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Ligusticum chuanxiong Hort.: a review of its phytochemistry, pharmacology, and toxicology. 川芎:植物化学、药理学和毒理学综述。
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2024-08-24 DOI: 10.1093/jpp/rgae105
Qinghe Kong, Yingshuo Niu, Hao Feng, Xiaofei Yu, Bingkang Wang, Xue Liu, Yueru Chen, Fulin Wang, Jingzhen Tian, Honglei Zhou
{"title":"Ligusticum chuanxiong Hort.: a review of its phytochemistry, pharmacology, and toxicology.","authors":"Qinghe Kong, Yingshuo Niu, Hao Feng, Xiaofei Yu, Bingkang Wang, Xue Liu, Yueru Chen, Fulin Wang, Jingzhen Tian, Honglei Zhou","doi":"10.1093/jpp/rgae105","DOIUrl":"https://doi.org/10.1093/jpp/rgae105","url":null,"abstract":"<p><strong>Background: </strong>Conioselinum anthriscoides (H. Boissieu) Pimenov & Kljuykov, also known as Ligusticum chuanxiong Hort. is a perennial Umbelliferae herb, whose dried rhizome commonly called Chuanxiong Rhizoma. Chuanxiong Rhizoma is widely used in TCM, especially for cardiocerebrovascular and gynecological diseases. However, these studies are scattered and there is no review that can centralize the results of these studies. The authors summarized this review by collecting research results on the chemical, pharmacological, and toxicological of Chuanxiong Rhizoma published in various publications over the past 20 years.</p><p><strong>Aims: </strong>The purpose of this review is to summarize the current experimental studies on Chuanxiong Rhizoma and explore its mechanism of action.</p><p><strong>Methods: </strong>Web of Science, PubMed, CBM, CNKI, Medline, Embase, Elsevier, Springer, Wiley Online Library, Scholar, and other databases were searched, and nearly one hundred experimental studies were collected to summarize this review.</p><p><strong>Results and discussion: </strong>Chuanxiong Rhizoma is composed of essential oil, terpenes, alkaloids, polysaccharide, organic acids, ceramides, and cerebrosides. It has the functions of promoting blood circulation, removing blood stasis, antibacterial, antiviral, and calming the mind to sleep. Now it can be used to treat cardiocerebrovascular and gynecological diseases, neurodegenerative disease, psoriasis, rectal cancer, osteoporosis, and osteoarthritis.</p><p><strong>Conclusions: </strong>In the past 20 years, a large number of research data have confirmed that Chuanxiong Rhizoma contains rich effective metabolites, has huge medicinal potential, and has a wide range of effective treatments.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046815","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}
引用次数: 0
The beneficial impact of curcumin on cardiac lipotoxicity. 姜黄素对心脏脂肪毒性的有益影响
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2024-08-24 DOI: 10.1093/jpp/rgae102
Sajad Abolfazli, Alexandra E Butler, Prashant Kesharwani, Amirhossein Sahebkar
{"title":"The beneficial impact of curcumin on cardiac lipotoxicity.","authors":"Sajad Abolfazli, Alexandra E Butler, Prashant Kesharwani, Amirhossein Sahebkar","doi":"10.1093/jpp/rgae102","DOIUrl":"https://doi.org/10.1093/jpp/rgae102","url":null,"abstract":"<p><p>Lipotoxicity is defined as a prolonged metabolic imbalance of lipids that results in ectopic fat distribution in peripheral organs such as the liver, heart, and kidney. The harmful consequences of excessive lipid accumulation in cardiomyocytes cause cardiac lipotoxicity, which alters the structure and function of the heart. Obesity and diabetes are linked to lipotoxic cardiomyopathy. These anomalies might be caused by a harmful metabolic shift that accumulates toxic lipids and shifts glucose oxidation to less fatty acid oxidation. Research has linked fatty acids, fatty acyl coenzyme A, diacylglycerol, and ceramide to lipotoxic stress in cells. This stress can be brought on by apoptosis, impaired insulin signaling, endoplasmic reticulum stress, protein kinase C activation, p38 Ras-mitogen-activated protein kinase (MAPK) activation, or modification of peroxisome proliferator-activated receptors (PPARs) family members. Curcuma longa is used to extract curcumin, a hydrophobic polyphenol derivative with a variety of pharmacological characteristics. Throughout the years, curcumin has been utilized as an anti-inflammatory, antioxidant, anticancer, hepatoprotective, cardioprotective, anti-diabetic, and anti-obesity drug. Curcumin reduces cardiac lipotoxicity by inhibiting apoptosis and decreasing the expression of apoptosis-related proteins, reducing the expression of inflammatory cytokines, activating the autophagy signaling pathway, and inhibiting the expression of endoplasmic reticulum stress marker proteins.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046816","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}
引用次数: 0
Exploration of medicinal plants as potential therapeutics against COVID-19: molecular insights and drug development prospects with other significant medicinal information a retrospective exposition. 探索药用植物作为抗 COVID-19 的潜在疗法:分子见解和药物开发前景与其他重要药用信息的回顾性阐述。
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2024-08-21 DOI: 10.1093/jpp/rgae074
