M. Ghaffari, D. Shanehbandi, Solmaz Sarhadi, Mina Hanifeh Ahagh, Mahsa Maleki Moghaddam, G. Dehghan, R. Ghodsi, Jafar Ezzati Nazhad Dolatabadi
Background: Quinoline and its derivatives display various biological activities based on versatility in designing a new drug class for medicinal applications. Hence, synthesizing innovative and varied derivatives of quinoline has gained considerable attention among chemists and biologists. This study evaluated the anti-proliferative and apoptotic effect of tetrahydrobenzo[h]quinoline on Michigan Cancer Foundation-7 (MCF-7) human breast cancer cells. Methods: The anti-proliferative effect of tetrahydrobenzo[h]quinoline was studied via MTT [3 0-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] assays. A quantitative and qualitative study of apoptosis was carried out via flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Quantitative real-time PCR (qPCR) and immunoblotting analysis were employed to identify the expression level of genes and proteins involved in the apoptosis signaling pathway. Results: The synthesized compound reduced 50% of cell growth at concentrations of 10 and 7.5 µM during 24 and 48h, respectively, and induced apoptosis up to 30% in MCF-7 cancer cells. Regarding the gene expression level, Bcl-2 displayed considerable alleviation, whereas Bax expression increased significantly. Despite the remarkable increase in caspase 9 expression, there was no noticeable difference in the caspase 8 expression in treated cells compared to the control group. Western blotting data showed that the protein expression level of Bcl-2, pro-caspase 8, and 9 reduced. The protein content of Bax, cleaved-caspase 8, and 9 increased significantly, of which the protein level of cleaved-caspase 9 exhibited a tremendous rise in the treated group. Conclusion: The newly synthesized tetrahydrobenzo[h]quinoline can be a promising organic compound for cancer treatment if its anti-cancer effect investigates by other types of breast cancer cells. In vivo studies should be used to investigate the anti-cancer efficiency of this compound.
{"title":"Anti-proliferative and apoptotic effect of tetrahydrobenzo[h]quinoline on MCF-7 human breast cancer cell","authors":"M. Ghaffari, D. Shanehbandi, Solmaz Sarhadi, Mina Hanifeh Ahagh, Mahsa Maleki Moghaddam, G. Dehghan, R. Ghodsi, Jafar Ezzati Nazhad Dolatabadi","doi":"10.34172/ps.2021.58","DOIUrl":"https://doi.org/10.34172/ps.2021.58","url":null,"abstract":"Background: Quinoline and its derivatives display various biological activities based on versatility in designing a new drug class for medicinal applications. Hence, synthesizing innovative and varied derivatives of quinoline has gained considerable attention among chemists and biologists. This study evaluated the anti-proliferative and apoptotic effect of tetrahydrobenzo[h]quinoline on Michigan Cancer Foundation-7 (MCF-7) human breast cancer cells. Methods: The anti-proliferative effect of tetrahydrobenzo[h]quinoline was studied via MTT [3 0-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] assays. A quantitative and qualitative study of apoptosis was carried out via flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Quantitative real-time PCR (qPCR) and immunoblotting analysis were employed to identify the expression level of genes and proteins involved in the apoptosis signaling pathway. Results: The synthesized compound reduced 50% of cell growth at concentrations of 10 and 7.5 µM during 24 and 48h, respectively, and induced apoptosis up to 30% in MCF-7 cancer cells. Regarding the gene expression level, Bcl-2 displayed considerable alleviation, whereas Bax expression increased significantly. Despite the remarkable increase in caspase 9 expression, there was no noticeable difference in the caspase 8 expression in treated cells compared to the control group. Western blotting data showed that the protein expression level of Bcl-2, pro-caspase 8, and 9 reduced. The protein content of Bax, cleaved-caspase 8, and 9 increased significantly, of which the protein level of cleaved-caspase 9 exhibited a tremendous rise in the treated group. Conclusion: The newly synthesized tetrahydrobenzo[h]quinoline can be a promising organic compound for cancer treatment if its anti-cancer effect investigates by other types of breast cancer cells. In vivo studies should be used to investigate the anti-cancer efficiency of this compound.","PeriodicalId":31004,"journal":{"name":"Infarma Pharmaceutical Sciences","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81118955","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: Sofosbuvir is a potent direct-acting antivirus agent that has been listed as a promising medicine for the treatment of all genotypes of hepatitis C virus. As antiviral drugs could be metabolized to their associated compounds and toxicologically and pharmacologically interfere with the parent drugs, identifying the therapeutic range of drugs would be notable. Methods: In the current study, copper nanoclusters (Cu NCs) are synthesized during the reduction of copper nitrate with hydrazine hydrate in a protected media and used as a nanoprobe for the determination of sofosbuvir in plasma samples. Herein, synchronous fluorescence spectroscopy (SFS) is used for monitoring of fluorescence variation of nanoprobe owing to the excessive benefits compared with the traditional fluorescence. Results: SFS peak of Cu NCs has appeared at 355 nm with ∆λ=80 nm which is decreased in the presence of sofosbuvir. To optimize the reaction factors, a response surface methodology is used and in the optimized conditions, a linear concentration-response plot is obtained in a range of 0.05-6.0 µg mL−1 with a limit of detection of 0.0147 µg mL−1. Conclusion: The developed method also reveals good repeatability and selectivity for sofosbuvir in plasma samples.
