title: Dehydrocorydaline inhibits elevated mitochondrial membrane potential in lipopolysaccharide-stimulated macrophages.
abstract: Activated macrophages play a critical role in the pathogenesis of numerous diseases by producing pro-inflammatory cytokines such as interleukin (IL)-1β and IL-6. While the mechanisms of bacterial component recognition and signal transduction have been well investigated, viability regulation in activated macrophages remains unclear. We screened herbal ingredients to find an agent that reduces the viability of lipopolysaccharide (LPS)-stimulated macrophages and observed that dehydrocorydaline, a component of Corydalis yanhusuo, reduced the viability of macrophage-derived RAW264.7 cells and primary macrophages in the presence of LPS. Dehydrocorydaline inhibited the elevation of mitochondrial membrane potential and induced ATP depletion in LPS-stimulated macrophages but neither affected basal mitochondrial membrane potential nor ATP content in non-stimulated macrophages. Dehydrocorydaline also prevented increased concentrations of IL-1β and IL-6 in culture media of LPS-stimulated macrophages. Mode of dehydrocorydaline action indicates that elevated mitochondrial membrane potential may be a novel target to specifically reduce viability and suppress cytokine production in LPS-stimulated macrophages.
authors.affiliation: Department of Advanced Research of Gastroenterology, Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya, Aichi, 466-8550, Japan. kio@med.nagoya-u.ac.jp
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ishiguro
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ando
authors.forename: Osamu
authors.initials: O
authors.lastname: Maeda
authors.forename: Osamu
authors.initials: O
authors.lastname: Watanabe
authors.forename: Hidemi
authors.initials: H
authors.lastname: Goto
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D051379:Mice; D008813:Mice, Inbred ICR; D010936:Plant Extracts / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D000093242:Interleukin-6 Inhibitors
chemical_list: D000255:Adenosine Triphosphate; D000470:Alkaloids; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010936:Plant Extracts; D000093242:Interleukin-6 Inhibitors; C007232:dehydrocorydalin