Saurabh Dilip Bhandare
{"title":"Exploration of medicinal plants as potential therapeutics against COVID-19: molecular insights and drug development prospects with other significant medicinal information a retrospective exposition.","authors":"Saurabh Dilip Bhandare","doi":"10.1093/jpp/rgae074","DOIUrl":"https://doi.org/10.1093/jpp/rgae074","url":null,"abstract":"<p><strong>Objectives: </strong>The study aims to explore the potential of medicinal plants and their phytoconstituents as effective inhibitors of the coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus. The focus is on investigating specific medicinal plants known for their pharmacological properties, such as: antioxidant, anti-inflammatory, and immunomodulatory effects, to determine their viability in developing COVID-19 treatments.</p><p><strong>Materials and methods: </strong>This study involves a comprehensive study of medicinal plants, including: Withania somnifera (Ashwagandha) and Ocimum sanctum (Holy Basil), known for their beneficial health effects. Molecular docking studies were conducted to assess the interactions between phytoconstituents from these plants and SARS-CoV-2 proteins. The compounds' drug-like characteristics and safety profiles were also evaluated to determine their potential as therapeutic agents.</p><p><strong>Results: </strong>The molecular docking studies revealed that the phytoconstituents from the studied medicinal plants exhibit favourable interactions with SARS-CoV-2 proteins, suggesting their potential as therapeutic targets. These compounds demonstrated promising drug-like characteristics and safety profiles, indicating their suitability for further development as COVID-19-fighting medications.</p><p><strong>Discussion: </strong>The results indicate that medicinal plants and their bioactive substances hold significant potential for developing therapies against COVID-19. The ability of these organic substances to interact with key viral proteins and provide various therapeutic benefits highlights their potential as multi-functional treatment options. However, further research is necessary to confirm these findings and to understand the full scope of their therapeutic efficacy and safety in clinical settings.</p><p><strong>Conclusions: </strong>Medicinal plants and their phyto-constituents represent a promising avenue for developing effective treatments for COVID-19. The favourable interactions with SARS-CoV-2 proteins and the promising drug-like characteristics observed in this study suggest that these natural compounds could be integral in the fight against the COVID-19 pandemic. Further research and clinical trials are essential to fully validating their potential and translating these findings into practical medical applications.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036060","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}
引用次数: 0
New insight into the molecular mechanism of TCM Bufei Huoxue formula for chronic obstructive pulmonary disease based on network pharmacology and experimental verification. 基于网络药理学和实验验证的慢性阻塞性肺疾病中药不老藿香正气液分子机制新认识
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2024-08-21 DOI: 10.1093/jpp/rgae071
Yuanying Zhu, Shengyuan Hao, Yan Wu, Yuxian Lin, Xuecun Liu, Ting Luo, Yubing Zhou, Xin Yang, Hui Xu
{"title":"New insight into the molecular mechanism of TCM Bufei Huoxue formula for chronic obstructive pulmonary disease based on network pharmacology and experimental verification.","authors":"Yuanying Zhu, Shengyuan Hao, Yan Wu, Yuxian Lin, Xuecun Liu, Ting Luo, Yubing Zhou, Xin Yang, Hui Xu","doi":"10.1093/jpp/rgae071","DOIUrl":"https://doi.org/10.1093/jpp/rgae071","url":null,"abstract":"<p><strong>Objectives: </strong>To unveil the mechanism of the Bufei Huoxue formula (BHF) for chronic obstructive pulmonary disease (COPD) through integrated network pharmacology (NP) and experimental verification.</p><p><strong>Methods: </strong>LC-MS was first applied to the analysis of both in vitro and in vivo samples from BHF for chemical profiling. Then a ligand library was prepared for NP to reveal the mechanism of BHF against COPD. Finally, verification was performed using an animal model related to the results from the NP.</p><p><strong>Key findings: </strong>A ligand library containing 170 compounds from BHF was obtained, while 357 targets related to COPD were filtered to construct a PPI network. GO and KEGG analysis demonstrated that bavachin, paeoniflorin, and demethylation of formononetin were the major compounds for BHF against COPD, which mainly by regulating the PI3K/Akt pathway. The experiments proved that BHF could alleviate lung injury and attenuate the release of TNF-α and IL-6 in the lung and BALF in a dose-dependent manner. Western blot further demonstrated the down-regulated effect of BHF on p-PI3K.</p><p><strong>Conclusion: </strong>BHF provides a potent alternative for the treatment of COPD, and the mechanism is probably associated with regulating the PI3K/AKT pathway to alleviate inflammatory injury by bavachin, paeoniflorin, and demethylation of formononetin.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036061","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}
