Pub Date : 2024-06-03DOI: 10.2174/0122127968300108240527090556
S. Merzouki, S. Boukeria, F. Louafi, M. H. Alma, R. Erenler, I. Yildiz, M. boulkroune, C. Mouats
This study aims to explore biologically active substances from natural sources, such as the Ocimum basilicum L. plant, for potential medicines. The LC-MS/MS analysis reveals that the majority of compounds in the aerial portion of this plant have Hesperidin and Vanillic acid, which are used in treating blood vessel fragility and neurological diseases (disorders) like Alzheimer's and Parkinson's. The study conducted a qualitative phytochemical screening of the hydromethanolic plant extract, revealing different secondary metabolites. Quantitative studies were conducted to determine the quantities of polyphenols, flavonoids, tannins, and alkaloids in the extract. Our investigations also assessed the antioxidant activity of the hydromethanolic plant extract using DPPH-free radical scavenging and cyclic voltammetry, providing insights into its potential to combat oxidative stress. Finally, the anticoagulant activity of the hydromethanolic plant extract was examined through Quick and Cephaline Kaolin time coagulation exploration tests, providing insights into its impact on coagulation pathways.
本研究旨在从天然资源（如 Ocimum basilicum L. 植物）中发掘生物活性物质，以寻找潜在的药物。LC-MS/MS 分析表明，该植物气生部分的大部分化合物具有橙皮甙和香草酸，可用于治疗血管脆性和神经系统疾病（失调），如阿尔茨海默氏症和帕金森氏症。我们的研究还通过 DPPH 自由基清除法和循环伏安法评估了水合甲醇植物提取物的抗氧化活性，从而深入了解了其抗氧化压力的潜力。最后，我们通过快速和头状高岭土时间凝固探索试验检测了水合甲醇植物提取物的抗凝血活性，从而深入了解了其对凝血途径的影响。
{"title":"Physico-chemical and Biological Investigations of Ocimum Basilicum L. Cultivated in Algeria","authors":"S. Merzouki, S. Boukeria, F. Louafi, M. H. Alma, R. Erenler, I. Yildiz, M. boulkroune, C. Mouats","doi":"10.2174/0122127968300108240527090556","DOIUrl":"https://doi.org/10.2174/0122127968300108240527090556","url":null,"abstract":"\u0000\u0000This study aims to explore biologically active substances from natural\u0000sources, such as the Ocimum basilicum L. plant, for potential medicines. The LC-MS/MS analysis\u0000reveals that the majority of compounds in the aerial portion of this plant have Hesperidin and Vanillic\u0000acid, which are used in treating blood vessel fragility and neurological diseases (disorders) like\u0000Alzheimer's and Parkinson's.\u0000\u0000\u0000\u0000The study conducted a qualitative phytochemical screening of the hydromethanolic plant\u0000extract, revealing different secondary metabolites. Quantitative studies were conducted to determine\u0000the quantities of polyphenols, flavonoids, tannins, and alkaloids in the extract.\u0000\u0000\u0000\u0000Our investigations also assessed the antioxidant activity of the hydromethanolic plant extract\u0000using DPPH-free radical scavenging and cyclic voltammetry, providing insights into its potential\u0000to combat oxidative stress.\u0000\u0000\u0000\u0000Finally, the anticoagulant activity of the hydromethanolic plant extract was examined\u0000through Quick and Cephaline Kaolin time coagulation exploration tests, providing insights into its\u0000impact on coagulation pathways.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"185 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141388530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-29DOI: 10.2174/0122127968256108231226074336
Rushikesh Patel, A. K. Raj, K. Lokhande, Mrudula Joshi, Kratika Khunteta, Jayanta K. Pal, Nilesh Kumar Sharma
As per the Warburg effect, cancer cells are known to convert pyruvate into lactate. The accumulation of lactate is associated with metabolic and epigenetic reprogramming, which has newly been suggested to involve lactylation. However, the role of secreted lactate in modulating the tumor microenvironment through lactylation remains unclear. Specifically, there are gaps in our understanding of the enzyme responsible for converting lactate to lactyl-CoA and the nature of the enzyme that performs lactylation by utilizing lactyl-CoA as a substrate. It is worth noting that there are limited papers focused on metabolite profiling that detect lactate and lactyl-CoA levels intracellularly and extracellularly in the context of cancer cells. Here, we have employed an in-house developed vertical tube gel electrophoresis (VTGE) and LC-HRMS assisted profiling of extracellular metabolites of breast cancer cells treated by anticancer compositions of cow urine DMSO fraction (CUDF) that was reported previously. Furthermore, we used molecular docking and molecular dynamics (MD) simulations to determine the potential enzyme that can convert lactate to lactyl-CoA. Next, the histone acetyltransferase p300 (HAT p300) enzyme (PDB ID: 6GYR) was evaluated as a potential enzyme that can bind to lactylCoA during the lactylation process. We collected evidence on the secretion of lactate in the extracellular conditioned medium of breast cancer cells treated by anticancer compositions. MD simulations data projected that acetyl-CoA synthetase could be a potential enzyme that may convert lactate into lactyl-CoA similar to a known substrate acetate. Furthermore, a specific and efficient binding (docking energy -9.6 kcal/mol) of lactyl-CoA with p300 HAT suggested that lactyl-CoA may serve as a substrate for lactylation similar to acetylation that uses acetyl-CoA as a substrate. In conclusion, our data provide a hint on the missing link for the lactylation process due to lactate in terms of a potential enzyme that can convert lactate into lactyl-CoA. This study helped us to project the HAT p300 enzyme that may use lactyl-CoA as a substrate in the lactylation process of the tumor microenvironment.
