Isolation, synthesis, and drug interaction potential of secondary metabolites derived from the leaves of miracle tree (Moringa oleifera) against CYP3A4 and CYP2D6 isozymes.
CC, column chromatography
CYP inhibition
CYP450, cytochrome P450
Cytotoxicity
HDI, herb-drug interaction
M. oleifera, Moringa oleifera
MeOH, methanol
Moringa oleifera
Moringaceae
Niazirin
Rhamnopyranoside synthesis
Journal
Phytomedicine : international journal of phytotherapy and phytopharmacology
ISSN: 1618-095X
Titre abrégé: Phytomedicine
Pays: Germany
ID NLM: 9438794
Informations de publication
Date de publication:
Jul 2019
Jul 2019
Historique:
received:
24
04
2019
revised:
21
06
2019
accepted:
01
07
2019
pubmed:
16
7
2019
medline:
18
12
2019
entrez:
15
7
2019
Statut:
ppublish
Résumé
Moringa oleifera Lam. is known as a drumstick tree that is widely cultivated in various subtropical and tropical provinces. Previous studies indicated that both aqueous and methanolic extracts of M. oleifera leaves have potent inhibitory effects on two major drug metabolizing Cytochrome P450 enzymes, namely, CYP3A4 and CYP2D6. The current study was aimed to isolate the secondary metabolites from M. oleifera and investigate their cytotoxicity and inhibitory effects on CYP3A4 and CYP2D6 to assess their herb-drug interaction (HDI) potential. Chemical structure elucidation was achieved by interpreting the spectroscopic data (UV, IR, 1D, and 2D NMR experiments), confirming by HR-ESI-MS, and comparing with the previously reported data in the literature. All the isolates were evaluated for their cytotoxicity against a panel of cell lines (SK-MEL, KB, BT-549, SK-OV-3, VERO, LLC-PK1, and HepG2) and inhibition of two principal CYP isozymes (CYP3A4 and CYP2D6). Phytochemical investigation of M. oleifera leaves resulted in the isolation and characterization of one new compound, namely omoringone (1), along with twelve known secondary metabolites (2-13) belonging to several chemical classes including flavonoids, terpenoids, lignans, and phenylalkanoids. A plausible biosynthetic pathway for compound 1 was provided. Because of the low isolation yield and limited supply, omoringone (1) and niazirin (12) were successively synthesized. No cytotoxicity was observed on any of the tested cell lines up to 50 µM. The extract exhibited an inhibitory effect on CYP3A4 isoform (IC This work aided in ascertaining components of M. oleifera contributing to CYP3A4 inhibition exhibited by the extract using an in vitro assay. Nonetheless, further studies are warranted to determine the bioavailability of the phytochemicals and extrapolate these findings in more physiologically relevant conditions to further establish the clinical relevance of in vitro observations.
Sections du résumé
BACKGROUND
BACKGROUND
Moringa oleifera Lam. is known as a drumstick tree that is widely cultivated in various subtropical and tropical provinces. Previous studies indicated that both aqueous and methanolic extracts of M. oleifera leaves have potent inhibitory effects on two major drug metabolizing Cytochrome P450 enzymes, namely, CYP3A4 and CYP2D6.
PURPOSE
OBJECTIVE
The current study was aimed to isolate the secondary metabolites from M. oleifera and investigate their cytotoxicity and inhibitory effects on CYP3A4 and CYP2D6 to assess their herb-drug interaction (HDI) potential.
METHODS
METHODS
Chemical structure elucidation was achieved by interpreting the spectroscopic data (UV, IR, 1D, and 2D NMR experiments), confirming by HR-ESI-MS, and comparing with the previously reported data in the literature. All the isolates were evaluated for their cytotoxicity against a panel of cell lines (SK-MEL, KB, BT-549, SK-OV-3, VERO, LLC-PK1, and HepG2) and inhibition of two principal CYP isozymes (CYP3A4 and CYP2D6).
RESULTS
RESULTS
Phytochemical investigation of M. oleifera leaves resulted in the isolation and characterization of one new compound, namely omoringone (1), along with twelve known secondary metabolites (2-13) belonging to several chemical classes including flavonoids, terpenoids, lignans, and phenylalkanoids. A plausible biosynthetic pathway for compound 1 was provided. Because of the low isolation yield and limited supply, omoringone (1) and niazirin (12) were successively synthesized. No cytotoxicity was observed on any of the tested cell lines up to 50 µM. The extract exhibited an inhibitory effect on CYP3A4 isoform (IC
CONCLUSION
CONCLUSIONS
This work aided in ascertaining components of M. oleifera contributing to CYP3A4 inhibition exhibited by the extract using an in vitro assay. Nonetheless, further studies are warranted to determine the bioavailability of the phytochemicals and extrapolate these findings in more physiologically relevant conditions to further establish the clinical relevance of in vitro observations.
Identifiants
pubmed: 31301970
pii: S0944-7113(19)30176-X
doi: 10.1016/j.phymed.2019.153010
pii:
doi:
Substances chimiques
Cytochrome P-450 CYP3A Inhibitors
0
Isoenzymes
0
Plant Extracts
0
Cytochrome P-450 CYP2D6
EC 1.14.14.1
Cytochrome P-450 CYP3A
EC 1.14.14.1
CYP3A4 protein, human
EC 1.14.14.55
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
153010Informations de copyright
Copyright © 2019 Elsevier GmbH. All rights reserved.