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Prodrugs of dexibuprofen having ester moieties instead of free carboxylic acid which involves in gastrointestinal side effects have been synthesized. Dexibuprofen acid was condensed with different alcohols/phenols to afford the ester prodrugs. All of the synthesized prodrugs were characterized by their physical attributes, elemental analysis, FT-IR, 1 H-NMR, and 13 C-NMR spectroscopy. The in vitro anti-inflammatory studies was done by chemiluminescence technique reflect prodrugs have been more potent, owing to the different chemical structures. Lipoxygenase enzyme inhibition assay was also assess and found compound DR7 with IC 50 =19.8 μM), DR9 (IC 50 =24.8 μM) and DR3 (IC 50 =47.2 μM) as compared with Dexibuprofen (IC 50 =156.6 μM). It was also evaluated for docking studies revealed that DR7 has found to be more potent anti-inflammatory against 5-LOX (3 V99) as well as analgesic against COX-II (5KIR) enzyme. Anti-oxidant activities were also performed, DR3 (86.9 %), DR5 (83.5 %), DR7 (93.9 %) and DR9 (87.4 %) were found to be more anti-oxidant as compared to (2S)-2-[4-(2-methylpropyl)phenyl]propanoic acid (52.7 %)., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Aim: The study was planned to investigate the phytochemicals, antidiabetic and antioxidant studies of A. consanguineum., Methods: The preliminary studies were performed on crude extract and different solvent fractions. Based on the potency, the chloroform fraction was semi-purified to phyto-fractions CHF-1 - 5. Furthermore, CHF-3 was subjected to isolation of pure compounds using column chromatography. The α-glucosidase, α-amylase and antioxidant assays (DPPH, ABTS, H 2 O 2 ) were performed on all samples. The in-vivo experiments on compounds 1 and 2 were also performed using oral glucose tolerance test. Docking studies were performed on α-glucosidase and α-amylase targets., Results: Among all fractions, the chloroform fraction exhibited excellent activities profile giving IC 50 values of 824, 55, 117, 58 and 85 μg/ml against α-glucosidase, α-amylase, DPPH, ABTS and H 2 O 2 targets respectively. Among the five semi-purified chloroform phyto-fractions (CHF-1-5), CHF-3 was the leading fraction in activities giving IC 50 values of 85.54, 61.19 and 26.58 μg/ml against α-glucosidase, α-amylase and DPPH respectively. Based on the overall potency and physical amount of CHF-3, it was subjected to purification to get compounds 1 and 2. The two compounds were also found potent in in-vitro activities. The observed IC 50 values for compound 1 were 7.93, 28.01 and 6.19 μg/ml against α-glucosidase, α-amylase and DPPH respectively. Similarly, the compound 2 exhibited IC 50 of 14.63, 24.82 and 7.654 μg/ml against α-glucosidase, α-amylase and DPPH respectively. Compounds 1 and 2 were potent in decreasing the blood glucose levels in experimental animals. Compounds 1 and 2 also showed interactions with the respective enzymes with molecular docking., Conclusions: We can conclude that A. Consanguineum is a rich source of natural antidiabetic agents. Bioguided isolation of compound 1 and 2 showed potential inhibitions in all tested in-vitro antidiabetic targets. Further, both the compounds were also able to decrease the blood glucose levels in experimental animals., (© 2022. The Author(s).)

Background: Diabetes mellitus is a common disease effecting the lifestyles of majority world population. In this research work, we have embarked the potential role of crude extracts and isolated compounds of Notholirion thomsonianum for the management diabetes mellitus., Methods: The crude extracts of N. thomsonianum were initially evaluated for α-glucosidase, α-amylase and antioxidant activities. The compounds were isolated from the activity based potent solvent fraction. The structures of isolated compounds were confirmed with NMR and MS analyses. The isolated compounds were tested for α-glucosidase, α-amylase, protein tyrosine phosphatase 1B (PTP1B) and DPPH activities. The molecular docking studies were carried out to find the binding interactions of isolated compounds for α-glucosidase, α-amylase and PTP1B., Results: Initially, we screened out crude extracts and subfractions of N. thomsonianum against different in-vitro targets. Among all, Nt.EtAc was observed a potent fraction among all giving IC 50 values of 67, 70, < 0.1, 89 and 16 μg/mL against α-glucosidase, α-amylase, DPPH, ABTS and H 2 O 2 respectively. Three compounds (Nt01, Nt02 and Nt03) were isolated from Nt.EtAc of N. thomsonianum. The isolated compounds Nt01, Nt02 and Nt03 exhibited IC 50 values of 58.93, 114.93 and 19.54 μM against α-glucosidase, while 56.25, 96.54 and 24.39 μM against α-amylase respectively. Comparatively, the standard acarbose observed IC 50 values were 10.60 and 12.71 μM against α-glucosidase, α-amylase respectively. In PTP1B assay, the compounds Nt01, Nt02 and Nt03 demonstrated IC 50 values of 12.96, 36.22 and 3.57 μM in comparison to the standard ursolic acid (IC 50 of 3.63 μM). The isolated compounds also gave overwhelming results in DPPH assay. Molecular docking based binding interactions for α-glucosidase, α-amylase and PTP1B were also encouraging., Conclusions: In the light of current results, it is obvious that N. thomsonianum is potential medicinal plant for the treatment of hyperglycemia. Overall, Nt.EtAc was dominant fraction in all in-vitro activities. Three compounds Nt01, Nt02 and Nt03 were isolated from ethyl acetate fraction. The Nt03 specifically was most potent in all in-vitro assays. The molecular docking studies supported our in-vitro results. It is concluded that N. thomsonianum is a rich source of bioactive antidiabetic compounds which can be further extended to in-vivo based experiments., (© 2021. The Author(s).)

