In vitro acetylcholinesterase inhibition by psoralen using molecular docking and enzymatic studies

Somani, Gauresh; Kulkarni, Chinmay; Shinde, Prashant; Shelke, Rupesh U.; Laddha, K. S.; Sathaye, Sadhana

doi:10.4103/0975-7406.148775

Cited by 32 publications

(13 citation statements)

References 17 publications

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“…Molecular docking : The procedure of molecular docking of cubebin was followed as described elsewhere 8 . Cubebin structure was constructed using ‘build option’ within Maestro using standard geometries and standard bond lengths as described earlier 8 .…”

Section: Methodsmentioning

confidence: 99%

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Neuroprotective effect of Cubebin

Somani

Nahire

Parikh

et al. 2017

Indian Journal of Medical Research

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Background & objectives:Acetylcholinesterase (AChE) inhibitors represent a major class of drugs which provide symptomatic relief and improvement in cognitive function in Alzheimer's disease (AD). In this study, cubebin, a dibenzylbutyrolactone lignan, was isolated from Piper cubeba and investigated for its AChE inhibitory activity in an attempt to explore its potential for memory-enhancing activities in mice.Methods:Molecular docking of cubebin was carried out followed by in vitro AChE activity. Mice were treated with cubebin (25 & 50 mg/kg; i.p.), for three days and memory impairment was induced by scopolamine (3 mg/kg; i.p.). Memory function was evaluated by Morris water maze (MWM) test. Biochemical parameters of oxidative stress and cholinergic function were estimated in brain.Results:Molecular docking study revealed that cubebin was well bound within the binding site of the AChE enzyme showing interactions such as π-π stacking and hydrogen bonding with residues present therein. Cubebin inhibited AChE enzyme in an in vitro assay with IC50 value of 992 μM. Scopolamine administration caused a significant impairment of learning and memory in mice, as indicated by a marked decrease in MWM performance. Scopolamine administration also produced a significant enhancement of brain AChE activity and oxidative stress in mice brain. Pre-treatment of cubebin (25 and 50 mg/kg; i.p.) significantly prevented scopolamine-induced learning and memory deficits along with attenuation of scopolamine-induced rise in brain AChE activity and oxidative stress level.Interpretation & conclusions:Cubebin showed promising protective activity in scopolamine-induced spatial memory impairment in mice. This could be attributed to its brain AChE inhibition and antioxidant activity.

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Section: Methodsmentioning

confidence: 99%

“…Experimental design : AChE enzyme was isolated from rat brain homogenate as reported earlier 8 9 . This crude enzyme was used in the study to observe inhibition by different concentrations of cubebin.…”

Section: Methodsmentioning

confidence: 99%

Neuroprotective effect of Cubebin

Somani

Nahire

Parikh

et al. 2017

Indian Journal of Medical Research

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“…Docking studies were carried out using standard grid-based ligand docking with energetics molecular docking protocol[ 21 ] implemented within maestro molecular modeling suite by Schrodinger, LLC, New York, USA, 2010, installed on AMD Athlon™ workstation (Glide, version 5.6). The protein structure used in the present study is a three-dimensional (3D) crystal structure of human AR in complex with NADP+ and the inhibitor IDD594 with a resolution of 0.81Å and was downloaded from protein data bank code2I16.…”

Section: Methodsmentioning

confidence: 99%

Thymol, a monoterpene, inhibits aldose reductase and high-glucose-induced cataract on isolated goat lens

et al. 2016

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Background:Overactivation of aldose reductase (AR) enzyme has been implicated in the development of various diabetic complications. In the present study, the inhibitory effect of thymol was investigated on AR enzyme and its anti-cataract activity was also examined on isolated goat lens.Materials and Methods:Various concentrations of thymol were incubated with AR enzyme prepared from isolated goat lens. Molecular docking studies were carried out using Schrodinger software to verify the binding of thymol with AR as well as to understand their binding pattern. Further, thymol was evaluated for its anti-cataract activity in high-glucose-induced cataract in isolated goat lens in vitro. Quercetin was maintained as standard (positive control) throughout the study.Results:Thymol showed potent inhibitory activity against goat lens AR enzyme with an IC50 value of 0.65 μg/ml. Docking studies revealed that thymol binds with AR in similar binding pattern as that of quercetin. The high–glucose-induced cataract in isolated goat lens was also improved by thymol treatment. Thymol was also able to significantly (P < 0.001) reduce the oxidative stress associated with cataract.Conclusion:The results suggest that thymol may be a potential therapeutic approach in the prevention of diabetic complications through its AR inhibitory and antioxidant activities.

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“…Research study suggests that psoralen competitively inhibits AChE activity in a concentration-dependent manner, which therefore activates the central cholinergic neuronal system, and tightly binds the residues at the enzyme binding site by π-π conjugation and hydrogen bonding ( Somani et al, 2015 ), indicating that psoralen may be a potential candidate to inhibit AChE. This should be further explored for clinical applications in Alzheimer’s disease.…”

Section: Neuroprotective Properties Of Psoralenmentioning

confidence: 99%

A Review of the Pharmacological Properties of Psoralen

et al. 2020

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Psoralen is the principal bioactive component in the dried fruits of Cullen corylifolium (L.) Medik (syn. Psoralea corylifolia L), termed "Buguzhi" in traditional Chinese medicine (TCM). Recent studies have demonstrated that psoralen displays multiple bioactive properties, beneficial for the treatment of osteoporosis, tumors, viruses, bacteria, and inflammation. The present review focuses on the research evidence relating to the properties of psoralen gathered over recent years. Firstly, multiple studies have demonstrated that psoralen exerts strong anti-osteoporotic effects via regulation of osteoblast/osteoclast/chondrocyte differentiation or activation due to the participation in multiple molecular mechanisms of the wnt/b-catenin, bone morphogenetic protein (BMP), inositol-requiring enzyme 1 (IRE1)/ apoptosis signaling kinase 1 (ASK1)/c-jun N-terminal kinase (JNK) and the Protein Kinase B (AKT)/activator protein-1 (AP-1) axis, and the expression of miR-488, peroxisome proliferators-activated receptor-gamma (PPARg), and matrix metalloproteinases (MMPs). In addition, the antitumor properties of psoralen are associated with the induction of ER stress-related cell death via enhancement of PERK: Pancreatic Endoplasmic Reticulum Kinase (PERK)/activating transcription factor (ATF), 78kD glucose-regulated protein (GRP78)/C/EBP homologous protein (CHOP), and 94kD glucose-regulated protein (GRP94)/CHOP signaling, and inhibition of P-glycoprotein (P-gp) or ATPase that overcomes multidrug resistance. Furthermore, multiple articles have shown that the antibacterial, anti-inflammatory and neuroprotective effects of psoralen are a result of its interaction with viral polymerase (Pol), destroying the formation of biofilm, and regulating the activation of tumor necrosis factor alpha (TNF-a), transforming growth factor beta (TGF-b), interleukin 4

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In vitro acetylcholinesterase inhibition by psoralen using molecular docking and enzymatic studies

Cited by 32 publications

References 17 publications

Neuroprotective effect of Cubebin

Neuroprotective effect of Cubebin

Thymol, a monoterpene, inhibits aldose reductase and high-glucose-induced cataract on isolated goat lens

A Review of the Pharmacological Properties of Psoralen

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