Detecting N-nitrosamine impurities in medicines has been a significant challenge for drug manufacturers and regulators, especially with the recent emergence of nitrosamine drug substance-related impurities (NDSRIs). The formation of NDSRIs is complex and primarily associated with reactions in the drug product. This paper explores the current technical knowledge on forming these impurities, including the risk factors, reaction conditions, and possible mitigation strategies. While significant scientific progress has been made in these areas, substantial gaps in mechanistic knowledge still make accurate predictions of NDSRI formation very difficult. The pharmaceutical industry's continued work on potential mitigation strategies and the generation of additional scientific data to address these knowledge gaps are crucial. Regulatory guidance and policy will continue to evolve in response to further changes in scientific understanding. In this article, we will delve into the detection methods, the mechanism of action, sample preparation techniques, and regulatory limits for nitrosamine impurities. We also discuss various reported nitrosamine impurities, their chemical structures, and their detection using methods like LC-MS/MS, GC-MS-HS, and HPLC. Additionally, we discuss different sample preparation techniques, such as solid-phase extraction, liquid-liquid extraction, and rapid-fire techniques. This review is intended to provide detailed information to analytical personnel working in various quality control laboratories and research organizations.
{"title":"The clinical and regulatory status of NDSRI: A global imperative","authors":"Ritu Tiwari, Gaurav Sanjay Mahalpure, Sakshi Mahalpure, Anuanshika Tiwari","doi":"10.25082/jpbr.2024.01.001","DOIUrl":"https://doi.org/10.25082/jpbr.2024.01.001","url":null,"abstract":"Detecting N-nitrosamine impurities in medicines has been a significant challenge for drug manufacturers and regulators, especially with the recent emergence of nitrosamine drug substance-related impurities (NDSRIs). The formation of NDSRIs is complex and primarily associated with reactions in the drug product. This paper explores the current technical knowledge on forming these impurities, including the risk factors, reaction conditions, and possible mitigation strategies. While significant scientific progress has been made in these areas, substantial gaps in mechanistic knowledge still make accurate predictions of NDSRI formation very difficult. The pharmaceutical industry's continued work on potential mitigation strategies and the generation of additional scientific data to address these knowledge gaps are crucial. Regulatory guidance and policy will continue to evolve in response to further changes in scientific understanding. In this article, we will delve into the detection methods, the mechanism of action, sample preparation techniques, and regulatory limits for nitrosamine impurities. We also discuss various reported nitrosamine impurities, their chemical structures, and their detection using methods like LC-MS/MS, GC-MS-HS, and HPLC. Additionally, we discuss different sample preparation techniques, such as solid-phase extraction, liquid-liquid extraction, and rapid-fire techniques. This review is intended to provide detailed information to analytical personnel working in various quality control laboratories and research organizations.","PeriodicalId":16703,"journal":{"name":"Journal of Pharmaceutical and Biopharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141803781","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}
The past decade has witnessed a tremendous surge of interest in herbal medicines throughout the world. Aflatoxins are naturally occurring mycotoxins that are mainly produced by Aspargillus flavus and Aspargillus parasiticus and primarily contaminate food crops such as corn, groundnuts, and tree nuts as well as herbal medicinal plants in tropical and subtropical regions of the world. It is a lethal substance that intensely or at slower ingestion influences the strength of humans and animals. Aflatoxin study is vital for a safety perspective as they are extremely lethal and cancer-causing; to overcome the health effect of aflatoxins and for better assessment and standardization of herbal plant drugs. The investigation includes worldwide regulations on aflatoxins with their acceptable ranges in commodities. With more controls for adequate dimensions of aflatoxins set up, present-day analytical techniques have turned out to be very modern, capable of accomplishing results with high accuracy and precision, appropriate for administrative research centers and post-reap sample testing in developed countries.
