Research in Pharmaceutical Sciences最新文献

{"title":"Chlorogenic acid suppresses angiogenesis in 4T1 breast tumors <i>via Cox-2, Vegf</i>, and <i>Mmp-9</i> downregulation.","authors":"Zahra Changizi, Shima Ababzadeh, Masoumeh Dolati, Azam Moslehi, Reihaneh Seyedebrahimi, Mohsen Eslami Farsani","doi":"10.4103/RPS.RPS_221_24","DOIUrl":"10.4103/RPS.RPS_221_24","url":null,"abstract":"<p><strong>Background and purpose: </strong>Angiogenesis, as a physiological process, plays a key role in the development of invasive tumors. However, polyphenol compounds such as chlorogenic acid (CGA) can help reduce the risk of metastasis. This study explored the anti-angiogenic properties of CGA in a metastatic tumor model.</p><p><strong>Experimental approach: </strong>Forty female BALB/c mice were randomly divided into 5 groups, including saline, receiving normal saline; breast cancer (BC), receiving 4T1 cells and normal saline; CGA group, receiving CGA solution; PR group, receiving simultaneously 4T1 cells and CGA; treatment group (TM), receiving CGA after tumor induction. The treatment period was 14 days. The anti-angiogenic effects of CGA were examined using the H&E and TB staining in breast, liver, and lung tissues of the metastatic tumor model. Real-time RT- PCR was also conducted to determine the expression of <i>Vegf, Cox-2,</i> and <i>Mmp-9</i> genes in tumor vessels and metastatic tissues.</p><p><strong>Findings/results: </strong>Histomorphological evaluations demonstrated a significant reduction in the number of all types of breast vessels and many vessels of lung tissue in the TM group compared with the BC group. Also, the diameter of sinusoid capillaries and veins of liver tissue significantly decreased with the administration of CGA compared with the BC group. Moreover, real-time RT-PCR results showed that CGA administration downregulated the expression of <i>Cox-2</i>, <i>Vegf</i>, and <i>Mmp-9</i> levels compared with the BC group, significantly.</p><p><strong>Conclusion and implications: </strong>CGA plays an important role in inhibiting angiogenesis by decreasing the expression of <i>Cox-2, Vegf,</i> and <i>Mmp-9</i> genes. It could improve the invasion of 4T1 breast cancer tumors in BALB/c mice.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 2","pages":"215-226"},"PeriodicalIF":2.3,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13186477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147983031","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":"GPR97 variants and their influence on pathological myopia: implications for glucocorticoid treatment.","authors":"Qi Zhao, Zhaoxia Mu, Huihui Gu, Wei Cheng, Yulian Xu, Yingying Jiang, Geping Wu, Lijun Pu","doi":"10.4103/RPS.RPS_217_24","DOIUrl":"10.4103/RPS.RPS_217_24","url":null,"abstract":"<p><strong>Background and purpose: </strong>Pathologic myopia (PM) is a severe form of myopia associated with structural changes in the eye, leading to vision impairment. Identifying genetic factors that contribute to PM can enhance the treatment of the condition. This study aimed to investigate the association between the <i>GPR97</i> and PM and to evaluate the impact of glucocorticoid treatment on PM.</p><p><strong>Experimental approach: </strong>A cohort of 412 sporadic PM patients underwent Sanger sequencing and genotyping for GPR97 gene variants. Thirty-one PM patients with various GPR97 genotypes received glucocorticoid and brinzolamide treatment over 24 months. Real-time PCR was employed to examine the target gene mRNA expression. A scratch assay was performed to detect cell migration ability.</p><p><strong>Findings/results: </strong>A significant association was identified between GPR97 rs76688596 genotypes and PM occurrence. The CC genotype was linked to elevated intraocular pressure (IOP). In human scleral fibroblasts, overexpression of GPR97 Arg396 resulted in upregulation of IOP-related genes serine/arginine-rich splicing factor 3, peptidyl-prolyl cis-trans isomerase 4, peptidyl-prolyl cis-trans isomerase 5, and nuclear receptor subfamily 3 group C member 1. The GPR97 Arg396 mutation inhibited the glucocorticoid-GPR97 axis and reduced cell migration ability. Clinically, CC genotype carriers exhibited significant improvements in axial length, spherical equivalent, IOP, best-corrected visual acuity, and visual field mean sensitivity with glucocorticoid treatment.</p><p><strong>Conclusion and implications: </strong>The study revealed that the GPR97 rs76688596 G > C variant is associated with PM pathogenesis, influencing gene expression related to IOP. The differential response to glucocorticoid treatment among GPR97 genotypes suggests personalized therapeutic potential.