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Non-Alkaloid Cholinesterase Inhibitory Compounds from Natural Sources.

ABSTRACT: Alzheimer's disease (AD) is a severe neurodegenerative disorder of different brain regions accompanied by distresses and affecting more than 25 million people in the world. This progressive brain deterioration affects the central nervous system and has negative impacts on a patient's daily activities such as memory impairment. The most important challenge concerning AD is the development of new drugs for long-term treatment or prevention, with lesser side effects and greater efficiency as cholinesterases inhibitors and the ability to remove amyloid-beta(Aβ) deposits and other related AD neuropathologies. Natural sources provide promising alternatives to synthetic cholinesterase inhibitors and many have been reported for alkaloids while neglecting other classes with potential cholinesterase inhibition. This review summarizes information about the therapeutic potential of small natural molecules from medicinal herbs, belonging to terpenoids, coumarins, and phenolic compounds, and others, which have gained special attention due to their specific modes of action and their advantages of low toxicity and high efficiency in the treatment of AD. Some show superior drug-like features in comparison to synthetic cholinesterase inhibitors. We expect that the listed phytoconstituents in this review will serve as promising tools and chemical scaffolds for the discovery of new potent therapeutic leads for the amelioration and treatment of Alzheimer's disease.

SUBMITTER: Tamfu AN

PROVIDER: S-EPMC8472022 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:In current study is done antioxidant, anticholinesterase, and carbonic anhydrase isoenzymes I and II inhibition assays, screening of biological active compounds and electronic microscopy analysis of secretory canals of fruits, flowers, roots, and aerial parts extracts and essential oils of Angelica purpurascens. Phenolic constituents, antioxidant, and anti-lipid peroxidation potentials of variants were estimated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and thiobarbituric acid (TBA) processes. Cholinesterase inhibition effect was detected through Ellman's method. The GC/ Mass Spectrometry (MS) and gas chromatography (GC)-flame Ionization Detector (FID) was used for essential oils analysis. NMR techniques was used for identification of the isolated compounds. The fruit hexane and dichloromethane fractions exhibited a greater antioxidant capacity and total phenolic content. The dichloromethane fraction of fruit demonstrated the most higher acetylcholinesterase inhibition (39.86 ± 2.63%), while the fruit hexane fraction displayed the best inhibition towards butyrylcholinesterase (84.02 ± 1.28%). Cytosolic isoenzymes of human carbonic anhydrase (hCA) I, and II isoenzymes were influentially suppressed by flower and fruit dichloromethane fractions with 1.650 and 2.020 µM IC50 values, respectively. The electronic microscopy analysis of secretory canals found that the small number of secretory canals were at leaf while the largest shape of secretory canals was at the fruit. The secretory canals of roots, aerial parts, and fruits include more monoterpene hydrocarbons, while the canals, existing in the flowers are qualified by a higher presence of sesquiterpenes β-caryophyllene (12.1%), germacrene D (4.5%) and ether octyl acetate (11.9%). The highest level of monoterpene β-phellandrene (47.6%) and limonene (8.2%) were found in the fruit essential oil. The next isolated compounds from fruits of A. purpurascens like stigmasterol, β-sitosterol, bergapten, and oxypeucedanin have shown high anticholinesterase and antioxidant activities.

Project description:The aim of this work was to enrich the knowledge on the potential applications of Elaeagnus mollis leaf extracts. For this purpose, the bioactive compounds (phenolic, flavonoid, alkaloid, proanthocyanidin, chlorophyll and carotene content), antioxidant activity, anti-HepG2 cell proliferation, and cholinesterase inhibitory potential (AChE and BChE) of E. mollis leaves which obtained from different habitats were quantitatively analyzed using various solvents (water, methanol, ethanol, and n-hexane). The results showed that the methanol extracts exhibited the strongest 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity and the water extracts showed the best antioxidant activity in the 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) free radical scavenging activity, ferric reducing antioxidant power (FRAP), and reducing power (RP) assays. Moreover, the methanol extracts showed the best inhibitory activity against cholinesterase and HepG2 cancer cells. Correlation analysis revealed that the high antioxidant and anti-HepG2 cell proliferation activities were mainly attributed to the total phenolics, flavonoids, and proanthocyanidins while AChE inhibition was attributed to the total alkaloid and carotene content. The statistical results showed that the effect of habitats was lower than that of different solvents used. Additionally, the metabolic profiles of E. mollis leaves were evaluated using HPLC-ESI-Q TRAP-MS/MS, and a total of 1,017 chemical components were detected and classified into 23 classes. The organic acids and derivatives ranked the first, followed by flavone, amino acid and derivatives, and so on. In conclusion, the effects of different solvents were more significant than the effects of different habitats and the methanol extracts of E. mollis leaves could be used as an effective source of functional active components, provide benefits to physical health care and be applied to the food and pharmaceutical industries.

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Non-Alkaloid Cholinesterase Inhibitory Compounds from Natural Sources.

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