Research in Pharmaceutical Sciences最新文献

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A novel approach to enhance the performance of kallikrein 6 enzyme using Pichia pastoris GS115 as a host. 一种以毕赤酵母GS115为宿主提高激肽释放酶6酶性能的新方法。
IF 2.1
Research in Pharmaceutical Sciences Pub Date : 2023-08-20 eCollection Date: 2023-09-01 DOI: 10.4103/1735-5362.383709
Fatemeh Mahmoodi, Hamid Bakherad, Navid Mogharrab, Mohammad Rabbani
{"title":"A novel approach to enhance the performance of kallikrein 6 enzyme using <i>Pichia pastoris</i> GS115 as a host.","authors":"Fatemeh Mahmoodi,&nbsp;Hamid Bakherad,&nbsp;Navid Mogharrab,&nbsp;Mohammad Rabbani","doi":"10.4103/1735-5362.383709","DOIUrl":"10.4103/1735-5362.383709","url":null,"abstract":"<p><strong>Background and purpose: </strong>Enzyme engineering is the process of raising enzyme efficiency and activity by altering amino acid sequences. Kallikrein 6 (KLK6) enzyme is a secreted serine protease involved in a variety of physiological and pathological activities. The increased expression of KLK6 plays a key role in various diseases. Instability and spontaneous activation and deactivation are major challenges in the study of this enzyme. This study aimed to create a stable pro-KLK6 enzyme by enzyme engineering, designing a specific cleavage site for enterokinase, and using <i>Pichia pastoris</i> GS115 as a host cell. Then, recombinant pro-KLK6 was used to introduce a novel inhibitor for it.</p><p><strong>Experimental approach: </strong>An engineered pro-KLK6 gene was cloned into the pPICZα A expression vector. Then, it was expressed in <i>P. pastoris</i> GS115 and purified by Ni-NTA chromatography. An inactive engineered pro-KLK6 gene was cleaved by enterokinase and converted to an active KLK6. The KLK6 enzyme activity and its kinetic parameters were measured using N-benzoyl-L-arginine ethyl ester (BAEE) substrates.</p><p><strong>Findings/results: </strong>The secretory form of the pro-KLK6 was expressed at about 11 mg/L in <i>P. pastoris</i> (GS115). Before activation with enterokinase, pro-KLK6 was inactive and did not activate spontaneously. The kinetic parameters, including K<sub>m</sub> and V<sub>max</sub>, were estimated at 113.59 μM and 0.432 μM/s, respectively.</p><p><strong>Conclusion and implications: </strong>A stable pro-KLK6 enzyme was produced using <i>P. pastoris</i> (GS115) as the host cell and a specific cleavage site for enterokinase. Additionally, this study assessed the kinetic parameters of the KLK6 enzyme using the BAEE substrate for the first time.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"18 5","pages":"541-550"},"PeriodicalIF":2.1,"publicationDate":"2023-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/01/57/RPS-18-541.PMC10568964.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41238116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Formulation and evaluation of taste-masked oral disintegrating tablet containing tolterodine-loaded montmorillonite. 含托特罗定负载蒙脱石的味觉掩蔽口腔崩解片的研制与评价。
IF 2.1
Research in Pharmaceutical Sciences Pub Date : 2023-08-20 eCollection Date: 2023-09-01 DOI: 10.4103/1735-5362.383708
Somayeh Taymouri, Abolfazl Mostafavi, Homa Talabaki
{"title":"Formulation and evaluation of taste-masked oral disintegrating tablet containing tolterodine-loaded montmorillonite.","authors":"Somayeh Taymouri,&nbsp;Abolfazl Mostafavi,&nbsp;Homa Talabaki","doi":"10.4103/1735-5362.383708","DOIUrl":"10.4103/1735-5362.383708","url":null,"abstract":"<p><strong>Background and purpose: </strong>The present study aimed to obtain a taste-masked oral disintegrating tablet (ODT) containing tolterodine tartrate (TT) intercalated into montmorillonite (MMT).