Background: Edible oils have proven health benefits in the prevention and treatment of various disorders since the establishment of human era. This study was aimed to appraise neuropharmacological studies on the commonly used edible oils including Cinnamomum verum (CV), Zingiber officinale (ZO) and Cuminum cyminum (CC)., Methods: The oils were analyzed via GC-MS for identifications of bioactive compounds. Anti-radicals capacity of the oils were evaluated via 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radicals scavenging assays. The samples were also tested against two important acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) which are among the important drug targets in Alzheimer's disease. Lineweaver-Burk plots were constructed for enzyme inhibition studies which correspond to velocity of enzymes (V max ) against the reciprocal of substrate concentration (K m ) in the presence of test samples and control drugs following Michaelis-Menten kinetics. Docking studies on AChE target were also carried out using Molecular Operating Environment (MOE 2016.0802) software., Results: (Gas chromatography-mass spectrometry GC-MS) analysis revealed the presence of thirty-four compounds in Cinnamon oil (Cv.Eo), fourteen in ginger oil (Zo.Eo) and fifty-six in cumin oil (Cc.Eo). In the antioxidant assays, Cv.Eo, Zo.Eo and Cc.Eo exhibited IC 50 values of 85, 121, 280 μg/ml sequentially against DPPH radicals. Whereas, in ABTS assay, Cv.Eo, Zo.Eo and Cc.Eo showed considerable anti-radicals potentials with IC 50 values of 93, 77 and 271 μg/ml respectively. Furthermore, Cv.Eo was highly active against AChE enzyme with IC 50 of 21 μg/ml. Zo.Eo and Cc.Eo exhibited considerable inhibitory activities against AChE with IC 50 values of 88 and 198 μg/ml respectively. In BChE assay, Cv.Eo, Zo.Eo and Cc.Eo exhibited IC 50 values of 106, 101 and 37 μg/ml respectively. Our results revealed that these oils possess considerable antioxidant and cholinesterase inhibitory potentials. As functional foods these oils can be effective remedy for the prevention and management of neurological disorders including AD. Synergistic effect of all the identified compounds was determined via binding energy values computed through docking simulations. Binding orientations showed that all the compounds interact with amino acid residues present in the peripheral anionic site (PAS) and catalytic anionic site (CAS) amino acid residues, oxyanion hole and acyl pocket via π-π stacking interactions and hydrogen bond interactions., (© 2021. The Author(s).)

Introduction: The current study was designed to synthesize derivatives of succinimide and compare their biological potency in anticholinesterase, alpha-glucosidase inhibition, and antioxidant assays., Methods: In this research, two succinimide derivatives including ( S )-1-(2,5-dioxo-1-phenylpyrrolidin-3-yl) cyclohexanecarbaldehyde (Compound 1 ) and ( R )-2-(( S )-2,5-dioxo-1-phenylpyrrolidin-3-yl)-2-phenylpropanal (Compound 2 ) were synthesized using Michael addition. Both the compounds, ie, 1 and 2 were evaluated for in-vitro acetylcholinesterase (AChE), butyrylctcholinesterase (BChE), antioxidant, and α-glucosidase inhibitory potentials. Furthermore, molecular docking was performed using Molecular Operating Environment (MOE) to explore the binding mode of both the compounds against different enzymes. Lineweaver-Burk plots of enzyme inhibitions representing the reciprocal of initial enzyme velocity versus the reciprocal of substrate concentration in the presence of synthesized compounds and standard drugs were constructed using Michaelis-Menten kinetics., Results: In AChE inhibitory assay, compounds 1 and 2 exhibited IC 50 of 343.45 and 422.98 µM, respectively, against AChE enzyme. Similarly, both the compounds showed IC 50 of 276.86 and 357.91 µM, respectively, against BChE enzyme. Compounds 1 and 2 displayed IC 50 of 157.71 and 471.79 µM against α-glucosidase enzyme, respectively. In a similar pattern, compound 1 exhibited to be more potent as compared to compound 2 in all the three antioxidant assays. Compound 1 exhibited IC 50 values of 297.98, 332.94, and 825.92 µM against DPPH, ABTS, and H 2 O 2 free radicals, respectively. Molecular docking showed a triple fold in the AChE and BChE activity for compound 1 compared with compound 2 . The compound 1 revealed good interaction against both the AChE and BChE enzymes which revealed the high potency of this compound compared to compound  2 ., Conclusion: Both succinimide derivatives exhibited considerable inhibitory activities against cholinesterases and α-glucosidase enzymes. Of these two, compound 1 revealed to be more potent against all the in-vitro targets which was supported by molecular docking with the lowest binding energies. Moreover, compound 1 also proved to have antiradical properties., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Ahmad et al.)

Background: Cancer is one of the chronic health conditions worldwide. Various therapeutically active compounds from medicinal plants were the current focus of this research in order to uncover a treatment regimen for cancer. Anchusa arvensis (A. anchusa) (L.) M.Bieb. contains many biologically active compounds., Methods: In the current study, new ester 3-hydroxyoctyl -5- trans -docosenoate (compound-1) was isolated from the chloroform soluble fraction of A. anchusa using column chromatography. Using MTT assay, the anticancer effect of the compound was determined in human hepatocellular carcinoma cells (HepG-2) compared with normal epithelial cell line (Vero). DPPH and ABTS radical scavenging assays were performed to assess the antioxidant potential. The Molecular Operating Environment (MOE-2016) tool was used against tyrosine kinase., Results: The structure of the compound was elucidated based on IR, EI, and NMR spectroscopy technique. It exhibited a considerable cytotoxic effect against HepG-2 cell lines with IC 50 value of 6.50 ± 0.70 µg/mL in comparison to positive control (doxorubicin) which showed IC 50 value of 1.3±0.21 µg/mL. The compound did not show a cytotoxic effect against normal epithelial cell line (Vero). The compound also exhibited significant DPHH scavenging ability with IC 50 value of 12 ± 0.80 µg/mL, whereas ascorbic acid, used as positive control, demonstrated activity with IC 50 = 05 ± 0.15 µg/mL. Similarly, it showed ABTS radical scavenging ability (IC 50 = 130 ± 0.20 µg/mL) compared with the value obtained for ascorbic acid (06 ± 0.85 µg/mL). In docking studies using MOE-2016 tool, it was observed that compound-1 was highly bound to tyrosine kinase by having two hydrogen bonds at the hinge region. This good bonding network by the compound might be one of the reasons for showing significant activity against this enzyme., Conclusion: Our findings led to the isolation of a new compound from A. anchusa which has significant cytotoxic activity against HepG-2 cell lines with marked antioxidant potential., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Hussain et al.)

Purpose: The current work was designed to synthesize a bioactive derivative of succinimide and evaluate it for anti-Alzheimer, anticancer and anti-diabetic potentials., Methods: The compound was synthesized by Michael addition of butyraldehyde with N -phenylmaleimide. The synthesized compound was screened for biological potentials including anti-cholinesterase, in-vitro anti-diabetic, antioxidant and anthelmintic potentials. The anti-cholinesterase potential was evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), anti-diabetic potential against α-glucosidase, antioxidant potential against ABTS, DPPH and H 2 O 2 and anthelmintic potential against Perethima posthuma and Ascaridia galli respectively., Results: The compound demonstrated significant AChE and BChE inhibition i.e., 71.34±1.92 and 73.42 ±1.92 at the concentration of 1000 µg/mL respectively. Other dilutions exhibited concentration-dependent inhibitory activity against both enzymes. In the MTT assay, the newly synthesized compound was found active against all of the cell lines viz, HCT-116, MDA-MB231, NIH/3T3 and MCF-7 and the highest cytotoxicity potential was observed against the colon cancer cell line (HCT-116) with an IC 50 value of 78 µg/mL exhibiting its highest potential. Moreover, the compound exhibited prominent α-glucosidase inhibitory potentials (79.86±2.54% at 1000 µg/mL) with IC 50 value of 156.23 µg/mL. Further, our test compound exhibited considerable scavenging activity against DPPH, ABTS and H 2 O 2 free radicals with percent inhibitions of 75.84±1.58, 72.85±1.17 and 54.82±1.82 and IC 50 values of 84.36, 139.74 and 752.21 µg/mL respectively. Our test sample exhibited significant anthelmintic potentials. It demonstrated significant paralysis and death of the test worms in an unbelievably short time in comparison with albendazole., Conclusion: Going into the detail of all observations, it may be deduced that the newly synthesized succinimide derivative could be an important drug candidate against neurodegenerative disorders like Alzheimer's disease, cancer, diabetes mellitus and worms. Further detailed studies in animal models are required for in-vivo analysis of the compound., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Ahmad et al.)

