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Phytomedicine, Jan 2025, 136 S0944-7113(24)00994-2 | https://doi.org/10.1016/j.phymed.2024.156339
The ethanolic extract of Rhaphidophora peepla prevents inflammation by inhibiting the activation of Syk/AKT/NF-κB and TAK1/MAPK/AP-1
Yuhao Wang a,1, Canglang Mou a,1, Lei Huang b, Jinghan Su a, Long You a,f, Jianmei Zhang a, Ziliang He a, Yeye Hu a, Khin Myo Htwe c, Seung-Gyu Lee d, Jinwhoa Yum d, Yerin Ha e, Ji Heun Lee e, Youngwoon Ju e, Wooram Choi a, Jae Youl Cho a,b
aDepartment of Integrative Biotechnology, and Biomedical Institute for Convergence at SKKU, Sungkyunkwan University, Suwon 16419, Republic of Korea
bDepartment of Biocosmetics, Sungkyunkwan University, Suwon 16419, Republic of Korea
cPopa Mountain Park, Forest Department, Kyaukpadaung Township, Mandalay Division, Kyaukpadaung 05241, Myanmar
dBiological and Genetic Resources Assessment Division, National Institute of Biological Resources, Incheon 22689, Republic of Korea
ePharmacoBio Inc., Jungwon-gu, Seongnam 13219, Republic of Korea
fSchool of Life Sciences, Huaiyin Normal University, Huaian 223300, China
1These authors contributed equally.
Corresponding author: Jae Youl Cho
aDepartment of Integrative Biotechnology, and Biomedical Institute for Convergence at SKKU, Sungkyunkwan University, Suwon 16419, Republic of Korea
bDepartment of Biocosmetics, Sungkyunkwan University, Suwon 16419, Republic of Korea
cPopa Mountain Park, Forest Department, Kyaukpadaung Township, Mandalay Division, Kyaukpadaung 05241, Myanmar
dBiological and Genetic Resources Assessment Division, National Institute of Biological Resources, Incheon 22689, Republic of Korea
ePharmacoBio Inc., Jungwon-gu, Seongnam 13219, Republic of Korea
fSchool of Life Sciences, Huaiyin Normal University, Huaian 223300, China
1These authors contributed equally.
Corresponding author: Jae Youl Cho
Abstract
Background: Inflammation is the body's innate reaction to foreign pathogens and serves as a self-regulating mechanism. However, the immune system can mistakenly target the body's own tissues, triggering unnecessary inflammation. For millennia, medicinal plants have been employed for the treatment of diseases. One such plant, Rhaphidophora peepla, has demonstrated potential anti-inflammatory properties. However, the precise mechanism underlying its anti-inflammatory effects remains elusive.
Study design: For this study, validation of target molecules by different experimental approaches and employing two different in vivo experiments were tried to improve the immunopharmacological value of Rhaphidophora peepla.
Purpose: Our goal is to elucidate the mechanism through which the ethanol extract of Rhaphidophora peepla (Rp-EE) demonstrates anti-inflammatory properties, both in vivo and in vitro.
Method: Rp-EE was phytochemically analyzed with gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC). Bioinformatic analysis with protein-protein interaction (PPI) networks and Kyoto Encyclopedia of Genes and Genomes (KEGG), nitric oxide (NO) assay, MTT assay, RT-PCR, ELISA, luciferase assay, CETSA, hematoxylin and eosin (H&E) staining, and Western blotting analysis were used to evaluate anti-inflammatory activity of Rp-EE and its mechanism.
Results: Rp-EE significantly reduced inflammatory responses including nitric oxide (NO) release induced by lipopolysaccharide (LPS) at the non-cytotoxic concentrations in vitro, and HCl/EtOH-induced gastritis and LPS-induced acute lung injury models in vivo. Mechanistically, it was revealed that Rp-EE can specifically target spleen tyrosine kinase (Syk) and transforming growth factor β-activated kinase 1 (TAK1) to suppress the phosphorylation levels of nuclear factor (NF)-κB subunits (p65 and p50) and activator protein (AP)-1 subunits (c-Jun and c-Fos).
Conclusion: Rp-EE can inhibit inflammatory reactions managed by Syk and TAK1, resulting in suppressing the Syk/AKT/NF-κB and TAK1/MAPK/AP-1 signaling pathways. These findings lead us to a possibility that Rp-EE can be developed as a promising anti-gastric ulcer and anti-lung injury remedy.
Study design: For this study, validation of target molecules by different experimental approaches and employing two different in vivo experiments were tried to improve the immunopharmacological value of Rhaphidophora peepla.
Purpose: Our goal is to elucidate the mechanism through which the ethanol extract of Rhaphidophora peepla (Rp-EE) demonstrates anti-inflammatory properties, both in vivo and in vitro.
Method: Rp-EE was phytochemically analyzed with gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC). Bioinformatic analysis with protein-protein interaction (PPI) networks and Kyoto Encyclopedia of Genes and Genomes (KEGG), nitric oxide (NO) assay, MTT assay, RT-PCR, ELISA, luciferase assay, CETSA, hematoxylin and eosin (H&E) staining, and Western blotting analysis were used to evaluate anti-inflammatory activity of Rp-EE and its mechanism.
Results: Rp-EE significantly reduced inflammatory responses including nitric oxide (NO) release induced by lipopolysaccharide (LPS) at the non-cytotoxic concentrations in vitro, and HCl/EtOH-induced gastritis and LPS-induced acute lung injury models in vivo. Mechanistically, it was revealed that Rp-EE can specifically target spleen tyrosine kinase (Syk) and transforming growth factor β-activated kinase 1 (TAK1) to suppress the phosphorylation levels of nuclear factor (NF)-κB subunits (p65 and p50) and activator protein (AP)-1 subunits (c-Jun and c-Fos).
Conclusion: Rp-EE can inhibit inflammatory reactions managed by Syk and TAK1, resulting in suppressing the Syk/AKT/NF-κB and TAK1/MAPK/AP-1 signaling pathways. These findings lead us to a possibility that Rp-EE can be developed as a promising anti-gastric ulcer and anti-lung injury remedy.
논문정보
- Research article
- 2025년 01월 (BRIC 등록일 2025-01-17)
- 국내(교신)+국외 연구진
- 생명과학 > 면역학
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