RESUMO
Traumatic brain injury (TBI) is a leading cause of morbidity and mortality among military service members and civilians in the United States. Despite significant advances in the understanding of TBI pathophysiology, several clinical reports indicate that multiple genetic and epigenetic factors can influence outcome. Homocysteine (HCY) is a non-proteinogenic amino acid, the catabolism of which can be dysregulated by stress, lifestyle, aging, or genetic abnormalities leading to hyperhomocysteinemia (HHCY). HHCY is a neurotoxic condition and a risk factor for multiple neurological and cardiovascular disorders that occurs when HCY levels is clinically > 15 µM. Although the deleterious impact of HHCY has been studied in human and animal models of neurological disorders such as stroke, Alzheimer's disease and Parkinson's disease, it has not been addressed in TBI models. This study tested the hypothesis that HHCY has detrimental effects on TBI pathophysiology. Moderate HHCY was induced in adult male Sprague Dawley rats via daily administration of methionine followed by impact-induced traumatic brain injury. In this model, HHCY increased oxidative stress, upregulated expression of proteins that promote blood coagulation, exacerbated TBI-associated blood-brain barrier dysfunction and promoted the infiltration of inflammatory cells into the cortex. We also observed an increase of brain injury-induced lesion size and aggravated anxiety-like behavior. These findings show that moderate HHCY exacerbates TBI outcomes and suggest that HCY catabolic dysregulation may be a significant biological variable that could contribute to TBI pathophysiology heterogeneity.
Assuntos
Lesões Encefálicas Traumáticas/etiologia , Lesões Encefálicas Traumáticas/patologia , Córtex Cerebral/patologia , Hiper-Homocisteinemia/complicações , Estresse Oxidativo , Animais , Ansiedade/sangue , Ansiedade/complicações , Comportamento Animal/efeitos dos fármacos , Coagulação Sanguínea/efeitos dos fármacos , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/patologia , Barreira Hematoencefálica/fisiopatologia , Lesões Encefálicas Traumáticas/sangue , Homocisteína/sangue , Homocisteína/toxicidade , Hiper-Homocisteinemia/sangue , Inflamação/sangue , Inflamação/patologia , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , Metionina/administração & dosagem , Ocludina/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Tirosina/análogos & derivados , Tirosina/metabolismo , Proteína da Zônula de Oclusão-1/metabolismoRESUMO
Saponins, prominent secondary plant metabolites, are recognized for their roles in plant defense and medicinal benefits. Soyasaponins, commonly derived from legumes, are a class of triterpenoid saponins that demonstrate significant potential for plant and human health applications. Previous research and reviews largely emphasize human health effects of soyasaponins. However, the biological effects of soyasaponins and their implications for plants in the context of human health have not been well-discussed. This review provides comprehensive discussions on the biological roles of soyasaponins in plant defense and rhizosphere microbial interactions; biosynthetic regulation and compound production; immunological effects and potential for therapeutics; and soyasaponin acquisition attributed to processing effects, bioavailability, and biotransformation processes based on recent soyasaponin research. Given the multifaceted biological effects elicited by soyasaponins, further research warrants an integrated approach to understand molecular mechanisms of regulations in their production as well as their applications in plant and human health.