Iranian Journal of Pharmaceutical Research最新文献

{"title":"Promising Therapeutic Potential of miR-220-3p Mimic Against Murine Trimethyltin Hippocampal Injury.","authors":"Roya Khosh Ravesh, Vahid Khodashenas, Mina Goudarzi, Leila Mohammadi, Tourandokht Baluchnejadmojarad, Mehrdad Roghani","doi":"10.5812/ijpr-165755","DOIUrl":"10.5812/ijpr-165755","url":null,"abstract":"<p><strong>Background: </strong>Trimethyltin (TMT) is an organotin compound known to induce neurotoxicity within the limbic system of the brain, particularly in the hippocampal region, with neurodegenerative changes resembling those of Alzheimer's disease (AD).</p><p><strong>Objectives: </strong>This investigation examined the impact of miRNA-220-3p (miR-220-3p) on TMT-induced neurotoxicity and associated behavioral abnormalities, such as spatial learning and memory impairments, and identified the potential molecular mechanisms.</p><p><strong>Methods: </strong>To induce neurotoxicity, TMT was injected (8 mg/kg, i.p. once), and after 1 hour, miR-220-3p was microinjected intraventricularly (ICV route, once) for the possible mitigation of TMT-induced neurotoxicity. Different behavioral assessments were employed to determine spatial learning and memory function. Moreover, hippocampal measurements of brain-derived neurotrophic factor (BDNF) and Sirtuin-1, oxidative stress-, apoptosis-, and neuroinflammation-related factors, and histochemical changes were performed.</p><p><strong>Results: </strong>The TMT injection led to behavioral abnormalities in the novel object discrimination and Barnes maze tests, heightened oxidative stress [elevating reactive oxygen species (ROS) levels, nitrite, and lipid peroxidation and decreasing the activities of antioxidant enzymes, including catalase (CAT) and superoxide dismutase (SOD)], reduced BDNF and Sirtuin-1 levels, increased neuroinflammation [escalating the secretion of pro-inflammatory mediators, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)], raised activities of acetylcholinesterase (AChE), myeloperoxidase (MPO), beta-secretase 1 (BACE-1), caspase-1, and caspase-3, accompanied by a reduced number of CA1 pyramidal neurons and higher glial fibrillary acidic protein (GFAP) immunoreactivity. In contrast, microinjection of miR-220-3p reversed most of these alterations.</p><p><strong>Conclusions: </strong>The findings of this investigation imply that miR-220-3p may mitigate TMT-induced neurotoxicity, which is attributed to the suppression of hippocampal oxidative stress, neuroinflammation, and caspase-dependent apoptosis and pyroptosis, and part of its beneficial effect is associated with the upregulation of BDNF and Sirtuin-1.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e165755"},"PeriodicalIF":1.7,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13180302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-inflammation and Anti-insulin Resistance of a Compound from Vietnamese <i>Clerodendrum chinense</i> Leaves.","authors":"Thu Thi Xuan Nguyen, Cuong Trinh Tat","doi":"10.5812/ijpr-169136","DOIUrl":"10.5812/ijpr-169136","url":null,"abstract":"<p><strong>Background: </strong><i>Clerodendrum chinense</i> has been reported to possess several important biological activities. However, the anti-inflammation and insulin-related properties of isolated compounds from this plant have not yet been investigated.</p><p><strong>Objectives: </strong>This study focuses on extracting compounds and evaluating improvements in insulin resistance through the anti-inflammatory potential and inhibition of reactive oxygen species (ROS) of hispidulin from Vietnamese <i>C. chinense</i> leaves.</p><p><strong>Methods: </strong>Ethanol was used to separate the compounds from the leaves of Vietnamese <i>C. chinense</i>. 1D, 2D-NMR, and ESI-MS spectra were used to analyze the structural identity of the isolated compounds. Compound 1 (hispidulin) was evaluated for anti-inflammation and ROS in Raw 264.7 cells: Anti-inflammatory cytokine inhibition ability was analyzed by the ELISA method; Western blotting was used for the expression levels of phosphorylated ERK1/2, p38, p47phox, and GLUT4. ROS was assessed by immunofluorescence; a luminometer device was used to measure NADPH oxidase activity. The ability to absorb glucose and counteract insulin resistance was evaluated in 3T3-L1 cells via insulin-induced glucose uptake using immunofluorescence dye.