</p><p><strong>Experimental approach: </strong>The TT-MMT hybrid was prepared by ion exchange reaction. The effect of the initial concentration of TT, MMT, temperature, and pH on the encapsulation efficiency (EE) % of the drug in MMT was evaluated. The selected TT-MMT hybrid was characterized by X-ray diffraction (XRD), Fourier transforms infrared (FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Then, the optimized TT-MMT hybrid was incorporated in the ODT prepared by direct compression method and taste-masking assessment performed by a human test panel.</p><p><strong>Findings/results: </strong>The EE% of TT was in the range of 22.67 to 71.06% in different formulations. It was found that increases in MMT concentration significantly increased EE%. DSC and XRD studies indicated that the TT was intercalated in the MMT interlayer space in an amorphous or molecular state. <i>In-vitro</i> release studies at pH 6.8 showed that the amount of the drug released from the TT-MMT hybrid was negligible for the first 3 min. The post-compression of ODT also showed satisfactory results in terms of friability, hardness, disintegration time, and taste.</p><p><strong>Conclusion and implications: </strong>MMT-ODT could be a suitable vehicle for the taste masking of TT, with the potential for use in patients with swallowing problems.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"18 5","pages":"528-540"},"PeriodicalIF":2.1,"publicationDate":"2023-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/48/23/RPS-18-528.PMC10568959.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41238180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Metabolomic identification of biochemical changes induced by fluoxetine in an insulinoma cell line (MIN6). 氟西汀在胰岛素瘤细胞系(MIN6)中诱导的生化变化的代谢组学鉴定。
IF 2.1
Research in Pharmaceutical Sciences Pub Date : 2023-08-20 eCollection Date: 2023-09-01 DOI: 10.4103/1735-5362.383707
Surachai Ngamratanapaiboon, Krittaboon Pornchokchai, Siriphattarinya Wongpitoonmanachai, Petchlada Pholkla, Napatarin Srikornvit, Jiajun Mo, Patipol Hongthawonsiri, Pracha Yambangyang, Pilaslak Akrachalanont
{"title":"Metabolomic identification of biochemical changes induced by fluoxetine in an insulinoma cell line (MIN6).","authors":"Surachai Ngamratanapaiboon,&nbsp;Krittaboon Pornchokchai,&nbsp;Siriphattarinya Wongpitoonmanachai,&nbsp;Petchlada Pholkla,&nbsp;Napatarin Srikornvit,&nbsp;Jiajun Mo,&nbsp;Patipol Hongthawonsiri,&nbsp;Pracha Yambangyang,&nbsp;Pilaslak Akrachalanont","doi":"10.4103/1735-5362.383707","DOIUrl":"https://doi.org/10.4103/1735-5362.383707","url":null,"abstract":"<p><strong>Background and purpose: </strong>The use of fluoxetine raises the risk of pancreatic beta-cell dysfunction. However, the specific mechanism behind its mechanism of action in beta cells is unknown. This study investigated the cellular response of MIN6 cells to fluoxetine using untargeted cell-based metabolomics.</p><p><strong>Experimental approach: </strong>Metabolic profiling of MIN6 cells was performed using liquid chromatography-high resolution mass spectrometry (LC-HRMS) analysis on samples prepared under optimized conditions, followed by principal component analysis, partial least squares-discriminant analysis, and pair-wise orthogonal projections to latent structures discriminant analyses.</p><p><strong>Findings/results: </strong>Sixty-six metabolites that had been differentially expressed between the control and fluoxetine-treated groups demonstrated that the citric acid cycle is mainly perturbed by fluoxetine treatment.</p><p><strong>Conclusion and implications: </strong>The current study provides insights into the molecular mechanisms of fluoxetine effects in MIN6 cells.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"18 5","pages":"517-527"},"PeriodicalIF":2.1,"publicationDate":"2023-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1b/15/RPS-18-517.PMC10568956.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41238183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Probiotic Lactobacillus and the potential risk of spreading antibiotic resistance: a systematic review. 益生菌乳酸杆菌与传播抗生素耐药性的潜在风险:一项系统综述。
IF 2.1
