Journal of Experimental Pharmacology最新文献

{"title":"Analgesic and Anti-Inflammatory Activities of 80% Methanol Extract and Solvent Fractions of <i>Ehretia cymosa Thonn</i> (<i>Boraginaceae</i>) Leaves in Rodents.","authors":"Getachew Ashagrie,&nbsp;Abiy Abebe,&nbsp;Shemsu Umer","doi":"10.2147/JEP.S396769","DOIUrl":"https://doi.org/10.2147/JEP.S396769","url":null,"abstract":"<p><strong>Background: </strong>Ethnobotanical studies in various districts of Ethiopia reported that <i>Ehretia cymosa</i> (<i>E. cymosa</i>) is used for the management of headache, abdominal pain, arthritis and rheumatism. However, there is no scientific investigation done so far to confirm these traditional claims. Thus, the aim of this study was to assess the analgesic and anti-inflammatory effects of the 80% methanol extract and fractions of <i>E. cymosa</i> leaves.</p><p><strong>Methods: </strong>The dried and pulverized leaves of <i>E. cymosa</i> were soaked with 80% methanol to obtain a crude extract. Fractionation was done using chloroform, ethyl acetate and water by a soxhlet apparatus. The analgesic effects of the crude extract and solvent fractions were assessed using acetic acid-induced writhing and hot plate tests whereas anti-inflammatory activities were investigated using carrageenan-induced paw edema and cotton-pellet-induced granuloma models.</p><p><strong>Results: </strong>In all the tested doses, the 80% methanol extract and solvent fractions revealed substantial (p < 0.001) analgesic activities in acetic acid induced writhing test. In the hot plate method, all the tested doses of <i>E. cymosa</i> crude extract and the solvent fractions produced significant analgesic activities (p < 0.05). In the carrageenan-induced acute inflammation model, all tested doses of the crude extract and solvent fractions resulted in a significant decline in paw edema. The 80% methanol extract and solvent fractions of <i>E. cymosa</i> at all the tested doses significantly reduced inflammatory exudates and granuloma mass formations (p < 0.001).</p><p><strong>Conclusion: </strong>From the results of this investigation, it can be stated that 80% methanol extract, aqueous, ethyl acetate and chloroform fractions of <i>E. cymosa</i> exhibited considerable analgesic and anti-inflammatory activities, supporting the plant's traditional use as a remedy for a variety of painful and inflammatory conditions.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"15 ","pages":"63-79"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/79/f1/jep-15-63.PMC9970881.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10832209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Moringa oleifera</i> Leaves Extract Ameliorates Doxorubicin-Induced Cardiotoxicity via Its Mitochondrial Biogenesis Modulatory Activity in Rats.","authors":"Cyntia Gracesella Patintingan,&nbsp;Melva Louisa,&nbsp;Vetnizah Juniantito,&nbsp;Wawaimuli Arozal,&nbsp;Silmi Hanifah,&nbsp;Septelia Inawati Wanandi,&nbsp;Rajarajan Thandavarayan","doi":"10.2147/JEP.S413256","DOIUrl":"https://doi.org/10.2147/JEP.S413256","url":null,"abstract":"<p><strong>Background: </strong>Doxorubicin, an anthracycline class of anticancer, is an effective chemotherapeutic agent with serious adverse effects, mainly cardiotoxicity. Several possible causes of doxorubicin cardiotoxicity are increased oxidative stress, nucleic acid and protein synthesis inhibition, cardiomyocyte apoptosis, and mitochondrial biogenesis disruptions. <i>Moringa oleifera</i> (MO), a naturally derived medicine, is known for its antioxidative properties and activity in alleviating mitochondrial dysfunction. To determine the potency and possible cardioprotective mechanism of MO leaves aqueous extract via the mitochondrial biogenesis pathway in doxorubicin-induced rats.