title: Differential Action between Schisandrin A and Schisandrin B in Eliciting an Anti-Inflammatory Action: The Depletion of Reduced Glutathione and the Induction of an Antioxidant Response.
abstract: Schisandrin A (Sch A) and schisandrin B (Sch B) are active components of Schisandrae Fructus. We compared the biochemical mechanism underlying the anti-inflammatory action of Sch A and Sch B, using cultured lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and concanavalin (ConA)-stimulated mouse splenocytes. Pre-incubation with Sch A or Sch B produced an anti-inflammatory action in LPS-stimulated RAW264.7 cells, as evidenced by the inhibition of the pro-inflammatory c-Jun N-terminal kinases/p38 kinase/nuclear factor-κB signaling pathway as well as the suppression of various pro-inflammatory cytokines and effectors, with the extent of inhibition by Sch A being more pronounced. The greater activity of Sch A in anti-inflammatory response was associated with a greater decrease in cellular reduced glutathione (GSH) level and a greater increase in glutathione S-transferase activity than corresponding changes produced by Sch B. However, upon incubation, only Sch B resulted in the activation of the nuclear factor (erythroid-derived 2)-like factor 2 and the induction of a significant increase in the expression of thioredoxin (TRX) in RAW264.7 cells. The Sch B-induced increase in TRX expression was associated with the suppression of pro-inflammatory cytokines and effectors in LPS-stimulated macrophages. Studies in a mouse model of inflammation (carrageenan-induced paw edema) indicated that while long-term treatment with either Sch A or Sch B suppressed the extent of paw edema, only acute treatment with Sch A produced a significant degree of inhibition on the inflammatory response. Although only Sch A decreased the cellular GSH level and suppressed the release of pro-inflammatory cytokines and cell proliferation in ConA-simulated splenocytes in vitro, both Sch A and Sch B treatments, while not altering cellular GSH levels, suppressed ConA-stimulated splenocyte proliferation ex vivo. These results suggest that Sch A and Sch B may act differentially on activating GST/ depleting cellular GSH and inducing an antioxidant response involved in their anti-inflammatory actions.
authors.affiliation: Division of Life Science, The Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong SAR, China.
authors.forename: Pou Kuan
authors.initials: PK
authors.lastname: Leong
authors.affiliation: Division of Life Science, The Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong SAR, China.
authors.forename: Hoi Shan
authors.initials: HS
authors.lastname: Wong
authors.affiliation: Division of Life Science, The Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong SAR, China.
authors.forename: Jihang
authors.initials: J
authors.lastname: Chen
authors.affiliation: Division of Life Science, The Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong SAR, China.
authors.forename: Wing Man
authors.initials: WM
authors.lastname: Chan
authors.affiliation: Division of Life Science, The Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong SAR, China.
authors.forename: Hoi Yan
authors.initials: HY
authors.lastname: Leung
authors.affiliation: Division of Life Science, The Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong SAR, China.
authors.forename: Kam Ming
authors.initials: KM
authors.lastname: Ko
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism*; D003208:Concanavalin A; D034242:Cyclooctanes / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D004487:Edema; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D007249:Inflammation; D017705:Lignans / Q000494:pharmacology*; D008070:Lipopolysaccharides; D051379:Mice; D008813:Mice, Inbred ICR; D011083:Polycyclic Compounds / Q000494:pharmacology*; D000067996:RAW 264.7 Cells
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D034242:Cyclooctanes; D016207:Cytokines; D017705:Lignans; D008070:Lipopolysaccharides; D011083:Polycyclic Compounds; C015499:schizandrin B; D003208:Concanavalin A; C034734:schizandrin A; D005982:Glutathione Transferase; D005978:Glutathione; D000111:Acetylcysteine