Structural Scaffolds as Anti- Alzheimer Agents.

BACKGROUND: Understanding the cognitive and behavioral aspects of Alzheimer's disease- related dementia is surely a sturdy task to deal with. In recent years, a broad search for novel anti-Alzheimer agents has been continuously conducted. The malfunctioning of various neurotransmitter systems and the accumulation of abnormal proteins in the brain are the two key characteristics of this disorder. This is supported by a growing amount of evidence. Some Pharmacophoric groups/combinations exhibit potential neuroprotective activity. METHODS: This study aims to compile the most recent and interesting target/target combinations/ pharmacophoric combinations to cure Alzheimer's disease. We concentrated our efforts to find the ability of certain pharmacophoric elements to interfere with various enzymatic and/or receptor systems or to work as neuroprotective agents. These pharmacophoric elements may be proved to be promising leads for future multi-target anti-Alzheimer drug discovery programs. RESULTS: Anticholinesterase drugs were mentioned as the best treatment thus far. Additionally, impairments in the serotonergic, GABAergic, noradrenergic, dopaminergic, and glutaminergic and a few other pathways have all been linked to memory, speech, behavioral and other alterations in Alzheimer's disease. CONCLUSION: This includes the study of workable pharmacophoric groups/combinations, receptors/ enzymatic systems and related hypotheses to find the promising therapeutic lead compounds which could work as future anti-Alzheimer drugs. We discuss future work that would improve our understanding of this Disease.

Antidepressant activity of Spathodea campanulata in mice and predictive affinity of spatheosides towards type A monoamine oxidase.

The antidepressant activity of Spathodea campanulata flowers was evaluated in mice and in silico. When tested at doses of 200 and 400 mg/kg, the methanol extract of S. campanulata (MESC) showed dose-dependent antidepressant activity in the force swim test (FST), tail suspension test (TST), lithium chloride-induced twitches test and the open field test. In FST and TST, animals treated with MESC demonstrated a significant decrease in the immobility period compared to the control group. The lithium chloride-induced head twitches were significantly reduced following administration of MESC. The latter, at the dose of 400 mg/kg, also significantly reduced locomotor activity. Following administration of MESC, changes in the levels of serum corticosterone, and of norepinephrine, dopamine, serotonin, 4-hydroxy-3-methoxyphenylglycol (MHPG), 4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) were measured in different brain regions using HPLC. The presence of spatheoside A (m/z 541) and spatheoside B (m/z 559) in MESC was detected using HPLC/ESI-MS. These two iridoids demonstrated a high predictive binding affinity for the active site of the type A monoamine oxidase (MAO-A) enzyme with scores of 99.40 and 93.54, respectively.  These data suggest that S. campanulata flowers warrants further investigation as a source of novel templates for antidepressive drugs.

Phytochemical evaluation and anti-hemorrhoidal activity of bark of Acacia ferruginea DC.

The present study has been carried out to evaluate antihemorrhoidal activity of bark of Acacia ferruginea DC. The total phenolic, total flavonoid and saponins were determined. Anti-hemorrhoidal potential of bark extract was determined by levels of inflammatory cytokines such as TNF-α, IL-6, PGE2 and recto-anal coefficient (RAC). The histopathological examination was done to evaluate the severity score in the treated and untreated groups. The results of phytochemical screening of the hydroalcoholic extract of A. ferruginea revealed the presence of alkaloids, flavonoids, triterpenoid, saponins, tannins and phenolic compounds The total phenolic, flavonoid and saponin contents were found to be 438.8mg/g GAE, 66.6mg/gRE and 34%w/w respectively. Hydroalcoholic extract of bark of A. ferruginea significantly reduced the inflammatory cytokines {TNF-α(8.40±0.188), IL-6(3.95±0.181), PGE2(53.27±2.956) and RAC(0.998±0.094)}as compared to positive control group{TNF-α(13.36±0.141), IL-6(7.25±0.161), PGE2(82.34±3.395) and RAC(1.131 ± 0.008)}. Noticeably the results were comparable to that of standard pilex granules {TNF-α (7.12±0.166), IL-6(3.01±0.156), PGE2(42.51±2.157) and RAC (0.968±0.084)}. Molecular docking and structure based pharmacophore mapping further confirmed the anti-inflammatory mediated antihemorrhoidal activity of the hydroalcoholic extract. The antihemorrhoidal activity of hydroalcoholic extract of A. ferruginea may attribute to the flavonoids.