背景:索非布韦是一种有效的直接作用抗病毒药物,已被列为治疗所有基因型丙型肝炎病毒的有前景的药物。由于抗病毒药物可能被代谢成其相关化合物,并在毒理学和药理学上干扰母体药物,因此确定药物的治疗范围将是值得注意的。方法:在保护介质中,用水合肼还原硝酸铜合成纳米铜簇(Cu NCs),并将其作为纳米探针用于血浆样品中索非布韦的检测。本文采用同步荧光光谱法(SFS)对纳米探针的荧光变化进行监测,与传统的荧光法相比具有极大的优势。结果:Cu NCs的SFS峰出现在355 nm处,∆λ=80 nm,在索非布韦存在下SFS峰减弱。为了优化反应因素,采用响应面法,在优化条件下,在0.05 ~ 6.0 μ g mL - 1范围内得到线性浓度响应图,检出限为0.0147 μ g mL - 1。结论:所建立的方法对索非布韦在血浆样品中具有良好的重复性和选择性。
{"title":"Development of a Nanocluster-Based Platform for Determination of Sofosbuvir","authors":"Z. Karimzadeh, A. Jouyban, E. Rahimpour","doi":"10.34172/ps.2021.57","DOIUrl":"https://doi.org/10.34172/ps.2021.57","url":null,"abstract":"Background: Sofosbuvir is a potent direct-acting antivirus agent that has been listed as a promising medicine for the treatment of all genotypes of hepatitis C virus. As antiviral drugs could be metabolized to their associated compounds and toxicologically and pharmacologically interfere with the parent drugs, identifying the therapeutic range of drugs would be notable. Methods: In the current study, copper nanoclusters (Cu NCs) are synthesized during the reduction of copper nitrate with hydrazine hydrate in a protected media and used as a nanoprobe for the determination of sofosbuvir in plasma samples. Herein, synchronous fluorescence spectroscopy (SFS) is used for monitoring of fluorescence variation of nanoprobe owing to the excessive benefits compared with the traditional fluorescence. Results: SFS peak of Cu NCs has appeared at 355 nm with ∆λ=80 nm which is decreased in the presence of sofosbuvir. To optimize the reaction factors, a response surface methodology is used and in the optimized conditions, a linear concentration-response plot is obtained in a range of 0.05-6.0 µg mL−1 with a limit of detection of 0.0147 µg mL−1. Conclusion: The developed method also reveals good repeatability and selectivity for sofosbuvir in plasma samples.","PeriodicalId":31004,"journal":{"name":"Infarma Pharmaceutical Sciences","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86629525","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}
Sahar Safaei, B. Baradaran, B. Mansoori, Masoumeh Fardi, E. Baghbani, Mohammad Amini, Nima Hemmat, E. Safarzadeh, Mahdi Abdoli Shadbad, D. Shanehbandi, Saeed Solali
Background: EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit), as one of the polycyclic group proteins (PcGs), is an epigenetic regulator that plays a crucial role in the pathophysiology of hematologic malignancies through regulating cell differentiation. Also, it is well known that aberrant expression of specific transcription factors can be involved in the pathogenesis of various cancers. Objective: Herein, we aimed to suppress EZH2 expression in MOLT-4 cells, T-ALL (T cell acute lymphoblastic leukemia) cell line, and evaluate the role of EZH2 on the expression of transcription factors that regulate T cell maturation, differentiation, and apoptosis. Methods: EZH2-siRNA was transfected into MOLT-4 cells, and the expression levels of EZH2, NOTCH1, TCF1, IKZF1, and NFATC1 were measured using real-time PCR. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was performed to study the effect of EZH2 knockdown on MOLT-4 cell viability. The apoptosis rate of EZH2-siRNA transfected cells was assessed by flow cytometry. The interaction of mentioned genes was investigated using STRING and GO (gene ontology). Results: Our results have shown that EZH2-siRNA transfection can substantially decrease EZH2 expression in MOLT-4 cells. Besides, EZH2 suppression can upregulate NOTCH1, TCF1, IKZF1, and NFATC1 expression levels. EZH2 knockdown does not affect the viability and apoptosis of MOLT-4 cells. The most remarkable protein-protein interaction of EZH2 has been with NOTCH1. Besides, GO analysis has demonstrated that EZH2, NOTCH1, TCF1, IKZF1, and NFATC1 were located within nucleoplasm and can regulate RNA polymerase II-mediated transcription. Conclusion: Our results have shown that MOLT-4 cells harbor increased expression of EZH2 in comparison with normal human T cells. EZH2 knockdown can upregulate the expression of the transcription factors involved in T cell differentiation. Thus, EZH2 can halt the differentiation of immature lymphoblastic T cells.
