Batiha GE

References (18)

Title : Papaverinol-N-Oxide: A Microbial Biotransformation Product of Papaverine with Potential Antidiabetic and Antiobesity Activity Unveiled with In Silico Screening - Eliwa_2023_Molecules_28_
Author(s) : Eliwa D , Kabbash A , El-Aasr M , Tawfik HO , Batiha GE , Mahmoud MH , De Waard M , Eldehna WM , Ibrahim AS
Ref : Molecules , 28 : , 2023
Abstract : Bioconversion of biosynthetic heterocyclic compounds has been utilized to produce new semisynthetic pharmaceuticals and study the metabolites of bioactive drugs used systemically. In this investigation, the biotransformation of natural heterocyclic alkaloid papaverine via filamentous fungi was explored. Molecular docking simulations, using protein tyrosine phosphatase 1B (PTP1B), alpha-glucosidase and pancreatic lipase (PL) as target enzymes, were performed to investigate the antidiabetic potential of papaverine and its metabolites in silico. The metabolites were isolated from biotransformation of papaverine with Cunninghamella elegans NRRL 2310, Rhodotorula rubra NRRL y1592, Penicillium chrysogeneum ATCC 10002 and Cunninghamella blackesleeana NRRL 1369 via reduction, demethylation, N-oxidation, oxidation and hydroxylation reactions. Seven metabolites were isolated: namely, 3,4-dihydropapaverine (metabolite 1), papaveroline (metabolite 2), 7-demethyl papaverine (metabolite 3), 6,4'-didemethyl papaverine (metabolite 4), papaverine-3-ol (metabolite 5), papaverinol (metabolite 6) and papaverinol N-oxide (metabolite 7). The structural elucidation of the metabolites was investigated with 1D and 2D NMR and mass spectroscopy (EI and ESI). The molecular docking studies showed that metabolite 7 exhibited better binding interactions with the target enzymes PTP1B, alpha-glucosidase and PL than did papaverine. Furthermore, papaverinol-N-oxide (7) also displayed inhibition of alpha-glucosidase and lipase enzymes comparable to that of their ligands (acarbose and orlistat, respectively), as unveiled with an in silico ADMET profile, molecular docking and molecular dynamics studies. In conclusion, this study provides evidence for enhanced inhibition of PTP1B, alpha-glucosidase and PL via some papaverine fungal transformation products and, therefore, potentially better antidiabetic and antiobesity effects than those of papaverine and other known therapeutic agents.
ESTHER : Eliwa_2023_Molecules_28_
PubMedSearch : Eliwa_2023_Molecules_28_
PubMedID: 36838572

Title : Benzimidazole-Based Schiff Base Hybrid Scaffolds: A Promising Approach to Develop Multi-Target Drugs for Alzheimer's Disease - Hussain_2023_Pharmaceuticals.(Basel)_16_
Author(s) : Hussain R , Khan S , Ullah H , Ali F , Khan Y , Sardar A , Iqbal R , Ataya FS , El-Sabbagh NM , Batiha GE
Ref : Pharmaceuticals (Basel) , 16 : , 2023
Abstract : A series of benzimidazole-based Schiff base derivatives (1-18) were synthesized and structurally elucidated through (1)H NMR, (13)C NMR and HREI-MS analysis. Subsequently, these synthetic derivatives were subjected to evaluation for their inhibitory capabilities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). All these derivatives showed significant inhibition against AChE with an IC(50) value in the range of 123.9 +/- 10.20 to 342.60 +/- 10.60 microM and BuChE in the range of 131.30 +/- 9.70 to 375.80 +/- 12.80 microM in comparison with standard Donepezil, which has IC(50) values of 243.76 +/- 5.70 microM (AChE) and 276.60 +/- 6.50 microM (BuChE), respectively. Compounds 3, 5 and 9 exhibited potent inhibition against both AChE and BuChE. Molecular docking studies were used to validate and establish the structure-activity relationship of the synthesized derivatives.
ESTHER : Hussain_2023_Pharmaceuticals.(Basel)_16_
PubMedSearch : Hussain_2023_Pharmaceuticals.(Basel)_16_
PubMedID: 37765088

