Calycosin attenuates Angiostrongylus cantonensis-induced parasitic meningitis through modulation of HO-1 and NF-κB activation. Issue 4 (7th April 2023)

• Record Type: Journal Article
• Authors: Lu, Cheng-You; Chen, Ke-Min; Kuo, Wei-Wen; Lai, Shih-Chan; Ho, Tsung-Jung; Lai, Po-Tang; Huang, Chih-Yang; Wang, Tso-Fu
• Is Part Of: Parasitology. Volume 150:Issue 4(2023)
• Page Start: 311
• Page End: 320
• Publication Date: 2023-04-07
• Subjects: Angiostrongylus cantonensis -- anti-inflammation -- calycosin -- eosinophilic meningitis -- HO-1; Parasitology -- Periodicals; Electronic journals; 616.96
• DOI: 10.1017/S0031182022001408
• Languages: English
• ISSNs: 0031-1820

Abstract

Abstract: Abstract: Angiostrongylus cantonensis causes a form of parasitic meningitis in humans. Albendazole (ABZ) kills nematode larvae in the brain. However, dead larvae can trigger a severe inflammatory response, resulting in brain damage. Accumulating evidence suggests that calycosin represents a potential anti-inflammatory therapeutic candidate. In this study, we investigated the combined effects of ABZ and calycosin in angiostrongyliasis caused by A. cantonensis in BALB/c mice. Inflammatory mediators (such as phospho-nuclear factor- κ B, cyclooxygenase-2, matrix metalloproteinase-9, tumour necrosis factor- α and interleukin-1 β ) are associated with the development of meningitis and immune inflammatory reactions. We found that A. cantonensis significantly induces inflammatory mediator production and increases the blood–brain barrier (BBB) permeability. However, co-administration of both ABZ and calycosin markedly suppressed meningitis and inflammatory mediator production and decreased the BBB permeability compared to treatment with a single drug. Furthermore, calycosin and ABZ plus calycosin treatment facilitated production of the antioxidant haem oxygenase-1 (HO-1). Moreover, co-therapy with ABZ and calycosin failed to mitigate angiostrongyliasis in the presence of tin-protoporphyrin IX, an HO-1-specific inhibitor. This finding suggests that the beneficial effects of ABZ plus calycosin treatment on the regulation of inflammation are mediated by the modulation of HO-1 activation. The present results provide new insights into the treatment of human angiostrongyliasis using co-therapy with ABZ and calycosin.