{"title":"A big threat : Aflatoxin","authors":"Ritu Tiwari, Aanal Pandaya, Poornima Gulati, Aishwarya Chahuan","doi":"10.25082/jpbr.2023.02.002","DOIUrl":"https://doi.org/10.25082/jpbr.2023.02.002","url":null,"abstract":"The past decade has witnessed a tremendous surge of interest in herbal medicines throughout the world. Aflatoxins are naturally occurring mycotoxins that are mainly produced by Aspargillus flavus and Aspargillus parasiticus and primarily contaminate food crops such as corn, groundnuts, and tree nuts as well as herbal medicinal plants in tropical and subtropical regions of the world. It is a lethal substance that intensely or at slower ingestion influences the strength of humans and animals. Aflatoxin study is vital for a safety perspective as they are extremely lethal and cancer-causing; to overcome the health effect of aflatoxins and for better assessment and standardization of herbal plant drugs. The investigation includes worldwide regulations on aflatoxins with their acceptable ranges in commodities. With more controls for adequate dimensions of aflatoxins set up, present-day analytical techniques have turned out to be very modern, capable of accomplishing results with high accuracy and precision, appropriate for administrative research centers and post-reap sample testing in developed countries.","PeriodicalId":16703,"journal":{"name":"Journal of Pharmaceutical and Biopharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141110551","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}
Heavy metals and pesticide residue analysis plays an important role in the quality control of medicinal plants like Vasaka (Adhatoda vasica). Hence a study was conducted to determine heavy metals and pesticide residues in this medicinal herb, which is a highly useful commodity in the health system. The reliable, rapid and nontoxic sample preparation method like QuEChERS and analytical methods like GC-MS were proposed for the simultaneous determination of pesticide residues and Heavy metal detection was carried out by ICP-MS. In this study, the presence of organophosphorus and organochlorine pesticides like alachlor, heptachlor, heptachlor epoxide, aldrin, dieldrin, endrin, etc was checked but not detected. Heavy metals like Arsenic (As), Cadmium (Cd), Mercury (Hg) and Lead (Pb) are traced in samples about 2.3005 ppb, 0.799 ppb, 2.290 ppb and 10.204 ppb respectively in the present study.
{"title":"Determination of pesticide residues and heavy metals in Adhatoda Vasaka Linn.","authors":"Ritu Tiwari, Aishwarya Chauhan, Madhavi Patel, Komal Patel","doi":"10.25082/jpbr.2023.02.001","DOIUrl":"https://doi.org/10.25082/jpbr.2023.02.001","url":null,"abstract":"Heavy metals and pesticide residue analysis plays an important role in the quality control of medicinal plants like Vasaka (Adhatoda vasica). Hence a study was conducted to determine heavy metals and pesticide residues in this medicinal herb, which is a highly useful commodity in the health system. The reliable, rapid and nontoxic sample preparation method like QuEChERS and analytical methods like GC-MS were proposed for the simultaneous determination of pesticide residues and Heavy metal detection was carried out by ICP-MS. In this study, the presence of organophosphorus and organochlorine pesticides like alachlor, heptachlor, heptachlor epoxide, aldrin, dieldrin, endrin, etc was checked but not detected. Heavy metals like Arsenic (As), Cadmium (Cd), Mercury (Hg) and Lead (Pb) are traced in samples about 2.3005 ppb, 0.799 ppb, 2.290 ppb and 10.204 ppb respectively in the present study.","PeriodicalId":16703,"journal":{"name":"Journal of Pharmaceutical and Biopharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140975697","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 : 2024-03-25DOI: 10.25082/jpbr.2023.01.004
Linyao Yu, Wei Zhang, Yaoqin Shi, Yingtian Zhang, Min Xu, Yang Xu, Chunmei Li, Jingwei Tian
Background: Bipolar disorder (BD) is a deleterious psychiatric disorder, and the available pharmacotherapies have limited efficacy with significant side effects. Trace amine-associated receptor 1 (TAAR1) is an emerging drug target for neuropsychiatric disorders such as schizophrenia and substance user disorders. However, it is unknown whether TAAR1 is involved in the pathogenesis of BD. This study examined the effects and underlying mechanisms of a novel TAAR1 agonist, PCC0105004, in a rat model of ouabain (OUA)-induced BD.Methods: Intracerebroventricular (ICV) administration of OUA-induced BD model was established. The in vitro cell-based cAMP assay was used to examine TAAR1 agonism of PCC0105004. The receptor specificity of PCC0105004 was determined by an off-target panel assay that included radioligand binding and enzymatic assays. The effects of PCC0105004 on manic-like and depressive-like behaviors were evaluated in the rat BD model. TAAR1-mediated signaling and oxidative stress parameters were biochemically determined in the prefrontal cortex and the hippocampus of rats.Results: Western blotting revealed reduced TAAR1 expression level in the prefrontal cortex but unchanged in the hippocampus in model rats. PCC0105004, a TAAR1 agonist with the agonism EC50 value of 0.06182 μM, attenuated the manic-like behaviors on the 7th day and the depressive-like behaviors on the 14th day at doses that did not affect locomotor activity in the BD rats. Mechanistically, PCC0105004 exerted its behavioral effects via the reduction of ROS damage through the phosphorylation activation of the TAAR1/Akt/GSK3β/BDNF signaling pathway.Conclusion: These results demonstrated the potential antimanic-like and antidepressant-like efficacy of a novel TAAR1 agonist PCC0105004 in rats and revealed its underlying molecular basis, which supports the possibility of TAAR1 agonists as candidate pharmacotherapeutics for BD.