Studies on analgesic, anti-inflammatory activities of stem and roots of Inula cuspidata C.B Clarke.

The present study was carried out to evaluate analgesic and anti-inflammatory activities in Inula cuspidata stem and root extracts along with heavy metals estimation in stem and root powder. Stem and roots were extracted with chloroform (ICSCE, ICRCE) and methanol (ICSME, ICRME). Acute oral toxicity of all extracts was determined by OECD guidelines 425. Analgesic activity was investigated by using hot plate and acetic acid induced writhing models. Anti-inflammatory activity (acute) of all extracts was evaluated by carrageenan induced paw edema model. In addition, root and stem powder was screened for heavy metals (As, Pb, Cd, Hg) estimation using atomic absorption spectroscopy. In acute toxicity study no mortality was observed when each extract was orally administered with 2.0 g/kg. At the doses (100 and 200 mg/kg) ICRME followed by ICSME showed significant and dose dependent analgesic and anti-inflammatory effects compared with chloroform extracts. The heavy metals concentration in stem and root powders was found to be within the permissible limits as recommended by WHO for herbal raw materials. The findings of the present study validated the folkloric use of Inula cuspidata as analgesic and anti-inflammatory. In addition, the results intimate that heavy metals present in raw material were found to be within the defined limits, and it exhibits that the therapeutic efficacy of plant may not be effected, which can be otherwise possibly effected if the plant sequester high concentration of heavy metals from the polluted environment as well as from the soil rich in pesticides and sewage sludge etc.

Comparative Evaluation of Polyphenol Contents and Antioxidant Activities between Ethanol Extracts of Vitex negundo and Vitex trifolia L. Leaves by Different Methods.

The in vitro antioxidant potential assay between ethanolic extracts of two species from the genus Vitex (Vitex negundo L. and Vitex trifolia L.) belonging to the Lamiaceae family were evaluated. The antioxidant properties of different extracts prepared from both plant species were evaluated by different methods. DPPH scavenging, nitric oxide scavenging, and ß-carotene-linoleic acid and ferrous ion chelation methods were applied. The antioxidant activities of these two species were compared to standard antioxidants such as butylated hydroxytoluene (BHT), ascorbic acid, and Ethylene diamine tetra acetic acid (EDTA). Both species of Vitex showed significant antioxidant activity in all of the tested methods. As compared to V. trifolia L. (60.87-89.99%; 40.0-226.7 µg/mL), V. negundo has been found to hold higher antioxidant activity (62.6-94.22%; IC50 = 23.5-208.3 µg/mL) in all assays. In accordance with antioxidant activity, total polyphenol contents in V. negundo possessed greater phenolic (89.71 mg GAE/g dry weight of extract) and flavonoid content (63.11 mg QE/g dry weight of extract) as compared to that of V. trifolia (77.20 mg GAE/g and 57.41 mg QE/g dry weight of extract respectively). Our study revealed the significant correlation between the antioxidant activity and total phenolic and flavonoid contents of both plant species.

Synthesis of the impurities during the manufacture of bulk drug midazolam and separation of these impurities by HPLC.

During the manufacture of bulk drug midazolam various impurities arised that can be the related products or degradation products. Structures of eight impurities that can arise during the manufacture of bulk drug midazolam were proposed. In the present work, synthesis of these impurities and their characterization by different spectroscopic techniques have been done. HPLC method was developed for the separation of impurities from the bulk drug. The developed method separates midazolam from its eight impurities/degradation products within a run time of 45 min.