Archives of Pharmacal Research最新文献

{"title":"Ionically bridged dexamethasone sodium phosphate–zinc–PLGA nanocomplex in alginate microgel for the local treatment of ulcerative colitis","authors":"Aruzhan Saparbayeva,&nbsp;Juho Lee,&nbsp;Shwe Phyu Hlaing,&nbsp;Jihyun Kim,&nbsp;Dongmin Kwak,&nbsp;Hyunwoo Kim,&nbsp;Eun Hee Lee,&nbsp;Seonghwan Hwang,&nbsp;Min-Soo Kim,&nbsp;Hyung Ryong Moon,&nbsp;Yunjin Jung,&nbsp;Jin-Wook Yoo","doi":"10.1007/s12272-023-01456-z","DOIUrl":"10.1007/s12272-023-01456-z","url":null,"abstract":"<div><p>Colon-targeted oral drug delivery systems comprising nanoparticles and microparticles have emerged as promising tools for the treatment of ulcerative colitis (UC) because they minimize side effects and maximize the local drug concentration. Dexamethasone sodium phosphate (DSP) is a potent anti-inflammatory glucocorticoid used for the treatment of UC. However, it remains a rather short-term treatment option owing to its side effects. In the present study, we developed the alginate gel encapsulating ionically bridged DSP-zinc-poly(lactic-co-glycolic acid) (PLGA) nanocomplex (DZP-NCs-in-microgel) for the oral local treatment of UC. The successful encapsulation of DSP-zinc-PLGA nanocomplex (DZP-NCs) in alginate microgel was confirmed by SEM imaging. The prepared gel released DZP-NCs in the stimulated intestinal fluid and dampened the release of DSP in the upper gastrointestinal tract. Furthermore, DZP-NCs-in-microgel alleviated colonic inflammation in a mouse model of dextran sodium sulfate-induced colitis by relieving clinical symptoms and histological marks. Our results suggest a novel approach for the oral colon-targeted delivery of dexamethasone sodium phosphate for the treatment of UC.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 7","pages":"646 - 658"},"PeriodicalIF":6.7,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01456-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10030785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myriocin suppresses tumor growth by modulating macrophage polarization and function through the PI3K/Akt/mTOR pathway","authors":"Hyeonha Jang,&nbsp;Uttam Ojha,&nbsp;Ji-Hak Jeong,&nbsp;Keun-Gyu Park,&nbsp;Shin Yup Lee,&nbsp;You Mie Lee","doi":"10.1007/s12272-023-01454-1","DOIUrl":"10.1007/s12272-023-01454-1","url":null,"abstract":"<div><p>Macrophages within the tumor microenvironment (TME), referred to as tumor-associated macrophages (TAMs), are involved in various aspects of tumor progression including initiation, angiogenesis, metastasis, immunosuppression, and resistance to therapy. Myriocin, a natural compound isolated from <i>Mycelia sterilia</i>, is an immunosuppressant that inhibits tumor growth and angiogenesis. However, the mechanisms underlying the effects of myriocin on TAMs and TAM-mediated tumor growth have not yet been elucidated. In this study, we determined the effects of myriocin on TAMs and the underlying mechanism in vitro and in vivo. Myriocin significantly suppressed monocyte–macrophage differentiation and M2 polarization of macrophages but not M1 polarization. In addition, myriocin inhibited the expression of anti-inflammatory cytokines and secretion of proangiogenic factors, such as vascular endothelial growth factor, in M2 macrophages as well as M2-induced endothelial cell permeability. Myriocin also inhibited the PI3K/Akt/mTOR signaling pathway in M2 macrophages. Myriocin reduced the population of M2-like TAMs within the tumor tissue of a mouse allograft tumor model but not that of M1-like TAMs. Moreover, combined treatment with myriocin and cisplatin synergistically suppressed tumor growth and enhanced survival rate in mice by reducing the population of M2-like TAMs. Overall, these results suggest that myriocin inhibits tumor growth by remodeling the TME through suppression of differentiation and polarization of M2-like TAMs via the PI3K/Akt/mTOR signaling pathway.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 7","pages":"629 - 645"},"PeriodicalIF":6.7,"publicationDate":"2023-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01454-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10030739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances on Pestalotiopsis genus: chemistry, biological activities, structure–activity relationship, and biosynthesis","authors":"Peng Jiang,&nbsp;Xiujuan Fu,&nbsp;Hong Niu,&nbsp;Siwei Chen,&nbsp;Feifei Liu,&nbsp;Yu Luo,&nbsp;Dan Zhang,&nbsp;Hui Lei","doi":"10.1007/s12272-023-01453-2","DOIUrl":"10.1007/s12272-023-01453-2","url":null,"abstract":"<div><p>Strains of the fungal genus <i>Pestalotiopsis</i> are reported as large promising