Archives of Pharmacal Research最新文献_第8页

Exploring new histone deacetylase 6 inhibitors and their effects on reversing the α-tubulin deacetylation and cell morphology changes caused by methamphetamine 探索新的组蛋白脱乙酰酶6抑制剂及其逆转甲基苯丙胺引起的α-微管蛋白脱乙酰化和细胞形态变化的作用。

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2023-09-30 DOI: 10.1007/s12272-023-01467-w

Sunil K. Gupta, Khan Hashim Ali, Sooyeun Lee, Young Ho Seo

引用次数: 0

Artemongolins A–K, undescribed germacrane-guaiane sesquiterpenoid dimers from Artemisia mongolica and their antihepatoma activities 沙蒿中的Artemonglins A-K、未描述的germacrane guaiane倍半萜二聚体及其抗肝癌活性。

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2023-09-28 DOI: 10.1007/s12272-023-01466-x

Chong Shang, Yun-Bao Ma, Yuan Wang, Xiao-Feng He, Tian-Ze Li, Ji-Jun Chen

引用次数: 0

Anti-osteoporosis effects of triterpenoids from the fruit of sea buckthorn (Hippophae rhamnoides) through the promotion of osteoblast differentiation in mesenchymal stem cells, C3H10T1/2 沙棘果实中三萜类化合物通过促进间充质干细胞C3H10T1/2的成骨细胞分化而发挥的抗骨质疏松作用。

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2023-09-26 DOI: 10.1007/s12272-023-01468-9

Da Eun Lee, Kun Hee Park, Joo-Hyun Hong, Seon Hee Kim, Ki-Moon Park, Ki Hyun Kim

{"title":"Anti-osteoporosis effects of triterpenoids from the fruit of sea buckthorn (Hippophae rhamnoides) through the promotion of osteoblast differentiation in mesenchymal stem cells, C3H10T1/2","authors":"Da Eun Lee, Kun Hee Park, Joo-Hyun Hong, Seon Hee Kim, Ki-Moon Park, Ki Hyun Kim","doi":"10.1007/s12272-023-01468-9","DOIUrl":"10.1007/s12272-023-01468-9","url":null,"abstract":"<div><p>In a previous study, we discovered that the ethanolic extract of sea buckthorn (<i>Hippophae rhamnoides</i>) fruits exhibited anti-osteoporosis effects both in vitro and in vivo. Through bioassay-guided fractionation, we identified the hexane fraction (HRH) as the active fraction, which was further fractionated using preparative HPLC. Among the resulting six fractions, HRHF4 showed significant activity. In the present study, we focused on the bioassay-guided isolation of bioactive compounds from the HRHF4 fraction. We successfully identified the active HRHF43 fraction, which led us to the isolation of potential bioactive compounds (<b>1–6</b>). The chemical structures of these compounds were determined using NMR data, LC-MS analysis, and HR-ESI-MS data as four triterpenes, ursolic acid (<b>1</b>), uvaol (<b>2</b>), oleanolic aldehyde (<b>3</b>), and ursolic aldehyde (<b>4</b>), together with two fatty acids, methyl linoleate (<b>5</b>) and ethyl oleate (<b>6</b>). To evaluate the efficacy of promoting osteoblast differentiation and the expression of mRNA biomarkers related to osteogenesis, we tested the isolated compounds in the mouse mesenchymal stem cell line, C3H10T1/2. Alkaline phosphate staining demonstrated that triterpenes (<b>1–4</b>) displayed osteogenic activity. Particularly noteworthy, ursolic aldehyde (<b>4</b>) exhibited the most potent effect, showing an 11.2-fold higher activity at a concentration of 10 μg/mL compared to the negative control. Moreover, ursolic aldehyde (<b>4</b>) upregulated the gene expression of bone formation-related biomarkers, including Runx2, Osterix, Alp, and Osteopontin. These findings suggest that the fruit extract of <i>H. rhamnoides</i> may have potential as a nutraceutical for promoting bone health, with ursolic aldehyde (<b>4</b>) identified as an active constituent.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 9-10","pages":"771 - 781"},"PeriodicalIF":6.7,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41112552","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}

