Introduction: Recognizing the importance of medicinal plants and the absence of specific medications for traumatic brain injury (TBI) treatment, this study was conducted to evaluate the effects of an aqueous extract of Aloe vera on oxidative stress, blood-brain barrier (BBB) permeability, and neurological scores following TBI.
Materials and methods: Adult male rats were categorized into five groups: sham, TBI, vehicle, low-dose Aloe vera (LA), and high-dose Aloe vera (HA). We induced diffuse TBI using the Marmaro model and administered the aqueous Aloe vera leaf extract, as well as vehicle, via intraperitoneal injection half an hour after TBI. Neurological outcomes were assessed both before and several hours after TBI. Additionally, oxidative stress factors were measured 24 hr after TBI, and Evans blue content (a BBB permeability index) was determined 5 hr after TBI in both serum and brain.
Results: Both LA and HA reduced the increase in BBB permeability after TBI, with HA having a more pronounced effect than LA. Both Aloe vera doses decreased brain MDA levels, increased brain TAC, and lowered both serum and brain PC levels. The impact of Aloe vera on brain oxidative parameters was more significant than on serum. HA also counteracted the declining effects of TBI on neurological outcomes at 4 and 24 hr post-TBI.
Conclusion: This study suggests that Aloe vera extract may reduce BBB permeability and improve neurological outcomes after TBI by decreasing oxidative factors and increasing antioxidant factors.
{"title":"<i>Aloe vera</i> Leaf Extract Reduced BBB Permeability and Improved Neurological Results after Traumatic Brain Injury: The Role of Oxidative Stress.","authors":"Mohammad Khaksari, Marzieh Shahryari, Alireza Raji-Amirhasani, Zahra Soltani, Bahram Bibak, Zakieh Keshavarzi, Farzaneh Shakeri","doi":"10.1155/2024/5586814","DOIUrl":"10.1155/2024/5586814","url":null,"abstract":"<p><strong>Introduction: </strong>Recognizing the importance of medicinal plants and the absence of specific medications for traumatic brain injury (TBI) treatment, this study was conducted to evaluate the effects of an aqueous extract of <i>Aloe vera</i> on oxidative stress, blood-brain barrier (BBB) permeability, and neurological scores following TBI.</p><p><strong>Materials and methods: </strong>Adult male rats were categorized into five groups: sham, TBI, vehicle, low-dose <i>Aloe vera</i> (LA), and high-dose <i>Aloe vera</i> (HA). We induced diffuse TBI using the Marmaro model and administered the aqueous <i>Aloe vera</i> leaf extract, as well as vehicle, via intraperitoneal injection half an hour after TBI. Neurological outcomes were assessed both before and several hours after TBI. Additionally, oxidative stress factors were measured 24 hr after TBI, and Evans blue content (a BBB permeability index) was determined 5 hr after TBI in both serum and brain.</p><p><strong>Results: </strong>Both LA and HA reduced the increase in BBB permeability after TBI, with HA having a more pronounced effect than LA. Both <i>Aloe vera</i> doses decreased brain MDA levels, increased brain TAC, and lowered both serum and brain PC levels. The impact of <i>Aloe vera</i> on brain oxidative parameters was more significant than on serum. HA also counteracted the declining effects of TBI on neurological outcomes at 4 and 24 hr post-TBI.</p><p><strong>Conclusion: </strong>This study suggests that <i>Aloe vera</i> extract may reduce BBB permeability and improve neurological outcomes after TBI by decreasing oxidative factors and increasing antioxidant factors.</p>","PeriodicalId":19657,"journal":{"name":"Oxidative Medicine and Cellular Longevity","volume":"2024 ","pages":"5586814"},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11262876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-26eCollection Date: 2024-01-01DOI: 10.1155/2024/4887877
Vikram Subramanian, Denise Juhr, Lydia S Johnson, Justin B Yem, Piero Giansanti, Isabella M Grumbach