Title : Apigetrin-enriched Pulmeria alba extract prevents assault of STZ on pancreatic beta-cells and neuronal oxidative stress with concomitant attenuation of tissue damage and suppression of inflammation in the brain of diabetic rats - Abdulrasheed-Adeleke_2023_Biomed.Pharmacother_162_114582
Author(s) : Abdulrasheed-Adeleke T , Lawal B , Agwupuye EI , Kuo Y , Eni AM , Ekoh OF , Lukman HY , Onikanni AS , Olawale F , Saidu S , Ibrahim YO , Al Ghamdi MAS , Aggad SS , Alsayegh AA , Aljarba NH , Batiha GE , Wu ATH , Huang HS
Ref : Biomed Pharmacother , 162 :114582 , 2023
Abstract : In the present study, in vitro, in vivo, and in silico models were used to evaluate the therapeutic potential of Pulmeria alba methanolic (PAm) extract, and we identified the major phytocompound, apigetrin. Our in vitro studies revealed dose-dependent increased glucose uptake and inhibition of alpha-amylase (50% inhibitory concentration (IC(50))= 217.19 microg/mL), antioxidant (DPPH, ferric-reducing activity of plasma (FRAP), and lipid peroxidation (LPO) [IC(50) = 103.23, 58.72, and 114.16 microg/mL respectively]), and anti-inflammatory potential (stabilizes human red blood cell (HRBC) membranes, and inhibits proteinase and protein denaturation [IC(50) = 143.73, 131.63, and 198.57 microg/mL]) by the PAm extract. In an in vivo model, PAm treatment reversed hyperglycemia and attenuated insulin deficiency in rats with streptozotocin (STZ)-induced diabetes. A post-treatment tissue analysis revealed that PAm attenuated neuronal oxidative stress, neuronal inflammation, and neuro-cognitive deficiencies. This was evidenced by increased levels of antioxidants enzymes (superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH)), and decreased malondialdehyde (MDA), proinflammatory markers (cyclooxygenase 2 (COX2), nuclear factor (NF)-kappaB and nitric oxide (NOx)), and acetylcholinesterase (AChE) activities in the brain of PAm-treated rats compared to the STZ-induced diabetic controls. However, no treatment-related changes were observed in levels of neurotransmitters, including serotonin and dopamine. Furthermore, STZ-induced dyslipidemia and alterations in serum biochemical markers of hepatorenal dysfunction were also reversed by PAm treatment. Extract characterization identified apigetrin (retention time: 21,227 s, 30.48%, m/z: 433.15) as the major bioactive compound in the PAm extract. Consequently, we provide in silico insights into the potential of apigetrin to target AChE/COX-2/NOX/NF-kappaB Altogether the present study provides preclinical evidence of the therapeutic potential of the apigetrin-enriched PAm extract for treating oxidative stress and neuro-inflammation associated with diabetes.
ESTHER : Abdulrasheed-Adeleke_2023_Biomed.Pharmacother_162_114582
PubMedSearch : Abdulrasheed-Adeleke_2023_Biomed.Pharmacother_162_114582
PubMedID: 36989727

Title : Sweroside: An iridoid glycoside of potential neuroprotective, antidiabetic, and antioxidant activities supported by molecular docking - Zengin_2023_Amino.Acids__
Author(s) : Zengin G , El-Raey M , El-Kashak W , Batiha GE , Althumairy D , Alamer S , Mostafa NM , Eldahshan OA
Ref : Amino Acids , : , 2023
Abstract : Oxidative stress can be a series burden on human health and may lead to many chronic diseases such as diabetes and neurological disorders. The use of natural products to scavenge the reactive oxygen species has attracted the attention of many researchers, to safely manage these conditions with fewer side effects, in available and cost-effective ways. The current study aimed at the isolation and structure elucidation of sweroside from Schenkia spicata (Gentianaceae) and the evaluation of its antioxidant, antidiabetic, neuroprotective, and enzyme inhibitory potential via in vitro and in silico studies. The antioxidant potential was evaluated by a variety of assays as ABTS, CUPRAC and FRAP, showing values of 0.34 +/- 0.08, 21.14 +/- 0.43, and 12.32 +/- 0.20 mg TE/g, respectively, while demonstrating 0.75 +/- 0.03 mmol TE/g for phosphomolybdenum (PBD) assay. Acetylcholinestrase (AChE), butyrylcholinesterase (BChE) and tyrosinase inhibitory activities were used to evaluate the neuroprotective effect, while the antidiabetic potential was evaluated by measuring alpha-amylase and glucosidase inhibitory activities. Results revealed that sweroside showed antioxidant and inhibitory effects on the enzymes tested with the exception of AChE. It demonstrated good tyrosinase inhibitory ability with 55.06 +/- 1.85 mg Kojic acid equivalent /g. Regarding the antidiabetic ability, the compound displayed both amylase and glucosidase (0.10 +/- 0.01 and 1.54 +/- 0.01 mmol Acarbose equivalent/g, respectively) inhibitory activities. Molecular docking studies of sweroside on the active sites of the aforementioned enzymes in addition to NADPH oxidase were performed using Discovery Studio 4.1 software. Results revealed good binding affinities of sweroside to these enzymes mainly through hydrogen bonds and van der Waals interactions. Sweroside can be an important antioxidant and enzyme inhibitory supplement, yet further in vivo and clinical studies are required.
ESTHER : Zengin_2023_Amino.Acids__
PubMedSearch : Zengin_2023_Amino.Acids__
PubMedID: 36939919

