Acetylcholinesterase Inhibitors Research Articles

A Case Report on Acotiamide’s Role in De-Prescribing PPI – An Offbeat Approach

Proton pump Inhibitors (PPI) are the commonest over the counter medications which are abused. Its prescribed even for minor gastric events and patients tend to take it for indefinite periods.PPI abuse can lead to wide range of toxic events like nephritis, osteoporosis, cardiac events, Clostridium infections, vitamin malabsorption. There are not many reports on management of pantaprazole abuse. Acotiamide is a drug which enhances acetylcholine release from enteric neurons through muscarinic receptor antagonism and acetylcholinesterase (AchE) inhibition, thereby enhancing gastric emptying and gastric accommodation. Here I am presenting a 36-year-old female with daily pantaprazole or omeprazole 40mg intake. She came for quitting the PPIs and was successfully managed with acotiamide and gradual tapering of the PPI.International Journal of Human and Health Sciences Vol. 08 No. 02 Apr’24 Page: 212-214

Letter to the editor: Limitations of acetylcholinesterase inhibitor (AChEI) therapy for Alzheimer's disease.

Letter to the editor: Limitations of acetylcholinesterase inhibitor (AChEI) therapy for Alzheimer's disease.

Environmental assessment of the central Atlantic coast of Morocco using a multibiomarker approach in Mytilus galloprovincialis.

A multibiomarker approach helps assess environmental health as it provides a complete tool to understand the effects of environmental stressors on ecosystems and human health. We applied this approach in the central Atlantic Ocean of Morocco, an area subjected to the impact of many types of pollutants, threatening the durability of its resources. In this study, four biomarkers acetylcholinesterase (AChE), glutathione-s-transferase (GST), metallothioneins (MTs), and catalase (CAT) were measured in the digestive gland of the mussel Mytilus galloprovincialis collected from four sites: Imsouane (S1), Cap Ghir (S2), Imi Ouaddar (S3), and Douira (S4). These sites were chosen due to the diversity of impacts ranging from industrial to agricultural and touristic. We also assembled all the enzymatic responses (AChE, GST, CAT, and MTs), using the integrated biomarker response (IBR), to estimate the degree of impact of pollutants at the prospected sites to reveal all the complex interactions between biomarkers and to classify sites via the integrated approach. Results show a seasonal change in biomarker responses with variability between sites. We also recorded the highest levels of AChE inhibition and GST induction in S1, higher levels of catalase activity in S4, and a significant impact on metallothionein concentration in S1 and S3. This project highlights the interest in using a multibiomarker approach to ensure accurate interpretation of biomarker variation to protect the Moroccan coast and its resources.

Labdanum Resin from Cistus ladanifer L. as a Source of Compounds with Anti-Diabetic, Neuroprotective and Anti-Proliferative Activity

Labdanum resin or “gum” can be obtained from Cistus ladanifer L. by two different extraction methods: the Zamorean and the Andalusian processes. Although its main use is in the fragrance and perfumery sectors, ethnobotanical reports describe its use for medicinal purposes in managing hyperglycemia and mental illnesses. However, data concerning the bioactivities and pharmacological applications are scarce. In this work, it was found that the yield of labdanum resin extracted by the Andalusian process was 25-fold higher than the Zamorean one. Both resins were purified as absolutes, and the Andalusian absolute was purified into diterpenoid and flavonoid fractions. GC-EI-MS analysis confirmed the presence of phenylpropanoids, labdane-type diterpenoids, and methylated flavonoids, which are already described in the literature, but revealed other compounds, and showed that the different extracts presented distinct chemical profile. The potential antidiabetic activity, by inhibition of α-amylase and α-glucosidase, and the potential neuroprotective activity, by inhibition of acetylcholinesterase, were investigated. Diterpenoid fraction produced the higher α-amylase inhibitory effect (~30% and ~40% at 0.5 and 1 mg/mL, respectively). Zamorean absolute showed the highest α-glucosidase inhibitory effect (~14% and ~24%, at 0.5 and 1 mg/mL, respectively). Andalusian absolute showed the highest acetylcholinesterase inhibitory effect (~70% and ~75%, at 0.5 and 1 mg/mL, respectively). Using Caco-2 and HepG2 cell lines, Andalusian absolute and its purified fractions showed moderate cytotoxic/anti-proliferative activity at 24 h exposure (IC50 = 45–70 µg/mL, for Caco-2; IC50 = 60–80 µg/mL, for HepG2), whereas Zamorean absolute did not produce cytotoxicity (IC50 ≥ 200.00 µg/mL). Here we show, for the first time, that labdanum resin obtained by the Andalusian process, and its fractions, are composed of phytochemicals with anti-diabetic, neuroprotective and anti-proliferative potential, which are worth investigating for the pharmaceutical industry. However, toxic side-effects must also be addressed when using these products by ingestion, as done traditionally.