{"title":"TAAR1 as a new target for the treatment of bipolar disorder: Anti-manic and anti-depressant activity of the novel agonist PCC0105004","authors":"Linyao Yu, Wei Zhang, Yaoqin Shi, Yingtian Zhang, Min Xu, Yang Xu, Chunmei Li, Jingwei Tian","doi":"10.25082/jpbr.2023.01.004","DOIUrl":"https://doi.org/10.25082/jpbr.2023.01.004","url":null,"abstract":"Background: Bipolar disorder (BD) is a deleterious psychiatric disorder, and the available pharmacotherapies have limited efficacy with significant side effects. Trace amine-associated receptor 1 (TAAR1) is an emerging drug target for neuropsychiatric disorders such as schizophrenia and substance user disorders. However, it is unknown whether TAAR1 is involved in the pathogenesis of BD. This study examined the effects and underlying mechanisms of a novel TAAR1 agonist, PCC0105004, in a rat model of ouabain (OUA)-induced BD.Methods: Intracerebroventricular (ICV) administration of OUA-induced BD model was established. The in vitro cell-based cAMP assay was used to examine TAAR1 agonism of PCC0105004. The receptor specificity of PCC0105004 was determined by an off-target panel assay that included radioligand binding and enzymatic assays. The effects of PCC0105004 on manic-like and depressive-like behaviors were evaluated in the rat BD model. TAAR1-mediated signaling and oxidative stress parameters were biochemically determined in the prefrontal cortex and the hippocampus of rats.Results: Western blotting revealed reduced TAAR1 expression level in the prefrontal cortex but unchanged in the hippocampus in model rats. PCC0105004, a TAAR1 agonist with the agonism EC50 value of 0.06182 μM, attenuated the manic-like behaviors on the 7th day and the depressive-like behaviors on the 14th day at doses that did not affect locomotor activity in the BD rats. Mechanistically, PCC0105004 exerted its behavioral effects via the reduction of ROS damage through the phosphorylation activation of the TAAR1/Akt/GSK3β/BDNF signaling pathway.Conclusion: These results demonstrated the potential antimanic-like and antidepressant-like efficacy of a novel TAAR1 agonist PCC0105004 in rats and revealed its underlying molecular basis, which supports the possibility of TAAR1 agonists as candidate pharmacotherapeutics for BD.","PeriodicalId":16703,"journal":{"name":"Journal of Pharmaceutical and Biopharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140382053","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 : 2024-03-14DOI: 10.25082/jpbr.2023.01.003
Wei Zhang, Linyao Yu, Yaoqin Shi, Yingtian Zhang, Min Xu, Yang Xu, Chunmei Li, Jingwei Tian
Objective: Bipolar disorder (BD) affects more than 1% of the global population with limited therapeutic options. The neurokinin B (NKB)-neurokinin B receptor (NK3R) is involved in a variety of emotional activities. This study explored the role of NK3 receptor signaling in bipolar disorder.Materials and methods: In this study, a model of intracerebroventricular (ICV) administration of OUA-induced BD was used to investigate the possible role of NK3R signaling in BD. The involvement of NK3R in the expression of OUA-induced BD was assessed by genetically knocking down the NK3R-encoding TACR3 gene with shRNA approach in the hippocampus and systemic administration of a NK3R antagonist ESN364,. Biochemical techniques were used to examine the NK3R-associated signaling changes and the oxidative stress parameters in the hippocampus of BD rats.Result: The NK3R expression level was elevated in the hippocampus BD rats. Both TACR3 knockdown in the hippocampus and ESN364 treatment reversed the manic-like and depression-like behaviors in BD rats Inhibition of the NK3R signaling reversed oxidative stress-induced damage via upregulating the BDNF signaling pathway in the hippocampus.Conclusion: These results demonstrated that NK3R signaling plays a key role in the pathogenesis of BD and that pharmacological antagonist of NK3R such as ESN364 could represent a novel therapeutic strategy for the management of BD.
