Journal of Pharmacy and Pharmacology最新文献

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A prediction method for the individual serum concentration and therapeutic effect for optimizing adalimumab therapy in inflammatory bowel disease. 用于优化阿达木单抗治疗炎症性肠病的个体血清浓度和疗效预测方法。
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2024-07-15 DOI: 10.1093/jpp/rgae092
Koji Kimura, Atsushi Yoshida
{"title":"A prediction method for the individual serum concentration and therapeutic effect for optimizing adalimumab therapy in inflammatory bowel disease.","authors":"Koji Kimura, Atsushi Yoshida","doi":"10.1093/jpp/rgae092","DOIUrl":"https://doi.org/10.1093/jpp/rgae092","url":null,"abstract":"<p><strong>Objectives: </strong>Adalimumab (ADM) therapy is effective for inflammatory bowel disease (IBD), but a significant number of IBD patients lose response to ADM. Thus, it is crucial to devise methods to enhance ADM's effectiveness. This study introduces a strategy to predict individual serum concentrations and therapeutic effects to optimize ADM therapy for IBD during the induction phase.</p><p><strong>Methods: </strong>We predicted the individual serum concentration and therapeutic effect of ADM during the induction phase based on pharmacokinetic and pharmacodynamic (PK/PD) parameters calculated using the empirical Bayesian method. We then examined whether the predicted therapeutic effect, defined as clinical remission or treatment failure, matched the observed effect.</p><p><strong>Results: </strong>Data were obtained from 11 IBD patients. The therapeutic effect during maintenance therapy was successfully predicted at 40 of 47 time points. Moreover, the predicted effects at each patient's final time point matched the observed effects in 9 of the 11 patients.</p><p><strong>Conclusion: </strong>This is the inaugural report predicting the individual serum concentration and therapeutic effect of ADM using the Bayesian method and PK/PD modelling during the induction phase. This strategy may aid in optimizing ADM therapy for IBD.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620260","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
Pharmacological investigation of genistein for its therapeutic potential against nitroglycerin-induced migraine headache. 基因素对硝酸甘油引起的偏头痛的治疗潜力的药理研究。
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2024-07-15 DOI: 10.1093/jpp/rgae084
Qirrat Sajjad, Arif-Ullah Khan, Aslam Khan
{"title":"Pharmacological investigation of genistein for its therapeutic potential against nitroglycerin-induced migraine headache.","authors":"Qirrat Sajjad, Arif-Ullah Khan, Aslam Khan","doi":"10.1093/jpp/rgae084","DOIUrl":"https://doi.org/10.1093/jpp/rgae084","url":null,"abstract":"<p><strong>Objectives: </strong>Migraine, typically occurs on one side of the head, lasts for hours to days. Trigemino-vascular system (TVS) plays a vital role in pain generation, with neurogenic inflammation and oxidative stress playing key roles in its pathophysiology.</p><p><strong>Methods: </strong>This study aimed to investigate genistein's potential as anti-inflammatory and anti-oxidant agent in mitigating migraine pain. Genistein (20 and 50 mg/kg) was administered intraperitoneally (IP) to nitroglycerin (NTG; 10 mg/kg)-induced migraine model in rats. Behavioral analysis, antioxidant assay, immunohistochemistry (IHC), histopathological examination, ELISA, and RT-PCR were conducted to evaluate the antimigraine potential of genistein.</p><p><strong>Key findings: </strong>In-silico analysis showed genestien's ACE values of -4.8 to -9.2 Kcal/mol against selected protein targets. Genistein significantly reversed mechanical and thermal nociception, light phobicity, and head scratching; increased the intensities of GST, GSH, catalase; and down regulated lipid peroxidase (LPO) in cortex and trigeminal nucleus caudalis (TNC). It also reduced Nrf2, NF-kB, and IL6 expression, analyzed through IHC, improved histopathological features, and increased COX-2 and decreased PPAR-γ expressions, while RT-PCR analysis revealed increased PPAR-γ expressions in genistein-treated rats.</p><p><strong>Conclusion: </strong>Genistein exhibited potent antioxidant and anti-inflammatory properties in migraine treatment, acting through multifactorial mechanisms by modulating the expression of numerous proteins in the region cortex and TNC.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620261","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