Advances in Therapeutics to Alleviate Cognitive Decline and Neuropsychiatric Symptoms of Alzheimer’s Disease

Dementia exists as a ‘progressive clinical syndrome of deteriorating mental function significant enough to interfere with activities of daily living’, with the most prevalent type of dementia being Alzheimer’s disease (AD), accounting for about 80% of diagnosed cases. AD is associated with an increased risk of comorbidity with other clinical conditions such as hypertension, diabetes, and neuropsychiatric symptoms (NPS) including, agitation, anxiety, and depression as well as increased mortality in late life. For example, up to 70% of patients diagnosed with AD are affected by anxiety. As aging is the major risk factor for AD, this represents a huge global burden in ageing populations. Over the last 10 years, significant efforts have been made to recognize the complexity of AD and understand the aetiology and pathophysiology of the disease as well as biomarkers for early detection. Yet, earlier treatment options, including acetylcholinesterase inhibitors and glutamate receptor regulators, have been limited as they work by targeting the symptoms, with only the more recent FDA-approved drugs being designed to target amyloid-β protein with the aim of slowing down the progression of the disease. However, these drugs may only help temporarily, cannot stop or reverse the disease, and do not act by reducing NPS associated with AD. The first-line treatment options for the management of NPS are selective serotonin reuptake inhibitors/selective noradrenaline reuptake inhibitors (SSRIs/SNRIs) targeting the monoaminergic system; however, they are not rational drug choices for the management of anxiety disorders since the GABAergic system has a prominent role in their development. Considering the overall treatment failures and side effects of currently available medication, there is an unmet clinical need for rationally designed therapies for anxiety disorders associated with AD. In this review, we summarize the current status of the therapy of AD and aim to highlight novel angles for future drug therapy in our ongoing efforts to alleviate the cognitive deficits and NPS associated with this devastating disease.

Assessing the Efficacy and Biological Benefits of Withanolide-rich Withania somnifera Root Extract

The medicinal plant Withania somnifera, usually referred to as Ashwagandha, is a member of the Solanaceae family. The presence of Withanolides in the roots is responsible for a number of pharmacological effects in Ashwagandha. Withanolides have been demonstrated to be an effective neuronal, immune, anti-stress, and anti-cancer agent. However, Withanolides demonstrated limited permeability, lowering the bioavailability and efficacy of active compounds. The goal of the study was to ascertain the biological efficacy of Ashwagandha Composition, a blend of W. somnifera milk extract and water extract (1:1) with a high concentration of Withanolides (3-5%), at lower dosages with improved bioabsorption compared to pure Ashwagandha Hydro ethanolic extracts fortified with 2.5% withanolides. The W. somnifera Composition was assessed for its bioabsorption and bioefficacy by exploring its intestinal absorption capacity, Acetylcholinesterase Inhibition (82%), antioxidant potential (91%), glutathione reduction potential (15.6%), anti-inflammatory activity (87.2%), and anti-cancer activity. Additionally, Ashwagandha Composition was also evaluated for its safety profile. We found W. somnifera Composition (1:1) is more bioavailable and showed higher biological activity than the Ashwagandha Hydro ethanolic extract fortified with 2.5% withanolides (Ashwagandha extract). Hence, the W. somnifera a Composition can be used as a therapeutic medication once its safety concerns are addressed by in vivo trials.

Naphthoquinones and anthraquinones: Exploring their impact on acetylcholinesterase enzyme activity.