α-Glucosidase is considered as a therapeutic target for the treatment of type 2 diabetes mellitus (DM2). In current study, we synthesized pyrrolidine-2,5-dione (succinimide) and thiazolidine-2,4-dione derivatives and evaluated for their ability to inhibit α-Glucosidase. Pyrrolidine-2,5-dione derivatives (11a-o) showed moderate to poor α-glucosidase inhibition. Compound 11o with the IC 50 value of 28.3 ± 0.28 µM emerged as a good inhibitor of α-glucosidase. Thiazolidine-2,4-dione and dihydropyrimidine (TZD-DHPM) hybrids (22a-c) showed excellent inhibitory activities. The most active compound 22a displayed IC 50 value of 0.98 ± 0.008 µM. Other two compounds of this series also showed activity in low micromolar range. The in-vivo antidiabetic study of three compounds 11n, 11o and 22a were also determined using alloxan induced diabetes mice model. Compounds 11o and 22a showed significant hypoglycemic effect compared to the reference drug. In-vivo acute toxicity study showed the safety of these selected compounds. In-silico docking studies were carried out to rationalize the in-vitro results. The binding modes and bioassay results of TZD-DHPM hybrids showed that interactions with important residues appeared significant for high potency., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A new series of N-acylhydrazone derivatives of 2-mercaptobenzimidazole (2-MBI) has been synthesized through S-alkylation with 1-bromotetradecane and N-alkylation with ethyl-2-chloroacetate. The resulting ester was synthetically modified through hydrazine hydrate to acyl hydrazide which was condensed with aromatic aldehydes to afford the title N-acylhydrazones (4-17). Chemical structures of the newly synthesized compounds have been confirmed through mass, FT-IR and 1 HNMR techniques. In vitro free radical scavenging and α-glucosidase inhibition activities of the compounds were investigated with reference to the standard ascorbic acid and acarbose, respectively. Amongst the target compounds, 13 showed the highest inhibition in DPPH scavenging assay (IC 50  = 131.50 µM) and α-glucosidase inhibition potential (IC 50  = 352 µg/ml). We extended our investigations to explore the mechanism of enzyme inhibition and conducted docking analysis by using Molecular Operating Environment (MOE 2016.08). A homology model for α-glucosidase was constructed and validated using Ramachandran plot. Docking studies were also carried out on human intestinal α-glucosidases. In view of the importance of the nucleus involved, the synthesized compounds might find extensive medicinal applications as reported in the literature., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: In this study Aesculus indica fruit was subjected to isolation of phytochemicals. Two antioxidants quercetin and Mandelic acid were isolated in pure state. The free radical scavenging and acetyl choline esterase inhibitory potential of the crude extract and sub fractions were also determined., Results: The antioxidant capacity of crude extract, fractions and isolated compounds were determined by DPPH and ABTS methods. Folin-Ciocalteu reagent method was used to estimate the total phenolic contents and were found to be 78.34 ± 0.96, 44.16 ± 1.05, 65.45 ± 1.29, 37.85 ± 1.44 and 50.23 ± 2.431 (mg/g of gallic acid) in crude extract, ethyl acetate, chloroform, n-hexane and aqueous fractions respectively. The flavonoid concentration in crude extract, ethyl acetate, chloroform, n-hexane and aqueous fraction were; 85.30 ± 1.20, 53.80 ± 1.07, 77.50 ± 1.12, 26.30 ± 1.35 and 37.78 ± 1.25 (mg/g of quercetin) respectively. The chloroform fraction was more potent against enzymes, acetyl choline esterase and butyryl choline esterase (IC 50  = 85 and 160 μg/ml respectively). The phenolic compounds in the crude extract and fractions were determined using HPLC standard method. Chlorogenic acid, quercetin, phloroglucinol, rutin, mandelic acid and hydroxy benzoic acid were detected at retention times 6.005, 10.062, 22.623, 30.597, 35.490 and 36.211 in crude extract and different fractions. The ethyl acetate fraction was rich in the targeted compounds and was therefore subjected to column isolation. The HPLC chromatogram of isolated compounds showed single peak at specified retention times which confirms their isolation in pure state. The isolated compounds were then characterized by FTIR and NMR spectrophotometric techniques., Conclusion: The Aesculus indica fruit extracts showed antioxidant and anticholine esterase inhibitory potentials. Two bioactive compounds were isolated in the pure form ethyl acetate fraction. From results it was concluded that the fruit of this plant could be used to minimize oxidative stress caused by reactive oxygen species.

Background: Nonea micrantha Boiss. & Reut . being an unexplored member of Boraginaceae was investigated for GC/MS analysis, acetylcholinesterase (AChE), butyrylcholinesterase (BChE) inhibitory and antioxidant activities in an attempt to find its effectiveness in neurological disorders., Methods: The AChE and BChE inhibitory activities of crude methanolic extract (Nm.Cr), subsequent fractions; n-hexane (Nm.Hex), chloroform (Nm.Cf), ethyl acetate (Nm.EtAc), aqueous (Nm.Aq) and crude saponins (Nm.Sp) from N. micrantha were conducted using Ellman's assay. The antioxidant activity of the plant samples using DPPH and ABTS free radical scavenging potential following quantitative spectrophotometric and qualitative TLC method were also studied. Moreover the total reducing power (TRP) of all the samples was also figured out., Results: The GC/Ms analysis confirmed that the plant is rich in bioactive molecules. Among different fractions, Nm.Hex, Nm.EtAc and Nm.Cf exhibited highest AChE inhibitory activities causing 75.51 ± 0.73, 68.54 ± 0.59 and 63.48 ± 0.59% enzyme inhibition respectively and IC 50 of 44, 100 and 144 μg/mL respectively. In BChE inhibiton assay, Nm.Aq, Nm.Sp and Nm.Cr showed highest activity causing 83.49 ± 0.27, 81.49 ± 0.89 and 75.31 ± 0.56% enzyme inhibition with IC 50 of 90, 110 and 44 μg/mL respectively. In DPPH assay, Nm.Aq, Nm.Cf, Nm.Hex and Nm.Cr were most potent exhibiting IC 50 values of 3, 5, 93 and 120 μg/ml respectively. In ABTS assay Nm.EtAc, Nm.Aq, Nm.Sp and Nm.Cr showed IC 50 values of 60, 95, 100 and 150 μg/mL respectively. Likewise ABTS inhibition was most prominent for Nm.Sp, Nm.EtAc and Nm.Aq causing 78.26 ± 0.49, 67.67 ± 0.73 and 63.58 ± 0.45% inhibition respectively at 1 mg/mL. These results were further confirmed by qualitative screening using DPPH and ABTS staining., Conclusions: Our anticholinesterase and antioxidant results signify the N. micrantha as a potential source of natural bioactive compounds. Moreover isolation of natural bioactive compounds from this plant may lead to novel drug candidates against neurodegenerative disorders.