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 2","pages":"164-177"},"PeriodicalIF":2.3,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13186431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147983033","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":"PD-1: CD28 chimeric receptors enhance phenotypic and functional features of T cell subsets.","authors":"Saba Feghhi-Najafabadi, Farhad Riazi-Rad, Mohammad Ali Shokrgozar, Shahriyar Abdoli, Fatemeh Hajari Taheri, Arash Arashkia, Zahra Sharifzadeh","doi":"10.4103/RPS.RPS_82_25","DOIUrl":"10.4103/RPS.RPS_82_25","url":null,"abstract":"<p><strong>Background and purpose: </strong>The PD-1/PD-L1 immune checkpoint pathway inhibits T cell function, allowing tumors to escape immune responses. This study aimed to reprogram this inhibitory signaling using a PD- 1:CD28 switch receptor (SR) to convert inhibitory signaling into a co-stimulatory signal and to assess its effects on the function of CD4⁺ and CD8⁺ T cells.</p><p><strong>Experimental approach: </strong>PBMCs isolated from both sources were retrovirally transduced with PD-1:CD28 SR. Intracellular expression of cytokines, including IFN-γ, IL-4, IL-10, as well as the surface CD25 in CD4⁺ and CD8⁺ T cells, and the rate of cell apoptosis during engineering and exposure to target cells were assessed.</p><p><strong>Findings/results: </strong>Both buffy coat (BC) and whole blood showed comparable transduction efficiency (21.4% versus 18.5%, respectively), but BC yielded nearly double the number of viable PBMCs per 50 mL. Upon stimulation and co-culture with target cells, CD4⁺ SR T cells produced significantly higher levels of IFN-γ, IL-4, and IL-10 compared to CD8⁺ SR T cells. These cytokines also significantly increased in co-culture supernatants exposed to PD-L1⁺ cells. No significant differences were found in CD4/CD8 ratios, CD25 expression, or cytokine profiles between PBMC sources. However, BC-derived T cells showed higher apoptosis rates during co-culture.</p><p><strong>Conclusion and implications: </strong>BC can be a practical and effective source of PBMCs for T cell engineering. These findings underscore the SR signaling in the activation of CD4⁺ T cells that may impact the activation of CD8⁺ T cells, which is essential for effective tumor eradication.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 2","pages":"236-250"},"PeriodicalIF":2.3,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13186483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147982471","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":"Comparative evaluation of microfluidic-synthesized nano-niosomes versus liposomal and micro-niosomal deferoxamine in murine iron overload models.","authors":"Ali Bazi, Somayyeh Karami-Mohajeri, Hajar Mardani Valandani, Elham Jafari, Fatemeh Oroojalian, Abbas Pardakhty, Roohollah Mirzaee Khalilabadi","doi":"10.4103/RPS.RPS_155_25","DOIUrl":"10.4103/RPS.RPS_155_25","url":null,"abstract":"<p><strong>Background and purpose: </strong>Microfluidic technology provides enhanced standardization for formulating nanoencapsulated drugs compared to traditional bulk methodologies. Here, microfluidic nano-niosomal deferoxamine (Nn-DFO) was compared to micro-niosomal (Mn-DFO) and liposomal (L-DFO) formulations synthesized by conventional thin-film hydration.</p><p><strong>Experimental approach: </strong>The formulations were subjected to physicochemical analyses. <i>In vivo</i> functional efficacy and safety were analyzed in mouse models of iron overload. Urinary and fecal iron excretion were also assessed.</p><p><strong>Findings/results: </strong>Mean particle sizes were 180.89±74.34 nm for L-DFO, 87.06±2.67 nm for Nn-DFO, and 7.41 ± 0.19 μm for Mn-DFO. Encapsulation efficiencies of L-DFO, Nn-DFO, and Mn-DFO formulations were 64.54%, 57.1%, and 70.72%, respectively. The 4-h drug release rates for L-DFO, Nn-DFO, and Mn-DFO formulations were 20.95%, 31.34%, and 26.30%, respectively, compared to 59.46% release from free DFO (F-DFO) within 4 h. Animals treated with F-DFO, L-DFO, Nn-DFO, and Mn-DFO showed significant reductions in the iron content of the liver (45.03%, 49.36%, 41.63%, and 23.52%, respectively). Urinary iron excretion on day 1^st and fecal iron excretion on day 3^rd after drug administration were the highest in the groups treated with F-DFO and Nn-DF O compared to other groups. Fecal iron excretion on day 7^th was the highest in mice receiving Nn-DFO compared to different formulations.</p><p><strong>Conclusion and implications: </strong>Nn-DFO synthesized by the microfluidic approach showed iron chelation efficacy and immediate iron excretion profile comparable to F-DFO, while being superior to Mn-DFO and L-DFO regarding delayed iron excretion.