Callerya atropurpurea suppresses inflammation in vitro and ameliorates gastric injury as well as septic shock in vivo via TLR4/MyD88-dependent cascade

• Published in: Phytomedicine (Stuttgart) Vol. 105; p. 154338
• Main Authors: You, Long, Huang, Lei, Jang, Jiwon, Hong, Yo Han, Kim, Han Gyung, Chen, Hongxi, Shin, Chae Yun, Yoon, Ji Hye, Manilack, Philaxay, Sounyvong, Bounthan, Lee, Woo-Shin, Jeon, Mi-Jeong, Lee, Sarah, Lee, Byoung-Hee, Cho, Jae Youl
• Format: Journal Article
• Language: English
• Published: Elsevier GmbH 01.10.2022
• Subjects: Anti-inflammation; Callerya atropurpurea; Gastritis; Macrophage; Septic shock; TLR4; NO; COX-2; DMSO; JNK; MTT; MyD88; TRAM; Anti-inflammation; LPS; DMEM; NF-κB; Ikβa; IFN-β; IRAK1; PI3K; p38; TAK1; FBS; NSAIDs; RT-PCR; iNOS; PAMPs; IKK a/β; PBS; L-NAME; poly (I:C); MKK3/6; EGCG; Septic shock; AKT; Ap-1; IL-1β; MAPK; Callerya atropurpurea; IL-6; Gastritis; SARM; TNF-α; TRAF6; MAL; TRIF; TLR4; TLRs; Macrophage; ERK
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2022.154338

Callerya atropurpurea is a traditional plant in a tropical zone discovered to have anti-inflammatory functions. we want to investigate the mechanism related to anti-inflammation of C. atropurpurea ethanol extract (Ca-EE) both in vitro and in vivo. Murine macrophage cells and mouse models for gastritis and septic shock were conducted to evaluate the abilities of Ca-EE in anti-inflammation. Ca-EE was tested by HPLC and LC-MS/MS. NO outcome was checked by Griess reagent test. Cell viabilities were evaluated using MTT assay. Inflammatory cytokines were determined via RT-PCR and ELISA. The mechanism of Ca-EE in anti-inflammation was investigated by luciferase reporter gene assay and immunoblot in transcription level and protein level respectively. Gastric injury and septic shock administrated with Ca-EE were studied by H&E, PCR, and immunoblot. Ca-EE significantly decreased LPS-induced NO production, but hardly stimulated the expression of NO itself. It not only showed no cytotoxicity, but also protected cells from LPS damage. Moreover, Ca-EE decreased TLR4 expression, altered MyD88 recruitment and TRAF6, and suppressed the phospho-Src/PI3K/AKT. Ca-EE inhibited downstream signaling P38, JNK and NF-κB. Finally, Ca-EE alleviated HCl/EtOH-induced gastritis and LPS/poly (I:C)-induced septic shock through the previously mentioned signaling cascades. Ca-EE exhibited an integrated and promising mechanism against TLR4-related inflammation, which shows potential for treating gastritis, septic shock, and other inflammatory diseases. [Display omitted]