Anticholinesterase Activity of Eight Medicinal Plant Species: In Vitro and in Silico Studies in the Search for Therapeutic Agents against Alzheimer's Disease

Many Bangladeshi medicinal plants have been used to treat Alzheimer's disease and other neurodegenerative diseases. In the present study, the anticholinesterase effects of eight selected Bangladeshi medicinal plant species were investigated. Species were selected based on the traditional uses against CNS-related diseases. Extracts were prepared using a gentle cold extraction method. In vitro cholinesterase inhibitory effects were measured by Ellman's method in 96-well microplates. Blumea lacera (Compositae) and Cyclea barbata (Menispermaceae) were found to have the highest acetylcholinesterase inhibitory (IC50, 150 11 and 176 14 g/mL, respectively) and butyrylcholinesterase inhibitory effect (IC50, 297 13 and 124 2 g/mL, respectively). Cyclea barbata demonstrated competitive inhibition, where Blumea lacera showed an uncompetitive inhibition mode for acetylcholinesterase. Smilax guianensis (Smilacaceae) and Byttneria pilosa (Malvaceae) were also found to show moderate AChE inhibition (IC50, 205 31 and 221 2 g/mL, respectively), although no significant BChE inhibitory effect was observed for extracts from these plant species. Among others, Thunbergia grandiflora (Acanthaceae) and Mikania micrantha (Compositae) were found to display noticeable AChE (IC50, 252 22 g/mL) and BChE (IC50, 314 15 g/mL) inhibitory effects, respectively. Molecular docking experiment suggested that compounds 5-hydroxy-3,6,7,3,4-pentamethoxyflavone (BL4) and kaempferol-3-O-α-L-rhamnopyranosyl-(1LongRightArrow6)-β-D-glucopyranoside (BL5) from Blumea lacera bound stably to the binding groove of the AChE and BChE by hydrogen-bond interactions, respectively. Therefore, these compounds could be candidates for cholinesterase inhibitors. The present findings demonstrated that Blumea lacera and Cyclea barbata are interesting objects for further studies aiming at future therapeutics for Alzheimer's disease

In Vitro Screening for Antioxidant and Anticholinesterase Effects of Uvaria littoralis Blume.: A Nootropic Phytotherapeutic Remedy

Background: Oxidative stress is strongly linked in the development of numerous chronic and degenerative disorders. Medicinal plants with antioxidant and anticholinesterase activities exert a key role for the management of oxidative stress related disorders mainly Alzheimer's disease (AD). Therefore the purpose of this study was to assess antioxidant potentiality and anticholinesterase inhibitory activity of crude methanolic extract (CME), petroleum ether fraction (PEF), chloroform fraction (CLF), ethyl acetate fraction (EAF) and aqueous fraction (AQF) of Uvaria littoralis (U. littoralis) leaves. Methods: The antioxidant compounds namely total flavonoids contents (TFCs) and total proanthocyanidins contents (TPACCs) were determined for quantities constituent’s characterization. Antioxidant capacity of U. littoralis leaves were estimated by the iron reducing power (IRPA), 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and nitric oxide (NO) radical scavenging capacity. Anticholinesterase effects were estimated for acetylcholinesterase (AChE) and butyrylcholinestrase (BChE) activity. Results: The EAF of U. littoralis leaves showed the highest TFCs as compared to CLF, CME, PEF and AQF. TPACCs were also found highest in EAF. The highest absorbance for IRPA was found in EAF (2.220 nm) with respect to CME and other fractions at the highest concentration. The EAF showed best DPPH and NO radical scavenging activity with IC50 values of 31.63 and 55.47 μg/mL, respectively with regard to CME and remaining fractions. The PEF represents highest AChE inhibitory activity with IC50 values of 35.19 μg/mL and CLF showed highest BChE inhibitory activity with IC50 values of 32.49 μg/mL. Conclusions: The findings of the current study demonstrate the presence of antioxidant phytochemicals, likewise, turns out antioxidant and anticholinesterase potentiality of U. littoralis leaves which could be a prestigious candidate for the treatment of neurodegenerative diseases especially AD

Bioactive Abietane-Type Diterpenoid Glycosides from Leaves of Clerodendrum infortunatum (Lamiaceae)

