Research in Pharmaceutical Sciences最新文献

{"title":"mPFC hemorrhage induces hippocampal CA1 dendritic spine plasticity and attentional deficits in mice.","authors":"Zahra Akhoond-Ali, Hamed Ghazavi, Mahmoud Hosseini, Masoud Fereidoni, Leyli Polgardani, Ali Nakhaei, Farzaneh Vafaee","doi":"10.4103/RPS.RPS_197_25","DOIUrl":"10.4103/RPS.RPS_197_25","url":null,"abstract":"<p><strong>Background and purpose: </strong>Damage to a specific brain region, in addition to its local effects, can influence brain function by inducing neuroplasticity in remote areas. This study hypothesized that hemorrhage of the medial prefrontal cortex (mPFC) is associated with deficits in shifting attention through structural alterations in the hippocampal CA1 region, an area with known functional connections to the mPFC.</p><p><strong>Experimental approach: </strong>C57BL/6 mice were subjected to intracerebral hemorrhage (ICH) or sham surgery. Neurological function was assessed using the neurological deficit score (NDS) on different days after injury, and cognitive flexibility was evaluated using the attentional set shifting task (AST) over a 17-day protocol. Structural changes were examined by assessing white matter and dendritic spine density using Luxol fast blue (LFB) and Golgi staining techniques on brain tissue. Statistical analysis was performed with SPSS-26.</p><p><strong>Findings/results: </strong>No significant difference was observed in NDS between the groups. Mice with ICH demonstrated a lower task completion rate, along with an increased number of trials and set-loss errors in the AST. Dendritic spine density in the CA1 region was higher in the ICH group compared to the sham group, particularly in the right hemisphere, but no significant changes were noted in the white matter.</p><p><strong>Conclusion and implications: </strong>The observed results following mPFC injury indicated an association between cortical damage, hippocampal plasticity, and cognitive dysfunction, consequently identifying hippocampal plasticity as a potential target for future therapeutic strategies aimed at improving post-stroke cognitive recovery.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 4","pages":"492-504"},"PeriodicalIF":2.3,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13441063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679886","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}

{"title":"IGFBP-3 enhances irinotecan efficacy in colorectal cancer <i>via</i> ROS-mediated apoptosis and β-catenin suppression.","authors":"Elahe Gharehkhani, Mohammad Karami, Abouzar Bagheri, Mahboube Rahmati Kukandeh, Mohammad Shokrzadeh","doi":"10.4103/RPS.RPS_153_25","DOIUrl":"10.4103/RPS.RPS_153_25","url":null,"abstract":"<p><strong>Background and purpose: </strong>Colorectal cancer, a leading cause of mortality, is treated with surgery early and irinotecan (IRI) chemotherapy in advanced stages. Insulin-like growth factor-binding protein 3 (IGFBP-3), regulated by p53, mediates tumor suppression and apoptosis. This study evaluates the combined therapeutic effects of IGFBP-3 and IRI in colorectal cancer.</p><p><strong>Experimental approach: </strong>SW480 colorectal cancer cells were treated with IGFBP-3, IRI, and their combination; IC₅₀ values were determined by MTT assay, and combination effects were analyzed by CompuSyn. Oxidative stress markers, apoptosis, and cell cycle progression were assessed utilizing flow cytometry. Furthermore, caspase 3/7 activity was measured, and expression levels of <i>Bax, Bcl2</i>, and <i>β-catenin</i> were determined using RT-PCR.</p><p><strong>Findings/results: </strong>The MTT assay revealed IC₅₀ of 8.4 μM for IRI and 43.03 nM for IGFBP-3, with CompuSyn confirming synergistic interaction (CI < 1). Compared to single agents, the combination treatment significantly enhanced apoptosis, induced greater G₂/M cell cycle arrest, and markedly increased levels of ROS, MDA, and protein carbonyls while significantly depleting GSH. At the molecular level, the combination synergistically upregulated pro-apoptotic <i>Bax</i> and downregulated anti-apoptotic <i>Bcl2</i> and oncogenic <i>β-catenin</i>.</p><p><strong>Conclusion and implications: </strong>Our results indicated that IRI and IGFBP-3 show cytotoxicity, with IGFBP-3 enhancing IRI effect by inhibiting Wnt/β-catenin and increasing drug uptake, warranting assessment in normal cells.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 4","pages":"521-535"},"PeriodicalIF":2.3,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13441036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679888","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}

