In Vivo Neuropharmacological Potential of Gomphandra tetrandra (Wall.) Sleumer and In-Silico Study against β-Amyloid Precursor Protein

Abstract

Medicinal plants possess a surplus of novel and biologically active secondary metabolites that are responsible for counteracting diseases. Traditionally, Gomphandra tetrandra (Wall.) Sleumer is used to treat mental disorders. The present research was designed to explore phytochemicals from the ethanol leaf extract of Gomphandra tetrandra (Wall.) Sleumer to identify the potential pharmacophore(s) in the treatment of neurological disorders. The chemical compounds of the experimental plant were identified through GC-MS analysis. In-vitro antioxidant activity was assessed using different methods. Furthermore, in-vivo neurological activity was assessed in Swiss-albino mice. Computer-aided analysis was appraised to determine the best-fit phytoconstituent of a total of fifteen identified compounds in the experimental plant extract against beta-amyloid precursor protein. The experimental extract revealed fifteen compounds in GC-MS analysis and the highest content was 9, 12, 15-octadecatrienoic acid (z,z,z). The extract showed potent antioxidant activity in in-vitro assays. Furthermore, in in-vivo neurological assays, the extract disclosed significant (p < 0.05) neurological activity. The most favorable phytochemicals as neurological agents were selected via ADMET profiling, and molecular docking was studied with beta-amyloid precursor protein. In the computer-aided study, 1, 5-diphenyl-2h-1, 2, 4-triazoline-3-thione (Pub Chem CID: 2802516) was more active than other identified compounds with strong binding affinity to beta-amyloid precursor protein. The present in vivo and in silico studies revealed neuropharmacological features of G. tetrandra leaf extract as a natural agent against neurological disorders, especially Alzheimer’s disease.

Amentoflavone derivatives significantly act towards the main protease (3CLPRO/MPRO) of SARS-CoV-2: in silico admet profiling, molecular docking, molecular dynamics simulation, network pharmacology

“…Amentoflavone (biflavonoid) is one of the plant derivatives compounds that were isolated by Okigawa et al [ 16 ], and due to a wider range of bioactivities, it has drawn much attention among the scientific community [ 3 , 66 , 67 ]. A compound should have some fundamental properties for becoming an ideal anti-COVID-19 drug candidate [ 44 ] such as (i) restriction ability of viral entrance, thereby inhibiting cellular attachment; (ii) inhibition of viral replication inside the host cells; (iii) cytotoxic effects on the existing viruses; and (iv) protection of the host normal cells from the viral origin oxidative stress and inflammatory responses.…”

“…A compound should have some fundamental properties for becoming an ideal anti-COVID-19 drug candidate [ 44 ] such as (i) restriction ability of viral entrance, thereby inhibiting cellular attachment; (ii) inhibition of viral replication inside the host cells; (iii) cytotoxic effects on the existing viruses; and (iv) protection of the host normal cells from the viral origin oxidative stress and inflammatory responses. And the compound amentoflavone is the evidence that followed all of these pathways and performed as potential anti-COVID-19 therapeutics; even not only this compound alone but also its derivatives showed the antioxidant [ 68 , 69 ] and anti-inflammatory [ 3 , 70 – 72 ] activities. Moreover, the M PRO should have the ability to break host polyproteins as well as induce the formation of protein for viral replication [ 73 ], and amentoflavone has the interaction capability with M PRO [ 28 ].…”

“…To find out the best drug candidates molecular docking is an excellent method [ 3 ]. This method is used for predicting the best drug candidates based on the scoring.…”

“…COVID-19 or Coronavirus disease-19 has caused by severe acute respiratory virus-2 (SARS-CoV-2) in December 2019 and has been spreading rapidly from Wuhan, China, to globally. World Health Organization (WHO) observed all circumstances and declared the COVID-19 as a global pandemic [ 1 – 3 ]. At present (16 December 2021), according to the worldometer ( https://www.worldometers.info/coronavirus/ ) estimated that 27,28,11,578 infected; 53,49,729 deaths; 24,51,13,998 recovered-covid-19 patients.…”

“…But researchers are trying to find out ideal plant-derived natural phytocompounds which address the diverse diseases conditions, and these bioactive compounds will hasten the drug discovery process [ 13 – 15 ]. Amentoflavone (i.e., biflavonoid in nature) is extremely found all over the world [ 2 , 3 , 16 ]. Clusiaceae, Caryophyllaceae, Euphorbiaceae, Cupressaceae, Calophyllum, and Selaginellaceae families are the major sources of amentoflavone [ 17 ].…”