Approximately 70% of all strokes occur in patients over 65 years old, and stroke increases the risk of developing dementia. The circle of Willis (CoW), the ring of arteries at the base of the brain, links the intracerebral arteries to one another to maintain adequate cerebral perfusion. The CoW proteome is affected in cerebrovascular and neurodegenerative diseases, but changes related to aging have not been described. Here, we report on a quantitative proteomics analysis comparing the CoW from five young (2-3-month-old) and five aged male (18-20-month-old) mice using gene ontology (GO) enrichment, ingenuity pathway analysis (IPA), and iPathwayGuide tools. This revealed 242 proteins that were significantly dysregulated with aging, among which 189 were upregulated and 53 downregulated. GO enrichment-based analysis identified blood coagulation as the top biological function that changed with age and integrin binding and extracellular matrix constituents as the top molecular functions. Consistent with these findings, iPathwayGuide-based impact analysis revealed associations between aging and the complement and coagulation, platelet activation, ECM-receptor interaction, and metabolic process pathways. Furthermore, IPA analysis revealed the enrichment of 97 canonical pathways that contribute to inflammatory responses, as well as 59 inflammation-associated upstream regulators including 39 transcription factors and 20 cytokines. Thus, aging-associated changes in the CoW proteome in male mice demonstrate increases in metabolic, thrombotic, and inflammatory processes.
{"title":"Changes in the Proteome of the Circle of Willis during Aging Reveal Signatures of Vascular Disease.","authors":"Vikram Subramanian, Denise Juhr, Lydia S Johnson, Justin B Yem, Piero Giansanti, Isabella M Grumbach","doi":"10.1155/2024/4887877","DOIUrl":"10.1155/2024/4887877","url":null,"abstract":"<p><p>Approximately 70% of all strokes occur in patients over 65 years old, and stroke increases the risk of developing dementia. The circle of Willis (CoW), the ring of arteries at the base of the brain, links the intracerebral arteries to one another to maintain adequate cerebral perfusion. The CoW proteome is affected in cerebrovascular and neurodegenerative diseases, but changes related to aging have not been described. Here, we report on a quantitative proteomics analysis comparing the CoW from five young (2-3-month-old) and five aged male (18-20-month-old) mice using gene ontology (GO) enrichment, ingenuity pathway analysis (IPA), and iPathwayGuide tools. This revealed 242 proteins that were significantly dysregulated with aging, among which 189 were upregulated and 53 downregulated. GO enrichment-based analysis identified blood coagulation as the top biological function that changed with age and integrin binding and extracellular matrix constituents as the top molecular functions. Consistent with these findings, iPathwayGuide-based impact analysis revealed associations between aging and the complement and coagulation, platelet activation, ECM-receptor interaction, and metabolic process pathways. Furthermore, IPA analysis revealed the enrichment of 97 canonical pathways that contribute to inflammatory responses, as well as 59 inflammation-associated upstream regulators including 39 transcription factors and 20 cytokines. Thus, aging-associated changes in the CoW proteome in male mice demonstrate increases in metabolic, thrombotic, and inflammatory processes.</p>","PeriodicalId":19657,"journal":{"name":"Oxidative Medicine and Cellular Longevity","volume":"2024 ","pages":"4887877"},"PeriodicalIF":0.0,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11221951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-20eCollection Date: 2024-01-01DOI: 10.1155/2024/4293391
Fatemeh Abbaszadeh, Pegah Javadpour, Mohammad Mehdi Mousavi Nasab, Masoumeh Jorjani
Spinal cord injury (SCI) is a common neurological disease worldwide, often resulting in a substantial decrease in quality of life, disability, and in severe cases, even death. Unfortunately, there is currently no effective treatment for this disease. Nevertheless, current basic and clinical evidence suggests that vitamins, with their antioxidant properties and biological functions, may play a valuable role in improving the quality of life for individuals with SCI. They can promote overall health and facilitate the healing process. In this review, we discuss the mechanisms and therapeutic potential of vitamins in the treatment of SCI.
