Andrographolide Inhibits Inflammatory Cytokines Secretion in LPS-Stimulated RAW264.7 Cells through Suppression of NF-κB/MAPK Signaling Pathway

Abstract

Andrographolide, the main active component extracted from Andrographis paniculata (Burm.f.) Wall. ex Nees, exerts anti-inflammatory effects; however, the principal molecular mechanisms remain unclear. The objective of this study was to investigate the molecular mechanisms of Andrographolide in modifying lipopolysaccharide- (LPS-) induced signaling pathway in RAW264.7 cells. An in vitro model of inflammation was induced by LPS in mouse RAW264.7 cells in the presence of Andrographolide. The concentration and expression levels of proinflammatory cytokines were determined by an enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. The nuclear level of NF-κB was measured by an electrophoretic mobility shift assay (EMSA). The expression levels of NF-κB, p38, ERK, and JNK were determined by western blot. Andrographolide dose-dependently inhibited the release and mRNA expression of TNF-α, IL-6, and IL-1β in LPS-stimulated RAW264.7 cells. The nuclear level of p65 protein was decreased in Andrographolide treatment group. Western blot analysis showed that Andrographolide suppressed LPS-induced NF-κB activation and the phosphorylation of IkBa, ERK1/2, JNK, and p38. These results suggest that Andrographolide exerts an anti-inflammatory effect by inhibiting the activation of NF-κB/MAPK signaling pathway and the induction of proinflammatory cytokines.

Ethanolic extract of Streblus asper leaves protects against glutamate-induced toxicity in HT22 hippocampal neuronal cells and extends lifespan of Caenorhabditis elegans

“…In addition, this compound protected neuronal cells from oxidative stress, A훽 and glutamate toxicities through activation of the Keap1/Nrf2 pathway [ 55 – 57 ]. Andrographolide has been reported to possess various pharmacological activities for treatment of cancer [ 58 ], inflammation [ 59 ], diabetes [ 60 ], and AD [ 61 ]. Moreover, derivative compounds bearing an oxazolopyridine core were identified as sirtuin activators and proposed to be used for treating a wide variety of diseases associated with aging [ 62 ].…”

Propofol inhibits the release of interleukin-6, 8 and tumor necrosis factor-α correlating with high-mobility group box 1 expression in lipopolysaccharides-stimulated RAW 264.7 cells

“…Murine macrophage RAW 264.7 cells are an example of inflammatory cells [ 12 ]. Studies have shown that it can produce the corresponding cytokines and inflammatory mediators, such as TNF-α, IL-1β and IL-6 and so on as long as the mouse macrophage RAW264.7 cells are stimulated by LPS [ 13 ]. Propofol is widely used in the induction and maintenance of general anesthesia, and recent studies have shown that propofol can down-regulate the expression levels of HMGB1 messenger ribonucleic acid and protein [ 10 ].…”

A double‐blind, randomized, placebo‐controlled study to assess the efficacy of Andrographis paniculata standardized extract (ParActin®) on pain reduction in subjects with knee osteoarthritis

“…In fact, andrographolide exerts a wide repertoire of biological responses in the inflammatory process, which includes interfering with NF‐kB binding in leukocytes (Hidalgo et al, ; Xia et al, ), reducing the transcription of several pro‐inflammatory proteins. In addition, andrographolide or neoandrographolide, two diterpene labdanes present in ParActin®, have been widely recognized as being effective in reducing several inflammatory markers associated with OA, such as COX‐2, iNOS, TNFα, and IL‐6 (Burgos et al, ; Chiou, Chen, & Lin, ; Gupta et al, ; Hidalgo et al, ; Li et al, ). It is well known that andrographolide interferes with NFAT activation in T cells and ERK1/2 and ERK5 phosphorylation (Burgos et al, ; Carretta et al, ).…”