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Abstract Background Vascular dysfunction can lead to many health problems including hypertension and heart disease. The complexities of vascular dysfunction and vascular disorder-related diseases have prompted the search for many new biologically active compounds in the efforts of resolving the problems. Previous studies have shown that Amaryllidaceae alkaloids exert multiple biological activities, including the vasorelaxation effect. Crinum amabile, which is a family member of Amaryllidaceae, is believed to possess a promising pharmacological activity as a vasorelaxant. Method The vasorelaxation activities of Crinum amabile extracts and fractions were determined using in vitro models of phenylephrine pre-contracted intact and denuded rat aortic rings. The mechanistic pathways of vasorelaxation were investigated by pre-treatment of endothelium-intact rat aortic rings with L-NG Nitro Arginine Methyl Ester (L-NAME), methylene blue (MB), indomethacin, atropine and propranolol, respectively. Results The results showed that chloroform extract (CE) of Crinum amabile exhibited the highest vasorelaxation activity, and further fractionation of CE found that its F5 fraction exerted the strongest activity. An in-depth study on the mechanistic pathway revealed that the endothelium-dependent vasorelaxation induced by F5 fraction was primarily achieved through stimulation of prostaglandin (PGI2) production and partially associated with NO/cGMP activation pathway. Conclusion Findings from this study suggest that Crinum amabile can serve as a promising candidate for the discovery and development of the new vasorelaxant drug.

Objective: To determine the involvement and the modulatory effects of IL-33 during Plasmodium berghei ANKA (PbA) infection. Methods: PbA infection in male ICR mice was utilized as a model of malaria. Systemically circulating IL-33 levels were determined in blood plasma by enzyme-linked immunosorbent assay (ELISA). After 24 hours post-inoculation of PbA, recombinant IL-33 and ST2, and antibodies against IL-33 and IgG treatments were administered daily for 3 days. Tissue expression and localization of IL-33 were assessed in organs generally affected by malaria via immunohistochemistry. Moreover, histopathological examination was performed to assess the effects of the treatments. Results: The levels of systemic IL-33 were elevated at the critical phase of PbA infection. Likewise, immunohistochemical analysis revealed a significant upregulation of IL-33 expression at the critical phase in the brain, lungs, and spleen of PbA-infected mice as compared to healthy controls. Treatment with IL-33 protected against experimental cerebral malaria development and reduced pathological features in the brain and lungs of the PbA-infected mice. Conclusions: A potential critical role and involvement of IL-33 in PbA infection may hint at the resolution of immunopathological sequelae associated with malaria. [ABSTRACT FROM AUTHOR]