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 2","pages":"146-163"},"PeriodicalIF":2.3,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13186486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147983032","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":"Protective effects of cilostazol against cisplatin-induced hepatorenal toxicity in male mice.","authors":"Elham Hakimizadeh, Fatemeh Khajehasani, Morteza Amirteimoury, Ayat Kaeidi, Jalal Hassanshahi, Iman Fatemi","doi":"10.4103/RPS.RPS_199_24","DOIUrl":"10.4103/RPS.RPS_199_24","url":null,"abstract":"<p><strong>Background and purpose: </strong>Cisplatin (CPN) is a widely used and potent chemotherapy drug for cancer treatment. However, one of the major side effects of CPN is hepatorenal toxicity. Recently, cilostazol (CSZ), a type III phosphodiesterase inhibitor, has promising effects against liver and kidney toxicities. We assessed the effects of CSZ against CPN-induced hepatorenal toxicity (CIHR) in male mice.</p><p><strong>Experimental approach: </strong>Twenty-four male mice were randomly assigned as follows: control group (no treatment), CPN group (treated with 20 mg/kg CPN on day one of the experiment), and CPN + CSZ 3 and 15 groups (treated with CPN on day one of the experiment plus CSZ (3 and 15 mg/kg) orally for four days). Biochemical, oxidative, and histological investigations were conducted to evaluate the effectiveness of CSZ in protecting the liver and kidneys from CPN-induced damage.</p><p><strong>Findings/results: </strong>The results showed that treatment with CSZ, especially at 15 mg/kg, significantly reduced the CPN-induced increase in serum concentrations of biochemical markers such as alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and creatinine. Furthermore, CSZ treatment at 15 mg/kg also restored the hepatorenal oxidative stress factors, including superoxide dismutase, malondialdehyde, and glutathione peroxidase. Histological examination revealed a significant improvement in groups receiving CSZ (15 mg/kg) compared to the CPN-treated group, alongside biochemical and oxidative results.</p><p><strong>Conclusion and implications: </strong>The findings of this investigation point towards the potential of CSZ as a viable contender for subsequent exploration in the realm of devising efficacious therapeutic approaches for CIHR.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 2","pages":"227-235"},"PeriodicalIF":2.3,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13186501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147982740","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":"Novel nanoliposomes for targeted codelivery of three anticancer agents against head and neck squamous cell carcinoma.","authors":"Maryam Mohammadi, Fahimeh Bagheri Tofighi, Maedeh Vakili Saatloo, Mehdi Talebi, Maryam Kouhsoltani, Hamed Hamishehkar","doi":"10.4103/RPS.RPS_54_24","DOIUrl":"10.4103/RPS.RPS_54_24","url":null,"abstract":"<p><strong>Background and purpose: </strong>Head and neck squamous cell carcinoma (HNSCC) is a malignant tumor in which the overexpression of epidermal growth factor receptor (EGFR) is associated with malignancy. For the treatment of HNSCC, cetuximab (CIT) as an anti-EGFR antibody is prescribed in combination with anticancer chemotherapy drugs for greater effectiveness.</p><p><strong>Experimental approach: </strong>In this work, a CIT-targeted immunoliposome loaded with cisplatin (CP) and docetaxel (DTX) was developed to allow co-administration of the antibody and the anticancer chemotherapy drugs and selective delivery to HNSCC cells. Developed immunoliposomes were characterized for particle sizes, PDI, zeta potential, surface morphologies, and encapsulation efficiency. Moreover, additional <i>in vitro</i> studies were conducted, including cytotoxicity against HN5 cell line, and cellular uptake studies.</p><p><strong>Findings/results: </strong>The final targeted liposomes exhibited an average diameter of 68.65 ± 3.4 nm; PDI and zeta- potential were respectively around -7.9 ± 1.7 mV and 0.35 ± 0.05. The encapsulation efficacy of DTX and CP within the immunoliposomes was approximately 95 ± 4% and 85 ± 4%, respectively. Flow cytometric analysis revealed that the cellular uptake rate of final immunoliposomes was significantly higher than that of the naked liposomes, indicating that CT conjugation on the surface of nanoliposomes facilitated higher accumulation <i>via</i> receptor-mediated endocytosis. Moreover, co-encapsulation of CP and DTX into CIT-immunoliposomes increased the apoptosis by 24.06% compared to single-drug nanoformulations.</p><p><strong>Conclusions and implications: </strong>The results indicated that nanoliposomes anchored with CIT enhanced drug accumulation and cytotoxicity in cancer cells and reduced the likelihood of adverse side effects, paving the way for more effective cancer therapies.