</p><p><strong>Results: </strong>One compound isolated from the leaves of Vietnamese <i>C. chinense</i> was identified as hispidulin. Hispidulin at a concentration of 50 μg/mL significantly inhibited tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 in LPS-induced macrophages (P < 0.001). Moreover, in LPS-stimulated macrophages, the phosphorylation of p38 and ERK1/2, NADPH oxidase activity, as well as the phosphorylation of p47phox, were reduced at a concentration of 50 μg/mL of hispidulin (P < 0.001). More importantly, 3T3-L1 cells with inhibited insulin activity were able to regain glucose uptake and insulin responsiveness through GLUT4 expression when treated with 50 µg/mL of hispidulin (P < 0.001).</p><p><strong>Conclusions: </strong>The data confirmed the presence of hispidulin in the chemical composition of Vietnamese <i>C. chinense</i> leaves. The results indicated that hispidulin inhibited LPS- and ROS-mediated inflammation in macrophages. More importantly, the data have shown that hispidulin enhances glucose uptake and improves insulin activity in 3T3-L1 cells.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e169136"},"PeriodicalIF":1.7,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13187690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147987487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer Effects of <i>Ziziphus jujuba</i> in Human Breast Carcinoma: An Integrated Study of Network Pharmacology, Molecular Docking and Dynamics Simulations and in-vitro Experimental Validation.","authors":"Jinxin Guo, Jing Shen","doi":"10.5812/ijpr-169917","DOIUrl":"10.5812/ijpr-169917","url":null,"abstract":"<p><strong>Background: </strong><i>Ziziphus jujuba</i> is a promising medicinal plant with ethnomedicinal claims and constitutes one of the important herbs in Traditional Chinese Medicine, yet it has not been explored for its anticancer effects against breast cancer (BC).</p><p><strong>Objectives: </strong>The current study aimed to use an integrated approach involving network pharmacology, in-silico molecular docking and dynamics simulations, as well as in-vitro experimental validation, to study the anticancer effects of <i>Z. jujuba</i> in BC.</p><p><strong>Methods: </strong>A total of 133 phytochemicals from <i>Z. jujuba</i> were screened using the TCMSP database, followed by toxicity screening (Protox 3.0) and ADMET analysis (ADMET AI). Soxhlet extraction was performed with a 70:30 ethanol:dichloromethane solvent mixture. Compound-target networks were constructed using SuperPred, SwissTargetPrediction, and Cytoscape (CytoHubba plugin, Degree method). Breast cancer targets (GeneCards, Gifts score ≥ 60%) were intersected with phytochemical targets (Venny 2.0), and a PPI network was generated (STRING, confidence ≥ 0.700). GO and KEGG analyses used ShinyGO 0.80. Expression analyses of hub genes were conducted using GEPIA2 (BRCA dataset). Molecular docking was performed with CB-Dock2, and MD simulations used iMODS (100 modes, 300 K) and Desmond. Bioassays included MTT, clonogenic, Annexin V/PI, and Western blot analyses on MDA-MB-231 and MCF-10A cells.</p><p><strong>Results: </strong>Five phytochemicals (Spiradine A, Jujubogenin, Malkangunin, Ceanothic Acid, Moupinamide) showed no toxicity risks. The compound-target network identified 305 targets, with 160 intersecting BC targets. The PPI network (160 nodes, 568 edges, P < 1.0e-16) revealed EGFR, HSP90AA1, and STAT3 as hubs. GO/KEGG analyses linked targets to cancer pathways. EGFR, HSP90AA1, and STAT3 showed higher expression in tumors (P < 0.05), with EGFR/STAT3 linked to poorer survival (P < 0.05). Jujubogenin docking yielded binding affinities of -8.7 (EGFR), -7.5 (HSP90AA1), and -8.2 kcal/mol (STAT3). MD simulations confirmed stable EGFR/STAT3 complexes. The extract exhibited selective cytotoxicity, reduced colony formation, induced apoptosis (P < 0.05), and downregulated EGFR (70%), HSP90AA1 (60%), and STAT3 (90%) at 100 µg/mL (P < 0.01).</p><p><strong>Conclusions: </strong>Network pharmacology revealed that <i>Z. jujuba</i> phytochemicals are predicted to show significant effects against BC. Out of these, Jujubogenin exhibited strong and stable interactions with network-predicted hubs. The extract showed selective cytotoxicity, induced apoptosis, inhibited colony formation, and significantly downregulated these hub proteins, validating its promising anticancer potential.