</p><p><strong>Methods: </strong>Twenty-four Sprague-Dawley rats were divided into four groups of six. The first group was normal rats; the second group was treated with doxorubicin 4 mg/kg BW intraperitoneally once weekly for four weeks; the third and fourth groups were treated with doxorubicin 4 mg/kg BW intraperitoneally once weekly, and MO leaves extract at 200 mg/kg BW or 400 mg/kg BW orally daily, for four weeks. At the end of the fourth week, blood and cardiac tissues were obtained and analyzed for cardiac biomarkers, mitochondrial DNA copy number, mRNA expressions of peroxisome-activated receptor-gamma coactivator-1 alpha (PGC-1α), the nuclear factor erythroid 2-related factor 2 (Nrf2), superoxide dismutase 2 (SOD2), caspase 3, the activity of glutathione peroxidase (GPx), levels of 8-hydroxy-2-deoxyguanosine (8-OH-dG), and malondialdehyde.</p><p><strong>Results: </strong>MO leaves extract was shown to decrease biomarkers of cardiac damage (LDH and CK-MB), malondialdehyde levels, and GPx activity. These changes align with the reduction of mRNA expressions of caspase-3, the increase of mRNA expressions of PGC-1α and Nrf2, and the elevation of mitochondrial DNA copy number. MO leaves extracts did not influence the mRNA expressions of superoxide dismutase 2 (SOD2) or the levels of 8-OH-dG.</p><p><strong>Conclusion: </strong><i>Moringa oleifera</i> leaves extract ameliorates doxorubicin-induced cardiotoxicity by reducing apoptosis and restoring gene expression of PGC-1α and Nrf2, a key regulator in mitochondrial biogenesis.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"15 ","pages":"307-319"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/33/49/jep-15-307.PMC10387274.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10277157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analgesic and Anti-Inflammatory Effects of 80% Methanol Extract and Solvent Fractions of the Leaves of <i>Vernonia auriculifera</i> Hiern. (Asteraceae).","authors":"Ephrem Ashenafi,&nbsp;Teferra Abula,&nbsp;Solomon Mequanente Abay,&nbsp;Mahlet Arayaselassie,&nbsp;Samson Taye,&nbsp;Rekik Ashebir Muluye","doi":"10.2147/JEP.S398487","DOIUrl":"https://doi.org/10.2147/JEP.S398487","url":null,"abstract":"<p><strong>Background: </strong>The leaves of <i>V. auriculifera</i> has been used traditionally for the treatment of inflammatory disorders, and pain in various parts of Ethiopia. However, to our knowledge, the analgesic and anti-inflammatory activity of the crude extract and solvent fractions has never been experimentally studied.</p><p><strong>Objective: </strong>To assess the analgesic and anti-inflammatory activities of <i>V. auriculifera</i> leaf extract and solvent fractions in rodent models.</p><p><strong>Material and methods: </strong>Air-dried leaves of <i>V. auriculifera </i>were grounded and macerated using 80% methanol. The air-dried, grounded leaves were also successively extracted with ethyl acetate, and methanol. The residue was then macerated in water for 72 hr. The extract's peripheral analgesic activity, as well as the solvent fractions, were determined using an acetic acid-induced writhing test. The hot plate model was used to assess the central analgesic effect. Carrageenan-induced hind paw edema and cotton pellet-induced granuloma models were used to assess the anti-inflammatory effect in rats.</p><p><strong>Results: </strong>The 80% methanol leaf extract and solvent fractions have demonstrated significant (p < 0.05) peripheral and central analgesic activity. Both 80% methanol leaf extract and solvent fractions of <i>V. auriculifera</i> were found to have anti-inflammatory activity in a carrageenan-induced rat paw edema model. In the cotton pellet-induced granuloma model, all concentrations of 80% methanol leaf extract (ME), methanol fraction (MEF), and aqueous fractions (AQF) of <i>V. auriculifera</i> inhibited exudate and granuloma formation. Although all tested doses significantly inhibited granuloma mass formation, only the medium and highest ethyl acetate fraction (EAF) doses significantly inhibited the generation of inflammatory exudate.</p><p><strong>Conclusion: </strong>This study's findings indicate that the solvent fractions and 80% methanol extract of <i>V. auriculifera</i> have analgesic and anti-inflammatory properties. This study's findings not only confirm the plants' traditional claim but also provide clues for further investigation of the active principles of this plant for the development of effective and safe analgesic and anti-inflammatory drugs.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"15 ","pages":"29-40"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/de/a6/jep-15-29.PMC9888398.