Research in Pharmaceutical Sciences Pub Date : 2023-08-20 eCollection Date: 2023-09-01 DOI: 10.4103/1735-5362.383703
Ali Shahali, Rasool Soltani, Vajihe Akbari
{"title":"Probiotic <i>Lactobacillus</i> and the potential risk of spreading antibiotic resistance: a systematic review.","authors":"Ali Shahali,&nbsp;Rasool Soltani,&nbsp;Vajihe Akbari","doi":"10.4103/1735-5362.383703","DOIUrl":"10.4103/1735-5362.383703","url":null,"abstract":"<p><strong>Background and purpose: </strong><i>Lactobacillus</i>, the most popular probiotic, has recently gained more attention because it is a potential reservoir of antibiotic resistance. This review summarized and discussed the phenotypic-genotypic characteristics of antibiotic resistance.</p><p><strong>Experimental approach: </strong>Google Scholar, PubMed, Web of Science, and Scopus were searched up to February 2022. The inclusion criteria were all studies testing antibiotic resistance of probiotic <i>Lactobacillus</i> strains present in human food supplementation and all human/animal model studies in which transferring antibiotic-resistant genes from <i>Lactobacillus</i> strains to another bacterium were investigated.</p><p><strong>Findings/results: </strong>Phenotypic and genotypic characterization of <i>Lactobacillus</i> probiotics showed that the most antibiotic resistance was against protein synthesis inhibitors (fourteen studies, 87.5%) and cell wall synthesis inhibitors (ten studies, 62.5%). Nine of these studies reported the transfer of antibiotic resistance from <i>Lactobacillus</i> probiotic as donor species to pathogenic bacteria and mostly used <i>in vitro</i> methods for resistance gene transfer.</p><p><strong>Conclusion and implications: </strong>The transferability of resistance genes such as <i>tet</i> and <i>erm</i> in <i>Lactobacillus</i> increases the risk of spreading antibiotic resistance. Further studies need to be conducted to evaluate the potential spread of antibiotic resistance traits <i>via</i> probiotics, especially in elderly people and newborns.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"18 5","pages":"468-477"},"PeriodicalIF":2.1,"publicationDate":"2023-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/68/74/RPS-18-468.PMC10568962.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41238185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Honokiol inhibits the growth of hormone-resistant breast cancer cells: its promising effect in combination with metformin. 厚朴酚抑制抗激素乳腺癌症细胞的生长:与二甲双胍联合使用具有良好效果。
IF 2.1
Research in Pharmaceutical Sciences Pub Date : 2023-08-20 eCollection Date: 2023-09-01 DOI: 10.4103/1735-5362.383712
Ekaterina I Mikhaevich, Danila V Sorokin, Alexander M Scherbakov
{"title":"Honokiol inhibits the growth of hormone-resistant breast cancer cells: its promising effect in combination with metformin.","authors":"Ekaterina I Mikhaevich,&nbsp;Danila V Sorokin,&nbsp;Alexander M Scherbakov","doi":"10.4103/1735-5362.383712","DOIUrl":"https://doi.org/10.4103/1735-5362.383712","url":null,"abstract":"<p><strong>Background and purpose: </strong>Primary and metastatic breast cancers still represent an unmet clinical need for improved chemotherapy and hormone therapy. Considerable attention has been paid to natural anticancer compounds, especially lignans. The study aimed to evaluate the activity of several lignans against breast cancer cells and assess the effect of leading lignans on signaling pathways in combination with metformin.</p><p><strong>Experimental approach: </strong>Human breast cancer cell lines MCF7 (hormone-dependent), MDA-MB-231, and SKBR3 (hormone-independent) were used. A hormone-resistant MCF7/hydroxytamoxifen (HT) subline was obtained by long-term cultivation of the MCF7 line with hydroxytamoxifen. Antiproliferative activity was assessed by the MTT test; the expression of signaling pathway proteins was evaluated by immunoblotting analysis.