RESUMO
Four flavonoid glycosides containing coumaroyl or feruloyl groups were isolated from the male flowers of Ginkgo biloba L., and compounds 3 and 4 were identified as novel compounds. The inhibitory activities against α-glucosidase were investigated by docking studies, in vitro assays and kinetic studies. The docking results showed that all compounds mainly formed hydrogen-bond and π-π-stacking interactions with α-glucosidase. Compound 4 had the lowest binding energy and maximum number of hydrogen bonds. Subsequently, the in vitro assays showed that compound 4 exhibited the strongest inhibitory potency. Finally, the kinetic studies indicated the inhibitory mode of compounds 1-4 against α-glucosidase were mixed types of competitive and non-competitive. Together, these findings suggested that the isolated flavonoid glycosides in this study, especially compound 4, have potential as α-glucosidase inhibitors.
Assuntos
Flavonoides , Ginkgo biloba , Flavonoides/química , Flores/química , Ginkgo biloba/química , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Glicosídeos/química , Cinética , Simulação de Acoplamento Molecular , alfa-Glucosidases/metabolismoRESUMO
Coptis chinensis inflorescence is traditionally used as tea and has been popular in the local market. C. chinensis inflorescence extract (CE) exhibits protective effects against carbon tetrachloride (CCl4)-induced damage, but the underlying mechanism remains unclear. The main chemicals of CE were detected, purified, and identified in this study. CE and linarin could reverse changes in cell viability, decrease alanine aminotransferase and aspartate transaminase levels, and reduce reactive oxygen species (ROS) generation induced by CCl4 in HepG2 cells. CE and linarin could also phosphorylate mitogen-activated protein kinases (MAPKs) and up-regulate Kelth-like ECH-associated protein (Keap1). The pathways of MAPKs and Keap1 lead to the separation of Keap1 and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Free Nrf2 transferred to the nucleus and enhanced the expression of phase II detoxification enzymes. This study provides a scientific basis for the use of C. chinensis inflorescence, which exhibits a hepatoprotective function, as a supplement in the food industry.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Coptis/química , Medicamentos de Ervas Chinesas/administração & dosagem , Glicosídeos/administração & dosagem , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Substâncias Protetoras/administração & dosagem , Tetracloreto de Carbono/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/análise , Glicosídeos/análise , Células Hep G2 , Humanos , Inflorescência/química , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Fator 2 Relacionado a NF-E2/genética , Substâncias Protetoras/análise , Transdução de SinaisRESUMO
Cyclophosphamide (CP) is a widely utilized chemotherapy drug. CP and its metabolite, acrolein, could induce hepatotoxicity. In this study, Cichorium glandulosum seed (CGS) effectively mitigated CP-induced hepatotoxicity in mice. Protection of cynarin, the major compound of CGS, against acrolein cytotoxicity in HepG2 cells was studied. Pretreatment with cynarin could improve cell survival against acrolein cytotoxicity. Cynarin restored the balance of glutathione (GSH) and reactive oxygen species (ROS), and inhibited mitochondrial depolarization. The kinetics of Nrf2 expression in cytosolic and nuclear fractions were observed after acrolein exposure. Intracellular Nrf2 expression was triggered within 6 h of exposure but did not translocate to the nucleus. Cynarin pretreatment ameliorated the expression and activity of GSH S-transferase and triggered Nrf2 nuclear translocation. In conclusion, treatment with CGS and cynarin protects liver injury against CP and acrolein hepatotoxicity via improvement of GSH activity and activation of the Nrf2 pathway.