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10643541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: Effect of Kaempferol on Tacrolimus-Induced Nephrotoxicity and Calcineurin B1 Expression Level in Animal Model [Corrigendum].","authors":"","doi":"10.2147/JEP.S405132","DOIUrl":"https://doi.org/10.2147/JEP.S405132","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.2147/JEP.S265359.].</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"15 ","pages":"27-28"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/83/4d/jep-15-27.PMC9875568.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10626057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Hyperglycemic and Hypoglycemic Activities of 80% Methanol Extract and Solvent Fractions of <i>Ocimum lamiifolium</i> Hochst Ex Benth. (Lamiaceae) Leaves in Mice.","authors":"Tilahun Tesfaye,&nbsp;Firehiwot Teka,&nbsp;Gudeta Duga,&nbsp;Temesgen Obsa,&nbsp;Beyene Dereje,&nbsp;Eyasu Makonnen","doi":"10.2147/JEP.S409997","DOIUrl":"https://doi.org/10.2147/JEP.S409997","url":null,"abstract":"<p><strong>Background: </strong>Globally, the prevalence of diabetes mellitus is rising. Due to the scarcity, high cost, and many adverse effects of modern treatments, traditional medicine is commonly used in rural areas to treat a variety of illnesses, including diabetes mellitus. The aim of this study was to assess the antihyperglycemic and hypoglycemic effects of <i>Ocimum lamiifolium</i> Hochst ex Benth leaves.</p><p><strong>Methods: </strong>A crude methanol 80% extract's and its solvent fractions' effects on healthy, oral glucose-given, and STZ-induced diabetic mice were examined. Swiss albino mice of either sex were assigned into sixteen groups, each containing six mice, for the OGTT and hypoglycemia tests. Male mice were used in the study, and they were divided into groups for the negative control (citrate buffer for diabetic mice), the normal control (Tween 2%), the test groups, and a positive control (glibenclamide) for the antihyperglycemic test in STZ (200 mg/kg body weight)-induced diabetic mice.</p><p><strong>Results: </strong>A crude 80% methanol extract of 200 mg/kg effectively lowered blood glucose levels (p <0.05) and none of the fractions extracts caused hypoglycemia shock in norma mice. The aqueous residue at 100, 200, and 400 mg/kg, the n-butanol fraction at 100 and 200 mg/kg, and the chloroform fraction at 200 mg/kg demonstrated higher glucose tolerance in orally glucose-loaded mice (p <0.05). The crude 400 mg/kg of an 80% methanol extract, 100 and 200 mg/kg of the n-butanol fraction, 200 and 400 mg/kg of the chloroform fraction, and 5 mg/kg of glibenclamide significantly reduced blood glucose levels in STZ-induced diabetic mice (p <0.05).</p><p><strong>Conclusion: </strong>The current research demonstrates that a crude 80% methanol extract of <i>Ocimum lamiifolium</i> Hochst ex Benth leaves, as well as its solvent fractions, significantly reduce blood sugar levels in mice that are healthy, loaded with glucose, and streptozotocin induced diabetic mice.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"15 ","pages":"255-266"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d0/18/jep-15-255.PMC10257431.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9620735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Oil Formulation Derived from <i>Moringa Oleifera</i> Seeds Ameliorates Behavioral Abnormalities in Water-immersion Restraint Stress Mouse Model.","authors":"Emni Purwoningsih, Wawaimuli Arozal, Hee Jae Lee, Agian Jeffilano Barinda, Yulvian Sani, Abdul Munim","doi":"10.2147/JEP.S386745","DOIUrl":"10.2147/JEP.S386745","url":null,"abstract":"<p><strong>Purpose: </strong>Repeated stress events are well known to be associated with the onset of behavioral abnormalities including depression, anxiety and memory impairment. In spite of the traditional uses of <i>Moringa oleifera</i> (MO), no experimental evidence for its use against chronic stress exists. Here, we investigated whether seed oil from MO (MOO) could improve behavior abnormalities of chronic stress mice induced by water-immersion restraint stress (WIRS) and the underlying mechanism.