Exploring the anxiolytic mechanism of Fructus gardeniae based on metabolomics, network pharmacology, and molecular docking. 基于代谢组学、网络药理学和分子对接,探索栀子的抗焦虑机制。
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2024-07-11 DOI: 10.1093/jpp/rgad102
Yue Tian, Fuli Yuan, Jiao Kong, Zhenshuang Yuan, Chunxue Jia, Hongqian Kui, Ziqiang Yin, Chuanxin Liu, Jianmei Huang
{"title":"Exploring the anxiolytic mechanism of Fructus gardeniae based on metabolomics, network pharmacology, and molecular docking.","authors":"Yue Tian, Fuli Yuan, Jiao Kong, Zhenshuang Yuan, Chunxue Jia, Hongqian Kui, Ziqiang Yin, Chuanxin Liu, Jianmei Huang","doi":"10.1093/jpp/rgad102","DOIUrl":"https://doi.org/10.1093/jpp/rgad102","url":null,"abstract":"<p><strong>Objective: </strong>To explore the effect and anxiolytic mechanism of a natural remedy called Fructus gardeniae (FG).</p><p><strong>Methods: </strong>The elevated-plus maze (EPM) test was used to confirm the anxiolytic effect of FG. The potential and anxiolytic components, targets, and route processes of FG were investigated using the network pharmacology method in conjunction with metabolomics and molecular docking technologies.</p><p><strong>Results: </strong>FG could greatly enhance the proportion of time and times of opening arms, according to the EPM data. As to the metabolomics findings, a total of 61 distinct metabolites were found, mainly involved in glycine, serine, and threonine metabolism as well as alanine, aspartate, and glutamate metabolism. The primary active ingredients of FG, nicotiflorin, jasminodiol, and crocetin, demonstrated substantial binding affinities with monoamine oxidase A (MAOA), monoamine oxidase A (ACHE), malate dehydrogenase 2 (MDH2), glutamate decarboxylase 2 (GAD2), glutamate decarboxylase 1 (GAD1), and nitric oxide synthase (NOS1), according to the findings of network pharmacology and molecular docking.</p><p><strong>Conclusion: </strong>FG exerts an anxiolytic action via targeting MAOA, ACHE, MDH2, GAD2, GAD1, and NOS1, and regulating the metabolism of glycine, serine, and threonine as well as alanine, aspartic acid, and glutamic acid.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590596","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
Protopanaxadiol prevents cisplatin-induced acute kidney injury by regulating ferroptosis. 原人参皂苷通过调节铁氧化防止顺铂引起的急性肾损伤
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2024-07-05 DOI: 10.1093/jpp/rgae050
Zeyu Song, Zhenyuan Li, Tao Pan, Teng Liu, Baifang Gong, Zhixia Wang, Ke Liu, Huaying Fan
{"title":"Protopanaxadiol prevents cisplatin-induced acute kidney injury by regulating ferroptosis.","authors":"Zeyu Song, Zhenyuan Li, Tao Pan, Teng Liu, Baifang Gong, Zhixia Wang, Ke Liu, Huaying Fan","doi":"10.1093/jpp/rgae050","DOIUrl":"10.1093/jpp/rgae050","url":null,"abstract":"<p><strong>Objectives: </strong>Acute kidney injury (AKI) caused by cisplatin (CDDP) is a complex, critical illness with no effective or specific treatment. The purpose of the study was to assess the protective effect of protopanaxadiol (PPD) on the kidneys in CDDP-induced AKI models and its possible mechanisms.</p><p><strong>Methods: </strong>In vitro, the protection of PPD was assessed in HK-2. KM mice were injected with CDDP to induce AKI models in vivo. The determination of blood urea nitrogen and serum creatinine (SCr) was performed, and pathological changes were examined by histopathological examination. Immunostaining and western blot analyses were used to analyze the expression levels of proteins.</p><p><strong>Results: </strong>PPD can increase the viability of HK-2 cells damaged by CDDP, improve cell morphology, and alleviate the symptoms of AKI in mice. In addition, PPD can down-regulate the protein expression of TRF and up-regulate the protein expression of Ferritin heavy chain, Glutathione peroxidase 4, and ferroptosis suppressor protein 1 reduce the iron content in cells and kidney tissues, and restore the antioxidant defense system.</p><p><strong>Conclusion: </strong>PPD has an inhibitory effect on cisplatin-induced nephrotoxicity, which may be related to the inhibition of ferroptosis by regulating iron metabolism and lipid peroxidation.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857339","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
Genipin improves obesity through promoting bile secretion and changing bile acids composition in diet-induced obese rats. 吉尼平通过促进胆汁分泌和改变饮食诱导肥胖大鼠的胆汁酸组成来改善肥胖。
