ABSTRACT
Alpinia officinarum is a commonly used spice with proven folk uses in various traditional medicines. In the current study, six compounds were isolated from its rhizomes, compounds 1-3 were identified as diarylheptanoids, while 4-6 were identified as flavonoids and phenolic acids. The isolated compounds were subjected to virtual screening against α-glucosidase, butyrylcholinesterase (BChE), and acetylcholinesterase (AChE) enzymes to evaluate their potential antidiabetic and anti-Alzheimer's activities. Molecular docking and dynamics studies revealed that 3 exhibited a strong binding affinity to human a α- glucosidase crystal structure compared to acarbose. Furthermore, 2 and 5 demonstrated high potency against AChE. The virtual screening results were further supported by in vitro assays, which assessed the compounds' effects on α-glucosidase, cholinesterases, and their antioxidant activities. 5-Hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-phenylheptan-3-one (2) showed potent antioxidant effect in both ABTs and ORAC assays, while p-hydroxy cinnamic acid (6) was the most potent in the ORAC assay. In contrary, kaempferide (4) and galangin (5) showed the most potent effect in metal chelation assay. 5-Hydroxy-1,7-diphenylhepta-4,6-dien-3-one (3) and 6 revealed the most potent effect as α-glucosidase inhibitors where compound 3 showed more potent effect compared to acarbose. Galangin (5) revealed a higher selectivity to BChE, while 2 showed the most potent activity to (AChE).
Subject(s)
Acetylcholinesterase , Alpinia , Antioxidants , Butyrylcholinesterase , Cholinesterase Inhibitors , Glycoside Hydrolase Inhibitors , Molecular Docking Simulation , Rhizome , Alpinia/chemistry , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/isolation & purification , Glycoside Hydrolase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/isolation & purification , Antioxidants/pharmacology , Antioxidants/chemistry , Antioxidants/isolation & purification , Rhizome/chemistry , Butyrylcholinesterase/metabolism , Acetylcholinesterase/metabolism , alpha-Glucosidases/metabolism , Quantitative Structure-Activity Relationship , Flavonoids/chemistry , Flavonoids/pharmacology , Flavonoids/isolation & purification , Hydroxybenzoates/pharmacology , Hydroxybenzoates/chemistry , Hydroxybenzoates/isolation & purification , HumansABSTRACT
Luteolin-7-O-glycoside (LG), an abundant component in many edible plants, was found to be one of the major constituents of the aqueous methanol extract of Trifolium alexandrinum L. family Fabaceae, a fodder plant widely cultivated in Egypt. The estrogenic activity of LG concerning the effect on uterotrophy, lipid profile, weight gain and bone enhancement activity was determined in ovariectomized rat model at a dose of 5 mg/kg. Luteolin-7-O-glycoside showed significant estrogenic effect through the preservation of normal uterine weight and plasma estradiol level. It also significantly inhibited the bone turnover markers plasma bone-specific alkaline phosphatase, plasma osteocalsin, type I procollagen N-terminal, and C-telopeptide of type II collagen levels. It induced a significant improvement in plasma lipid profile. The effect of LG was comparable with estradiol with lower effect on uterine weight. Liver and kidney functions revealed a wide safety of LG at this dose level. The present study revealed that LG may be a promising hormone replacement therapy after being examined thoroughly on human. Copyright © 2016 John Wiley & Sons, Ltd.