The identification of novel acetylcholinesterase inhibitors holds significant relevance in the treatment of Alzheimer's disease (AD), the prevailing form of dementia. The exploration of alternative inhibitors to the conventional acetylcholinesterase inhibitors is steadily gaining prominence. Quinones, categorized as plant metabolites, represent a specific class of compounds. In this study, the inhibitory effects of various naphthoquinone derivatives, along with anthraquinone and its derivatives, on the acetylcholinesterase (AChE) enzyme were investigated for this purpose. An in vitro investigation was conducted to examine the effects of these compounds in order to clarify the possible mechanism of inhibition in the interaction between the enzyme and chemicals. In addition, an in silico investigation was carried out to understand the conceivable inhibitor binding process to the enzyme's active site. The acquired outcomes corroborated the in vitro results. The AChE enzyme was found to be effectively inhibited by both naphthoquinones and anthraquinones, with inhibition constant (KI) values ranging from 0.014 to 0.123μM (micormolar). The AChE enzyme was inhibited differently by this quinone and its derivatives. Although derivatives of naphthoquinone and anthraquinone exhibited a competitive inhibitory effect, derivatives of anthraquinone exhibited a noncompetitive inhibition effect. Furthermore, because it had the lowest KI value of any of these substances, 1,5-dihydroxyanthraquinone (1c) was shown to be the most potent inhibitor. The findings will add to the body of knowledge on the creation of fresh, potent, and successful treatment approaches.

Chemical Constituents and Bioactivities of Nepeta Taxa Essential Oils from Turkey: Principal Component Analysis, Molecular Docking Study, Molecular Dynamics, MM‐PBSA and Drug‐Likeness Estimation

AbstractNepeta taxa are popular plants and sources of traditional Turkish medicine. Chemical constituents in the essential oils (EOs) hydrodistilled from above‐ground parts of Nepeta aristata (NA), N. baytopii (NB), N. italica (NI), N. nuda (NN), and N. stenantha (NS) were determined using GC‐MS. The pharmacological activities of EOs, such as biological activities, were evaluated in vitro. DNA protection activities of NS‐EO were found to be the most effective. The NA‐EO, NI‐EO, and NS‐EO were more potent urease inhibitors, while the NS‐EO exhibited potent AChE inhibitors. Their molecular docking, molecular dynamics and enzyme inhibition results were compatible with the major components. Furthermore, MolDock and binding affinity results were found to be high. Moreover, AChE‐tau‐cadinol, BChE‐tau‐cadinol and tyrosinase‐Caryophyllene oxide complexes showed stability when simulated for 100 ns, with high MM‐PBSA energy values. In addition, the main components′ pharmacokinetic properties were observed to be effective. The present study showed that EOs may be valuable natural products for future pharmacological research, food, and the cosmetic industry according to in vitro and in silico values.

Structures and Acetylcholinesterase Inhibition Abilities of some Derivatives Bearing (Pyridin-2-yl)tetrazole Scaffold

Tetrazole derivatives are a prominent class of heterocycles that hold significant value in medicinal chemistry and drug design. Their importance stems from their bioisosteric resemblance to carboxylic acid and amide moieties and their favorable metabolic stability and other beneficial physicochemical properties. In light of this, novel derivatives bearing the (pyridine-2-yl)tetrazol scaffold were synthesized with the presence of acid, ester and amide moieties and evaluated for their inhibitory effects on the enzyme acetylcholinesterase (AChE). Through a three-step synthesis reaction initiated with 2-pyridine carbonitrile, compound IV was successfully obtained with II and III as the intermediates. All substances II - III - IV demonstrated inhibitory activity against the enzyme acetylcholinesterase. Notably, substance IV exhibited the highest percentage of inhibition, achieving 23,7 % at a concentration of 75 µM. Based on molecular docking simulations, compounds containing stronger nucleophilic substituents exhibit more robust AChE enzyme inhibitory activity due to a greater abundance of hydrogen bonds. This drug-likeness simulation and ADME prediction highlight the potential of tetrazole derivatives as a promising treatment for Alzheimer's disease.

