{"title":"Assessment of efficacy of chrysin in diabetes-associated cardiac complications in chick embryo and murine model.","authors":"Joyani Das, Suparna Roy Sarkar, Ankita Das, Ananya Barui, Papiya Mitra Mazumder","doi":"10.1093/jpp/rgae088","DOIUrl":"10.1093/jpp/rgae088","url":null,"abstract":"<p><strong>Objectives: </strong>Patients with type 2 diabetes or prolonged diabetic condition are webbed into cardiac complications. This study aimed to ascertain the utility of chick embryo as an alternative to the mammalian model for type 2 diabetes-induced cardiac complications and chrysin as a protective agent.</p><p><strong>Methods: </strong>Diabetes was activated in ovo model (chick embryo) using glucose along with β-hydroxybutyric acid. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Alamar, and Kenacid blue assay were used to compare with chrysin-administered group. Blood glucose level, total cholesterol, triglyceride, and high-density lipoprotein were considered as endpoints. Diabetes was induced in Wistar albino rats by administering a high-fat diet and a subdued dose of streptozotocin (35 mg/kg, b.w). Percentage of glycated hemoglobin, creatinine kinase-MB, tumor necrosis factor-α, and C-reactive protein were evaluated and compared with chrysin administered group.</p><p><strong>Key findings: </strong>Chrysin treatment improved elevated blood glucose levels and dyslipidemia in a diabetic group of whole embryos. Condensed cellular growth and protein content as well as enhanced cytotoxicity in ovo were shielded by chrysin. Chrysin reduced cardiac and inflammatory markers in diabetic rats and provided cellular protection to damage the heart of diabetic rats.</p><p><strong>Conclusion: </strong>The protective action of chrysin in ovo model induced a secondary complication associated with diabetes, evidenced that the ovo model is an effective alternative in curtailing higher animal use in scientific research.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1225-1235"},"PeriodicalIF":2.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Therapeutic effects of Tanshinone IIA and Tetramethylpyrazine nanoemulsions on cognitive impairment and neuronal damage in Alzheimer's disease rat models.","authors":"Liang Fang, Hongyan Cheng, Weidong Chen, Can Peng, Yuanxu Liu, Caiyun Zhang","doi":"10.1093/jpp/rgae069","DOIUrl":"10.1093/jpp/rgae069","url":null,"abstract":"<p><strong>Objectives: </strong>The aim of this study was to investigate the therapeutic effects and related mechanisms of Tanshinone IIA and Tetramethylpyrazine O/W composite nanoemulsions on Alzheimer's disease (AD) rats.</p><p><strong>Methods: </strong>The therapeutic effect of TSN/TMP O/W NEs on AD rats was evaluated by behavioral tests, H&E, Nissl, and Immunohistochemistry staining. ELISA and Western blot were used to analyze the mechanism.</p><p><strong>Key findings: </strong>The results showed that TSN/TMP O/W NEs could down-regulate the expression of Bax and Caspase-3 proteins, decrease the level of MDA, increase the expression of SOD and GSH-Px, and alleviate cognitive impairment in AD rats.</p><p><strong>Conclusions: </strong>TSN/TMP O/W NEs can inhibit MAPK/ERK/CREB signaling pathway and effectively alleviate cognitive impairment, oxidative stress injury, and neuronal apoptosis in AD rats.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1169-1177"},"PeriodicalIF":2.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141457646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to: Investigation of polysaccharide from Radix Aconiti Lateralis Preparata (Fuzi) cardio protective effect on doxorubicin-induced chronic cardiotoxicity.","authors":"","doi":"10.1093/jpp/rgae029","DOIUrl":"10.1093/jpp/rgae029","url":null,"abstract":"","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1237"},"PeriodicalIF":2.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140065383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mesenchymal stem cell-derived exosomal microRNA-367-3p mitigates lower limb ischemia/reperfusion injury in mouse skeletal muscle via EZH2 targeting.","authors":"Huanhuan Sun, Jueqiong Wang, Wei Bi, Feng Zhang, Kai Zhang, Xitao Tian, Xiang Gao, Yanrong Zhang","doi":"10.1093/jpp/rgae086","DOIUrl":"https://doi.org/10.1093/jpp/rgae086","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the protective effect of bone marrow mesenchymal stem cell-derived exosomes (BMSCs-exo) against lower limb ischemia/reperfusion (I/R) injury-induced pyroptosis in skeletal muscle.