Title : Attenuation of hyperglycemia-associated dyslipidemic, oxidative, cognitive, and inflammatory crises via modulation of neuronal ChEs\/NF-B\/COX-2\/NOx, andhepatorenal functional deficits by the Tridax procumbens extract - Hogan_2022_Biomed.Pharmacother_158_114114
Author(s) : Hogan IA , Kuo YC , Abubakar AN , Lawal B , Agboola AR , Lukman HY , Onikanni SA , Olawale F , Fadaka AO , Ibrahim YO , Babalola SB , Batiha GE , Albogami SM , Alorabi M , De Waard M , Huang HS
Ref : Biomed Pharmacother , 158 :114114 , 2022
Abstract : Tridax procumbens (cotton buttons) is a flowering plant with a medicinal reputation for treating infections, wounds, diabetes, and liver and kidney diseases. The present research was conducted to evaluate the possible protective effects of the T. procumbens methanolic extract (TPME) on an experimentally induced type 2 diabetes rat model. Wistar rats with streptozotocin (STZ)-induced diabetes were randomly allocated into five groups of five animals each, viz., a normal glycemic group (I), diabetic rats receiving distilled water group (II), diabetic rats with 150 (III) and 300smg/kg of TPME (IV) groups, and diabetic rats with 100smg/kg metformin group (V). All treatments were administered for 21 consecutive days through oral gavage. Results: Administration of the T. procumbens extract to diabetic rats significantly restored alterations in levels of fasting blood glucose (FBG), body weight loss, serum and pancreatic insulin levels, and pancreatic histology. Furthermore, T. procumbens significantly attenuated the dyslipidemia (increased cholesterol, low-density lipoprotein-cholesterol (LDL-C), triglycerides, and high-density lipoprotein (HDL) in diabetic rats), serum biochemical alterations (alanine transaminase (ALT), aspartate transaminase (AST), alanine phosphatase (ALP), blood urea nitrogen (BUN), creatinine, uric acid, and urea) and full blood count distortion in rats with STZ-induced diabetes. The TPME also improved the antioxidant status as evidenced by increased superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and decreased malondialdehyde (MDA); and decreased levels of cholinesterases (acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)), and proinflammatory mediators including nuclear factor (NF)-kappaB, cyclooxygenase (COX)-s2, and nitrogen oxide (NOx) in the brain of rats with STZ-induced diabetes compared to rats with STZ-induced diabetes that received distilled water. However, TPME treatment failed to attenuate the elevated monoamine oxidases and decreased dopamine levels in the brain of rats with STZ-induced diabetes. Extract characterization by liquid chromatography mass spectrometry (LC-MS) identified isorhamnetin (retention time (RT)=s3.69smin, 8.8%), bixin (RT: 25.06smin, 4.72%), and lupeol (RT: 25.25smin, 2.88%) as the three most abundant bioactive compounds that could be responsible for the bioactivity of the plant. In conclusion, the TPME can be considered a promising alternative therapeutic option for managing diabetic complications owing to its antidiabetic, antihyperlipidemic, antioxidant, and anti-inflammatory effects in rats with STZ-prompted diabetes.
ESTHER : Hogan_2022_Biomed.Pharmacother_158_114114
PubMedSearch : Hogan_2022_Biomed.Pharmacother_158_114114
PubMedID: 36525818

Title : 4-Phthalimidobenzenesulfonamide Derivatives as Acetylcholinesterase and Butyrylcholinesterase Inhibitors: DFTs, 3D-QSAR, ADMET, and Molecular Dynamic Simulation - Ejaz_2022_Neurodegener.Dis__
Author(s) : Ejaz SA , Fayyaz A , Mahmood HMK , Aziz M , Ejaz SR , Alkhuriji AF , WA IA-M , Aborode AT , Batiha GE
Ref : Neurodegener Dis , : , 2022
Abstract : INTRODUCTION: Alzheimer's disease (AD) is a form of dementia which affects majority of the people. It is characterized by memory loss and other cognitive functions disabilities and is one of the most challenging neurodegenerative disorders to treat, because of its progressive nature. The disease affects millions of people all around the world, and the number of those affected is expanding every day. In the previous study, the 4-phthalimidobenzenesulfonamide derivatives were synthesized as AChE and BChE inhibitors and here we are aiming to further reporting in-silico studies of these compounds for efficient drug discovery process and to find out the potential lead compounds. METHODS: In-silico characterization included: Density functional theory (DFT) studies, 3D-QSAR, ADMET properties, molecular docking and molecular dynamic simulations. The geometries of all derivatives were optimized using B3LYP method and 6-311G basis set. RESULTS: The findings of the current study revealed that 4-phthalimidobenzenesulfonamide derivatives exhibited a reactive electronic property which is essential for anti-cholinesterase activity. Moreover, optimized structures were subjected to molecular docking studies with targeted protein. The compound 2c and 2g showed excellent binding score of -37.44 and -33.67 kJ/mol with BChE and AChE, respectively and exhibited strong binding affinity. The potent derivatives produced stable complex with amino acid residues of active pocket of both BChE and AChE. The stability of protein-ligand complexes was determined by molecular dynamic simulation studies and results were found in correlation with molecular docking findings. CONCLUSION: Findings of current study suggested that these derivatives are potent inhibitors of cholinesterase enzyme.
ESTHER : Ejaz_2022_Neurodegener.Dis__
PubMedSearch : Ejaz_2022_Neurodegener.Dis__
PubMedID: 36288689

Title : Zingiber officinale and Vernonia amygdalina Infusions Improve Redox Status in Rat Brain - Rotimi_2022_Evid.Based.Complement.Alternat.Med_2022_9470178
Author(s) : Rotimi DE , Ben-Goru GM , Evbuomwan IO , Elebiyo TC , Alorabi M , Farasani A , Batiha GE , Adeyemi OS
Ref : Evid Based Complement Alternat Med , 2022 :9470178 , 2022
Abstract : The study investigated the effects of Zingiber officinale root and Vernonia amygdalina leaf on the brain redox status of Wistar rats. Twenty-four (24) rats weighing 160 +/- 20 g were randomly assigned into four (4) groups, each with six (6) rats. Animals in Group 1 (control) were orally administered distilled water (1 mL), while the test groups were orally administered 5 mg/mL of either Z. officinale, V. amygdalina infusion, or a combination of both, respectively, for 7 days. The rats were sacrificed at the end of treatments and blood and tissue were harvested and prepared for biochemical assays. Results showed that administration of V. amygdalina and Z. officinale, as well as their coadministration, reduced the levels of malondialdehyde (MDA), nitric oxide (NO), acetylcholinesterase (AChE), and myeloperoxidase (MPO) in rat brain tissue compared with the control group. Conversely, coadministration of V. amygdalina and Z. officinale increased the levels of reduced glutathione (GSH) in rat brain tissue compared with the control group. However, the administration of the infusions singly, as well as the combination of both infusions, did not have any effect on the rat brain levels of glutathione peroxidase (GPx) and catalase (CAT) antioxidant enzymes compared to the control. Taken together, the findings indicate that the V. amygdalina and Z. officinale tea infusions have favorable antioxidant properties in the rat brain. The findings are confirmatory and contribute to deepening our understanding of the health-promoting effects of V. amygdalina and Z. officinale tea infusions.
ESTHER : Rotimi_2022_Evid.Based.Complement.Alternat.Med_2022_9470178
PubMedSearch : Rotimi_2022_Evid.Based.Complement.Alternat.Med_2022_9470178
PubMedID: 36199544