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e169917"},"PeriodicalIF":1.7,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13558866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astragalus Polysaccharide Suppresses Inflammation and Promotes Apoptosis in Hypertrophic Scars by Suppressing OGT-Mediated Nrf2 O-GlcNAcylation.","authors":"Hengfei Wang","doi":"10.5812/ijpr-168614","DOIUrl":"10.5812/ijpr-168614","url":null,"abstract":"<p><strong>Background: </strong>Hypertrophic scars (HS) arise from excessive tissue proliferation during wound healing, with Nrf2 involved, though the underlying mechanism remains unclear. Astragalus polysaccharides (APS) have anti-inflammatory and antioxidant properties, but their therapeutic effects and mechanisms in HS remain unreported.</p><p><strong>Objectives: </strong>This study intends to clarify how APS target protein O-GlcNAcylation to treat HS.</p><p><strong>Methods: </strong>A HS mouse model was established by subcutaneous injection of bleomycin (BLM) in C57BL/6 mice. Histopathology (H&E and Masson staining), ELISA, CCK-8, flow cytometry, western blot, and co-immunoprecipitation were performed to assess pathological changes, cell viability, apoptosis, inflammatory cytokine levels, and protein O-GlcNAcylation.</p><p><strong>Results: </strong>Astragalus polysaccharides treatment significantly inhibited scar formation and reduced inflammatory cytokine levels in HS mice. In human hypertrophic scar fibroblasts (HHSFs), APS suppressed cell viability and inflammation while promoting apoptosis. Mechanistically, APS decreased global O-GlcNAcylation levels and downregulated the protein expression of OGT and Nrf2. Mechanistically, OGT interacted with Nrf2, enhancing its stability via O-GlcNAcylation at S199. Moreover, Nrf2 overexpression reversed APS-induced changes in HHSF viability, inflammation, and apoptosis.</p><p><strong>Conclusions: </strong>This study identifies the OGT-mediated O-GlcNAcylation of Nrf2 as a novel regulatory mechanism in HS progression. By suppressing this axis, APS demonstrates therapeutic potential for HS. These findings highlight O-GlcNAcylation as a promising therapeutic target and support the clinical development of APS for fibrotic skin disorders.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e168614"},"PeriodicalIF":1.7,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probiotics Ameliorate Atrial Fibrillation-Associated Biomarkers and Inflammation in Rats via Modulation of the Gut Microbiota and NLRP3 Inflammasome Pathway.","authors":"Yeran Zhu, Long Bai, Ruibin Li, Yichen Li, Hongxia Hou, Jidong Zhang","doi":"10.5812/ijpr-168612","DOIUrl":"10.5812/ijpr-168612","url":null,"abstract":"<p><strong>Background: </strong>The gut-heart axis, particularly the role of gut microbiota and the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, is increasingly implicated in the pathogenesis of atrial fibrillation (AF). While probiotics show therapeutic potential, their mechanism in AF remains unclear.</p><p><strong>Objectives: </strong>This study investigates whether probiotics mitigate AF pathology by restoring gut microbiota homeostasis and inhibiting NLRP3 activation.</p><p><strong>Methods: </strong>An AF model was induced in rats via acetylcholine (ACH)/CaCl₂ infusion. Animals were divided into five groups: Sham, AF, AF+Probiotics, AF+MCC950 (NLRP3 inhibitor), and AF+Probiotics+MCC950. We analyzed gut microbiota (16S rRNA sequencing), serum short-chain fatty acids (SCFAs; GC-MS), and the expression of NLRP3 pathway components [NLRP3, caspase-1, interleukin-1β (IL-1β)] and AF biomarkers [pentraxin 3 (PTX3), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), chemerin, galectin-3 (Gal-3)] via immunohistochemistry (IHC), Western blot, and real-time quantitative polymerase chain reaction (RT-qPCR).</p><p><strong>Results: </strong>Atrial fibrillation rats exhibited gut dysbiosis, characterized by reduced diversity (Shannon index significantly decreased vs. Sham, P < 0.01), decreased beneficial bacteria (e.g., Lactobacillus), and lower SCFA levels (acetic, propionic, and butyric acids reduced by 40 - 50%, P < 0.05). Probiotics restored microbial diversity, increased SCFA production (to levels comparable to Sham, P < 0.05), and suppressed NLRP3 inflammasome activation, as evidenced by reduced levels of NLRP3, caspase-1, and IL-1β (protein and mRNA expression decreased by 50 - 70%, P < 0.01). Consequently, the expression of key AF biomarkers was significantly downregulated (PTX3, IL-6, TNF-α, chemerin, Gal-3 reduced by 40 - 60%, P < 0.05). The combined intervention of probiotics and MCC950 yielded the most pronounced effects (all markers further reduced vs. either treatment alone, P < 0.05).