Tenuigenin exhibits anti-inflammatory activity via inhibiting MAPK and NF-κB and inducing Nrf2/HO-1 signaling in macrophages

Abstract

Tenuigenin (TNG), isolated from the root of the Chinese herb Polygala tenuifolia, possesses various biological and pharmacological activities, including anti-oxidation and anti-inflammation activities. In this study, we aimed to further investigate whether its anti-inflammatory activity is associated with the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Our results showed that TNG treatment dramatically reduced prostaglandin E2 (PGE2) and NO production, decreased iNOS and COX-2 gene expression, inhibited JNK1/2, ERK1/2, p38 and NF-κB (p65) phosphorylation, and blocked IκBα phosphorylation and degradation. Further studies revealed that TNG dramatically up-regulated heme oxygenase (HO)-1 and nuclear factor erythroid 2-related factor 2 (Nrf2) expression, which was related to the induction of Nrf2 nuclear translocation and decreased Keap1 protein expression. Additionally, treatment with JNK1/2, ERK1/2 or p38 inhibitors had no effect on the TNG-induced HO-1 protein expression. Furthermore, the LPS-induced iNOS and COX-2 expression levels were inhibited by TNG, which was partially reversed by the HO-1-siRNA and HO-1 inhibitors. Together, these results showed that TNG's anti-inflammatory activity is related to the inhibition of iNOS and COX-2 expression via down-regulation of the MAPK and NF-κB, and up-regulation of the Nrf2/HO-1 signaling pathways.

7-deacetylgedunin suppresses inflammatory responses through activation of Keap1/Nrf2/HO-1 signaling

“…Decreased HO-1 and other anti-oxidant enzymes can induce over-production of iNOS and COX-2, and up-regulation of HO-1 has been reported to exert anti-inflammation as well as anti-oxidant effects [ 21 ]. Therefore, we further examined whether or not the inhibitory effect of 7-DGD is resulted from up-regulation of NQO1, HO-1 and UGT1A1.…”

Tenuigenin protects dopaminergic neurons from inflammation via suppressing NLRP3 inflammasome activation in microglia

“…It had reported tenuigenin possesses various pharmacological activities for anti-oxidant, anti-aging, and anti-inflammatory. For example, in vitro, tenuigenin inhibited LPS-triggered inflammatory cytokine production including prostaglandin E 2 (PGE 2 ), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in macrophages [ 12 ]. Furthermore, tenuigenin exhibited protective effects against LPS-induced acute kidney injury in mice [ 13 ].…”

Evaluation of antioxidant, anti-inflammatory and anti-proliferative activities of ethanol extracts from different varieties of Sanghuang species

“…However, excess or persistent inammation is associated with the pathogenesis of various diseases. 31,32 NO and pro-inammatory cytokines, secreted by activated macrophages, play an important role during the inammatory response and are used for the detection and quantication of inammation. 32 It has been reported that extracts of T. linteus and S. baumii, which have been mistakenly applied as Sanghuangporus species in the past, exhibit a good anti-inammatory effect in LPSinduced mouse macrophages, and can inhibit the activation of NF-kB and MAPKs pathways to exert an anti-inammatory effect.…”

“…31,32 NO and pro-inammatory cytokines, secreted by activated macrophages, play an important role during the inammatory response and are used for the detection and quantication of inammation. 32 It has been reported that extracts of T. linteus and S. baumii, which have been mistakenly applied as Sanghuangporus species in the past, exhibit a good anti-inammatory effect in LPSinduced mouse macrophages, and can inhibit the activation of NF-kB and MAPKs pathways to exert an anti-inammatory effect. 21,23 On the other hand, our experimental results indicated that S. sanghuang can inhibit the expression of iNOS and COX-2, and can attenuate the production of pro-inammatory cytokines.…”