scholarly journals Biphenylalkoxyamine Derivatives–Histamine H3 Receptor Ligands with Butyrylcholinesterase Inhibitory Activity

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3580
Author(s):  
Dorota Łażewska ◽  
Paula Zaręba ◽  
Justyna Godyń ◽  
Agata Doroz-Płonka ◽  
Annika Frank ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Inhibitory Activity ◽  
Symptomatic Treatment ◽  
In Vivo Studies ◽  
Avoidance Task ◽  
Receptor Ligands ◽  
Mao B ◽  
Histamine H3

Neurodegenerative diseases, e.g., Alzheimer’s disease (AD), are a key health problem in the aging population. The lack of effective therapy and diagnostics does not help to improve this situation. It is thought that ligands influencing multiple but interconnected targets can contribute to a desired pharmacological effect in these complex illnesses. Histamine H3 receptors (H3Rs) play an important role in the brain, influencing the release of important neurotransmitters, such as acetylcholine. Compounds blocking their activity can increase the level of these neurotransmitters. Cholinesterases (acetyl- and butyrylcholinesterase) are responsible for the hydrolysis of acetylcholine and inactivation of the neurotransmitter. Increased activity of these enzymes, especially butyrylcholinesterase (BuChE), is observed in neurodegenerative diseases. Currently, cholinesterase inhibitors: donepezil, rivastigmine and galantamine are used in the symptomatic treatment of AD. Thus, compounds simultaneously blocking H3R and inhibiting cholinesterases could be a promising treatment for AD. Herein, we describe the BuChE inhibitory activity of H3R ligands. Most of these compounds show high affinity for human H3R (Ki < 150 nM) and submicromolar inhibition of BuChE (IC50 < 1 µM). Among all the tested compounds, 19 (E153, 1-(5-([1,1′-biphenyl]-4-yloxy)pentyl)azepane) exhibited the most promising in vitro affinity for human H3R, with a Ki value of 33.9 nM, and for equine serum BuChE, with an IC50 of 590 nM. Moreover, 19 (E153) showed inhibitory activity towards human MAO B with an IC50 of 243 nM. Furthermore, in vivo studies using the Passive Avoidance Task showed that compound 19 (E153) effectively alleviated memory deficits caused by scopolamine. Taken together, these findings suggest that compound 19 can be a lead structure for developing new anti-AD agents.

Xanthine oxidase inhibitory activity of nicotino/isonicotinohydrazides: A systematic approach from in vitro , in silico to in vivo studies

2017 ◽  
Vol 25 (8) ◽  
pp. 2351-2371 ◽  
Author(s):  
Humaira Zafar ◽  
Muhammad Hayat ◽  
Sumayya Saied ◽  
Momin Khan ◽  
Uzma Salar ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
Inhibitory Activity ◽  
In Silico ◽  
Systematic Approach ◽  
In Vivo Studies

scholarly journals Scientific Evaluation of Dhuma Yoga (An Ayurvedic Fumigation Medicine) as Preventive and Curative on Symptoms of Covid-19 Disease

2021 ◽  
pp. 49-61
Author(s):  
Siva Ram
Keyword(s):  
Scientific Explanation ◽  
Cannabis Sativa ◽  
Symptomatic Treatment ◽  
In Vivo Studies ◽  
Scientific Evaluation ◽  
Systematic Effects ◽  
Novel Coronavirus ◽  
Fast Acting

Covid-19, an infectious disease caused by a novel coronavirus SARS-CoV-2 spreads primarily through droplets of saliva or discharge from the nose when an infected person talks, coughs or sneezes where the viruses are active in the environment within the suspended micro droplets. Sanitization of environment to weaken/terminate the virus and halting the replication of virus inside the host along with symptomatic treatment is the primary approach to end the pandemic. In Ayurveda, Dhupana (medicated fumigation of vicinity) and Dhumapana (medicated smoking) therapies done by drugs of herbal/animal/mineral origin are a swift way to decontaminate the environment and Respiratory system. Dhuma (medicated fumes) is a unique drug delivery system acting directly on respiratory tissues which can deliver quick results in this Covid-19 pandemic by its local and systematic effects recommended by AYUSH ministry in the guidelines for Covid-19. We intend to put forward the scientific explanation of powerful Ayurvedic Cannabis based polyherbal dhumapana (medicated smoking) medication named Dhuma Yoga available in the market as an alternate remedy for Covid-19 whose four out of five herbal ingredients are in the list of WHO manual of traditional medicine. We emphasized on Vijaya (Cannabis sativa Linn.) as the centre of formulation because it is a Rasayana (rejuvenative) herb having Vyavayi (fast acting) and Yogavahi (synergetic) properties. Phytochemicals of all the herbal ingredients of Dhuma Yoga formulation are studied through in silico, In vitro and In vivo studies for Covid-19 with favourable outcomes.

