Cargando…
Cardamom Extract Alleviates the Oxidative Stress, Inflammation and Apoptosis Induced during Acetaminophen-Induced Hepatic Toxicity via Modulating Nrf2/HO-1/NQO-1 Pathway
Acetaminophen (APAP) is the most extensively used and safest analgesic and antipyretic drug worldwide; however, its toxicity is associated with life-threatening acute liver failure. Cardamom (CARD), a sweet, aromatic, commonly used spice, has several pharmacological actions. In the current study, we...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9688982/ https://www.ncbi.nlm.nih.gov/pubmed/36354677 http://dx.doi.org/10.3390/cimb44110365 |
_version_ | 1784836407842308096 |
---|---|
author | Alkhalifah, Essraa A. R. Alobaid, Amjad A. Almajed, Marwah A. Alomair, Manar K. Alabduladheem, Lama S. Al-Subaie, Sarah F. Akbar, Abdullah Attimarad, Mahesh V. Younis, Nancy S. Mohamed, Maged E. |
author_facet | Alkhalifah, Essraa A. R. Alobaid, Amjad A. Almajed, Marwah A. Alomair, Manar K. Alabduladheem, Lama S. Al-Subaie, Sarah F. Akbar, Abdullah Attimarad, Mahesh V. Younis, Nancy S. Mohamed, Maged E. |
author_sort | Alkhalifah, Essraa A. R. |
collection | PubMed |
description | Acetaminophen (APAP) is the most extensively used and safest analgesic and antipyretic drug worldwide; however, its toxicity is associated with life-threatening acute liver failure. Cardamom (CARD), a sweet, aromatic, commonly used spice, has several pharmacological actions. In the current study, we tried to explore the chemical composition and the hepato-protective effect of ethanolic aqueous extract of CARD to mitigate APAP-induced hepatic toxicity and elucidate its underlying mechanism of action. Material and methods: Aqueous CARD extract was subjected to LC-TOF-MS analysis to separate and elucidate some of its components. In vivo animal experiments involved five groups of animals. In the normal and cardamom groups, mice were administered either saline or CARD (200 mg/kg), respectively, orally daily for 16 days. In the APAP group, the animals were administered saline orally daily for 15 days, and on the 16th day, animals were administered APAP (300 mg/kg) IP for the induction of acute hepatic failure. In the CARD 200 + APAP group, mice were administered CARD (200 mg/kg) for 15 days, followed by APAP on the 16th day. Results: The aqueous extract of CARD showed several compounds, belonging to polyphenol, flavonoids, cinnamic acid derivatives and essential oil components. In the in vivo investigations, APAP-induced impaired liver function, several histopathological alterations, oxidative stress and inflammatory and apoptotic status signified severe hepatic failure. Whereas, pretreatment with the CARD extract prior to APAP administration diminished serum levels of the hepatic function test and augmented Nrf2 nucleoprotein and HO-1 and NQO-1. CARD down-regulated MDA, inflammatory mediators (IL-1β, IL-6, TNF-α and NF-κB) and apoptotic markers (caspase 3 and 9 and Bax) and amplified the activities of SOD, catalase, GSH-Px and GSH-R in hepatic tissue samples. Conclusion: CARD extract mitigated the hepatic toxicity induced by APAP. The underlying mechanism of action of such hepato-protective action may be through upregulation of the Nrf2/HO-1/NQO-1 pathway with subsequent alleviation of the oxidative stress, inflammation and apoptosis induced by APAP. Many of the compounds identified in the CARD extract could be attributed to this pharmacological action of the extract. |
format | Online Article Text |
id | pubmed-9688982 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96889822022-11-25 Cardamom Extract Alleviates the Oxidative Stress, Inflammation and Apoptosis Induced during Acetaminophen-Induced Hepatic Toxicity via Modulating Nrf2/HO-1/NQO-1 Pathway Alkhalifah, Essraa A. R. Alobaid, Amjad A. Almajed, Marwah A. Alomair, Manar K. Alabduladheem, Lama S. Al-Subaie, Sarah F. Akbar, Abdullah Attimarad, Mahesh V. Younis, Nancy S. Mohamed, Maged E. Curr Issues Mol Biol Article Acetaminophen (APAP) is the most extensively used and safest analgesic and antipyretic drug worldwide; however, its toxicity is associated with life-threatening acute liver failure. Cardamom (CARD), a sweet, aromatic, commonly used spice, has several pharmacological actions. In the current study, we tried to explore the chemical composition and the hepato-protective effect of ethanolic aqueous extract of CARD to mitigate APAP-induced hepatic toxicity and elucidate its underlying mechanism of action. Material and methods: Aqueous CARD extract was subjected to LC-TOF-MS analysis to separate and elucidate some of its components. In vivo animal experiments involved five groups of animals. In the normal and cardamom groups, mice were administered either saline or CARD (200 mg/kg), respectively, orally daily for 16 days. In the APAP group, the animals were administered saline