Herbal snuff (AK-47 and HAM) induce oxidative stress and increase acetylcholinesterase enzyme activity in rat brain

Snuff has resurfaced not only in western countries but in Africa including Nigeria. It is now almost generally acceptable, among young and old in Nigeria. This research was designed to investigate the Effect of Hajiya Aisha Manpower (HAM) and AK-47 on Antioxidant Status and Acetylcholinesterase enzyme activity (AchE) of Wister Albino Rats. Thirty (30) Wister rats (110-120 g) were arbitrarily divided into five groups. Group1 (control); received only distilled water. Groups 2 and 3 (received 6 mg and 3 mg/kg b.w.t of HAM respectively). Groups 4 and 5 (received 6 mg and 3 mg/kg b.w.t AK-47 of respectively). After two months of treatments, the rats were anesthetized, blood samples were taken through heart puncture and brains of all rats were isolated and homogenized. The Result revealed Non-significant decrease in Superoxide dismutase (SOD), glutathione peroxidase (GPx) activities and concomitant increase in GSH levels in treatment groups were observed in relation to the control. While a substantial increase (p˂ 0.5) in MDA was detected in treatment groups. Brain AchE activity increased significantly in all treatment groups in relation to the control. We conclude that Both AK-47 and HAM at high concentration induce oxidative stress, decreased antioxidant enzyme activities and promote degradation of acetylcholine in rat brain homogenate.

The Valorization of Spent Coffee Grounds Extract as A Prospective Insecticidal Agent Against Some Main Key Pests of Phesolus Vulgaris in Laboratory and Field

Exploiting massive amounts of food and agro-waste represents a severe social, economic, and environmental issue. Under the growing demand toward food products free of toxic synthetic insecticides, the methanolic extract of spent coffee grounds (SCGs), which represent the main by-product of coffee production, was applied in the current study as a bioinsecticide against the main pests of the green bean; Spodoptera littoralis, Agrotis ipsilon, Bemisia tabaci, Empoasca fabi and Aphis craccivora. Deterrent assay, contact bioassay, and lethal concentration analysis were performed to reveal the repellent, antifeedant, and oviposition deterrent effects. Parallel to the above-performed bioassays, the phytochemical composition of the SCGs methanolic extract was investigated via High-Performance Liquid Chromatography (HPLC) analysis. Fourteen phenolic acids and five flavonoids in addition to caffeine (alkaloid) have been identified in the extract. Cinnamic, rosmarinic, and gallic acids were the predominant phenolics, while apigenin-7-glucoside was the main flavonoid, followed by naringin, catechin, and epicatechin. The extract of SCGs showed an insecticidal effect, with mortality between 27.5-76% compared to the control (7.4%) and based on the concentration of the extract used. In the same trend, oviposition efficiency revealed different laid egg batches (0.67, 2.33, 7.33, and 8.67 batch/jar) for 100, 50, 25% of the SCGs extract and control. Finally, the major components of SCGs extract were docked into insecticide acetylcholinesterase enzyme to explore their potential of inhibition, where apigenin-7-glucoside showed a higher binding affinity, followed by catechin, compared to the control (lannate). Obtained findings could be a starting point to develop novel bioinsecticides from SCGs.

Using Virtual AChE Homology Screening to Identify Small Molecules With the Ability to Inhibit Marine Biofouling

The search for effective yet environmentally friendly strategies to prevent marine biofouling is hampered by the large taxonomic diversity amongst fouling organisms and a lack of well-defined conserved molecular targets. The acetylcholinesterase enzyme catalyses the breakdown of the neurotransmitter acetylcholine, and several natural antifouling allelochemicals have been reported to display acetylcholinesterase inhibitory activity. Our study is focussed on establishing if acetylcholinesterase can be used as a well-defined molecular target to accelerate discovery and development of novel antifoulants via sequential high-throughput in silico screening, in vitro enzymatic studies of identified compound libraries, and in vivo assessment of the most promising lead compounds. Using this approach, we identified potent cholinesterase inhibitors with inhibitory concentrations down to 3 μM from a 10,000 compound library. The most potent inhibitors were screened against five microfouling marine bacteria and marine microalgae and the macrofouling tunicate Ciona savignyi. No activity was seen against the microfoulers but a potent novel inhibitor of tunicate settlement and metamorphosis was discovered. Although only one of the identified active cholinesterase inhibitors displayed antifouling activity suggesting the link between cholinesterase inhibition and antifouling is limited to certain compound classes, the study highlights how in silico screening employed regularly for drug discovery can also facilitate discovery of antifouling leads.