{"title":"Predicted Role of Acetyl-CoA Synthetase and HAT p300 in Extracellular Lactate Mediated Lactylation in the Tumor: In vitro and In silico Models","authors":"Rushikesh Patel, A. K. Raj, K. Lokhande, Mrudula Joshi, Kratika Khunteta, Jayanta K. Pal, Nilesh Kumar Sharma","doi":"10.2174/0122127968256108231226074336","DOIUrl":"https://doi.org/10.2174/0122127968256108231226074336","url":null,"abstract":"As per the Warburg effect, cancer cells are known to convert pyruvate into lactate. The accumulation of lactate is associated with metabolic and epigenetic reprogramming, which has newly been suggested to involve lactylation. However, the role of secreted lactate in modulating the tumor microenvironment through lactylation remains unclear. Specifically, there are gaps in our understanding of the enzyme responsible for converting lactate to lactyl-CoA and the nature of the enzyme that performs lactylation by utilizing lactyl-CoA as a substrate. It is worth noting that there are limited papers focused on metabolite profiling that detect lactate and lactyl-CoA levels intracellularly and extracellularly in the context of cancer cells. Here, we have employed an in-house developed vertical tube gel electrophoresis (VTGE) and LC-HRMS assisted profiling of extracellular metabolites of breast cancer cells treated by anticancer compositions of cow urine DMSO fraction (CUDF) that was reported previously. Furthermore, we used molecular docking and molecular dynamics (MD) simulations to determine the potential enzyme that can convert lactate to lactyl-CoA. Next, the histone acetyltransferase p300 (HAT p300) enzyme (PDB ID: 6GYR) was evaluated as a potential enzyme that can bind to lactylCoA during the lactylation process. We collected evidence on the secretion of lactate in the extracellular conditioned medium of breast cancer cells treated by anticancer compositions. MD simulations data projected that acetyl-CoA synthetase could be a potential enzyme that may convert lactate into lactyl-CoA similar to a known substrate acetate. Furthermore, a specific and efficient binding (docking energy -9.6 kcal/mol) of lactyl-CoA with p300 HAT suggested that lactyl-CoA may serve as a substrate for lactylation similar to acetylation that uses acetyl-CoA as a substrate. In conclusion, our data provide a hint on the missing link for the lactylation process due to lactate in terms of a potential enzyme that can convert lactate into lactyl-CoA. This study helped us to project the HAT p300 enzyme that may use lactyl-CoA as a substrate in the lactylation process of the tumor microenvironment.","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":" 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139143787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-28DOI: 10.2174/0122127968276934231219052232
A. Swargiary, Harmonjit Boro, Dulur Brahma
Drug resistance is an important phenomenon in helminth parasites. Microtubules are among the key chemotherapeutic targets, mutations of which lead to drug resistance. The present study investigated the role of F167Y, E198A, and F200Y mutations in βtubulin protein and their effect on albendazole binding. Brugia malayi β-tubulin protein models were generated using the SwissModel platform by submitting amino acid sequences. Mutations were carried out at amino acid sequences by changing F167Y, E198A, and F200Y. All the model proteins (one wild and three mutated) were docked with the anthelmintic drug albendazole using AutoDock vina-1.1.5. Docking complexes were further investigated for their binding stability by a Molecular Dynamic Simulation study using Gromacs-2023.2. The binding free energies of protein-ligand complexes were analyzed using the MM/PBSA package. The docking study observed decreased ligand binding affinity in F167Y and E198A mutant proteins compared to wild proteins. MD simulation revealed the overall structural stability of the protein complexes during the simulation period. The simulation also observed more stable binding of albendazole in the active pocket of mutant proteins compared to wild-type proteins. Like ligand RMSD, wild-type protein also showed higher amino acid residual flexibility. The flexibility indicates the less compactness of wild β-tubulin protein complexes compared to mutant proteinligand complexes. Van der Waals and electrostatic interactions were found to be the major energy in protein-ligand complexes. However, due to higher solvation energy, wild-type protein showed more flexibility compared to others. The study, therefore, concludes that mutations at positions 167 and 198 of the βtubulin protein contribute to resistance to albendazole through weakened binding affinity. However, the binding of albendazole binding to the proteins leads to structures becoming more stable and compact.