背景:EZH2 (enhancer of zeste 2 polycomb suppressicomplex 2亚单位)作为多环蛋白(polycyclic group protein, PcGs)的一种,是一种表观遗传调节剂,通过调节细胞分化在血液系统恶性肿瘤的病理生理中发挥重要作用。此外,众所周知,特定转录因子的异常表达可能参与各种癌症的发病机制。目的:在MOLT-4细胞、T细胞急性淋巴母细胞白血病(T - all)细胞系中抑制EZH2的表达,探讨EZH2对T细胞成熟、分化和凋亡调控转录因子表达的影响。方法:将EZH2- sirna转染MOLT-4细胞,采用实时荧光定量PCR检测EZH2、NOTCH1、TCF1、IKZF1、NFATC1的表达水平。采用MTT(3-[4,5-二甲基噻唑-2-基]-2,5二苯基溴化四氮唑)法研究EZH2敲除对MOLT-4细胞活力的影响。流式细胞术检测转染EZH2-siRNA的细胞凋亡率。利用STRING和GO(基因本体)对上述基因的相互作用进行了研究。结果:我们的研究结果表明,转染EZH2- sirna可以显著降低MOLT-4细胞中EZH2的表达。此外,EZH2抑制可上调NOTCH1、TCF1、IKZF1、NFATC1表达水平。EZH2敲低不影响MOLT-4细胞的活力和凋亡。EZH2蛋白与NOTCH1蛋白间最显著的相互作用。此外,GO分析表明EZH2、NOTCH1、TCF1、IKZF1和NFATC1位于核质内,可以调节RNA聚合酶ii介导的转录。结论:我们的研究结果表明,与正常人T细胞相比,MOLT-4细胞中EZH2的表达增加。EZH2敲低可上调T细胞分化相关转录因子的表达。因此,EZH2可以阻止未成熟淋巴母细胞T细胞的分化。
{"title":"EZH2 knockdown upregulates expression of the genes involved in T-ALL cell differentiation","authors":"Sahar Safaei, B. Baradaran, B. Mansoori, Masoumeh Fardi, E. Baghbani, Mohammad Amini, Nima Hemmat, E. Safarzadeh, Mahdi Abdoli Shadbad, D. Shanehbandi, Saeed Solali","doi":"10.34172/ps.2021.56","DOIUrl":"https://doi.org/10.34172/ps.2021.56","url":null,"abstract":"Background: EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit), as one of the polycyclic group proteins (PcGs), is an epigenetic regulator that plays a crucial role in the pathophysiology of hematologic malignancies through regulating cell differentiation. Also, it is well known that aberrant expression of specific transcription factors can be involved in the pathogenesis of various cancers. Objective: Herein, we aimed to suppress EZH2 expression in MOLT-4 cells, T-ALL (T cell acute lymphoblastic leukemia) cell line, and evaluate the role of EZH2 on the expression of transcription factors that regulate T cell maturation, differentiation, and apoptosis. Methods: EZH2-siRNA was transfected into MOLT-4 cells, and the expression levels of EZH2, NOTCH1, TCF1, IKZF1, and NFATC1 were measured using real-time PCR. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was performed to study the effect of EZH2 knockdown on MOLT-4 cell viability. The apoptosis rate of EZH2-siRNA transfected cells was assessed by flow cytometry. The interaction of mentioned genes was investigated using STRING and GO (gene ontology). Results: Our results have shown that EZH2-siRNA transfection can substantially decrease EZH2 expression in MOLT-4 cells. Besides, EZH2 suppression can upregulate NOTCH1, TCF1, IKZF1, and NFATC1 expression levels. EZH2 knockdown does not affect the viability and apoptosis of MOLT-4 cells. The most remarkable protein-protein interaction of EZH2 has been with NOTCH1. Besides, GO analysis has demonstrated that EZH2, NOTCH1, TCF1, IKZF1, and NFATC1 were located within nucleoplasm and can regulate RNA polymerase II-mediated transcription. Conclusion: Our results have shown that MOLT-4 cells harbor increased expression of EZH2 in comparison with normal human T cells. EZH2 knockdown can upregulate the expression of the transcription factors involved in T cell differentiation. Thus, EZH2 can halt the differentiation of immature lymphoblastic T cells.","PeriodicalId":31004,"journal":{"name":"Infarma Pharmaceutical Sciences","volume":"601 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77306377","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}
Introduction: In the pharmaceutical industry, liposomes and polymeric nanoparticles are the two most commonly studied delivery vehicles. A new technique uses lipid-polymeric hybrid nanoparticles (LPHNPs) with a polymeric core, and a shell made up of lipid-lipid-PEG lipids. They have properties which complement polymer nanoparticles and liposomes, and they have the potential to improve the physical stability and biocompatibility of the active pharmaceutical ingredient encapsulated in them. Evaporating the solvent from a dual-phase solution containing lipid and polymer is one of the most effective methods for producing the lipid polymeric hybrid nanoparticles. The LPHNPs applications has also been significantly expanded to include combinational and active targeted drug delivery, as well as delivery of genetic materials, vaccines, and diagnostic imaging agents, in addition to single drug delivery for anticancer therapy, like Glioblastoma. Main goal: The main agenda of this compilation was to address the effects of LPHNPs on Glioblastoma treatment. This compilation also highlights some of the formulation techniques and issues that arise during the preparation of LPHNPs. This review also discusses recent developments in core-shell lipid-polymer hybrid nanoparticles, which were conferred in considerable detail later in this article. Conclusion: The main issue which arises while using nanoparticles with polymer is entrapment efficiency. Because of their hybrid components, LPHNPs have proven to solve this problem to a large extent. The recent research trends suggest that lipid polymeric hybrid nanoparticles will prove to be highly effective or productive in treating diseases such as Glioblastoma.