</p><p><strong>Conclusions: </strong>Probiotics alleviate AF-related inflammation and biomarker expression, potentially by modulating the gut microbiota and inhibiting the NLRP3 inflammasome pathway. These findings highlight the gut-heart axis as a promising target for AF management.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e168612"},"PeriodicalIF":1.7,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wedelolactone Inhibits Hepatitis B Virus Replication by Modulating NF-κB and Nrf2/HO-1 Signaling: An in-vitro Huh7 1.3-mer HBV Plasmid Model.","authors":"Bin Wang, Xuehui Bu, Umar Saeed, Zahra Zahid Piracha, Di Xiao","doi":"10.5812/ijpr-168329","DOIUrl":"10.5812/ijpr-168329","url":null,"abstract":"<p><strong>Background: </strong>Chronic hepatitis B virus (HBV) infection is a well-recognized cause of hepatic injury through prolonged viral replication, inflammation, and oxidative stress. Existing antiviral drugs limit viral replication but cannot eliminate viral transcription or even totally preclude liver injury, thus reemphasizing the significance of drugs with combined antiviral and hepatoprotective effects.</p><p><strong>Objectives: </strong>To evaluate the effects of wedelolactone on HBV replication, gene expression, inflammation, and oxidative stress in an in-vitro model of HBV plasmid transfection with human hepatic cells.</p><p><strong>Methods: </strong>Human hepatocellular carcinoma cells (Huh7) were transfected with a 1.3-mer plasmid and treated with wedelolactone (2.5 - 10 µM). Luciferase assays for HBV promoter activity, Northern blotting and Southern blotting for transcripts and replicative intermediates, qPCR for extracellular HBV DNA, and western blotting for viral antigens such as HBx were performed. Cell cytotoxicity was measured. NF-κB/IκB, inflammatory cytokines (TNF-α, IL-6), and antioxidant markers (Nrf2, HO-1, Keap1) were assessed to evaluate inflammatory and oxidative responses.</p><p><strong>Results: </strong>Wedelolactone significantly suppresses HBV promoter activity, RNAs, core particle formation, and extracellular HBV DNA. It reduced the expression of HBcAg and HBsAg. It inhibited NF-κB activation and cytokine release, while simultaneously enhancing Nrf2/HO-1 signaling, including induction of heme oxygenase-1 by lowering levels of Keap1.</p><p><strong>Conclusions: </strong>Wedelolactone exerts dual antiviral and hepatoprotective actions by inhibiting HBV replication and modulating inflammatory and oxidative stress pathways.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e168329"},"PeriodicalIF":1.7,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-146a-Enriched Extracellular Vesicles Attenuate Neuroinflammation and Promote Recovery After Ischemic Stroke.","authors":"Nana Hao, FuHua Gong","doi":"10.5812/ijpr-167245","DOIUrl":"10.5812/ijpr-167245","url":null,"abstract":"<p><strong>Background: </strong>Ischemic stroke triggers a strong neuroinflammatory response involving cytokines, which are fundamentally involved in tissue damage and repair.</p><p><strong>Objectives: </strong>The present study was designed to investigate the therapeutic potential of miR-146a-enriched extracellular vesicles derived from bone marrow mesenchymal stem cells (BMSC-EVs) in a rat model of middle cerebral artery occlusion (MCAO).</p><p><strong>Methods: </strong>miR-146a was transfected into BMSCs using Lipofectamine 3000. Extracellular vesicles (EVs) were isolated from transfected BMSCs using ultracentrifugation. Thirty rats were randomly assigned to three groups (n = 10 per group): (1) Control (received FBS), (2) miR-control EVs (miR-NC), and (3) miR-146a-enriched EVs, administered intravenously post-ischemia. Neurological deficits were evaluated with the Bederson score, and cytokine levels, including tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin (IL)-6, IL-10, as well as transforming growth factor β (TGF-β), were measured in splenocyte culture and brain tissues using enzyme-linked immunoassay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR), respectively. The expression of Interleukin-1 Receptor-Associated Kinase 1 (IRAK1), Tumor Necrosis Factor Receptor-Associated Factor 6 (TRAF6), and nuclear factor kappa B (NF-κB) was also measured using RT-PCR.