Journal of Pharmacy and Pharmacology最新文献

{"title":"Alleviating vascular calcification with Bushen Huoxue formula in rats with chronic kidney disease by inhibiting the PTEN/PI3K/AKT signaling pathway through exosomal microRNA-32.","authors":"Xingyun Guo, Shiwei Liu, Xiaoyi Wu, Ronglu Yang, Qiuyue Ren, Yanyan Zhou, Kaifeng Shi, Lisha Yuan, Ning Zhang, Shiyi Liu","doi":"10.1093/jpp/rgae120","DOIUrl":"10.1093/jpp/rgae120","url":null,"abstract":"<p><strong>Background: </strong>Vascular calcification (VC) significantly raises cardiovascular mortality in chronic kidney disease (CKD) patients. VC is characterized by the phenotypic transformation of vascular smooth muscle cells (VSMCs) to osteoblast-like cells, mediated by exosomes derived from calcified VSMCs and the exosomal microRNAs (miRNA) which may trigger some signals to recipient VSMCs. Bushen Huoxue (BSHX) formula has demonstrated its clinical efficacy in CKD and its protective role in CKD-VC rats has also been observed. However, little is known about its underlying mechanism.</p><p><strong>Methods: </strong>To establish a VC model, aortic VSMCs from rats were induced to osteogenic differentiation by high-level phosphate (HP) in vitro. The expression of exosome and calcification makers were analyzed by western blot, including CD9, CD63, α-SMA, BMP-2, and Runx2, respectively. Differential expression of exosomal miRNAs in normal and HP-induced VSMCs were identified by using whole miRNA microarray technology. GO and KEGG analyses were performed to determine the significant enrichment of functions and signaling pathways in the target genes. In vivo, the CKD-VC rat model was established by administering adenine gavage combined with a high phosphorus diet. The rats were divided into normal control, model, low-dose BSHX, medium-dose BSHX, high-dose BSHX groups, and sevelamer groups. The blood biochemical parameters were measured. Renal histopathology and aortic calcification were observed. Western blot detected the levels of the calcification markers. Quantitative real-time PCR (qPCR) assay detected exosomal microRNA-32 (miR-32) mRNA expression in the aorta, the most differentially expressed exosomal miRNA previously identified. Phosphatase and tensin homolog located on chromosome ten (PTEN)/phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT) signaling pathway components were also tested by western blot.</p><p><strong>Results: </strong>Exosomal miRNA-32 and PI3K/AKT signaling pathways were highly differentially expressed between normal and HP-induced VSMCs. In vivo, BSHX improved blood biochemical parameters, renal histopathology, and aortic calcification in CKD-VC rats. BSHX increased the expression level of α-SMA and decreased the level of BMP-2 and Runx2. BSHX also lowered the expression level of exosomal miR-32 mRNA, enhanced PTEN expression, therefore, reduced p-PI3K and p-AKT levels in the aorta.</p><p><strong>Conclusion: </strong>BSHX alleviated VC in CKD rats by downregulating exosomal miR-32 expression in the aorta, thereby promoting PTEN expression and inhibiting the PI3K/AKT signaling pathway.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"550-563"},"PeriodicalIF":2.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502625","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":"Liposomal topical drug administration surpasses alternative methods in glaucoma therapeutics: a novel paradigm for enhanced treatment.","authors":"Nor Asyikin Nordin, Muhammad Zulfiqah Sadikan, Lidawani Lambuk, Sabarisah Hashim, Syahira Airuddin, Nur-Azida Mohd Nasir, Rohimah Mohamud, Jamal Ibrahim, Ramlah Kadir","doi":"10.1093/jpp/rgae129","DOIUrl":"10.1093/jpp/rgae129","url":null,"abstract":"<p><strong>Objectives: </strong>Glaucoma is a leading cause of permanent blindness. Despite therapeutic advancements, glaucoma management remains challenging due to limitations of conventional drug delivery, primarily topical eye drops, resulting in suboptimal outcomes and a global surge in cases. To address these issues, liposomal drug delivery has emerged as a promising approach.</p><p><strong>Key findings: </strong>This review explores the potential of liposomal-based medications, with a particular focus on topical administration as a superior alternative to enhance therapeutic efficacy and improve patient compliance compared to existing treatments. This writing delves into the therapeutic prospects of liposomal formulations across different administration routes, as evidenced by ongoing clinical trials. Additionally, critical aspects of liposomal production and market strategies are discussed herein.