{"title":"Tubulin-gene Mutation in Drug Resistance in Helminth Parasite: Docking and Molecular Dynamics Simulation Study","authors":"A. Swargiary, Harmonjit Boro, Dulur Brahma","doi":"10.2174/0122127968276934231219052232","DOIUrl":"https://doi.org/10.2174/0122127968276934231219052232","url":null,"abstract":"Drug resistance is an important phenomenon in helminth parasites. Microtubules are among the key chemotherapeutic targets, mutations of which lead to drug resistance. The present study investigated the role of F167Y, E198A, and F200Y mutations in βtubulin protein and their effect on albendazole binding. Brugia malayi β-tubulin protein models were generated using the SwissModel platform by submitting amino acid sequences. Mutations were carried out at amino acid sequences by changing F167Y, E198A, and F200Y. All the model proteins (one wild and three mutated) were docked with the anthelmintic drug albendazole using AutoDock vina-1.1.5. Docking complexes were further investigated for their binding stability by a Molecular Dynamic Simulation study using Gromacs-2023.2. The binding free energies of protein-ligand complexes were analyzed using the MM/PBSA package. The docking study observed decreased ligand binding affinity in F167Y and E198A mutant proteins compared to wild proteins. MD simulation revealed the overall structural stability of the protein complexes during the simulation period. The simulation also observed more stable binding of albendazole in the active pocket of mutant proteins compared to wild-type proteins. Like ligand RMSD, wild-type protein also showed higher amino acid residual flexibility. The flexibility indicates the less compactness of wild β-tubulin protein complexes compared to mutant proteinligand complexes. Van der Waals and electrostatic interactions were found to be the major energy in protein-ligand complexes. However, due to higher solvation energy, wild-type protein showed more flexibility compared to others. The study, therefore, concludes that mutations at positions 167 and 198 of the βtubulin protein contribute to resistance to albendazole through weakened binding affinity. However, the binding of albendazole binding to the proteins leads to structures becoming more stable and compact.","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"87 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139151718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thrombotic events and oxidative stress are major complications of certain ischemic disorders. The fight against these complications requires very intense research to develop new therapeutic agents of natural origin. The general objective of this work is the scientific valorization of five medicinal plants: Rhus pentaphylla, Zizyphus lotus, Ammodaucus leucotrichus, Inula viscosa, and Cinnamomum zeylanicum by exploring their effects on rat platelet aggregation, antioxidant potential and determining their phytochemical composition. e aggregation test was monitored by stimulating isolated washed platelets suspension in the absence and presence of extracts. The antioxidant activity was conducted in vitro according to three methods: DPPH free radical scavenging activity, β-carotene bleaching test, and ferric reducing antioxidant power test. The quantitative determination of total polyphenols and flavonoids are determined respectively according to the Folin-Ciocalteu method and the colorimetric method with aluminum chloride. The results obtained show that the aqueous extract of the fruits of Rhus pentaphylla and the aerial part of Inula viscosa, as well as the stalk peel of Cinnamomum zeylanicum, significantly (p˂0.001) inhibit thrombin-platelet aggregation, while the other plant extracts have a slightly, but significant effect. These extracts exert a remarkable antioxidant activity with the three methods used. But, their IC50 values are still higher than those of the antioxidant references (ascorbic acid and butyl hydroxyanisole). Qualitative phytochemical analysis revealed the presence of secondary metabolites with varying contents. Additionally, the results of quantitative phytochemical analysis showed that the aqueous extracts of the leaves of Rhus pentaphylla and the aerial part of Inula viscosa contain the highest amount of polyphenols and flavonoids. These secondary metabolites are also present in the other extracts but in smaller quantities. These results could contribute to the validation of the medical use of these extracts that exert an antiplatelet effect to treat hemostatic and thrombotic disorders.
