title: Protective effect of higenamine ameliorates collagen-induced arthritis through heme oxygenase-1 and PI3K/Akt/Nrf-2 signaling pathways.
abstract: Existing in RanunculaceaeAconitumand tomato, with the chemical name 1-phydroxybenzyl-1,2,3,4-tetrahy-droisoquinoline, higenamine is widely distributed in China. Higenamine's anti-inflammatory, antioxidant and anti-apoptotic effects have been identified in previous studies. The present study attempted to determine the protective effect of higenamine against collagen-induced arthritis through heme oxygenase-1 (HO-1) and PI3K/Akt/Nrf-2 signaling pathways. A type II collagen (CII)-induced arthritis (CIA) model was established and clinical arthritis scores were used to appraise the curative effect of higenamine. Inflammatory reactions, oxidative damage and caspase-3/9 activation were detected using specific ELISA kits. In addition, western blotting was used to evaluate the expression of HO-1, Akt and Nrf-2 protein in CII-induced CIA mice. In CII-induced CIA mice, the clinical arthritis scores, inflammatory reactions, oxidation damage and caspase-3/9 activation were increased and activated. The results demonstrated that treatment with higenamine significantly reduced the elevation of clinical arthritis scores (P<0.01), and suppressed the promotion of inflammatory reactions, oxidation damage and caspase-3/9 activation. Furthermore, higenamine significantly increased HO-1 protein expression (P<0.01) and upregulated the PI3K/Akt/Nrf-2 signal pathway in CII-induced CIA mice. Collectively, it is concluded that higenamine protects against CII-induced CIA through the induction of HO-1 and the upregulation of the PI3K/Akt/Nrf-2 signaling pathway. In conclusion, higenamine may be a beneficial drug for protecting against CIA.
authors.affiliation: Department of Orthopaedics, Jingdu Hospital, Nanjing, Jiangsu 210000, P.R. China.
authors.forename: Wenjiang
authors.initials: W
authors.lastname: Duan
authors.affiliation: Department of Orthopaedics, Jingdu Hospital, Nanjing, Jiangsu 210000, P.R. China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics, Jingdu Hospital, Nanjing, Jiangsu 210000, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Orthopaedics, Jingdu Hospital, Nanjing, Jiangsu 210000, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, Jingdu Hospital, Nanjing, Jiangsu 210000, P.R. China.
authors.forename: Yuansheng
authors.initials: Y
authors.lastname: Xu
keywords: heme oxygenase-1; higenamine; phosphatidylinositol-3-kinase/protein kinase B/nuclear factor (erythroid-derived 2)-like 2; type I collagen-induced arthritis