Isolation, characterization and therapeutic potential of a novel furanoid diterpene lactone from Hedychium spicatum rhizomes: Insights into antioxidant, anxiolytic, and circadian rhythm modulating properties

Abstract

BackgroundHedychium spicatum rhizomes is widely used in ayurvedic medicine and traditional medicine systems around the Himalayas. PurposeStandardization of Hedychium spicatum rhizome SCFE extract by Identification, Isolation, characterization, and screening of pharmacological activity of phytoconstituents. Study designSupercritical fluid extraction, column chromatography, spectroscopic analysis, in-silico, and in-vivo study of compound 1 (3-((E) -2-((1S,8aR)-3,5,5,8a-tetramethyl-4-oxo-1,4,4a,5,6,7,8,8a-octahydro-naphthalen-1-yl) vinyl) furan-2(5H)-one). MethodsA supercritical fluid extract was prepared and further purified to obtain a novel Furanoid diterpene lactone compound 1 (3-((E) -2-((1S,8aR)-3,5,5,8a-tetramethyl-4-oxo-1,4,4a,5,6,7,8,8a-octahydro-naphthalen-1-yl) vinyl) furan-2(5H)-one). It was characterised using IR, LC-ESI/MS, 1H, 13C NMR, 2D NMR-COSY, NOESY, HMBC, and HSQC and thin-layer chromatography. Compound was tested for anxiolytic activity using various animal behavioural model included elevated maze plus test, light and dark box test, social interaction, actophotometer test, rotarod test. ResultsThe compound gives a false Dragendorff's test in favour of the presence of lactone. HPLC profiling was done using DAD using 30 % v/v of o-phosphoric acid (0.1 % v/v) in water and 70 % v/v of acetonitrile (ACN) in the mobile phase. Compound 1 having significant anxiolytic effect tested in animal behavioural model ****p < 0.0001 diazepam as standard. ConclusionFree radical scavenging activity suggested that compound 1 has good potential as an antioxidant, having IC50 values of 75.62 µg and 96.556 µg using DPPH and ABTS inhibition assays. ADMET prediction suggested that compound 1 follows Lipinski's rules of five, absorbed through the intestine, and penetrates the blood-brain barrier and CNS. In-silico studies, suggested that compound 1 has an affinity to bind with GABA, melatonin 1, and glutamate receptor 5 and In-vivo study suggest compound 1 will be a good candidate as anxiolytic agent. It can be used as a promising natural remedy for oxidative stress, mental health issues, and sleep-related disorders, warranting further exploration and clinical investigation.