Naturally Occurring Cholinesterase Inhibitors from Plants, Fungi, Algae, and Animals: A Review of the Most Effective Inhibitors Reported in 2012-2022.

Since the development of the "cholinergic hypothesis" as an important therapeutic approach in the treatment of Alzheimer's disease (AD), the scientific community has made a remarkable effort to discover new and effective molecules with the ability to inhibit the enzyme acetylcholinesterase (AChE). The natural function of this enzyme is to catalyze the hydrolysis of the neurotransmitter acetylcholine in the brain. Thus, its inhibition increases the levels of this neurochemical and improves the cholinergic functions in patients with AD alleviating the symptoms of this neurological disorder. In recent years, attention has also been focused on the role of another enzyme, butyrylcholinesterase (BChE), mainly in the advanced stages of AD, transforming this enzyme into another target of interest in the search for new anticholinesterase agents. Over the past decades, Nature has proven to be a rich source of bioactive compounds relevant to the discovery of new molecules with potential applications in AD therapy. Bioprospecting of new cholinesterase inhibitors among natural products has led to the discovery of an important number of new AChE and BChE inhibitors that became potential lead compounds for the development of anti-AD drugs. This review summarizes a total of 260 active compounds from 142 studies which correspond to the most relevant (IC 50 ≤ 15 µM) research work published during 2012-2022 on plant-derived anticholinesterase compounds, as well as several potent inhibitors obtained from other sources like fungi, algae, and animals.

Antioxidant activity and chemical composition of essential oil from Atriplex undulata.

The essential oil from aerial parts (stems and leaves) of Atriplex undulata (Moq) D. Dietr. (Chenopodiaceae) has been studied for its in vitro antioxidant activity. The chemical composition of the oil obtained by hydrodistillation was determined by GC and GC-MS. The major constituents were p-acetanisole (28.1%), beta-damascenone (9.3%), beta-ionone (5.1%), viridiflorene (4.7%) and 3-oxo-alpha-ionol (2.2%). The antioxidant activity of the oil was determined by two methods: Crocin bleaching inhibition (Krel = 0.72 +/- 0.15) and scavenging of the DPPH radical (IC50 = 36.2 +/- 1.6 microg/mL). The presence of active compounds like p-acetanisole, carvone, vanillin, 4-vinylguaiacol, guaiacol, terpinen-4-ol and alpha-terpineol could explain the antioxidant activity observed for this oil.

Acetylcholinesterase inhibition and antioxidant activity of essential oils from Schinus areira L. and Schinus longifolia (Lindl.) Speg.

The essential oils of Schinus areira L. and S. longifolia (Lindl.) Speg. (Anacardiaceae) have been studied for their in vitro anti-acetylcholinesterase and antioxidant activities. The chemical composition of the oils obtained by hydrodistillation was determined by GC-MS. Fruit and leaf oils of S. areira were analyzed separately. The essential oil from S. longifolia elicited marked enzymatic inhibition (IC50 = 20.0 +/- 1.0 microg/mL) and showed radical scavenger activity (IC50 = 25.2 +/- 2.4 microg/mL). The essential oil from S. areira leaves was more active than that of the fruits in both bioassays.