RESUMO
Six diarylheptanoids (1-6) and two flavonoids (7 and 8) derived from Alpinia officinarum were evaluated for their ability to inhibit acetylcholinesterase. Compound 1 showed the highest degree of inhibition, with an IC50 of approximately 2⯵M, followed by moderate degrees of inhibition by 2, 4 and 7, with IC50 values ranging from 20 to 40⯵M. The remaining isolated compounds 3, 5, 6 and 8 had IC50 values greater than 50⯵M. Enzyme kinetic studies showed that the compounds with high or moderate activity were competitive inhibitors, anchored to the active site of acetylcholinesterase. In particular, compounds 1 and 2 were docked at slightly different positions from those occupied by 4 and 7. Furthermore, molecular dynamics studies showed that compound 1 maintained its interactions with residues Thr74 and Phe295 throughout the simulation trajectory. Our findings suggest that compound 1 is a potential therapeutically relevant inhibitor of acetylcholinesterase.
Assuntos
Alpinia/química , Inibidores da Colinesterase/farmacologia , Colinesterases/metabolismo , Simulação por Computador , Simulação de Dinâmica Molecular , Extratos Vegetais/farmacologia , Rizoma/química , Domínio Catalítico , Inibidores da Colinesterase/química , Inibidores da Colinesterase/metabolismo , Concentração Inibidora 50 , Simulação de Acoplamento Molecular , Extratos Vegetais/química , Extratos Vegetais/metabolismoRESUMO
While an anti-allergic effect of Chaga mushroom (Inonotus obliquus) has been indicated, its therapeutic effect on allergy and immunoregulatory mechanisms and chemical constituents directly responsible for that are hardly known. We examined the effect of 70% ethanol extract of Chaga mushroom (EE) and its dichloromethane (DF) and aqueous (AF) fractions using a mouse model of chicken ovalbumin (cOVA)-induced food allergy, and found that only EE and DF ameliorated allergy symptoms to a significant extent. The in vivo mast cell-stabilizing activity was also found only in EE and DF whereas the activities to suppress Th2 and Th17 immune responses and cOVA-specific IgE production in the small intestine were observed in all three treatment regimens, implying that inhibition of the mast cell function by lipophilic compounds was vital for the therapeutic effect. Results also indicated that inotodiol, a triterpenoid predominantly present in DF, played an active role as a mast cell stabilizer.
Assuntos
Antialérgicos/uso terapêutico , Hipersensibilidade Alimentar/tratamento farmacológico , Lanosterol/análogos & derivados , Mastócitos/imunologia , Células Th17/imunologia , Células Th2/imunologia , Animais , Basidiomycota/imunologia , Modelos Animais de Doenças , Etanol , Feminino , Humanos , Imunoglobulina E/sangue , Lanosterol/uso terapêutico , Cloreto de Metileno , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologiaRESUMO
The subchronic toxicity of Aristolochiae fructus containing aristolochic acids (AAs), a natural component in the Aristolochiaceae family, was investigated. The A. fructus was daily administered by gavage to male and female rats for 90 d at dose levels of 21.35, 213.5, and 2135 mg/kg (equivalent to 0.05, 0.5, and 5 mg/kg as AAs, respectively). During the test period, clinical signs, mortality, body weights, food and water consumption, hematology, serum biochemistry, organ weights, and histopathology were examined. Significant decreases in body weight gain were noted in the high-dose group receiving both the aqueous extract of A. fructus and AAs. Decreases in food consumption were noted beginning at 50 d and did not recover in the high-dose group of aqueous extract of A. fructus and AAs. Irrespective of dose, water consumption was not affected. There was no mortality or adverse clinical signs, hematology, or serum biochemistry in the treatment groups versus control. Nephrotoxicity and hyperplasia of epithelial cells in the forestomach were observed in rats receiving the highest dose of aqueous extract of A. fructus and at doses of >or= 0.5 mg/kg/day AAs. For both genders, the no-observed-adverse-effect level (NOAEL) for A. fructus based on this subchronic study in rats was considered to be 21.3 mg/kg/d.
Assuntos
Aristolochiaceae/química , Ácidos Aristolóquicos/toxicidade , Animais , Comportamento Alimentar/efeitos dos fármacos , Feminino , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Nível de Efeito Adverso não Observado , Extratos Vegetais/toxicidade , Ratos , Ratos Sprague-Dawley , Estômago/efeitos dos fármacos , Estômago/patologia , Aumento de PesoRESUMO
A new flavonoid glucuronide, apigenin 7-O-beta-D-(4'-caffeoyl)glucuronide (1), and the known compound, apigenin 7-O-beta-D-glucurnoide, were isolated from the flowers of Chrysanthemum morifolium, along with five known flavonoids. The structure of 1 was elucidated by the aid of spectroscopic analyses. Among isolated compounds, apigenin 7-O-beta-D-(4"-caffeoyl)glucuronide showed strong HIV-1 integrase inhibitory activity (IC (50) = 7.2 +/- 3.4 microg/ml) and anti-HIV activity in a cell culture assay (EC (50) = 41.86 +/- 1.43 microg/ml) using HIV-I (IIIB) infected MT-4 cells.
Assuntos
Fármacos Anti-HIV/farmacologia , Chrysanthemum , HIV-1/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Flavonoides/administração & dosagem , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Flores , Glucuronídeos/administração & dosagem , Glucuronídeos/farmacologia , Glucuronídeos/uso terapêutico , Humanos , Concentração Inibidora 50 , Testes de Sensibilidade Microbiana , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêuticoRESUMO
Three new dimeric iridoid glucosides, named asperuloides A (1), B (2), and C (3), were isolated from Asperula maximowiczii, along with the known compound picconioside II. The structures of the new compounds were determined by spectroscopic and chemical methods and by the single-crystal X-ray diffraction analysis of 1.