Cardioprotective effects of arjunolic acid in LPS-stimulated H9C2 and C2C12myotubes via the MyD88-dependent TLR4 signaling pathway

Context: Arjunolic acid (AA) is a triterpenoid saponin found in Terminalia arjuna (Roxb.) Wight & Arn. (Combretaceae). It exerts cardiovascular protective effects as a phytomedicine. However, it is unclear how AA exerts the effects at the molecular level. Objective: This study investigates the c...

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Main Authors: Md Mahmudul Hasana, Priya Madhavan, Nur Adelina Ahmad Noruddin, Wai, Kwan Lau, Qamar Uddin Ahmed, Aditya Aryab, Zainul Amiruddin Zakaria
Format: Article
Language:English
English
Published: Taylor & Francis Group 2023
Subjects:
Online Access:https://eprints.ums.edu.my/id/eprint/38594/1/ABSTRACT.pdf
https://eprints.ums.edu.my/id/eprint/38594/2/FULL%20TEXT.pdf
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author Md Mahmudul Hasana
Priya Madhavan
Nur Adelina Ahmad Noruddin
Wai, Kwan Lau
Qamar Uddin Ahmed
Aditya Aryab
Zainul Amiruddin Zakaria
author_facet Md Mahmudul Hasana
Priya Madhavan
Nur Adelina Ahmad Noruddin
Wai, Kwan Lau
Qamar Uddin Ahmed
Aditya Aryab
Zainul Amiruddin Zakaria
author_sort Md Mahmudul Hasana
collection UMS
description Context: Arjunolic acid (AA) is a triterpenoid saponin found in Terminalia arjuna (Roxb.) Wight & Arn. (Combretaceae). It exerts cardiovascular protective effects as a phytomedicine. However, it is unclear how AA exerts the effects at the molecular level. Objective: This study investigates the cardioprotective effects of arjun Olic acid (AA)viaMyD88-dependantTLR4 downstream signaling marker expression. Materials and methods: The MTT viability assay was used to assess the cytotoxicity of AA. LPS induced in vitro cardiovascular disease model was developed in H9C2 and C2C12 myotubes. The treatment groups were designed such as control (untreated), LPS control, positive control (LPS þ pyrrolidine dithiocarbamate (PDTC)-25mM), and treatment groups were co-treated with LPS and three concentrations of AA (50, 75, and 100mM) for 24h. The changes in the expression of TLR4 downstream signaling markers were evaluated through High Content Screening (HCS) and Western Blot (WB) analysis. Results: After 24 h of co-treatment, the expression of TLR4, MyD88, MAPK, JNK, and NF-jB markers were upregulated significantly (2-6 times) in the LPS-treated groups compared to the untreated control in both HCS and WB experiments. Evidently, the HCS analysis revealed that MyD88, NF-jB, p38, and JNK were significantly downregulated in the H9C2 myotube in the AA treated groups. In HCS, the expression of NF-jB was downregulated in C2C12. Additionally, TLR4 expression was downregulated in both H9C2 and C2C12myotubes in the WB experiment. Discussion and conclusions: TLR4 marker expression in H9C2 and C2C12 myotubes was subsequently decreased by AA treatment, suggesting possible cardioprotective effects of AA.