{"title":"Lipid Polymeric Hybrid Nanoparticles: Formulation Techniques and Effects on Glioblastoma","authors":"Yudhishtir Singh Baghel, Sankha Bhattacharya","doi":"10.34172/ps.2021.55","DOIUrl":"https://doi.org/10.34172/ps.2021.55","url":null,"abstract":"Introduction: In the pharmaceutical industry, liposomes and polymeric nanoparticles are the two most commonly studied delivery vehicles. A new technique uses lipid-polymeric hybrid nanoparticles (LPHNPs) with a polymeric core, and a shell made up of lipid-lipid-PEG lipids. They have properties which complement polymer nanoparticles and liposomes, and they have the potential to improve the physical stability and biocompatibility of the active pharmaceutical ingredient encapsulated in them. Evaporating the solvent from a dual-phase solution containing lipid and polymer is one of the most effective methods for producing the lipid polymeric hybrid nanoparticles. The LPHNPs applications has also been significantly expanded to include combinational and active targeted drug delivery, as well as delivery of genetic materials, vaccines, and diagnostic imaging agents, in addition to single drug delivery for anticancer therapy, like Glioblastoma. Main goal: The main agenda of this compilation was to address the effects of LPHNPs on Glioblastoma treatment. This compilation also highlights some of the formulation techniques and issues that arise during the preparation of LPHNPs. This review also discusses recent developments in core-shell lipid-polymer hybrid nanoparticles, which were conferred in considerable detail later in this article. Conclusion: The main issue which arises while using nanoparticles with polymer is entrapment efficiency. Because of their hybrid components, LPHNPs have proven to solve this problem to a large extent. The recent research trends suggest that lipid polymeric hybrid nanoparticles will prove to be highly effective or productive in treating diseases such as Glioblastoma.","PeriodicalId":31004,"journal":{"name":"Infarma Pharmaceutical Sciences","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89469761","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}
F. Fathi, S. Nejad Ebrahimi, D. Pereira, B. Estevinho, F. Rocha
Background: Phenolic compounds are one of the main groups of secondary metabolites responsible for multiple biological and pharmacological properties that play a vital role in improving human health quality. Encapsulation by spray dryer creates protection toward the phenolic compounds as an efficient way for increasing product performance. Method: The phenolic compounds of Satureja khuzistanica Jamzad (SKH) and S. rechingeri Jamzad (SRH) were enriched based on adsorbent resin column chromatography and the enrichment index was confirmed by HPLC-UV analysis. Gum Arabic, carboxylated chitosan, and pectin with the optimum percentage of 1% w/w used to encapsulate SKH and SRH by the spray drying technique. Result: Encapsulation yield was 38.18 – 59.00 %, particle size ranged 2.278 - 4.689 µm, and release time was between 4.08 - 82.08 min. The gum Arabic-based capsules showed the fastest and pectin-based revealed the slowest release time. The best statistical model explained a release mechanism was Korsmeyer model. Anomalous transport was observed from all formulas except SKH-gum Arabic (case-I transport), SKH-pectin, and SRH-carboxylated-chitosan (super case-II transport). The cytotoxic activity of encapsulate SKH’s revealed reducing the viability of AGS evaluated by the MTT compared with SRH’s. Conclusion: Encapsulation by spray drying has proven to be a promising technique to improve the bioavailability, release time, and mechanism of functional polyphenolic compounds as medicines, food supplements, and food additives.