Niacin based MOF as efficient nano-catalyst in the synthesis of some new benzothiazoles and benzimidazoles as anti-Alzheimer (AChE inhibitors)

Metal-organic frameworks (MOFs) presented as an efficient, economic, sustainable and green stable catalyst. Co/Niacin-MOF in nano shape was prepared by hydrothermal method and illustrated by IR, SEM and XRD. The prepared Co/Niacin-MOF used in the synthesis of some new benzothiazoles and benzimidazoles (3a-3f, 4a-4f). The prepared benzo heterocyclic compounds were checked as acetylcholine esterase inhibitors (AChE inhibitors) and the data obtained from in vitro and molecular docking explained that there two promised values for compounds 4-(benzo[d]thiazol-2-yl)phenyl benzoate (3e) and 4-(1H-benzo[d]imidazol-2-yl)phenyl 4-methylbenzenesulfonate (4f) compared with Donepezil as a reference Alzheimer drug.

Discovery of novel cholinesterase inhibitors easily crossing the blood-brain barrier via structure-property relationship investigation: Methylenedioxy-cinnamicamides containing tertiary amine side chain.

In the present investigation, a series of dimethoxy or methylenedioxy substituted-cinnamamide derivatives containing tertiary amine moiety (N. N-Dimethyl, N, N-diethyl, Pyrrolidine, Piperidine, Morpholine) were synthesized and evaluated for cholinesterase inhibition and blood-brain barrier (BBB) permeability. Although their chemical structures are similar, their biological activities exhibit diversity. The results showed that all compounds except for those containing morpholine group exhibited moderate to potent acetylcholinesterase inhibition. Preliminary screening of BBB permeability shows that methylenedioxy substituted compounds have better brain permeability than the others. Compound 10c, containing methylenedioxy and pyrrolidine side chain, showed a better acetylcholinesterase inhibition (IC50: 1.52±0.19 μmol/L) and good blood-brain barrier permeability. Further pharmacokinetic investigation of compound 10c using ultra high performance liquid chromatography-mass/mass spectrometry (UPLC-MS/MS) in mice showed that compound 10c in brain tissue reached its peak concentration (857.72 ± 93.56 ng/g) after dosing 30 min. Its half-life in the serum is 331 min (5.52 h), and the CBrain/CSerum at various sampling points is ranged from 1.65 to 4.71(Mean: 2.76) within 24 hours. This investigation provides valuable information on the chemistry and pharmacological diversity of cinnamic acid derivatives and may be beneficial for the discovery of central nervous system drugs.

Nanoencapsulation of Colchicum speciosum for Alleviating Lower Back Pain

Nanoencapsulation of Colchicum speciosum for Alleviating Lower Back Pain

Acetylcholinesterase inhibitors are ineffective in MuSK-antibody positive myasthenia gravis: Results of a study on 202 patients

BackgroundMyasthenia gravis (MG) with MuSK antibodies (MuSK-MG) represents a distinct subtype with different responses to treatments compared to patients with AChR antibodies, especially in terms of tolerance to acetylcholinesterase inhibitors (AChEI). However, AChEI are often used as first line symptomatic treatment in MuSK-MG, despite reports that they are poorly tolerated, seldom effective or even deleterious. MethodsWe analyzed demographic, clinical and therapeutic responses and side-effects in the large cohort of 202 MuSK-MG patients cared for at the MG Clinic of Azienda Ospedaliero-Universitaria Pisana. Results165 patients had received AChEI at first evaluation. Only 7/165 patients (4.2%) reported an initial clinical benefit. Conversely, 76.9% of patients reported at least one side effect, most commonly neuromuscular hyperexcitability (68.4%), gastrointestinal (53.9%) and neurovegetative (35.8%) disturbances. 56 (33.9%) patients reported a concomitant worsening of muscle weakness and twelve patients (7.3%) suffered a cholinergic crisis. According to these patients, the severity of cholinergic side effects was greater at higher doses of AChEI, but side effects occurred regardless of the dose administered and ceased once the drug was discontinued. ConclusionsThis is the largest population of MuSK-MG patients reported for perceived responsiveness and tolerance to AChEI treatment. Our obervations strongly suggest avoiding this treatment in MuSK-MG.