Title : Therapeutic efficacy of Clompanus pubescens leaves fractions via downregulation of neuronal cholinesterases\/Na(+)-K(+)ATPase\/IL-1 beta, and improving the neurocognitive and antioxidants status of streptozotocin-induced diabetic rats - Onikanni_2022_Biomed.Pharmacother_148_112730
Author(s) : Onikanni AS , Lawal B , Oyinloye BE , Mostafa-Hedeab G , Alorabi M , Cavalu S , Olusola AO , Wang CH , Batiha GE
Ref : Biomed Pharmacother , 148 :112730 , 2022
Abstract : The increasing global burden of diabetes mellitus has called for the search for a therapeutic alternative that offers better activities and safety than conventional chemotherapy. Herein, we evaluated the neuroprotective and antioxidant properties of different fractions (ethyl acetate, N-butanol and residual aqueous) of Clompanus pubescens leaves in streptozotocin (STZ)-induced diabetic rats. Our results revealed a significant elevation in the levels of blood glucose, pro-inflammatory cytokines, lipid peroxidation, neuronal activities of acetylcholinesterase, butyrylcholinesterase, nitric oxide, epinephrine, norepinephrine, and Na+/K+-ATPase in diabetic non treated rats. In addition, decreased levels of enzymatic and non-enzymatic antioxidants were observed. Treatment with different fractions of C. pubescens leaves resulted in significant reversal of the biochemical alteration and improved the neurocognitive deficit in STZ induced diabetic rats. However, the ethyl-acetate fraction demonstrated higher activities than the other fractions and was characterized for its phytoconstituents, revealing the presence of Gallic acid (713.00 ppm), catechin (0.91 ppm), ferulic acid (0.98 ppm), rutin (59.82 ppm), quercetin (3.22 ppm) and kaempferol (4.07 ppm). Our molecular docking analysis revealed that these compounds exhibited different binding affinities and potentials for targeting BChE/AChE/ IL-1 beta/Na+ -K+ -ATPase. However, only Kampferol and ferulic exhibited good drug-like, ADMET, and permeability properties suitable for use as a neuronal drug target agent. Hence, the ethyl-acetate fraction of C. pubescens leaves could be considered as a source of promising bioactive metabolite for the treatment and management of cognitive impairments related to type II diabetes mellitus.
ESTHER : Onikanni_2022_Biomed.Pharmacother_148_112730
PubMedSearch : Onikanni_2022_Biomed.Pharmacother_148_112730
PubMedID: 35183996

Title : Cholinesterase activity as a potential biomarker for neurotoxicity induced by pesticides in vivo exposed Oreochromis niloticus (Nile tilapia) - Amin_2021_Environ.Technol__1
Author(s) : Amin M , Yousuf M , Attaullah M , Ahmad N , Azra MN , Latif M , Buneri ID , Zekker I , Batiha GE , Aboelenin SM , Zahoor M , Ikram M , Naeem M
Ref : Environ Technol , :1 , 2021
Abstract : Organophosphates (OPs) and synthetic pyrethroids (SPs) are the most popular broad spectrum pesticides, used in agriculture as they have a strong pesticidal activity while also being biodegradable in the environment. The present study aimed to demonstrate the effects of these pesticides on the Acetylcholinesterase (AChE) activity in brain, gills and body muscles of Oreochromis niloticus- an important enzyme for the assessment and biomonitoring pollution caused by neurotoxins in the environment. The fish were exposed for 24 and 48h to the LC(0) concentrations of the malathion (1.425mg/L), the chlorpyrifos (0.125mg/L) and the lambda-cyhalothrin (0.0039mg/L), respectively. The activity of the AChE was significantly increased (p < 0.05) at 24hours and decreased at 48hours (except for the chlorpyrifos- treated brain and gills while tissues had shown no activity at 48 hours' exposure) in all pesticides- treated tissues. The maximum increase in the activity and inhibition in the AChE activity were recorded as +92% and -52% in the chlorpyrifos and the lambda -cyhalothrin exposed brain tissues, respectively. Thus, the alterations in the AChE activities indicated that the applied pesticides are highly neurotoxic to fish and the enzyme (AChE) could be used as a useful biomarker for estimation of water pollution.
ESTHER : Amin_2021_Environ.Technol__1
PubMedSearch : Amin_2021_Environ.Technol__1
PubMedID: 34962184

