Protective effect of higenamine ameliorates collagen-induced arthritis through heme oxygenase-1 and PI3K/Akt/Nrf-2 signaling pathways

Abstract

Abstract. Existing in Ranunculaceae Aconitum and tomato, with the chemical name 1-phydroxybenzyl-1,2,3,4-tetrahydroisoquinoline, 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.

Synthesis and Detailed Examination of Spectral Properties of (S) and (R)-Higenamine 4′-O-β-d-Glucoside and HPLC Analytical Conditions to Distinguish the Diastereomers

“…Higenamine (synonym norcoclaurine) is a tetrahydroisoquinoline found in several plants, including aconite root [ 1 ], lotus ( Nelumbo nucifera ) [ 2 ], Gnetum parvifolium [ 3 ], Tinospora crispa [ 4 ], and Tinospora cordifolia [ 5 ]. It possesses β-adrenergic receptor agonist activity owing to its structural similarity to catecholamine, has been shown to have a tracheal relaxation effect on guinea pig trachea [ 6 ]; it can protect against myocyte apoptosis in ischemia/reperfusion injury [ 7 ], collagen-induced arthritis, and spinal cord injury [ 8 , 9 ]; and it is clinically studied for therapeutic effects [ 10 , 11 ].…”

Higenamin Ratlarda İskemi Reperfüzyonunun Neden Olduğu Oksidatif Böbrek Hasarını Azaltır

“…Induction of ROS and MDA production, and SOD activity inhibition arising from neuronal cell injury triggered by oxygen-glucose deprivation/reperfusion were attenuated by Hig [46] . Hig increased antioxidant level and reduced MDA, TNF-α and IL-1β levels in a collagen-induced arthritis study [47] . According to published reports, Hig possesses a variety of pharmacological properties, including dilatation of blood vessels and bronchi, immunomodulatory, antiinflammatory, antiapoptocic and antioxidation features [18] .…”

Pharmacological effects of higenamine based on signalling pathways and mechanism of action

“…These findings suggested that the NRF-2/HO-1/HMGB1 signalling pathway is involved in the anti-apoptotic activity of HG, which is consistent with the findings of Ha et al (2012), indicating that HG promotes HO-1 secretion and inhibits HMGB1 expression via the PI3K/ AKT/NRF-2 signalling pathway to improve cerebral ischaemia-reperfusion injury. HG not only inhibits apoptosis in ischaemia-reperfusion injury but also alleviates collageninduced arthritis by promoting HO-1 release and regulating the PI3K/AKT/NRF-2 signalling pathway (Duan et al, 2016). The proliferation, differentiation and apoptosis of normal cells are tightly regulated by the PI3K/AKT signalling pathway.…”