Momordica charantia Inhibits Inflammatory Responses in Murine Macrophages via Suppression of TAK1

Abstract

Momordica charantia known as bitter melon is a representative medicinal plant reported to exhibit numerous pharmacological activities such as antibacterial, antidiabetic, anti-inflammatory, anti-oxidant, antitumor, and hypoglycemic actions. Although this plant has high ethnopharmacological value for treating inflammatory diseases, the molecular mechanisms by which it inhibits the inflammatory response are not fully understood. In this study, we aim to identify the anti-inflammatory mechanism of this plant. To this end, we studied the effects of its methanol extract (Mc-ME) on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Specifically, we evaluated nitric oxide (NO) production, mRNA expression of inflammatory genes, luciferase reporter gene activity, and putative molecular targets. Mc-ME blocked NO production in a dose-dependent manner in RAW264.7 cells; importantly, no cytotoxicity was observed. Moreover, the mRNA expression levels of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 were decreased by Mc-ME treatment in a dose-dependent manner. Luciferase assays and nuclear lysate immunoblotting analyses strongly indicated that Mc-ME decreases the levels of p65 [a nuclear factor (NF)-[Formula: see text]B subunit] and c-Fos [an activator protein (AP)-1 subunit]. Whole lysate immunoblotting assays, luciferase assays, and overexpression experiments suggested that transforming growth factor [Formula: see text]-activated kinase 1 (TAK1) is targeted by Mc-ME, thereby suppressing NF-[Formula: see text]B and AP-1 activity via downregulation of extracellular signal-regulated kinases (ERKs) and AKT. These results strongly suggest that Mc-ME exerts its anti-inflammatory activity by reducing the action of TAK1, which also affects the activation of NF-[Formula: see text]B and AP-1.

Momordica charantia, a Nutraceutical Approach for Inflammatory Related Diseases

“…Moreover, MC showed reduction of LPS-induced NO and prostaglandin E2 production together with a reduction of inducible NO synthase and IL-1β expression (Lii et al, 2009). In the same cell model, a dose-dependent inhibition of NO production for MC extract was demonstrated (Svobodova et al, 2017); but it was also reported that MC extracts reduced expression levels of inducible NO synthase and cyclooxygenase-2, suppressing NF-κB, and activator protein-1 (AP-1) activity via downregulation of ERKs and Akt (Hsu et al, 2013; Yang et al, 2018). The effects of a triterpene purified from bitter melon was investigated against TNF-α-induced inflammation via AMP-activated protein kinase in FL83B cells.…”

Momordica charantia Suppresses Inflammation and Glycolysis in Lipopolysaccharide-Activated RAW264.7 Macrophages

“…Cells in T25 flask with 80% confluency pre-treated with or without 12.5% v/v MC water extract (final concentration equivalent to 5 mg/mL soluble MC extract) for four hours were incubated with 1 μg/mL LPS for four hours [ 40 ]. The total treatment time was 8 h and it was adequate to see changes in mRNA levels [ 41 ]. Total RNAs were extracted using TRIzol (Invitrogen, Waltham, MA, USA).…”

Radiation-induced heart disease: a review of classification, mechanism and prevention

“…Colchicine inhibits the inflammatory response by inhibiting microtubule polymerization and can reduce platelet aggregation, protecting the heart through its anti-inflammatory and anti-coagulant properties 106. Some Chinese herbal extracts have been shown to inhibit the inflammatory response induced by radiation and the formation of myocardial fibrosis 121, 122.…”