This study was designed to investigate antioxidant and anticholinesterase potential of Iris germanica var; florentina. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory potential of plant samples were investigated by Ellman's assay. Antioxidant activity was performed using DPPH, H2O2 and ABTS free radical scavenging assays. Total phenolics and flavonoids contents were expressed in mg GAE/g dry weight and mg RTE/g, respectively. In AChE inhibition assay, Ig.Fl, Ig.Sp and Ig.Cf fractions exhibited highest activity with IC50 values of < 0.1, 5.64 and 19 μg/mL, respectively. In BChE inhibitory assay, Ig.Fl, Ig.Sp, Ig.Cf and Ig.Cr were most active with IC50 of < 0.1, < 0.1, 31 and 78 μg/mL, respectively. In DPPH assay, Ig.Fl and Ig.Cf exhibited highest inhibition of free radicals, 80.52% (IC50 = 9 μg/mL) and 78.30% (IC50 = 8 μg/mL), respectively. In ABTS assay Ig.Cr, Ig.Cf, Ig.Fl and Ig.Sp exhibited IC50 values of < 0.1, 2, 2 and 3 μg/mL, respectively.

Background: Ethnomedicinally Rumex hastatus D. Don has been used since long for various ailments especially in neurological disorders. The reported data and the importance of Rumex genus demonstrate the vital medicinal value of R. hastatus., Methods: In the current investigational study, isolation of essential oil and its antioxidant and anticholinesterase assays were performed. The essential oil of R. hastatus was analyzed by GC-MS for the first time. The essential oil was evaluated for anticholinesterase and antioxidant assays. The anticholinesterase assay was conducted at various concentrations (62.5 to 1000 μg/ml) against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Similarly, the antioxidant potential was determined using DPPH and ABTS free radicals., Results: The GC-MS analysis of essential oil showed 123 components. The result recorded for the anticholinesterase assays demonstrated a marked potential against AChE and BChE with IC50 values of 32.54 and 97.38 μg/ml respectively which were comparable with the positive control i.e., galanthamine (AChE, IC50 = 4.73 μg/ml and BChE, IC50 = 11.09 μg/ml). The antioxidant assays against DPPH and ABTS free radicals also exhibited significant scavenging potential with IC50 values of 3.71 and 6.29 μg/ml respectively, while for ascorbic acid the IC50 value was <0.1 μg/ml against both free radicals., Conclusions: Based on the current investigational studies, it may be concluded that R. hastatus is an effective source of essential oil's components having anticholinesterase and antioxidant potentials, which after subjecting to drug development may lead to novel drug candidates against neurodegenerative disorders.

Background: Atriplex laciniata L. was investigated for phenolic, flavonoid contents, antioxidant, anticholinesterase activities, in an attempt to explore its effectiveness in Alzheimer's and other neurological disorders. Plant crude methanolic extract (Al.MeF), subsequent fractions; n-hexane (Al.HxF), chloroform (Al.CfF), ethyl acetate (Al.EaF), aqueous (Al.WtF), Saponins (Al.SPF) and Flavonoids (Al.FLVF) were investigated for DPPH, ABTS and H2O2 free radical scavenging activities. Further these extracts were subjected to acetylcholinesterase (AChE) & butyrylcholinesterase (BChE) inhibitory activities using Ellman's assay. Phenolic and Flavonoid contents were determined and expressed in mg Gallic acid GAE/g and Rutin RTE/g of samples respectively., Results: In DPPH free radicals scavenging assay, Al.FLVF, Al.SPF and Al.MeF showed highest activity causing 89.41 ± 0.55, 83.37 ± 0.34 and 83.37 ± 0.34% inhibition of free radicals respectively at 1 mg/mL concentration. IC50 for these fractions were 33, 83 and 82 μg/mL respectively. Similarly, plant extracts showed high ABTS scavenging potential, i.e. Al.FLVF (90.34 ± 0.55), Al.CfF (83.42 ± 0.57), Al.MeF (81.49 ± 0.60) with IC50 of 30, 190 and 70 μg/ml respectively. further, H2O2 percent scavenging was highly appraised in Al.FLVF (91.29 ± 0.53, IC50 75), Al.SPF (85.35 ± 0.61, IC50 70) and Al.EaF (83.48 ± 0.67, IC50 270 μg/mL). All fractions exhibited concentration dependent AChE inhibitory activity as; Al.FLVF, 88.31 ± 0.57 (IC50 70 μg/mL), Al.SPF, 84.36 ± 0.64 (IC50 90 μg/mL), Al.MeF, 78.65 ± 0.70 (IC50 280 μg/mL), Al.EaF, 77.45 ± 0.46 (IC50 270 μg/mL) and Al.WtF 72.44 ± 0.58 (IC50 263 μg/mL) at 1 mg/mL. Likewise the percent BChE inhibitory activity was most obvious in Al.FLVF 85.46 ± 0.62 (IC50 100 μg/mL), Al.CfF 83.49 ± 0.46 (IC50 160 μg/mL), Al.MeF 82.68 ± 0.60 (IC50 220 μg/mL) and Al.SPF 80.37 ± 0.54 (IC50 120 μg/mL)., Conclusions: These results stipulate that A. laciniata is enriched with phenolic and flavonoid contents that possess significant antioxidant and anticholinestrase effects. This provide pharmacological basis for the presence of compounds that may be effective in Alzheimer's and other neurological disorders.