{"title":"The Role of Vitamins in Spinal Cord Injury: Mechanisms and Benefits.","authors":"Fatemeh Abbaszadeh, Pegah Javadpour, Mohammad Mehdi Mousavi Nasab, Masoumeh Jorjani","doi":"10.1155/2024/4293391","DOIUrl":"https://doi.org/10.1155/2024/4293391","url":null,"abstract":"<p><p>Spinal cord injury (SCI) is a common neurological disease worldwide, often resulting in a substantial decrease in quality of life, disability, and in severe cases, even death. Unfortunately, there is currently no effective treatment for this disease. Nevertheless, current basic and clinical evidence suggests that vitamins, with their antioxidant properties and biological functions, may play a valuable role in improving the quality of life for individuals with SCI. They can promote overall health and facilitate the healing process. In this review, we discuss the mechanisms and therapeutic potential of vitamins in the treatment of SCI.</p>","PeriodicalId":19657,"journal":{"name":"Oxidative Medicine and Cellular Longevity","volume":"2024 ","pages":"4293391"},"PeriodicalIF":0.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sonia Thapa, Yedukondalu Nalli, Ajeet Singh, Shashank Kr. Singh, Asif Ali
The endocannabinoid system is found throughout the central nervous system, and its cannabinoids receptor 1 is critical in preventing neurotoxicity caused by N-methyl-D-aspartate receptor activation (NMDARs). The activity of NMDARs places demands on endogenous cannabinoids to regulate their calcium currents. Endocannabinoids keep NMDAR activity within safe limits, protecting neural cells from excitotoxicity. Cannabinoids are remembered to deliver this outcome by repressing presynaptic glutamate discharge or obstructing postsynaptic NMDAR-managed flagging pathways. The endocannabinoid system must exert a negative influence proportional to the strength of NMDAR signaling for such control to be effective. The goal of this paper is to draw the attention towards the neuroprotective mechanism of constituents of Cannabis sativa against NMDA-induced excitotoxic result. Phytochemical investigation of the cannabis flowers led to the isolation of nine secondary metabolites. A spiro-compound, Cannabispirenone A, which on treatment of the cells prior to NMDA exposure significantly increases cell survival while decreasing ROS production, lipid peroxidation, and intracellular calcium. Our findings showed that this compound showed neuroprotection against NMDA-induced excitotoxic insult, has antioxidative properties, and increased cannabinoid receptor 1 expression, which may be involved in the signaling pathway for this neuroprotection.
{"title":"Neuroprotective Effects of Cannabispirenone A against NMDA-Induced Excitotoxicity in Differentiated N2a Cells","authors":"Sonia Thapa, Yedukondalu Nalli, Ajeet Singh, Shashank Kr. Singh, Asif Ali","doi":"10.1155/2024/3530499","DOIUrl":"https://doi.org/10.1155/2024/3530499","url":null,"abstract":"The endocannabinoid system is found throughout the central nervous system, and its cannabinoids receptor 1 is critical in preventing neurotoxicity caused by N-methyl-D-aspartate receptor activation (NMDARs). The activity of NMDARs places demands on endogenous cannabinoids to regulate their calcium currents. Endocannabinoids keep NMDAR activity within safe limits, protecting neural cells from excitotoxicity. Cannabinoids are remembered to deliver this outcome by repressing presynaptic glutamate discharge or obstructing postsynaptic NMDAR-managed flagging pathways. The endocannabinoid system must exert a negative influence proportional to the strength of NMDAR signaling for such control to be effective. The goal of this paper is to draw the attention towards the neuroprotective mechanism of constituents of <i>Cannabis sativa</i> against NMDA-induced excitotoxic result. Phytochemical investigation of the cannabis flowers led to the isolation of nine secondary metabolites. A spiro-compound, Cannabispirenone A, which on treatment of the cells prior to