In this study, two previously undescribed diterpenoids, (5R,10S,16R)-11,16,19-trihydroxy-12-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranosyl-17(15→16),18(4→3)-diabeo-3,8,11,13-abietatetraene-7-one (1) and (5R,10S,16R)-11,16-dihydroxy-12-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranosyl-17(15→16),18(4→3)-diabeo-4-carboxy-3,8,11,13-abietatetraene-7-one (2), and one known compound, the C13-nor-isoprenoid glycoside byzantionoside B (3), were isolated from the leaves of Clerodendrum infortunatum L. (Lamiaceae). Structures were established based on spectroscopic and spectrometric data and by comparison with literature data. The three terpenoids, along with five phenylpropanoids: 6'-O-caffeoyl-12-glucopyranosyloxyjasmonic acid (4), jionoside C (5), jionoside D (6), brachynoside (7), and incanoside C (8), previously isolated from the same source, were tested for their in vitro antidiabetic (α-amylase and α-glucosidase), anticancer (Hs578T and MDA-MB-231), and anticholinesterase activities. In an in vitro test against carbohydrate digestion enzymes, compound 6 showed the most potent effect against mammalian α-amylase (IC50 3.4 ± 0.2 μM) compared to the reference standard acarbose (IC50 5.9 ± 0.1 μM). As yeast α-glucosidase inhibitors, compounds 1, 2, 5, and 6 displayed moderate inhibitory activities, ranging from 24.6 to 96.0 μM, compared to acarbose (IC50 665 ± 42 μM). All of the tested compounds demonstrated negligible anticholinesterase effects. In an anticancer test, compounds 3 and 5 exhibited moderate antiproliferative properties with IC50 of 94.7 ± 1.3 and 85.3 ± 2.4 μM, respectively, against Hs578T cell, while the rest of the compounds did not show significant activity (IC50 > 100 μM)

Ethnomedicinal Value of Antidiabetic Plants in Bangladesh: A Comprehensive Review

The use of conventional drugs to treat metabolic disorders and the pathological consequences of diabetes further increases the complications because of the side effects, and is sometimes burdensome due to relatively higher costs and occasionally painful route of administration of these drugs. Therefore, shifting to herbal medicine may be more effective, economical, have fewer side effects and might have minimal toxicity. The present review amasses a list of ethnomedicinal plants of 143 species belonging to 61 families, from distinctive domestic survey literature, reported to have been used to treat diabetes by the ethnic and local people of Bangladesh. Leaves of the medicinal plants were found leading in terms of their use, followed by fruits, whole plants, roots, seeds, bark, stems, flowers, and rhizomes. This review provides starting information leading to the search for and use of indigenous botanical resources to discover bioactive compounds for novel hypoglycemic drug development

Insights into the leaves of Ceriscoides campanulata: Natural proanthocyanidins alleviate diabetes, inflammation, and esophageal squamous cell cancer via in vitro and in silico models

Fourteen flavones (1–14) including twelve polymethoxylated flavones, two A-type proanthocyanidins (oligomeric flavonoids) (15, 16), one benzoyl glucoside (17), one triterpenoid (18), and one phenylpropanoid (19) were isolated from the leaves of the South Asian medicinal plant Ceriscoides campanulata (Roxb.) Tirveng (Rubiaceae). The structures of the compounds were identified based on their spectroscopic and spectrometric data and in comparison with literature data. Isolated compounds were tested in vitro against inflammatory enzymes (COX-2, iNOS), pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), esophageal squamous carcinoma cell line (TE13), and carbohydrate digestion enzymes (α-amylase, α-glucosidase). Proanthocyanidins 15 and 16 significantly attenuated the LPS-induced inflammatory response of COX-2, iNOS, IL-1β, IL-6, TNF-α in RAW 264.7 cells. Proanthocyanidins also satisfactorily inhibited the regrowth (64%), migration (51%), and formation of tumor-spheres (48%) in ESCC cell line TE13 at 50% toxic concentration. Compounds 15 and 16 showed the most potent effect against mammalian α-amylase (IC50 8.4 ± 0.3 μM and 3.5 ± 0.0 μM, respectively) compared to reference standard acarbose (IC50 5.9 ± 0.1 μM). As yeast α-glucosidase inhibitors, compounds 15 and 16 also displayed significant activities (IC50 6.2 ± 0.3 and 4.7 ± 0.1 μM, respectively), while compounds 1–6 displayed weaker α-glucosidase inhibitory activities, ranging from 49 to 142 μM, compared to acarbose (IC50 665 ± 42 μM). In an anticholinesterase assay, compounds 1, 2, 6 (IC50 51 ± 2, 53 ± 7, 64 ± 5 μM, respectively), and 4 (IC50 44 ± 1 μM) showed moderate inhibitory activities against acetylcholinesterase and butyrylcholinesterase, respectively. Furthermore, molecular docking and molecular dynamic simulation analyses of compounds 15 and 16 were performed against human pancreatic α-amylase and human lysosomal acid α-glucosidase to elucidate the interactions of these compounds in the respective enzymes\u27 active sites