ACETYLCHOLINESTERASE, AS A POTENTIAL BIOMARKER OF NAPHTHALENE TOXICITY IN DIFFERENT TISSUES OF FRESHWATER TELEOST, ANABAS TESTUDINEUS

Naphthalene, a Polycyclic Aromatic Hydrocarbon is widely used as a fumigant and disinfectant despite its toxic effect and is ranked as the ninth most threatening compound. The present study was carried out to determine the in vivo effect of naphthalene at different concentrations on acetylcholinesterase (AChE) enzyme activity in different tissues of Anabas testudineus. The fishes were exposed to varying concentrations of naphthalene (4.2 mgL–1, 4.4 mgL–1, 4.6 mgL–1, 4.8 mgL–1 and 5 mgL–1) for a period of 72 hours. Acetylcholinesterase enzyme activity was found to be significantly inhibited, in a dose-response manner. The inhibition percentage of AChE activity varied from 9.34–43.95% in brain tissue, 2.56–35.81% in liver tissue, 5.94–34.15% in muscle tissue and 3.92–33.75% in gills in comparison to the tissues of the control group. Maximum inhibition of acetylcholinesterase enzyme activity in treated fish was observed in the brain followed by liver, muscles, and gills. This study highlights the significance and role of acetylcholinesterase as a potential stress biomarker of naphthalene toxicity.

A Systematic Review on Nerve Chemical Warfare Agents

The recent poisoning of Russian opposition figure and critic Alexei Navalny on August 20th , 2020 with a Soviet-era Novichok nerve agent reminded the world of the use of chemical agents, especially nerve agents to eliminate individual targets or for mass destruction. Nerve agents are a class of organophosphorus compounds. Soman, Sarin, Tabun, Cyclosarin, VX are a few examples of nerve agents. Nerve agents affect a person by disrupting the mechanism by which nerve signals are passed in the body. They inhibit the action of acetylcholinesterase enzyme which is responsible for the breakdown of acetylcholine neurotransmitters leading to accumulation of acetylcholine in the body. Nerve agents have a range of chemical effects on the eye, gastro-intestinal (GI) tract, Central nervous system (CNS), Respiratory system, Cardiovascular system and Neurological system. The management of nerve agent poisoning is done by administering Atropine or Pralidoxime chloride or also by administering anticonvulsants like Benzodiazepines or Diazepam. This review presents all such detailed information on this class of chemical Warfare agents. Keywords: Chemical Warfare Weapon, Nerve Agents, Acetylcholinesterase, Toxicity, Instrumentation

Acetylcholinesterase Enzyme Inhibitor Molecules with Therapeutic Potential for Alzheimer's Disease

: Acetylcholinesterase (AchE), hydrolase enzyme, regulates the hydrolysis of acetylcholine neurotransmitter in the neurons. AchE is found majorly in the central nervous system at the site of cholinergic neurotransmission. It is involved in the pathophysiology of Alzheimer’s disease-causing dementia, cognitive impairment, behavioral and psychological symptoms. Recent findings involved the inhibition of AchE that could aid in the treatment of Alzheimer's. Many drugs of different classes being analyzed in the clinical trials and examined for their potency. Drugs that are used in the treatment of Alzheimer’s disease are donepezil, galantamine, tacrine, rivastigmine shows major adverse effects. To overcome this, researchers work on novel drugs to elicit inhibition. This review comprises the many hybrids and non-hybrid forms of heteroaromatic and non-heteroaromatic compounds that were designed and evaluated for AchE inhibition by Ellman’s method of assay. These novel compounds may assist the future perspectives in the discovery of novel moieties against Alzheimer’s disease by the inhibition of AchE.

Polystyrene Microplastics Exposure: An Insight into Multiple Organ Histological Alterations, Oxidative Stress and Neurotoxicity in Javanese Medaka Fish (Oryzias javanicus Bleeker, 1854)

Microplastics (MPs) have become pollutants of concern due to their unknown human health effect and negative impact on terrestrial and aquatic ecosystems. There is increasing number of experimental research on MPs globally with its effects not fully understood; recent animal studies explore its effects on the intestines, yet on other vital organs. Javanese medaka fish was exposed to polystyrene microplastics (PS-MPs) beads for a period of 21 days. Histological alterations, intestinal oxidative stress, permeability and neurotoxicity were evaluated. Significant inflammatory changes and tissue damage were observed in the intestine, liver and kidney. Intestinal oxidative stress and permeability were found to be significantly increased. In the brain, neurotoxicity characterised by a significant induction of oxidative stress, lipid peroxidation and the inhibition of acetylcholinesterase enzyme were elucidated. This study provided an insight into the multiple organ effect of microplastics exposure, necessitating further exploration and identification of biomarkers to be utilised for biomonitoring population at risk in the future.