{"title":"Microencapsulation of enriched extracts of two Satureja species by spray drying, evaluation of the controlled release mechanism and cytotoxicity","authors":"F. Fathi, S. Nejad Ebrahimi, D. Pereira, B. Estevinho, F. Rocha","doi":"10.34172/ps.2021.54","DOIUrl":"https://doi.org/10.34172/ps.2021.54","url":null,"abstract":"Background: Phenolic compounds are one of the main groups of secondary metabolites responsible for multiple biological and pharmacological properties that play a vital role in improving human health quality. Encapsulation by spray dryer creates protection toward the phenolic compounds as an efficient way for increasing product performance. Method: The phenolic compounds of Satureja khuzistanica Jamzad (SKH) and S. rechingeri Jamzad (SRH) were enriched based on adsorbent resin column chromatography and the enrichment index was confirmed by HPLC-UV analysis. Gum Arabic, carboxylated chitosan, and pectin with the optimum percentage of 1% w/w used to encapsulate SKH and SRH by the spray drying technique. Result: Encapsulation yield was 38.18 – 59.00 %, particle size ranged 2.278 - 4.689 µm, and release time was between 4.08 - 82.08 min. The gum Arabic-based capsules showed the fastest and pectin-based revealed the slowest release time. The best statistical model explained a release mechanism was Korsmeyer model. Anomalous transport was observed from all formulas except SKH-gum Arabic (case-I transport), SKH-pectin, and SRH-carboxylated-chitosan (super case-II transport). The cytotoxic activity of encapsulate SKH’s revealed reducing the viability of AGS evaluated by the MTT compared with SRH’s. Conclusion: Encapsulation by spray drying has proven to be a promising technique to improve the bioavailability, release time, and mechanism of functional polyphenolic compounds as medicines, food supplements, and food additives.","PeriodicalId":31004,"journal":{"name":"Infarma Pharmaceutical Sciences","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73713714","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}
M. Hosseini, Sima Askari Sadat-Mahaleh, H. Ghavimi
Background: Methamphetamine (METH) is considered the second most commonly abused drug in the world. There is limited or no evidence concerning the effective treatment of METH withdrawal symptoms, such as depression and anxiety. Mode of action of selegiline (increase of the brain neurotransmitter activity) suggests that it might be useful in METH withdrawal syndrome treatment, being capable of diminishing the preference and depression involved in drug degeneration and addictive activities. Methods: Mice were randomly divided into 10 groups (n= 10): five METH-nondependent groups treated with normal saline intraperitoneal (i.p) for two weeks, to which, from the 15th day, selegiline (10, 20 and 40 mg/kg; i.p) or fluoxetine (5 mg/kg; i.p) was administrated for 10 consecutive days. Other groups injected METH (2 mg/kg, at 12-h intervals) for 14 days. From the 15th day, the 10-day period of METH abstinence started and the above-mentioned doses of selegiline or fluoxetine were injected. Then, the mice were evaluated for depression and biochemical assessments from the 25th day of the study. Results: Our data indicated that post-treatment with selegiline (10-40 mg/kg; i.p) for 10 days reversed METH-induced depressive-like behaviors in the forced swimming test (FST), tail suspension test (TST), and splash test with exerting no effects on the locomotor activity. Furthermore, none of the previously proposed treatments affected the behavioral abnormality in the control animals. Moreover, both selegiline and fluoxetine as standard antidepressant drug, substantially improved the levels of mitochondrial reduced glutathione (GSH), malondialdehyde (MDA), and adenosine triphosphate (ATP). Conclusion: Our findings demonstrated that selegiline produced antidepressant-like effects following METH withdrawal and prevented the mitochondrial dysfunction in the male mice.
{"title":"Selegiline alleviates the depressive-like behaviors of methamphetamine withdrawal syndrome through modulating mitochondrial function and energy hemostasis","authors":"M. Hosseini, Sima Askari Sadat-Mahaleh, H. Ghavimi","doi":"10.34172/ps.2021.53","DOIUrl":"https://doi.org/10.34172/ps.2021.53","url":null,"abstract":"Background: Methamphetamine (METH) is considered the second most commonly abused drug in the world. There is limited or no evidence concerning the effective treatment of METH withdrawal symptoms, such as depression and anxiety. Mode of action of selegiline (increase of the brain neurotransmitter activity) suggests that it might be useful in METH withdrawal syndrome treatment, being capable of diminishing the preference and depression involved in drug degeneration and addictive activities. Methods: Mice were randomly divided into 10 groups (n= 10): five METH-nondependent groups treated with normal saline intraperitoneal (i.p) for two weeks, to which, from the 15th day, selegiline (10, 20 and 40 mg/kg; i.p) or fluoxetine (5 mg/kg; i.p) was administrated for 10 consecutive days. Other groups injected METH (2 mg/kg, at 12-h intervals) for 14 days. From the 15th day, the 10-day period of METH abstinence started and the above-mentioned doses of selegiline or fluoxetine were injected. Then, the mice were evaluated for depression and biochemical assessments from the 25th day of the study. Results: Our data indicated that post-treatment with selegiline (10-40 mg/kg; i.p) for 10 days reversed METH-induced depressive-like behaviors in the forced swimming test (FST), tail suspension test (TST), and splash test with exerting no effects on the locomotor activity. Furthermore, none of the previously proposed treatments affected the behavioral abnormality in the control animals. Moreover, both selegiline and fluoxetine as standard antidepressant drug, substantially improved the levels of mitochondrial reduced glutathione (GSH), malondialdehyde (MDA), and adenosine triphosphate (ATP). Conclusion: Our findings demonstrated that selegiline produced antidepressant-like effects following METH withdrawal and prevented the mitochondrial dysfunction in the male mice.","PeriodicalId":31004,"journal":{"name":"Infarma Pharmaceutical Sciences","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83317418","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}