Background: Rumex species are traditionally used for the treatment of neurological disorders including headache, migraine, depression, paralysis etc. Several species have been scientifically validated for antioxidant and anticholinestrase potentials. This study aims to investigate Rumex hastatus D. Don crude methanolic extract, subsequent fractions, saponins and flavonoids for acetylcholinestrase, butyrylcholinestrase inhibition and diverse antioxidant activities to validate its folkloric uses in neurological disorders. Rumex hastatus crude methanolic extract (Rh. Cr), subsequent fractions; n-hexane (Rh. Hex), chloroform (Rh. Chf), ethyl acetate (Rh. EtAc), aqueous fraction (Rh. Aq), crude saponins (Rh. Sp) and flavonoids (Rh. Fl) were investigated against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) at various concentrations (125, 250, 500, 1000 μg/mL) using Ellman's spectrophotometric analysis. Antioxidant potentials of Rh. Sp and Rh. Fl were evaluated using DPPH, H2O2 and ABTS free radical scavenging assays at 62.5, 125, 250, 500, 1000 μg/mL., Results: All the test samples showed concentration dependent cholinesterase inhibition and radicals scavenging activity. The AChE inhibition potential of Rh. Sp and Rh. Fl were most prominent i.e., 81.67 ± 0.88 and 91.62 ± 1.67 at highest concentration with IC50 135 and 20 μg/mL respectively. All the subsequent fractions exhibited moderate to high AChE inhibition i.e., Rh. Cr, Rh. Hex, Rh. Chf, Rh. EtAc and Rh. Aq showed IC50 218, 1420, 75, 115 and 1210 μg/mL respectively. Similarly, against BChE various plant extracts i.e., Rh. Sp, Rh. Fl, Rh. Cr, Rh. Hex, Rh. Chf, Rh. EtAc and Rh. Aq resulted IC50 165, 175, 265, 890, 92, 115 and 220 μg/mL respectively. In DPPH free radical scavenging assay, Rh. Sp and Rh. Fl showed comparable results with the positive control i.e., 63.34 ± 0.98 and 76.93 ± 1.13% scavenging at 1 mg/mL concentration (IC50 312 and 104 μg/mL) respectively. The percent ABTS radical scavenging potential exhibited by Rh. Sp and Rh. Fl (1000 μg/mL) were 82.58 ± 0.52 and 88.25 ± 0.67 with IC50 18 and 9 μg/mL respectively. Similarly in H2O2 scavenging assay, the Rh. Sp and Rh. Fl exhibited IC50 175 and 275 μg/mL respectively., Conclusion: The strong anticholinesterase and antioxidant activities of Rh. Sp, Rh. Fl and various fractions of R. hastatus support the purported ethnomedicinal uses and recommend R. hastatus as a possible remedy for the treatment of AD and neurodegenerative disorders.

Background: Based on the ethnomedicinal uses and the effective outcomes of natural products in various diseases, this study was designed to evaluate Isodon rugosus as possible remedy in oxidative stress, alzheimer's and other neurodegenerative diseases. Acetylecholinestrase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of crude methanolic extract (Ir.Cr), resultant fractions (n-hexane (Ir.Hex), chloroform (Ir.Cf), ethyl acetate (Ir.EtAc), aqueous (Ir.Aq)), flavonoids (Ir.Flv) and crude saponins (Ir.Sp) of I. rugosus were investigated using Ellman's spectrophotometric method. Antioxidant potential of I. rugosus was determined using DPPH, H2O2 and ABTS free radicals scavenging assays. Total phenolic and flavonoids contents of plant extracts were determined and expressed in mg GAE/g dry weight and mg RTE/g of dry sample respectively., Results: Among different fractions Ir.Flv and Ir.Cf exhibited highest inhibitory activity against AChE (87.44 ± 0.51, 83.73 ± 0.64%) and BChE (82.53 ± 0.71, 88.55 ± 0.77%) enzymes at 1 mg/ml with IC50 values of 45, 50 for AChE and 40, 70 μg/ml for BChE respectively. Activity of these fractions were comparable to galanthamine causing 96.00 ± 0.30 and 88.61 ± 0.43% inhibition of AChE and BChE at 1 mg/ml concentration with IC50 values of 20 and 47 μg/ml respectively. In antioxidant assays, Ir.Flv, Ir.Cf, and Ir.EtAc demonstrated highest radicals scavenging activities in DPPH and H2O2 assays which were comparable to ascorbic acid. Ir.Flv was found most potent with IC50 of 19 and 24 μg/ml against DPPH and H2O2 radicals respectively. Whereas antioxidant activates of plant samples against ABTS free radicals was moderate. Ir.Cf, Ir.EtAc and Ir.Cr showed high phenolic and flavonoid contents and concentrations of these compounds in different fractions correlated well to their antioxidant and anticholinestrase activities., Conclusion: It may be inferred from the current investigations that the Ir.Sp, Ir.Flv and various fractions of I. rugosus are good sources of anticholinesterase and antioxidant compounds. Different fractions can be subjected to activity guided isolation of bioactive compounds effective in neurological disorders.

Background: Oxidative stress and analgesia are connected with different pathological conditions. The drug candidates from synthetic sources are associated with various side effects; therefore, researchers are giving priority to find novel, effective and safe phytomedicines. Teucrium species possesses antioxidant, analgesic, anti-inflammatory and hepatoprotective activities. The essential oils of Teucrium stocksianum have shown strong antinociceptive potential. Our current study is designed to embark total phenolic content (TPC), antioxidant and antinociceptive potential of the methanolic extract of Teucrium stocksianum (METS)., Method: Phytochemical composition was determined by using standard methods. Free radical scavenging potential and TPC of METS were assessed by using 2, 2-diphenyl-1-picryl-hydrazyl (DPPH) and Folin-Ciocalteu Reagent (FCR) respectively. Antinociceptive potential was determined by acetic acid induced abdominal writhing, formalin induced paw licking and tail immersion tests. Different test dose 50, 100 and 150 mg/kg body weight of METS were administered intra peritonealy (i.p) to various groups of mice for the evaluation of analgesic potential., Results: Phytochemical screening confirmed the presence of flavonoids, tannins, saponins, anthraquinone, steroid, phlobatannin, terpenoid, glycoside and reducing sugars. METS was found safe at a dose of 1000 mg/kg body weight. A concentration dependent free radical scavenging effect was observed with methanolic aerial parts extract of Teucrium stocksianum (MAPETS) and methanolic roots extracts of Teucrium stocksianum (MRETS). MAPETS and MRETS have shown highest antioxidant activity 91.72% and 86.19% respectively at 100 μg/ml. MAPETS was found more rich (115.32 mg of GAE/g of dry material) in TPC as compared to MAPETS (105.41 mg of GAE/g). METS demonstrated a dose dependent antinociceptive potential in different pain models, like in acetic acid, formalin and tail immersion showing 83.103%, 80.872% and 67.58% at a dose of 150 mg/kg, similar to acetylsalicylic acid (74.79%, 82.87%, 100 mg/kg) and TramadolR (74%, 30 mg/kg) respectively., Conclusion: Strong antioxidant potential and high TPCs are residing in the methanolic extract of T. stocksianum. METS showed analgesic potential in all models of nociception implying that both peripheral and central pathways of analgesia are involved. This might be due to the presence of various classes of phytochemicals in the plant extract.