Title : COVID-19 in Relation to Hyperglycemia and Diabetes Mellitus - Al-Kuraishy_2021_Front.Cardiovasc.Med_8_644095
Author(s) : Al-Kuraishy HM , Al-Gareeb AI , Alblihed M , Guerreiro SG , Cruz-Martins N , Batiha GE
Ref : Front Cardiovasc Med , 8 :644095 , 2021
Abstract : Coronavirus disease 2019 (COVID-19), triggered by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), may lead to extrapulmonary manifestations like diabetes mellitus (DM) and hyperglycemia, both predicting a poor prognosis and an increased risk of death. SARS-CoV-2 infects the pancreas through angiotensin-converting enzyme 2 (ACE2), where it is highly expressed compared to other organs, leading to pancreatic damage with subsequent impairment of insulin secretion and development of hyperglycemia even in non-DM patients. Thus, this review aims to provide an overview of the potential link between COVID-19 and hyperglycemia as a risk factor for DM development in relation to DM pharmacotherapy. For that, a systematic search was done in the database of MEDLINE through Scopus, Web of Science, PubMed, Embase, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), and Wanfang Data. Data obtained underline that SARS-CoV-2 infection in DM patients is more severe and associated with poor clinical outcomes due to preexistence of comorbidities and inflammation disorders. SARS-CoV-2 infection impairs glucose homeostasis and metabolism in DM and non-DM patients due to cytokine storm (CS) development, downregulation of ACE2, and direct injury of pancreatic beta-cells. Therefore, the potent anti-inflammatory effect of diabetic pharmacotherapies such as metformin, pioglitazone, sodium-glucose co-transporter-2 inhibitors (SGLT2Is), and dipeptidyl peptidase-4 (DPP4) inhibitors may mitigate COVID-19 severity. In addition, some antidiabetic agents and also insulin may reduce SARS-CoV-2 infectivity and severity through the modulation of the ACE2 receptor expression. The findings presented here illustrate that insulin therapy might seem as more appropriate than other anti-DM pharmacotherapies in the management of COVID-19 patients with DM due to low risk of uncontrolled hyperglycemia and diabetic ketoacidosis (DKA). From these findings, we could not give the final conclusion about the efficacy of diabetic pharmacotherapy in COVID-19; thus, clinical trial and prospective studies are warranted to confirm this finding and concern.
ESTHER : Al-Kuraishy_2021_Front.Cardiovasc.Med_8_644095
PubMedSearch : Al-Kuraishy_2021_Front.Cardiovasc.Med_8_644095
PubMedID: 34124187

Title : Pharmacological Screening of Viola odorata L. for Memory-Enhancing Effect via Modulation of Oxidative Stress and Inflammatory Biomarkers - Saleem_2021_Front.Pharmacol_12_664832
Author(s) : Saleem U , Hira S , Anwar F , Shah MA , Bashir S , Baty RS , Badr RH , Blundell R , Batiha GE , Ahmad B
Ref : Front Pharmacol , 12 :664832 , 2021
Abstract : Purpose: Alzheimer disease (AD) is a progressive neurodegenerative disorder that is caused by neuroinflammation and oxidative stress. The present study aimed to characterize and then investigate the memory-enhancing potential of Viola odorata methanolic extract in lipopolysaccharide (LPS)-treated mice. Methods: V. odorata characterization was done by using the GCMS technique. Neuroinflammation was induced by the intracerebroventricular administration of LPS at a dose of 12 microg. Animals were divided randomly into six groups (n = 10). Group I was normal control, which was given vehicle. Group II was disease control, which received LPS (12 microg) via the intracerebroventricular route. Group III was standard, which was administered with donepezil (3 microg) orally for 21 days. Groups IV-VI were the treatment groups, which were administered with the extract at 100, 200, and 400 mg/kg dose levels orally respectively for 21 days. Groups III-VI received LPS (12 microg) on the first day along with their treatments. During the treatment, the animals were assessed for memory retention by employing different behavioral paradigms namely elevated plus maze, passive avoidance, foot shock and open field. Various mediators [endogenous antioxidants, neurotransmitters, and acetylcholinesterase (AChE)] involved in the pathogenesis of AD were quantified by using the UV spectrophotometric method. Results: Extract-treated groups showed a remarkable improvement in cognitive impairment in all behavioral paradigms. Oxidative stress biomarkers, that is, superoxide dismutase, catalase, and glutathione were raised dose-dependently in the treatment groups with a dose-dependent decrease in the malonaldehyde and AChE levels in the brains of the treated animals. The treatment groups showed decreased levels of inflammatory biomarkers, that is, tumor necrosis factor-alpha, nuclear factor kappa light-chain enhancer of activated beta-cells, and cyclo-oxygenase, which supports the therapeutic effectiveness of the treatment. Conclusion: Based on behavioral, oxidative stress biomarker, and neuroinflammatory data, it is concluded that V. odorata possesses memory-enhancing activity and may prove a beneficial role in the management of AD.
ESTHER : Saleem_2021_Front.Pharmacol_12_664832
PubMedSearch : Saleem_2021_Front.Pharmacol_12_664832
PubMedID: 34149418

