Cargando…

Commiphora myrrha (Nees) Engl. resin extracts induce phase-I cytochrome P450 2C8, 2C9, 2C19, and 3A4 isoenzyme expressions in human hepatocellular carcinoma (HepG2) cells

Commiphora myrrha (Nees) Engl. (C. myrrha) resin is the most Middle Eastern herbal medicine used against numerous diseases. After being decocted or macerated, this resin is widely consumed among Saudi Arabian patients who are already under prescribed medication. Despite its popularity, no studies ha...

Descripción completa

Detalles Bibliográficos
Autores principales: Alehaideb, Zeyad, Alatar, Ghada, Nehdi, Atef, Albaz, Abeer, Al-Eidi, Hamad, Almutairi, Mansour, Hawsa, Esraa, Alshuail, Nora, Matou-Nasri, Sabine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180464/
https://www.ncbi.nlm.nih.gov/pubmed/34135662
http://dx.doi.org/10.1016/j.jsps.2021.03.002
_version_ 1783704004112416768
author Alehaideb, Zeyad
Alatar, Ghada
Nehdi, Atef
Albaz, Abeer
Al-Eidi, Hamad
Almutairi, Mansour
Hawsa, Esraa
Alshuail, Nora
Matou-Nasri, Sabine
author_facet Alehaideb, Zeyad
Alatar, Ghada
Nehdi, Atef
Albaz, Abeer
Al-Eidi, Hamad
Almutairi, Mansour
Hawsa, Esraa
Alshuail, Nora
Matou-Nasri, Sabine
author_sort Alehaideb, Zeyad
collection PubMed
description Commiphora myrrha (Nees) Engl. (C. myrrha) resin is the most Middle Eastern herbal medicine used against numerous diseases. After being decocted or macerated, this resin is widely consumed among Saudi Arabian patients who are already under prescribed medication. Despite its popularity, no studies have been reported on potential modulation effects of these resin extracts on drug metabolism. Therefore, we studied C. myrrha resin extracts on the expression of cytochrome P450 (CYP) drug-metabolizing isoenzyme in human hepatocellular carcinoma cell line HepG2. The C. myrrha extracts were prepared by sonication and boiling, resembling the most popular traditional preparations of maceration and decoction, respectively. Both boiled and sonicated aqueous extracts were fingerprinted using high-performance liquid chromatography equipped with ultra-violet detector (HPLC-UVD). The viability of HepG2 cells treated with these aqueous extracts was determined using CellTiter-Glo® assay in order to select the efficient and non-toxic resin extract concentrations for phase-I metabolic CYP isoenzyme expression analysis. The isoenzyme gene and protein expression levels of CYP 2C8, 2C9, 2C19, and 3A4 were assessed using reverse transcription-quantitative polymerase chain reaction and Western blot technologies. The HPLC-UVD fingerprinting revealed different chromatograms for C. myrrha boiled and sonicated aqueous extracts. Both aqueous extracts were toxic to HepG2 cells when tested at concentrations exceeding 150 µg/ml of the dry crude extract. The CYP 2C8, 2C9, and 2C19 mRNA expression levels increased up to 4.0-fold in HepG2 cells treated with either boiled or sonicated C. myrrha aqueous extracts tested between 1 and 30 µg/ml, as compared with the untreated cells. However, CYP3A4 mRNA expression level exceeded the 2.0-fold cutoff when the cells were exposed to 30 µg/ml of C. myrrha extracts. The up-regulation of CYP mRNA expression levels induced by both boiled and sonicated C. myrrha aqueous extracts was confirmed at the CYP protein expression levels. In conclusion, both sonicated and boiled C. myrrha aqueous extracts modulate CYP 2C8, 2C9, 2C19, and 3A4 gene expression at clinically-relevant concentrations regardless of preparation methods. Further in vitro and in vivo experiments are required for CYP isoenzyme activity assessment and the establishment of herb-drug interaction profile for these traditional medicinal resin extracts.
format Online
Article
Text
id pubmed-8180464
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-81804642021-06-15 Commiphora myrrha (Nees) Engl. resin extracts induce phase-I cytochrome P450 2C8, 2C9, 2C19, and 3A4 isoenzyme expressions in human hepatocellular carcinoma (HepG2) cells Alehaideb, Zeyad Alatar, Ghada Nehdi, Atef Albaz, Abeer Al-Eidi, Hamad Almutairi, Mansour Hawsa, Esraa Alshuail, Nora Matou-Nasri, Sabine Saudi Pharm J Original Article Commiphora myrrha (Nees) Engl. (C. myrrha) resin is the most Middle Eastern herbal medicine used against numerous diseases. After being decocted or macerated, this resin is widely consumed among Saudi Arabian patients who are already under prescribed medication. Despite its popularity, no studies have been reported on potential modulation effects of these resin extracts on drug metabolism. Therefore, we studied C. myrrha resin extracts on the expression of cytochrome P450 (CYP) drug-metabolizing isoenzyme in human hepatocellular carcinoma cell line HepG2. The C. myrrha extracts were prepared by sonication and boiling, resembling the most popular traditional preparations of maceration and decoction, respectively. Both boiled and sonicated aqueous extracts