Background: We investigated Polygonum hydropiper L. (P. hydropiper) for phenolic contents, antioxidant, anticholinesterase activities, in an attempt to rationalize its use in neurological disorders., Methods: Plant crude extract (Ph.Cr), its subsequent fractions: n-hexane (Ph.Hex), chloroform (Ph.Chf), ethyl acetate (Ph.EtAc), n-Butanol (Ph.Bt), aqueous (Ph.Aq) and saponins (Ph.Sp) were evaluated for 1,1-diphenyl,2-picrylhydrazyl (DPPH), 2,2-azinobis[3-ethylbenzthiazoline]-6-sulfonic acid (ABTS) free radical scavenging potential. Further, acetylcholinesterase (AChE) & butyrylcholinesterase (BChE) inhibitory activities were performed using Ellman's assay. Moreover, total phenolic contents of plant extracts were determined and expressed in mg of gallic acid equivalent per gram of dry sample (mg GAE/g dry weight)., Results: Among different fractions, Ph.Cr (90.82), Ph.Chf (178.16), Ph.EtAc (203.44) and Ph.Bt (153.61) exhibited high phenolic contents. All fractions showed concentration dependent DPPH scavenging activity, with Ph.EtAc 71.33% (IC50 15 μg/ml), Ph.Bt 71.40% (IC50 3 μg/ml) and Ph.Sp 71.40% (IC50 35 μg/ml) were most potent. The plant extracts exhibited high ABTS scavenging ability i.e. Ph.Bt (91.03%), Ph.EtAc (90.56%), Ph.Sp (90.84%), Ph.Aq (90.56%) with IC50<0.01 μg/ml. All fractions showed moderate to high AChE inhibitory activity as; Ph.Cr, 86.87% (IC50 330 μg/ml), Ph.Hex, 87.49% (IC50 35 μg/ml), Ph.Chf, 84.76% (IC50 55 μg/ml), Ph.Sp, 87.58% (IC50 108 μg/ml) and Ph.EtAc 79.95% (IC50 310 μg/ml) at 1 mg/ml). Furthermore the BChE inhibitory activity was most prominent in Ph.Hex 90.30% (IC50 40 μg/ml), Ph.Chf 85.94% (IC50 215 μg/ml), Ph.Aq 87.62% (IC50 3 μg/ml) and Ph.EtAc 81.01% (IC50 395 μg/ml) fractions., Conclusions: In this study, for the first time, we determined phenolic contents, isolated crude saponins, investigated antioxidant and anticholinestrase potential of P. hydropiper extracts. The results indicate that P. hydropiper is enriched with potent bioactive compounds and warrant further investigation by isolation and structural elucidation to find novel and affordable compounds for the treatment of various neurological disorders.

Aceclofenac (ACF) is a newer derivative of diclofenac, and one of the emerging NSAIDs for the treatment of various inflammatory diseases. In this research we have develop a set of 2‐(2‐(2‐((2,6‐dichlorophenyl)amino)phenyl)acetoxy)acetic acid derivatives (AR1‐AR12) using Fischer esterification in good yields and in an efficient manner. All the compounds were fully characterized physical (solubility and melting points) and chemical by spectral data analysis of FTIR, 1HNMR and 13CNMR and elemental analysis. In‐vitro anti‐inflammatory activity was performed by Chemiluminescence technique in which we found 2‐oxo‐1,2‐diphenylethyl2‐(2‐(2((2,6‐dichlorophenyl)amino)phenyl) acetoxy)acetate (AR2 71 %), 2‐(4‐formyl‐2‐methoxyphenoxy)‐2‐oxoethyl2‐(2‐((2,6 dichloro‐phenyl) amino)phenyl)acetate (AR3 74.7 %),2‐(2‐(2‐(2‐((2,6‐dichloropheny l)amino) phenyl) acetoxy) acetoxy)‐3‐(2‐(2‐(3‐((2,6‐dichlorophenyl) amino) phenyl) acetoxy)acetoxy)succinic acid (AR6 89.2 %), 2‐(4‐aminophenoxy)‐2‐oxoethyl2‐(2‐((2,6‐dichloro‐phenyl) amino) phenyl) acetate (AR8 71.1 %), 1,3‐dioxo‐2,3‐dihydro‐1H‐indene‐2,2‐diyl bis(2‐(2‐(2‐((2,6‐dichlorophenyl)amino)phenyl)acetoxy)acetate) (AR9 76.3 %) found more potent as compared to parent compound while AR3, AR6 and AR9 highly potent than standard reference ibuprofen (73.2 %). The current molecular docking study was performed In order to check the suitable method for the binding of target ligands and proteins Glide docking with extra precision (XP) mode. The hydrogen bonding interactions of Aceclofenac are prominent with Isoleucine moiety, those of compound AR‐6 shows hydrophobic interaction with active amino acid Leucine and Phenylalanine moieties. Anti‐oxidant activities were also performed, AR‐3 (79.30 %), AR‐5 (91.23 %), AR‐9 (83.43 %) AR‐12 (92.43 %) were found to be more anti‐oxidant as compared to aceclofenac (ACF) (66.46 %). These derivatives were synthesized with different aliphatic and aromatic alcohols and phenols. [ABSTRACT FROM AUTHOR]

Based on the diverse pharmacological potency and the structural features of succinimide, this research considered to synthesize succinimide derivatives. Moreover, these compounds were estimated for their biological potential in terms of anti-diabetic, anti-cholinesterase, and anti-oxidant capacities. The compounds were synthesized through Michael addition of various ketones to N-aryl maleimides. Similarly, the MOE software was used for the molecular docking study to explore the binding mode of the potent compounds against different enzymes. In the anti-cholinesterase activity, the compounds MSJ2 and MSJ10 exhibited outstanding activity against acetylcholinesterase (AChE), i.e., 91.90, 93.20%, and against butyrylcholinesterase (BChE), i.e., 97.30, 91.36% inhibitory potentials, respectively. The compounds MSJ9 and MSJ10 exhibited prominent α-glucosidase inhibitory potentials, i.e., 87.63 and 89.37 with IC50 value of 32 and 28.04 μM, respectively. Moreover, the compounds MSJ2 and MSJ10 revealed significant scavenging activity against DPPH free radicals with IC50 values of 2.59 and 2.52, while against ABTS displayed excellent scavenging potential with IC50 values 7.32 and 3.29 μM, respectively. The tentative results are added with molecular docking studies in the active sites of enzymes to predict the theoretical protein-ligand binding modes. Further detailed mechanism-based studies in animal models are essential for the in vivo evaluation of the potent compound. [ABSTRACT FROM AUTHOR]

