Critical evaluation of current Alzheimer’s drug discovery (2018–19) &amp; futuristic Alzheimer drug model approach

Dorababu, Atukuri

doi:10.1016/j.bioorg.2019.103299

Cited by 23 publications

(5 citation statements)

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“…This analogy further corroborates previous studies highlighting the tight relationships between antiradical and enzyme inhibition properties [ 33 ]. Considering that these enzymes are key targets in the pharmacotherapy of neurodegenerative diseases, type 2 diabetes, and hyperpigmentation [ 34 , 35 , 36 ], and all characterized by an increased burden of inflammation and oxidative stress, the present data suggest the rationale for testing the P. mahaleb water extract in experimental paradigms simulating these disorders. Furthermore, considering that the observed biological properties of the extract are related, albeit partially, to the presence of phenolic compounds [ 37 , 38 ], a quantitative determination of selected phenols and flavonoids was conducted via HPLC-DAD-MS ( Figure 2 ).…”

Section: Resultsmentioning

confidence: 99%

Unravelling the Phytochemical Composition and the Pharmacological Properties of an Optimized Extract from the Fruit from Prunus mahaleb L.: From Traditional Liqueur Market to the Pharmacy Shelf

et al. 2021

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Prunus mahaleb L. fruit has long been used in the production of traditional liqueurs. The fruit also displayed scavenging and reducing activity, in vitro. The present study focused on unravelling peripheral and central protective effects, antimicrobial but also anti-COVID-19 properties exerted by the water extract of P. mahaleb. Anti-inflammatory effects were studied in isolated mouse colons exposed to lipopolysaccharide. Neuroprotection, measured as a blunting effect on hydrogen-peroxide-induced dopamine turnover, was investigated in hypothalamic HypoE22 cells. Antimicrobial effects were tested against different Gram+ and Gram- bacterial strains. Whereas anti-COVID-19 activity was studied in lung adenocarcinoma H1299 cells, where the gene expression of ACE2 and TMPRSS2 was measured after extract treatment. The bacteriostatic effects induced on Gram+ and Gram- strains, together with the inhibition of COX-2, TNFα, HIF1α, and VEGFA in the colon, suggest the potential of P. mahaleb water extract in contrasting the clinical symptoms related to ulcerative colitis. The inhibition of the hydrogen peroxide-induced DOPAC/DA ratio indicates promising neuroprotective effects. Finally, the downregulation of the gene expression of ACE2 and TMPRSS2 in H1299 cells, suggests the potential to inhibit SARS-CoV-2 virus entry in the human host. Overall, the results support the valorization of the local cultivation of P. mahaleb.

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Section: Resultsmentioning

confidence: 99%

Unravelling the Phytochemical Composition and the Pharmacological Properties of an Optimized Extract from the Fruit from Prunus mahaleb L.: From Traditional Liqueur Market to the Pharmacy Shelf

et al. 2021

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“…For example, cholinesterase is a key enzyme in the management of Alzheimer’s disease, which hydrolyzing acetylcholine in the synaptic gap. At this point, the inhibition of cholinesterase could increase the level of acetylcholine in the synaptic cleft and these effects may help to improve cognitive dysfunctions in Alzheimer patients [ 38 ]. In another example, the blood glucose level in diabetes mellitus patients was controlled by the inhibition of amylase and glucosidase, which are the main clinically relevant carbohydrate-hydrolyzing enzymes [ 39 ].…”

Section: Resultsmentioning

confidence: 99%

Chemical Characterization, Antioxidant, Enzyme Inhibition and Antimutagenic Properties of Eight Mushroom Species: A Comparative Study

