RESUMO
Combretum quadrangulare Kurz is widely used in folk medicine in Eastern Asia and is associated with various ethnopharmacological properties including hepatoprotective, antipyretic, analgesic, antidysenteric, and anthelmintic activities. Previous phytochemical investigations reported the presence of numerous triterpenes (mostly cycloartanes, ursanes, lupanes, and oleananes) along with dozens of flavonoids. However, the extracts of C. quadrangulare and isolated flavonoids have not been evaluated for their alpha-glucosidase inhibition. In the frame of our efforts dedicated to the chemical investigation of Vietnamese medicinal plants and their biological activities, a phytochemical study of the MeOH extract of the leaves of C. quadrangulare using bioactive guided isolation was undertaken. In this paper, the isolation and structure elucidation of twelve known compounds, 5-hydroxy-3,7,4'-trimethoxyflavone (1), ayanin (2), kumatakenin (3), rhamnocitrin (4), ombuin (5), myricetin-3,7,3',5'-tetramethyl ether (6), gardenin D (7), luteolin (12), apigenin (13), mearnsetin (14), isoorientin (15), and vitexin (16) were reported. Bromination was applied to compounds 2 and 3 to provide four new synthetic analogues 8-11. All isolated and synthesized compounds were evaluated for alpha-glucosidase inhibition and antibacterial activity. Compounds 4 and 5 showed moderate antibacterial activity against methicillin-resistant Staphylococcus aureus while others were inactive. All compounds failed to reveal any activity toward extended spectrum beta-lactamase-producing Escherichia coli. Compounds 2, 4, 6-9, and 11-14 showed good alpha-glucosidase inhibition with IC50 values in the range of 30.5-282.0 µM. The kinetic of enzyme inhibition showed that 8 and 11 were noncompetitive type inhibition against alpha-glucosidase. In silico molecular docking model indicated that compounds 8 and 11 were potential inhibitors against enzyme α-glucosidase.
Assuntos
Combretum/química , Flavonas/química , Flavonas/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Relação Dose-Resposta a Droga , Flavonas/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Ligação de Hidrogênio , Ligantes , Modelos Moleculares , Conformação Molecular , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Compostos Fitoquímicos/química , Extratos Vegetais/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
BACKGROUND: During hepatectomy, intermittent portal triad clamping (IPC) reduces ischemia-reperfusion injuries. Pharmacological preconditioning with sevoflurane revealed similar properties. The aim of the study was to evaluate the combination of a sevoflurane preconditioning regimen with IPC on ischemia-reperfusion injuries. METHODS: Three regimens of anesthesia were applied: group SEV with continuous application of sevoflurane, group PRO with continuous propofol infusion and group PC where continuous propofol was substituted by sevoflurane (adjusted to reach MAC∗1.5) for 15 min before IPC. Endpoints were the values of AST and ALT, factor V, prothrombin time, bilirubinemia over the 5-postoperative days (POD), morbidity and mortality at POD30 and POD90. RESULTS: The ALT values at POD5 were lower in the PC group (n = 27) 74 (48 -98) IU/L compared to PRO (n = 26) and SEV (n = 67) respectively 110 (75 -152) and 100 (64 -168) IU/L (p = 0.038). The variation of factor V compared to preoperative values was less important in the PC and SEV groups respectively -14% and -16% vs -30% (PRO) (p = 0.047). CONCLUSION: Our study suggests that sevoflurane attenuates ischemia-reperfusion injuries on liver function, compared to propofol, without benefit for a specific regimen of pharmacological preconditioning when IPC is applied.