</p><p><strong>Findings/results: </strong>We evaluated the antiproliferative activity of lignans in breast cancer cells with different levels of hormone dependence and determined the relevant IC<sub>50</sub> values. Honokiol was chosen as the leading compound, and its IC<sub>50</sub> ranged from 12 to 20 μM, whereas for other tested lignans, the IC<sub>50</sub> exceeded 50 μM. The accumulation of cleaved PARP and a decrease in the expression of Bcl-2 and ERα in MCF7/HT were induced following the combination of honokiol with metformin.</p><p><strong>Conclusions and implications: </strong>Honokiol demonstrated significant antiproliferative activity against both hormone-dependent breast cancer cells and lines with primary and acquired hormone resistance. The combination of honokiol with metformin is considered an effective approach to induce death in hormone-resistant cells. Honokiol is of interest as a natural compound with antiproliferative activity against breast cancers, including resistant tumors.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"18 5","pages":"580-591"},"PeriodicalIF":2.1,"publicationDate":"2023-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/56/97/RPS-18-580.PMC10568957.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41238181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bioinformatic analysis of highly consumed phytochemicals as P-gp binders to overcome drug-resistance. 高消耗植物化学物质作为P-gp结合物的生物信息学分析,以克服耐药性。
IF 2.1
Research in Pharmaceutical Sciences Pub Date : 2023-08-20 eCollection Date: 2023-09-01 DOI: 10.4103/1735-5362.383706
Narges Rajaei, Ghazaleh Rahgouy, Nasrin Panahi, Nima Razzaghi-Asl
{"title":"Bioinformatic analysis of highly consumed phytochemicals as P-gp binders to overcome drug-resistance.","authors":"Narges Rajaei,&nbsp;Ghazaleh Rahgouy,&nbsp;Nasrin Panahi,&nbsp;Nima Razzaghi-Asl","doi":"10.4103/1735-5362.383706","DOIUrl":"https://doi.org/10.4103/1735-5362.383706","url":null,"abstract":"<p><strong>Background and purpose: </strong>P-glycoprotein (P-gp) is an adenosine triphosphate (ATP)-dependent membrane efflux pump for protecting cells against xenobiotic compounds. Unfortunately, overexpressed P-gp in neoplastic cells prevents cell entry of numerous chemotherapeutic agents leading to multidrug resistance (MDR). MDR cells may be re-sensitized to chemotherapeutic drugs <i>via</i> P-gp inhibition/modulation. Side effects of synthetic P-gp inhibitors encouraged the development of natural products.</p><p><strong>Experimental approach: </strong>Molecular docking and density functional theory (DFT) calculations were used as fast and accurate computational methods to explore a structure binding relationship of some dietary phytochemicals inside distinctive P-gp binding sites (modulatory/inhibitory). For this purpose, top-scored docked conformations were subjected to per-residue energy decomposition analysis in the B3LYP level of theory with a 6-31g (d, p) basis set by Gaussian98 package.</p><p><strong>Findings/results: </strong>Consecutive application of computational techniques revealed binding modes/affinities of nutritive phytochemicals within dominant binding sites of P-gp. Blind docking scores for best-ranked compounds were superior to verapamil and rhodamine-123. Pairwise amino acid decomposition of superior docked conformations revealed Tyr303 as an important P-gp binding residue. DFT-based induced polarization analysis revealed major electrostatic fluctuations at the atomistic level and confirmed larger effects for amino acids with energy-favored binding interactions. Conformational analysis exhibited that auraptene and 7,4',7'',4'''-tetra-<i>O</i>-methylamentoflavone might not necessarily interact to P-gp binding sites through minimum energy conformations.</p><p><strong>Conclusion and implications: </strong>Although there are still many hurdles to overcome, obtained results may propose a few nutritive phytochemicals as potential P-gp binding agents. Moreover; top-scored derivatives may have the chance to exhibit tumor chemo-sensitizing effects.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"18 5","pages":"505-516"},"PeriodicalIF":2.1,"publicationDate":"2023-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4f/74/RPS-18-505.PMC10568960.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41238179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
