Juniperus rigida Sieb. extract inhibits inflammatory responses via attenuation of TRIF-dependent signaling and inflammasome activation

• Published in: Journal of ethnopharmacology 2016-08, Vol.190, p.91-99
• Main Authors: Han, Ji-Won, Shim, Do-Wan, Shin, Woo-Young, Kim, Myong-Ki, Shim, Eun-Jeong, Sun, Xiao, Koppula, Sushruta, Kim, Tack-Joong, Kang, Tae-Bong, Lee, Kwang-Ho
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Vesicular Transport - metabolism; Animals; Anti-Inflammatory Agents - isolation & purification; Anti-Inflammatory Agents - pharmacology; Apoptosis Regulatory Proteins - metabolism; ASC; Blood Glucose - drug effects; Blood Glucose - metabolism; CARD Signaling Adaptor Proteins; Chromatography, High Pressure Liquid; Cytokines - metabolism; Diabetes Mellitus, Experimental - immunology; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - prevention & control; Diabetes Mellitus, Type 2 - immunology; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - prevention & control; Diet, High-Fat; Dose-Response Relationship, Drug; Female; Hypoglycemic Agents - isolation & purification; Hypoglycemic Agents - pharmacology; IL-1β; Inflammasome; Inflammasomes - drug effects; Inflammasomes - immunology; Inflammasomes - metabolism; Inflammation - immunology; Inflammation - metabolism; Inflammation - prevention & control; Inflammation Mediators - metabolism; Janus Kinase 1 - metabolism; Juniperus - chemistry; Juniperus rigida; Lipopolysaccharides - pharmacology; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Mice; Mice, Inbred C57BL; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Peritonitis - chemically induced; Peritonitis - immunology; Peritonitis - metabolism; Peritonitis - prevention & control; Phosphorylation; Phytotherapy; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Plants, Medicinal; RAW 264.7 Cells; Signal Transduction - drug effects; STAT1 Transcription Factor - metabolism; TRIF; Type-II diabetes; Uric Acid
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2016.05.059

Juniperus rigida Sieb. (J. rigida) is used for medicinal purposes in Asian countries to treat inflammation-related disorders, such as neuralgia, dropsy, and gout. The anti-inflammatory effects of J. rigida extract (JR) and its underlying mechanisms were explored both in in vitro cell lines and in vivo metabolic disease models. Lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages were used to study the changes in inflammatory responses in vitro. Bone marrow-derived macrophages (BMDMs) were used to study the regulatory effect of JR on inflammasome activation. The murine model for monosodium urate (MSU)-induced peritonitis and high-fat diet (HFD)-induced type 2 diabetes were employed to study the effect of JR on in vivo efficacy. JR suppressed the MSU-induced in vivo inflammatory response by attenuation of proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α). In the in vitro study, JR suppressed IL-1β secretion via regulation of apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization, leading to the inhibition of inflammasome activation. JR also inhibited the LPS-stimulated release of proinflammatory mediators, such as nitric oxide (NO), TNF-α, and IL-6 in RAW264.7 cells. The inhibitory effects of JR were mediated through the regulation of the TRIF-dependent signaling pathway from JAK1/STAT1 phosphorylation. Furthermore, JR showed inhibitory effects on HFD-induced type 2 diabetes in a mouse model through the regulation of blood glucose and serum IL-1β. Our results indicate that JR attenuates both LPS-stimulated and danger-signal-induced inflammatory responses in macrophages via regulation of the key inflammatory mechanisms, providing scientific support for its traditional use in the treatment of various inflammation-related metabolic disorders. [Display omitted]