Artemisia Extract Suppresses NLRP3 and AIM2 Inflammasome Activation by Inhibition of ASC Phosphorylation.

Artemisia princeps var. orientalis (Asteraceae, A. princeps) is a well-known traditional medicinal herb used for treating various inflammatory disorders in Korea, Japan, China, and other Asian countries. In the present study, we investigated the effects of A. princeps extract (APO) on interleukin- (IL-) 1ß regulation and inflammasome activation in bone marrow-derived macrophages (BMDMs) and monosodium urate- (MSU-) induced peritonitis mouse model in vivo. The APO treatment to BMDMs primed with lipopolysaccharide (LPS) attenuated the NLRP3 and AIM2 inflammasome activation induced by danger signals, such as ATP, nigericin, silica crystals, and poly (dA:dT), respectively. Mechanistic study revealed that APO suppressed the ASC oligomerization and speck formation, which are required for inflammasome activation. APO treatment also reduced the ASC phosphorylation induced by the combination of LPS and a tyrosine phosphatase inhibitor. In vivo evaluation revealed that intraperitoneal administration of APO reduced IL-1ß levels, significantly (p < 0.05) and dose dependently, in the MSU-induced peritonitis mouse model. In conclusion, our study is the first to report that the extract of A. princeps inhibits inflammasome activation through the modulation of ASC phosphorylation. Therefore, APO might be developed as therapeutic potential in the treatment of inflammasome-mediated inflammatory disorders, such as gouty arthritis.

Inhibitory Effect and Mechanism of Arctium lappa Extract on NLRP3 Inflammasome Activation.

Arctium lappa (A. lappa), Compositae, is considered a potential source of nutrition and is used as a traditional medicine in East Asian countries for centuries. Although several studies have shown its biological activities as an anti-inflammatory agent, there have been no reports on A. lappa with regard to regulatory role in inflammasome activation. The purpose of this study was to investigate the inhibitory effects of A. lappa extract (ALE) on NLRP3 inflammasome activation and explore the underlying mechanisms. We found that ALE inhibited IL-1ß secretion from NLRP3 inflammasome activated bone marrow derived macrophages but not that secreted by NLRC4 and AIM2 inflammasomes activation. Mechanistic studies revealed that ALE suppressed the ATPase activity of purified NLRP3 and reduced mitochondrial reactive oxygen species (mROS) generated during NLRP3 activation. Therefore, the inhibitory effect of ALE on NLRP3 inflammasome might be attributed to its ability to inhibit the NLRP3 ATPase function and attenuated the mROS during inflammasome activation. In addition, ALE significantly reduced the LPS-induced increase of plasma IL-1ß in mouse peritonitis model. These results provide evidence of novel anti-inflammatory mechanisms of A. lappa, which might be used for therapeutic applications in the treatment of NLRP3 inflammasome-associated inflammatory disorders.

Anti-inflammatory properties of Morus bombycis Koidzumi via inhibiting IFN-ß signaling and NLRP3 inflammasome activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Morus bombycis Koidzumi (M. bombycis, Moraceae) has been used in Asian countries as a traditional medicine for the treatment of hypertension, diabetes, and inflammation-related disorders. AIM OF STUDY: Although its anti-inflammatory actions have been partly documented, scientific evidence involving its molecular mechanisms related to inflammasome activation signaling pathways remains unknown. MATERIALS AND METHODS: Lipopolysaccharide-stimulated RAW 264.7 cells and bone marrow-derived murine macrophages were used to study the in vitro effect of methanolic extract of M. bombycis (MB) on inflammatory responses. A monosodium urate crystal (MSU)-induced peritonitis murine model was used to study the in vivo effects. RESULTS: MB attenuated the production of nitric oxide and interleukin-6, through the regulation of the interferon-ß receptor signaling pathway. MB also inhibited IL-1ß secretion via attenuation of NLRP3 inflammasome activation. Furthermore, MB inhibited MSU-induced peritonitis in the in vivo murine model. CONCLUSIONS: This study provides the key molecular mechanisms involved in the anti-inflammatory effects of M. bombycis, substantiating the traditional claims of its use in the treatment of inflammation-related disorders.

Syneilesis palmata (Thunb.) Maxim. extract attenuates inflammatory responses via the regulation of TRIF-dependent signaling and inflammasome activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Syneilesis palmata (Thunb.) Maxim. (S. palmata, Asteraceae) is a traditional Korean therapeutic herb widely used to treat pain, arthritis, and other symptoms. This study provides the scientific basis for the anti-inflammatory effects of S. palmata extract (SP) in both in vitro and in vivo experimental models. MATERIALS AND METHODS: Lipopolysaccharide (LPS)-stimulated murine macrophages were used to study the regulatory effect of SP on the inflammatory mediators in vitro. Bone marrow-derived macrophages were used to study the effects of SP on inflammasome activation. Escherichia coli-induced sepsis mouse model and LPS-induced endotoxin shock model were employed to study the effect of SP on in vivo efficacy. RESULTS: SP inhibited the LPS-stimulated release of proinflammatory mediators, such as nitric oxide and interleukin (IL)-6 in RAW 264.7 cells. SP treatment also attenuated IL-1ß secretion via the inhibition of NLRP3 inflammasome activation induced by monosodium urate, ATP, and nigericin. Further, SP ameliorated the severity of NLRP3 inflammasome-mediated symptoms in LPS-induced endotoxin and E. coli-induced sepsis mouse models. Mechanistic studies revealed that inhibitory effects of SP were mediated through the regulation of TRIF-dependent signaling and inflammasome activation. CONCLUSION: This study was the first to reveal mechanistic-based evidence substantiating the traditional claims of SP in the treatment of inflammation-related disorders, such as pain and arthritis.