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 2","pages":"251-261"},"PeriodicalIF":2.3,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13186495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147982475","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":"Perspective in 3D mesenchymal stromal cells as tools for potential diabetes treatment.","authors":"Alessia Dallatana, Linda Cremonesi, Damiano Coato, Giulio Innamorati, Luca Giacomello","doi":"10.4103/RPS.RPS_55_24","DOIUrl":"10.4103/RPS.RPS_55_24","url":null,"abstract":"<p><strong>Background and purpose: </strong>Diabetes represents one of the major global health issues, and the number of cases is expected to increase dramatically in the coming years. In the new century, many strategies have been developed to meet the urge for new therapies through technological innovations. Innovative pharmacological treatments, such as electronic insulin pumps, represent one of the gold standards for diabetes, even if cell replacement therapy is preferred in the most severe cases. Mesenchymal stromal cells (MSCs) can be differentiated into insulin-producing cells or islet-like cell clusters. Consequently, understanding the role of the extracellular matrix and three-dimensional (3D) structure in guiding MSC differentiation is crucial for advancing regenerative therapies.</p><p><strong>Experimental approach: </strong>The literature was examined using Google Scholar, PubMed, and Scopus, analyzing the pertinence with the focus of this manuscript.</p><p><strong>Findings: </strong>MSCs derived from birth tissues are characterized by a high level of plasticity and represent the best candidates for regenerative treatments. Together with MSCs, 3D approaches can be integrated to obtain complex structures supporting many biological requirements, namely the possibility of reproducing better physiological conditions, as well as supporting vascular network development. Furthermore, the incorporation of extracellular matrix components like laminin and collagen IV into hydrogels has been shown to enhance the insulin secretion and survival of insulin-producing cells.</p><p><strong>Conclusions and implications: </strong>In this review, we present an overview of the different strategies applied as of today in regenerative medicine, by unraveling the different cellular and matrix characteristics that can be crucial for future and potential diabetes treatment. Ultimately, the convergence of MSC biology with advanced 3D bioprinting and biomaterial science holds significant promise for creating a functional, implantable bioartificial pancreas to treat diabetes.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 2","pages":"135-145"},"PeriodicalIF":2.3,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13186439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147982517","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":"The effects of <i>Vitex agnus-castus</i> supplementation on inflammatory markers in women with PCOS: a randomized, double-blind, placebocontrolled trial.","authors":"Aniseh Hatami, Hanieh Taheri, Ali Khosrowbeygi, Fateme Seidi, Mohadeseh Azimi, Farideh Jalali-Mashayekhi","doi":"10.4103/RPS.RPS_152_25","DOIUrl":"10.4103/RPS.RPS_152_25","url":null,"abstract":"<p><strong>Background and purpose: </strong>To evaluate the effects of <i>Vitex agnus-castus</i> supplementation on serum levels of inflammatory cytokines (primary outcomes: tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6); secondary outcome: anti-Mullerian hormone (AMH)) in women with polycystic ovary syndrome (PCOS).</p><p><strong>Experimental approach: </strong>This secondary analysis included 40 serum samples (20 <i>Vitex</i> and 20 placebo) randomly selected from a previously registered randomized, double-blind, placebo-controlled trial in women with PCOS. Participants received either <i>Vitex</i> (5.8 mg/day, standardized to 0.42-0.82 mg aucubin) or a placebo for 12 weeks. Serum TNF-α, IL-6, and AMH were measured at baseline and week 12 using ELISA. Within- group changes were assessed with paired t-tests, and between-group differences were analyzed using independent t-tests and ANCOVA using SPSS v23.0 software.</p><p><strong>Findings/results: </strong><i>Vitex</i> supplementation significantly reduced serum TNF-α (141.27 ± 24.27 to 91.28 ± 19.57 pg/mL), IL-6 (71.72 ± 13.63 to 48.91 ± 24.19 pg/mL), and AMH (11.21 ± 3.89 to 7.88 ± 4.87 ng/mL) levels, whereas the placebo group showed no significant changes. The between-group differences were significant for all markers. These findings suggest potential benefits in reducing inflammation and improving ovarian function, pending confirmation in future clinical outcome studies.</p><p><strong>Conclusion and implications: </strong><i>Vitex</i> supplementation may offer a complementary approach to managing inflammation and hormonal disturbances in women with PCOS.