RESUMEN
BACKGROUND/AIM: Acute lung injury (ALI) is associated with a high mortality rate and cancer patients who receive chemotherapy are at high risk of ALI during neutropenia recovery. Galantamine is a cholinesterase inhibitor used for Alzheimer's disease treatment. Previous studies have shown that galantamine reduced inflammatory response in lipopolysaccharide (LPS)-induced ALI in rats. Mer protein was negatively associated with inflammatory response. The aim of the study was to investigate whether galantamine is effective in LPS-induced ALI during neutropenia recovery and its effect on Mer tyrosine kinase (MerTK) expression in mice. MATERIALS AND METHODS: Intraperitoneal cyclophosphamide was given to mice to induce neutropenia. After 7 days, LPS was administered by intratracheal instillation. Intraperitoneal galantamine was given once before LPS administration and in another group, galantamine was given twice before LPS administration. RESULTS: Galantamine attenuated LPS-induced ALI in histopathological analysis. The neutrophil percentage was lower in the group where galantamine was injected once, compared to the LPS group (p=0.007). MerTK expression was also higher in the group where galantamine was injected once but did not reach statistical significance (p=0.101). CONCLUSION: Galantamine attenuated inflammation in LPS-induced ALI during neutropenia recovery.
Asunto(s)
Lesión Pulmonar Aguda , Neutropenia , Humanos , Ratones , Ratas , Animales , Galantamina/efectos adversos , Galantamina/metabolismo , Lipopolisacáridos/efectos adversos , Tirosina Quinasa c-Mer/metabolismo , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Neutropenia/inducido químicamente , Neutropenia/tratamiento farmacológico , Proteínas Tirosina Quinasas/metabolismo , Pulmón/patologíaRESUMEN
Lycoris radiata is the main source of galanthamine, a clinical drug used in Alzheimer's disease; however, the galanthamine content in L. radiata is low. Lycoris aurea is another Lycoris species with high galanthamine content. Fungal endophytes can enhance plant secondary metabolite accumulation; thus, we compared the fungal communities in these two Lycoris species to identify certain fungal taxa in L. aurea capable of enhancing galanthamine accumulation. Several fungal endophytes, which were enriched in, exclusively isolated from L. aurea, or showed significant correlations with galanthamine, were demonstrated to enhance the accumulation of only galanthamine but no other Amaryllidaceae alkaloids (AAs) in L. radiata. These fungal endophytes mainly upregulated the downstream genes in the biosynthesis pathways of AAs in L. radiata, suggesting that they may allocate more precursors for galanthamine biosynthesis. This study demonstrated that fungal endophytes from L. aurea with higher galanthamine content can specifically enhance the accumulation of this medicinal alkaloid in other Lycoris species, thereby increasing the galanthamine source and reducing galanthamine separation and purification costs. This study broadens our understanding of the complex interactions between plant secondary metabolites and fungal endophytes.