Potential therapeutic natural products against Alzheimer's disease with Reference of Acetylcholinesterase

Ahmed, Sibtain; Khan, Sidrah Tariq; Zargaham, Muhammad Kazim; Khan, Arif Ullah; Khan, Saeed; Hussain, Abrar; Uddin, Jalal; Khan, Ajmal; Al‐Harrasi, Ahmed

doi:10.1016/j.biopha.2021.111609

Cited by 66 publications

(49 citation statements)

References 129 publications

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“…Among them, natural enzyme inhibitors play an important role in the treatment of the above-mentioned diseases. These natural compounds could inhibit the actions of enzymes associated with different chronic inflammatory and degenerative diseases [62][63][64][65][66]. Therefore, natural extracts and compounds are often tested against enzymes such as cholinesterases, α-amylase, α-glucosidase, lipase, and tyrosinase as pharmaceutical targets.…”

Section: Enzyme Inhibitory Propertiesmentioning

confidence: 99%

Shedding Light into the Connection between Chemical Components and Biological Effects of Extracts from Epilobium hirsutum: Is It a Potent Source of Bioactive Agents from Natural Treasure?

Zengin

Mahomoodally

et al. 2021

Antioxidants

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Epilobium hirsutum is extensively used as a traditional remedy in folk medicine, especially against prostate inflammation. Therefore, we evaluated the chemical profiles and biopharmaceutical potentials of different extracts of E. hirsutum aerial parts and roots. Metabolomic, antioxidant, and enzyme inhibitory profiles were investigated. Human prostate cancer PC3 cells were exposed to the extracts to evaluate antiproliferative effects. Gene expression and bioinformatics analyses were performed to investigate anti-inflammatory mechanisms. Oenothein B and myricetin were prominent compounds in the extracts. In scavenging/reducing assays, the methanol, infusion, and methanol/water extracts exhibited similar activities. We also observed the reduction of PC3 viability occurring following exposure to methanol and methanol/water extracts. According to bioinformatics analysis, myricetin was predicted to interact with COX-2 and TNFα. The interaction between TNFα and oxo-dihydroxy-octadecenoic acid was predicted as well. Intriguingly, the gene expression of COX-2 and TNFα was reduced in PC3 cells after exposure to methanol and methanol/water extracts. These effects were paralleled by the decreased gene expression of IL-8 and NFkB and the inhibition of PGE2 release. Therefore, the present findings suggest the potential use of E. hirsutum for the management of the burden of inflammation and oxidative stress occurring in lower urinary tract diseases, including prostatitis.

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Section: Enzyme Inhibitory Propertiesmentioning

confidence: 99%

Shedding Light into the Connection between Chemical Components and Biological Effects of Extracts from Epilobium hirsutum: Is It a Potent Source of Bioactive Agents from Natural Treasure?

Zengin

Mahomoodally

et al. 2021

Antioxidants

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“…The pathogenicity of Alzheimer’s disease is complex and includes genetic and environmental factors and therefore demands multiple therapeutic approaches. Some of the more well-known processes involved in Alzheimer’s disease pathogenesis include cholinergic deficit, oxidative stress, inflammatory pathways (especially NFκB) and the hyperphosphorylation and aggregation of tau proteins and β and γ secretases responsible for APP processing [ 2 ]. The most important changes observed in the brain are a decrease in cortical levels of the neurotransmitter acetylcholine.…”

Section: Introductionmentioning

confidence: 99%

“…The treatment of Alzheimer’s disease is limited to symptomatic and palliative medications and, despite the enormous effort aimed at understanding the etiology and pathogenesis of the disease, no drugs have so far been able to effectively stop for a long time the progression of the disease. Figure 1 presents schematic diagram showing five of the most important therapeutic targets in Alzheimer’s disease [ 2 ]. The treatment of Alzheimer’s disease has as its main aim an increase in the levels of acetylcholine in the synaptic cleft by inhibiting cholinesterase enzymes, which are responsible for the degradation of acetylcholine.…”

Section: Introductionmentioning

confidence: 99%

“…Most of the drugs currently used for treating Alzheimer’s disease (galanthamine, donezepil, tacrine, rivastigmine) are inhibitors of acetylcholinesterase activity [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…Often, for the evaluation of acetylcholinesterase inhibition activity, besides the spectrophotometric method, in silico investigations using quantitative structure–activity relationship (QSAR) model analysis and molecular docking are performed [ 13 ]. QSARs are important determinants of safety and efficacy after the primary screening of compounds, help in lead optimization and are therefore critical for the drug discovery and development process [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

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Determination of Anti-Alzheimer’s Disease Activity of Selected Plant Ingredients