NMDA exposure significantly increases cell survival while decreasing ROS production, lipid peroxidation, and intracellular calcium. Our findings showed that this compound showed neuroprotection against NMDA-induced excitotoxic insult, has antioxidative properties, and increased cannabinoid receptor 1 expression, which may be involved in the signaling pathway for this neuroprotection.","PeriodicalId":19657,"journal":{"name":"Oxidative Medicine and Cellular Longevity","volume":"52 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141192270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Myocardial infarction (MI) is irreversible damage to the myocardial tissue caused by prolonged ischemia/hypoxia, subsequently leading to loss of contractile function and myocardial damage. However, after a perilous period, ischemia-reperfusion (IR) itself causes the generation of oxygen free radicals, disturbance in cation homeostasis, depletion of cellular energy stores, and activation of innate and adaptive immune responses. The present study employed Abatacept (ABT), which is an anti-inflammatory drug, originally used as an antirheumatic response agent. To investigate the cardioprotective potential of ABT, primarily, the dose was optimized in a chemically induced model of myocardial necrosis. Thereafter, ABT optimized the dose of 5 mg/kg s.c. OD was investigated for its cardioprotective potential in a surgical model of myocardial IR injury, where animals (n = 30) were randomized into five groups: Sham, IR-C, Telmi10 + IR (Telmisartan, 10 mg/kg oral OD), ABT5 + IR, ABT perse. ABT and telmisartan were administered for 21 days. On the 21st day, animals were subjected to LAD coronary artery occlusion for 60 min, followed by reperfusion for 45 min. Further, the cardioprotective potential was assessed through hemodynamic parameters, oxidant–antioxidant biochemical enzymatic parameters, cardiac injury, inflammatory markers, histopathological analysis, TUNEL assay, and immunohistochemical evaluation, followed by immunoblotting to explore signaling pathways. The statistics were performed by one-way analysis of variance, followed by the Tukey comparison post hoc tests. Noteworthy, 21 days of ABT pretreatment amended the hemodynamic and ventricular functions in the rat models of MI. The cardioprotective potential of ABT is accompanied by inhibiting MAP kinase signaling and modulating Nrf-2/HO-1 proteins downstream signaling cascade. Overall, the present work bolsters the previously known anti-inflammatory role of ABT in MI and contributes a mechanistic insight and application of clinically approved drugs in averting the activation of inflammatory response.
心肌梗死（MI）是由于长时间缺血/缺氧对心肌组织造成的不可逆损伤，随后导致收缩功能丧失和心肌损伤。然而，在危险期过后，缺血再灌注（IR）本身会导致氧自由基的产生、阳离子平衡的紊乱、细胞能量储存的耗竭以及先天性和适应性免疫反应的激活。本研究采用的阿巴他赛普（ABT）是一种抗炎药物，最初用作抗风湿反应剂。为了研究 ABT 的心脏保护潜力，首先在化学诱导的心肌坏死模型中优化了剂量。此后，在心肌红外损伤的手术模型中，将动物（n = 30）随机分为五组，以 5 mg/kg s.c. OD 的剂量对 ABT 的心脏保护潜力进行了研究：Sham 组、IR-C 组、Telmi10 + IR 组（替米沙坦，10 毫克/千克口服）、ABT5 + IR 组、ABT perse.ABT和替米沙坦给药21天。第21天，对动物进行LAD冠状动脉闭塞60分钟，然后再灌注45分钟。此外，还通过血液动力学参数、氧化-抗氧化生化酶学参数、心脏损伤、炎症标志物、组织病理学分析、TUNEL检测和免疫组织化学评估来评估心脏保护潜力，然后通过免疫印迹来探索信号通路。统计采用单因素方差分析，然后进行Tukey比较事后检验。值得注意的是，ABT 预处理 21 天可改善心肌梗死大鼠模型的血液动力学和心室功能。ABT的心脏保护潜力伴随着抑制MAP激酶信号转导和调节Nrf-2/HO-1蛋白下游信号级联。总之，本研究加强了之前已知的 ABT 在心肌梗死中的抗炎作用，并有助于从机理上深入了解和应用临床批准的药物来避免炎症反应的激活。
{"title":"Abatacept: A Promising Repurposed Solution for Myocardial Infarction-Induced Inflammation in Rat Models","authors":"Vipin Kumar Verma, Ekta Mutneja, Salma Malik, Anil Kumar Sahu, Vaishali Prajapati, Priya Bhardwaj, Ruma Ray, Tapas Chandra Nag, Jagriti Bhatia, Dharamvir Singh Arya","doi":"10.1155/2024/3534104","DOIUrl":"https://doi.org/10.1155/2024/3534104","url":null,"abstract":"Myocardial infarction (MI) is irreversible damage to the myocardial tissue caused by prolonged ischemia/hypoxia, subsequently leading to loss of contractile function and myocardial damage. However, after a perilous period, ischemia-reperfusion (IR) itself causes the generation of