{"title":"Computational investigation for exploring botanical ingredients as potential negative allosteric modulators targeting metabotropic glutamate receptor 5.","authors":"Pracheta Singh, Jeevan Patra, Abdulaziz S Saeedan, Sara A Aldossary, Mohd Nazam Ansari","doi":"10.4103/RPS.RPS_61_25","DOIUrl":"10.4103/RPS.RPS_61_25","url":null,"abstract":"<p><strong>Background and purpose: </strong>Metabotropic glutamate receptors are class C G-protein-coupled receptors that respond to the neurotransmitter glutamate. In particular, metabotropic glutamate receptor 5 (mGluR5) has been a valuable drug target for the management of psychiatric and neurodegenerative disorders such as fragile X syndrome, autism, depression, anxiety, addiction, and movement disorders through negative allosteric modulators (NAMs). Despite the discovery of several NAMs, limited clinical efficacy was observed, thus preventing them from reaching the clinical stage. Natural products are indispensable, with a plethora of pharmacological actions. This study aimed to identify potential natural compounds as novel natural NAMs modulating mGluR5 using a comprehensive <i>in silico</i> approach.</p><p><strong>Experimental approach: </strong>Utilizing receptor-based pharmacophore modelling, we virtually screened a natural library comprised of ~1.2 million compounds to study their molecular binding behavior against mGluR5. Furthermore, the best hits were evaluated using the end-point method (molecular mechanics Poisson-Boltzmann surface area), molecular dynamics (MD) simulations, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling.</p><p><strong>Findings/results: </strong>Based on the augmented computational modelling, we identified four promising natural hits-3'-HPS, gigantol, isorhapontigenin, and coclaurine that demonstrated higher affinities than the standard clinical candidate 2-methyl-6-phenylethynyl-pyridine (MPEP), and co-crystal 2-[2-(3-methoxyphenyl)ethynyl]-6-methyl-pyridine (M-MPEP). The top selected hits demonstrated optimal binding energies, molecular interactions, and favorable ADMET properties with a few toxicity liabilities, warranting further lead optimization and experimental validations. MD simulations validated their structural stability through RMSD, RMSF, and principal component analysis.</p><p><strong>Conclusion and implications: </strong>Our findings provided compelling evidence for a structure-based drug design approach in developing potent small-molecule natural modulators for the treatment of neurodegenerative disorders.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 4","pages":"437-451"},"PeriodicalIF":2.3,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13441033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679913","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}

{"title":"Phenolic compounds from <i>Diarthron lessertii</i>: isolation, cytotoxicity, and interaction with cancer signaling pathway, FOXO3a.","authors":"Hussein Biganeh, Morteza Sadeghi, Mehran Miroliaei, Mahnaz Khanavi, Mustafa Ghanadian","doi":"10.4103/RPS.RPS_233_25","DOIUrl":"10.4103/RPS.RPS_233_25","url":null,"abstract":"<p><strong>Background and purpose: </strong>Natural products are valuable sources of anticancer agents. This study investigated the phytochemical composition of <i>Diarthron lessertii</i> shoot extract and evaluated the anticancer potential of its isolated phenolic constituents.</p><p><strong>Experimental approach: </strong>Phenolic compounds were isolated using chromatographic techniques and identified by one- and two-dimensional NMR spectroscopy and ESI-MS analysis. Cytotoxicity against HeLa cervical cancer cells was assessed using the MTT assay. A luciferase reporter assay evaluated the effect of the most active compound on FOXO3a was examined through molecular docking.