</p><p><strong>Results: </strong>Results showed that EVs enriched in miR-146a significantly decreased pro-inflammatory cytokines, TNF-α, IFN-γ, and IL-6, and increased anti-inflammatory markers, IL-10 and TGF-β, when compared with miR-control EVs and FBS-treated groups. miR-146a-EV-treated rats also displayed better Bederson scores, which reflected better neurological recovery. Results also demonstrated that miR-146a-enriched EVs downregulated IRAK1, TRAF6, and NF-κB signaling in ischemic brain tissue.</p><p><strong>Conclusions: </strong>These results indicate that miR-146a overexpression in BMSC-EVs can significantly inhibit neuroinflammation and promote functional improvement in ischemic stroke models, supporting its targeted therapeutic potential.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e167245"},"PeriodicalIF":1.7,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gamabufotalin Suppresses Colorectal Cancer Growth via Oxidative Stress-Induced Apoptosis and DNA Synthesis Inhibition.","authors":"Hui Nie, Anfang Cui, Zhicheng Sun, Zhaoyang Li, Jianhua Guo, Shuhao Fan, Xiangchen Wang, Yong Xia","doi":"10.5812/ijpr-169859","DOIUrl":"10.5812/ijpr-169859","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) continues to be a major cause of cancer-related mortality worldwide, creating an urgent need to develop novel therapeutic agents that are both highly effective and minimally toxic. Gamabufotalin (GA), a bioactive bufadienolide compound, has shown promising antitumor potential, including against CRC; however, its precise mechanisms of action in CRC remain incompletely understood.</p><p><strong>Objectives: </strong>The aim of this study was to investigate the therapeutic effect of GA on CRC and explore the underlying molecular mechanisms.</p><p><strong>Methods: </strong>A combination of in vitro and in vivo approaches was employed, including cell viability assays, colony formation, EdU incorporation, cell cycle and apoptosis analyses by flow cytometry, ROS and mitochondrial membrane potential detection, as well as integrated transcriptomic and proteomic profiling. The in vivo antitumor efficacy was further validated in a nude mouse xenograft model.</p><p><strong>Results: </strong>Gamabufotalin exhibited potent, dose-dependent anti-CRC activity in vitro (IC₅₀: 24-30 nM) with high selectivity over normal cells. It triggered mitochondrial apoptosis via ROS generation and arrested the cell cycle, suppressing DNA synthesis. Integrated omics revealed TP53I3/PIG3 upregulation and RFC3/NUCKS1 downregulation as key mechanisms. Critically, these effects converged to suppress tumor growth in vivo without systemic toxicity.</p><p><strong>Conclusions: </strong>Gamabufotalin selectively and potently inhibits CRC through dual mechanisms: Inducing ROS-mediated apoptosis and suppressing proliferation. With a favorable therapeutic index and defined molecular targets, GA represents a promising candidate for CRC therapy.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e169859"},"PeriodicalIF":1.7,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatoprotective and Antioxidant Activities of a Medicine-Food Homology Formula and Its <i>Lactiplantibacillus plantarum</i>-Fermented Product Against Acetaminophen-Induced Oxidative Stress in HepG2 Cells.","authors":"Ching-Hui Hu, Simon Anthony Kayombo, Chih Min Yang","doi":"10.5812/ijpr-168131","DOIUrl":"10.5812/ijpr-168131","url":null,"abstract":"<p><strong>Background: </strong>Acetaminophen (APAP) overdose depletes glutathione (GSH) and induces oxidative liver injury. The medicine-food homology formula (MFHF) is composed of <i>Chrysanthemi flos</i> (CF), <i>Cassiae semen</i> (CS), and <i>Lycii fructus</i> (LF) (3:20:10, w/w/w). However, the effects of MFHF and its <i>Lactiplantibacillus plantarum</i>-fermented products (MFHFF) on quality markers and activities remain unclear.</p><p><strong>Objectives: </strong>This study investigated the prebiotic potential of MFHF; examined the stability of chlorogenic acid and chrysophanol before and after fermentation; compared hepatoprotective effects between MFHF and MFHFF in APAP-treated HepG2 cells; evaluated antioxidant activities; and assessed intra-formula interactions (additive/synergistic) among CF, CS, and LF.