oxygen free radicals, disturbance in cation homeostasis, depletion of cellular energy stores, and activation of innate and adaptive immune responses. The present study employed Abatacept (ABT), which is an anti-inflammatory drug, originally used as an antirheumatic response agent. To investigate the cardioprotective potential of ABT, primarily, the dose was optimized in a chemically induced model of myocardial necrosis. Thereafter, ABT optimized the dose of 5 mg/kg s.c. OD was investigated for its cardioprotective potential in a surgical model of myocardial IR injury, where animals (<i>n</i> = 30) were randomized into five groups: Sham, IR-C, Telmi10 + IR (Telmisartan, 10 mg/kg oral OD), ABT5 + IR, ABT <i>perse</i>. ABT and telmisartan were administered for 21 days. On the 21st day, animals were subjected to LAD coronary artery occlusion for 60 min, followed by reperfusion for 45 min. Further, the cardioprotective potential was assessed through hemodynamic parameters, oxidant–antioxidant biochemical enzymatic parameters, cardiac injury, inflammatory markers, histopathological analysis, TUNEL assay, and immunohistochemical evaluation, followed by immunoblotting to explore signaling pathways. The statistics were performed by one-way analysis of variance, followed by the Tukey comparison post hoc tests. Noteworthy, 21 days of ABT pretreatment amended the hemodynamic and ventricular functions in the rat models of MI. The cardioprotective potential of ABT is accompanied by inhibiting MAP kinase signaling and modulating Nrf-2/HO-1 proteins downstream signaling cascade. Overall, the present work bolsters the previously known anti-inflammatory role of ABT in MI and contributes a mechanistic insight and application of clinically approved drugs in averting the activation of inflammatory response.","PeriodicalId":19657,"journal":{"name":"Oxidative Medicine and Cellular Longevity","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140116735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The extracellular signal-regulated kinase (ERK) MAPK pathway is dysregulated in various human cancers and is considered an attractive therapeutic target for cancer. Therefore, several inhibitors of this pathway are being developed, and some are already used in the clinic. We have previously identified an anticancer compound, ACA-28, with a unique property to preferentially induce ERK-dependent apoptosis in melanoma cells. To comprehensively understand the biological cellular impact induced by ACA-28, we performed a global gene expression analysis of human melanoma SK-MEL-28 cells exposed to ACA-28 using a DNA microarray. The transcriptome analysis identified nuclear factor erythroid 2-related factor 2 (Nrf2), a master transcription factor that combats oxidative stress, as the most upregulated genetic pathway after ACA-28 treatment. Consistently, ACA-28 showed properties to increase the levels of reactive oxygen species (ROS) as well as Nrf2 protein, which is normally repressed by proteasomal degradation and activated in response to oxidative stresses. Furthermore, the ROS scavenger N-acetyl cysteine significantly attenuated the anticancer activity of ACA-28. Thus, ACA-28 activates Nrf2 signaling and exerts anticancer activity partly via its ROS-stimulating property. Interestingly, human A549 cancer cells with constitutively high levels of Nrf2 protein showed resistance to ACA-28, as compared with SK-MEL-28. Transient overexpression of Nrf2 also increased the resistance of cells to ACA-28, while knockdown of Nrf2 exerted the opposite effect. Thus, upregulation of Nrf2 signaling protects cancer cells from ACA-28-mediated cell death. Notably, the Nrf2 inhibitor ML385 substantially enhanced the cell death-inducing property of ACA-28 in pancreatic cancer cells, T3M4 and PANC-1. Our data suggest that Nrf2 plays a key role in determining cancer cell susceptibility to ACA-28 and provides a novel strategy for cancer therapy to combine the Nrf2 inhibitor and ACA-28.
