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Anti-Alzheimer's Studies on ?-Sitosterol Isolated from Polygonum hydropiper L.

ABSTRACT: The family Polygonaceae is known for its traditional use in the management of various neurological disorders including Alzheimer's disease (AD). In search of new anti-AD drugs, ?-sitosterol isolated from Polygonum hydropiper was subjected to in vitro, in vivo, behavioral and molecular docking studies to confirm its possibility as a potential anti-Alzheimer's agent. The in vitro AChE, BChE inhibitory potentials of ?-sitosterol were investigated following Ellman's assay. The antioxidant activity was tested using DPPH, ABTS and H2O2 assays. Behavioral studies were performed on a sub-strain of transgenic mice using shallow water maze (SWM), Y-maze and balance beam tests. ?-sitosterol was tested for in vivo inhibitory potentials against cholinesterase's and free radicals in the frontal cortex (FC) and hippocampus (HC). The molecular docking study was performed to predict the binding mode of ?-sitosterol in the active sites of AChE and BChE as inhibitor. Considerable in vitro and in vivo cholinesterase inhibitory effects were observed in the ?-sitosterol treated groups. ?-sitosterol exhibited an IC50 value of 55 and 50 ?g/ml against AChE and BChE respectively. Whereas, the activity of these enzymes were significantly low in FC and HC homogenates of transgenic animals. Molecular docking studies also support the binding of ?-sitosterol with the target enzyme and further support the in vitro and in vivo results. In the antioxidant assays, the IC50 values were observed as 140, 120, and 280 ?g/ml in the DPPH, ABTS and H2O2 assays respectively. The free radicals load in the brain tissues was significantly declined in the ?-sitosterol treated animals as compared to the transgenic-saline treated groups. In the memory assessment and coordination tasks including SWM, Y-maze and balance beam tests, ?-sitosterol treated transgenic animals showed gradual improvement in working memory, spontaneous alternation behavior and motor coordination. These results conclude that ?-sitosterol is a potential compound for the management of memory deficit disorders like AD.

SUBMITTER: Ayaz M

PROVIDER: S-EPMC5635809 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Anti-Alzheimer's Studies on β-Sitosterol Isolated from Polygonum hydropiper L.

Ayaz Muhammad M Junaid Muhammad M Ullah Farhat F Subhan Fazal F Sadiq Abdul A Ali Gowhar G Ali Gowhar G Ovais Muhammad M Shahid Muhammad M Ahmad Ashfaq A Wadood Abdul A El-Shazly Mohamed M Ahmad Nisar N Ahmad Sajjad S

Frontiers in pharmacology 20171006

The family Polygonaceae is known for its traditional use in the management of various neurological disorders including Alzheimer's disease (AD). In search of new anti-AD drugs, β-sitosterol isolated from Polygonum hydropiper was subjected to in vitro, in vivo, behavioral and molecular docking studies to confirm its possibility as a potential anti-Alzheimer's agent. The in vitro AChE, BChE inhibitory potentials of β-sitosterol were investigated following Ellman's assay. The a ...[more]