In vitro antioxidative and cholinesterase inhibitory properties of Thunbergia grandiflora leaf extract

Among the pathologic hypotheses of Alzheimer’s disease (AD), cholinergic deficit and oxidative stress have been implicated as two major hallmarks. Therefore, inhibition of cholinesterase and oxidation are the two promising strategies in the development of a drug for AD. Thunbergia grandiflora leaf extract (TGEx) is used in this research to investigate its anticholinesterase and antioxidant potentials. Anticholinesterase activity was measured by modified Ellman method. Antioxidant potentials were evaluated by the assay of reducing power, radical scavenging and inhibition of lipid peroxidation. The Methanolic extract showed strong anticholinesterase effect. Additionally, the extract exhibited pronounced reducing capacity, radical scavenging ability, and lipid peroxidation inhibitory effect. The IC50 values of the extract for DPPH and hydroxyl free radical scavenging and lipid peroxidation were 10.50 ± 0.68, 24.98 ± 1.39 and 21.84 ± 0.91 μg/ml, respectively. Phytochemical screening of the extract revealed the presence of significant amount of total phenolics and flavonoids. The tested sample reflects potential antioxidative and anticholinesterase inhibitory effect which may warrant its effectiveness in the treatment of AD

Antinociceptive and Anxiolytic and Sedative Effects of Methanol Extract of Anisomeles indica: An Experimental Assessment in Mice and Computer Aided Models

Anisomeles indica (L.) kuntze is widely used in folk medicine against various disorders including allergy, sores, inflammation, and fever. This research investigated the antinociceptive, anxiolytic and sedative effects of A. indica methanol extract. The antinociceptive activity was assessed with the acetic acid-induced writhing test and formalin-induced flicking test while sedative effects with open field and hole cross tests and anxiolytic effects with elevated plus maze (EPM) and thiopental-induced sleeping time tests were assayed. Computer aided (pass prediction, docking) analyses were undertaken to find out the best-fit phytoconstituent of total 14 isolated compounds of this plant for aforesaid effects. Acetic acid treated mice taking different concentrations of extract (50, 100, and 200 mg/kg, intraperitoneal) displayed reduced the writhing number. In the formalin-induced test, extract minimized the paw licking time of mice during the first phase and the second phase significantly. The open field and hole-cross tests were noticed with a dose-dependent reduction of locomotor activity. The EPM test demonstrated an increase of time spent percentage in open arms. Methanol extract potentiated the effect of thiopental-induced hypnosis in lesser extent comparing with Diazepam. The results may account for the use of A. indica as an alternative treatment of antinociception and neuropharmacological abnormalities with further intensive studies. The compound, 3,4-dihydroxybenzoic acid was found to be most effective in computer aided models

In vitro antioxidant and cholinesterase inhibitory activities of Elatostema papillosum leaves and correlation with their phytochemical profiles: a study relevant to the treatment of Alzheimer’s disease

Abstract Background Alzheimer’s disease (AD), one of the major causes of dementia, is an overwhelming neurodegenerative disease that particularly affects the brain, leading to memory loss and impairment of language and judgment capacity. The aim of the present study was to investigate the antioxidant and anticholinesterase properties of the leaves of Elatostema papillosum (EPL) and correlate with their phytochemical profiles, which are relevant to the treatment of AD. Methods The dried coarse powder of EPL was extracted with 80% methanol (EPL-M80) by cold extraction method. The resultant EPL-M80 was assessed for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity by the Ellman method. The antioxidant activity was determined by DPPH (1, 1-diphenyl-2-picrylhydrazyl) and hydroxyl radical scavenging assays. Quantitative phytochemical (phenolic and flavonoid contents) analysis of endogenous substances in EPL-M80 was performed by standard spectrophotometric methods. Results EPL-M80 significantly (p < 0.05) inhibited AChE and BChE activity with IC50 of 165.40 ± 4.01 and 213.81 ± 3.57 μg/mL, respectively in a dose-dependent manner. Additionally, EPL-M80 exhibited strong radical scavenging activity against DPPH (IC50 = 32.35 ± 0.68 μg/mL) and hydroxyl radical (IC50 = 19.67 ± 1.42 μg/mL) when compared to that of standards. EPL-M80 was found to be rich in phenolic (23.74 mg gallic acid equivalent/g of dry extract) and flavonoid (31.18 mg quercetin equivalent/g of dry extract) content. Furthermore, a positive correlation (p < 0.001) was observed between the total phenolics and antioxidant as well as the anticholinesterase potential. Conclusions The marked inhibition of AChE and BChE, and potent antioxidant activity of the leaves of Elatostema papillosum highlight its potential to provide an effective treatment for AD