引用次数: 0

Multifaceted roles of mitochondrial dysfunction in diseases: from powerhouses to saboteurs 线粒体功能障碍在疾病中的多方面作用：从权力机构到破坏者。

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2023-09-26 DOI: 10.1007/s12272-023-01465-y

Surapriya Surendranath Prabhu, Aathira Sujathan Nair, Saiprabha Vijayakumar Nirmala

{"title":"Multifaceted roles of mitochondrial dysfunction in diseases: from powerhouses to saboteurs","authors":"Surapriya Surendranath Prabhu, Aathira Sujathan Nair, Saiprabha Vijayakumar Nirmala","doi":"10.1007/s12272-023-01465-y","DOIUrl":"10.1007/s12272-023-01465-y","url":null,"abstract":"<div><p>The fact that mitochondria play a crucial part in energy generation has led to the nickname “powerhouses” of the cell being applied to them. They also play a significant role in many other cellular functions, including calcium signalling, apoptosis, and the creation of vital biomolecules. As a result, cellular function and health as a whole can be significantly impacted by mitochondrial malfunction. Indeed, malignancies frequently have increased levels of mitochondrial biogenesis and quality control. Adverse selection exists for harmful mitochondrial genome mutations, even though certain malignancies include modifications in the nuclear-encoded tricarboxylic acid cycle enzymes that generate carcinogenic metabolites. Since rare human cancers with mutated mitochondrial genomes are often benign, removing mitochondrial DNA reduces carcinogenesis. Therefore, targeting mitochondria offers therapeutic options since they serve several functions and are crucial to developing malignant tumors. Here, we discuss the various steps involved in the mechanism of cancer for which mitochondria plays a significant role, as well as the role of mitochondria in diseases other than cancer. It is crucial to understand mitochondrial malfunction to target these organelles for therapeutic reasons. This highlights the significance of investigating mitochondrial dysfunction in cancer and other disease research.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 9-10","pages":"723 - 743"},"PeriodicalIF":6.7,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41096445","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}

引用次数: 0

Review on pharmacological effects of gastrodin 天麻素药理作用研究进展。

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2023-09-25 DOI: 10.1007/s12272-023-01463-0

Guirong Xiao, Rong Tang, Nan Yang, Yanhua Chen

引用次数: 0

Hyperoside attenuates pyrrolizidine alkaloids-induced liver injury by ameliorating TFEB-mediated mitochondrial dysfunction 金丝桃苷通过改善TFEB介导的线粒体功能障碍来减轻吡咯烷酮生物碱诱导的肝损伤。

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2023-09-21 DOI: 10.1007/s12272-023-01460-3

Jie Xu, Aizhen Xiong, Xunjiang Wang, Xing Yan, Yilin Chen, Xuanling Ye, Zhengtao Wang, Lili Ding, Li Yang

{"title":"Hyperoside attenuates pyrrolizidine alkaloids-induced liver injury by ameliorating TFEB-mediated mitochondrial dysfunction","authors":"Jie Xu, Aizhen Xiong, Xunjiang Wang, Xing Yan, Yilin Chen, Xuanling Ye, Zhengtao Wang, Lili Ding, Li Yang","doi":"10.1007/s12272-023-01460-3","DOIUrl":"10.1007/s12272-023-01460-3","url":null,"abstract":"<div><p>Pyrrolizidine alkaloids (PAs) are potent hepatotoxins that can cause liver damage. Hyperoside (Hyp), a natural flavonoid, can be extracted from medicinal plants. Hyp displays hepatoprotective activity in various liver diseases. However, the potential effect and mechanism of action of Hyp in ameliorating PA-induced liver injury remain obscure. This study aimed to explore the protective effect of Hyp against PA-induced hepatotoxicity and its underlying mechanism. We established an in vitro model of PAs in mouse primary hepatocytes and developed a mouse model of acute PA toxicity to investigate the protective effect of Hyp. We found that Hyp notably attenuated PA-induced hepatotoxicity. RNA-sequencing showed that the beneficial effect of Hyp against PA-induced hepatotoxicity was associated with the transcription factor EB (TFEB)-peroxisome proliferator-activated receptor-γ coactivator-1-α (PGC1α) pathway. Our results confirmed that both the autophagy-lysosomal pathway and mitochondrial biogenesis were induced by Hyp through TFEB nuclear translocation in PA-induced liver injury. Furthermore, we demonstrated that activation of the mechanistic target of rapamycin complex 1 (mTORC1) by MHY 1485 decreased TFEB nuclear translocation and abrogated the protective effect of Hyp against PA-induced liver injury in mice. In contrast, inhibition of mTORC1 activity increased the level of TFEB and reduced hepatotoxicity induced by PAs in mouse livers. Likewise, Hyp-induced TFEB activation was validated in vitro. In conclusion, Hyp can activate the TFEB-mediated autophagy-lysosomal pathway and mitochondrial biogenesis through inhibition of mTORC1 activity, alleviating the liver injury induced by PAs, thus suggesting the potential value of Hyp in the treatment of PA-induced hepatotoxicity.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 8","pages":"694 - 712"},"PeriodicalIF":6.7,"publicationDate":"2023-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41102997","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}