</p><p><strong>Methods: </strong>BALB/C male mice at 12 weeks of age were exposed to chronic WIRS for two weeks and divided in to four groups: normal group, WIRS group, WIRS+MOO1 group (treated with MOO at the dose of 1 mL/kg BW), and WIRS+MOO2 group (treated with MOO 2 mL/kg BW). The MOO treatment was given orally for 23 days. On day 24, we checked the behavior parameters, the plasma level of cortisol, acetylcholinesterase (AChE) activity in hippocampus, mRNA expression level of brain-derived neurotrophic factor (<i>BDNF</i>) and oxidative stress parameters in brain tissues. In addition, we also checked the histopathological features of the gastric mucosa wall.</p><p><strong>Results: </strong>Administration of MOO ameliorated anxiety-like, depression-like and memory impairment phenotypes in the WIRS mouse model although the plasma cortisol concentrations were comparable among the groups. Of note, MOO both in two doses could suppress the AChE activity in hippocampus tissue and ameliorated the MDA level in prefrontal cortex tissue in mice exposed to WIRS. Although only WIRS+MOO2 group could increase the mRNA expression of <i>BDNF</i>, the histopathological gastric mucosa wall features were improved in all MOO groups.</p><p><strong>Conclusion: </strong>Taken together, these finding suggested that MOO may have a neuroprotective effect in the mouse model of WIRS as evidenced by improving the abnormal behaviors through enhancing mRNA expression level of <i>BDNF</i>, inhibited AChE activity, and prevented the increase of MDA level in the brain.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"14 ","pages":"395-407"},"PeriodicalIF":0.0,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/68/81/jep-14-395.PMC9792812.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10455904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antidepressant-Like Activity of Solvent Fractions of the Root Bark of <i>Carissa spinarum</i> Linn. (Apocynaceae) in Rodents Involves Multiple Signaling Pathways.","authors":"Hana Saif Ali, Ephrem Engidawork","doi":"10.2147/JEP.S386015","DOIUrl":"10.2147/JEP.S386015","url":null,"abstract":"<p><strong>Background: </strong>The root bark of <i>Carissa spinarum </i>Linn. (Apocynaceae) is claimed to be used for the management of depression in Ethiopian folkloric medicine, and the crude extract has been reported to possess antidepressant-like activity in rodents.</p><p><strong>Objective: </strong>This study aimed to evaluate the antidepressant-like effect of different fractions of the root bark in rodents and the possible underlying mechanisms in rats.</p><p><strong>Methods: </strong>A 70% ethanol extract of the root bark was successively fractionated with n-butanol, ethyl acetate, and water. Animals of both sexes received 2% Tween 80, imipramine (30 mg/kg), or various doses (50, 100, 200 mg/kg) of the fractions. Duration of immobility was determined using the tail suspension test and the forced swim test. Locomotor activity was evaluated in the open field test. Serum corticosterone levels, total phenols, flavonoids, and alkaloids were determined. Preliminary mechanistic studies were also performed to explore possible mechanisms of action of the active fraction.</p><p><strong>Results: </strong>All fractions but the aqueous fraction significantly (p<0.001) decreased the duration of immobility in both tests, with the ethyl acetate fraction being the most active. The locomotor test revealed that the activity was not due to non-specific psycho-stimulant effects. Serum corticosterone levels were reduced by both fractions, with the ethyl acetate fraction again being the most effective. Mechanistic studies showed the involvement of multiple neurotransmission systems, including adrenergic, dopaminergic and cholinergic as well as L-Arginine-NO-cGMP pathway. Higher contents of phenols (42.42 vs 29.8 mgGAE/g), flavonoids (12.43 vs 2.07 mgQE/g), and alkaloids (0.17 vs 0.07 mgATE/g) were found in the ethyl acetate than in the n-butanol fraction.</p><p><strong>Conclusion: </strong>The present findings collectively indicate that the ethyl acetate and n-butanol fractions are endowed with antidepressant-like activity due to the presence of phenols, flavonoids, and alkaloids, which are medium polar in nature.