Introduction. Natural products are among the most useful sources for the discovery of new drugs against various diseases. Keeping in view the ethnobotanical relevance ethnopharmacological significance of Polygonaceae family in diabetes, the current study was designed to isolate pure compounds from Persicaria hydropiper L. leaves and evaluate their in vitro and in silico antidiabetic potentials. Methods. Six compounds were isolated from the chloroform-ethyl acetate fractions using gravity column chromatography and were subjected to structure elucidation process. Structures were confirmed using 1H-NMR, 13C-NMR, and mass spectrometry techniques. Isolated phytochemicals were subjected to in vitro antidiabetic studies, including α-glucosidase, α-amylase inhibition, and DPPH, and ABTS antioxidant studies. Furthermore, the in silico binding mode of these compounds in the target enzymes was elucidated via MOE-Dock software. Results. The isolated compounds revealed concentration-dependent inhibitions against α-glucosidase enzyme. Ph-1 and Ph-2 were most potent with 81.84 and 78.79% enzyme inhibitions at 1000 µg·mL−1, respectively. Ph-1 and Ph-2 exhibited IC50s of 85 and 170 µg·mL−1 correspondingly. Likewise, test compounds showed considerable α-amylase inhibitions with Ph-1 and Ph-2 being the most potent. Tested compounds exhibited considerable antioxidant potentials in both DPPH and ABTS assays. Molecular simulation studies also revealed top-ranked confirmations for the majority of the compounds in the target enzymes. Highest observed potent compound was Ph-1 with docking score of −12.4286 and formed eight hydrogen bonds and three H-pi linkages with the Asp 68, Phe 157, Phe 177, Asn 241, Glu 276, His 279, Phe 300, Glu 304, Ser 308, Pro 309, Phe 310, Asp 349, and Arg 439 residues of α-glucosidase binding packets. Asp 68, Glu 276, Asp 349, and Arg 439 formed polar bonds with the 3-ethyl-2-methylpentane moiety of the ligand. Conclusions. The isolated compounds exhibited considerable antioxidant and inhibitory potentials against vital enzymes implicated in T2DM. The docking scores of the compounds revealed that they exhibit affinity for binding with target ligands. The enzyme inhibition and antioxidant potential of the compounds might contribute to the hypoglycemic effects of the plant and need further studies. [ABSTRACT FROM AUTHOR]

Isodon rugosus Wall. ex. Benth is an important species and is used in folk medicine for different types of pains such as abdominal pain, earache, toothache, gastric, and generalized body pain. Recently, we also have reported the antinociceptive potential of chloroform fraction of I. rugosus. In this research, we have investigated the antinociceptive, antioxidant and anti-cholinesterase potentials of essential oils from I. rugosus (Ir.EO), and have determined a possible mechanism of anti-nociception. The Ir.EO was subjected to gas chromatography-mass spectroscopy analysis to find out its chemical constituents. The Ir.EO was assayed for analgesic potential following acetic acid induced writhing, formalin test and hot plate method in animal models. The antioxidant activity was conducted against DPPH and ABTS free radicals following spectroscopic analysis. The cholinesterase inhibitory assays were performed using Ellman's assay. The GC-MS analysis of Ir.EO revealed the identification of 141 compounds. Ir.EO demonstrated strong antinociceptive potential in all three in-vivo models. With the use of nalaxone, it was confirmed that the essential oil was acting on the central pathway of nociception. The Ir.EO also exhibited strong free radicals scavenging potential, exhibiting IC50 values of 338 and 118μg/ml for DPPH and ABTS free radicals respectively. In AChE and BChE inhibitory assays, the observed IC50 values were 93.56 and 284.19μg/ml respectively. The encouraging antinociceptive, antioxidant and anticholinesterase results revealed that Ir.EO is a rich source of bioactive compounds as obvious from the GC-MS results. [ABSTRACT FROM AUTHOR]

Coordination behavior of 4,5,6,7-tetrahydro-1H-indazole (H-Ind) with Cu(II), Co(II), and Ag(I) was studied. The ligand affords complexes bearing different geometries depending upon the metal and anion present in the starting salts. Five compounds with different structural perspectives, trans-[CuCl2(H-Ind)4] (1), trans-[CuBr2(H-Ind)4] (2), trans-[Cu(CH3COO)2(H-Ind)2] (3), trans-[CoCl2(H-Ind)4] (4), and [Ag(H-Ind)2]NO3 (5), were obtained. The ligand adopts tetrahydro-1H-indazole isomeric form in Cu(II) and Co(II) complexes and with Ag(I) ion the same ligand adopts tetrahydro-2H-indazole form. In the case of sterically demanding acetate counter ion in contrast to Cl or Br, the Cu(II) ion accepts two equivalents of the ligand and four-coordinated square planar complex was obtained. With AgNO3, the expected complex was obtained. The yield of reactions was >80% and all complexes were obtained as crystalline material from the reaction mixtures. Their structures were determined by X-ray diffraction and all complexes were tested for antibacterial (Enterobacter sakazkii, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniea), antifungal (Aspergillus flavus, Aspergillus fumegatus, Aspergillus nigar, Fusarium oxysporium), and antioxidant (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH)) activities. The same were also tested as inhibitors against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). [ABSTRACT FROM AUTHOR]

Crataegus oxyacantha is an important herbal supplement and famous for its antioxidant potential. The antioxidant in combination with anticholinesterase activity can be considered as an important target in the management of Alzheimer's disease. The compounds isolated from C. oxyacantha were evaluated for cholinesterases inhibitory activity using Ellman's assay with Galantamine as standard drug. Total of nine (1-9) compounds were isolated. Compounds 1 and 2 were isolated for the first time from natural source. Important natural products like b-Sitosterol-3-O-b-D-Glucopyranoside (3), lupeol (4), b-sitosterol (5), betulin (6), betulinic acid (7), oleanolic acid (8), and chrysin (9) have also been isolated from C. oxyacantha. Overall, all the compounds exhibited an overwhelming acetylcholinesterase (AChE) inhibition potential in the range 5.22-44.47 μM. The compound 3 was prominent AChE inhibitor with IC50 value of 5.22 μM. Likewise, all the compounds were also potent in butyrylcholinesterase (BChE) inhibitions with IC50s of up to 0.55-15.36 mM. All the compounds, except 3, were selective toward BChE. Mechanism of the inhibition of both the enzymes were further studied by docking procedures using Genetic Optimization for Ligand Docking suit v5.4.1. Furthermore, computational blood brain barrier prediction of the isolated compounds suggest that these are BBBC. [ABSTRACT FROM AUTHOR]