</p><p><strong>Findings/results: </strong>Nine phenolic compounds were isolated and characterized from <i>D. lessertii</i>, including two lignans (epinortrachelogenin and isolariciresinol), one biflavonoid (stelleranol), one bicoumarin (daphnoretin), and five flavonoids (genkwanin, apigenin 7,4'-dimethyl ether, naringenin, apigenin, and dihydrokaempferol). Among the isolated compounds, epinortrachelogenin (compound <b>1</b>) showed the strongest cytotoxic activity against HeLa cells, with an IC₅₀ value of 80.37 ± 4.72 μM. In luciferase assays, compound <b>1</b> selectively activated FOXO3a, reaching 2274 relative luminescence units at 100 pM. Molecular docking further supported these findings, revealing favorable binding of compound <b>1</b> within the FOXO3a binding pocket.</p><p><strong>Conclusion and implications: </strong>Epinortrachelogenin exhibited notable cytotoxicity and selective FOXO3a activation, supported by docking analysis. These findings identify this lignan as a promising lead compound for the development of FOXO3a-targeted anticancer agents.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 4","pages":"481-491"},"PeriodicalIF":2.3,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13441029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679850","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}

{"title":"<i>In silico</i> anti-leishmanial potential of algal and coral compounds using molecular dynamic simulation and docking methods.","authors":"Hajar Shabandoust, Negar Balmeh, Najaf Allahyari Fard, Sedighe Saberi, Afsaneh Yegdaneh, Seyed Mahmoud Mousavi, Zahra Alimardan, Zahra Ghayour Najafabadi, Seyed Hossein Hejazi","doi":"10.4103/RPS.RPS_223_24","DOIUrl":"10.4103/RPS.RPS_223_24","url":null,"abstract":"<p><strong>Background and purpose: </strong>Leishmaniasis is a parasitic disease prevalent in subtropical and tropical regions, with limited and often toxic treatments ineffective against drug-resistant strains. This study explored 1,013 compounds from algae and corals for potential anti-leishmanial effects.</p><p><strong>Experimental approach: </strong>Three-dimensional structures of <i>Leishmania</i> major proteins, zinc leishmanolysin glycoprotein 63 (GP63), farnesyl diphosphate synthase (FPPS), and N-myristoyltransferase (NMT), as well as 389 coral compounds and 624 algal compounds, were obtained from the PubChem database. Molecular docking analysis was performed using PyRx and AutoDock Vina software for each of the three <i>Leishmania</i> proteins with individual protein-ligand combinations. The properties, including activity, daily carcinogenicity, and absorption, distribution, metabolism, excretion, and toxicity (ADMET), were predicted using SwissADME, Lazar, and Way2Drug tools. Using the GROMACS program, coral and algal compounds with the highest binding scores for each protein were selected for molecular dynamics (MD) simulations.</p><p><strong>Findings/results: </strong>Alga-utd-01 and Coral-utd-01 exhibited strong affinity for the GP63. Additionally, Alga-utd-05 and Coral-utd-02 showed the highest binding affinity to FPPS, while the top compounds for NMT were Alga-utd-14 and Coral-utd-03. Moreover, Alga-utd-05, Alga-utd-22, and Alga-utd-16 were common algal compounds interacting with all three proteins, and Coral-utd-01, Coral-utd-02, Coral-utd-03, Coral-utd-06, and Coral-utd-12 were common coral compounds. The MD results confirmed relatively stable interactions between the proposed compounds and the three important <i>Leishmania</i> proteins.</p><p><strong>Conclusion and implications: </strong>The algae- and coral-derived compounds exhibited promising anti-parasitic and anti-inflammatory properties, warranting further experimental validation for leishmaniasis treatment.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 4","pages":"536-565"},"PeriodicalIF":2.3,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13441065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679859","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}

