title: Schisandrin B induces an Nrf2-mediated thioredoxin expression and suppresses the activation of inflammasome in vitro and in vivo.
abstract: Reactive oxygen species (ROS)-mediated activation of inflammasome is involved in the development of a wide spectrum of diseases. We aimed to investigate whether (-)schisandrin B [(-)Sch B], a phytochemical that can induce cellular antioxidant response, can suppress the inflammasome activation. Results showed that (-)Sch B can induce an nuclear factor erythroid 2-related factor 2-driven thioredoxin expression in primary peritoneal macrophages and cultured RAW264.7 macrophages. A 4-h priming of peritoneal macrophages with LPS followed by a 30-min incubation with ATP caused the activation of caspase 1 and the release of IL-1β, indicative of inflammasome activation. Although LPS/ATP did not activate inflammasome in RAW264.7 macrophages, it caused the ROS-dependent c-Jun N-terminal kinase1/2 (JNK1/2) activation and an associated lactate dehydrogenase (LDH) release in RAW264.7 macrophages, an indication of cytotoxicity. (-)Sch B suppressed the LPS/ATP-induced activation of caspase 1 and release of IL-1β in peritoneal macrophages. (-)Sch B also attenuated the LPS/ATP-induced ROS production, JNK1/2 activation and LDH release in RAW264.7 macrophages. The ability of (-)Sch B to suppress LPS/ATP-mediated inflammation in vitro was further confirmed by an animal study, in which schisandrin B treatment (2 mmol/kg p.o.) ameliorated the Imject Alum-induced peritonitis, as indicated by suppressions of caspase1 activation and plasma IL-1β level. The ensemble of results suggests that (-)Sch B may offer a promising prospect for preventing the inflammasome-mediated disorders.
authors: Division of Life Science, The Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong SAR, China.
authors: Pou Kuan
authors: PK
authors: Leong
authors: Division of Life Science, The Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong SAR, China.
authors: Kam Ming
authors: KM
authors: Ko
mesh_terms: D000534:Alum Compounds / Q000633:toxicity; D000818:Animals; D020170:Caspase 1 / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D034242:Cyclooctanes / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D058847:Inflammasomes / Q000187:drug effects*; D053583:Interleukin-1beta / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology* / Q000627:therapeutic use; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D011083:Polycyclic Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism*
chemical_list: D000534:Alum Compounds; D034242:Cyclooctanes; D058847:Inflammasomes; D053583:Interleukin-1beta; D017705:Lignans; D011083:Polycyclic Compounds; D017382:Reactive Oxygen Species; C015499:schizandrin B; D013879:Thioredoxins; D020170:Caspase 1
keywords: caspase 1; inflammasome; macrophage; schisandrin B; thioredoxin