Vasicinone, a pyrroloquinazoline alkaloid from Adhatoda vasica Nees enhances memory and cognition by inhibiting cholinesterases in Alzheimer's disease

Bhanukiran, Kancharla; Singh, Ravi; Gajendra, T A; Ramakrishna, Kakarla; Singh, Sushil Kumar; Krishnamurthy, Sairam; Kumar, Ashok; Hemalatha, S

doi:10.1016/j.phyplu.2023.100439

Cited by 15 publications

(6 citation statements)

References 30 publications

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“…Moreover, these agents only provide symptomatic relief [ 41 , 43 ]. To date, there are no disease-modifying agents to treat AD [ 44 ]. Therefore, neurorestorative therapies need to be studied in AD to prevent neurodegeneration and its associated complications [ 45 , 46 ].…”

Section: Wβc Signaling In Alzheimer’s Diseasementioning

confidence: 99%

WNT-β Catenin Signaling as a Potential Therapeutic Target for Neurodegenerative Diseases: Current Status and Future Perspective

et al. 2023

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Wnt/β-catenin (WβC) signaling pathway is an important signaling pathway for the maintenance of cellular homeostasis from the embryonic developmental stages to adulthood. The canonical pathway of WβC signaling is essential for neurogenesis, cell proliferation, and neurogenesis, whereas the noncanonical pathway (WNT/Ca2+ and WNT/PCP) is responsible for cell polarity, calcium maintenance, and cell migration. Abnormal regulation of WβC signaling is involved in the pathogenesis of several neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and spinal muscular atrophy (SMA). Hence, the alteration of WβC signaling is considered a potential therapeutic target for the treatment of neurodegenerative disease. In the present review, we have used the bibliographical information from PubMed, Google Scholar, and Scopus to address the current prospects of WβC signaling role in the abovementioned neurodegenerative diseases.

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Section: Wβc Signaling In Alzheimer’s Diseasementioning

confidence: 99%

WNT-β Catenin Signaling as a Potential Therapeutic Target for Neurodegenerative Diseases: Current Status and Future Perspective

et al. 2023

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“…The cholinesterase enzymes hAChE, eeAChE, and eqBuChE were purchased from Sigma-Aldrich (USA). The spectrometric analysis method was followed to evaluate the ChEs inhibitory activity of compounds . The test compound stock solutions were prepared by dissolving the compounds in biological grade DMSO (1 mg/mL).…”

Section: Experimental Sectionmentioning

confidence: 99%

“…The drugs which act on CNS have the ideal lipophilicity, which is advantageous to cross the blood–brain barrier (BBB). To evaluate compound lipophilicity, the Parrel artificial membrane permeability assay (PAMPA) was performed . Biological grade DMSO was used to make the test compound stock solutions and then further diluted with phosphate buffer pH 7.4.…”

Section: Experimental Sectionmentioning

confidence: 99%

“…The scopolamine-induced amnesia (Y maze test) model is most commonly used to evaluate spatial working memory in rats. , The rats were divided into six groups ( n = 6), with group 1 being the vehicle alone (control group), group 2 being scopolamine 0.5 mg/kg, po (disease control), group 3 being PD07 2.5 mg/kg, po, group 4 being PD07 5 mg/kg, po, group 5 being PD07 10 mg/kg, po, and group 6 being DPZ 5 mg/kg, po. Groups 3 to 6 received compound PD07/DPZ orally (po) for 7 days in the as stated above doses, whereas groups 1 and 2 received vehicle alone (0.5% CMC).…”

Section: Experimental Sectionmentioning

confidence: 99%

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Discovery of Multitarget-Directed Ligands from Piperidine Alkaloid Piperine as a Cap Group for the Management of Alzheimer’s Disease

Bhanukiran

Singh

et al. 2023

ACS Chem. Neurosci.