引用次数: 1

Androgen receptor and hyaluronan-mediated motility receptor as new molecular targets of baicalein: new molecular mechanisms for its anticancer properties 雄激素受体和透明质酸介导的运动受体作为黄芩素的新分子靶标：其抗癌特性的新分子机制。

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2023-09-10 DOI: 10.1007/s12272-023-01461-2

Mingyue Jiang, Suman Poudel, Kyung Song

{"title":"Androgen receptor and hyaluronan-mediated motility receptor as new molecular targets of baicalein: new molecular mechanisms for its anticancer properties","authors":"Mingyue Jiang, Suman Poudel, Kyung Song","doi":"10.1007/s12272-023-01461-2","DOIUrl":"10.1007/s12272-023-01461-2","url":null,"abstract":"<div><p>Natural compounds known as phytochemicals have served as valuable resources for the development of new anti-cancer drugs and treatment of malignancies. Among these phytochemicals, baicalein is an emerging anti-tumor flavonoid obtained from <i>Scutellaria baicaleinsis</i> (Lamiaceae), but its underlying mechanisms of action and molecular targets have not yet been completely elucidated. Here, we identified new mechanisms for the anti-tumor activities of baicalein, providing evidence that hyaluronan-mediated motility receptor (HMMR) and androgen receptor (AR) are new molecular targets of baicalein in human cancer cells. We observed that HMMR, known to be highly associated with poor prognosis in a wide range of human cancers, was substantially downregulated by baicalein at mRNA and protein levels. Reporter assays further revealed that the suppression of HMMR by baicalein might occur through a transcriptional regulatory mechanism with the participation of Egr-1, E2F3α, and serum response factor (SRF). We also found that baicalein significantly inhibits androgenic responses in hormone-responsive prostate cancer cells, indicating that this might be attributed to the downregulation of AR promoter activity by baicalein. Additionally, baicalein markedly induced the expression of tumor suppressive miR-30C, which might be partly involved in baicalein-mediated autophagy and anti-cancer effects. Overall, our study sheds light on new diverse mechanisms of the anti-cancer effects exhibited by baicalein, implying that baicalein could be a potential therapeutic agent against human cancers and function as an inhibitor of HMMR and AR.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 8","pages":"679 - 693"},"PeriodicalIF":6.7,"publicationDate":"2023-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10199766","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}

引用次数: 0

Stabilization of RNA G-quadruplexes in the SARS-CoV-2 genome inhibits viral infection via translational suppression SARS-CoV-2基因组中RNA g -四联体的稳定通过翻译抑制抑制病毒感染

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2023-08-10 DOI: 10.1007/s12272-023-01458-x

Maria Razzaq, Ji Ho Han, Subramaniyam Ravichandran, Jaehyun Kim, Joon-Yong Bae, Man-Seong Park, Shrute Kannappan, Woo-Chang Chung, Jin-Hyun Ahn, Moon Jung Song, Kyeong Kyu Kim