Tuzimski

Petruczynik

2022

Molecules

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Neurodegenerative diseases, among which one of the more common is Alzheimer’s disease, are the one of the biggest global public health challenges facing our generation because of the increasing elderly population in most countries. With the growing burden of these diseases, it is essential to discover and develop new treatment options capable of preventing and treating them. Neurodegenerative diseases, among which one of the most common is Alzheimer’s disease, are a multifactorial disease and therefore demand multiple therapeutic approaches. One of the most important therapeutic strategies is controlling the level of acetylcholine—a neurotransmitter in cholinergic synapses—by blocking the degradation of acetylcholine using acetylcholinesterase inhibitors such as tacrine, galantamine, donepezil and rivastigmine. However, these drugs can cause some adverse side effects, such as hepatotoxicity and gastrointestinal disorder. Thus, the search for new, more effective drugs is very important. In the last few years, different active constituents from plants have been tested as potential drugs in neurodegenerative disease therapy. The availability, lower price and less toxic effects of herbal medicines compared with synthetic agents make them a simple and excellent choice in the treatment of neurodegenerative diseases. The empirical approach to discovering new drugs from the systematic screening of plant extracts or plant-derived compounds is still an important strategy when it comes to finding new biologically active substances. The aim of this review is to identify new, safe and effective compounds that are potential candidates for further in vivo and clinical tests from which more effective drugs for the treatment of Alzheimer’s disease could be selected. We reviewed the methods used to determine anti-Alzheimer’s disease activity. Here, we have discussed the relevance of plant-derived compounds with in vitro activity. Various plants and phytochemical compounds have shown different activity that could be beneficial in the treatment of Alzheimer’s disorders. Most often, medicinal plants and their active components have been investigated as acetylcholinesterase and/or butyrylcholinesterase activity inhibitors, modifiers of β-amyloid processing and antioxidant agents. This study also aims to highlight species with assessed efficacy, usable plant parts and the most active plant components in order to identify species and compounds of interest for further study. Future research directions are suggested and recommendations made to expand the use of medicinal plants, their formulations and plant-derived active compounds to prevent, mitigate and treat Alzheimer’s disease.

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N‐Substituted piperidine‐3‐carbohydrazide‐hydrazones against Alzheimer's disease: Synthesis and evaluation of cholinesterase, beta‐amyloid inhibitory activity, and antioxidant capacity

Parlar

Sayar

Tarikogullari

et al. 2022

Archiv der Pharmazie

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A series of piperidine‐3‐carbohydrazide‐hydrazones bearing phenylethyl, phenylpropyl, and phenylbutyl substituents on piperidine nitrogen were designed and synthesized as cholinesterase (ChE) inhibitors. The title compounds were screened for acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) inhibitory activities and antioxidant capacities, and the active ones for Aβ42 self‐aggregation inhibition, in vitro. The chemiluminescence method was used to determine the effect of the selected compounds on the reactive oxygen species (ROS) levels in brain tissue. Physicochemical properties were calculated by the MOE program. Kinetic analysis and molecular modeling studies were also carried out for the most active compounds. Generally, the final compounds exhibited moderate to good AChE or BuChE inhibitory activity. Among them, 3g and 3j showed the most potent activity against AChE (IC50 = 4.32 µM) and BuChE (IC50 = 1.27 µM), respectively. The kinetic results showed that both compounds exhibited mixed‐type inhibition. Among the selected compounds, nitro derivatives (3g, 4g, and 5g) provided better Aβ42 inhibition. According to the chemiluminescence assay, 4i exhibited the most active superoxide free‐radical scavenger activity and 3g, 3j, and 4i showed similar scavenger activity on other ROS. All results suggested that 3g, 3j, and 4i have good AChE/BuChE, Aβ42 inhibitory potentials and antioxidant capacities and can therefore be suggested as promising multifunctional agents to combat Alzheimer's disease.

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Potential therapeutic natural products against Alzheimer's disease with Reference of Acetylcholinesterase

Cited by 66 publications

References 129 publications

Shedding Light into the Connection between Chemical Components and Biological Effects of Extracts from Epilobium hirsutum: Is It a Potent Source of Bioactive Agents from Natural Treasure?

Shedding Light into the Connection between Chemical Components and Biological Effects of Extracts from Epilobium hirsutum: Is It a Potent Source of Bioactive Agents from Natural Treasure?

Determination of Anti-Alzheimer’s Disease Activity of Selected Plant Ingredients

N‐Substituted piperidine‐3‐carbohydrazide‐hydrazones against Alzheimer's disease: Synthesis and evaluation of cholinesterase, beta‐amyloid inhibitory activity, and antioxidant capacity

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