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"14 ","pages":"379-394"},"PeriodicalIF":0.0,"publicationDate":"2022-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/66/84/jep-14-379.PMC9748120.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10404935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Local Anesthetic Like Inhibition of the Cardiac Na⁺ Channel Nav1.5 by Chloroquine and Hydroxychloroquine.","authors":"Axel Hage,&nbsp;Mathis de Vries,&nbsp;Andreas Leffler,&nbsp;Carsten Stoetzer","doi":"10.2147/JEP.S375349","DOIUrl":"https://doi.org/10.2147/JEP.S375349","url":null,"abstract":"<p><strong>Introduction: </strong>Chloroquine (CQ) and its derivate hydroxychloroquine (HCQ) are successfully deployed for different diseases beyond the prophylaxis and treatment of malaria. Both substances exhibit antiviral properties and have been proposed for prophylaxis and treatment of COVID-19 caused by SARS-CoV-2. CQ and HCQ cause similar adverse events including life-threatening cardiac arrhythmia generally based on QT-prolongation, which is one of the most reported adverse events for both agents associated with the treatment of COVID-19. Various drugs known to induce QT-prolongation have been proven to exert local anesthetic (LA)-like properties regarding their impact on the cardiac Na⁺ channel Nav1.5. Inhibition of Nav1.5 is considered as the primary mechanism of cardiotoxicity caused by LAs. However, the mechanism of the arrhythmogenic effects of CQ and HCQ related to Nav1.5 has not yet been fully investigated. Therefore, the exact mechanism of how CQ and HCQ affect the sodium currents generated by Nav1.5 need to be further elucidated.</p><p><strong>Objective: </strong>This in vitro study aims to investigate the effects of CQ and HCQ on Nav1.5-generated sodium currents to identify possible LA-like mechanisms that might contribute to their arrhythmogenic properties.</p><p><strong>Methods: </strong>The effects of CQ and HCQ on Nav1.5-generated sodium currents by HEK-293 cells expressing either wild-type human Nav1.5 or mutant Nav1.5 F1760A are measured using the whole-cell patch-clamp technique.</p><p><strong>Results: </strong>Both agents induce a state-dependent inhibition of Nav1.5. Furthermore, CQ and HCQ produce a use-dependent block of Nav1.5 and a shift of fast and slow inactivation. Results of experiments investigating the effect on the LA-insensitive mutant Nav1.5-F1760A indicate that both agents at least in part employ the proposed LA-binding site of Nav1.5 to induce inhibition.</p><p><strong>Conclusion: </strong>This study demonstrated that CQ and HCQ exert LA-typical effects on Nav1.5 involving the proposed LA binding site, thus contributing to their arrhythmogenic properties.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":" ","pages":"353-365"},"PeriodicalIF":0.0,"publicationDate":"2022-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/39/b9/jep-14-353.PMC9653037.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40688827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review of Advanced Drug Trials Focusing on the Reduction of Brain Beta-Amyloid to Prevent and Treat Dementia.","authors":"Boris Decourt, Keith Noorda, Kevin Noorda, Jiong Shi, Marwan N Sabbagh","doi":"10.2147/JEP.S265626","DOIUrl":"10.2147/JEP.S265626","url":null,"abstract":"<p><p>Alzheimer disease (AD) is the most common neurodegenerative disease and typically affects patients older than age 65. Around this age, the number of neurons begins to gradually decrease in healthy brains, but brains of patients with AD show a marked increase in neuron death, often resulting in a significant loss of cognitive abilities. Cognitive skills affected include information retention, recognition capabilities, and language skills. At present, AD can be definitively diagnosed only through postmortem brain biopsies via the detection of extracellular amyloid beta (Aβ) plaques and intracellular hyperphosphorylated tau neurofibrillary tangles. Because the levels of both Aβ plaques and tau tangles are increased, these 2 proteins are thought to be related to disease progression. Although relatively