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The naturally inspired multitarget-directed ligands (PC01–PC10 and PD01–PD26) were synthesized from piperine for the management of Alzheimer’s disease (AD). The compound PD07 showed significant inhibitory activity on ChEs, BACE1, and Aβ1–42 aggregation in in vitro studies. Further, compound PD07 effectively displaced the propidium iodide at the AChE PAS site. The compound PD07 exhibited significant lipophilicity in PAMPA studies. Additionally, PD07 demonstrated neuroprotective properties in the Aβ1–42 induced SH-SY5Y cell line. Furthermore, DFT calculations were performed using B3LYP/6-311G(d,p) basis sets to explore the PD07 physical and chemical properties. The compound PD07 showed a similar binding interaction profile at active sites of AChE, BuChE, and BACE1 proteins as compared to reference ligands (donepezil, tacrine, and BSD) in molecular docking and dynamic simulation studies. In acute oral toxicity studies, compound PD07 exhibited no toxicity symptoms up to 300 mg/kg, po. The compound PD07 (10 mg/kg, po) improved memory and cognition in scopolamine-induced amnesia rats. Further, PD07 increased ACh levels in the brain by inhibiting the AChE activity. The results from in vitro, in silico, and in vivo studies suggested that compound PD07 is a potent multitarget-directed lead from piperine to overcome Alzheimer’s disease.

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“…4B). The diagram manifests assorted peculiar interactions of the ligature in the company of amino acid residues of the target protein, additionally designated as hydrogen, hydrophobic, ionic bonds, and water aqueducts [22]. Two target protein-ligand complexes, BACE1-isorhoifolin and AChE inhibitor-isorhoifolin, were deliberated through MD simulations to inaugurate the steadiness of the complex.…”

Section: Molecular Dynamics Studiesmentioning

confidence: 99%

Neuroprotective upshot of isorhoifolin flavonoid of Gmelina asiatica for multitargeted approach in Alzheimer's disease: Exploration through in-silico studies

Andarghiske,

Kancharla,

Siva

2023

Preprint

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Alzheimer's is a progressive neurodegenerative disease with amyloid-beta peptide deposition that impairs memory and cognitive decline. In previous reports, the plant Gmelina asiatica was reported to have anti-Alzheimer’s disease (AD) activity. However, the responsible chemical constituents of G. asiatica for anti-Alzheimer’s activity have not been explored. Therefore, the present study aimed to investigate hit compounds through an in silico approach. The reported phytoconstituents were initially screened through auto dock software. Then, the lead compound was further evaluated through molecular dynamic studies. Further hit compound isorhoifolin physicochemical and ADMET properties were analyzed. In docking studies, isorhoifolin showed the least binding energy and well resided at the active sites of AchE (-10.9 kcal/mol), BACE1 (-10.2 kcal/mol), GSK-3 (-9.7 kcal/mol), TACE1 (-9 kcal/mol). Further molecular dynamic simulation revealed that isorhoifolin is stable up to 200 ns. Furthermore, density functional theory (DFT) was analyzed using Gaussian software, where the quantum mechanics objective was focused. Besides, the physicochemical properties of isorhoifolin were studied, such as absorption, distribution, metabolism, excretion, and toxicity, through the pkcsm software. The study suggests isorhoifolin from the Gmelina asiatica plant may be responsible for anti-Alzheimer's activity, which may be considered for further investigation.

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Vasicinone, a pyrroloquinazoline alkaloid from Adhatoda vasica Nees enhances memory and cognition by inhibiting cholinesterases in Alzheimer's disease

Cited by 15 publications

References 30 publications

WNT-β Catenin Signaling as a Potential Therapeutic Target for Neurodegenerative Diseases: Current Status and Future Perspective

WNT-β Catenin Signaling as a Potential Therapeutic Target for Neurodegenerative Diseases: Current Status and Future Perspective

Discovery of Multitarget-Directed Ligands from Piperidine Alkaloid Piperine as a Cap Group for the Management of Alzheimer’s Disease

Neuroprotective upshot of isorhoifolin flavonoid of Gmelina asiatica for multitargeted approach in Alzheimer's disease: Exploration through in-silico studies

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