were fingerprinted using high-performance liquid chromatography equipped with ultra-violet detector (HPLC-UVD). The viability of HepG2 cells treated with these aqueous extracts was determined using CellTiter-Glo® assay in order to select the efficient and non-toxic resin extract concentrations for phase-I metabolic CYP isoenzyme expression analysis. The isoenzyme gene and protein expression levels of CYP 2C8, 2C9, 2C19, and 3A4 were assessed using reverse transcription-quantitative polymerase chain reaction and Western blot technologies. The HPLC-UVD fingerprinting revealed different chromatograms for C. myrrha boiled and sonicated aqueous extracts. Both aqueous extracts were toxic to HepG2 cells when tested at concentrations exceeding 150 µg/ml of the dry crude extract. The CYP 2C8, 2C9, and 2C19 mRNA expression levels increased up to 4.0-fold in HepG2 cells treated with either boiled or sonicated C. myrrha aqueous extracts tested between 1 and 30 µg/ml, as compared with the untreated cells. However, CYP3A4 mRNA expression level exceeded the 2.0-fold cutoff when the cells were exposed to 30 µg/ml of C. myrrha extracts. The up-regulation of CYP mRNA expression levels induced by both boiled and sonicated C. myrrha aqueous extracts was confirmed at the CYP protein expression levels. In conclusion, both sonicated and boiled C. myrrha aqueous extracts modulate CYP 2C8, 2C9, 2C19, and 3A4 gene expression at clinically-relevant concentrations regardless of preparation methods. Further in vitro and in vivo experiments are required for CYP isoenzyme activity assessment and the establishment of herb-drug interaction profile for these traditional medicinal resin extracts. Elsevier 2021-05 2021-04-01 /pmc/articles/PMC8180464/ /pubmed/34135662 http://dx.doi.org/10.1016/j.jsps.2021.03.002 Text en © 2021 King Abdullah International Medical Research Center https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Alehaideb, Zeyad
Alatar, Ghada
Nehdi, Atef
Albaz, Abeer
Al-Eidi, Hamad
Almutairi, Mansour
Hawsa, Esraa
Alshuail, Nora
Matou-Nasri, Sabine
Commiphora myrrha (Nees) Engl. resin extracts induce phase-I cytochrome P450 2C8, 2C9, 2C19, and 3A4 isoenzyme expressions in human hepatocellular carcinoma (HepG2) cells
title Commiphora myrrha (Nees) Engl. resin extracts induce phase-I cytochrome P450 2C8, 2C9, 2C19, and 3A4 isoenzyme expressions in human hepatocellular carcinoma (HepG2) cells
title_full Commiphora myrrha (Nees) Engl. resin extracts induce phase-I cytochrome P450 2C8, 2C9, 2C19, and 3A4 isoenzyme expressions in human hepatocellular carcinoma (HepG2) cells
title_fullStr Commiphora myrrha (Nees) Engl. resin extracts induce phase-I cytochrome P450 2C8, 2C9, 2C19, and 3A4 isoenzyme expressions in human hepatocellular carcinoma (HepG2) cells
title_full_unstemmed Commiphora myrrha (Nees) Engl. resin extracts induce phase-I cytochrome P450 2C8, 2C9, 2C19, and 3A4 isoenzyme expressions in human hepatocellular carcinoma (HepG2) cells
title_short Commiphora myrrha (Nees) Engl. resin extracts induce phase-I cytochrome P450 2C8, 2C9, 2C19, and 3A4 isoenzyme expressions in human hepatocellular carcinoma (HepG2) cells
title_sort commiphora myrrha (nees) engl. resin extracts induce phase-i cytochrome p450 2c8, 2c9, 2c19, and 3a4 isoenzyme expressions in human hepatocellular carcinoma (hepg2) cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180464/
https://www.ncbi.nlm.nih.gov/pubmed/34135662
http://dx.doi.org/10.1016/j.jsps.2021.03.002
work_keys_str_mv AT alehaidebzeyad commiphoramyrrhaneesenglresinextractsinducephaseicytochromep4502c82c92c19and3a4isoenzymeexpressionsinhumanhepatocellularcarcinomahepg2cells
AT alatarghada commiphoramyrrhaneesenglresinextractsinducephaseicytochromep4502c82c92c19and3a4isoenzymeexpressionsinhumanhepatocellularcarcinomahepg2cells
AT nehdiatef commiphoramyrrhaneesenglresinextractsinducephaseicytochromep4502c82c92c19and3a4isoenzymeexpressionsinhumanhepatocellularcarcinomahepg2cells
AT albazabeer commiphoramyrrhaneesenglresinextractsinducephaseicytochromep4502c82c92c19and3a4isoenzymeexpressionsinhumanhepatocellularcarcinomahepg2cells
AT aleidihamad commiphoramyrrhaneesenglresinextractsinducephaseicytochromep4502c82c92c19and3a4isoenzymeexpressionsinhumanhepatocellularcarcinomahepg2cells
AT almutairimansour commiphoramyrrhaneesenglresinextractsinducephaseicytochromep4502c82c92c19and3a4isoenzymeexpressionsinhumanhepatocellularcarcinomahepg2cells
AT hawsaesraa commiphoramyrrhaneesenglresinextractsinducephaseicytochromep4502c82c92c19and3a4isoenzymeexpressionsinhumanhepatocellularcarcinomahepg2cells
AT alshuailnora commiphoramyrrhaneesenglresinextractsinducephaseicytochromep4502c82c92c19and3a4isoenzymeexpressionsinhumanhepatocellularcarcinomahepg2cells
AT matounasrisabine commiphoramyrrhaneesenglresinextractsinducephaseicytochromep4502c82c92c19and3a4isoenzymeexpressionsinhumanhepatocellularcarcinomahepg2cells