Title : Sterculia tragacantha Lindl Leaf Extract Ameliorates STZ-Induced Diabetes, Oxidative Stress, Inflammation and Neuronal Impairment - Onikanni_2021_J.Inflamm.Res_14_6749
Author(s) : Onikanni AS , Lawal B , Olusola AO , Olugbodi JO , Sani S , Ajiboye BO , Ilesanmi OB , Alqarni M , Mostafa-Hedeab G , Obaidullah AJ , Batiha GE , Wu ATH
Ref : J Inflamm Res , 14 :6749 , 2021
Abstract : BACKGROUND: Sterculia tragacantha is a medicinal plant commonly used in the western part of Nigeria, for managing diabetes mellitus. However, there is a dearth of scientific information on the antidiabetic and neuroprotective properties of the plant. METHODS: The in silico, in vitro and in vivo models were used to evaluate the antioxidants, antidiabetic, anti-inflammatory and neuroprotective potential of aqueous extract of Sterculia tragacantha leaf (AESTL) in streptozotocin (STZ)-induced diabetic rats. Thirty (30) male albino rats (155.34+/-6.33 g) were intraperitoneal injected with 40 mg/kg of freshly prepared streptozotocin and were divided into 5 groups (A-E) of 6 animals each. Groups A-D were treated with 0, 150 and 300 mg/kg of AESTL, and 200 mg/kg body weight of metformin respectively, while group E serve as the normal control. RESULTS: The results of in vitro analysis revealed dose-dependent antioxidant activities; ABTS (IC(50) = 63.03+/-2.57 microg/mL), DPPH (117.49+/-2.35 microg/mL), FRAP (15.19+/-0.98 mmol/100g), TAC (43.38+/-0.96 mg/100g), hypoglycaemic effect; alpha-amylase (IC(50) = 77.21+/-4.35 microg/mL) and alpha-glucosidase (IC(50) = 443.25+/-12.35), and anti-cholinesterase; AChE (IC(50) = 113.07+/-3.42 microg/mL) and BChE (IC(50) = 87.50+/-4.32 microg/mL) activities of AESTL. In vivo study revealed dose-dependent hypoglycemic effect and body weight improvement in rats treated with the AESTL. In addition, AESTL improved the antioxidant status and attenuated STZ-induced dysregulations of Na(+)-K(+)-ATPase, cholinesterases and neurotransmitters in the brain tissue of experimental rats. The results also demonstrated that AESTL could regulate anti-inflammatory response via inhibition of COX-2/NO signaling axis in the brain of diabetic rats. Molecular docking analysis revealed that epicatechin and procyanidin B2, the bioactive compounds from AESTL, docked well to the binding cavities of acetylcholinesterase, butyrylcholinesterase, alpha-amylase and alpha-glucosidase with binding affinities ranges between -8.0 and -11.4 kcal/mol, suggesting that these compounds are the bioactive component that could be responsible for the antidiabetic and neuroprotective activities of AESTL. CONCLUSION: The results of the present study strongly suggested that the AESTL extract could be very useful for halting diabetes progression and its associated neuroinflammation complications.
ESTHER : Onikanni_2021_J.Inflamm.Res_14_6749
PubMedSearch : Onikanni_2021_J.Inflamm.Res_14_6749
PubMedID: 34916823

Title : Deciphering the Interactions of Bioactive Compounds in Selected Traditional Medicinal Plants against Alzheimer's Diseases via Pharmacophore Modeling, Auto-QSAR, and Molecular Docking Approaches - Ojo_2021_Molecules_26_
Author(s) : Ojo OA , Ojo AB , Okolie C , Nwakama MC , Iyobhebhe M , Evbuomwan IO , Nwonuma CO , Maimako RF , Adegboyega AE , Taiwo OA , Alsharif KF , Batiha GE
Ref : Molecules , 26 : , 2021
Abstract : Neurodegenerative diseases, for example Alzheimer's, are perceived as driven by hereditary, cellular, and multifaceted biochemical actions. Numerous plant products, for example flavonoids, are documented in studies for having the ability to pass the blood-brain barrier and moderate the development of such illnesses. Computer-aided drug design (CADD) has achieved importance in the drug discovery world; innovative developments in the aspects of structure identification and characterization, bio-computational science, and molecular biology have added to the preparation of new medications towards these ailments. In this study we evaluated nine flavonoid compounds identified from three medicinal plants, namely T. diversifolia, B. sapida, and I. gabonensis for their inhibitory role on acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and monoamine oxidase (MAO) activity, using pharmacophore modeling, auto-QSAR prediction, and molecular studies, in comparison with standard drugs. The results indicated that the pharmacophore models produced from structures of AChE, BChE and MAO could identify the active compounds, with a recuperation rate of the actives found near 100% in the complete ranked decoy database. Moreso, the robustness of the virtual screening method was accessed by well-established methods including enrichment factor (EF), receiver operating characteristic curve (ROC), Boltzmann-enhanced discrimination of receiver operating characteristic (BEDROC), and area under accumulation curve (AUAC). Most notably, the compounds' pIC(50) values were predicted by a machine learning-based model generated by the AutoQSAR algorithm. The generated model was validated to affirm its predictive model. The best models achieved for AChE, BChE and MAO were models kpls_radial_17 (R(2) = 0.86 and Q(2) = 0.73), pls_38 (R(2) = 0.77 and Q(2) = 0.72), kpls_desc_44 (R(2) = 0.81 and Q(2) = 0.81) and these externally validated models were utilized to predict the bioactivities of the lead compounds. The binding affinity results of the ligands against the three selected targets revealed that luteolin displayed the highest affinity score of -9.60 kcal/mol, closely followed by apigenin and ellagic acid with docking scores of -9.60 and -9.53 kcal/mol, respectively. The least binding affinity was attained by gallic acid (-6.30 kcal/mol). The docking scores of our standards were -10.40 and -7.93 kcal/mol for donepezil and galanthamine, respectively. The toxicity prediction revealed that none of the flavonoids presented toxicity and they all had good absorption parameters for the analyzed targets. Hence, these compounds can be considered as likely leads for drug improvement against the same.
ESTHER : Ojo_2021_Molecules_26_
PubMedSearch : Ojo_2021_Molecules_26_
PubMedID: 33915968