orally daily for 15 days, and on the 16th day, animals were administered APAP (300 mg/kg) IP for the induction of acute hepatic failure. In the CARD 200 + APAP group, mice were administered CARD (200 mg/kg) for 15 days, followed by APAP on the 16th day. Results: The aqueous extract of CARD showed several compounds, belonging to polyphenol, flavonoids, cinnamic acid derivatives and essential oil components. In the in vivo investigations, APAP-induced impaired liver function, several histopathological alterations, oxidative stress and inflammatory and apoptotic status signified severe hepatic failure. Whereas, pretreatment with the CARD extract prior to APAP administration diminished serum levels of the hepatic function test and augmented Nrf2 nucleoprotein and HO-1 and NQO-1. CARD down-regulated MDA, inflammatory mediators (IL-1β, IL-6, TNF-α and NF-κB) and apoptotic markers (caspase 3 and 9 and Bax) and amplified the activities of SOD, catalase, GSH-Px and GSH-R in hepatic tissue samples. Conclusion: CARD extract mitigated the hepatic toxicity induced by APAP. The underlying mechanism of action of such hepato-protective action may be through upregulation of the Nrf2/HO-1/NQO-1 pathway with subsequent alleviation of the oxidative stress, inflammation and apoptosis induced by APAP. Many of the compounds identified in the CARD extract could be attributed to this pharmacological action of the extract. MDPI 2022-11-02 /pmc/articles/PMC9688982/ /pubmed/36354677 http://dx.doi.org/10.3390/cimb44110365 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Alkhalifah, Essraa A. R. Alobaid, Amjad A. Almajed, Marwah A. Alomair, Manar K. Alabduladheem, Lama S. Al-Subaie, Sarah F. Akbar, Abdullah Attimarad, Mahesh V. Younis, Nancy S. Mohamed, Maged E. Cardamom Extract Alleviates the Oxidative Stress, Inflammation and Apoptosis Induced during Acetaminophen-Induced Hepatic Toxicity via Modulating Nrf2/HO-1/NQO-1 Pathway |
title | Cardamom Extract Alleviates the Oxidative Stress, Inflammation and Apoptosis Induced during Acetaminophen-Induced Hepatic Toxicity via Modulating Nrf2/HO-1/NQO-1 Pathway |
title_full | Cardamom Extract Alleviates the Oxidative Stress, Inflammation and Apoptosis Induced during Acetaminophen-Induced Hepatic Toxicity via Modulating Nrf2/HO-1/NQO-1 Pathway |
title_fullStr | Cardamom Extract Alleviates the Oxidative Stress, Inflammation and Apoptosis Induced during Acetaminophen-Induced Hepatic Toxicity via Modulating Nrf2/HO-1/NQO-1 Pathway |
title_full_unstemmed | Cardamom Extract Alleviates the Oxidative Stress, Inflammation and Apoptosis Induced during Acetaminophen-Induced Hepatic Toxicity via Modulating Nrf2/HO-1/NQO-1 Pathway |
title_short | Cardamom Extract Alleviates the Oxidative Stress, Inflammation and Apoptosis Induced during Acetaminophen-Induced Hepatic Toxicity via Modulating Nrf2/HO-1/NQO-1 Pathway |
title_sort | cardamom extract alleviates the oxidative stress, inflammation and apoptosis induced during acetaminophen-induced hepatic toxicity via modulating nrf2/ho-1/nqo-1 pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9688982/ https://www.ncbi.nlm.nih.gov/pubmed/36354677 http://dx.doi.org/10.3390/cimb44110365 |
work_keys_str_mv | AT alkhalifahessraaar cardamomextractalleviatestheoxidativestressinflammationandapoptosisinducedduringacetaminopheninducedhepatictoxicityviamodulatingnrf2ho1nqo1pathway AT alobaidamjada cardamomextractalleviatestheoxidativestressinflammationandapoptosisinducedduringacetaminopheninducedhepatictoxicityviamodulatingnrf2ho1nqo1pathway AT almajedmarwaha cardamomextractalleviatestheoxidativestressinflammationandapoptosisinducedduringacetaminopheninducedhepatictoxicityviamodulatingnrf2ho1nqo1pathway AT alomairmanark cardamomextractalleviatestheoxidativestressinflammationandapoptosisinducedduringacetaminopheninducedhepatictoxicityviamodulatingnrf2ho1nqo1pathway AT alabduladheemlamas cardamomextractalleviatestheoxidativestressinflammationandapoptosisinducedduringacetaminopheninducedhepatictoxicityviamodulatingnrf2ho1nqo1pathway AT alsubaiesarahf cardamomextractalleviatestheoxidativestressinflammationandapoptosisinducedduringacetaminopheninducedhepatictoxicityviamodulatingnrf2ho1nqo1pathway AT akbarabdullah cardamomextractalleviatestheoxidativestressinflammationandapoptosisinducedduringacetaminopheninducedhepatictoxicityviamodulatingnrf2ho1nqo1pathway AT attimaradmaheshv cardamomextractalleviatestheoxidativestressinflammationandapoptosisinducedduringacetaminopheninducedhepatictoxicityviamodulatingnrf2ho1nqo1pathway AT younisnancys cardamomextractalleviatestheoxidativestressinflammationandapoptosisinducedduringacetaminopheninducedhepatictoxicityviamodulatingnrf2ho1nqo1pathway AT mohamedmagede cardamomextractalleviatestheoxidativestressinflammationandapoptosisinducedduringacetaminopheninducedhepatictoxicityviamodulatingnrf2ho1nqo1pathway |