{"title":"Exploring the Therapeutic Potential: Antiplatelet and Antioxidant\u0000Activities of Some Medicinal Plants in Morocco","authors":"Lafdil Fatima Zahra, Amirou Asmae, Bnouham Mohamed, Legssyer Abdelkhaleq, Ziyyat Abderrahim, M. Hassane","doi":"10.2174/0122127968271295231212043119","DOIUrl":"https://doi.org/10.2174/0122127968271295231212043119","url":null,"abstract":"\u0000\u0000Thrombotic events and oxidative stress are major complications of certain\u0000ischemic disorders. The fight against these complications requires very intense research to develop\u0000new therapeutic agents of natural origin.\u0000\u0000\u0000\u0000The general objective of this work is the scientific valorization of five medicinal plants:\u0000Rhus pentaphylla, Zizyphus lotus, Ammodaucus leucotrichus, Inula viscosa, and Cinnamomum\u0000zeylanicum by exploring their effects on rat platelet aggregation, antioxidant potential and determining\u0000their phytochemical composition.\u0000\u0000\u0000\u0000e aggregation test was monitored by stimulating isolated washed platelets suspension\u0000in the absence and presence of extracts. The antioxidant activity was conducted in vitro according\u0000to three methods: DPPH free radical scavenging activity, β-carotene bleaching test, and ferric\u0000reducing antioxidant power test. The quantitative determination of total polyphenols and flavonoids\u0000are determined respectively according to the Folin-Ciocalteu method and the colorimetric method\u0000with aluminum chloride.\u0000\u0000\u0000\u0000The results obtained show that the aqueous extract of the fruits of Rhus pentaphylla and\u0000the aerial part of Inula viscosa, as well as the stalk peel of Cinnamomum zeylanicum, significantly\u0000(p˂0.001) inhibit thrombin-platelet aggregation, while the other plant extracts have a slightly, but\u0000significant effect. These extracts exert a remarkable antioxidant activity with the three methods\u0000used. But, their IC50 values are still higher than those of the antioxidant references (ascorbic acid\u0000and butyl hydroxyanisole). Qualitative phytochemical analysis revealed the presence of secondary\u0000metabolites with varying contents. Additionally, the results of quantitative phytochemical analysis\u0000showed that the aqueous extracts of the leaves of Rhus pentaphylla and the aerial part of Inula viscosa\u0000contain the highest amount of polyphenols and flavonoids. These secondary metabolites are\u0000also present in the other extracts but in smaller quantities.\u0000\u0000\u0000\u0000These results could contribute to the validation of the medical use of these extracts that\u0000exert an antiplatelet effect to treat hemostatic and thrombotic disorders.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":" 536","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138960596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-07DOI: 10.2174/0122127968263950231127051454
Farah Kenza Benattia, Z. Arrar, F. Dergal, Youssef Khabbal
Prickly pear "Opuntia ficus indica (L.) Mill. "otherwise known as the Indian fig tree, belongs to the family Cactaceae, and was known as a medicinal plant for its rich source of bioactive substances. The present work aims to promote prickly pear seeds for traditional therapy by phenolic profiling and pharmacological tests of aqueous extract. An analytical quantification was performed by UV-Visible, and the identification of different bioactive compounds was done by HPLC-DAD. For pharmacological screening, an in vivo evaluation of the various tests, neuroleptic activity which consists of testing the recovery reflex; catatonic activity which is a test to detect catalepsy that can be characterized in animals by the administration of neuroleptic drugs; and for hypoglycemic activity a test was performed to assess glucose tolerance. The administration of aqueous extract of the prickly pear seeds at a dose (400 mg/kg) allows a reduction in blood sugar with a maximum decrease of one and a half hours compared to the control group. This work makes it possible to postulate that the extract of prickly pear seeds is associated with a very interesting antihyperglycemic activity given its high content of phenolic compounds.
{"title":"Synergistic Effect, and Therapeutic Potential of Aqueous Prickly Pear Extract. In vivo Neuroleptic, Catatonic, and Hypoglycemic Activity","authors":"Farah Kenza Benattia, Z. Arrar, F. Dergal, Youssef Khabbal","doi":"10.2174/0122127968263950231127051454","DOIUrl":"https://doi.org/10.2174/0122127968263950231127051454","url":null,"abstract":"\u0000\u0000Prickly pear \"Opuntia ficus indica (L.) Mill. \"otherwise known as the Indian fig tree, belongs to the family Cactaceae, and was known as a medicinal plant for its rich source\u0000of bioactive substances.\u0000\u0000\u0000\u0000The present work aims to promote prickly pear seeds for traditional therapy by phenolic\u0000profiling and pharmacological tests of aqueous extract.\u0000\u0000\u0000\u0000An analytical quantification was performed by UV-Visible, and the identification of different bioactive compounds was done by HPLC-DAD. For pharmacological screening, an in vivo\u0000evaluation of the various tests, neuroleptic activity which consists of testing the recovery reflex;\u0000catatonic activity which is a test to detect catalepsy that can be characterized in animals by the administration of neuroleptic drugs; and for hypoglycemic activity a test was performed to assess glucose tolerance.\u0000\u0000\u0000\u0000The administration of aqueous extract of the prickly pear seeds at a dose (400 mg/kg) allows a reduction in blood sugar with a maximum decrease of one and a half hours compared to the\u0000control group.\u0000\u0000\u0000\u0000This work makes it possible to postulate that the extract of prickly pear seeds is associated with a very interesting antihyperglycemic activity given its high content of phenolic compounds.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"34 23","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138594117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
background: Stenotrophomonas maltophilia is a pathogenic bacteria that causes serious infectious complications in humans, especially in immune-compromised patients. Stenotrophomonas maltophilia is a gram-negative bacterium that is multidrug-resistant. objective: The purpose of the study is to understand the diverse cellular and biological functions of cadmium-binding metalloproteins and to predict their role in pathogenicity, regulation, and growth. methodology: Different in silico approaches were used to check the Functional Annotation, Subcellular Localization, Gene Ontology, and Bacterial toxin prediction have been used to identify the cellular and biological function of Cd-binding metalloproteins in Stenotrophomonas maltophilia. results: Identified 116 Cd-binding proteins from the whole proteome sequence and functional domain, family, localization, and toxicity were also studied. conclusion: The outcomes revealed that this study could be used in understanding the 116 cadmium-binding proteins from the whole proteome sequence. This study shows the survival, growth, and pathogenicity of the bacteria.