Title : Thiourea Derivatives, Simple in Structure but Efficient Enzyme Inhibitors and Mercury Sensors - Rahman_2021_Molecules_26_
Author(s) : Rahman FU , Bibi M , Khan E , Shah AB , Muhammad M , Tahir MN , Shahzad A , Ullah F , Zahoor M , Alamery S , Batiha GE
Ref : Molecules , 26 : , 2021
Abstract : In this study six unsymmetrical thiourea derivatives, 1-isobutyl-3-cyclohexylthiourea (1), 1-tert-butyl-3-cyclohexylthiourea (2), 1-(3-chlorophenyl)-3-cyclohexylthiourea (3), 1-(1,1-dibutyl)-3-phenylthiourea (4), 1-(2-chlorophenyl)-3-phenylthiourea (5) and 1-(4-chlorophenyl)-3-phenylthiourea (6) were obtained in the laboratory under aerobic conditions. Compounds 3 and 4 are crystalline and their structure was determined for their single crystal. Compounds 3 is monoclinic system with space group P2(1)/n while compound 4 is trigonal, space group R(3):H. Compounds (1-6) were tested for their anti-cholinesterase activity against acetylcholinesterase and butyrylcholinesterase (hereafter abbreviated as, AChE and BChE, respectively). Potentials (all compounds) as sensing probes for determination of deadly toxic metal (mercury) using spectrofluorimetric technique were also investigated. Compound 3 exhibited better enzyme inhibition IC(50) values of 50, and 60 microg/mL against AChE and BChE with docking score of -10.01, and -8.04 kJ/mol, respectively. The compound also showed moderate sensitivity during fluorescence studies.
ESTHER : Rahman_2021_Molecules_26_
PubMedSearch : Rahman_2021_Molecules_26_
PubMedID: 34361659

Title : Piperazine-substituted chalcones: a new class of MAO-B, AChE, and BACE-1 inhibitors for the treatment of neurological disorders - Mathew_2021_Environ.Sci.Pollut.Res.Int__1
Author(s) : Mathew B , Oh JM , Baty RS , Batiha GE , Parambi DGT , Gambacorta N , Nicolotti O , Kim H
Ref : Environ Sci Pollut Res Int , :1 , 2021
Abstract : Eleven piperazine-containing 1,3-diphenylprop-2-en-1-one derivatives (PC1-PC11) were evaluated for their inhibitory activities against monoamine oxidases (MAOs), cholinesterases (ChEs), and beta-site amyloid precursor protein cleaving enzyme 1 (BACE-1) with a view toward developing new treatments for neurological disorders. Compounds PC10 and PC11 remarkably inhibited MAO-B with IC(50) values of 0.65 and 0.71 microM, respectively. Ten of the eleven compounds weakly inhibited AChE and BChE with > 50% of residual activities at 10 microM, although PC4 inhibited AChE by 56.6% (IC(50) = 8.77 microM). Compound PC3 effectively inhibited BACE-1 (IC(50) = 6.72 microM), and PC10 and PC11 moderately inhibited BACE-1 (IC(50) =14.9 and 15.3 microM, respectively). Reversibility and kinetic studies showed that PC10 and PC11 were reversible and competitive inhibitors of MAO-B with K(i) values of 0.63 +/- 0.13 and 0.53 +/- 0.068 microM, respectively. ADME predictions for lead compounds revealed that PC10 and PC11 have central nervous system (CNS) drug-likeness. Molecular docking simulations showed that fluorine atom and trifluoromethyl group on PC10 and PC11, respectively, interacted with the substrate cavity of the MAO-B active site. Our results suggested that PC10 and PC11 can be considered potential candidates for the treatment of neurological disorders such as Alzheimer's disease and Parkinson's disease.
ESTHER : Mathew_2021_Environ.Sci.Pollut.Res.Int__1
PubMedSearch : Mathew_2021_Environ.Sci.Pollut.Res.Int__1
PubMedID: 33743158

Title : Ameliorative Role of Cerium Oxide Nanoparticles Against Fipronil Impact on Brain Function, Oxidative Stress, and Apoptotic Cascades in Albino Rats - Elshony_2021_Front.Neurosci_15_651471
Author(s) : Elshony N , Nassar AMK , El-Sayed YS , Samak D , Noreldin A , Wasef L , Saleh H , Elewa YHA , Tawfeek SE , Saati AA , Batiha GE , Tomczyk M , Umezawa M , Shaheen HM
Ref : Front Neurosci , 15 :651471 , 2021
Abstract : Fipronil (FIP) is an N-phenylpyrazole insecticide that is used extensively in public health and agriculture against a wide range of pests. Exposure to FIP is linked to negative health outcomes in humans and animals including promoting neuronal cell injury, which results in apoptosis through the production of reactive oxygen species (ROS). Therefore, the purpose of the current study was to investigate the neuroprotective effects of cerium oxide nanoparticles (CeNPs) on neuronal dysfunction induced by FIP in albino rats. Male rats were randomly classified into four groups: control, FIP (5 mg/kg bwt), CeNPs (35 mg/kg bwt), and FIP + CeNPs (5 (FIP) + 35 (CeNPs) mg/kg bwt), which were treated orally once daily for 28 consecutive days. Brain antioxidant parameters, histopathology, and mRNA expression of genes related to brain function were evaluated. The results revealed oxidative damage to brain tissues in FIP-treated rats indicated by the elevated levels of malondialdehyde (MDA) and nitric oxide (NO) levels and reduced activities of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx). On the other hand, the FIP's group that was treated with CeNPs showed decrease in MDA and NO levels and increase in SOD and GPx enzymes activity. Besides, FIP-treated rats showed decreased butyrylcholinesterase (BuChE) activity in comparison to the FIP + CeNPs group. Moreover, FIP caused up-regulation of the expression of neuron-specific enolase (NSE), caspase-3, and glial fibrillary acidic protein (GFAP) but down-regulation of B-cell lymphoma-2 (BCL-2) expression. But the FIP + CeNPs group significantly down-regulated the GFAP, NSE, and caspase-3 and up-regulated the gene expression of BCL-2. Additionally, the FIP-treated group of rats had clear degenerative lesions in brain tissue that was reversed to nearly normal cerebral architecture by the FIP + CeNPs treatment. Immunohistochemical examination of brain tissues of rats-treated with FIP showed abundant ionized calcium-binding adaptor molecule 1 (Iba-1) microglia and caspase-3 and apoptotic cells with nearly negative calbindin and synaptophysin reaction, which were countered by FIP + CeNPs treatment that revealed a critical decrease in caspase-3, Iba-1 reaction with a strong calbindin positive reaction in most of the Purkinje cells and strong synaptophysin reaction in the cerebrum and cerebellum tissues. Based on reported results herein, CeNPs treatment might counteract the neurotoxic effect of FIP pesticide via an antioxidant-mediated mechanism.
ESTHER : Elshony_2021_Front.Neurosci_15_651471
PubMedSearch : Elshony_2021_Front.Neurosci_15_651471
PubMedID: 34054412

