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TAK1/AP-1-Targeted Anti-Inflammatory Effects of Barringtonia augusta Methanol Extract.

ABSTRACT: Barringtonia augusta methanol extract (Ba-ME) is a folk medicine found in the wetlands of Thailand that acts through an anti-inflammatory mechanism that is not understood fully. Here, we examine how the methanol extract of Barringtonia augusta (B. augusta) can suppress the activator protein 1 (AP-1) signaling pathway and study the activities of Ba-ME in the lipopolysaccharide (LPS)-treated RAW264.7 macrophage cell line and an LPS-induced peritonitis mouse model. Non-toxic concentrations of Ba-ME downregulated the mRNA expression of cytokines, such as cyclooxygenase and chemokine ligand 12, in LPS-stimulated RAW264.7 cells. Transfection experiments with the AP-1-Luc construct, HEK293T cells, and luciferase assays were used to assess whether Ba-ME suppressed the AP-1 functional activation. A Western blot assay confirmed that C-Jun N-terminal kinase is a direct pharmacological target of Ba-ME action. The anti-inflammatory effect of Ba-ME, which functions by β-activated kinase 1 (TAK1) inhibition, was confirmed by using an overexpression strategy and a cellular thermal shift assay. In vivo experiments in a mouse model of LPS-induced peritonitis showed the anti-inflammatory effect of Ba-ME on LPS-stimulated macrophages and acute inflammatory mouse models. We conclude that Ba-ME is a promising anti-inflammatory drug targeting TAK1 in the AP-1 pathway.

SUBMITTER: Ha AT

PROVIDER: S-EPMC8160894 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background Pain and inflammation are the major devastating health problems commonly treated with traditional medicinal plants in Ethiopia. Echinops kebericho M. (Asteraceae) is the one which is frequently used to treat pain and inflammation by traditional healers in Ethiopian folk medicine. However, the plant has not been scientifically evaluated for its traditionally claimed use. The present study aimed at the investigation of analgesic and anti-inflammatory activities of 80% methanol root extract of Echinops kebericho M. in mice model. Methods Successive maceration was used as a method of extraction using solvents of increasing polarity: methanol and water. After extraction of the roots with 80% hydro methanol, the crude extract was evaluated for its peripheral and central analgesic activities using acetic acid-induced writhing test and hot plate method, respectively, while its anti-inflammatory activity was evaluated using carrageenan- and formalin-induced paw edema. The extract was evaluated at 100, 200 and 400 mg/kg doses. The positive control groups were treated with ASA 150 mg/kg for writhing test, morphine 10 mg/kg for hot plat method, indomethacin 25 mg/kg and diclofenac 10 mg/kg for paw edema tests and vehicle, distilled water (10 mL/kg) treated mice were assigned as negative controls. All treatment administrations were performed orally. Results E. kebericho extract at all test doses showed statistically significant antinociceptive activity in both chemicals-induced peripheral and thermal-induced central pain in a dose dependent manner (p < 0.01 and p < 0.001). The greater analgesic activity was observed by the maximum dose of the extract (400 mg/kg) in both acetic acids-induced writhing test (57.84%) and hot plate method (69.40%). The effect of the extract was also statistically significant (p < 0.01 and p < 0.001) in both carrageenan and formalin-induced paw edema in dose dependent manner. Greater edema inhibition was observed by the highest dose (400 mg/kg) in both observations with the respective percentage values of 70.00% and 79.87%, respectively. Conclusion In general, the data obtained from the present study elucidated that the extract possessed a significant analgesic and anti-inflammatory activities and recommended for further studies.

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TAK1/AP-1-Targeted Anti-Inflammatory Effects of Barringtonia augusta Methanol Extract.

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