</p><p><strong>Methods: </strong>Fermentations were performed with <i>L. plantarum</i> BCRC12251 in 0 - 5% (w/v) MFHF substrates. Viable counts and pH were used to assess prebiotic effects. The HPLC was used to determine the content of chlorogenic acid and chrysophanol before and after fermentation. Antioxidant activities were measured by DPPH and potassium ferricyanide reducing antioxidant power (PFRAP) assays. Hepatoprotection was evaluated in APAP-treated HepG2 cells using cell viability, intracellular GSH, and malondialdehyde (MDA) as endpoints. Intra-formula interactions were evaluated by comparing observed and expected values. Data were analyzed using independent-sample t-tests and one-way ANOVA followed by Duncan's multiple range test (P < 0.05).</p><p><strong>Results: </strong>MFHF enhanced <i>L. plantarum</i> growth by 26-fold and retained phytochemical markers after fermentation. Both MFHF and MFHFF increased viability and GSH and decreased MDA in a dose-dependent manner in APAP-challenged HepG2 cells. MFHF and MFHFF showed comparable antioxidant activities. Viability and DPPH activity were synergistic, whereas GSH, MDA, and PFRAP showed additive effects.</p><p><strong>Conclusions: </strong>MFHF could act as a prebiotic for <i>L. plantarum</i>. Fermentation preserved MFHF's chemical integrity and hepatoprotective efficacy. Both preparations demonstrated comparable antioxidant and cytoprotective properties, supporting their potential as multifunctional candidates against oxidative liver injury in vitro and warranting further in vivo validation.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e168131"},"PeriodicalIF":1.7,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytochemicals Characterization and Antidiabetic Efficacy of <i>Muntingia calabura</i> L. Leaves Extract: In vitro and in vivo Studies.","authors":"Raden Maya Febriyanti, Mayra Fauzia, Nurqisthi Iqlimia, Aalbrecht Alby Irawan, Dwintha Lestari, Yoppi Iskandar, Yasmiwar Susilawati, Ajeng Diantini","doi":"10.5812/ijpr-169399","DOIUrl":"10.5812/ijpr-169399","url":null,"abstract":"<p><strong>Background: </strong><i>Muntingia calabura</i> L. leaves are traditionally used in West Java to manage hyperglycemia, yet integrated evidence linking their chemical profile with bioactivity remains limited.</p><p><strong>Objectives: </strong>To profile secondary metabolites in <i>M. calabura</i> leaf extract (MCLE), evaluate antioxidat capacity, and perform an assessment of antihyperglycemic efficacy in a diabetic rat model.</p><p><strong>Methods: </strong><i>Muntingia calabura</i> L. leaves extract was characterized by ultra-high-performance liquid chromatography-high-resolution tandem mass spectrometry (UHPLC-HRMS/MS). Antioxidant activity was measured using the ABTS•⁺ decolorization assay. Antihyperglycemic activity was evaluated in streptozotocin (STZ)-induced diabetic rats treated orally with MCLE (125 or 250 mg/kgBW) for 14 days. Fasting blood glucose (FBG), 2-hour postprandial glucose (2hPP), and body weight were analyzed using two-way repeated-measures analysis of variance (ANOVA).</p><p><strong>Results: </strong>Ultra-high-performance liquid chromatography-high-resolution tandem mass spectrometry annotated diverse secondary metabolites, with the most intense signals assigned to 5-hydroxy-6,7-dimethoxy-2-phenyl-4H-chromen-4-one (19.99%), isokaempferide (16.94%), and scrophulein (10.90%). <i>Muntingia calabura</i> L. leaves extract and its n-hexane and ethyl acetate fractions exhibited ABTS•⁺ radical scavenging activity. In STZ-induced rats, significant group × day interactions were observed for all outcomes (P < 0.001). The 250 mg/kgBW dose attenuated diabetes-associated weight loss and reduced FBG (P < 0.01), and 2hPP at this dose (134.0 ± 4.0 mg/dL) was not significantly different from the normal control or glibenclamide groups (P > 0.05).</p><p><strong>Conclusions: </strong><i>Muntingia calabura</i> L. leaves extract demonstrated antihyperglycemic activity in STZ-induced diabetic rats, improving both FBG and 2hPP alongside measurable antioxidant capacity.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e169399"},"PeriodicalIF":1.7,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}