PCL/Agarose 3D-printed scaffold for tissue engineering applications: fabrication, characterization, and cellular activities. PCL/琼脂糖3D打印支架用于组织工程应用:制造、表征和细胞活性。
IF 2.1
Research in Pharmaceutical Sciences Pub Date : 2023-08-20 eCollection Date: 2023-09-01 DOI: 10.4103/1735-5362.383711
Sho'leh Ghaedamini, Saeed Karbasi, Batool Hashemibeni, Ali Honarvar, Abbasali Rabiei
{"title":"PCL/Agarose 3D-printed scaffold for tissue engineering applications: fabrication, characterization, and cellular activities.","authors":"Sho'leh Ghaedamini,&nbsp;Saeed Karbasi,&nbsp;Batool Hashemibeni,&nbsp;Ali Honarvar,&nbsp;Abbasali Rabiei","doi":"10.4103/1735-5362.383711","DOIUrl":"https://doi.org/10.4103/1735-5362.383711","url":null,"abstract":"<p><strong>Background and purpose: </strong>Biomaterials, scaffold manufacturing, and design strategies with acceptable mechanical properties are the most critical challenges facing tissue engineering.</p><p><strong>Experimental approach: </strong>In this study, polycaprolactone (PCL) scaffolds were fabricated through a novel three-dimensional (3D) printing method. The PCL scaffolds were then coated with 2% agarose (Ag) hydrogel. The 3D-printed PCL and PCL/Ag scaffolds were characterized for their mechanical properties, porosity, hydrophilicity, and water absorption. The construction and morphology of the printed scaffolds were evaluated <i>via</i> Fourier-Transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The attachment and proliferation of L929 cells cultured on the scaffolds were investigated through MTT assay on the cell culture study upon the 1<sup>st</sup>, 3<sup>rd</sup>, and 7<sup>th</sup> days.</p><p><strong>Findings/results: </strong>The incorporation of Ag hydrogel with PCL insignificantly decreased the mechanical strength of the scaffold. The presence of Ag enhanced the hydrophilicity and water absorption of the scaffolds, which could positively influence their cell behavior compared to the PCL scaffolds. Regarding cell morphology, the cells on the PCL scaffolds had a more rounded shape and less cell spreading, representing poor cell attachment and cell-scaffold interaction due to the hydrophobic nature of PCL. Conversely, the cells on the PCL/Ag scaffolds were elongated with a spindle-shaped morphology indicating a positive cell-scaffold interaction.</p><p><strong>Conclusion and implications: </strong>PCL/Ag scaffolds can be considered appropriate for tissue-engineering applications.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"18 5","pages":"566-579"},"PeriodicalIF":2.1,"publicationDate":"2023-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9e/3f/RPS-18-566.PMC10568963.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41238184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Anti-proliferative, anti-migration, and anti-invasion activity of novel hesperidin glycosides in non-small cell lung cancer A549 cells. 新型橙皮苷苷苷对非小细胞肺癌癌症A549细胞的抗增殖、抗迁移和抗侵袭活性。
IF 2.1
Research in Pharmaceutical Sciences Pub Date : 2023-08-20 eCollection Date: 2023-09-01 DOI: 10.4103/1735-5362.383704
Natwadee Poomipark, Titaporn Chaisin, Jarunee Kaulpiboon