K. Priya, S. Manandhar, R. Sankhe, M. Setty, UV Babu, S. Pai
Background: Oral contraceptives are very widely used agents to check unwanted pregnancies. They contain synthetic analogues of estrogen and progesterone hormones. Estrogen is an important hormone that plays a significant role in menstrual cycle, ovulation, fertilization and implantation. Estrogen receptor α (ERα) can modulate the ovulation, fertilization or receptivity of the uterus. Oral contraceptives pose mild to severe adverse effects such as menstrual cycle disorders, metabolic alterations and increased risk of cancers. It is essential to identify and screen alternative contraceptives that are safer to use. The present study was aimed at identifying the compounds from Cissampelos pareira that is traditionally used for antifertility activity. Methods: The compounds reported from the plant are collected and prepared using the protein preparation wizard. The protein, ERα was selected from protein data bank (1G5O) and prepared. The ligands were docked with the protein and the hits were selected for further screening of free energy calculation, induced fit docking and molecular dynamics simulations based on the respective scores and various interactions. Results: Among various compounds, Coclaurine and Norruffscine have been identified to interact with ERα and possess similar interactions as that of the endogenous ligand, estradiol. The compounds also showed drug-like properties in Qikprop analysis and promising result in the molecular dynamics simulation studies. Conclusion: Considering the dock scores, molecular interactions with the ERα receptor and energy calculations, the compounds Coclaurine and Norruffscine were found to have good binding properties. Further in vitro and in vivo evaluation are warranted for confirmation.
{"title":"Structure based virtual docking and molecular dynamics guided identification of potential phytoconstituents from traditionally used female antifertility plant","authors":"K. Priya, S. Manandhar, R. Sankhe, M. Setty, UV Babu, S. Pai","doi":"10.34172/ps.2021.52","DOIUrl":"https://doi.org/10.34172/ps.2021.52","url":null,"abstract":"Background: Oral contraceptives are very widely used agents to check unwanted pregnancies. They contain synthetic analogues of estrogen and progesterone hormones. Estrogen is an important hormone that plays a significant role in menstrual cycle, ovulation, fertilization and implantation. Estrogen receptor α (ERα) can modulate the ovulation, fertilization or receptivity of the uterus. Oral contraceptives pose mild to severe adverse effects such as menstrual cycle disorders, metabolic alterations and increased risk of cancers. It is essential to identify and screen alternative contraceptives that are safer to use. The present study was aimed at identifying the compounds from Cissampelos pareira that is traditionally used for antifertility activity. Methods: The compounds reported from the plant are collected and prepared using the protein preparation wizard. The protein, ERα was selected from protein data bank (1G5O) and prepared. The ligands were docked with the protein and the hits were selected for further screening of free energy calculation, induced fit docking and molecular dynamics simulations based on the respective scores and various interactions. Results: Among various compounds, Coclaurine and Norruffscine have been identified to interact with ERα and possess similar interactions as that of the endogenous ligand, estradiol. The compounds also showed drug-like properties in Qikprop analysis and promising result in the molecular dynamics simulation studies. Conclusion: Considering the dock scores, molecular interactions with the ERα receptor and energy calculations, the compounds Coclaurine and Norruffscine were found to have good binding properties. Further in vitro and in vivo evaluation are warranted for confirmation.","PeriodicalId":31004,"journal":{"name":"Infarma Pharmaceutical Sciences","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74938623","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}
Mansour Tayebi-khorami, N. Chegeni, M. Tahmasebi Birgani, A. Danyaei, R. Fardid, Jaber Zafari
Background: Nowadays, ovarian cancer is the most lethal gynecological cancer worldwide. Tumor debulking surgery followed by Cisplatin-based chemotherapy is the first line of ovarian cancer therapy. However, many patients experience a relapse of the disease due to chemotherapy resistance. Accordingly, this study aims to investigate the ability of microwave (MW) radiation to increase the susceptibility of ovarian cancer cells toward Cisplatin (Cis). Methods: Firstly we designed a hand-made electromagnetic field exposure system and CO2 incubator to irradiate cells with a frequency equal to 2450±30 MHz and a power density of 2.47 mW/cm2 at a distance of 30 cm from the antenna. Two ovarian cancer cell lines A2780 (Cisplatin-sensitive) and A2780CP (Cisplatin-resistant) were subjected to either Cis, MW alone or Cisplatin + microwave radiation (Cis+MW). Cell viability, apoptosis, and P53 gene expression was assessed following drug/radiation exposure. Results: After 48 hours of treatment the combination of Cis and MW radiation has significantly inhibited the growth of the A2780 and A2780CP cell lines in comparison with Cis-control groups. The percentages of early apoptosis induced by Cis+MW was significantly increased in comparison with Cis alone. P53 expression was significantly upregulated after treatment with Cis+MW. Conclusion: It can be concluded that MW radiation has been able to decrease the resistance of ovarian cancer cells to Cis and it may improve the chemotherapy protocol for ovarian cancer treatment.
