Studies on the mechanism of anti-inflammatory action of swietenine, a tetranortriterpenoid isolated from Swietenia macrophylla seeds
Background: Swietenia macrophylla seeds possess diverse biological activities in which inflammation is the primary cause, and swietenine is the main tetranortriterpenoid present. Purpose: The purpose of the study is to investigate the molecular mechanisms involved in the anti-inflammatory activity o...
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Elsevier
2021-02-01
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Series: | Phytomedicine Plus |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S266703132030018X |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kit-Kay Mak Zhang Shiming Madhu Katyayani Balijepalli Albena T. Dinkova-Kostova Ola Epemolu Zulkefeli Mohd Mallikarjuna Rao Pichika |
spellingShingle |
Kit-Kay Mak Zhang Shiming Madhu Katyayani Balijepalli Albena T. Dinkova-Kostova Ola Epemolu Zulkefeli Mohd Mallikarjuna Rao Pichika Studies on the mechanism of anti-inflammatory action of swietenine, a tetranortriterpenoid isolated from Swietenia macrophylla seeds Phytomedicine Plus Swietenine NRF2 NQO1 Anti-inflammatory Metabolic stability |
author_facet |
Kit-Kay Mak Zhang Shiming Madhu Katyayani Balijepalli Albena T. Dinkova-Kostova Ola Epemolu Zulkefeli Mohd Mallikarjuna Rao Pichika |
author_sort |
Kit-Kay Mak |
title |
Studies on the mechanism of anti-inflammatory action of swietenine, a tetranortriterpenoid isolated from Swietenia macrophylla seeds |
title_short |
Studies on the mechanism of anti-inflammatory action of swietenine, a tetranortriterpenoid isolated from Swietenia macrophylla seeds |
title_full |
Studies on the mechanism of anti-inflammatory action of swietenine, a tetranortriterpenoid isolated from Swietenia macrophylla seeds |
title_fullStr |
Studies on the mechanism of anti-inflammatory action of swietenine, a tetranortriterpenoid isolated from Swietenia macrophylla seeds |
title_full_unstemmed |
Studies on the mechanism of anti-inflammatory action of swietenine, a tetranortriterpenoid isolated from Swietenia macrophylla seeds |
title_sort |
studies on the mechanism of anti-inflammatory action of swietenine, a tetranortriterpenoid isolated from swietenia macrophylla seeds |
publisher |
Elsevier |
series |
Phytomedicine Plus |
issn |
2667-0313 |
publishDate |
2021-02-01 |
description |
Background: Swietenia macrophylla seeds possess diverse biological activities in which inflammation is the primary cause, and swietenine is the main tetranortriterpenoid present. Purpose: The purpose of the study is to investigate the molecular mechanisms involved in the anti-inflammatory activity of swietenine and its cytoprotective effect. Methods: The anti-inflammatory activity of swietenine and its molecular mechanisms were evaluated using LPSEc- stimulated RAW 264.7 cells. The cytoprotective effect of swietenine was evaluated via determining NRF2 inducing activity in Hepa-1c1c7 cells. The in vitro metabolic stability of swietenine was assessed using mouse, rat and human liver microsomes. Results: Swietenine showed dose-dependent effect in inhibiting NO production, downregulating pro-inflammatory cytokines (IL-1β, IFN-γ, TNF-α, and IL-6) and mediators (NF-κB and COX-2); and increasing the levels of NRF2, and HO-1 in LPSEc-stimulated RAW264.7 cells. Swietenine also induced NQO1 activity, a classical marker of NRF2 activation, in Hepa-1c1c7 cells. In addition, swietenine was metabolically stable in mouse, rat, and human liver microsomes. Conclusion: The results suggest that the anti-inflammatory effect of swietenine is mediated by the down-regulation of pro-inflammatory cytokines and mediators and the activation of cytoprotective NRF2/HO-1 pathway. |
topic |
Swietenine NRF2 NQO1 Anti-inflammatory Metabolic stability |
url |
http://www.sciencedirect.com/science/article/pii/S266703132030018X |
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spelling |