{"title":"ACA-28, an ERK MAPK Signaling Modulator, Exerts Anticancer Activity through ROS Induction in Melanoma and Pancreatic Cancer Cells","authors":"Teruaki Takasaki, Yasuyuki Hamabe, Kenta Touchi, Golam Iftakhar Khandakar, Takeshi Ueda, Hitoshi Okada, Kazuko Sakai, Kazuto Nishio, Genzoh Tanabe, Reiko Sugiura","doi":"10.1155/2024/7683793","DOIUrl":"https://doi.org/10.1155/2024/7683793","url":null,"abstract":"The extracellular signal-regulated kinase (ERK) MAPK pathway is dysregulated in various human cancers and is considered an attractive therapeutic target for cancer. Therefore, several inhibitors of this pathway are being developed, and some are already used in the clinic. We have previously identified an anticancer compound, ACA-28, with a unique property to preferentially induce ERK-dependent apoptosis in melanoma cells. To comprehensively understand the biological cellular impact induced by ACA-28, we performed a global gene expression analysis of human melanoma SK-MEL-28 cells exposed to ACA-28 using a DNA microarray. The transcriptome analysis identified nuclear factor erythroid 2-related factor 2 (Nrf2), a master transcription factor that combats oxidative stress, as the most upregulated genetic pathway after ACA-28 treatment. Consistently, ACA-28 showed properties to increase the levels of reactive oxygen species (ROS) as well as Nrf2 protein, which is normally repressed by proteasomal degradation and activated in response to oxidative stresses. Furthermore, the ROS scavenger N-acetyl cysteine significantly attenuated the anticancer activity of ACA-28. Thus, ACA-28 activates Nrf2 signaling and exerts anticancer activity partly via its ROS-stimulating property. Interestingly, human A549 cancer cells with constitutively high levels of Nrf2 protein showed resistance to ACA-28, as compared with SK-MEL-28. Transient overexpression of Nrf2 also increased the resistance of cells to ACA-28, while knockdown of Nrf2 exerted the opposite effect. Thus, upregulation of Nrf2 signaling protects cancer cells from ACA-28-mediated cell death. Notably, the Nrf2 inhibitor ML385 substantially enhanced the cell death-inducing property of ACA-28 in pancreatic cancer cells, T3M4 and PANC-1. Our data suggest that Nrf2 plays a key role in determining cancer cell susceptibility to ACA-28 and provides a novel strategy for cancer therapy to combine the Nrf2 inhibitor and ACA-28.","PeriodicalId":19657,"journal":{"name":"Oxidative Medicine and Cellular Longevity","volume":"89 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140098316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Razieh Amini, Shadi Moradi, Rezvan Najafi, Mehrdokht Mazdeh, Amir Taherkhani
Background. Neurological disorders like Alzheimer’s disease (AD) and Parkinson’s disease (PD) manifest through gradually deteriorating cognitive functions. An encouraging strategy for addressing these disorders involves the inhibition of precursor-cleaving enzyme 1 (BACE1). Objectives. In the current research, a virtual screening technique was employed to identify potential BACE1 inhibitors among selected herbal isolates. Methods. This study evaluated 79 flavonoids, anthraquinones (AQs), and cinnamic acid derivatives for their potential blood–brain barrier (BBB) permeability. Using the AutoDock 4.0 tool, molecular docking analysis was conducted to determine the binding affinity of BBB permeable compounds to the BACE1 active site. Molecular dynamics (MD) simulations were performed to assess the stability of the docked poses of the most potent inhibitors. The interactions between the most effective plant-based inhibitors and the residues within the BACE1 catalytic site were examined before and after MD simulations. Results. Ponciretin, danthron, chrysophanol, and N-p-coumaroyltyramine were among the highest-ranking BACE1 inhibitors, with inhibition constant values calculated in the nanomolar range. Furthermore, during 10 ns simulations, the docked poses of these ligands were observed to be stable. Conclusion. The findings propose that ponciretin, danthron, chrysophanol, and N-p-coumaroyltyramine might serve as potential choices for the treatment of AD and PD, laying the groundwork for the creation of innovative BACE1 inhibitors.