scholarly journals Dual Target Ligands with 4-tert-Butylphenoxy Scaffold as Histamine H3 Receptor Antagonists and Monoamine Oxidase B Inhibitors

2020 ◽  
Vol 21 (10) ◽  
pp. 3411 ◽  
Author(s):  
Dorota Łażewska ◽  
Agnieszka Olejarz-Maciej ◽  
David Reiner ◽  
Maria Kaleta ◽  
Gniewomir Latacz ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Inhibitory Activity ◽  
In Vivo Studies ◽  
Monoamine Oxidase B ◽  
Histamine H3 Receptor ◽  
Mao B ◽  
Positive Effects ◽  
H3 Receptor ◽  
Dual Target ◽  
Histamine H3

Dual target ligands are a promising concept for the treatment of Parkinson’s disease (PD). A combination of monoamine oxidase B (MAO B) inhibition with histamine H3 receptor (H3R) antagonism could have positive effects on dopamine regulation. Thus, a series of twenty-seven 4-tert-butylphenoxyalkoxyamines were designed as potential dual-target ligands for PD based on the structure of 1-(3-(4-tert-butylphenoxy)propyl)piperidine (DL76). Probed modifications included the introduction of different cyclic amines and elongation of the alkyl chain. Synthesized compounds were investigated for human H3R (hH3R) affinity and human MAO B (hMAO B) inhibitory activity. Most compounds showed good hH3R affinities with Ki values below 400 nM, and some of them showed potent inhibitory activity for hMAO B with IC50 values below 50 nM. However, the most balanced activity against both biological targets showed DL76 (hH3R: Ki = 38 nM and hMAO B: IC50 = 48 nM). Thus, DL76 was chosen for further studies, revealing the nontoxic nature of DL76 in HEK293 and neuroblastoma SH-SY5Ycells. However, no neuroprotective effect was observed for DL76 in hydrogen peroxide-treated neuroblastoma SH-SY5Y cells. Furthermore, in vivo studies showed antiparkinsonian activity of DL76 in haloperidol-induced catalepsy (Cross Leg Position Test) at a dose of 50 mg/kg body weight.

Brain histamine H3 receptors in rats with portacaval anastomosis: in vitro and in vivo studies

1998 ◽  
Vol 358 (5) ◽  
pp. 574-581 ◽  
Author(s):  
V. Lozeva ◽  
Martti Attila ◽  
Eeva Anttila ◽  
Kirsti Laitinen ◽  
Mikko Hippeläinen ◽  
...  
Keyword(s):  
In Vivo Studies ◽  
Portacaval Anastomosis ◽  
Brain Histamine ◽  
Histamine H3 Receptors ◽  
H3 Receptors ◽  
Histamine H3

scholarly journals In Vitro and In Vivo Studies on Quercus acuta Thunb. (Fagaceae) Extract: Active Constituents, Serum Uric Acid Suppression, and Xanthine Oxidase Inhibitory Activity

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
In-Soo Yoon ◽  
Dae-Hun Park ◽  
Min-Suk Bae ◽  
Deuk-Sil Oh ◽  
Nan-Hui Kwon ◽  
...  
Keyword(s):  
South Korea ◽  
Xanthine Oxidase ◽  
Inhibitory Activity ◽  
In Vivo Studies ◽  
Gas Chromatography Mass Spectrometry ◽  
Similar Extent ◽  
Active Constituents ◽  
Quercus Acuta

Quercus acuta Thunb. (Fagaceae) (QA) is cultivated as a dietary and ornamental plant in China, Japan, South Korea, and Taiwan. It has been widely used as the main ingredient of acorn tofu, a traditional food in China and South Korea. The aim of this study was to determine in vitro and in vivo xanthine oxidase (XO) inhibitory and antihyperuricemic activities of an ethyl acetate extract of QA leaf (QALE) and identify its active phytochemicals using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography (LC) systems. The QALE was found to possess potent in vitro antioxidant and XO inhibitory activities. In vivo study using hyperuricemic mice induced with potassium oxonate demonstrated that the QALE could inhibit hepatic XO activity at a relatively low oral dose (50 mg/kg) and significantly alleviate hyperuricemia to a similar extent as allopurinol. Several active compounds including vitamin E known to possess XO inhibitory activity were identified from the QALE. To the best of our knowledge, this is the first study that reports the active constituents and antihyperuricemic effect of QA, suggesting that it is feasible to use QALE as a food therapy or alternative medicine for alleviating hyperuricemia and gout.