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2024-07-05 DOI: 10.1093/jpp/rgae055
Lili Guan, Lei Zhang, Dezheng Gong, Pengcheng Li, Shengnan Zhu, Jiulan Tang, Man Du, Maokun Zhang, Yuan Zou
{"title":"Genipin improves obesity through promoting bile secretion and changing bile acids composition in diet-induced obese rats.","authors":"Lili Guan, Lei Zhang, Dezheng Gong, Pengcheng Li, Shengnan Zhu, Jiulan Tang, Man Du, Maokun Zhang, Yuan Zou","doi":"10.1093/jpp/rgae055","DOIUrl":"10.1093/jpp/rgae055","url":null,"abstract":"<p><strong>Objectives: </strong>Bile acids (BAs), as signaling molecules to regulate metabolism, have received considerable attention. Genipin is an iridoid compound extracted from Fructus Gradeniae, which has been shown to relieve adiposity and metabolic syndrome. Here, we investigated the mechanism of genipin counteracting obesity and its relationship with BAs signals in diet-induced obese (DIO) rats.</p><p><strong>Methods: </strong>The DIO rats were received intraperitoneal injections of genipin for 10 days. The body weight, visceral fat, lipid metabolism in the liver, thermogenic genes expressions in brown fat, BAs metabolism and signals, and key enzymes for BAs synthesis were determined.</p><p><strong>Key findings: </strong>Genipin inhibited fat synthesis and promoted lipolysis in the liver, and upregulated thermogenic gene expressions in brown adipose tissue of DIO rats. Genipin increased bile flow rate and upregulated the expressions of aquaporin 8 and the transporters of BAs in liver. Furthermore, genipin changed BAs composition by promoting alternative pathways and inhibiting classical pathways for BAs synthesis and upregulated the expressions of bile acid receptors synchronously.</p><p><strong>Conclusions: </strong>These results suggest that genipin ameliorate obesity through BAs-mediated signaling pathways.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140898503","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
Brusatol's anticancer activity and its molecular mechanism: a research update. Brusatol 的抗癌活性及其分子机制:最新研究进展。
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2024-07-05 DOI: 10.1093/jpp/rgae017
Wenyi Xi, Chenhui Zhao, Zeyu Wu, Tongtong Ye, Rui Zhao, Xiaochun Jiang, Shizhang Ling
{"title":"Brusatol's anticancer activity and its molecular mechanism: a research update.","authors":"Wenyi Xi, Chenhui Zhao, Zeyu Wu, Tongtong Ye, Rui Zhao, Xiaochun Jiang, Shizhang Ling","doi":"10.1093/jpp/rgae017","DOIUrl":"10.1093/jpp/rgae017","url":null,"abstract":"<p><strong>Objective: </strong>Brusatol (BT) is a quassinoid compound extracted from Brucea javanica that is a traditional Chinese herbal medicine. Brusatol possesses biological and medical activity, including antitumor, antileukemia, anti-inflammatory, antitrypanosomal, antimalarial, and antitobacco mosaic virus activity. To summarize and discuss the antitumor effects of BT and its mechanisms of actions, we compiled this review by combining the extensive relevant literature and our previous studies.</p><p><strong>Methods: </strong>We searched and retrieved the papers that reported the pharmacological effects of BT and the mechanism of BT antitumor activity from PubMed until July 2023.</p><p><strong>Key findings: </strong>Numerous studies have shown that BT is a unique nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor that acts on various signaling pathways and has good antitumor properties. Brusatol shows great potential in cancer therapy by inhibiting cell proliferation, blocking the cell cycle, promoting tumor cell differentiation, accelerating tumor cell apoptosis, inducing autophagy, suppressing angiogenesis, inhibiting tumor invasion and metastasis, and reversing multidrug resistance.</p><p><strong>Conclusion: </strong>This review summarizes recent updates on the antitumor activity and molecular mechanisms of BT and provides references for future development and clinical translation of BT and its derivatives as antitumor drugs.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139940139","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
LINC01572 promotes the malignant progression of lung adenocarcinoma by modulating p53 mediated by miRNA-338-5p/TTK axis. LINC01572 通过调节 miRNA-338-5p/TTK 轴介导的 p53 来促进肺腺癌的恶性进展。
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2024-07-05 DOI: 10.1093/jpp/rgad128
Shilan Liu, Xiao Liu, Qinghui Yang, Chunhua Zeng, Gang Hu, Bochen Ren