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 2","pages":"206-214"},"PeriodicalIF":2.3,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13186487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147982918","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":"High-intensity interval training and <i>Crataegus pentagyna</i> extract enhance metabolic and oxidant profiles in ovariectomized Wistar rats.","authors":"Parvin Babaei, Fatemeh Sadeghi-Noghlebari, Sahar Falahati, Arsalinean Damirchi, Fatemeh Yousefbeyk, Maghsoud Nabilpour, Farnaz Seifi-Asgshahr","doi":"10.4103/RPS.RPS_70_25","DOIUrl":"10.4103/RPS.RPS_70_25","url":null,"abstract":"<p><strong>Background and purpose: </strong>High-intensity interval training (HIIT) improves body composition in obese individuals but increases fat oxidation and oxidative stress. This study aimed to evaluate the effects of chronic supplementation with <i>Crataegus pentagyna</i> fruit extract (CPE), combined with HIIT, on metabolic syndrome indices and oxidative stress.</p><p><strong>Experimental approach: </strong>Female Wistar rats (200-220 g) were randomized into seven groups (8 rats each) including: ovariectomized control (Ovx + saline), exercise (Ovx + Exe), CPE alone (100, 200, 300 mg/kg), Ovx + CPE + Exe: HIIT plus CPE (100 mg/kg, i.p); and sham. . At the end of the training, body weight, body mass index, waist circumference, visceral fat, fasting blood glucose, serum insulin, lipid profiles, MDA, TAC, Nrf2, and adiponectin were measured. The phytochemical contents were evaluated.</p><p><strong>Findings/results: </strong>Co-treatment with HIIT and CPE (100 mg/kg) produced greater reductions in visceral fat (-72.8%) than HIIT alone (-33.7%) and comparable reductions to CPE alone (-65.5% visceral fat, -20.3% waist circumference), with no dose-dependent effects across 100-300 mg/kg (P > 0.05).</p><p><strong>Conclusion and implications: </strong>Combined HIIT and 100 mg/kg CPE extract supplementation for 8 weeks significantly ameliorated metabolic syndrome and oxidative stress in ovariectomized rats, likely <i>via</i> adiponectin and Nrf2 upregulation, suggesting a potential adjunctive therapy for postmenopausal women.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 2","pages":"178-190"},"PeriodicalIF":2.3,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13186434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147983052","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":"Design, synthesis, and biological evaluation of novel aryl isoxazoles as potential Hsp90 inhibitors.","authors":"Mina Ardestani, Fariba Keshavarzipour, Maryam Abbasi, Afshin Zarghi, Mahmoud Aghaei, Mehran Ghiaci, Hojjat Sadeghi-Aliabadi","doi":"10.4103/RPS.RPS_173_25","DOIUrl":"10.4103/RPS.RPS_173_25","url":null,"abstract":"<p><strong>Background and purpose: </strong>Heat shock protein 90 (Hsp90) is a molecular chaperone critical for the stabilization of numerous oncoproteins, making it a promising target for anticancer drug development. This study aimed to design, synthesize, and evaluate novel 3,5-diarylisoxazole derivatives as potential Hsp90 inhibitors.</p><p><strong>Experimental approach: </strong>A series of 3,5-diarylisoxazole compounds (5R_1-6) was designed using molecular docking to predict binding affinity. Compounds were synthesized <i>via</i> cyclization of 4-chloroacetophenone with hydroxylamine hydrochloride, followed by condensation with various aldehydes. Structures were confirmed by melting point, FT-IR, and 1H-NMR spectroscopy. The MTT assay assessed cytotoxicity, and Hsp90 inhibitory activity was evaluated using an Hsp ELISA kit. The stability of the 5R3 compound in the Hsp90 active site was investigated using molecular dynamics simulation.</p><p><strong>Findings/results: </strong>All compounds showed favorable binding energies. Compound 5R3 showed the highest binding affinity (ΔG = -7.83 kcal/mol) and the highest cytotoxicity against MCF-7 cells (IC50 = 0.014 μM) and significantly reduced Hsp90 concentration from 5.54 ng/mL (untreated) to 1.56 ng/mL. Furthermore, molecular dynamics simulation studies confirmed the stability of the Hsp90-5R₃ complex during a 100 ns simulation.</p><p><strong>Conclusion and implications: </strong>Compound 5R₃ with an electronegative substituent (F) on the aromatic ring showed the highest cytotoxic effect, also decreased the concentration of Hsp90 protein more than others.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 2","pages":"191-205"},"PeriodicalIF":2.3,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13186490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147983001","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}