{"title":"Anti-proliferative, anti-migration, and anti-invasion activity of novel hesperidin glycosides in non-small cell lung cancer A549 cells.","authors":"Natwadee Poomipark,&nbsp;Titaporn Chaisin,&nbsp;Jarunee Kaulpiboon","doi":"10.4103/1735-5362.383704","DOIUrl":"https://doi.org/10.4103/1735-5362.383704","url":null,"abstract":"<p><strong>Background and purpose: </strong>Several attempts have been made to synthesize and investigate modified flavonoids to improve their potential anticancer efficacy. This study aimed to determine the <i>in vitro</i> anti-viability, anti-migration, and anti-invasive effects of two novel hesperidin glycosides, hesperidin glucoside (HG1) and hesperidin maltoside (HG2), compared to original hesperidin and diosmin.</p><p><strong>Experimental approach: </strong>Inhibitory effects on normal (MRC5) and cancer (A549) cell viability of hesperidin glycosides were investigated by the trypan blue and MTS assays. A scratch assay determined the suppressive effects on cancer cell migration, and inhibition of cancer cell invasion was investigated through Matrigel™. The selectivity index (SI), a marker of cell toxicity, was also determined for A549 relative to MRC5 cells.</p><p><strong>Findings/results: </strong>The cell viability trypan blue and MTS assays showed similar results of the inhibition of A549 cancer cells; HG1 and HG2 had lower IC<sub>50</sub> than original hesperidin and diosmin. The SI of HG1 and HG2 was > 2 after 72-h culture. Investigation of cell migration showed that HG1 and HG2 inhibited the ability of gap closure in a time- and dose-dependent manner. The infiltration of the Matrigel™-coated filter by A549 cells was suppressed in the presence of HG1 and HG2. This result implied that HG1 and HG2 could inhibit cancer cell invasion.</p><p><strong>Conclusion and implication: </strong>Our results suggest the inhibition of cancer cell migration and invasion in a time- and concentration-related manner with a favorable toxic profile. Moreover, HG<sub>1</sub> and HG<sub>2</sub> appeared potentially better agents than the original hesperidin for future anticancer development.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"18 5","pages":"478-488"},"PeriodicalIF":2.1,"publicationDate":"2023-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4c/1f/RPS-18-478.PMC10568961.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41238178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lupeol attenuated the NAFLD and PCOS-induced metabolic, oxidative, hormonal, histopathological, and molecular injuries in mice. 狼疮减轻了NAFLD和PCOS诱导的小鼠代谢、氧化、激素、组织病理学和分子损伤。
IF 2.1
Research in Pharmaceutical Sciences Pub Date : 2023-08-20 eCollection Date: 2023-09-01 DOI: 10.4103/1735-5362.383710
Hassan Malekinejad, Shima Zeynali-Moghaddam, Ali Rezaei-Golmisheh, Aylar Alenabi, Faezeh Malekinejad, Arash Alizadeh, Vahid Shafie-Irannejad
{"title":"Lupeol attenuated the NAFLD and PCOS-induced metabolic, oxidative, hormonal, histopathological, and molecular injuries in mice.","authors":"Hassan Malekinejad,&nbsp;Shima Zeynali-Moghaddam,&nbsp;Ali Rezaei-Golmisheh,&nbsp;Aylar Alenabi,&nbsp;Faezeh Malekinejad,&nbsp;Arash Alizadeh,&nbsp;Vahid Shafie-Irannejad","doi":"10.4103/1735-5362.383710","DOIUrl":"10.4103/1735-5362.383710","url":null,"abstract":"<p><strong>Background and purpose: </strong>The current study aimed to study the therapeutic effects of lupeol as a nutritional triterpene on non-alcoholic fatty liver disease (NAFLD) and polycystic ovarian syndrome (PCOS) disorders in separate and concurrent models.</p><p><strong>Experimental approach: </strong>This study was performed in three sets and each set contained 4 groups of female mice (n = 6), including control, NAFLD or PCOS and/or NAFLD/PCOS, lupeol, and metformin (MET). The treatment groups following the induction of disorders were treated with lupeol (40 mg/kg, orally) or MET (500 mg/kg, orally) for 28 days. The insulin resistance index and hormonal assessments were conducted on the collected serum samples. Moreover, oxidative stress biomarkers were measured in the liver and ovaries. Histopathological studies and ultimately any changes in the expression of androgen receptors, toll-like receptor (TLR)-2 and TLR-4 were analyzed.