Alkan

Uysal

Kaşik

et al. 2020

JoF

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This study aimed to determine the chemical composition and biologic activities of eight mushroom species (Amanita crocea, Hemileccinum depilatum, Cyclocybe cylindracea, Lactarius deliciosus, Hygrocybe acutoconica, Neoboletus erythropus, Russula aurea and Russula sanguinea). The antioxidant, enzyme inhibitory and mutagenic/antimutagenic activities were evaluated to provide data on the biologic activities. With respect to the chemical composition, LC–MS/MS technique was used to determine individual phenolic compounds present in the extracts. Antioxidant properties were investigated by different chemical methods including radical quenching (DPPH and ABTS), reducing power (CUPRAC and FRAP), phosphomolybdenum and metal chelating. In the enzyme inhibitory assays, cholinesterases, tyrosinase, amylase and glucosidase were used. Mutagenic and antimutagenic properties were evaluated by the Ames assay. In general, the best antioxidant abilities were observed from H. depilatum and N. erythropus, which also showed highest level of phenolics. The best cholinesterase inhibition ability was found from C. cylindracea (1.02 mg GALAE/g for AChE; 0.99 mg GALAE/g for BChE). Tyrosinase inhibition ability varied from 48.83 to 54.18 mg KAE/g. The extracts exhibited no mutagenic effects and showed significant antimutagenic potential. H. acutoconica, in particular depicted excellent antimutagenicity with a ratio of 97% for TA100 and with a rate of 96% for TA98 strain against mutagens in the presence of metabolic activation system. Results presented in this study tend to show that the mushroom species could be exploited as potential sources of therapeutic bioactive agents, geared towards the management of oxidative stress, global health problems and cancer.

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“…Hence, several compounds are synthetically produced as enzyme inhibitors in the pharmaceutical industry. However, several studies have reported that synthetic compounds have unpleasant side effects [ 47 , 48 ]. Thus, enzyme inhibitors from natural sources are needed to replace these synthetic ones.…”

Section: Discussionmentioning

confidence: 99%

Screening of Bioactive Metabolites and Biological Activities of Calli, Shoots, and Seedlings of Mertensia maritima (L.) Gray

Song

Sivanesan

et al. 2020

Plants

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Mertensia maritima (L.) Gray is threatened with extinction owing to climate change, poor seed germination, and ocean warming. In vitro explant-culture is used for ex situ preservation and plantlet massive production. In vitro cell and organ cultures serve as an alternative plant material source to investigate the biological activities and phytochemical profiles of rare plants. We aimed to develop an efficient callus and shoot production protocol and investigate bioactive metabolites, antioxidants, and enzyme inhibitory potential of M. maritima calli, shoots, and in vivo seedlings. The effects of combinations of different plant growth regulators, 6-BA (N6-benzyladenine), 6-KN (Kinetin), TDZ (Thidiazuron), and NAA (1-Naphthylacetic acid), in MS (Murashige and Skoog) nutrient medium were studied. The highest callus proliferation was obtained after 5-week cultivation over a 16-h photoperiod on growth medium MS enriched with 4 µM each of 6-BA and NAA. The medium with 2 µM 6-BA and 4 µM 6-KN had the best shoot induction rate (91.1%) with a mean of 13.4 shoots. The combination of two cytokinins (6-BA and 6-KN) was found to be effective in M. maritima shoot regeneration. The rooting frequency was 100% in ½ MS with Indole-3-butyric acid (IBA 2 µM). The number of detected compounds and chemical composition in the M. maritima shoots and seedlings extracts were similar. The total amount of phenolics in the shoots was 216.4% and 369.5% higher than in seedlings and calli, respectively. The total amount of flavonoids in the shoots was 241.1% and 429.3% higher than in seedlings and calli, respectively. The best antioxidant activity was obtained in the shoots, followed by seedlings and calli. However, the order was seedlings > calli > shoots regarding metal chelating ability. The strongest acetylcholinesterase inhibition properties were obtained in the calli, followed by seedlings and shoots. However, the tested samples can be ranked as seedlings > shoots > calli in butylcholinestrase inhibition assay. This study is the first report on the enzyme inhibitory effects of M. maritima extracts, providing valuable contributions to the scientific community.

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Critical evaluation of current Alzheimer’s drug discovery (2018–19) & futuristic Alzheimer drug model approach

Cited by 23 publications

References 292 publications

Unravelling the Phytochemical Composition and the Pharmacological Properties of an Optimized Extract from the Fruit from Prunus mahaleb L.: From Traditional Liqueur Market to the Pharmacy Shelf

Unravelling the Phytochemical Composition and the Pharmacological Properties of an Optimized Extract from the Fruit from Prunus mahaleb L.: From Traditional Liqueur Market to the Pharmacy Shelf

Chemical Characterization, Antioxidant, Enzyme Inhibition and Antimutagenic Properties of Eight Mushroom Species: A Comparative Study

Screening of Bioactive Metabolites and Biological Activities of Calli, Shoots, and Seedlings of Mertensia maritima (L.) Gray

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