little is known about the cause of AD and its exact pathobiological development, many forms of treatment have been investigated to determine an effective method for managing AD symptoms by targeting Aβ. These treatments include but are not limited to using small molecules to alter the interactions of Aβ monomers, reducing hyperactivation of neuronal circuits altering Aβ's molecular pathway of synthesis, improving degradation of Aβ, employing passive immunity approaches, and stimulating patients' active immunity to target Aβ. This review summarizes the current therapeutic interventions in Phase II/III of clinical development or higher that are capable of reducing abnormal brain Aβ levels to determine which treatments show the greatest likelihood of clinical efficacy. We conclude that, in the near future, the most promising therapeutic interventions for brain Aβ pathology will likely be passive immunotherapies, with aducanumab and donanemab leading the way, and that these drugs may be combined with antidepressants and acetylcholine esterase inhibitors, which can modulate Aβ synthesis.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"14 ","pages":"331-352"},"PeriodicalIF":0.0,"publicationDate":"2022-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/aa/ed/jep-14-331.PMC9632331.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9230343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of in vivo Antidiabetic, Antidyslipidemic and in vitro Anti-Oxidant Activity of Extract and Solvent Fractions of <i>Discopodium penninervum Hoschst</i> Leaf in Mice: Normoglycemic and Streptozocin-Induced Model.","authors":"Wakuma Wakene Jifar,&nbsp;Gebiso Roba Debele,&nbsp;Shuma Gosha Kanfe,&nbsp;Chaltu Takele Mule","doi":"10.2147/JEP.S378166","DOIUrl":"https://doi.org/10.2147/JEP.S378166","url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus has become a huge global public health and economic issue. The shortcomings of current medicines, as well as their serious side effects, prompted a focused quest for natural medicinal agents. In Ethiopia, the leaf of <i>Discopodium penninervum Hoschst</i> has been utilized in the traditional health system to treat diabetes. The goal of this study was to confirm the anti-diabetic, anti-dyslipidemia, and anti-oxidant activity of <i>Discopodium penninervum Hoschst</i> leaf in both in vitro and in vivo.</p><p><strong>Methods: </strong>In the normoglycemic, glucose-loaded, and streptozotocin-induced diabetic mouse models, the blood glucose-lowering effects of extract and solvent fractions of the leaf of <i>Discopodium penninervum Hoschst</i> were tested. The weight and lipid profile of streptozotocin-induced diabetic mice were assessed after treatment with leaf extract and solvent fractions for 14 days. The DPPH test was used to assess the antioxidant activity of the plant leaf extract.</p><p><strong>Results: </strong>In the normoglycemic model and glucose loaded test, the leaf extract of <i>Discopodium penninervum Hoschst</i> demonstrated significant blood glucose decrease (34.1%, p<0.001) and 44.5%, p<0.001, respectively, when compared to the normal control. When compared to a diabetic control group, extract and solvent fractions significantly (p<0.001) reduced blood glucose levels on the 14th day in the streptozotocin-induced diabetic model. In addition, serum TC, STG, TG, LDL, and VLDL levels were reduced significantly (p<0.001). IC50 values of leaf extract and a standard medication (ascorbic acid) in the antioxidant activity test were 4.1g/mL and 10.23g/mL, respectively.</p><p><strong>Conclusion: </strong>The hydro-alcoholic leaf extract and solvent fractions of <i>Discopodium penninervum Hoschst</i> leaves have demonstrated blood glucose-lowering effect, which justify ethnobotanical use, and can therefore be used as a good insight for new anti-diabetic medication source with a call for additional studies.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":" ","pages":"317-330"},"PeriodicalIF":0.0,"publicationDate":"2022-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/52/4e/jep-14-317.PMC9624165.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40446177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}