{"title":"Ethyl acetate extract of <i>Elephantopus mollis</i> Kunth. induced apoptosis, senescence, and inhibited metastasis-associated traits of human lung cancer cells.","authors":"Tran Thanh Long, Dang Minh Phuc, Phan Dang Khoi, Dang Thi Phuong Thao, Nguyen Thi My Trinh","doi":"10.4103/RPS.RPS_115_25","DOIUrl":"10.4103/RPS.RPS_115_25","url":null,"abstract":"<p><strong>Background and purpose: </strong><i>Elephantopus mollis</i> Kunth. (EM) is an attractive candidate for cancer treatment research due to its long history of use in traditional cancer remedies. As lung cancer is the most widespread and among the most lethal carcinomas, we assessed the toxicity and anti-metastatic ability of EM extracts on the lung cancer NCI-H1299 cells.</p><p><strong>Experimental approach: </strong>The cytotoxicity of EM extracts was evaluated <i>via</i> the MTT assay. Phytopolyphenol constituents of the potent extract were evaluated by HPLC. The underlying mechanisms of this toxicity were scrutinized by cellular and nuclear morphologies, cleaved caspase-3/8/9 staining, senescence-associated beta-galactosidase activity, and gene expression analysis. The scratch, invasion, adhesion assays, and RT-qPCR were employed for the anti-metastasis study.</p><p><strong>Findings/results: </strong>The ethyl acetate fraction (EMEA) was the most potent extract against NCI-H1299 cells, with a low IC₅₀ and an impressive selective effect. Most attractively, this is the very first study showing that EMEA induced both apoptosis and senescence in a cancer cell line. The underlying mechanisms involved the extrinsic apoptotic pathway, DNA damage, p21-dependent cell-cycle arrest, and oxidative stress response. EMEA could also strongly inhibit the migration, invasion, and collagen I adhesion abilities of NCI-H1299 cells. This might stem from the reduction of two crucial metastatic <i>MMP2</i> and <i>VIM</i> genes. As interesting as the cytotoxic findings, this is among the surprisingly sparse studies on the anti-metastasis activity of EM extracts and compounds.</p><p><strong>Conclusion and implications: </strong>Our research contributed considerably to the knowledge of anticancer properties of EM and cemented its role as a promising source for novel cancer treatment therapies.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 4","pages":"418-436"},"PeriodicalIF":2.3,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13441040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679872","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}

{"title":"Pinostrobin pentanoate as a selective estrogen receptor-<i>α</i> antagonist in breast cancer: integrated <i>in silico</i> and <i>in vitro</i> evaluation.","authors":"Tri Widiandani, Delis Susilawati, Ave Rahman, Siti Rahmah, Melanny Ika Sulistyowaty, A Mu'thi Andy Suryadi, Bambang Tri Purwanto, Siswandono Siswodihardjo","doi":"10.4103/RPS.RPS_108_25","DOIUrl":"10.4103/RPS.RPS_108_25","url":null,"abstract":"<p><strong>Background and purpose: </strong>Breast cancer remains the most commonly diagnosed cancer and the leading cause of cancer-related death among women worldwide. Estrogen receptor alpha (ERα) plays a major role in breast cancer cell proliferation, and approximately 70-80% of breast cancer cases are classified as Erα-positive. This study aims to predict the pinostrobin pentanoate potential against ERα by docking and molecular dynamics, and determine its cytotoxic activity against T47D breast cancer cells and normal cells.</p><p><strong>Experimental approach: </strong>Docking was analyzed using MOE 2022.02. Furthermore, AMBER 20 was used for molecular dynamics. Cytotoxicity was assessed using the MTT assay against T47D breast cancer cells and Vero cells for its selectivity index (SI).