Anti-Inflammatory and Gastroprotective Roles of Rabdosia inflexa through Downregulation of Pro-Inflammatory Cytokines and MAPK/NF-κB Signaling Pathways

Abstract

Globally, gastric ulcer is a vital health hazard for a human. Rabdosia inflexa (RI) has been used in traditional medicine for inflammatory diseases. The present study aimed to investigate the protective effect and related molecular mechanism of RI using lipopolysaccharide (LPS)-induced inflammation in RAW 246.7 cells and HCl/EtOH-induced gastric ulcer in mice. We applied 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), nitric oxide (NO), reactive oxygen species (ROS), histopathology, malondialdehyde (MDA), quantitative real-time polymerase chain reaction (qPCR), immunohistochemistry (IHC), and Western blot analyses to evaluate the protective role of RI. Study revealed that RI effectively attenuated LPS-promoted NO and ROS production in RAW 246.7 cells. In addition, RI mitigated gastric oxidative stress by inhibiting lipid peroxidation, elevating NO, and decreasing gastric inflammation. RI significantly halted elevated gene expression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), inducible nitric oxide synthetase (iNOS), and cyclooxygenase-2 (COX-2) in gastric tissue. Likewise, RI markedly attenuated the mitogen-activated protein kinases (MAPKs) phosphorylation, COX-2 expression, phosphorylation and degradation of inhibitor kappa B (IκBα) and activation of nuclear factor kappa B (NF-κB). Thus, experimental findings suggested that the anti-inflammatory and gastroprotective activities of RI might contribute to regulating pro-inflammatory cytokines and MAPK/NF-κB signaling pathways.

RETRACTED ARTICLE: Gastroprotective activity of a novel Schiff base derived dibromo substituted compound against ethanol-induced acute gastric lesions in rats

“…Pre-treatment with CNBP, significantly suppressed gastric acidity and also suppress the destruction of GWM in the rats treated with ethanol, indicating that the gastro protective effect of CNBP was mediated partially by preservation of the gastric wall mucus. Balance perturbation between gastro-protective mechanisms and gastrotoxicity of different agents is the basis of acute inflammation which could cause secretion of various inflammatory cytokines [40]. It is reported that acute inflammation induced by ethanol is accompanied by neutrophils infiltration of gastric wall mucus [21].…”

Protective Effects of Wheat Peptides against Ethanol-Induced Gastric Mucosal Lesions in Rats: Vasodilation and Anti-Inflammation

“…Ethanol, a recognized necrotizing agent, induces inflammation response in the gastric mucosal epithelium cells and activates the nuclear factor kappa B (NF-κB) signaling pathway [ 29 , 30 ]. Pro-inflammatory cytokines and enzymes play an essential role in the ethanol-triggered gastric injury model of rats [ 31 ]. Tumor necrosis factor-α (TNF-α) is one of the most aggressive factors in the process of inflammation, injury, and carcinogenesis in gastric tissues [ 32 ].…”

Mechanisms underlying isoliquiritigenin‐induced apoptosis and cell cycle arrest via ROS‐mediated MAPK/STAT3/NF‐κB pathways in human hepatocellular carcinoma cells

“…Our results revealed that ISL increased the generation of ROS in a time‐dependent manner, and ISL‐induced apoptosis was inhibited after pretreatment with NAC, in accordance with the results of a previous study (Figure a,b). In addition, some studies have indicated that ROS are second messengers that activate the MAPK cascade and the NF‐κB transcription factor, and it has been suggested that ROS‐induced apoptosis is mediated via the MAPK and NF‐κB pathways (Akanda et al, ; Liu et al, ; Panahi, Pasalar, Zare, Rizzuto, & Meshkani, ). A recent study indicated that ISL induces apoptosis by inhibiting NF‐κB in chondrocyte‐like ATDC5 cells, and can also exert its antiproliferative effects by regulating ROS levels and MAPK signaling in B16F0 melanoma cells (Chen et al, ; Ji et al, ).…”