The use of essential oils (EOs) and their components is known since long in traditional medicine and aromatherapy for the management of various diseases, and is further increased in the recent times. The neuroprotective and anti-aging potentials of EOs and their possible mechanism of actions were evaluated by numerous researchers around the globe. Several clinically important EOs and their components from Nigella sativa, Acorus gramineus, Lavandula angustifolia, Eucalyptus globulus, Mentha piperita, Rosmarinus officinalis, Jasminum sambac, Piper nigrum and so many other plants are reported for neuroprotective effects. This review article was aimed to summarize the current finding on EOs tested against neurodegenerative disorders like Alzheimer disease (AD) and dementia. The effects of EOs on pathological targets of AD and dementia including amyloid deposition (Ab), neurofibrillary tangles (NFTs), cholinergic hypofunction, oxidative stress and glutamatergic abnormalities were focused. Furthermore, effects of EOs on other neurological disorders including anxiety, depression, cognitive hypofunction epilepsy and convulsions were also evaluated in detail. In conclusion, EOs were effective on several pathological targets and have improved cognitive performance in animal models and human subjects. Thus, EOs can be developed as multi-potent agents against neurological disorders with better efficacy, safety and cost effectiveness. [ABSTRACT FROM AUTHOR]

Background: Ethnomedicinally Rumex hastatus D. Don has been used since long for various ailments especially in neurological disorders. The reported data and the importance of Rumex genus demonstrate the vital medicinal value of R. hastatus. Methods: In the current investigational study, isolation of essential oil and its antioxidant and anticholinesterase assays were performed. The essential oil of R. hastatus was analyzed by GC-MS for the first time. The essential oil was evaluated for anticholinesterase and antioxidant assays. The anticholinesterase assay was conducted at various concentrations (62.5 to 1000 µg/ml) against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Similarly, the antioxidant potential was determined using DPPH and ABTS free radicals. Results: The GC-MS analysis of essential oil showed 123 components. The result recorded for the anticholinesterase assays demonstrated a marked potential against AChE and BChE with IC50 values of 32.54 and 97.38 µg/ml respectively which were comparable with the positive control i.e., galanthamine (AChE, IC50 = 4.73 µg/ml and BChE, IC50 = 11.09 µg/ ml). The antioxidant assays against DPPH and ABTS free radicals also exhibited significant scavenging potential with IC50 values of 3.71 and 6.29 µg/ml respectively, while for ascorbic acid the IC50 value was <0.1 µg/ml against both free radicals. Conclusions: Based on the current investigational studies, it may be concluded that R. hastatus is an effective source of essential oil's components having anticholinesterase and antioxidant potentials, which after subjecting to drug development may lead to novel drug candidates against neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Background: Cholinesterase inhibition is a vital target for the development of novel and mechanism based inhibitors, owing to their role in the breakdown of acetylcholine (ACh) neurotransmitter to treat various neurological disorders including Alzheimer's disease (AD). Similarly, free radicals are implicated in the progression of various diseases like neurodegenerative disorders. Due to lipid solubility and potential to easily cross blood brain barrier, this study was designed to investigate the anticholinesterase and antioxidant potentials of the standardized essential oils from the leaves and flowers of Polygonum hydropiper. Methods: Essential oils from the leaves (Ph.LO) and flowers (Ph.FO) of P. hdropiper were isolated using Clevenger apparatus. Oil samples were analyzed by GC-MS to identify major components and to attribute the antioxidant and anticholinesterase activity to specific components. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory potentials of the samples were determined following Ellman's assay. Antioxidant assays were performed using 1,1-diphenyl,2-picrylhydrazyl (DPPH), 2,2-azinobis[3-ethylbenzthiazoline]-6-sulfonic acid (ABTS) and hydrogen peroxide (H2O2) free radical scavenging assays. Results: In the GC-MS analysis 141 and 122 compounds were indentified in Ph.LO and Ph.FO respectively. Caryophylene oxide (41.42 %) was the major component in Ph.FO while decahydronaphthalene (38.29 %) was prominent in Ph.LO. In AChE inhibition, Ph.LO and Ph.FO exhibited 87.00** and 79.66***% inhibitions at 1000 µg/ml with IC50 of 120 and 220 µg/ml respectively. The IC50 value for galanthamine was 15 µg/ml. In BChE inhibitory assay, Ph.LO and Ph.FO caused 82.66*** (IC50 130 µg/ml) and 77.50***% (IC50 225 µg/ml) inhibitions respectively at 1000 µg/ml concentration. In DPPH free radical scavenging assay, Ph.LO and Ph.FO exhibited IC50 of 20 and 200 µg/ml respectively. The calculated IC50s were 180 & 60 µg/ml for Ph.LO, and 45 & 50 µg/ml for Ph.FO in scavenging of ABTS and H2O2 free radicals respectively. Conclusions: In the current study, essential oils from leaves and flowers of P. hydropiper exhibited dose dependent anticholinesterase and antioxidant activities. Leaves essential oil were more effective and can be subjected to further in-vitro and in-vivo anti-Alzheimer's studies. [ABSTRACT FROM AUTHOR]

Polygonum hydropiper L. and related species are reported to possess neuroprotective potentials. In an attempt to validate its anti-Alzheimer's potentials, leaf oils (Ph. Lo) were extensively evaluated in this study against several in vitro and in vivo models of Alzheimer's disease. The Ph. Lo were tested against pathological targets of Alzheimer's diseases (ADs). The in vitro and in vivo assays were done for cholinesterase inhibition, anti-radical properties and cognitive assessments using transgenic animal models. In preliminary cholinesterase inhibition assays, Ph. Lo were more active against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2-azinobis (3-ethylbenzthiazoline)-6-sulfonic acid (ABTS), and hydrogen peroxide (H2O2) radicals. Subsequently, Ph. Lo was evaluated for its effects on special memory, exploratory behavior, and coordination using shallow water maze (SWM), Y-maze, open filed, and balance beam tests. Animal pre-genotyping was done via polymerase chain reaction (PCR) to confirm amyloid precursor protein (APP) transgene, and after completion of drug therapy, brain homogenates from the cortex and hippocampus were evaluated for cholinesterase and free radical studies. In SWM task, disease control animals treated with 10 mg/kg of Ph. Lo for 5 days exhibited significant improvement in cognitive performance indicated by low escape times on 5th day compared with normal animals. In the Y-maze test, transgenic animals showed higher spontaneous alternation behavior than disease control animals and standard control group animals. Ph. Lo therapy has improved the exploratory behavior and declined anxiety behavior in diseased animals as accessed via open field test. Ph. Lo administration significantly augmented the motor and coordination abilities of transgenic animals when compared to other groups of animals and declined AChE, BChE activities as well as free radicals load in the cortex and hippocampus tissues. Based on our finding, it is concluded that Ph. Lo exhibit significant neuroprotective potentials preliminary due to their anti-radicals and cholinesterase inhibitory activities. Ph. Lo need further detailed studies as potential aromatherapy against neurodegenerative disorders. [ABSTRACT FROM AUTHOR]