{"title":"LINC01572 promotes the malignant progression of lung adenocarcinoma by modulating p53 mediated by miRNA-338-5p/TTK axis.","authors":"Shilan Liu, Xiao Liu, Qinghui Yang, Chunhua Zeng, Gang Hu, Bochen Ren","doi":"10.1093/jpp/rgad128","DOIUrl":"10.1093/jpp/rgad128","url":null,"abstract":"<p><strong>Objectives: </strong>Lung cancer is one of the malignant tumors that threaten human health seriously. Long non-coding RNA (lncRNA) is an important factor affecting tumorigenesis and development. However, the mechanism of lncRNA in lung cancer progression remains to be further explored.</p><p><strong>Methods: </strong>In this study, the TCGA database was analyzed, and LINC01572 was found to be increased in lung adenocarcinoma (LUAD) tissues. Thereafter, with the help of databases including lncBase, TargetScan, and mirDIP, as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, LINC01572/miRNA-338-5p/TTK regulatory axis and downstream p53 signaling pathway were excavated. qRT-PCR was adopted to detect levels of LINC01572, miRNA-338-5p, and TTK in LUAD cells. The role that LINC01572 played in LUAD cells was validated by CCK-8 assay, flow cytometry, colony formation, Transwell, and scratch healing assays. The binding ability between LINC01572/TTK and miRNA-338-5p was then verified by dual-luciferase and RIP analysis.</p><p><strong>Key findings: </strong>The results of this study demonstrated that LINC01572 was elevated in LUAD cells compared with normal cells. The overexpression of LINC01572 promoted the proliferative and migratory properties of LUAD cells but inhibited cell apoptosis. The inhibition of LINC01572 resulted in the opposite result. In addition, rescue experiments revealed that LINC01572, as a molecular sponge of miRNA-338-5p, targeted TTK to manipulate p53 for facilitating LUAD cell malignant progression. Apart from this, we constructed a mouse xenograft model and confirmed that the knockdown of LINC01572 hindered the growth of LUAD solid tumors in vivo.</p><p><strong>Conclusions: </strong>Our findings illuminated the molecular mechanism of LINC01572 influencing LUAD and provided new insights for targeted therapy of LUAD cells.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140850143","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
Phillyrin alleviates high glucose-induced oxidative stress and inflammation in HBZY-1 cells through inhibition of the PI3K/Akt signaling pathway. 菲利林通过抑制 PI3K/Akt 信号通路,减轻高葡萄糖诱导的 HBZY-1 细胞氧化应激和炎症反应。
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2024-07-05 DOI: 10.1093/jpp/rgae028
Chunjing Yang, Li Bao, Zhengyuan Shi, Xiqiao Xv, Dechun Jiang, Longtai You
{"title":"Phillyrin alleviates high glucose-induced oxidative stress and inflammation in HBZY-1 cells through inhibition of the PI3K/Akt signaling pathway.","authors":"Chunjing Yang, Li Bao, Zhengyuan Shi, Xiqiao Xv, Dechun Jiang, Longtai You","doi":"10.1093/jpp/rgae028","DOIUrl":"10.1093/jpp/rgae028","url":null,"abstract":"<p><strong>Background: </strong>Phillyrin, the major lignin compound of Forsythia suspense (Thunb.) Vahl, has been shown the effects of anti-inflammatory and antioxidant. Our study was aimed to explore the protective effect of phillyrin on glomerular mesangial cells (HBZY-1) and the potential mechanism.</p><p><strong>Methods: </strong>Cell viability, cytokine production, levels of reactive oxygen radicals (ROS), glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD), as well as autophagy and apoptosis levels were determined to verify the mechanism of phillyrin on HBZY-1 cells.</p><p><strong>Results: </strong>Our result indicated that phillyrin significantly inhibited HG-induced HBZY-1 proliferation by inhibiting Bcl-2 expression and upregulating Bad, cleaved caspase-3, and -9 expression. Also, phillyrin suppressed HG-induced mesangial extracellular matrix accumulation by inhibiting the expression of fibronectin and transforming growth factor-β1. Further, phillyrin inhibited oxidative stress and inflammation by decreasing ROS, MDA, TNF-α, IL-1β, and IL-6 contents and increasing SOD and GSH expression. Phillyrin also promoted autophagy by increasing LC3-II/LC3-I ratio and down-regulating p62 expression. Furthermore, WB assay showed that phillyrin inhibited oxidative stress caused by HG via activating Nrf2 signaling pathway, while attenuated proliferation and inflammation in HBZY-1 cells through inactivating PI3K/Akt/mTOR and NF-κB pathways.</p><p><strong>Conclusion: </strong>All results showed that phillyrin might be a promising therapeutic agent for the treatment of DN.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140175117","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