</p><p><strong>Summary: </strong>By overcoming ocular barriers and optimizing drug delivery, liposomal topical administration holds the key to significantly improving glaucoma treatment outcomes.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"475-491"},"PeriodicalIF":2.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695624","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":"GC-MS- and LC-TOF-MS/MS-based ginger volatile oil serum analysis and the potential mechanism of the anticancer effect of serum component citral on MCF-7 breast cancer cells.","authors":"Wenkai Zhang, Zhiyong Liu, Liming Luo, Lei Xu, Qiuting Ma, Shuai Huang, Tao Hong","doi":"10.1093/jpp/rgae116","DOIUrl":"10.1093/jpp/rgae116","url":null,"abstract":"<p><strong>Background: </strong>To explore the blood components of ginger volatile oil (GVO) after gastric perfusion in rats and its different metabolites from blank serum and the network pharmacological analysis and preliminary verification of the main components against breast cancer.</p><p><strong>Methods: </strong>A total of 20 male rats were randomly allocated to 10 control groups and 10 experimental groups. The administration group was given diluted GVO and the blank group was given the same amount of soybean oil (weigh 12 g of GVO diluted to 100 ml with soybean oil), the serum of rats in the given and blank groups was analyzed by gas chromatography-time-of-flight mass spectrometry, and the differential metabolites were screened and enriched, and the blood components were analyzed by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS).</p><p><strong>Results: </strong>A total of 34 different metabolites were screened, and 31 original components were identified. The content of citral in volatile oil and serum is high, and the pathway of action is also closely related to the results of network pharmacology. Cell experiments showed that both drug-containing serum and citral significantly inhibited the proliferation and lateral transfer ability of breast cancer MCF-7 cells in a concentration and time-dependent manner, flow cytometry was used to measure apoptosis, and the experimental results showed that the proportion of early and late apoptosis was significantly increased in each group compared with the control group, and the proportion of total apoptosis showed a certain concentration-dependent trend.</p><p><strong>Conclusions: </strong>A combination of serum metabolism, network pharmacology, and experiments was employed; this study offers a significant contribution to the clarification of the material basis and molecular mechanism of GVO- medicated serum against breast cancer.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"532-549"},"PeriodicalIF":2.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716344","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":"Inhaled exogenous thymosin beta 4 suppresses bleomycin-induced pulmonary fibrosis in mice via TGF-β1 signalling pathway.","authors":"Rui Yu, Shimeng Li, Li Chen, Enbo Hu, Dan Chai, Zhichao Liu, Qianyi Zhang, Yunyun Mao, Yanfang Zhai, Kai Li, Yanhong Liu, Xiaohe Li, Honggang Zhou, Cheng Yang, Junjie Xu","doi":"10.1093/jpp/rgae143","DOIUrl":"10.1093/jpp/rgae143","url":null,"abstract":"<p><strong>Objectives: </strong>Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fibrotic interstitial lung disease. The two drugs indicated for IPF have limited efficacy and there is an urgent need to develop new drugs. Thymosin β4 (Tβ4) is a natural endogenous repair factor whose antifibrotic effects have been reported. This study aimed to evaluate the effect of exogenous recombinant human thymosin beta 4 (rhTβ4) on pulmonary fibrosis.</p><p><strong>Methods: </strong>Pulmonary fibrosis was induced in mice with bleomycin, and rhTβ4 was administrated by nebulization following three strategies: early dosing, mid-term dosing, and late dosing. The rhTβ4 efficacy was assessed by hydroxyproline, lung function, and lung histopathology. In vitro, the effects of rhTβ4 on fibroblast and lung epithelial cell phenotypes, as well as the TGF-β1 pathway, were evaluated.</p><p><strong>Key findings: </strong>Aerosol administration of rhTβ4 could alleviate bleomycin-induced pulmonary fibrosis in mice at different stages of fibrosis. Studies conducted in vitro suggested that rhTβ4 could suppress lung fibroblasts from proliferating, migrating, and activation via regulating the TGF-β1 signalling pathway. In vitro, rhTβ4 also inhibited the epithelial-mesenchymal transition-like process of pulmonary epithelial cells.