<i>Cissus subtetragona</i> Planch. Ameliorates Inflammatory Responses in LPS-induced Macrophages, HCl/EtOH-induced Gastritis, and LPS-induced Lung Injury via Attenuation of Src and TAK1
Laily Rahmawati,
Nur Aziz,
Jieun Oh,
Yo Han Hong,
Byoung Young Woo,
Yong Deog Hong,
Philaxay Manilack,
Phetlasy Souladeth,
Ji Hwa Jung,
Woo Shin Lee,
Mi Jeong Jeon,
Taewoo Kim,
Mohammad Amjad Hossain,
Jinwhoa Yum,
Jong-Hoon Kim,
Jae Youl Cho
Affiliations
Laily Rahmawati
Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea
Nur Aziz
Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea
Jieun Oh
Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea
Yo Han Hong
Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea
Byoung Young Woo
AmorePacific R&D Center, Yongin 17074, Korea
Yong Deog Hong
AmorePacific R&D Center, Yongin 17074, Korea
Philaxay Manilack
Department of Forestry, Ministry of Agriculture and Forestry, Vientiane P.O. Box 811, Laos
Phetlasy Souladeth
Department of Forest Management, Faculty of Forest Science, National University of Laos, Vientiane P.O. Box 7322, Laos
Ji Hwa Jung
Division of Zoology, Honam National Institute of Biological Resources, Mokpo 58762, Korea
Woo Shin Lee
Department of Forest Sciences, College of Agriculture and Life Science, Seoul National University, Seoul 08826, Korea
Mi Jeong Jeon
Animal Resources Division, National Institute of Biological Resources, Incheon 22689, Korea
Taewoo Kim
Animal Resources Division, National Institute of Biological Resources, Incheon 22689, Korea
Mohammad Amjad Hossain
Department of Veterinary Physiology, College of Medicine, Chonbuk National University, Iksan 54596, Korea
Jinwhoa Yum
Animal Resources Division, National Institute of Biological Resources, Incheon 22689, Korea
Jong-Hoon Kim
Department of Veterinary Physiology, College of Medicine, Chonbuk National University, Iksan 54596, Korea
Jae Youl Cho
Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea
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.