{"title":"In silico identification of cadmium binding protein and its secreted metalloproteins in Stenotrophomonas maltophilia","authors":"Nandhana Ganapathy Salini, Rikhia Majumdar, Shahjahan Ahamad, Shobana Sugumar","doi":"10.2174/2212796817666230911094043","DOIUrl":"https://doi.org/10.2174/2212796817666230911094043","url":null,"abstract":"background: Stenotrophomonas maltophilia is a pathogenic bacteria that causes serious infectious complications in humans, especially in immune-compromised patients. Stenotrophomonas maltophilia is a gram-negative bacterium that is multidrug-resistant. objective: The purpose of the study is to understand the diverse cellular and biological functions of cadmium-binding metalloproteins and to predict their role in pathogenicity, regulation, and growth. methodology: Different in silico approaches were used to check the Functional Annotation, Subcellular Localization, Gene Ontology, and Bacterial toxin prediction have been used to identify the cellular and biological function of Cd-binding metalloproteins in Stenotrophomonas maltophilia. results: Identified 116 Cd-binding proteins from the whole proteome sequence and functional domain, family, localization, and toxicity were also studied. conclusion: The outcomes revealed that this study could be used in understanding the 116 cadmium-binding proteins from the whole proteome sequence. This study shows the survival, growth, and pathogenicity of the bacteria.","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"106 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135981344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.2174/0122127968249184231018072135
Zahra Yarahmadi, Atefeh Sadeghi, Fahimeh Mohammadian, Farzad Roustaei, Mohammadreza Hajizadeh, Mohamamdreza Mirzaei, Jennifer Swann, Reza Hosseiniara, Mehdi Mahmoodi
Various forms of epigenetic modification, including DNA methylation, contribute to hepatocellular carcinoma (HCC) dissemination, invasion, and metastasis. The Persian shallot (Allium hirtifolium Bioss.) is reported to have antibacterial, antifungal, antioxidant, and anticarcinogenic properties. In the present study, we examined the expression of DNA (cytosine-5)-methyltransferase 1 (DNMT1) and ten-eleven translocation methylcytosine dioxygenase 1 (TET1) at the mRNA level in HepG2 cells following treatment with Persian shallot extract. Ethanolic extracts of Persian shallot were prepared and dried at 80°C and 50°C for 20 and 30 minutes, respectively. Different concentrations of dried shallot extract over the range of 0-250 µg/ml were prepared. HepG2 cells were cultured and the cytotoxicity of each extract concentration was measured using an MTT assay. The gene expression in treated and untreated cells was assessed by Real-time polymerase chain reaction (RT-PCR). The half maximal inhibitory concentration (IC50) was determined to be 149 µg/ml using an MTT assay. A concentration of 175 µg/ml was found to reduce the expression of DNMT1 in the treated group compared to the control group (P<0.001). Furthermore, the TET1 mRNA of HepG2 cells was down-regulated significantly after treatment with 100 and 1000 µg/ml of Persian shallot extract (P<0.05). These doses reduced the viability of the samples by 60% or higher. This study provides evidence for the potential use of Persian shallot extract as a supplementary herbal agent for the treatment of HCC. The concentrations of extract used in this study are near or above the level required for toxicity, and as such, further study is warranted.
