title: Higenamine promotes M2 macrophage activation and reduces Hmgb1 production through HO-1 induction in a murine model of spinal cord injury.
abstract: Spinal cord injury (SCI) is considered to be primarily associated with loss of motor function and leads to the activation of diverse cellular mechanisms in the central nervous system to attempt to repair the damaged spinal cord tissue. Higenamine (HG) (1-[(4-hydroxyphenyl) methyl]-1,2,3,4-tetrahydroisoquinoline-6,7-diol), an active ingredient of Aconiti Lateralis Radix Praeparata, has been traditionally used as a heart stimulant and anti-inflammatory agent in oriental countries. However, the function and related mechanism of HG on SCI have never been investigated. In our current study, HG treatment displayed increased myelin sparring and enhanced spinal cord repair process. The numbers of CD4(+) T cells, CD8(+) T cells, Ly6G(+) neutrophils and CD11b(+) macrophages were all significantly lower in the HG-treated group than that in the control group after SCI. HG administration increased the expression of IL-4 and IL-10 and promoted M2 macrophage activation. Significantly reduced Hmgb1 expression was also observed in HG-treated mice with SCI. Furthermore, HG treatment promoted HO-1 production. The increased number of M2 macrophages, decreased expression of Hmgb1 and promoted locomotor recovery induced by HG were all reversed with additional HO-1 inhibitor treatment. In conclusion, HG promotes M2 macrophage activation and reduces Hmgb1 expression dependent on HO-1 induction and then promotes locomotor function after SCI.
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, China. Electronic address: zhenyzhang@126.com.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, China.
authors.forename: Mingchao
authors.initials: M
authors.lastname: Li
authors.affiliation: Microscopic Hand Surgery, Hainan Provincial People's Hospital, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, China.
authors.forename: Jiaping
authors.initials: J
authors.lastname: Li
mesh_terms: D019264:Adoptive Transfer; D000470:Alkaloids / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D004195:Disease Models, Animal; D024243:HMGB1 Protein / Q000096:biosynthesis / Q000097:blood*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D008262:Macrophage Activation / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000276:immunology; D044005:Tetrahydroisoquinolines / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D000470:Alkaloids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D008565:Membrane Proteins; D044005:Tetrahydroisoquinolines; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; C012348:higenamine
keywords: HO-1; Higenamine; Hmgb1; M2 macrophages; SCI