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Article

Cissus subtetragona Planch. Ameliorates Inflammatory Responses in LPS-induced Macrophages, HCl/EtOH-induced Gastritis, and LPS-induced Lung Injury via Attenuation of Src and TAK1

by
Laily Rahmawati
1,
Nur Aziz
1,
Jieun Oh
1,
Yo Han Hong
1,
Byoung Young Woo
2,
Yong Deog Hong
2,
Philaxay Manilack
3,
Phetlasy Souladeth
4,
Ji Hwa Jung
5,
Woo Shin Lee
6,
Mi Jeong Jeon
7,
Taewoo Kim
7,
Mohammad Amjad Hossain
8,
Jinwhoa Yum
7,
Jong-Hoon Kim
8,* and
Jae Youl Cho
1,*
1
Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea
2
AmorePacific R&D Center, Yongin 17074, Korea
3
Department of Forestry, Ministry of Agriculture and Forestry, Vientiane P.O. Box 811, Laos
4
Department of Forest Management, Faculty of Forest Science, National University of Laos, Vientiane P.O. Box 7322, Laos
5
Division of Zoology, Honam National Institute of Biological Resources, Mokpo 58762, Korea
6
Department of Forest Sciences, College of Agriculture and Life Science, Seoul National University, Seoul 08826, Korea
7
Animal Resources Division, National Institute of Biological Resources, Incheon 22689, Korea
8
Department of Veterinary Physiology, College of Medicine, Chonbuk National University, Iksan 54596, Korea
*
Authors to whom correspondence should be addressed.
Molecules 2021, 26(19), 6073; https://doi.org/10.3390/molecules26196073
Submission received: 28 August 2021 / Revised: 2 October 2021 / Accepted: 4 October 2021 / Published: 8 October 2021
(This article belongs to the Special Issue Biological Activity of Plant Compounds and Extracts)
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Abstract

Several Cissus species have been used and reported to possess medicinal benefits. However, the anti-inflammatory mechanisms of Cissus subtetragona have not been described. In this study, we examined the potential anti-inflammatory effects of C. subtetragona ethanol extract (Cs-EE) in vitro and in vivo, and investigated its molecular mechanism as well as its flavonoid content. Lipopolysaccharide (LPS)-induced macrophage-like RAW264.7 cells and primary macrophages as well as LPS-induced acute lung injury (ALI) and HCl/EtOH-induced acute gastritis mouse models were utilized. Luciferase assays, immunoblotting analyses, overexpression strategies, and cellular thermal shift assay (CETSA) were performed to identify the molecular mechanisms and targets of Cs-EE. Cs-EE concentration-dependently reduced the secretion of NO and PGE2, inhibited the expression of inflammation-related cytokines in LPS-induced RAW264.7 cells, and decreased NF-κB- and AP-1-luciferase activity. Subsequently, we determined that Cs-EE decreased the phosphorylation events of NF-κB and AP-1 pathways. Cs-EE treatment also significantly ameliorated the inflammatory symptoms of HCl/EtOH-induced acute gastritis and LPS-induced ALI mouse models. Overexpression of HA-Src and HA-TAK1 along with CETSA experiments validated that inhibited inflammatory responses are the outcome of attenuation of Src and TAK1 activation. Taken together, these findings suggest that Cs-EE could be utilized as an anti-inflammatory remedy especially targeting against gastritis and acute lung injury by attenuating the activities of Src and TAK1.
Keywords: Cissus subtetragona Planch; inflammation; Src; TAK1; gastritis; acute lung injury Cissus subtetragona Planch; inflammation; Src; TAK1; gastritis; acute lung injury

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MDPI and ACS Style

Rahmawati, L.; Aziz, N.; Oh, J.; Hong, Y.H.; Woo, B.Y.; Hong, Y.D.; Manilack, P.; Souladeth, P.; Jung, J.H.; Lee, W.S.; et al. Cissus subtetragona Planch. Ameliorates Inflammatory Responses in LPS-induced Macrophages, HCl/EtOH-induced Gastritis, and LPS-induced Lung Injury via Attenuation of Src and TAK1. Molecules 2021, 26, 6073. https://doi.org/10.3390/molecules26196073

AMA Style

Rahmawati L, Aziz N, Oh J, Hong YH, Woo BY, Hong YD, Manilack P, Souladeth P, Jung JH, Lee WS, et al. Cissus subtetragona Planch. Ameliorates Inflammatory Responses in LPS-induced Macrophages, HCl/EtOH-induced Gastritis, and LPS-induced Lung Injury via Attenuation of Src and TAK1. Molecules. 2021; 26(19):6073. https://doi.org/10.3390/molecules26196073

Chicago/Turabian Style

Rahmawati, Laily, Nur Aziz, Jieun Oh, Yo Han Hong, Byoung Young Woo, Yong Deog Hong, Philaxay Manilack, Phetlasy Souladeth, Ji Hwa Jung, Woo Shin Lee, and et al. 2021. "Cissus subtetragona Planch. Ameliorates Inflammatory Responses in LPS-induced Macrophages, HCl/EtOH-induced Gastritis, and LPS-induced Lung Injury via Attenuation of Src and TAK1" Molecules 26, no. 19: 6073. https://doi.org/10.3390/molecules26196073

APA Style

Rahmawati, L., Aziz, N., Oh, J., Hong, Y. H., Woo, B. Y., Hong, Y. D., Manilack, P., Souladeth, P., Jung, J. H., Lee, W. S., Jeon, M. J., Kim, T., Hossain, M. A., Yum, J., Kim, J.-H., & Cho, J. Y. (2021). Cissus subtetragona Planch. Ameliorates Inflammatory Responses in LPS-induced Macrophages, HCl/EtOH-induced Gastritis, and LPS-induced Lung Injury via Attenuation of Src and TAK1. Molecules, 26(19), 6073. https://doi.org/10.3390/molecules26196073

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