</p><p><strong>Conclusions: </strong>This study suggests that nebulized rhTβ4 is a potential treatment for IPF.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"582-592"},"PeriodicalIF":2.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695621","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":"Tiaogan Jiejiu Tongluo formula alleviates hepatic steatosis in NAFLD mice by regulating AMPK signaling pathway.","authors":"Yuting Lei, Lianping Wang, Linze Song, Jiajun Han, He Ma, Haoming Luo, Yan Ma, Dong Han","doi":"10.1093/jpp/rgaf005","DOIUrl":"10.1093/jpp/rgaf005","url":null,"abstract":"<p><strong>Objectives: </strong>Tiaogan Jiejiu Tongluo formula (TJTF) is a traditional Chinese medicine formula for liver disease. The purpose of this study was to explore the protective effects and mechanisms of TJTF on nonalcoholic fatty liver disease (NAFLD) mice.</p><p><strong>Methods: </strong>A NAFLD model of mice was established by a combination of a high-fat diet and CCL4 and then treated with TJTF. The damage to liver tissue was observed through histopathology, and the levels of AST, ALT, TG, TC, LDL-C, and HDL-C in the serum, as well as SOD, GSH, and MDA in the liver tissue were determined using biochemistry or ELISA kit. The expression of proteins related to the AMPK pathway was detected by western blotting.</p><p><strong>Results: </strong>Biochemical indicators and pathological examination showed that TJTF could enhance the antioxidant capacity of liver tissue and significantly reduce liver lipid deposition. In addition, TJTF significantly increased levels of LKB1 and p-AMPK, and decreased the levels of HMGCR, SREBP-1c, FAS, and ACC.</p><p><strong>Conclusion: </strong>TJTF can alleviate hepatic steatosis and effectively improve NAFLD by regulating AMPK signaling pathway in NAFLD mice.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"492-500"},"PeriodicalIF":2.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414475","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":"Activation of HSPA5 contributes to pazopanib-induced hepatotoxicity through l-ornithine metabolism pathway and endoplasmic reticulum stress.","authors":"Jian Chen, Tieming Zhu, Yaping Deng, Jinliang Chen, Guojun Jiang, Qiaojun He","doi":"10.1093/jpp/rgae130","DOIUrl":"10.1093/jpp/rgae130","url":null,"abstract":"<p><strong>Objectives: </strong>The clinical application of Pazopanib (Paz) is often accompanied by hepatotoxicity. However, the mechanisms of hepatic toxicity induced by pazopanib are not entirely clarified.</p><p><strong>Methods: </strong>Male C57BL/6J mice were treated with pazopanib every day for 2, 4, or 8 weeks. Transcriptomics and metabolomics analyses of liver tissues were performed. In vitro experiments were carried out to estimate cell viability, apoptosis, and autophagy in L02 cells after Paz treatment. We also examined apoptosis and autophagy-related genes under 4-PBA, l-ornithine, nor-NOHA treatments, and HSPA5 knockdown.</p><p><strong>Key findings: </strong>Repeated Paz treatment for 8 weeks resulted in more severe hypofunction of the liver in mice. Moreover, Paz treatment inhibited L02 cells cell viability in a dose-dependent manner. We also discovered activation of endoplasmic reticulum stress, apoptosis, and autophagy in Paz-treated L02 cells, as evidenced by the boosted expression of HSPA5, p-IRE1α, ATF4, ATF6, p-eIF2α, LC3, Beclin-1, and a decrease of phosphorylated PI3K, AKT, and mTOR levels. Moreover, 4-PBA, l-ornithine, and HSPA5 knockdown inhibited apoptosis and autophagy, while nor-NOHA weakened the effects of HSPA5 knockdown on apoptosis in Paz-treated L02 cells.</p><p><strong>Conclusions: </strong>In summary, our study revealed that Paz-induced liver toxicity is related to HSPA5 expression and l-ornithine metabolism pathway in mice.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"564-581"},"PeriodicalIF":2.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824285","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":"Brazilian red propolis synergistically with imipenem modulates immunological parameters and the bactericidal activity of human monocytes against methicillin-resistant Staphylococcus aureus (MRSA).","authors":"Nicolas Ripari, Mariana da Silva Honorio, Arthur Alves Sartori, Larissa Ragozo Cardoso de Oliveira, Jairo Kenupp Bastos, José Maurício Sforcin","doi":"10.1093/jpp/rgae135","DOIUrl":"10.1093/jpp/rgae135","url":null,"abstract":"<p><strong>Objectives: </strong>Propolis is a bee product found all over the globe and has a well-known antibacterial activity. Previous findings of our group revealed that the combination of Brazilian red propolis (BRP) with a lower concentration of imipenem (IPM) exerted a bactericidal action against methicillin-resistant Staphylococcus aureus (MRSA) in vitro. Here, we aimed at investigating the effects of BRP in combination or not with IPM on human monocytes to assess a possible immunomodulatory action.