{"title":"Enhancement of Cisplatin Sensitivity by Microwave Radiation in Ovarian Cancer Cells","authors":"Mansour Tayebi-khorami, N. Chegeni, M. Tahmasebi Birgani, A. Danyaei, R. Fardid, Jaber Zafari","doi":"10.34172/ps.2021.51","DOIUrl":"https://doi.org/10.34172/ps.2021.51","url":null,"abstract":"Background: Nowadays, ovarian cancer is the most lethal gynecological cancer worldwide. Tumor debulking surgery followed by Cisplatin-based chemotherapy is the first line of ovarian cancer therapy. However, many patients experience a relapse of the disease due to chemotherapy resistance. Accordingly, this study aims to investigate the ability of microwave (MW) radiation to increase the susceptibility of ovarian cancer cells toward Cisplatin (Cis). Methods: Firstly we designed a hand-made electromagnetic field exposure system and CO2 incubator to irradiate cells with a frequency equal to 2450±30 MHz and a power density of 2.47 mW/cm2 at a distance of 30 cm from the antenna. Two ovarian cancer cell lines A2780 (Cisplatin-sensitive) and A2780CP (Cisplatin-resistant) were subjected to either Cis, MW alone or Cisplatin + microwave radiation (Cis+MW). Cell viability, apoptosis, and P53 gene expression was assessed following drug/radiation exposure. Results: After 48 hours of treatment the combination of Cis and MW radiation has significantly inhibited the growth of the A2780 and A2780CP cell lines in comparison with Cis-control groups. The percentages of early apoptosis induced by Cis+MW was significantly increased in comparison with Cis alone. P53 expression was significantly upregulated after treatment with Cis+MW. Conclusion: It can be concluded that MW radiation has been able to decrease the resistance of ovarian cancer cells to Cis and it may improve the chemotherapy protocol for ovarian cancer treatment.","PeriodicalId":31004,"journal":{"name":"Infarma Pharmaceutical Sciences","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72530881","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}
S. Niknam, Arezoo Rastegari, M. Bozorgi, Yasaman Vahedi-Mazdabadi, Mina Saeedi, T. Akbarzadeh
Background: According to the Iranian Traditional Medicine (ITM) references, Platanus orientalis L. possesses wound healing properties. Herein, we developed different topical formulations based on the ethanolic extract of P. orientalis leaves and evaluated its wound healing effects through an in vivo model. Methods: Hydroalcoholic extract of the leaves was obtained from ethanol 80% and it was evaluated for DPPH radical scavenging activity, total phenolic and flavonoid contents as well as the presence of tannins. Different topical formulations including ointment (D-O) and polymer film (D-F), were prepared and an in vivo test was run for 14 days in an excision wound model consisting of 5 groups of 6 rats. Results: Our results indicated the higher efficacy of D-O comparing with D-F, as wound surface area remarkably reduced within 14 days post-injury. Also, histological features including epitheliogenesis score, neovascularization, and collagen density indicated the potential wound healing effect of D-O. Conclusion: Wound healing properties of the ethanolic extract of P. orientalis leaves depended on the type of formulation and D-O was found to be much more potent than D-F, from reducing wound surface area, maximum epitheliogenesis score, proper neovascularization pattern, and early type I collagenization points of view.