{"title":"A novel role of NK3 receptor signaling in bipolar disorder","authors":"Wei Zhang, Linyao Yu, Yaoqin Shi, Yingtian Zhang, Min Xu, Yang Xu, Chunmei Li, Jingwei Tian","doi":"10.25082/jpbr.2023.01.003","DOIUrl":"https://doi.org/10.25082/jpbr.2023.01.003","url":null,"abstract":"Objective: Bipolar disorder (BD) affects more than 1% of the global population with limited therapeutic options. The neurokinin B (NKB)-neurokinin B receptor (NK3R) is involved in a variety of emotional activities. This study explored the role of NK3 receptor signaling in bipolar disorder.Materials and methods: In this study, a model of intracerebroventricular (ICV) administration of OUA-induced BD was used to investigate the possible role of NK3R signaling in BD. The involvement of NK3R in the expression of OUA-induced BD was assessed by genetically knocking down the NK3R-encoding TACR3 gene with shRNA approach in the hippocampus and systemic administration of a NK3R antagonist ESN364,. Biochemical techniques were used to examine the NK3R-associated signaling changes and the oxidative stress parameters in the hippocampus of BD rats.Result: The NK3R expression level was elevated in the hippocampus BD rats. Both TACR3 knockdown in the hippocampus and ESN364 treatment reversed the manic-like and depression-like behaviors in BD rats Inhibition of the NK3R signaling reversed oxidative stress-induced damage via upregulating the BDNF signaling pathway in the hippocampus.Conclusion: These results demonstrated that NK3R signaling plays a key role in the pathogenesis of BD and that pharmacological antagonist of NK3R such as ESN364 could represent a novel therapeutic strategy for the management of BD.","PeriodicalId":16703,"journal":{"name":"Journal of Pharmaceutical and Biopharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140243300","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}
Objective: Fuyuekang Lotion (FYKL) is an improved traditional Chinese medicine (TCM) prescription widely used to treat acute eczema (AE). However, the mechanism of action remains unclear. This study aimed to explore the therapeutic mechanism of FYKL in AE.Methods: We revealed the underlying mechanism by utilizing a network pharmacology approach, molecular docking studies, and in vitro verification. The active compounds in FYKL were identified, and their targets were predicted. These targets were subsequently mapped to a component-target interaction network, with their therapeutic mechanisms predicted through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Molecular docking was used to verify protein-binding efficacy. Potential key targets of FYKL against AE were further confirmed via reverse transcription quantitative polymerase chain reaction (RT-qPCR).Results: The study identified 59 potential active compounds of FYKL, with quercetin, luteolin, and gallic acid suggested as critical active ingredients. Our findings suggest that these ingredients could exert their effects mainly by modulating the inflammatory immune response and promoting epidermal repair. FYKL was found to be a multi-target, multi-component drug that could potentially regulate the inflammatory immune response in AE through numerous pathways.Conclusions: The findings from this study provide a scientific basis for further research into the therapeutic effects and mechanisms of FYKL in treating AE, underscoring the potential of TCM in modern therapeutics.