{"title":"Stabilization of RNA G-quadruplexes in the SARS-CoV-2 genome inhibits viral infection via translational suppression","authors":"Maria Razzaq, Ji Ho Han, Subramaniyam Ravichandran, Jaehyun Kim, Joon-Yong Bae, Man-Seong Park, Shrute Kannappan, Woo-Chang Chung, Jin-Hyun Ahn, Moon Jung Song, Kyeong Kyu Kim","doi":"10.1007/s12272-023-01458-x","DOIUrl":"10.1007/s12272-023-01458-x","url":null,"abstract":"<div><p>The G-quadruplex (G4) formed in single-stranded DNAs or RNAs plays a key role in diverse biological processes and is considered as a potential antiviral target. In the genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 25 putative G4-forming sequences are predicted; however, the effects of G4-binding ligands on SARS-CoV-2 replication have not been studied in the context of viral infection. In this study, we investigated whether G4-ligands suppressed SARS-CoV-2 replication and whether their antiviral activity involved stabilization of viral RNA G4s and suppression of viral gene expression. We found that pyridostatin (PDS) suppressed viral gene expression and genome replication as effectively as the RNA polymerase inhibitor remdesivir. Biophysical analyses revealed that the 25 predicted G4s in the SARS-CoV-2 genome formed a parallel G4 structure. In particular, G4-644 and G4-3467 located in the 5′ region of ORF1a, formed a G4 structure that could be effectively stabilized by PDS. We also showed that PDS significantly suppressed translation of the reporter genes containing these G4s. Taken together, our results demonstrate that stabilization of RNA G4s by PDS in the SARS-CoV-2 genome inhibits viral infection via translational suppression, highlighting the therapeutic potential of G4-ligands in SARS-CoV-2 infection.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 7","pages":"598 - 615"},"PeriodicalIF":6.7,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10030493","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}

引用次数: 0

Ubiquitin–proteasome system as a target for anticancer treatment—an update 泛素-蛋白酶体系统作为抗癌治疗靶点的最新进展

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2023-08-05 DOI: 10.1007/s12272-023-01455-0

Yeon Jung Kim, Yeonjoo Lee, Hyungkyung Shin, SuA Hwang, Jinyoung Park, Eun Joo Song

{"title":"Ubiquitin–proteasome system as a target for anticancer treatment—an update","authors":"Yeon Jung Kim, Yeonjoo Lee, Hyungkyung Shin, SuA Hwang, Jinyoung Park, Eun Joo Song","doi":"10.1007/s12272-023-01455-0","DOIUrl":"10.1007/s12272-023-01455-0","url":null,"abstract":"<div><p>As the ubiquitin–proteasome system (UPS) regulates almost every biological process, the dysregulation or aberrant expression of the UPS components causes many pathological disorders, including cancers. To find a novel target for anticancer therapy, the UPS has been an active area of research since the FDA’s first approval of a proteasome inhibitor bortezomib in 2003 for treating multiple myeloma (MM). Here, we summarize newly described UPS components, including E3 ubiquitin ligases, deubiquitinases (DUBs), and immunoproteasome, whose malfunction leads to tumorigenesis and whose inhibitors have been investigated in clinical trials as anticancer therapy since 2020. We explain the mechanism and effects of several inhibitors in depth to better comprehend the advantages of targeting UPS components for cancer treatment. In addition, we describe attempts to overcome resistance and limited efficacy of some launched proteasome inhibitors, as well as an emerging PROTAC-based tool targeting UPS components for anticancer therapy. </p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 7","pages":"573 - 597"},"PeriodicalIF":6.7,"publicationDate":"2023-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01455-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10030468","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}

引用次数: 3

Myriocin suppresses tumor growth by modulating macrophage polarization and function through the PI3K/Akt/mTOR pathway 肉豆蔻素通过PI3K/Akt/mTOR通路调节巨噬细胞极化和功能，抑制肿瘤生长

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2023-07-19 DOI: 10.1007/s12272-023-01454-1

Hyeonha Jang, Uttam Ojha, Ji-Hak Jeong, Keun-Gyu Park, Shin Yup Lee, You Mie Lee

{"title":"Myriocin suppresses tumor growth by modulating macrophage polarization and function through the PI3K/Akt/mTOR pathway","authors":"Hyeonha Jang, Uttam Ojha, Ji-Hak Jeong, Keun-Gyu Park, Shin Yup Lee, 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}

引用次数: 0