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.

Rhanteriol, a New Rhanterium suaveolens Desf. Lignan with Pharmacological Potential as an Inhibitor of Enzymes Involved in Neurodegeneration and Type 2 Diabetes

“…In the latter case, the effect of the harvesting time on R. adpressum bioactivity was investigated, demonstrating an IC 50 vs. α-amylase ranging from 1370 ± 0.07 µg/mL to 2710 ± 0.26 µg/mL [ 33 ]. However, this difference in bioactivity between the two species may be due to the different extractive solvents used, as MeOH was used for R. suaveleons , while acetone and water (70:30) were used for R. adpressum , which may result in extracts with a different phytocomplex [ 34 ]. This hypothesis is confirmed by the fact that, contrary to R. adpressum [ 33 ], R. suaveleons had no inhibitory activity against α-glucosidase.…”

“…In particular, for α-glucosidase, the new lignan exerts an inhibition higher than that observed for the acarbose used as the standard (IC 50 241.32 ± 4.49 µM) and other lignans such as patulinone A, B, and C, isolated from Melicope patulinervia (Merr. & Chun) Huang (IC 50 ranging from 41.68 ± 3.54 to 95.77 ± 3.63 µM) [ 34 ]. Hence, it is possible that other active molecules present in the R. suaveleons BuOH fraction may contrast with the α-glucosidase inhibitory activity of rhanteriol.…”

HPLC-DAD Phenolic Composition, Antioxidant, Anticholinesterase, Antidiabetic and Anti-quorum Sensing Properties of Bitter Kola (Garcinia kola) and Kolanut (Cola acuminata)

“…The cholinergic hypothesis suggests that inhibiting Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) can relieve cholinergic functions by increasing the levels of acetylcholine in the synapse necessary for neurotransmission and this is a suitable strategy to overcome AD. [67,68] Various natural plant extracts, essential oils and compounds have been searched and reported as potential AChE and BChE inhibitors with higher efficacy and safety than synthetic drugs. [67,69] Inhibition of enzymes such as cholinesterase and carbohydrate enzymes like α-amylase and α-glucosidase are beneficial in the treatment of AD and diabetes.…”

Causal Relationships Between Osteoarthritis and Senile Central Nerve System Dysfunction: A Bidirectional Two-Sample Mendelian Randomization Study

“…With the advent of an aging society, there has been a sharp increase in the number of patients suffering from senile CNSD. Previous studies have shown that the number of AD cases will increase to around 115–135 million by 2050 ( Tamfu et al, 2021 ), and the incidence rates of PD are about 108–257/100,000 and 11–19/100,000 per year in Europe ( Balestrino and Schapira, 2020 ). Thus, much more attention should be paid to senile CNSD, its complications, etiologies, etc.…”