{"title":"BACE1 Inhibition Utilizing Organic Compounds Holds Promise as a Potential Treatment for Alzheimer’s and Parkinson’s Diseases","authors":"Razieh Amini, Shadi Moradi, Rezvan Najafi, Mehrdokht Mazdeh, Amir Taherkhani","doi":"10.1155/2024/6654606","DOIUrl":"https://doi.org/10.1155/2024/6654606","url":null,"abstract":"<i>Background</i>. Neurological disorders like Alzheimer’s disease (AD) and Parkinson’s disease (PD) manifest through gradually deteriorating cognitive functions. An encouraging strategy for addressing these disorders involves the inhibition of precursor-cleaving enzyme 1 (BACE1). <i>Objectives</i>. In the current research, a virtual screening technique was employed to identify potential BACE1 inhibitors among selected herbal isolates. <i>Methods</i>. This study evaluated 79 flavonoids, anthraquinones (AQs), and cinnamic acid derivatives for their potential blood–brain barrier (BBB) permeability. Using the AutoDock 4.0 tool, molecular docking analysis was conducted to determine the binding affinity of BBB permeable compounds to the BACE1 active site. Molecular dynamics (MD) simulations were performed to assess the stability of the docked poses of the most potent inhibitors. The interactions between the most effective plant-based inhibitors and the residues within the BACE1 catalytic site were examined before and after MD simulations. <i>Results</i>. Ponciretin, danthron, chrysophanol, and N-p-coumaroyltyramine were among the highest-ranking BACE1 inhibitors, with inhibition constant values calculated in the nanomolar range. Furthermore, during 10 ns simulations, the docked poses of these ligands were observed to be stable. <i>Conclusion</i>. The findings propose that ponciretin, danthron, chrysophanol, and N-p-coumaroyltyramine might serve as potential choices for the treatment of AD and PD, laying the groundwork for the creation of innovative BACE1 inhibitors.","PeriodicalId":19657,"journal":{"name":"Oxidative Medicine and Cellular Longevity","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139927195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sajeev Wagle, Julie Anne Lee, H. P. Vasantha Rupasinghe
Chaga mushroom (Inonotus obliquus) contains bioactive metabolites and has been used to treat various ailments, including cancer. Similarly, marine microalgae are considered a sustainable food supplement with anticancer and antioxidant properties. This study investigated the cytotoxicity of different extracts prepared from I. obliquus and microalgae using cultured human and canine cancer cell lines (MCF-7, HepG2, HOS, D-17, and DH-82). MTS cell viability assay was used to study the cytotoxicity of I. obliquus and microalgae extracts, and a synergy matrix effect was used to study the combined effect of the extracts. Isobologram analysis and the highest single agent synergy model were applied to study and validate the synergy between the extracts from I. obliquus and microalgae. Ethanol-based extraction and supercritical water extract significantly inhibited the growth of various mammalian cancer cells compared to aqueous extracts. Osteosarcoma cells were more susceptible to the supercritical extracts of I. obliquus and chlorophyll-free and sugar-free ethanol extracts of microalgae. A combination of ethanol-based I. obliquus extract and chlorophyll-free microalgae extract resulted in a synergistic interaction with various tested cancer cells. This study provides experimental evidence supporting the potential therapeutic application of I. obliquus and microalgae extracts with a synergistic effect to inhibit the growth of various mammalian cancer cells. Additional in vivo studies are required to fully explore possible therapeutic applications of these unique mixtures to be used in treating cancers.