</p><p><strong>Methods: </strong>A mouse model of lower limb I/R injury was utilized to assess the impact of BMSCs-exo, particularly when loaded with microRNA-367-3p (miR-367-3p), on pyroptosis. Histological examination, wet weight/dry weight ratio measurements, and luciferase assays were employed to elucidate the mechanisms involved.</p><p><strong>Key findings: </strong>BMSCs-exo effectively suppressed pyroptosis in injured skeletal muscle tissue. Loading BMSCs-exo with miR-367-3p enhanced this protective effect by downregulating key pyroptosis-related proteins. Luciferase assays identified enhancer of zeste homolog 2 (EZH2) as a direct target of miR-367-3p in BMSCs-exo.</p><p><strong>Conclusions: </strong>BMSCs-exo loaded with miR-367-3p safeguarded mouse skeletal muscle against pyroptosis-induced I/R injury by targeting EZH2. These findings offer valuable insights into potential therapeutic strategies for lower limb I/R injuries, emphasizing the therapeutic potential of BMSCs-exo in mitigating tissue damage caused by pyroptosis.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Current treatments for oropharyngeal squamous cell carcinoma and the move towards molecular therapy.","authors":"Mitra Elmi, Joshua H Dass, Crispin R Dass","doi":"10.1093/jpp/rgae107","DOIUrl":"10.1093/jpp/rgae107","url":null,"abstract":"<p><strong>Objectives: </strong>In this review, we discuss oropharyngeal squamous cell carcinoma (OPSCC) treatment options with a focus on the molecular mechanisms of OPSCC in head and neck squamous cell carcinoma (HNSCC) and head and neck cancers (HNCs). Treatment can be radical intent (aim for cure) or palliative intent (aim for disease control and symptom management). OPSCC is a prominent subset of HNSCCs in Australia and the Western World.</p><p><strong>Method: </strong>We looked at the current conventional treatment options with an overview of recent advances and future endeavours.</p><p><strong>Key findings: </strong>We identified that radiotherapy is the primary management for OPSCC in most countries, including the USA, UK, NZ, and Australia. In contrast, surgery is only considered for superficial OPSCC or neck surgery. If surgery is incomplete, then definitive management still requires radiotherapy.</p><p><strong>Conclusion: </strong>Molecular therapy is largely at the preclinical stage, with cetuximab, nivolumab, pembrolizumab, Lenvatinib, and bevacizumab being tested clinically currently.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Research progress on ethnobotany, phytochemistry, pharmacological action, and applications of Engelhardia roxburghiana Wall: a review.","authors":"Yuxin Li, Wenxin Xia, Tingting Li, Yuanyuan Zhang, Wenjin Zhang, Jiahui Yue, Lulu Wang, Xiangdong Zhu, Xueyan Fu","doi":"10.1093/jpp/rgae021","DOIUrl":"10.1093/jpp/rgae021","url":null,"abstract":"<p><strong>Objectives: </strong>Engelhardia roxburghiana Wall is a plant of the Juglandaceae family, and its leaves is the main part used as a medicine. It is used to relieve heat and pain, gasification, and dampness. The purpose of this review is to provide a systematic review about the botany, traditional uses, phytochemistry, pharmacology, and toxicology of this plant.</p><p><strong>Key findings: </strong>Many compounds have been isolated and identified from the plant, including flavonoids, triterpenoids, steroids, quinones, essential oils, and other types of chemical constituents. Extensive pharmacological activities of the extracts or compounds of E. roxburghiana Wall in vivo and in vitro were mainly confirmed, including anti-cancer, anti-diabetic, anti-inflammatory, and anti-allergic effects.