{"title":"Epigenetic Modification of HepG2 Cells by Modulating DNA (cytosine-5)- methyltransferase 1 (DNMT1) and Ten-eleven Translocation Methylcytosine Dioxygenase 1 (TET1) Expression using Persian Shallot Extract","authors":"Zahra Yarahmadi, Atefeh Sadeghi, Fahimeh Mohammadian, Farzad Roustaei, Mohammadreza Hajizadeh, Mohamamdreza Mirzaei, Jennifer Swann, Reza Hosseiniara, Mehdi Mahmoodi","doi":"10.2174/0122127968249184231018072135","DOIUrl":"https://doi.org/10.2174/0122127968249184231018072135","url":null,"abstract":"Various forms of epigenetic modification, including DNA methylation, contribute to hepatocellular carcinoma (HCC) dissemination, invasion, and metastasis. The Persian shallot (Allium hirtifolium Bioss.) is reported to have antibacterial, antifungal, antioxidant, and anticarcinogenic properties. In the present study, we examined the expression of DNA (cytosine-5)-methyltransferase 1 (DNMT1) and ten-eleven translocation methylcytosine dioxygenase 1 (TET1) at the mRNA level in HepG2 cells following treatment with Persian shallot extract. Ethanolic extracts of Persian shallot were prepared and dried at 80°C and 50°C for 20 and 30 minutes, respectively. Different concentrations of dried shallot extract over the range of 0-250 µg/ml were prepared. HepG2 cells were cultured and the cytotoxicity of each extract concentration was measured using an MTT assay. The gene expression in treated and untreated cells was assessed by Real-time polymerase chain reaction (RT-PCR). The half maximal inhibitory concentration (IC50) was determined to be 149 µg/ml using an MTT assay. A concentration of 175 µg/ml was found to reduce the expression of DNMT1 in the treated group compared to the control group (P<0.001). Furthermore, the TET1 mRNA of HepG2 cells was down-regulated significantly after treatment with 100 and 1000 µg/ml of Persian shallot extract (P<0.05). These doses reduced the viability of the samples by 60% or higher. This study provides evidence for the potential use of Persian shallot extract as a supplementary herbal agent for the treatment of HCC. The concentrations of extract used in this study are near or above the level required for toxicity, and as such, further study is warranted.","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"59 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139345357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Argania spinosa L. seed oil is a Moroccan endemic product that is used traditionally as an alternative treatment for diabetes. Objective: The present work aims to evaluate the hemoglobin antiglycation and the antioxidant effect of roasted (Roil) and unroasted (UnRoil) Argan seed oil in vitro. Methods: The antioxidant activity was evaluated by different methods (total antioxidant capacity by the ammonium molybdate, metal chelating activity, ferric reducing antioxidant power, 1, 1-diphenyl-2- picrylhydrazyl free radical scavenging, and β-carotene bleaching test), and the protein antiglycation effect was tested using hemoglobin, in vitro. Results: The results showed that both oils possess an important antioxidant effect and the roasting process did not influence the total antioxidant capacity, metal chelating activity, and β-carotene bleaching test. Although, it significantly influences the antiradical activity of Argania spinosa L. seed oil (p < 0.05) with IC50 values of 21.47 ± 0.076 μg/mL for Roil and 4.01 ± 1.13 μg/mL for UnRoil. Besides, Roil and UnRoil it significantly inhibit the hemoglobin glycation activity, with IC50 values of 1.09 ± 0.31 and 0.16 ± 0.031 mg/ml respectively. Moreover, it was noted that UnRoil has a lower IC50 value than Roil, which means that UnRoil has a more potent activity than Roil (p < 0.05). Conclusion: Argania spinosa L. seed oil is an essential source of natural antioxidants and hemoglobin antiglycation that plays a key role in scavenging of free radicals and might be used for reducing the development of diabetic complications.