PMID: 29056913

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Project description:BackgroundAccording to the recent global cancer statistics, breast cancer is the leading cause of deaths among women with 2.3 million new cases globally. Likewise, cervical cancer is also among the leading causes of mortality among women. Polygonum hydropiper is traditionally known for its cytotoxic effects and several bioactive cytotoxic compounds were isolated from it. This study was aimed to isolate potential anticancer compounds from its most potent fractions and evaluate their anticancer potentials.MethodsBased on our earlier studies, active fractions including chloroform and ethyl acetate were subjected to column chromatography for isolation of compounds. Chemical structures of isolated compounds were confirmed via 1H NMR, 13C NMR, mass spectrometry. Purified compounds were tested for cytotoxicity against breast cancer cells (MCF-7), cervical cancer cells (HeLA) and NIH/3T3 fibroblasts cells cultures using MTT assy. Anti-angiogenic potentials of isolated compounds were evaluated via chorioallantoic membrane assay. Anti-tumor studies were done using Agrobacterium tumefaciens induced potato tumor assay. Furthermore, to understand the binding modes of Isolated compounds, molecular docking was performed against EGFR, HER2 and VEGFR using MOE as docking software.ResultsTwo bioactive compounds PH-1 (4-methyl-5-oxo-tetrahydrofuran-3-yl acetate) and PH-2 (methyl 4-hydroxy-3-methoxybenzoate) were purified from the active fractions. In cytotoxicity studies, PH-1 exhibited highest cytotoxicity against HeLA cells with 87.50% lethality at 1 mgmL-1 concentration and LD50 of 60 µgmL-1. Likewise, PH-2 showed 82.33% cytotoxicity against HeLA cells with LD50 of 160 µgmL-1. Similarly, PH-1 and PH-2 exhibited LD50 of 170 and 380 µgmL-1 respectively. Moreover, PH-1 and PH-2 were also very potent cytotoxic compounds against NIH/3T3 cells with 81.45 and 85.55% cytotoxicity at 1 mgL-1 concentration and LD50 of 140 and 58 µgL-1 respectively. Isolated compounds exhibited considerable anti-angiogenic potentials with IC50 of 340 and 500 µgL-1 respectively for PH-1 and PH-2. In anti-tumor assay, PH-1 and PH-2 exhibited 81.15 and 76.09% inhibitions with LD50 of 340 and 550 µgL-1 respectively. Both compounds selectively binds with EGFR and HER2 receptors with low binding energies. Both compounds exhibited stronger interactions with VEGFR through binding pocket residues Lys868, Val916 and Asp1046.ConclusionsBoth compounds cause considerable cytotoxicity against cancer cells. The anti-angiogenic and anti-tumor results suggests additional tumor suppressive properties. Docking analysis suggests that these compound not only has the ability to bind to EGFR and HER2 but also equally binds to VEGFR and may act as potential anti-angiogenic agents.

Project description:BackgroundPolygonum hydropiper L. is widely used as a traditional remedy for the treatment of dysentery, gastroenteritis. It has been used to relieve swelling and pain, dispel wind and remove dampness, eliminate abundant phlegm and inflammatory for a long time. Previous study showed that antioxidants especially flavonoids pretreatment alleviated sepsis-induced injury in vitro and in vivo. In the present study, the possible anti-inflammatory effect of flavonoids from normal butanol fraction of Polygonum hydropiper L. extract (FNP) against inflammation induced by lipopolysaccharide (LPS) was evaluated in vivo and in vitro.MethodsThe content of total flavonoid of FNP was determined by the aluminum colorimetric method. The content of rutin, quercetin and quercitrin was determined by HPLC method. Mice received FNP orally 3 days before an intra-peritoneal (i.p.) injection of lipopolysaccharide (LPS). Total superoxidase dismutase (T-SOD), total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-PX), glutathione (GSH), myeloperoxidase (MPO) and malondialdehyde (MDA) levels were measured. Tumor necrosis factor-α levels in serum and tissue was measured. mRNA expressions of pro-inflammatory cytokines in lung were assessed by Real-Time PCR. Histopathological changes were evaluated in lung, ileum and colon. We also investigated FNP on reactive oxygen species (ROS), nitric oxide (NO) and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-8) production, inducible nitric oxide synthase (iNOS), Cyclooxygenase-2 (COX-2) protein expression, phosphorylation of MAPKs and AMPK in LPS-stimulated RAW264.7 cells.ResultsFNP increased the levels of T-SOD, T-AOC, GSH-PX and GSH, decreased the levels of TNF-α, MPO and MDA, attenuate the histopathological lesion in LPS-stimulated mice. FNP inhibited production of inflammatory cytokines, ROS and NO, protein expressions of iNOS and COX-2, phosphorylation of ERK, JNK and c-JUN in MAPKs, promoted phosphorylation of AMPKα suppressed by LPS.ConclusionThese results suggested in vivo anti-inflammatory activities of FNP might contributed to its enhancement in antioxidant capacity, its inhibitory effects may be mediated by inhibiting the phosphorylation of JNK, ERK and c-JUN in MAPKs signaling pathways.