引用次数: 0
Mesenchymal stem cell-derived exosomal microRNA-367-3p mitigates lower limb ischemia/reperfusion injury in mouse skeletal muscle via EZH2 targeting. 间充质干细胞衍生的外泌体microRNA-367-3p通过EZH2靶向缓解小鼠骨骼肌下肢缺血再灌注损伤
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2024-08-13 DOI: 10.1093/jpp/rgae086
Huanhuan Sun, Jueqiong Wang, Wei Bi, Feng Zhang, Kai Zhang, Xitao Tian, Xiang Gao, Yanrong Zhang
{"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":null,"pages":null},"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}
引用次数: 0
Current treatments for oropharyngeal squamous cell carcinoma and the move towards molecular therapy. 口咽鳞状细胞癌的现有治疗方法以及分子疗法的发展。
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2024-08-13 DOI: 10.1093/jpp/rgae107
Mitra Elmi, Joshua H Dass, Crispin R Dass
{"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":"https://doi.org/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":null,"pages":null},"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}
引用次数: 0
Evaluating the protective effect of dapsone on experimental osteoarthritis models induced by MIA in male rats. 评估达索酮对 MIA 诱导的雄性大鼠实验性骨关节炎模型的保护作用。
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2024-08-03 DOI: 10.1093/jpp/rgae087
Kimia Nazari, Saereh Hosseindoost, Ahmad Reza Dehpour, Yasaman Kheirandish, Hamed Shafaroodi
{"title":"Evaluating the protective effect of dapsone on experimental osteoarthritis models induced by MIA in male rats.","authors":"Kimia Nazari, Saereh Hosseindoost, Ahmad Reza Dehpour, Yasaman Kheirandish, Hamed Shafaroodi","doi":"10.1093/jpp/rgae087","DOIUrl":"https://doi.org/10.1093/jpp/rgae087","url":null,"abstract":"<p><strong>Objectives: </strong>Osteoarthritis, a degenerative condition that results in significant morbidity, is typically managed with treatments aimed at symptom relief rather than addressing the underlying degeneration. Dapsone, recognized for its anti-inflammatory, antioxidant, antiexcitotoxic, and antiapoptotic properties, has demonstrated promising effects in various neurodegenerative diseases. This study explores the potential of dapsone to mitigate articular destruction, inflammation, and pain in rat models of osteoarthritis.</p><p><strong>Methods: </strong>Osteoarthritis was induced in rats by injecting MIA into the right knee joint. Dapsone was then administered intraperitoneally at 5, 10, or 20 mg/kg every 2 days for 2 weeks. Behavioural tests were done on days 0, 7, and 14. On day 14, the articular cartilage was histologically analysed using H&E staining. Serum levels of NF-kB, IL-1β, and TNF-α were evaluated by ELISA.</p><p><strong>Results: </strong>Dapsone effectively reduces pain, inflammation, and articular cartilage damage in osteoarthritis. Specifically, it improves mechanical allodynia and thermal hyperalgesia, reduces inflammatory markers (TNF-α, IL-1β, and NF-κB), and protects against cartilage destruction and chondrocyte loss, with the most significant effects at 20 mg/kg.</p><p><strong>Conclusions: </strong>Dapsone effectively prevents pain, inflammation, and cartilage damage in osteoarthritis rats, suggesting its potential as a therapeutic option for managing osteoarthritis.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889572","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}
引用次数: 0
Research progress on ethnobotany, phytochemistry, pharmacological action, and applications of Engelhardia roxburghiana Wall: a review. 关于 Engelhardia roxburghiana Wall 的民族植物学、植物化学、药理作用和应用的研究进展:综述。
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2024-08-02 DOI: 10.1093/jpp/rgae021
Yuxin Li, Wenxin Xia, Tingting Li, Yuanyuan Zhang, Wenjin Zhang, Jiahui Yue, Lulu Wang, Xiangdong Zhu, Xueyan Fu
{"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":null,"pages":null},"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}
引用次数: 0
GL-V9 synergizes with oxaliplatin of colorectal cancer via Wee1 degradation mediated by HSP90 inhibition. 通过抑制 HSP90 使 Wee1 降解,GL-V9 可与奥沙利铂协同治疗结直肠癌。
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2024-08-02 DOI: 10.1093/jpp/rgae060
Hongyu Chen, Fan Yang, Qianying Zhao, Hongzheng Wang, Mengyuan Zhu, Hui Li, Zheng Ge, Shuai Zhang, Qinglong Guo, Hui Hui
{"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":null,"pages":null},"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}
引用次数: 0
YiQi GuBen formula alleviates airway inflammation and airway remodeling in OVA-induced asthma mice through TLR4/NF-κB signaling pathway. 益气固本方通过TLR4/NF-κB信号通路减轻OVA诱导的哮喘小鼠的气道炎症和气道重塑。
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2024-08-02 DOI: 10.1093/jpp/rgae064
Yibu Kong, Zhongtian Wang, Hongjun Yu, Aiai Dong, Yongfu Song, Lei Guo, Jinpu Zhu, Liping Sun, Yinan Guo
{"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":null,"pages":null},"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}
引用次数: 0
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