{"title":"Investigation of In Vitro Antioxidant and Hemoglobin Antiglycation Effect of Roasted and Unroasted Argania spinosa L. Seed Oil from Morocco","authors":"Nour Elhouda Daoudi, Rhizlan Abdnim, Ghariba Elkhadraoui, Hassane Mekhfi, Abdelkhaleq Legssyer, Abderrahim Ziyyat, Mohamed Bnouham","doi":"10.2174/2212796817666230803141223","DOIUrl":"https://doi.org/10.2174/2212796817666230803141223","url":null,"abstract":"Background: Argania spinosa L. seed oil is a Moroccan endemic product that is used traditionally as an alternative treatment for diabetes. Objective: The present work aims to evaluate the hemoglobin antiglycation and the antioxidant effect of roasted (Roil) and unroasted (UnRoil) Argan seed oil in vitro. Methods: The antioxidant activity was evaluated by different methods (total antioxidant capacity by the ammonium molybdate, metal chelating activity, ferric reducing antioxidant power, 1, 1-diphenyl-2- picrylhydrazyl free radical scavenging, and β-carotene bleaching test), and the protein antiglycation effect was tested using hemoglobin, in vitro. Results: The results showed that both oils possess an important antioxidant effect and the roasting process did not influence the total antioxidant capacity, metal chelating activity, and β-carotene bleaching test. Although, it significantly influences the antiradical activity of Argania spinosa L. seed oil (p < 0.05) with IC50 values of 21.47 ± 0.076 μg/mL for Roil and 4.01 ± 1.13 μg/mL for UnRoil. Besides, Roil and UnRoil it significantly inhibit the hemoglobin glycation activity, with IC50 values of 1.09 ± 0.31 and 0.16 ± 0.031 mg/ml respectively. Moreover, it was noted that UnRoil has a lower IC50 value than Roil, which means that UnRoil has a more potent activity than Roil (p < 0.05). Conclusion: Argania spinosa L. seed oil is an essential source of natural antioxidants and hemoglobin antiglycation that plays a key role in scavenging of free radicals and might be used for reducing the development of diabetic complications.","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"145 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136327454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-01DOI: 10.2174/2212796817666230801121826
Adriana Okayama, Hamilton Cabral, Gustavo Orlando Bonilla-Rodriguez
Aims: This work performed a preliminary characterization of two new peptidases from Ananas ananassoides. Background: Proteolytic enzymes, also known as peptidases, are found in all living things and play critical physiological roles in metabolism and cellular regulation. They account for roughly 60% of the enzymes used in industry and have high proteolytic activity, such as papain from Carica papaya latex and stem and fruit bromelains from the edible pineapple Ananas comosus. Objective: The wild pineapple Ananas ananassoides contains proteolytic enzymes, which motivated this study due to the potential applications of this type of enzyme. Methods: The fruit and stem of A. ananassoides were blended, clarified, and purified using chromatography (SP-Sepharose and Sephadex G-50). The molecular mass was determined using mass spectrometry (M.S.), and the N-terminal sequences were obtained and compared to other Bromeliaceae proteases. Fluorogenic substrates were used to determine the kinetic parameters. Results: As determined by M.S., the fruit and stem contain cysteine-peptidases with Mr of 27,329.6 and 23,912.5 Da, respectively, values that are very similar to those found in edible pineapple bromelains. Despite Mr and carbohydrate composition differences, both proteases have similar optimum pH values. They have similar temperature effects, though the stem protease is more thermally stable. Both proteases have a stronger preference for hydrophobic, polar, and basic residues. Both proteases hydrolyzed substrates containing polar and basic residues. Conclusion: A comparison of the N-terminal sequences (AVPQIIDW for fruit ananassains and AVPEIIDW for stem ananassains) reveals a high degree of homology when compared to other Bromeliaceae proteases such as papain.
{"title":"Isolation and biochemical characterization of ananassains, cysteine peptidases from the fruits of Ananas ananassoides","authors":"Adriana Okayama, Hamilton Cabral, Gustavo Orlando Bonilla-Rodriguez","doi":"10.2174/2212796817666230801121826","DOIUrl":"https://doi.org/10.2174/2212796817666230801121826","url":null,"abstract":"Aims: This work performed a preliminary characterization of two new peptidases from Ananas ananassoides. Background: Proteolytic enzymes, also known as peptidases, are found in all living things and play critical physiological roles in metabolism and cellular regulation. They account for roughly 60% of the enzymes used in industry and have high proteolytic activity, such as papain from Carica papaya latex and stem and fruit bromelains from the edible pineapple Ananas comosus. Objective: The wild pineapple Ananas ananassoides contains proteolytic enzymes, which motivated this study due to the potential applications of this type of enzyme. Methods: The fruit and stem of A. ananassoides were blended, clarified, and purified using chromatography (SP-Sepharose and Sephadex G-50). The molecular mass was determined using mass spectrometry (M.S.), and the N-terminal sequences were obtained and compared to other Bromeliaceae proteases. Fluorogenic substrates were used to determine the kinetic parameters. Results: As determined by M.S., the fruit and stem contain cysteine-peptidases with Mr of 27,329.6 and 23,912.5 Da, respectively, values that are very similar to those found in edible pineapple bromelains. Despite Mr and carbohydrate composition differences, both proteases have similar optimum pH values. They have similar temperature effects, though the stem protease is more thermally stable. Both proteases have a stronger preference for hydrophobic, polar, and basic residues. Both proteases hydrolyzed substrates containing polar and basic residues. Conclusion: A comparison of the N-terminal sequences (AVPQIIDW for fruit ananassains and AVPEIIDW for stem ananassains) reveals a high degree of homology when compared to other Bromeliaceae proteases such as papain.","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"70 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136021787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-26DOI: 10.2174/2212796817666230626120825