</p><p><strong>Findings/results: </strong>Results revealed that lupeol reduced significantly the insulin resistance index in NAFLD and NAFLD/PCOS-positive animals. Lupeol attenuated remarkably the PCOS and PCOS/NAFLD-elevated concentration of testosterone. lupeol recovered the metabolic disorders-induced oxidative stress and restored the disorders-depleted glutathione. The NAFLD/PCOS-induced hepatic damages such as microvesicular or macrovesicular steatosis and atretic follicles number in the ovary were attenuated in the lupeol-treated mice. Serum level of TNF-α was reduced and the expression of androgen receptors, TLR-4 and TLR-2 were downregulated in the lupeol-treated NAFLD/PCOS-positive animals.</p><p><strong>Conclusions and implication: </strong>The results suggest that lupeol could be a novel nutraceutical for the treatment of metabolic disorders. Lupeol's anti-metabolic disorders effects attribute to its anti-dyslipidemia, antioxidant, and anti-inflammatory properties.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"18 5","pages":"551-565"},"PeriodicalIF":2.1,"publicationDate":"2023-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/06/5a/RPS-18-551.PMC10568958.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41238182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The role of Mas receptor on renal hemodynamic responses to angiotensin II administration in chronic renal sympathectomized male and female rats. Mas受体在慢性肾交感神经切除雄性和雌性大鼠对血管紧张素II给药的肾血液动力学反应中的作用。
IF 2.1
Research in Pharmaceutical Sciences Pub Date : 2023-08-20 eCollection Date: 2023-09-01 DOI: 10.4103/1735-5362.383705
Hajaralsadat Hosseini-Dastgerdi, Ali-Asghar Pourshanazari, Mehdi Nematbakhsh
{"title":"The role of Mas receptor on renal hemodynamic responses to angiotensin II administration in chronic renal sympathectomized male and female rats.","authors":"Hajaralsadat Hosseini-Dastgerdi,&nbsp;Ali-Asghar Pourshanazari,&nbsp;Mehdi Nematbakhsh","doi":"10.4103/1735-5362.383705","DOIUrl":"10.4103/1735-5362.383705","url":null,"abstract":"Background and purpose: Renal hemodynamics is influenced by renal sympathetic nerves and the renin-angiotensin system. On the other hand, renal sympathetic denervation impacts kidney weight by affecting renal hemodynamics. The current study evaluated the role of the Mas receptor on renal hemodynamic responses under basal conditions and in response to angiotensin II (Ang II) in chronic renal sympathectomy in female and male rats. Experimental approach: Forty-eight nephrectomized female and male rats were anesthetized and cannulated. Afterward, the effect of chronic renal sympathectomy was investigated on hemodynamic parameters such as renal vascular resistance (RVR), mean arterial pressure (MAP), and renal blood flow (RBF). In addition, the effect of chronic sympathectomy on kidney weight was examined. Findings/Results: Chronic renal sympathectomy increased RVR and subsequently decreased RBF in both sexes. Renal perfusion pressure also increased after sympathectomy in male and female rats, while MAP did not change, significantly. In response to the Ang II injection, renal sympathectomy caused a greater decrease in RBF in all experimental groups, while it did not affect the MAP response. In addition, chronic sympathectomy increased left kidney weight in right nephrectomized rats. Conclusion and implications: Chronic renal sympathectomy changed systemic/renal hemodynamics in baseline conditions and only renal hemodynamics in response to Ang II administration. Moreover, chronic sympathectomy increased compensatory hypertrophy in nephrectomized rats. These changes are unaffected by gender difference and Mas receptor blocker.","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"18 5","pages":"489-504"},"PeriodicalIF":2.1,"publicationDate":"2023-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7d/8e/RPS-18-489.PMC10568965.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41238186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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