Background: Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance, leading to right ventricular failure and death. Recent studies have suggested that chronic inflammatory processes are involved in the pathogenesis of PAH. Several studies have demonstrated that betaine possesses outstanding anti-inflammatory effects. However, whether betaine exerts protective effects on PAH by inhibiting inflammatory responses in the lungs needs to be explored. To test our hypothesis, we aimed to investigate the effects of betaine on monocrotaline-induced PAH in rats and attempted to further clarify the possible mechanisms. Methods: PAH was induced by monocrotaline (50 mg/kg) and oral administration of betaine (100, 200, and 400 mg/kg/day). The mean pulmonary arterial pressure, right ventricular systolic pressure, and right ventricle hypertrophy index were used to evaluate the development of PAH. Hematoxylin and eosin staining and Masson staining were performed to measure the extents of vascular remodeling and proliferation in fibrous tissue. Monocyte chemoattractant protein-1 (MCP-1) and endothelin-1 (ET-1) were also detected by immunohistochemical staining. Nuclear factor-κB (NF-κB), tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β) were assessed by Western blot. Results: This study showed that betaine improved the abnormalities in right ventricular systolic pressure, mean pulmonary arterial pressure, right ventricle hypertrophy index, and pulmonary arterial remodeling induced by monocrotaline compared with the PAH group. The levels of MCP-1 and ET-1 also decreased. Western blot indicated that the protein expression levels of NF-κB, TNF-α, and IL-1β significantly decreased (p < 0.01). Conclusion: Our study demonstrated that betaine attenuated PAH through its anti-inflammatory effects. Hence, the present data may offer novel targets and promising pharmacological perspectives for treating monocrotaline-induced PAH.

This study aimed to investigate the anti-inflammatory effects of N-methylcytisine (NMC) in a dextran sulfate sodium (DSS)-induced colitis model and explore its possible mechanisms. Experimental colitis was induced by administering the mice with 5% DSS for 7 days. Different doses of NMC (1, 4 and 16 mg/kg) and 5-aminosalicylic acid (100 mg/kg) were given orally once every day for 7 days. The protective effect of NMC was evaluated using the disease activity index, colon length and results of histopathological examination. The possible mechanisms of NMC were explored by evaluating the expression levels of tumour necrosis factor-α, interleukin-1β and interleukin-6 (IL-6) using ELISA and analysing the protein expression levels of nuclear factor (NF)-κB p65, p-NF-κB p65, p-IκB, IκB, IκB kinase (IKK) and p-IKK using western blots. Results demonstrated that the oral administration of NMC attenuated the DSS-induced clinical symptoms and pathological damage. In addition, NMC treatment significantly reduced myeloperoxidase activity and level of pro-inflammatory cytokines. Further studies revealed that NMC blocked the activation of NF-κB by inhibiting IκB and IKK phosphorylation. These findings suggested that NMC exerts anti-inflammatory effects on DSS-induced colitis, and its mechanism may be related to the suppression of NF-κB activation. Thus, NMC may have potential therapeutic value in the treatment of colitis.