Project description:Riparian plants are exposed to harmful stress induced by flooding, which is often accompanied by eutrophication in the Three Gorges Reservoir Region. The phenomenon is mainly caused by domestic sewage discharges, slow water flow, and agricultural fertilizer pollution. Simulating abiotic stress, such as flooding at the initial period, can act as a signal and induce positive responses of plants to subsequent severe stress. In addition, eutrophication supplies nutrients, provides a favorable environment in the early stages of plant, and facilitates good performance in later development. However, whether early flooding (with or without eutrophication) acts as positive cue or as stress on plants at different developmental stages remains unclear. To address this question, seeds of Polygonum hydropiper were collected from low and high elevations in the hydro-fluctuation belt of the Three Gorges Reservoir Region. Plants germinated from these seeds were subjected to shallower and shorter early flooding treatments with or without eutrophication. Subsequently, plants were subjected to deeper and longer flooding treatments with or without eutrophication. Early flooding and eutrophic flooding significantly induced generation of adventitious roots, suggesting morphological adaptation to flooding. Although early flooding and eutrophic flooding treatments did not increase plant biomass in subsequent treatments compared with control, stem length, length and width of the 1st fully expanded leaf, and biomass of plants in the early eutrophic treatment were higher than these of the early flooding treatment plants. These results suggest a negative lag-effect of early flooding, and also indicate that nutrient inputs can alleviate such effects. Similarly, subsequent eutrophic flooding also enhanced plant growth compared with subsequent flooding, showing significantly higher values of leaf traits and adventitious root number. Plants originated from low elevation had significantly higher functional leaf length and stem biomass compared with those from high elevation. These results suggest that nutrient inputs can alleviate negative effects of early and subsequent flooding on growth of P. hydropiper with the generation of adventitious roots.

Project description:BackgroundPolygonum chinense Linn. is a common medicinal plant in Southeast Asia and has been used in traditional medicine in Vietnam. The plant contains phytochemicals with various biological properties; however, its antiviral effect has not yet been demonstrated. This study was aimed to evaluate the anti-influenza virus activity of crude extracts of P. chinense, to characterize antiviral metabolites therefrom and to investigate their mechanisms of antiviral action.MethodsThe methanol (MeOH) extract and organic solvent layers of P. chinense were prepared by extraction and partition with relevant solvents. The ethyl acetate (EtOAc) layer showing antiviral activity was chromatographed repeatedly on SiO2 and Sephadex LH-20 columns to give eight pure metabolites. Their chemical structures were determined by NMR and MS spectral data. Anti-influenza virus activity of the eight metabolites against virus strains A/Puerto Rico/8/34 (H1N1, PR8), A/Hong Kong/8/68 (H3N2, HK) and B/Lee/40 (Lee) was evaluated on the basis of cytopathic effect (CPE) and plaque inhibition assays. Time-of-addition, confocal microscopy and neuraminidase inhibition assay were performed for mode-of-action studies of active ingredients.ResultsThe MeOH extract of P. chinense showed anti-influenza virus activity with EC50 values ranging from 38.4 to 55.5 μg/mL in a CPE inhibition assay. Among the eight pure metabolites isolated from P. chinense, ellagic acid (PC5), methyl gallate (PC7) and caffeic acid (PC8) significantly inhibited viral replication in a dose-dependent manner in both plaque inhibition and CPE inhibition assays with EC50 values ranging from 14.7 to 81.1 μg/mL and CC50 values higher than 300 μg/mL. Mode-of-action studies suggested that PC5 and PC7 suppress virus entry into or replication in cells, while PC8 targets influenza viral neuraminidase, even oseltamivir-resistant one.ConclusionThese results demonstrated that P. chinense and its metabolites possess effective anti-influenza virus activities. The botanical materials of P. chinense could be a promising multitargeted inhibitor of influenza A and B viruses and applied to development of a novel herbal medicine.

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Anti-Alzheimer's Studies on ?-Sitosterol Isolated from Polygonum hydropiper L.

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Anti-Alzheimer's Studies on β-Sitosterol Isolated from <i>Polygonum hydropiper</i> L.

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