{"title":"Network pharmacology-based prediction for therapeutic mechanism of FuYueKang Lotion on acute eczema","authors":"Xiaowen Wen, Shaokang Cui, Minzhi Li, Yongping Zheng, Haoyou Xu","doi":"10.25082/jpbr.2023.01.002","DOIUrl":"https://doi.org/10.25082/jpbr.2023.01.002","url":null,"abstract":"Objective: Fuyuekang Lotion (FYKL) is an improved traditional Chinese medicine (TCM) prescription widely used to treat acute eczema (AE). However, the mechanism of action remains unclear. This study aimed to explore the therapeutic mechanism of FYKL in AE.Methods: We revealed the underlying mechanism by utilizing a network pharmacology approach, molecular docking studies, and in vitro verification. The active compounds in FYKL were identified, and their targets were predicted. These targets were subsequently mapped to a component-target interaction network, with their therapeutic mechanisms predicted through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Molecular docking was used to verify protein-binding efficacy. Potential key targets of FYKL against AE were further confirmed via reverse transcription quantitative polymerase chain reaction (RT-qPCR).Results: The study identified 59 potential active compounds of FYKL, with quercetin, luteolin, and gallic acid suggested as critical active ingredients. Our findings suggest that these ingredients could exert their effects mainly by modulating the inflammatory immune response and promoting epidermal repair. FYKL was found to be a multi-target, multi-component drug that could potentially regulate the inflammatory immune response in AE through numerous pathways.Conclusions: The findings from this study provide a scientific basis for further research into the therapeutic effects and mechanisms of FYKL in treating AE, underscoring the potential of TCM in modern therapeutics.","PeriodicalId":16703,"journal":{"name":"Journal of Pharmaceutical and Biopharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135321089","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 : 2023-04-19DOI: 10.25082/jpbr.2023.01.001
Minjun Wang
Background: Atherosclerosis (AS) is one of the leading causes of cardiovascular diseases. The traditional China herb pairs such as Huanglian-Gualou, Honghua-Taoren, and Suhexiang-Bingpian showed therapeutic effects on AS by clearing heat and resolving phlegm, invigorating blood and removing blood stasis, as well as aromatic resuscitation, respectively. However, the common and specific mechanisms of these pairs against the same disease are elusive.Objective: This study aimed to explore the molecular mechanisms of 3 herb pairs treating AS by network pharmacology, molecular modeling and mechanism experiments.Methods: The components and their corresponding targets of 3 herb pairs, as well as AS-related targets, were collected from multiple databases and literature. Then the protein-protein interaction network was built to identify the key components and targets associated with AS. The pathway enrichment analysis using KEGG was carried out for analyzing the common mechanisms of 3 herb pairs against AS. Finally, the binding modes of the key components and targets were analyzed by molecular docking and molecular dynamic simulation.Results: The PPI network indicated that the common targets of 3 herb pairs focused on four pathways, including regulated vascular shear stress, TNF, ARE-RAGE, and IL-17 pathways. The molecular docking analysis indicated that the key component quercetin showed highest docking score with PTGS2 in comparison to other targets. Molecular dynamics simulations revealed that quercetin stably anchored to the active pocket of PTGS2 by forming hydrogen bonds with Thr175, Asn351, and Trp356.Conclusion: The molecular mechanism of Huanglian-Gualou, Honghua-Taoren, and Suhexiang-Bingpian against AS was preliminarily expounded, and we wish to provide a theoretical instruction for clinical treatment of AS.
{"title":"Exploring the mechanism of three herb pairs for the treatment of atherosclerosis through network pharmacology and molecular modeling","authors":"Minjun Wang","doi":"10.25082/jpbr.2023.01.001","DOIUrl":"https://doi.org/10.25082/jpbr.2023.01.001","url":null,"abstract":"Background: Atherosclerosis (AS) is one of the leading causes of cardiovascular diseases. The traditional China herb pairs such as Huanglian-Gualou, Honghua-Taoren, and Suhexiang-Bingpian showed therapeutic effects on AS by clearing heat and resolving phlegm, invigorating blood and removing blood stasis, as well as aromatic resuscitation, respectively. However, the common and specific mechanisms of these pairs against the same disease are elusive.Objective: This study aimed to explore the molecular mechanisms of 3 herb pairs treating AS by network pharmacology, molecular modeling and mechanism experiments.Methods: The components and their corresponding targets of 3 herb pairs, as well as AS-related targets, were collected from multiple databases and literature. Then the protein-protein interaction network was built to identify the key components and targets associated with AS. The pathway enrichment analysis using KEGG was carried out for analyzing the common mechanisms of 3 herb pairs against AS. Finally, the binding modes of the key components and targets were analyzed by molecular docking and molecular dynamic simulation.Results: The PPI network indicated that the common targets of 3 herb pairs focused on four pathways, including regulated vascular shear stress, TNF, ARE-RAGE, and IL-17 pathways. The molecular docking analysis indicated that the key component quercetin showed highest docking score with PTGS2 in comparison to other targets. Molecular dynamics simulations revealed that quercetin stably anchored to the active pocket of PTGS2 by forming hydrogen bonds with Thr175, Asn351, and Trp356.Conclusion: The molecular mechanism of Huanglian-Gualou, Honghua-Taoren, and Suhexiang-Bingpian against AS was preliminarily expounded, and we wish to provide a theoretical instruction for clinical treatment of AS.","PeriodicalId":16703,"journal":{"name":"Journal of Pharmaceutical and Biopharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79614396","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}