sources of structurally varied biologically active metabolites. Many bioactive secondary metabolites with diverse structural features have been derived from <i>Pestalotiopsis</i>. Moreover, some of these compounds can potentially be developed into lead compounds. Herein, we have systematically reviewed the chemical constituents and bioactivities of the fungal genus <i>Pestalotiopsis</i>, covering a period ranging from January 2016 to December 2022. As many as 307 compounds, including terpenoids, coumarins, lactones, polyketides, and alkaloids, were isolated during this period. Furthermore, for the benefit of readers, the biosynthesis and potential medicinal value of these new compounds are also discussed in this review. Finally, the perspectives and directions for future research and the potential applications of the new compounds are summarized in various tables.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 6","pages":"449 - 499"},"PeriodicalIF":6.7,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01453-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9856754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond DNA sensing: expanding the role of cGAS/STING in immunity and diseases","authors":"Jin Kyung Seok,&nbsp;Minhyuk Kim,&nbsp;Han Chang Kang,&nbsp;Yong-Yeon Cho,&nbsp;Hye Suk Lee,&nbsp;Joo Young Lee","doi":"10.1007/s12272-023-01452-3","DOIUrl":"10.1007/s12272-023-01452-3","url":null,"abstract":"<div><p>Cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) is a DNA sensor that elicits a robust type I interferon response by recognizing ubiquitous danger-associated molecules. The cGAS/stimulator of interferon genes (cGAS/STING) is activated by endogenous DNA, including DNA released from mitochondria and extranuclear chromatin, as well as exogenous DNA derived from pathogenic microorganisms. cGAS/STING is positioned as a key axis of autoimmunity, the inflammatory response, and cancer progression, suggesting that the cGAS/STING signaling pathway represents an efficient therapeutic target. Based on the accumulated evidence, we present insights into the prevention and treatment of cGAS/STING-related chronic immune and inflammatory diseases. This review presents the current state of clinical and nonclinical development of modulators targeting cGAS/STING, providing useful information on the design of therapeutic strategies.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 6","pages":"500 - 534"},"PeriodicalIF":6.7,"publicationDate":"2023-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01452-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9855801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paritaprevir ameliorates experimental acute lung injury in vitro and in vivo","authors":"Rui Ren,&nbsp;Xin Wang,&nbsp;Zehui Xu,&nbsp;Wanglin Jiang","doi":"10.1007/s12272-023-01451-4","DOIUrl":"10.1007/s12272-023-01451-4","url":null,"abstract":"<div><p>Paritaprevir is a potent inhibitor of the NS3/4A protease used to treat chronic hepatitis C virus infection. However, its therapeutic effect on acute lung injury (ALI) remains to be elucidated. In this study, we investigated the effect of paritaprevir on a lipopolysaccharide (LPS)-induced two-hit rat ALI model. The anti-ALI mechanism of paritaprevir was also studied in human pulmonary microvascular endothelial (HM) cells following LPS-induced injury in <i>vitro</i>. Administration of 30 mg/kg paritaprevir for 3 days protected rats from LPS-induced ALI, as reflected by the changes in the lung coefficient (from 0.75 to 0.64) and lung pathology scores (from 5.17 to 5.20). Furthermore, the levels of the protective adhesion protein VE-cadherin and tight junction protein claudin-5 increased, and the cytoplasmic p-FOX-O1 and nuclear β-catenin and FOX-O1 levels decreased. Similar effects were observed in vitro with LPS-treated HM cells, including decreased nuclear β-catenin and FOX-O1 levels and higher VE-cadherin and claudin-5 levels. Moreover, β-catenin inhibition resulted in higher p-FOX-O1 levels in the cytoplasm. These results suggested that paritaprevir could alleviate experimental ALI via the β-catenin/p-Akt/ FOX-O1 signaling pathway.