</p><p><strong>Findings/results: </strong>Based on docking results, the binding free energy of pinostrobin pentanoate (-7.682 ± 0.145 kcal/mol) was lower compared to pinostrobin (-6.503 ± 0.153 kcal/mol) against ERα, indicating the stronger binding affinity. In addition, the stability interaction using 100 ns molecular dynamics showed a stable interaction. Moreover, the IC₅₀ values of pinostrobin and pinostrobin pentanoate against T47D cells were 160 ± 5.30 μM and 32 ± 3.64 μM, respectively, compared to doxorubicin 0.14 ± 0.04 μM. Meanwhile, the CC₅₀ values of pinostrobin and pinostrobin pentanoate from the cytotoxicity test on Vero cells were estimated to be > 2500 and > 1500 μM, respectively. Therefore, the SI value of pinostrobin (SI > 15.6) is estimated to be smaller than that of pinostrobin pentanoate (SI > 46.8). Additionally, the combination of pinostrobin pentanoate and doxorubicin showed synergistic efficacy.</p><p><strong>Conclusion and implications: </strong>Pinostrobin pentanoate is more selective than pinostrobin, and it can be used as an anti-breast cancer candidate against the ERα for further research.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 4","pages":"466-480"},"PeriodicalIF":2.3,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13441030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679847","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}

{"title":"Investigating the <i>in vivo</i> effects of the human adipose tissue-derived stem cell transplantation and bromelain in myelin regeneration.","authors":"Sharare Rahnama, Nazem Ghasemi","doi":"10.4103/RPS.RPS_183_25","DOIUrl":"10.4103/RPS.RPS_183_25","url":null,"abstract":"<p><strong>Background and purpose: </strong>Natural compounds combined with human adipose-derived stem cell (hADSCs) transplantation could be considered an effective treatment for multiple sclerosis (MS). In the present study, the effects of bromelain administration in combination with hADSCs transplantation were evaluated for oligodendrocyte differentiation, myelin tissue regeneration, and improvement of motor function.</p><p><strong>Experimental approach: </strong>After inducing an MS mouse model, the mice were randomly divided into 4 groups: MS, MS + bromelain, MS + stem cell, and MS + bromelain + stem cell. Besides, 16 mice were designated for the control and sham groups. Finally, the behavioral test is used to evaluate motor function and motor defects. Furthermore, immunofluorescent staining was used to evaluate the cell markers. The serum levels of IgG, as well as inflammatory and anti-inflammatory factors, were assessed using an ELISA test.</p><p><strong>Findings/results: </strong>The mean percentages of Olig2- and Mog-positive cells, myelin density, and the serum levels of IL-10 and TGF-β were significantly higher in the treated groups than in the MS group. However, the serum levels of IL-17 and IFN-γ in the MS group were significantly higher compared to the other groups. Also, the serum level of IgG in the MS group was significantly higher than in the other groups.</p><p><strong>Conclusion and implications: </strong>It can be said that hADSCs transplantation, along with bromelain administration, is able to increase myelination and improve balance function. Therefore, the use of these agents could be a fundamental step towards finding a suitable method for the treatment of neurodegenerative diseases.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 4","pages":"403-417"},"PeriodicalIF":2.3,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13441042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679914","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}

{"title":"Harmine reduces ROS-mediated hepatotoxicity in a cisplatin mouse model.","authors":"Cyrus Jalili, Nasim Akhshi, Hossein Mohebi, Touraj Zamir-Nasta, Mohammad Reza Tabandeh, Mojtaba Esmaeli, Saeed Ravankhah, Ali Ghanbari","doi":"10.4103/RPS.RPS_194_25","DOIUrl":"10.4103/RPS.RPS_194_25","url":null,"abstract":"<p><strong>Background and purpose: </strong>Cisplatin, a widely used anticancer agent, has adverse effects on normal tissues during cancer treatment. This study aimed to investigate the use of harmine, a plant β-carboline alkaloid, against pathways associated with ROS-induced apoptosis in the livers of mice administered with cisplatin.