Trichosanthes tricuspidata Lour. Methanol Extract Exhibits Anti-Inflammatory Activity by Targeting Syk, Src, and IRAK1 Kinase Activity

Abstract

Trichosanthes tricuspidata Lour., also known as T. palmata Roxb, T. bracteata Lam., T. puber Blume, and Modecca bracteata, is a vine belonging to the Cucurbitaceae family (English name: redball snake gourd). Distributed in China, South and East Asia, and tropical Australia, it has been traditionally used as a medicinal plant for its antifever, laxative, anthelmintic properties and for migraine treatment. In this paper, we examined the effects of Trichosanthes tricuspidata Lour. ethanol extract (Tt-ME) in vitro and in vivo. To confirm the effects of Tt-ME on inflammatory responses, we conducted experimental analyses including level of nitric oxide (NO) production, RT-PCR, and immunoblotting and using a HCl/EtOH-induced gastritis animal model. Tt-ME attenuated the release of NO and decreased mRNA levels of inducible NO synthase (iNOS), TNF-α, and IL-6 in lipopolysaccharide- (LPS-) induced macrophages in a concentration-dependent manner. Tt-ME time-dependently suppressed nuclear translocation of nuclear factor kappa B (NF-κB) subunits p50 and p65, activator protein (AP-1) subunits c-Fos and c-Jun, and STAT3 transcriptional activity by inhibiting nuclear translocation of p50, p65, c-Fos, c-Jun, and STAT3. Tt-ME significantly downregulated NF-κB, MAPK, and JAK2 signaling by targeting Syk, Src, and IRAK1 protein kinases. Furthermore, matrix metalloproteinase-9 (MMP-9) expression and cell migration were observed to be downregulated by Tt-ME in LPS-activated macrophages. In vivo studies on Tt-ME also produced similar trends in Hcl/EtOH-induced gastritis mouse models by inhibiting proinflammatory cytokines and the inflammatory signaling pathway. Our results strongly suggest that Tt-ME exerted anti-inflammatory activity in LPS-stimulated macrophages and mouse models of acute inflammatory disease.

STAT3 Differentially Regulates TLR4-Mediated Inflammatory Responses in Early or Late Phases

“…STAT3 inhibition has also shown preventive effects in controlling lung inflammation and Th2 cell differentiation in mouse models with asthma [ 30 ]. Moreover, plant-derived natural compounds have also been observed to be effective in inflammatory and cancerous conations by inhibiting STAT3 and nuclear factor (NF)- κB transcription factors and various pro-inflammatory cytokines [ 31 , 32 ]. Small molecule inhibitors of JAK2/STAT3 signaling like FLLL32 reduced the growth of established neurofibromas in mouse models [ 33 ].…”

Chemical constituents of the genus Trichosanthes (Cucurbitaceae) and their biological activities: A review

“…The extract attenuated the release of NO and decreased mRNA levels of inducible NO synthase (iNOS), TNF-α, and IL-6 in LPS-induced macrophages and significantly downregulated NF-κB, MAPK, and JAK2 signalling by targeting Syk, Src, and IRAK1 protein kinases. In vivo studies on this extract also produced similar trends in HCl/EtOH-induced gastritis mouse models by inhibiting proinflammatory cytokines and the inflammatory signalling pathway [47].…”

LOMIX, a Mixture of Flaxseed Linusorbs, Exerts Anti-Inflammatory Effects through Src and Syk in the NF-κB Pathway

“…Anti-inflammatory activity of LOMIX was first evaluated by determining inhibition of NO production in RAW264.7 cells, as NO production is a central sign of the inflammatory response [ 25 ]. For this, we tested LOMIX up to 200 µg/mL, since LOMIX is a mixture of six different cyclolinopeptides and mixtures or extracts are normally tested at concentrations ranging from 150 to 200 µg/mL [ 26 , 27 ]. Treatment with LOMIX significantly inhibited NO production in RAW264.7 cells stimulated with either Pam3CSK4 (10 µg/mL), Poly (I:C) (200 µg/mL), or LPS (1 µg/mL), molecular ligands of TLR2, TLR3, and TLR4, respectively, in a dose-dependent manner ( Figure 1 B).…”