Newly synthesized Bis-Hydrazono[1,3,4] thiadiazoles as Anti-Alzheimer’s Agents: Greener past and In-Vitro acetylcholinesterase inhibition assay investigations

The designed and synthesized multifunctional properties of bis-hydrazono[1,3,4]thiadiazoles became important for developing an efficient medication for Alzheimer’s disease. Thiadiazoles were characterized and studied towards this target as an acetylcholinesterase inhibitor (ChEIs). In this study, one-pot synthetic strategy was applied for the synthesis of bis-hydrazono[1,3,4]thiadiazole series from 2,2′-(1,2-diphenylethane-1,2-diylidene)bis(hydrazine-1-carbodithioic acid) and hydrazonoyl chlorides. The greener pastures, in silico, an environmentally-friendly and free computer-aided method, bioactivity studies of the bis-hydrazono[1,3,4]thiadiazoles 4a-h exhibited various possible interesting inhibitory activities against AChE showing similar behaviour to the approved drugs, Donepezil, Galantamine and Rivastigmine. For a fair comparison, the superpositions of 4a-h, and Donepezil, Galantamine and Rivastigmine docked together into the functional domain (binding pocket) of 1EVE to reveal interesting different molecular laydowns of the compounds. On the other side, the display of the molecules before and after docking was discussed. The binding affinity slightly differs between Donepezil, Galantamine, Rivastigmine, and the ligands 4a-h. The range of the recorded binding affinity for 4a-h is from (−9.4 to −8.4 kcal/mol−1), whereas the binding affinity for Donepezil, Galantamine and Rivastigmine is (−11.1, −9.8 and −8.0 kcal/mol−1 respectively), which is higher than all the prepared ligands.Furthermore, the binding amino acids also varied among the studied compounds in this study. Phe290, Phe330, Phe331, Trp279, Tyr70, Tyr121 and Tyr334 are the common amino acids binding with the FDA-approved AChE inhibitors for treating AD, Donepezil, Galantamine and Rivastigmine and ligands. Notably, the number of hydrophobic and hydrogen interactions studied between the ligands 4a-h and the Donepezil, Galantamine and Rivastigmine drugs were compared as a preliminary indicator towards a successful inhibitor. The comparative study in this research work aims to rank our compounds with respect to the approved medications. This is a friendly environmental preliminary helpful indication before leaping into time and energy-consuming experimental work. Organ toxicological endpoints and toxicity-predicted activity were obtained using the ProTox-II web server for both the approved medication and ligands. Later, in-vitro acetylcholinesterase inhibition assays were conducted to assess the efficacy of bis-hydrazono[1,3,4]thiadiazoles 4a-h as inhibitors of acetylcholinesterase (AChE) in comparison to Donepezil. Results indicated promising inhibition activities for example 4 h, 4 g and 4d to the testing drug Donepezil for breaking down the neurotransmitter acetylcholine.

Investigation of novel benzimidazole-based indole/thiazole hybrids derivatives as effective anti-diabetics and anti-alzheimer's agents: Structure-activity relationship insight, in vitro and in silico approaches

Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are common in developed countries and their incidence is increasing. The research is mostly concentrated on the exploration of novel therapies to remedy or avert these ailments. AD and T2DM have several molecular pathways in common that contributes to their degenerative development.A novel series of ten hybrid analogues (1-10) based on benzimidazole bearing indole analogues were synthesized and these scaffolds were characterized by spectroscopic techniques like HR-EIMS, 13CNMR and 1HNMR. Furthermore,the synthesized moieties were screened for α-amylase and α-glucosidase inhibitory activities. All these synthesized analogues showed good to moderate α-amylase and α-glucosidase inhibition potency ranging (4.90 ± 0.10 to 15.30 ± 0.60 µM) and (5.30 ± 0.10 to 16.10 ± 0.60 µM) while acarbose was used as a reference standard (IC50 = 10 .30 ±0.20µM), (IC50 = 9.80 ± 0.20 µM). Another series of ten hybrid analogues (11-20) based on benzimidazole bearing thiazole moieties were synthesized and were evaluated for AChE and BuChE inhibition activities. All these newly afforded analogues showed good to moderate AChE and BuChE inhibitory potential ranging of (IC50 = 0.20 ± 0.01 µM), (IC50 = 0.15 ± 0.01 µM) to (IC50 = 3.90 ± 0.20 µM), (IC50 = 3.80 ± 0.10 µM) while Donepezil was taken as a reference standard with (IC50 = 0.016 ± 0.01 µM), (IC50 = 0.30 ± 0.010 µM).The scaffolds were also characterized using spectroscopic techniques such as HR-EIMS, 13CNMR and 1HNMR for a better understanding of their structure. SAR was done for all synthesized analogues for substituents.In addition, docking research was conducted to determine the binding mode of interaction between the active site of analogues and targeted enzymes. This work aims to estimate the potential of the synthesized scaffolds as competitors to existing drugs. Incorporating molecular docking analysis with in vitro activities improves the accuracy of predictions and validates the possibility of these compounds as options for treating type-2 diabetes and Alzheimer's disease.