doaj-f07182f86aa545c1847d569235f6754d2021-06-08T04:44:49ZengElsevierPhytomedicine Plus2667-03132021-02-0111100018Studies on the mechanism of anti-inflammatory action of swietenine, a tetranortriterpenoid isolated from Swietenia macrophylla seedsKit-Kay Mak0Zhang Shiming1Madhu Katyayani Balijepalli2Albena T. Dinkova-Kostova3Ola Epemolu4Zulkefeli Mohd5Mallikarjuna Rao Pichika6Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, 126. Jalan Jalil Perkasa 19, Bukit Jalil 57000, Kuala Lumpur, Malaysia; Centre of Excellence for Bioactive Molecules and Drug Delivery, Institute for Research, Development & Innovation, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil 57000, Kuala Lumpur, Malaysia; School of Postgraduate studies and Research, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil 57000, Kuala Lumpur, MalaysiaSchool of Postgraduate studies and Research, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil 57000, Kuala Lumpur, MalaysiaDepartment of Pharmacology, Faculty of Medicine, MAHSA University, Jln SP 2, Bandar Saujana Putra, 42610 Jenjarom, Selangor, MalaysiaDivision of Cellular Medicine, School of Medicine, Jacqui Wood Cancer Centre, University of Dundee, Dundee, Scotland, United Kingdom; Departments of Medicine and Pharmacology and Molecular Sciences, Johns Hopkins University, School of Medicine, Baltimore, MA, United StatesDrug Discovery Unit, Wellcome Centre for Anti-infectives Research, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, Scotland, United KingdomDepartment of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, 126. Jalan Jalil Perkasa 19, Bukit Jalil 57000, Kuala Lumpur, Malaysia; Centre of Excellence for Bioactive Molecules and Drug Delivery, Institute for Research, Development & Innovation, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil 57000, Kuala Lumpur, MalaysiaDepartment of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, 126. Jalan Jalil Perkasa 19, Bukit Jalil 57000, Kuala Lumpur, Malaysia; Centre of Excellence for Bioactive Molecules and Drug Delivery, Institute for Research, Development & Innovation, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil 57000, Kuala Lumpur, Malaysia; Corresponding author at: Professor, Pharmaceutical Chemistry Department, School of Pharmacy; Head, Centre of Excellence for Bioactive Moelcules & Drug Delivery; International Medical Univeristy, 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000, Kuala Lumpur, Malaysia.Background: Swietenia macrophylla seeds possess diverse biological activities in which inflammation is the primary cause, and swietenine is the main tetranortriterpenoid present. Purpose: The purpose of the study is to investigate the molecular mechanisms involved in the anti-inflammatory activity of swietenine and its cytoprotective effect. Methods: The anti-inflammatory activity of swietenine and its molecular mechanisms were evaluated using LPSEc- stimulated RAW 264.7 cells. The cytoprotective effect of swietenine was evaluated via determining NRF2 inducing activity in Hepa-1c1c7 cells. The in vitro metabolic stability of swietenine was assessed using mouse, rat and human liver microsomes. Results: Swietenine showed dose-dependent effect in inhibiting NO production, downregulating pro-inflammatory cytokines (IL-1β, IFN-γ, TNF-α, and IL-6) and mediators (NF-κB and COX-2); and increasing the levels of NRF2, and HO-1 in LPSEc-stimulated RAW264.7 cells. Swietenine also induced NQO1 activity, a classical marker of NRF2 activation, in Hepa-1c1c7 cells. In addition, swietenine was metabolically stable in mouse, rat, and human liver microsomes. Conclusion: The results suggest that the anti-inflammatory effect of swietenine is mediated by the down-regulation of pro-inflammatory cytokines and mediators and the activation of cytoprotective NRF2/HO-1 pathway.http://www.sciencedirect.com/science/article/pii/S266703132030018XSwietenineNRF2NQO1Anti-inflammatoryMetabolic stability |