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 6","pages":"564 - 572"},"PeriodicalIF":6.7,"publicationDate":"2023-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01451-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9797082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing deep learning into hidden mutations of neurological disorders for therapeutic challenges","authors":"Sumin Yang,&nbsp;Sung-Hyun Kim,&nbsp;Mingon Kang,&nbsp;Jae-Yeol Joo","doi":"10.1007/s12272-023-01450-5","DOIUrl":"10.1007/s12272-023-01450-5","url":null,"abstract":"<div><p>The relevant study of transcriptome-wide variations and neurological disorders in the evolved field of genomic data science is on the rise. Deep learning has been highlighted utilizing algorithms on massive amounts of data in a human-like manner, and is expected to predict the dependency or druggability of hidden mutations within the genome. Enormous mutational variants in coding and noncoding transcripts have been discovered along the genome by far, despite of the fine-tuned genetic proofreading machinery. These variants could be capable of inducing various pathological conditions, including neurological disorders, which require lifelong care. Several limitations and questions emerge, including the use of conventional processes via limited patient-driven sequence acquisitions and decoding-based inferences as well as how rare variants can be deduced as a population-specific etiology. These puzzles require harnessing of advanced systems for precise disease prediction, drug development and drug applications. In this review, we summarize the pathophysiological discoveries of pathogenic variants in both coding and noncoding transcripts in neurological disorders, and the current advantage of deep learning applications. In addition, we discuss the challenges encountered and how to outperform them with advancing interpretation.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 6","pages":"535 - 549"},"PeriodicalIF":6.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9785968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in GPR35 pharmacology; 5-HIAA serotonin metabolite becomes a ligand","authors":"Dong-Soon Im","doi":"10.1007/s12272-023-01449-y","DOIUrl":"10.1007/s12272-023-01449-y","url":null,"abstract":"<div><p>GPR35, an orphan receptor, has been waiting for its ligand since its cloning in 1998. Many endogenous and exogenous molecules have been suggested to act as agonists of GPR35 including kynurenic acid, zaprinast, lysophosphatidic acid, and CXCL17. However, complex and controversial responses to ligands among species have become a huge hurdle in the development of therapeutics in addition to the orphan state. Recently, a serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), is reported to be a high potency ligand for GPR35 by investigating the increased expression of GPR35 in neutrophils. In addition, a transgenic knock-in mouse line is developed, in which GPR35 was replaced with a human ortholog, making it possible not only to overcome the different selectivity of agonists among species but also to conduct therapeutic experiments on human GPR35 in mouse models. In the present article, I review the recent advances and prospective therapeutic directions in GPR35 research. Especially, I’d like to draw attention of readers to the finding of 5-HIAA as a ligand of GPR35 and lead to apply the 5-HIAA and human GPR35 knock-in mice to their research fields in a variety of pathophysiological conditions.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 6","pages":"550 - 563"},"PeriodicalIF":6.7,"publicationDate":"2023-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9785380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of gliclazide in healthy subjects","authors":"Pureum Kang,&nbsp;Chang-Keun Cho,&nbsp;Choon-Gon Jang,&nbsp;Seok-Yong Lee,&nbsp;Yun Jeong Lee,&nbsp;Chang-Ik Choi,&nbsp;Jung-Woo Bae","doi":"10.1007/s12272-023-01448-z","DOIUrl":"10.1007/s12272-023-01448-z","url":null,"abstract":"<div><p>Gliclazide metabolism is mediated by genetically polymorphic CYP2C9 and CYP2C19 enzymes. We investigated the effects of <i>CYP2C9</i> and <i>CYP2C19</i> genetic polymorphisms on the pharmacokinetics and pharmacodynamics of gliclazide. Twenty-seven Korean healthy volunteers were administered a single oral dose of gliclazide 80 mg. The plasma concentration of gliclazide was quantified for the pharmacokinetic analysis and plasma concentrations of glucose and insulin were measured as pharmacodynamic parameters. The pharmacokinetics of gliclazide showed a significant difference according to the number of defective alleles of combined <i>CYP2C9</i> and <i>CYP2C19</i>. The two defective alleles group (group 3) and one defective allele group (group 2) showed 2.34- and 1.46-fold higher AUC_0–∞ (<i>P</i> &lt; 0.001), and 57.1 and 32.3% lower CL/F (<i>P</i> &lt; 0.001), compared to those of the no defective allele group (group 1), respectively. The <i>CYP2C9IM–</i><i>CYP2C19IM</i> group had AUC_0–∞ increase of 1.49-fold (<i>P</i> &lt; 0.05) and CL/F decrease by 