Cyanidin improves spatial memory and cognition in bisphenol A-induced rat model of Alzheimer's-like neuropathology by restoring canonical Wnt signaling

IntroductionResearch has unveiled the neurotoxicity of Bisphenol A (BPA) linked to neuropathological traits of Alzheimer's disease (AD) through varied mechanisms. This study aims to investigate the neuroprotective properties of cyanidin, an anthocyanin, in an in vivo model of BPA-induced Alzheimer's-like neuropathology. MethodsThree-week-old Sprague-Dawley rats were randomly assigned to four groups: vehicle control, negative control (BPA exposure), low-dose cyanidin treatment (BPA + cyanidin 5 mg/kg), and high-dose cyanidin treatment (BPA + cyanidin 10 mg/kg). Spatial memory was assessed through behavioral tests, including the Y-maze, novel object recognition, and Morris water maze. After behavioral tests, animals were euthanized, and brain regions were examined for acetylcholinesterase inhibition, p-tau, Wnt3, GSK3β, and β-catenin levels, antioxidant activities, and histopathological changes. ResultsBPA-exposed groups displayed memory impairments, while cyanidin-treated groups showed significant memory improvement (p < 0.0001). Cyanidin down regulated p-tau and glycogen synthase kinase-3β (GSK3β) and restored Wnt3 and β-catenin levels (p < 0.0001). Moreover, cyanidin exhibited antioxidant properties, elevating catalase and superoxide dismutase levels. The intervention significantly reduced the concentrations of acetylcholinesterase in the cortex and hippocampus in comparison to the groups treated with BPA (p < 0.0001). Significant gender-based disparities were not observed. ConclusionCyanidin demonstrated potent neuroprotection against BPA-induced Alzheimer's-like neuropathology by enhancing antioxidant defenses, modulating tau phosphorylation by restoring the Wnt/β-catenin pathway, and ameliorating spatial memory deficits. This study highlights the therapeutic potential of cyanidin in countering neurotoxicity linked to BPA exposure.

Advancing the understanding of VAMP1-related congenital myasthenic syndrome: phenotypic insights, favorable response to 3,4-diaminopyridine, and clinical characterization of five new cases

Congenital myasthenic syndromes (CMS) are a group of inherited neuromuscular junction (NMJ) disorders arising from gene variants encoding diverse NMJ proteins. Recently, the VAMP1 gene, responsible for encoding the vesicle-associated membrane protein 1 (VAMP1), has been associated with CMS. This study presents a characterization of five new individuals with VAMP1-related CMS, providing insights into the phenotype.The individuals with VAMP1-related CMS exhibited early disease onset, presenting symptoms prenatally or during the neonatal period, alongside severe respiratory involvement and feeding difficulties. Generalized weakness at birth was a common feature, and none of the individuals achieved independent walking ability. Notably, all cases exhibited scoliosis. The clinical course remained stable, without typical exacerbations seen in other CMS types.The response to anticholinesterase inhibitors and salbutamol was only partial, but the addition of 3,4-diaminopyridine (3,4-DAP) led to significant and substantial improvements, suggesting therapeutic benefits of 3,4-DAP for managing VAMP1-related CMS symptoms. Noteworthy is the identification of the VAMP1 (NM_014231.5): c.340delA; p.Ile114SerfsTer72 as a founder variant in the Iberian Peninsula and Latin America.This study contributes valuable insights into VAMP1-related CMS, emphasizing its early onset, arthrogryposis, facial and generalized weakness, respiratory involvement, and feeding difficulties. Furthermore, the potential efficacy of 3,4-DAP as a useful therapeutic option warrants further exploration. The findings have implications for clinical management and genetic counseling in affected individuals. Additional research is necessary to elucidate the long-term outcomes of VAMP1-related CMS.