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spelling ums.eprints-385942024-04-29T02:53:49Z https://eprints.ums.edu.my/id/eprint/38594/ Cardioprotective effects of arjunolic acid in LPS-stimulated H9C2 and C2C12myotubes via the MyD88-dependent TLR4 signaling pathway Md Mahmudul Hasana Priya Madhavan Nur Adelina Ahmad Noruddin Wai, Kwan Lau Qamar Uddin Ahmed Aditya Aryab Zainul Amiruddin Zakaria R5-920 Medicine (General) RC666-701 Diseases of the circulatory (Cardiovascular) system Context: Arjunolic acid (AA) is a triterpenoid saponin found in Terminalia arjuna (Roxb.) Wight & Arn. (Combretaceae). It exerts cardiovascular protective effects as a phytomedicine. However, it is unclear how AA exerts the effects at the molecular level. Objective: This study investigates the cardioprotective effects of arjun Olic acid (AA)viaMyD88-dependantTLR4 downstream signaling marker expression. Materials and methods: The MTT viability assay was used to assess the cytotoxicity of AA. LPS induced in vitro cardiovascular disease model was developed in H9C2 and C2C12 myotubes. The treatment groups were designed such as control (untreated), LPS control, positive control (LPS þ pyrrolidine dithiocarbamate (PDTC)-25mM), and treatment groups were co-treated with LPS and three concentrations of AA (50, 75, and 100mM) for 24h. The changes in the expression of TLR4 downstream signaling markers were evaluated through High Content Screening (HCS) and Western Blot (WB) analysis. Results: After 24 h of co-treatment, the expression of TLR4, MyD88, MAPK, JNK, and NF-jB markers were upregulated significantly (2-6 times) in the LPS-treated groups compared to the untreated control in both HCS and WB experiments. Evidently, the HCS analysis revealed that MyD88, NF-jB, p38, and JNK were significantly downregulated in the H9C2 myotube in the AA treated groups. In HCS, the expression of NF-jB was downregulated in C2C12. Additionally, TLR4 expression was downregulated in both H9C2 and C2C12myotubes in the WB experiment. Discussion and conclusions: TLR4 marker expression in H9C2 and C2C12 myotubes was subsequently decreased by AA treatment, suggesting possible cardioprotective effects of AA. Taylor & Francis Group 2023 Article NonPeerReviewed text en https://eprints.ums.edu.my/id/eprint/38594/1/ABSTRACT.pdf text en https://eprints.ums.edu.my/id/eprint/38594/2/FULL%20TEXT.pdf Md Mahmudul Hasana and Priya Madhavan and Nur Adelina Ahmad Noruddin and Wai, Kwan Lau and Qamar Uddin Ahmed and Aditya Aryab and Zainul Amiruddin Zakaria (2023) Cardioprotective effects of arjunolic acid in LPS-stimulated H9C2 and C2C12myotubes via the MyD88-dependent TLR4 signaling pathway. Pharmaceutical Biology, 61. pp. 1135-1151. ISSN 1388-0209 https://doi.org/10.1080/13880209.2023.2230251
spellingShingle R5-920 Medicine (General)
RC666-701 Diseases of the circulatory (Cardiovascular) system
Md Mahmudul Hasana
Priya Madhavan
Nur Adelina Ahmad Noruddin
Wai, Kwan Lau
Qamar Uddin Ahmed
Aditya Aryab
Zainul Amiruddin Zakaria
Cardioprotective effects of arjunolic acid in LPS-stimulated H9C2 and C2C12myotubes via the MyD88-dependent TLR4 signaling pathway
title Cardioprotective effects of arjunolic acid in LPS-stimulated H9C2 and C2C12myotubes via the MyD88-dependent TLR4 signaling pathway
title_full Cardioprotective effects of arjunolic acid in LPS-stimulated H9C2 and C2C12myotubes via the MyD88-dependent TLR4 signaling pathway
title_fullStr Cardioprotective effects of arjunolic acid in LPS-stimulated H9C2 and C2C12myotubes via the MyD88-dependent TLR4 signaling pathway
title_full_unstemmed Cardioprotective effects of arjunolic acid in LPS-stimulated H9C2 and C2C12myotubes via the MyD88-dependent TLR4 signaling pathway
title_short Cardioprotective effects of arjunolic acid in LPS-stimulated H9C2 and C2C12myotubes via the MyD88-dependent TLR4 signaling pathway
title_sort cardioprotective effects of arjunolic acid in lps stimulated h9c2 and c2c12myotubes via the myd88 dependent tlr4 signaling pathway
topic R5-920 Medicine (General)
RC666-701 Diseases of the circulatory (Cardiovascular) system
url https://eprints.ums.edu.my/id/eprint/38594/1/ABSTRACT.pdf
https://eprints.ums.edu.my/id/eprint/38594/2/FULL%20TEXT.pdf
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