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

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

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URL: https://www.tandfonline.com/doi/full/10.1080/13880...

Abstract

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.

Item Type:	Article
Keyword:	H9C2 myotube, C2C12 myotube, Skeletal muscle cell, Cardiovascular disease, High content screening, MyD88
Subjects:	R Medicine > R Medicine (General) > R5-920 Medicine (General) R Medicine > RC Internal medicine > RC31-1245 Internal medicine > RC581-951 Specialties of internal medicine > RC666-701 Diseases of the circulatory (Cardiovascular) system
Department:	FACULTY > Faculty of Medicine and Health Sciences
Depositing User:	SITI AZIZAH BINTI IDRIS -
Date Deposited:	29 Apr 2024 10:53
Last Modified:	29 Apr 2024 10:53
URI:	https://eprints.ums.edu.my/id/eprint/38594

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