</p><p><strong>Methods: </strong>Monocyte metabolic activity was analysed by MTT assay, cytokine production (TNF-α, IL-1β, IL-6, IL-8, and IL-10) by ELISA, and the expression of cell markers (TLR-2, TLR-4, HLA-DR, and CD80) by flow cytometry. The bactericidal activity of monocytes over MRSA was determined by colony-forming units' count.</p><p><strong>Key findings: </strong>BRP alone or in combination with IPM exerted no cytotoxic effects on monocytes. BRP downregulated TLR-2 expression and inhibited TNF-α, IL-1β, and IL-6 production, while BRP + IPM stimulated these parameters. BPR alone or in combination increased the bactericidal activity similarly to LPS-activated monocytes.</p><p><strong>Conclusions: </strong>Data indicated the potential of BRP as an anti-inflammatory agent increasing the bactericidal activity of monocytes against MRSA. The combination of BRP + IPM exhibited a stimulatory profile that may be potentially useful in treating patients with MRSA infection.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"524-531"},"PeriodicalIF":2.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502626","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":"Capsaicin: pharmacological applications and prospects for drug designing.","authors":"Anshita Gupta, Renjil Joshi, Lokkanya Dewangan, Kamal Shah, Deependra Soni, Umesh K Patil, Nagendra Singh Chauhan","doi":"10.1093/jpp/rgae150","DOIUrl":"10.1093/jpp/rgae150","url":null,"abstract":"<p><strong>Objectives: </strong>A primary objective of this review is to summarize the evidence-based pharmacological applications of capsaicin, particularly its use to manage pain and treat various health conditions. A second goal of the review is to research how recent technological advances are improving the bioavailability and therapeutic index of capsaicin, as well as the development of novel capsaicin-mimetics that are able to enhance therapeutic responses in various human diseases.</p><p><strong>Methods: </strong>In the review, numerous human clinical trials and preclinical studies are examined to determine how effective, safe, and optimal dosages of capsaicin can be used in pain management and therapeutic applications. Furthermore, it discusses capsaicin's mechanisms of action, specifically its interactions with the transient receptor potential vanilloid 1 (TRPV1) channel. As a result of this review, the potential of nanotechnology systems for bypassing the limits of capsaicin's pungency is discussed. The review takes into account individual factors such as pain tolerance and skin sensitivity.</p><p><strong>Key findings: </strong>For topical applications, capsaicin is typically used in concentrations ranging from 0.025% to 0.1%, with higher concentrations being used under medical supervision for neuropathic pain. The formulation can come in the form of creams, gels, or patches, which provide sustained release over the course of time. A condition such as arthritis or neuropathy can be relieved with capsaicin as it depletes substance P from nerves. Neuropathy and osteoarthritis as well as musculoskeletal disorders have been treated successfully with this herbal medicine. A major mechanism through which capsaicin relieves pain is through activating TRPV1 channels, which induce calcium influx and neurotransmitter release. Additionally, it affects the transcription of genes related to pain modulation and inflammation, particularly when disease conditions or stress are present. There have been recent developments in technology to reduce capsaicin's pungency and improve its bioavailability, including nanotechnology.</p><p><strong>Conclusions: </strong>It is proven that capsaicin is effective in pain management as well as a variety of therapeutic conditions because of its ability to deplete substance P and desensitize nerve endings. Although capsaicin is highly pungent and associated with discomfort, advancements in delivery technologies and the development of capsaicin-mimetics promise improved therapeutic outcomes. There is a great deal of complexity in the pharmacological action of capsaicin due to its interaction with TRPV1 channels and its ability to affect gene transcription. There is a need for further research and development in order to optimize capsaicin's clinical applications and to enhance its therapeutic index in a variety of human diseases.