Title : The Pharmacological Activity, Biochemical Properties, and Pharmacokinetics of the Major Natural Polyphenolic Flavonoid: Quercetin - Batiha_2020_Foods_9_
Author(s) : Batiha GE , Beshbishy AM , Ikram M , Mulla ZS , El-Hack MEA , Taha AE , Algammal AM , Elewa YHA
Ref : Foods , 9 : , 2020
Abstract : Flavonoids are a class of natural substances present in plants, fruits, vegetables, wine, bulbs, bark, stems, roots, and tea. Several attempts are being made to isolate such natural products, which are popular for their health benefits. Flavonoids are now seen as an essential component in a number of cosmetic, pharmaceutical, and medicinal formulations. Quercetin is the major polyphenolic flavonoid found in food products, including berries, apples, cauliflower, tea, cabbage, nuts, and onions that have traditionally been treated as anticancer and antiviral, and used for the treatment of allergic, metabolic, and inflammatory disorders, eye and cardiovascular diseases, and arthritis. Pharmacologically, quercetin has been examined against various microorganisms and parasites, including pathogenic bacteria, viruses, and Plasmodium, Babesia, and Theileria parasites. Additionally, it has shown beneficial effects against Alzheimer's disease (AD), and this activity is due to its inhibitory effect against acetylcholinesterase. It has also been documented to possess antioxidant, antifungal, anti-carcinogenic, hepatoprotective, and cytotoxic activity. Quercetin has been documented to accumulate in the lungs, liver, kidneys, and small intestines, with lower levels seen in the brain, heart, and spleen, and it is extracted through the renal, fecal, and respiratory systems. The current review examines the pharmacokinetics, as well as the toxic and biological activities of quercetin.
ESTHER : Batiha_2020_Foods_9_
PubMedSearch : Batiha_2020_Foods_9_
PubMedID: 32210182

Title : Selected 1,3-Benzodioxine-Containing Chalcones as Multipotent Oxidase and Acetylcholinesterase Inhibitors - Jeong_2020_ChemMedChem_15_2257
Author(s) : Jeong GS , Kaipakasseri S , Lee SR , Marraiki N , Batiha GE , Dev S , Palakkathondi A , Kavully FS , Gambacorta N , Nicolotti O , Mathew B , Kim H
Ref : ChemMedChem , 15 :2257 , 2020
Abstract : Chalcones are considered effective templates for the development of monoamine oxidase (MAO) and cholinesterase (ChE) inhibitors. The present work describes the syntheses of selected 1,3-benzodioxine-containing chalcones (CD3, CD8 and CD10), and their inhibitory activities against MAO-A, MAO-B, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE). Compound CD8 most potently inhibited MAO-B with an IC(50) value of 0.026microM, followed by CD10 and CD3 (1.54 and 1.68microM, respectively). CD8 potently and non-selectively inhibited MAO-A (IC(50) value of 0.023microM). On the other hand, CD10 and CD8 inhibited AChE with IC(50) values of 5.40 and 9.57microM, respectively. Kinetics and reversibility experiments showed that all synthesized molecules were competitive and reversible inhibitors, and the K(i) values of CD8 for MAO-A and MAO-B were 0.018 and 0.0019microM, respectively. By invitro and in silico analyses, all compounds were found to have high passive human gastrointestinal absorptions, blood-brain barrier permeabilities, and non-toxicities. Molecular docking simulations revealed that docking affinity of each compound for MAO-B was higher than that for MAO-A. The results indicate that CD8 is a potent non-selective MAO inhibitor, and CD10 is an effective selective MAO-B inhibitor, and both possess AChE inhibitory activity. Therefore, we suggest that CD8 and CD10 be considered potential dual-targeting inhibitors of MAO and AChE for the treatment of various neurodegenerative disorders.
ESTHER : Jeong_2020_ChemMedChem_15_2257
PubMedSearch : Jeong_2020_ChemMedChem_15_2257
PubMedID: 32924264