An Upcoming Approach to Alzheimer's Disease: Ethnopharmacological Potential of Plant Bioactive Molecules

2020 ◽  
Vol 27 (26) ◽  
pp. 4344-4371 ◽  
Author(s):  
Natália Martins ◽  
Sandrina A. Heleno ◽  
Isabel C.F.R. Ferreira
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Present Report ◽  
Symptomatic Treatment ◽  
The Elderly ◽  
Bioactive Molecules ◽  
In Vivo Studies ◽  
Limited Effectiveness

Background:: Neurodegenerative disorders have achieved epidemic levels in the last decades; not only the elderly but also adult individuals have been increasingly affected. Among them, Alzheimer’s disease is one of the most prevalent and crippling diseases, associated with high rates of multi-morbidities and dependency. Despite the existence of a wide variety of drugs used as the symptomatic treatment, they have some side effects and toxicity, apart from their limited effectiveness. Botanical preparations have a secular use, being widely recommended for a multitude of purposes, such as for the improvement of brain health. Objective: The aim of the present report is to systematize the knowledge on plant-food derived bioactive molecules with promising in vitro enzymatic inhibitory activities. Results: Alkaloids, phenolic compounds and terpenes are the most studied phytochemicals, both derived from natural and commercial sources. In spite of their efficient activity as enzymatic inhibitors, the number of in vivo studies and even clinical trials have confirmed that their real bioactive potential remains scarce. Conclusions: Thus, it is of the utmost importance to deepen knowledge in this area, once those relevant and informative tools can significantly contribute to the promising advances in the field of Alzheimer’s disease treatment.

scholarly journals Carbohydrate Hydrolase-Inhibitory Activity of Juice-Based Phenolic Extracts in Correlation to Their Anthocyanin/Copigment Profile

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5224
Author(s):  
Kirsten Berger ◽  
Johanna Josefine Ostberg-Potthoff ◽  
Tamara Bakuradze ◽  
Peter Winterhalter ◽  
Elke Richling
Keyword(s):  
Inhibitory Activity ◽  
Phenolic Content ◽  
In Vivo Studies ◽  
Size Dependent ◽  
Inhibitory Activities ◽  
Sugar Levels ◽  
Red Grape ◽  
Phenolic Extracts

Red fruits and their juices are rich sources of polyphenols, especially anthocyanins. Some studies have shown that such polyphenols can inhibit enzymes of the carbohydrate metabolism, such as α-amylase and α-glucosidase, that indirectly regulate blood sugar levels. The presented study examined the in vitro inhibitory activity against α-amylase and α-glucosidase of various phenolic extracts prepared from direct juices, concentrates, and purees of nine different berries which differ in their anthocyanin and copigment profile. Generally, the extracts with the highest phenolic content—aronia (67.7 ± 3.2 g GAE/100 g; cyanidin 3-galactoside; chlorogenic acid), pomegranate (65.7 ± 7.9 g GAE/100 g; cyanidin 3,5-diglucoside; punicalin), and red grape (59.6 ± 2.5 g GAE/100 g; malvidin 3-glucoside; quercetin 3-glucuronide)—showed also one of the highest inhibitory activities against α-amylase (326.9 ± 75.8 μg/mL; 789.7 ± 220.9 μg/mL; 646.1 ± 81.8 μg/mL) and α-glucosidase (115.6 ± 32.5 μg/mL; 127.8 ± 20.1 μg/mL; 160.6 ± 68.4 μg/mL) and, partially, were even more potent inhibitors than acarbose (441 ± 30 μg/mL; 1439 ± 85 μg/mL). Additionally, the investigation of single anthocyanins and glycosylated flavonoids demonstrated a structure- and size-dependent inhibitory activity. In the future in vivo studies are envisaged.

