left”][vc_column_text]Averrhoa,Cytochrome P-450 CYP2D6 Inhibitors,Cytochrome P-450 CYP3A Inhibitors,Herb-Drug Interactions,Plants, Medicinal[/vc_column_text][vc_empty_space][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][vc_empty_space][megatron_heading title=”Indexed keywords” size=”size-sm” text_align=”text-left”][vc_column_text]Averrhoa bilimbi,Blimbing wuluh,Cytochrome P450 2D6 (CYP2D6),Cytochrome P450 3A4 (CYP3A4),Drug-herb interaction,Mechanism-based inactivation[/vc_column_text][vc_empty_space][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][vc_empty_space][megatron_heading title=”Funding details” size=”size-sm” text_align=”text-left”][vc_column_text][/vc_column_text][vc_empty_space][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][vc_empty_space][megatron_heading title=”DOI” size=”size-sm” text_align=”text-left”][vc_column_text]https://doi.org/10.1177/1934578×1501000116[/vc_column_text][/vc_column_inner][vc_column_inner width=”1/4″][vc_column_text]Widget Plumx[/vc_column_text][/vc_column_inner][/vc_row_inner][/vc_column][/vc_row][vc_row][vc_column][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][/vc_column][/vc_row]