29.9% (<i>P</i> &lt; 0.01), compared with the <i>CYP2C9 Normal Metabolizer</i> (<i>CYP2C9NM</i>)–<i>CYP2C19IM</i> group. The <i>CYP2C9NM–CYP2C19PM</i> group and <i>CYP2C9NM–CYP2C19IM</i> group showed 2.41- and 1.51-fold higher AUC_0–∞ (<i>P</i> &lt; 0.001), and 59.6 and 35.4% lower CL/F (<i>P</i> &lt; 0.001), compared to those of the <i>CYP2C9NM–CYP2C19NM</i> group, respectively. The results represented that <i>CYP2C9</i> and <i>CYP2C19</i> genetic polymorphisms significantly affected the pharmacokinetics of gliclazide. Although the genetic polymorphism of <i>CYP2C19</i> had a greater effect on the pharmacokinetics of gliclazide, the genetic polymorphism of <i>CYP2C9</i> also had a significant effect. On the other hand, plasma glucose and insulin responses to gliclazide were not significantly affected by the <i>CYP2C9–CYP2C19</i> genotypes, requiring further well-controlled studies with long-term dosing of gliclazide in diabetic patients.\u0000</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 5","pages":"438 - 447"},"PeriodicalIF":6.7,"publicationDate":"2023-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01448-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9423494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibody drug conjugates as targeted cancer therapy: past development, present challenges and future opportunities","authors":"Ritwik Maiti,&nbsp;Bhumika Patel,&nbsp;Nrupesh Patel,&nbsp;Mehul Patel,&nbsp;Alkesh Patel,&nbsp;Nirav Dhanesha","doi":"10.1007/s12272-023-01447-0","DOIUrl":"10.1007/s12272-023-01447-0","url":null,"abstract":"<div><p>Antibody drug conjugates (ADCs) are promising cancer therapeutics with minimal toxicity as compared to small cytotoxic molecules alone and have shown the evidence to overcome resistance against tumor and prevent relapse of cancer. The ADC has a potential to change the paradigm of cancer chemotherapeutic treatment. At present, 13 ADCs have been approved by USFDA for the treatment of various types of solid tumor and haematological malignancies. This review covers the three structural components of an ADC—antibody, linker, and cytotoxic payload—along with their respective structure, chemistry, mechanism of action, and influence on the activity of ADCs. It covers comprehensive insight on structural role of linker towards efficacy, stability &amp; toxicity of ADCs, different types of linkers &amp; various conjugation techniques. A brief overview of various analytical techniques used for the qualitative and quantitative analysis of ADC is summarized. The current challenges of ADCs, such as heterogeneity, bystander effect, protein aggregation, inefficient internalization or poor penetration into tumor cells, narrow therapeutic index, emergence of resistance, etc., are outlined along with recent advances and future opportunities for the development of more promising next-generation ADCs.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 5","pages":"361 - 388"},"PeriodicalIF":6.7,"publicationDate":"2023-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9772168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytochemistry and pharmacology of natural prenylated flavonoids","authors":"Hua-Wei Lv,&nbsp;Qiao-Liang Wang,&nbsp;Meng Luo,&nbsp;Meng-Di Zhu,&nbsp;Hui-Min Liang,&nbsp;Wen-Jing Li,&nbsp;Hai Cai,&nbsp;Zhong-Bo Zhou,&nbsp;Hong Wang,&nbsp;Sheng-Qiang Tong,&nbsp;Xing-Nuo Li","doi":"10.1007/s12272-023-01443-4","DOIUrl":"10.1007/s12272-023-01443-4","url":null,"abstract":"<div><p>Prenylated flavonoids are a special kind of flavonoid derivative possessing one or more prenyl groups in the parent nucleus of the flavonoid. The presence of the prenyl side chain enriched the structural diversity of flavonoids and increased their bioactivity and bioavailability. Prenylated flavonoids show a wide range of biological activities, such as anti-cancer, anti-inflammatory, neuroprotective, anti-diabetic, anti-obesity, cardioprotective effects, and anti-osteoclastogenic activities. In recent years, many compounds with significant activity have been discovered with the continuous excavation of the medicinal value of prenylated flavonoids, and have attracted the extensive attention of pharmacologists. This review summarizes recent progress on research into natural active prenylated flavonoids to promote new discoveries of their medicinal value.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 4","pages":"207 - 272"},"PeriodicalIF":6.7,"publicationDate":"2023-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01443-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9348366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}