</p><p><strong>Summary: </strong>In this paper, the botany, traditional uses, phytochemistry, and pharmacology of E. roxburghiana Wall were reviewed. In the future, E. roxburghiana Wall needs further study, such as paying more attention to quality control and the utilization on agriculture. In addition, discussing the medicinal components of decoction as well as the toxicity will also contribute to the progress of clinical trial studies.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"909-929"},"PeriodicalIF":2.8,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140175118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"GL-V9 synergizes with oxaliplatin of colorectal cancer via Wee1 degradation mediated by HSP90 inhibition.","authors":"Hongyu Chen, Fan Yang, Qianying Zhao, Hongzheng Wang, Mengyuan Zhu, Hui Li, Zheng Ge, Shuai Zhang, Qinglong Guo, Hui Hui","doi":"10.1093/jpp/rgae060","DOIUrl":"10.1093/jpp/rgae060","url":null,"abstract":"<p><strong>Objectives: </strong>GL-V9 exhibited anti-tumour effects on various types of tumours. This study aimed to verify if GL-V9 synergized with oxaliplatin in suppressing colorectal cancer (CRC) and to explore the synergistic mechanism.</p><p><strong>Methods: </strong>The synergy effect was tested by MTT assays and the mechanism was examined by comet assay, western blotting and immunohistochemistry (IHC). Xenograft model was constructed to substantiated the synergy effect and its mechanism in vivo.</p><p><strong>Results: </strong>GL-V9 was verified to enhance the DNA damage effect of oxaliplatin, so as to synergistically suppress colon cancer cells in vitro and in vivo. In HCT-116 cells, GL-V9 accelerated the degradation of Wee1 and induced the abrogation of cell cycle arrest and mis-entry into mitosis, bypassing the DNA damage response caused by oxaliplatin. Our findings suggested that GL-V9 binding to HSP90 was responsible for the degradation of Wee1 and the vulnerability of colon cancer cells to oxaliplatin. Functionally, overexpression of either HSP90 or WEE1 annulled the synergistic effect of GL-V9 and oxaliplatin.</p><p><strong>Conclusions: </strong>Collectively, our findings revealed that GL-V9 synergized with oxaliplatin to suppress CRC and displayed a promising strategy to improve the efficacy of oxaliplatin.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1006-1017"},"PeriodicalIF":2.8,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"YiQi GuBen formula alleviates airway inflammation and airway remodeling in OVA-induced asthma mice through TLR4/NF-κB signaling pathway.","authors":"Yibu Kong, Zhongtian Wang, Hongjun Yu, Aiai Dong, Yongfu Song, Lei Guo, Jinpu Zhu, Liping Sun, Yinan Guo","doi":"10.1093/jpp/rgae064","DOIUrl":"10.1093/jpp/rgae064","url":null,"abstract":"<p><strong>Background: </strong>We aim to investigate the effect of YiQi GuBen formula (YQGB) on airway inflammation and airway remodeling in the ovalbumin (OVA)-induced asthma model to further explore the potential mechanisms of YQGB in treating allergic asthma.</p><p><strong>Methods: </strong>Mice were divided into five groups randomly (n = 10): the control group, OVA group, OVA + Dex (0.1 mg/kg) group, OVA + low-dose (1.1 g/kg) YQGB group, and OVA + high-dose (2.2 g/kg) YQGB group. Inflammatory cell count and IgE were detected in bronchoalveolar lavage fluid (BALF). Lung tissue histopathology was observed by using H&E, PAS, Masson, and immunohistochemistry staining. qRT-PCR and western blot were applied to analyze key genes and proteins associated with TLR4 and NF-κB signaling pathways.</p><p><strong>Results: </strong>In OVA-induced asthma mice, YQGB decreased eosinophils and IgE in BALF. YQGB alleviated the OVA-induced inflammatory infiltration and declined IL-4, IL-5, IL-13, Eotaxin, ECP, GM-CSF, LTC4, and LTD4. YQGB attenuated the OVA-induced goblet cell metaplasia and mucus hypersecretion. YQGB mitigated the OVA-induced subepithelial fibrosis and lowered TGF-β1, E-Cadherin, Vimentin, and Fibronectin. YQGB ameliorated the OVA-induced airway smooth muscle thickening and lessened α-SMA and PDGF levels. YQGB reduced the expression of TLR4, MyD88, TRAF6, IκBα, and p65 mRNAs, and IκBα and p-p65 protein levels were also reduced.</p><p><strong>Conclusion: </strong>YQGB exhibits the anti-asthma effect by reducing airway inflammation and airway remodeling through suppressing TLR4/NF-κB signaling pathway, and is worth promoting clinically.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1028-1037"},"PeriodicalIF":2.8,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Queen Saikia, Kamal Adhikari, Airy Sanjeev, Ajit Hazarika, Kishore Sarma