FoxO1 as the critical target of puerarin to inhibit osteoclastogenesis and bone resorption. FoxO1 是葛根素抑制破骨细胞生成和骨吸收的关键靶点。
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2024-07-05 DOI: 10.1093/jpp/rgae033
Yanling Feng, Xulei Tang
{"title":"FoxO1 as the critical target of puerarin to inhibit osteoclastogenesis and bone resorption.","authors":"Yanling Feng, Xulei Tang","doi":"10.1093/jpp/rgae033","DOIUrl":"10.1093/jpp/rgae033","url":null,"abstract":"<p><strong>Background: </strong>Elevated reactive oxygen species levels promote excessive osteoclastogenesis and bone resorption. Puerarin, a natural antioxidant, can prevent bone loss through its antioxidant effects; however, the underlying molecular mechanism remains unclear. This study aimed to explore the effects of puerarin on osteoclast differentiation and bone resorption by regulating the PI3K/AKT/FoxO1 signaling pathway.</p><p><strong>Materials and methods: </strong>An ovariectomized (OVX) rat model of osteoporosis and H2O2-induced oxidative cell model of RAW 264.7 cells were established. The following indices were measured including bone μ-CT scanning and the protein expression levels of FoxO1, p-FoxO1, and catalase were detected using western blotting.</p><p><strong>Results: </strong>Puerarin strongly alleviated oxidative stress-induced bone loss in OVX rats in vivo owing to its antioxidant effects. Puerarin improved the oxidative stress status of cells and inhibited osteoclast formation in vitro. Moreover, the protein expression of FoxO1 and its downstream target, catalase, was upregulated by puerarin.</p><p><strong>Conclusions: </strong>Puerarin improved the OPG/RANKL ratio, upregulated the protein expression and transcriptional activity of FoxO1, and suppressed the differentiation of RAW264.7 cells into osteoclasts. FoxO1 is a pivotal target of puerarin to confer anti-osteoporosis effects.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140329906","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
Network pharmacology prediction and molecular docking-based strategy to explore the potential mechanism of Duhuo-Jisheng pair against osteoarthritis. 基于网络药理学预测和分子对接策略探索杜霍-济生配对抗骨关节炎的潜在机制
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2024-07-05 DOI: 10.1093/jpp/rgad117
Haiyang Kou, Jianbing Ma
{"title":"Network pharmacology prediction and molecular docking-based strategy to explore the potential mechanism of Duhuo-Jisheng pair against osteoarthritis.","authors":"Haiyang Kou, Jianbing Ma","doi":"10.1093/jpp/rgad117","DOIUrl":"10.1093/jpp/rgad117","url":null,"abstract":"<p><strong>Objective: </strong>The Duhuo-Jisheng pair is the ruling herb in Duhuo Jisheng decoction, which is a classic formula first recorded in the preparedness and urgency of the thousand jewels.</p><p><strong>Methods: </strong>We obtained the primary constituents of Duhuo-Jisheng and their associated protein targets from the TCMSP database. We constructed a composite target network using Cytoscape 3.9.1. To identify potential targets for the treatment of osteoarthritis (OA), we retrieved disease targets from OMIM and GeneCards databases and compared them with the composite targets. We imported the overlapping targets into the STRING database to construct a protein-protein interaction (PPI) network. We also conducted Gene ontology (GO) and KEGG enrichment analyses on the targets.</p><p><strong>Results: </strong>The component target network consisted of numerous nodes and edges. Notably, quercetin, ammidin, and β-sitosterol were identified as the compounds with high degrees. The PPI network identified tumour necrosis factor (TNF), TP53, and NOS2 as proteins with high degrees. The results of GO and KEGG analyses revealed that the signalling pathways used by DHQJD to treat OA included the NF-κB, PI3K-AKT, and TNF pathways.</p><p><strong>Conclusion: </strong>Our study provides insights into the effective components and potential molecular mechanisms of Duhuo-Jisheng in treating OA, thus serving as a reference for further basic research in this field.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139111034","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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