M. Dib, Marieme Kacem, S. Talbi, H. Ouchetto, Khadija Ouchetto, A. Essoumhi, A. Hafid, M. Khouili
The 4H-pyran compounds are an important class of heterocyclic compounds due to their diverse biological and pharmaceutical properties. Moreover, 4H-pyran is a crucial structural component commonly encountered in the pharmaceutical industry. Thus, it has recently gained significant attention from industry researchers and academic organizations. Herein, we report an efficient and eco-friendly one-pot strategy to synthesize bioactive compounds containing 4H-pyran motifs via a multicomponent reaction. This reaction occurs by reacting equimolar amounts of ethyl acetoacetate, malononitrile, and substituted aldehyde under mild conditions in the presence of a solid catalyst, MgO-MgAl2O4. This latter, was obtained by heat treatment, at 800°C, of a layered double hydroxide with the metal cation ratio of Mg2+/Al3+ = 3:1, and it was characterized by some techniques including XRD, TG-DTA, FT-IR and N2 adsorption-desorption. Therefore, bioactive compounds containing the pyran unit may possess intriguing biological properties. The synthetic protocol offers advantages such as a simple procedure, good to excellent yields, and easy catalyst separation from the reaction mixture. Substituted 4H-pyran derivatives were prepared by the condensation reaction of substituted aldehydes, ethyl acetoacetate and malononitrile using MgO-MgAl2O4 catalyst under mild conditions. This study aims to develop an efficient methodology for synthesizing 4H-pyran heterocyclic compounds that have potential applications in biological sciences. The study utilizes MgO-MgAl2O4 as a highly effective heterogeneous catalyst. The present research details the synthesis of 4H-pyran bioactive compounds using sustainable reaction conditions, which resulted in high yields and facilitated the easy separation of the catalyst from the reaction mixture. In summary, the MgO-MgAl2O4 spinel nanostructure has been successfully prepared and fully characterized by using different physicochemical techniques such as XRD, TG-DTA, FT-IR and N2 adsorption-desorption. Afterwards, its catalytic activity was investigated through the one-pot condensation of aryl aldehyde, malononitrile and ethyl acetoacetate. Moreover, it exhibits good catalytic activity for the synthesis of 4H-pyran derivatives under green conditions. These latter have many benefits, such as simple procedure, good to excellent yields and easy separation of the catalyst from the reaction mixture.
{"title":"MgO-MgAl2O4: An efficient catalyst for multicomponent synthesis of substituted 4H-pyran","authors":"M. Dib, Marieme Kacem, S. Talbi, H. Ouchetto, Khadija Ouchetto, A. Essoumhi, A. Hafid, M. Khouili","doi":"10.2174/2212796817666230626120825","DOIUrl":"https://doi.org/10.2174/2212796817666230626120825","url":null,"abstract":"\u0000\u0000The 4H-pyran compounds are an important class of heterocyclic compounds due to their diverse biological and pharmaceutical properties. Moreover, 4H-pyran is a crucial structural component commonly encountered in the pharmaceutical industry. Thus, it has recently gained significant attention from industry researchers and academic organizations. Herein, we report an efficient and eco-friendly one-pot strategy to synthesize bioactive compounds containing 4H-pyran motifs via a multicomponent reaction. This reaction occurs by reacting equimolar amounts of ethyl acetoacetate, malononitrile, and substituted aldehyde under mild conditions in the presence of a solid catalyst, MgO-MgAl2O4. This latter, was obtained by heat treatment, at 800°C, of a layered double hydroxide with the metal cation ratio of Mg2+/Al3+ = 3:1, and it was characterized by some techniques including XRD, TG-DTA, FT-IR and N2 adsorption-desorption. Therefore, bioactive compounds containing the pyran unit may possess intriguing biological properties. The synthetic protocol offers advantages such as a simple procedure, good to excellent yields, and easy catalyst separation from the reaction mixture.\u0000\u0000\u0000\u0000Substituted 4H-pyran derivatives were prepared by the condensation reaction of substituted aldehydes, ethyl acetoacetate and malononitrile using MgO-MgAl2O4 catalyst under mild conditions.\u0000This study aims to develop an efficient methodology for synthesizing 4H-pyran heterocyclic compounds that have potential applications in biological sciences. The study utilizes MgO-MgAl2O4 as a highly effective heterogeneous catalyst.\u0000\u0000\u0000\u0000The present research details the synthesis of 4H-pyran bioactive compounds using sustainable reaction conditions, which resulted in high yields and facilitated the easy separation of the catalyst from the reaction mixture.\u0000\u0000\u0000\u0000In summary, the MgO-MgAl2O4 spinel nanostructure has been successfully prepared and fully characterized by using different physicochemical techniques such as XRD, TG-DTA, FT-IR and N2 adsorption-desorption. Afterwards, its catalytic activity was investigated through the one-pot condensation of aryl aldehyde, malononitrile and ethyl acetoacetate. Moreover, it exhibits good catalytic activity for the synthesis of 4H-pyran derivatives under green conditions. These latter have many benefits, such as simple procedure, good to excellent yields and easy separation of the catalyst from the reaction mixture.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73734188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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