{"title":"Synergistic Cytotoxicity of Extracts of Chaga Mushroom and Microalgae against Mammalian Cancer Cells In Vitro","authors":"Sajeev Wagle, Julie Anne Lee, H. P. Vasantha Rupasinghe","doi":"10.1155/2024/7944378","DOIUrl":"https://doi.org/10.1155/2024/7944378","url":null,"abstract":"Chaga mushroom (<i>Inonotus obliquus</i>) contains bioactive metabolites and has been used to treat various ailments, including cancer. Similarly, marine microalgae are considered a sustainable food supplement with anticancer and antioxidant properties. This study investigated the cytotoxicity of different extracts prepared from <i>I. obliquus</i> and microalgae using cultured human and canine cancer cell lines (MCF-7, HepG2, HOS, D-17, and DH-82). MTS cell viability assay was used to study the cytotoxicity of <i>I. obliquus</i> and microalgae extracts, and a synergy matrix effect was used to study the combined effect of the extracts. Isobologram analysis and the highest single agent synergy model were applied to study and validate the synergy between the extracts from <i>I. obliquus</i> and microalgae. Ethanol-based extraction and supercritical water extract significantly inhibited the growth of various mammalian cancer cells compared to aqueous extracts. Osteosarcoma cells were more susceptible to the supercritical extracts of <i>I. obliquus</i> and chlorophyll-free and sugar-free ethanol extracts of microalgae. A combination of ethanol-based <i>I. obliquus</i> extract and chlorophyll-free microalgae extract resulted in a synergistic interaction with various tested cancer cells. This study provides experimental evidence supporting the potential therapeutic application of <i>I. obliquus</i> and microalgae extracts with a synergistic effect to inhibit the growth of various mammalian cancer cells. Additional in vivo studies are required to fully explore possible therapeutic applications of these unique mixtures to be used in treating cancers.","PeriodicalId":19657,"journal":{"name":"Oxidative Medicine and Cellular Longevity","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139483002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Retracted: Rhodiola Rosea Extract Counteracts Stress in an Adaptogenic Response Curve Manner via Elimination of ROS and Induction of Neurite Outgrowth","authors":"Oxidative Medicine and Cellular Longevity","doi":"10.1155/2024/9782834","DOIUrl":"https://doi.org/10.1155/2024/9782834","url":null,"abstract":"<jats:p />","PeriodicalId":19657,"journal":{"name":"Oxidative Medicine and Cellular Longevity","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139441370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Retracted: Pinosylvin Extract Retinari™ Sustains Electrophysiological Function, Prevents Thinning of Retina, and Enhances Cellular Response to Oxidative Stress in NFE2L2 Knockout Mice","authors":"Oxidative Medicine and Cellular Longevity","doi":"10.1155/2024/9835864","DOIUrl":"https://doi.org/10.1155/2024/9835864","url":null,"abstract":"<jats:p />","PeriodicalId":19657,"journal":{"name":"Oxidative Medicine and Cellular Longevity","volume":"60 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139441489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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