Objective: In this study, we aimed to analyze the effects and underlying mechanisms of LPM570065 on behavioral phenotypes in rats with generalized anxiety disorder (GAD).Methods: The chronic unpredictable mild stress (CUMS) rats were used to observe the results of LPM570065. Total 72 male Sprague Dawley rats were divided into control, vehicle (0.5% CMC-Na), LPM570065 (32 mg/kg) and diazepam (3 mg/kg) groups, 12 rats in each group. Anxiety-like behaviors of rats were observed by elevated zero maze test and novelty-suppressed feeding test. Depressive-like behaviors of rats were detected by forced swimming test. DNA methylation in hippocampi of rats were measured by reduced representation bisulfite sequencing (RRBS). In hippocampi of rats, expressions of DNA methyltransferase (DNMT) 1 and DNMT3a proteins were measured by western blot, and density of dendritic spines was observed by Golgi staining.Results: Compared with the control group, the weights of rats were obviously decreased (p < 0.001) and the rats showed anxiety-like and depressive-like behaviors (p < 0.001) in the vehicle group. Compared with the vehicle group, the weights of rats were significantly increased (p < 0.001) and the anxiety-like and depressive-like behaviors were improved (p < 0.001) in the LPM570065 group. The results of RRBS showed that there were 49964 promoters showed hypermethylation in the LPM570065 treatment rats contrasted to the vehicle treatment rats. In addition, these promoters were enriched in signal transduction and immune function. Furthermore, the expressions of DNMT1 and DNMT3a were significantly decreased, the density of dendritic spines was significantly increased in hippocampi of LPM570065 treatment rats compared with the vehicle treatment rats.Conclusions: LPM570065 ameliorates anxiety-like and depressive-like behaviors in CUMS rats, and its mechanism is possible associated with downregulating DNA methylation in hippocampus.
{"title":"LPM570065 ameliorates anxiety-like and depressive-like behaviors in CUMS rats through regulating DNA methylation in hippocampus","authors":"Shengmin Ji, Chunmei Li, Wei Zhang, Linyao Yu, Yue Yang, Yaoqin Shi, Hongbo Wang, Jingwei Tian","doi":"10.25082/jpbr.2022.02.005","DOIUrl":"https://doi.org/10.25082/jpbr.2022.02.005","url":null,"abstract":"Objective: In this study, we aimed to analyze the effects and underlying mechanisms of LPM570065 on behavioral phenotypes in rats with generalized anxiety disorder (GAD).Methods: The chronic unpredictable mild stress (CUMS) rats were used to observe the results of LPM570065. Total 72 male Sprague Dawley rats were divided into control, vehicle (0.5% CMC-Na), LPM570065 (32 mg/kg) and diazepam (3 mg/kg) groups, 12 rats in each group. Anxiety-like behaviors of rats were observed by elevated zero maze test and novelty-suppressed feeding test. Depressive-like behaviors of rats were detected by forced swimming test. DNA methylation in hippocampi of rats were measured by reduced representation bisulfite sequencing (RRBS). In hippocampi of rats, expressions of DNA methyltransferase (DNMT) 1 and DNMT3a proteins were measured by western blot, and density of dendritic spines was observed by Golgi staining.Results: Compared with the control group, the weights of rats were obviously decreased (p < 0.001) and the rats showed anxiety-like and depressive-like behaviors (p < 0.001) in the vehicle group. Compared with the vehicle group, the weights of rats were significantly increased (p < 0.001) and the anxiety-like and depressive-like behaviors were improved (p < 0.001) in the LPM570065 group. The results of RRBS showed that there were 49964 promoters showed hypermethylation in the LPM570065 treatment rats contrasted to the vehicle treatment rats. In addition, these promoters were enriched in signal transduction and immune function. Furthermore, the expressions of DNMT1 and DNMT3a were significantly decreased, the density of dendritic spines was significantly increased in hippocampi of LPM570065 treatment rats compared with the vehicle treatment rats.Conclusions: LPM570065 ameliorates anxiety-like and depressive-like behaviors in CUMS rats, and its mechanism is possible associated with downregulating DNA methylation in hippocampus.","PeriodicalId":16703,"journal":{"name":"Journal of Pharmaceutical and Biopharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85047729","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 : 2023-03-22DOI: 10.25082/jpbr.2022.02.004
F. Kenari, S. Molnár, Z. Pintér, Sobhan Bitaraf, P. Perjési
Biotransformation of the antiproliferative (E)-2-[(4’-methoxyphenyl)methylene]-benzosuberon-1-one (2c) was studied using rat liver microsomes. As a result of the CYP-catalyzed transformations, one monooxygenated (2c+O) and the demethylated (2c-CH2) metabolites were identified by HPLC-MS. (E)-2-[(4’-methoxyphenyl)methylene]-benzosuberon-1-ol, the expected product of rat liver microsomal carbonyl reductase, was not found in the incubates. Microsomal GST-catalyzed reaction of the compound resulted in formation of diastereomeric GST-conjugates. Under the present HPLC conditions, the diastereomeric adducts were separated into two chromatographic peaks (2c-GSH-1 and 2c-GSH-2).