Synthesis and Evaluation of Aminothiazole Hybrids as Potential Acetylcholinesterase Inhibitors

This study aimed to synthesize aminothiazole derivatives with 1,3,4-oxadiazole moiety and evaluated their acetylcholinesterase (AChE) and antioxidant activity in order to check their potency against Alzheimer's disease. Inhibition screening against AChE indicated that  synthesized derivatives expressed well to moderate AChE inhibitory activity in vitro. Of the examined synthetic compounds (3a-i), compound 3d expressed the best inhibition with IC50-0.35 µM. The antioxidant activity of all the synthesized compounds was also  analyzed by the DPPH assay. Finally, in molecular docking analysis, the best docking score was displayed by the most active compound  3d supported the in vitro inhibition results. Compound 3d emerged to be promising lead for the further development of anti- Alzheimer’s drugs.

Essential oil from Piper tuberculatum Jacq. (Piperaceae) and its majority compound β-caryophyllene: mechanism of larvicidal action against Aedes aegypti (Diptera: Culicidae) and selective toxicity.

Synthetic insecticides have been the primary approach in controlling Aedes aegypti; however, their indiscriminate use has led to the development of resistance and toxicity to non-target animals. In contrast, essential oils (EOs) are alternatives for vector control. This study investigated the mechanism of larvicidal action of the EO and β-caryophyllene from Piper tuberculatum against A. aegypti larvae, as well as evaluated the toxicity of both on non-target animals. The EO extracted from P. tuberculatum leaves was majority constituted of β-caryophyllene (54.8%). Both demonstrated larvicidal activity (LC50 of 48.61 and 57.20ppm, p < 0.05), acetylcholinesterase inhibition (IC50 of 57.78 and 71.97ppm), and an increase in the production of reactive oxygen and nitrogen species in larvae after exposure to the EO and β-caryophyllene. Furthermore, EO and β-caryophyllene demonstrate no toxicity to non-target animals Toxorhynchites haemorrhoidalis, Anisops bouvieri, and Diplonychus indicus (100% of survival rate), while the insecticide α-cypermethrin was highly toxic (100% of death). The results demonstrate that the EO from P. tuberculatum and β-caryophyllene are important larvicidal agents.

Use of sugammadex in prevention of post-operative urinary retention in minimally invasive hernia surgery.

Post-operative urinary retention (POUR) is a known complication of hernia surgery. Minimally invasive inguinal hernia repair (IHR) is typically done under general anesthesia with neuromuscular blockade (NMB), which is commonly reversed with an anticholinesterase inhibitor paired with an anticholinergic agent. Sugammadex is a unique NMB reversal agent that does not have to be paired with an anticholinergic. We sought to explore the role of sugammadex in reducing the rate of POUR following these procedures. Data were collected retrospectively at a single institution between February 2016 and October 2019. We identified and studied patients who underwent minimally invasive IHR and received either sugammadex or neostigmine/glycopyrrolate for NMB reversal. The primary endpoint was POUR requiring bladder catheterization. Secondary endpoints included post-operative and 30-day readmissions. 274 patients were included in this study (143 received neostigmine and glycopyrrolate, 131 sugammadex). The sugammadex patients were on average 5years older than the neostigmine/ glycopyrrolate patients (63.2 vs 58.2, p = 0.003), and received less median intravenous fluids (IVF) (900ml vs 1000ml; p = 0.015). There was a significant difference in the rate of POUR between the sugammadex and neostigmine/glycopyrrolate patients (0.0% vs 8.4%, p ≤ 0.001). The difference remained significant after controlling for age and IVF. The odds of POUR for those who received neostigmine/glycopyrrolate were 25 × higher than the odds of those who received sugammadex. The results of this study reflect the protective role of sugammadex against POUR in minimally invasive IHR cases.