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"459-474"},"PeriodicalIF":2.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807440","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":"In vitro antidiabetic activity of Treculia africana leaf extracts: identification of chlorogenic acid and α-mangostin.","authors":"Victorine Lorette Yimgang, Elisa Pangrazzi, Francine Medjiofack Djeujo, Yanick Kevin Dongmo Melogmo, Franklin Loïc Tchinda Taghu, Rufin Marie Toghueo Kouipou, Fabrice Fekam Boyom, Guglielmina Froldi","doi":"10.1093/jpp/rgaf003","DOIUrl":"10.1093/jpp/rgaf003","url":null,"abstract":"<p><strong>Objective: </strong>This research studied two extracts from Treculia africana leaves for their potential against hyperglycaemia-related disorders.</p><p><strong>Methods: </strong>The influence of the extracts on α-glucosidase activity and albumin glycation was investigated, and cell viability was estimated in HT-29 human colorectal cells. Phenolic and flavonoid contents and antiradical activity were also detected. The extracts were examined using HPLC-DAD analysis.</p><p><strong>Key findings: </strong>The methanol and dichloromethane leaf extracts showed a significant concentration-dependent inhibition of α-glucosidase activity (IC50= 3.73 and 21.28 µg/ml, respectively). Both extracts also inhibited ribose-induced glycation of bovine serum albumin from 250 µg/ml. Phytochemical analysis revealed the presence of chlorogenic acid and α-mangostin in the extracts. The extracts did not change HT-29 cell viability up to 250 µg/ml, thus showing very low cytotoxicity.</p><p><strong>Conclusions: </strong>The methanol leaf extract of T. africana inhibited α-glucosidase activity in a concentration-dependent manner, supporting the use of the leaves in traditional medicine to control hyperglycaemia. Chlorogenic acid and α-mangostin, the latter identified for the first time in this species, were found in the T. africana leaves. Further, in vivo studies and pilot clinical trials should be conducted using standardized T. africana leaf extracts to evaluate their potential effectiveness in diabetes mellitus.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"501-510"},"PeriodicalIF":2.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414466","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":"Mechanism of Guishao Yigong decoction in treating colorectal cancer based on network pharmacology and experimental validation.","authors":"Yuwen Fan, Quyi Wang, Yun Zhang, Yu Wang, Wenwen Li, Shu Jiang, Ji-Nao Duan","doi":"10.1093/jpp/rgae045","DOIUrl":"10.1093/jpp/rgae045","url":null,"abstract":"<p><strong>Objectives: </strong>To explore the effective components of Guishao Yigong decoction (GYD) in the treatment of colorectal cancer and reveal its potential mechanism of action.</p><p><strong>Methods: </strong>Through network pharmacology, the main target and signaling pathway of GYD therapy for colorectal cancer (CRC) were found. Subsequently, the effect of GYD was verified by in vitro cell viability measurements, colony formation, and scratch healing tests. The effects of GYD on metabolic pathways in vivo were found through plasma metabolomics. Finally, flow cytometry and qPCR experiments were used to verify the cycle-blocking effect of GYD on CRC cells.</p><p><strong>Key findings: </strong>Based on the network pharmacological analysis and molecular docking technology, it was found that GYD could restrain the growth of CRC cells by affecting lipid metabolic pathways and mitogen-activated protein kinase (MAPK) signaling pathways. A series of cell experiments showed that GYD could inhibit the proliferation, migration and clonogenic ability of CRC cells. Furthermore, the plasma metabolomics results showed that GYD could affect the production of unsaturated fatty acids in mice. Flow cytometry and qPCR experiments further proved that GYD blocked the CRC cells in the G1 phase and modulated the expression of cell cycle-related targets, such as AKT, TP53, CDKN1A, and CDK2.</p><p><strong>Conclusions: </strong>All the results indicated that GYD could regulate the related metabolism of unsaturated fatty acids. Thus, the cell cycle was blocked and the expressions of the key proteins such as AKT and TP53 were regulated, which achieved the purpose of intervention in colorectal cancer.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"430-445"},"PeriodicalIF":2.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348962","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}