Antioxidant Effect of Flavonoids Present in Euterpe oleracea Martius and Neurodegenerative Diseases: A Literature Review

2019 ◽  
Vol 19 (2) ◽  
pp. 75-99 ◽  
Author(s):  
Nayana Keyla Seabra de Oliveira ◽  
Marcos Rafael Silva Almeida ◽  
Franco Márcio Maciel Pontes ◽  
Mariana Pegrucci Barcelos ◽  
Carlos Henrique Tomich de Paula da Silva ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Therapeutic Potential ◽  
Antioxidant Properties ◽  
In Vivo Studies ◽  
Euterpe Oleracea ◽  
Case Review ◽  
The Central Nervous System

Introduction:Neurodegenerative diseases (NDDs) are progressive, directly affecting the central nervous system (CNS), the most common and recurrent are Alzheimer's disease (AD) and Parkinson's disease (PD). One factor frequently mentioned in the etiology of NDDs is the generation of free radicals and oxidative stress, producing cellular damages. Studies have shown that the consumption of foods rich in polyphenols, especially those of the flavonoid class, has been related to the low risk in the development of several diseases. Due to the antioxidant properties present in the food, a fruit that has been gaining prominence among these foods is the Euterpe oleracea Mart. (açaí), because it presents in its composition significant amounts of a subclass of the flavonoids, the anthocyanins.Methods:In the case review, the authors receive a basic background on the most common NDDs, oxidative stress and antioxidants. In addition, revisiting the various studies related to NDDs, including flavonoids and consumption of açaí.Results:Detailed analysis of the recently reported case studies reveal that dietary consumption of flavonoid-rich foods, such as açaí fruits, suggests the efficacy to attenuate neurodegeneration and prevent or reverse the age-dependent deterioration of cognitive function.Conclusion:This systematic review points out that flavonoids presenting in açaí have the potential for the treatment of diseases such as PD and AD and are candidates for drugs in future clinical research. However, there is a need for in vitro and in vivo studies with polyphenol that prove and ratify the therapeutic potential of this fruit for several NDDs.

A Search for New 5-HT1A/5-HT2A Receptor Ligands. In Vitro and in vivo Studies of 1-[ω-(4-Aryl-1-piperazinyl)alkyl]indolin-2(1H)-ones

1998 ◽  
Vol 331 (10) ◽  
pp. 325-330 ◽  
Author(s):  
Maria J. Mokrosz ◽  
Beata Duszyńska ◽  
Stanisław Misztal ◽  
Aleksandra Kłodzińska ◽  
Ewa Tatarczyńska ◽  
...  
Keyword(s):  
In Vivo Studies ◽  
Receptor Ligands

scholarly journals Therapeutics Effects of Oral Cavity Derived Stem Cells on the Neurodegenerative Diseases: A Systematic Review

2021 ◽  
pp. 1-29
Author(s):  
Emel Uzunoglu-Ozyurek ◽  
◽  
Gizem Önal ◽  
Serap Dökmeci ◽  
◽  
...  
Keyword(s):  
Stem Cells ◽  
Oral Cavity ◽  
Neurodegenerative Diseases ◽  
In Vitro Studies ◽  
In Vivo Studies ◽  
Published Data ◽  
Moderate Evidence ◽  
The Impact

Objective: Published data obtained from in vitro and in vivo studies was reviewed systematically and analyzed critically in order to evaluate the effect of oral cavity derived stem cells (OCDSCs) on the recovery/therapy of neurodegenerative diseases (NDs) such as Alzheimer’s (AD), Amyotrophic Lateral Sclerosis (ALS), Huntington’s (HD) and Parkinson’s (PD). Methods: An electronic search was accomplished. References of included articles were also searched manually. Studies were critically evaluated for suitability against inclusion/exclusion criteria and data was extracted. Bias risk evaluation of the studies and evidence synthesis were conducted. Results: Fourteen in vivo and 10 in vitro studies met inclusion criteria. PD was induced in 10 in vivo and 7 in vitro studies, while AD was induced in 2 in vivo and 4 in vitro studies. Two studies (1 in vitro and 1 in vivo) evaluated ALS disease and 1 in vivo study evaluated HD. Moderate evidence was found for in vitro studies reporting positive effect of OCDSCs on either PD or AD recovery. Strong evidence was found for in vivo studies in which PD animal models were used; while moderate evidence was found for the impact of OCDSCs on the recovery of the AD. Limited evidence was found for in vivo studies evaluating HD and ALS. Conclusion: Although studies included reported favorable data regarding the OCDSCs on NDs, they presented considerable risk of bias. Because of heterogenous study characteristics, current study recommends the improvement of standardized methods to evaluate the therapeutics effects of OCDSCs on the NDs.

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