背景:根据伊朗传统医学(ITM)文献,Platanus orientalis L.具有伤口愈合特性。在此,我们开发了不同的局部配方的基础上,乙醇提取物的东洋叶片,并通过体内模型评估其伤口愈合效果。方法:以乙醇含量为80%的水酒精提取物,对其DPPH自由基清除活性、总酚和类黄酮含量以及单宁含量进行评价。制备软膏(D-O)和聚合物膜(D-F)等不同的外用制剂,在5组6只大鼠的切除创面模型上进行14 d的体内实验。结果:与D-F相比,D-O的疗效更高,在伤后14天内伤口表面积显著减少。此外,组织学特征包括上皮发生评分、新生血管形成和胶原蛋白密度表明D-O具有潜在的伤口愈合作用。结论:从减少创面面积、最大上皮生成评分、适当的新生血管形成模式和早期I型胶原形成的角度来看,东夏叶乙醇提取物的创面愈合性能与剂型有关,D-O明显优于D-F。
{"title":"In vivo evaluation of wound healing properties of Platanus orientalis L.","authors":"S. Niknam, Arezoo Rastegari, M. Bozorgi, Yasaman Vahedi-Mazdabadi, Mina Saeedi, T. Akbarzadeh","doi":"10.34172/ps.2021.50","DOIUrl":"https://doi.org/10.34172/ps.2021.50","url":null,"abstract":"Background: According to the Iranian Traditional Medicine (ITM) references, Platanus orientalis L. possesses wound healing properties. Herein, we developed different topical formulations based on the ethanolic extract of P. orientalis leaves and evaluated its wound healing effects through an in vivo model. Methods: Hydroalcoholic extract of the leaves was obtained from ethanol 80% and it was evaluated for DPPH radical scavenging activity, total phenolic and flavonoid contents as well as the presence of tannins. Different topical formulations including ointment (D-O) and polymer film (D-F), were prepared and an in vivo test was run for 14 days in an excision wound model consisting of 5 groups of 6 rats. Results: Our results indicated the higher efficacy of D-O comparing with D-F, as wound surface area remarkably reduced within 14 days post-injury. Also, histological features including epitheliogenesis score, neovascularization, and collagen density indicated the potential wound healing effect of D-O. Conclusion: Wound healing properties of the ethanolic extract of P. orientalis leaves depended on the type of formulation and D-O was found to be much more potent than D-F, from reducing wound surface area, maximum epitheliogenesis score, proper neovascularization pattern, and early type I collagenization points of view.","PeriodicalId":31004,"journal":{"name":"Infarma Pharmaceutical Sciences","volume":"515 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77098163","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}
F. Beheshti, Somaieh Ahmadabady, Baghcheghi Yousef, A. Anaeigoudari, M. Hosseini
Background: Rosa damascena Herrm (R. damascena) is a species of the Rosaceae family. The R. damascena has been shown to improve depression, anxiety and grief, it also suppresses allergic reactions and migraine headache. In addition, amelioration of learning and memory deficits, delay in onset of seizure attacks, alleviation of pain and improvement of sleep disorders have been attributed to extract and essential oil of R. damascena. This review was conducted to integrate the neuropharmacological effects of R. damascena. Methods: Employed scientific databases for collecting information were including PubMed, Web of Science, Scopus and Google Scholar. Results: The results of animal and clinical trial studies indicate that the extract of R. damascena and its essential oil apply useful therapeutic effects on depressant and anxiety- like behaviors, epileptic seizures, learning and memory impairments, sleep disturbances and pain. Conclusion: Based on scientific findings, the neuroprotective effects of R. damascena can be mainly linked to its antioxidant and anti-inflammatory properties.
背景:大马士革玫瑰(Rosa damascena Herrm)是蔷薇科的一种。大马藤已被证明能改善抑郁、焦虑和悲伤,还能抑制过敏反应和偏头痛。此外,改善学习和记忆缺陷,延缓癫痫发作,减轻疼痛和改善睡眠障碍已归因于大马藤提取物和精油。本文就大黄的神经药理作用进行综述。方法:采用PubMed、Web of Science、Scopus、Google Scholar等科学数据库进行信息收集。结果:动物和临床研究结果表明,大马花提取物及其精油对抑郁和焦虑样行为、癫痫发作、学习记忆障碍、睡眠障碍和疼痛有有益的治疗作用。结论:根据科学研究结果,大马藤的神经保护作用可能主要与其抗氧化和抗炎作用有关。
{"title":"A mini review of neuropharmacological effects of Rosa damascena Herrm.","authors":"F. Beheshti, Somaieh Ahmadabady, Baghcheghi Yousef, A. Anaeigoudari, M. Hosseini","doi":"10.34172/ps.2021.49","DOIUrl":"https://doi.org/10.34172/ps.2021.49","url":null,"abstract":"Background: Rosa damascena Herrm (R. damascena) is a species of the Rosaceae family. The R. damascena has been shown to improve depression, anxiety and grief, it also suppresses allergic reactions and migraine headache. In addition, amelioration of learning and memory deficits, delay in onset of seizure attacks, alleviation of pain and improvement of sleep disorders have been attributed to extract and essential oil of R. damascena. This review was conducted to integrate the neuropharmacological effects of R. damascena. Methods: Employed scientific databases for collecting information were including PubMed, Web of Science, Scopus and Google Scholar. Results: The results of animal and clinical trial studies indicate that the extract of R. damascena and its essential oil apply useful therapeutic effects on depressant and anxiety- like behaviors, epileptic seizures, learning and memory impairments, sleep disturbances and pain. Conclusion: Based on scientific findings, the neuroprotective effects of R. damascena can be mainly linked to its antioxidant and anti-inflammatory properties.","PeriodicalId":31004,"journal":{"name":"Infarma Pharmaceutical Sciences","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82477868","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}