{"title":"Isoliquiritigenin: a potential drug candidate for the management of erectile dysfunction.","authors":"Queen Saikia, Kamal Adhikari, Airy Sanjeev, Ajit Hazarika, Kishore Sarma","doi":"10.1093/jpp/rgae054","DOIUrl":"10.1093/jpp/rgae054","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to assess the erectogenic properties of isoliquiritigenin taking sildenafil (SDF) as the standard.</p><p><strong>Methods: </strong>The binding affinity of isoliquiritigenin (ISL) with the erectile marker proteins (endothelial nitric oxide synthase [eNOS] and enzyme phosphodiesterase type 5 [PDE5]) was investigated using Autodock Vina, which was validated using molecular dynamics simulation. Furthermore, the effect of ISL on the eNOS and PDE5 messenger ribonucleic acid (mRNA) expression and the sexual behavior of mice was investigated, along with the assessment of the pharmacokinetics of ISL.</p><p><strong>Key findings: </strong>The results revealed that the binding affinity of ISL-eNOS/PDE5 and SDF-eNOS/PDE5 was in the range of -7.5 to -8.6 kcal/mol. The ISL-eNOS/PDE5 complexes remained stable throughout the 100 ns simulation period. Root mean square deviation, Rg, SASA, hydrogen, and hydrophobic interactions were similar between ISL-eNOS/PDE5 and SDF-eNOS/PDE5. Analysis of mRNA expressions in paroxetine (PRX)-induced ED mice showed that the co-administration of PRX with ISL reduced PDE5 and increased eNOS mRNA expression, similar to the co-administered group (PRX+SDF). The sexual behavior study revealed that the results of PRX+ISL were better than those of the PRX+SDF group. Pharmacokinetic evaluation further demonstrated that ISL possesses drug-like properties.</p><p><strong>Conclusions: </strong>The results showed that ISL is equally potent as SDF in terms of binding affinity, specific pharmacological properties, and modulating sexual behavior.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1065-1077"},"PeriodicalIF":2.8,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Salma N Fahmy, Lobna H Khedr, Sara A Wahdan, Esther T Menze, Samar S Azab, Ebtehal El-Demerdash
{"title":"Effect of carvedilol on pharmacokinetics of sofosbuvir and its metabolite GS-331007: role of P-glycoprotein.","authors":"Salma N Fahmy, Lobna H Khedr, Sara A Wahdan, Esther T Menze, Samar S Azab, Ebtehal El-Demerdash","doi":"10.1093/jpp/rgae070","DOIUrl":"10.1093/jpp/rgae070","url":null,"abstract":"<p><p>Sofosbuvir (SOF) is a P-glycoprotein (P-gp) substrate, and carvedilol (CAR) is an inhibitor of P-gp, suggesting that it may affect the oral pharmacokinetics and safety of SOF. The current study investigated the pharmacokinetic interaction of CAR with SOF and its metabolite, GS-331007, and the possible consequent toxicities in rats. To assess the pharmacokinetics of SOF and GS-331007, rats were divided into three groups; all received a single oral dose of SOF preceded with saline (SAL), verapamil (VER) as a standard P-gp inhibitor, or CAR, respectively. The serosal, plasma, and hepatic tissue contents of SOF and GS-331007 were assessed using LC-MS/MS. Renal and hepatic toxicities were assessed using biochemical and histopathological tests. Serosal and plasma concentrations of SOF and GS-331007 were increased in the presence of CAR, suggesting a significant inhibitory effect of CAR on intestinal P-gp. Simultaneously, the pharmacokinetic profile of SOF showed a significant increase in the Cmax, AUC(0-t), AUC (0-∞), t1/2, and a reduction in its apparent oral clearance. While the pharmacokinetic profile of GS-331007 was not significantly affected. However, this notable elevation in drug oral bioavailability was corroborated by a significant alteration in renal functions. Hence, further clinical investigations are recommended to ensure the safety and dosing of CAR/SOF combination.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1051-1064"},"PeriodicalIF":2.8,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}