{"title":"(E)-2-Benzylidenecyclanones: Part XVII. An LC-MS study of microsomal transformation reactions of (E)-2-[(4'-methoxyphenyl)methylene]-benzosuberon-1-one: A cyclic chalcone analog","authors":"F. Kenari, S. Molnár, Z. Pintér, Sobhan Bitaraf, P. Perjési","doi":"10.25082/jpbr.2022.02.004","DOIUrl":"https://doi.org/10.25082/jpbr.2022.02.004","url":null,"abstract":"Biotransformation of the antiproliferative (E)-2-[(4’-methoxyphenyl)methylene]-benzosuberon-1-one (2c) was studied using rat liver microsomes. As a result of the CYP-catalyzed transformations, one monooxygenated (2c+O) and the demethylated (2c-CH2) metabolites were identified by HPLC-MS. (E)-2-[(4’-methoxyphenyl)methylene]-benzosuberon-1-ol, the expected product of rat liver microsomal carbonyl reductase, was not found in the incubates. Microsomal GST-catalyzed reaction of the compound resulted in formation of diastereomeric GST-conjugates. Under the present HPLC conditions, the diastereomeric adducts were separated into two chromatographic peaks (2c-GSH-1 and 2c-GSH-2).","PeriodicalId":16703,"journal":{"name":"Journal of Pharmaceutical and Biopharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88847583","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 : 2023-02-17DOI: 10.25082/jpbr.2022.02.003
Xiaohui Sun, Tian Wang, Lin Zhou, Yawen Yu, Zhaofen Liu, Runchen Ma, Fenghua Fu
Ischemic stroke is the main cause of long-term disability and death worldwide. Studies have pointed out that antidepressants not only can be used to treat depression, but also promote nerve regeneration, nerve plasticity, and recovery of nerve function after stroke. Some evidences indicated that antidepressants have beneficial effects on ischemic stroke. At the same time, there are also risks in treatment process. The mechanisms of the effects of antidepressants on ischemic stroke are complicated and rarely reported. This review summarizes the roles of antidepressants in patients and animal models of stroke, the possible mechanisms of antidepressants against brain injury induced by stroke, and the risks and challenges of antidepressants treatment in patients with ischemia.
{"title":"How antidepressants affect the cerebral ischemic injury and ischemic stroke","authors":"Xiaohui Sun, Tian Wang, Lin Zhou, Yawen Yu, Zhaofen Liu, Runchen Ma, Fenghua Fu","doi":"10.25082/jpbr.2022.02.003","DOIUrl":"https://doi.org/10.25082/jpbr.2022.02.003","url":null,"abstract":"Ischemic stroke is the main cause of long-term disability and death worldwide. Studies have pointed out that antidepressants not only can be used to treat depression, but also promote nerve regeneration, nerve plasticity, and recovery of nerve function after stroke. Some evidences indicated that antidepressants have beneficial effects on ischemic stroke. At the same time, there are also risks in treatment process. The mechanisms of the effects of antidepressants on ischemic stroke are complicated and rarely reported. This review summarizes the roles of antidepressants in patients and animal models of stroke, the possible mechanisms of antidepressants against brain injury induced by stroke, and the risks and challenges of antidepressants treatment in patients with ischemia.","PeriodicalId":16703,"journal":{"name":"Journal of Pharmaceutical and Biopharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88956875","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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