Improvement of memory deficits via acetylcholinesterase inhibitory activity of Nepeta nuda ssp. nuda essential oil in rats

Nepeta L. (Lamiaceae) species are belonging to aromatic and medicinal plants. Many biological activities of Nepeta species have been reported. In this study, memory-enhancing activities of Nepeta nuda ssp. nuda essential oil was aimed to be evaluated in laboratory rats treated with scopolamine. GC-MS/GC-FID system was used to identify oil composition. Memory performances of the rats were tested using Y-maze and radial-arm maze. Acetylcholinesterase enzyme activity and molecular docking analysis were also performed in this study. In total, 44 different compounds were identified in Nepeta nuda ssp. nuda essential oil. Trans-cis nepetalactone was showed to be the most abundant constituent in the oil. In the Y-maze test, the oil improved the performances of the animals on spontaneous alternation. Besides, in the radial-arm maze test, the oil improved working and reference memory significantly impaired in the rats subjected to scopolamine. The oil also showed acetylcholinesterase inhibitory activity in vitro. The molecular docking method, in the meantime, revealed that some of the compounds in the oil could interact with the acetylcholinesterase enzyme, theoretically. Nepeta nuda ssp. nuda essential oil improved spatial memory of scopolamine-induced rats. Neuroprotective effects of the oil are probably related to the anti-cholinesterase activity of the oil. Therefore, Nepeta nuda ssp. nuda essential oil could be used as a complementary therapy to improve memory in Alzheimer’s and related diseases.

In silico Analysis of Alkaloids for Therapeutic Use in Treatment of Alzheimer's Disease by Targeting Acetylcholinesterase Enzyme

Alzheimer’s is a progressive mental deterioration associated with the degeneration of the cognition activities and memory loss. It is considered to be a multifactorial disease. One of the causes of the Alzheimer’s disease is the low concentration of the neurotransmitter named acetylcholine (ACh) at the synaptic cleft. Thus, inhibitor of Acetylcholinesterase (AChE), an enzyme whose function is to degrade the acetylcholine, is proved to be a promising candidate to treat this disease. Among the inhibitors are the natural alkaloids that also have an inhibitory effect on the AChE. In this study we have focused on the simple derivates of beta carbolime (a group of alkaloids) and studied their interaction with AChE via rigid protein-ligand docking approach.

Biological activity survey of Pereskia aculeata Mill. and Pereskia grandifolia Haw. (Cactaceae)

Background: Pereskia aculeata and P. grandifolia are non-traditional Brazilian vegetables with high nutritional value used in traditional medicine. The antioxidant, anticholinesterase, molluscicidal, cytotoxic, and antiproliferative properties of hydroethanolic extracts of P. aculeata and P. grandifolia leaves (PAL, PGL) and fruits (PAF, PGF) are investigated in this study. Methods: All extracts were prepared by maceration with ethanol 70%. Their antioxidant properties were assessed through DPPH, ABTS, FRAP, and β-carotene bleaching inhibition assays. A TLC bioautography method was employed to evaluate the inhibiting capacity of the acetylcholinesterase enzyme. The molluscicidal activity was tested against the snail Biomphalaria glabrata, which serves as an intermediate host for Schistosoma mansoni. The cytotoxic activity was assessed by a Artemia salina lethality test and the antiproliferative properties against seven human carcinoma cell lines. Results: Compounds with anticholinesterase activity were found in all extracts. Polar compounds present in PAF and PGL extracts were the most active (IC50 < 25 μg of dry mass) and had an adequate inhibition capacity of the AChE. PGF and PGL were classified as moderate (LC50 = 19.2 μg/ml) and modest molluscicidal agents (LC50 = 66.6 μg/ml), respectively. All extracts exhibited selective antiproliferative activity against human chronic myeloid leukemia cell lines (K562). PAL, PGL, and PGF presented potent antiproliferative activity (TGI ≤ 5 μg/ml). Conclusion: Both species exhibited anticholinesterase, cytotoxic and antiproliferative properties. This research supports the potential of these species as sustainable sources of nutraceutical compounds.