</p><p><strong>Experimental approach: </strong>Twenty-four male Balb/c mice were randomly assigned to four groups (n = 6): (1) control group received daily intraperitoneal injections of saline for four days, (2) harmine group (15 mg/kg, intraperitoneally, daily for 4 days), (3) cisplatin group (5.5 mg/kg, intraperitoneally, one injection), and (4) cisplatin + harmine co-administration group. After sacrificing the animals under deep anesthesia, blood and liver tissue samples were collected for biochemical and molecular experiments.</p><p><strong>Findings/results: </strong>Cisplatin significantly elevated histopathological criteria (both qualitative and quantitative), levels of enzyme activity, malondialdehyde, nitric oxide, ROS, and apoptosis, and decreased glutathione, superoxide dismutase, and total antioxidant capacity. However, these factors were improved in the co-administration group compared to the cisplatin group. Furthermore, cisplatin treatment significantly upregulated <i>caspase-8, BAX, p53, caspase-3, TNF-α</i>, and <i>NF-κB</i> gene expression, while downregulating <i>BCL-2</i>. Co-administration with harmine led to significant changes in gene expression relative to the cisplatin group. Cisplatin notably increased protein levels of caspase-8, BAX, and TNF-α, but these levels were significantly reduced in the co-treatment group.</p><p><strong>Conclusion and implications: </strong>Harmine effectively ameliorates cisplatin-induced hepatitis by suppressing ROS production, thereby reducing intrinsic, extrinsic, and inflammation-induced apoptosis. These findings suggest that the antioxidant and anti-inflammatory properties of Harmine play a key role in its hepatoprotective actions.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 4","pages":"452-465"},"PeriodicalIF":2.3,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13441039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679823","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}

{"title":"In silico discovery of CETP inhibitors from ZINC15 compounds using docking, ADMET filtering, and molecular dynamics simulations.","authors":"Kimia Mohammadi, Mojgan Nejabat, Forough Mirabi, Amirhossein Sahebkar, Farzin Hadizadeh","doi":"10.4103/RPS.RPS_109_25","DOIUrl":"10.4103/RPS.RPS_109_25","url":null,"abstract":"<p><strong>Background and purpose: </strong>Cholesteryl ester transfer protein is a crucial regulator of lipid metabolism and is considered a promising target for treating atherosclerotic cardiovascular disease. Given the clinical limitations and adverse effects of previous cholesteryl ester transfer protein inhibitors, such as torcetrapib, this study aimed to identify safer, more effective alternatives through computational drug discovery.</p><p><strong>Experimental approach: </strong>A diverse set of natural compounds from the ZINC15 database was screened using a multi-step <i>in silico</i> workflow comprising drug-likeness assessment, ADMET profiling, molecular docking, and molecular dynamics simulations. This integrated process narrowed down a large compound library to a refined selection of candidates with favorable safety and pharmacokinetic properties.</p><p><strong>Findings/results: </strong>Calebin, a bioactive compound derived from turmeric, emerged as the most promising cholesteryl ester transfer protein inhibitor. It demonstrated binding interactions with cholesteryl ester transfer protein (-8.4 Kcal/mol) that were comparable to curcumin (-8.5 kcal/mol) and lower than the reference x-ray inhibitor torcetrapib (-9.4 kcal/mol), along with similar molecular dynamic complex stability (RMSD of 2.515 ± 0.282 Å in comparison to torcetrapib 2.502 ± 0.332 Å).</p><p><strong>Conclusion and implications: </strong>These findings highlight the value of computational drug discovery for identifying natural inhibitors of cholesteryl ester transfer protein and provide a strong foundation for future experimental validation. Calebin A demonstrated a promising binding affinity and interaction stability with cholesteryl ester transfer protein, but proof-of-concept studies are warranted to confirm this potential activity.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 4","pages":"505-520"},"PeriodicalIF":2.3,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13441038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679870","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}