Nature as a source of metabolites with cholinesterase-inhibitory activity: an approach to Alzheimer's disease treatment

Abstract

Objectives Alzheimer's disease (AD) is the most common cause of dementia, being responsible for high healthcare costs and familial hardships. Despite the efforts of researchers, no treatment able to delay or stop AD progress exists. Currently, the available treatments are only symptomatic, cholinesterase inhibitors being the most widely used drugs. Here we describe several natural compounds with anticholinesterase (acetylcholinesterase and butyrylcholinesterase) activity and also some synthetic compounds whose structures are based on those of natural compounds. Key findings Galantamine and rivastigmine are two cholinesterase inhibitors used in therapeutics: galantamine is a natural alkaloid that was extracted for the first time from Galanthus nivalis L., while rivastigmine is a synthetic alkaloid, the structure of which is modelled on that of natural physostigmine. Alkaloids include a high number of compounds with anticholinesterases activity at the submicromolar range. Quinones and stilbenes are less well studied regarding cholinesterase inhibition, although some of them, such as sargaquinoic acid or (+)-a-viniferin, show promising activity. Among flavonoids, flavones and isoflavones are the most potent compounds. Xanthones and monoterpenes are generally weak cholinesterase inhibitors. Summary Nature is an almost endless source of bioactive compounds. Several natural compounds have anticholinesterase activity and others can be used as leader compounds for the synthesis of new drugs.

Resveratrol and its oligomers: modulation of sphingolipid metabolism and signaling in disease

“…α-Viniferin also reduces both early and late stages of LPS-induced inflammation in BV2 microglial cells through inhibition of PI3K/Akt-dependent NF-κB activation, reduced formation of pro-inflammatory molecules such as nitric oxide and prostaglandin E2 and suppression of nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated heme oxygenase-1 expression (Dilshara et al 2014). In vitro enzyme assays show that α-viniferin has favorable anti-cholinesterase activity that might be useful for the treatment of Alzheimer's disease (Pinho et al 2013;Sung et al 2002;Yan et al 2012). α-Viniferin also exhibits activity against serotonin (5-HT 6 ) receptor (Kim et al 2010), DNA topoisomerase II (Yamada et al 2006), multidrug resistance-associated protein 1 (MRP1/ABCC1) (Bobrowska-Hagerstrand et al 2006), COX-1 (Lee et al 1998), COX-2 (Chung et al 2003) and protein kinase C (PKC) (Kulanthaivel et al 1995;Xu et al 1994).…”

Cassia tora A Potential Cognition Enhancer in Rats with Experimentally Induced Amnesia

“…Also, evaluation of natural products may be useful in identification of a potential new drug that can be used to treat cognitive impairment. 3 Cassia tora (Senna tora L.) belongs to family Leguminosae, is a small shrub which is found throughout the tropical parts of Asian and African countries. C. tora is a well-known medicinal plant, consumed by Indians in the form of vegetable, traditionally used as laxative and in treatment of leprosy and various other skin disorders.…”

Synthesis and inhibitory properties of some carbamates on carbonic anhydrase and acetylcholine esterase

“…The hCA II is not only a very effective catalyst for interconversion between CO 2 and HCO 3 À , but also shows some catalytic versatility, participating in several other hydrolytic processes, which presumably involve non-physiological On the other hand, AZA, which may interact with the distinct hydrophilic and hydrophobic halves of the CA II active site, and showed K i of 9.07 ± 2.68 nM. Carbonic anhydrase isoenzymes are physiologically very important enzymes.…”

“…Carbonic anhydrases are mainly Zn 2+ containing metalloenzymes that catalyze the reversible interconversion of CO 2 and H 2 O to HCO 3 À and a proton (H + ) for the hydration reaction or consumes one equivalent of H + for the dehydration reaction [15][16][17][18][19][20] . This makes these isoenzymes crucial for many physiological and biochemical processes including electrolyte secretion, respiration, pH and CO 2 homeostasis, bone calcification, ureagenesis, gluconeogenesis, tumorigenicity, lipogenesis, transport of CO 2 / HCO 3 À between metabolizing tissues and the lungs, and some other physiologic or pathologic processes [21][22][23][24][25] . This enzyme class is present either in eukaryote or prokaryote cells.…”

“…Carbon dioxide (CO 2 ) and bicarbonate (HCO 3 À ) are essential components in living organism. The required CO 2 by the cell is transported into the cell by hydration reaction depending upon the HCO 3 À and CO 2 concentration inside and outside the cells. This transportation is performed depending upon the amount of CO 2 conversion into HCO 3 À and occurs very frequently in the cells.…”