1. Anti-inflammatory effect of Barringtonia angusta methanol extract is mediated by targeting of Src in the NF-κB signalling pathway.
- Author
-
Jo M, Lee J, Kim HG, Kim JK, Kim H, Shin KK, Bach TT, Eum SM, Lee JS, Choung ES, Yang Y, Kim KH, Sung GH, Yoo BC, and Cho JY
- Subjects
- Animals, Anti-Inflammatory Agents isolation & purification, Anti-Inflammatory Agents metabolism, Dose-Response Relationship, Drug, Gastritis chemically induced, Gastritis metabolism, HEK293 Cells, Humans, Male, Methanol administration & dosage, Methanol metabolism, Mice, Mice, Inbred ICR, NF-kappa B, Plant Extracts isolation & purification, Plant Extracts metabolism, Plant Leaves, Plant Stems, RAW 264.7 Cells, Signal Transduction drug effects, Signal Transduction physiology, src-Family Kinases metabolism, Anti-Inflammatory Agents administration & dosage, Barringtonia, Drug Delivery Systems methods, Gastritis drug therapy, Plant Extracts administration & dosage, src-Family Kinases antagonists & inhibitors
- Abstract
Context: Among the plants in the genus Barringtonia (Lecythidaceae) used as traditional medicines to treat arthralgia, chest pain, and haemorrhoids in Indonesia, Barringtonia racemosa L. and Barringtonia acutangula (L.) Gaertn. have demonstrated anti-inflammatory activity in systemic inflammatory models., Objective: The anti-inflammatory activity of Barringtonia angusta Kurz has not been investigated. We prepared a methanol extract of the leaves and stems of B. angusta (Ba-ME) and systemically evaluated its anti-inflammatory effects in vitro and in vivo ., Materials and Methods: RAW264.7 cells stimulated with LPS or Pam3CSK4 for 24 h were treated with Ba-ME (12.5, 25, 50, 100, and 150 µg/mL), and NO production and mRNA levels of inflammatory genes were evaluated. Luciferase reporter gene assay, western blot analysis, overexpression experiments, and cellular thermal shift assay were conducted to explore the mechanism of Ba-ME. In addition, the anti-gastritis activity of Ba-ME (50 and 100 mg/kg, administered twice per day for two days) was evaluated using an HCl/EtOH-induced gastritis mouse model., Results: Ba-ME dose-dependently suppressed NO production [IC
50 = 123.33 µg/mL (LPS) and 46.89 µg/mL (Pam3CSK4)] without affecting cell viability. Transcriptional expression of iNOS , IL-1β , COX-2 , IL-6 , and TNF-α and phosphorylation of Src, IκBα, p50/105, and p65 were inhibited by Ba-ME. The extract specifically targeted the Src protein by binding to its SH2 domain. Moreover, Ba-ME significantly ameliorated inflammatory lesions in the HCl/EtOH-induced gastritis model., Discussion and Conclusions: The anti-inflammatory activity of Ba-ME is mediated by targeting of the Src/NF-κB signalling pathway, and B. angusta has potential as an anti-inflammatory drug.- Published
- 2021
- Full Text
- View/download PDF