Archives of Pharmacal Research最新文献_第5页

Arsenic trioxide: applications, mechanisms of action, toxicity and rescue strategies to date 三氧化二砷：迄今为止的应用、作用机制、毒性和救治策略。

IF 6.9 3区医学

Archives of Pharmacal Research Pub Date : 2023-12-26 DOI: 10.1007/s12272-023-01481-y

Meng Yan, Hao Wang, Rui Wei, Wenwen Li

引用次数: 0

Physiologically based pharmacokinetic (PBPK) modeling to predict the pharmacokinetics of irbesartan in different CYP2C9 genotypes 基于生理学的药代动力学（PBPK）模型预测不同 CYP2C9 基因型的厄贝沙坦药代动力学

IF 6.9 3区医学

Archives of Pharmacal Research Pub Date : 2023-12-08 DOI: 10.1007/s12272-023-01472-z

Chang-Keun Cho, Pureum Kang, Choon-Gon Jang, Seok-Yong Lee, Yun Jeong Lee, Chang-Ik Choi

{"title":"Physiologically based pharmacokinetic (PBPK) modeling to predict the pharmacokinetics of irbesartan in different CYP2C9 genotypes","authors":"Chang-Keun Cho, Pureum Kang, Choon-Gon Jang, Seok-Yong Lee, Yun Jeong Lee, Chang-Ik Choi","doi":"10.1007/s12272-023-01472-z","DOIUrl":"10.1007/s12272-023-01472-z","url":null,"abstract":"<div><p>Irbesartan, a potent and selective angiotensin II type-1 (AT<sub>1</sub>) receptor blocker (ARB), is one of the representative medications for the treatment of hypertension. Cytochrome P450 (CYP) 2C9 is primarily involved in the oxidation of irbesartan. CYP2C9 is highly polymorphic, and genetic polymorphism of this enzyme is the leading cause of significant alterations in the pharmacokinetics of irbesartan. This study aimed to establish the physiologically based pharmacokinetic (PBPK) model to predict the pharmacokinetics of irbesartan in different <i>CYP2C9</i> genotypes. The irbesartan PBPK model was established using the PK-Sim<sup>®</sup> software. Our previously reported pharmacogenomic data for irbesartan was leveraged in the development of the PBPK model and collected clinical pharmacokinetic data for irbesartan was used for the validation of the model. Physicochemical and ADME properties of irbesartan were obtained from previously reported data, predicted by the modeling software, or optimized to fit the observed plasma concentration–time profiles. Model evaluation was performed by comparing the predicted plasma concentration–time profiles and pharmacokinetic parameters to the observed results. Predicted plasma concentration–time profiles were visually similar to observed profiles. Predicted AUC<sub>inf</sub> in <i>CYP2C9*1/*3</i> and <i>CYP2C9*1/*13</i> genotypes were increased by 1.54- and 1.62-fold compared to <i>CYP2C9*1/*1</i> genotype, respectively. All fold error values for AUC and C<sub>max</sub> in non-genotyped and <i>CYP2C9</i> genotyped models were within the two-fold error criterion. We properly established the PBPK model of irbesartan in different <i>CYP2C9</i> genotypes. It can be used to predict the pharmacokinetics of irbesartan for personalized pharmacotherapy in individuals of various races, ages, and <i>CYP2C9</i> genotypes.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138556746","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

Phytochemistry and pharmacology of plants in the genus Chaenomeles Chaenomeles属植物的植物化学和药理学

IF 6.9 3区医学

Archives of Pharmacal Research Pub Date : 2023-12-07 DOI: 10.1007/s12272-023-01475-w

Ruoling Xu, Mengting Kuang, Ning Li

{"title":"Phytochemistry and pharmacology of plants in the genus Chaenomeles","authors":"Ruoling Xu, Mengting Kuang, Ning Li","doi":"10.1007/s12272-023-01475-w","DOIUrl":"10.1007/s12272-023-01475-w","url":null,"abstract":"<div><p><i>Chaenomeles</i> plants belong to the <i>Rosaceae</i> family and include five species, <i>Chaenomeles speciosa</i> (Sweet) Nakai, <i>Chaenomeles sinensis</i> (Thouin) Koehne, <i>Chaenomeles japonica</i> (Thunb.) Lindl, <i>Chaenomeles cathayensis</i> (Hemsl.) Schneid and <i>Chaenomeles thibetica</i> Yu. <i>Chaenomeles</i> plants are found and cultivated in nearly every country worldwide. China serves as both the origin and distribution hub for the plants in the <i>Chaenomeles</i> genus, and all <i>Chaenomeles</i> species except for <i>C. japonica</i> are indigenous to China. <i>Chaenomeles</i> spp. is a type of edible medicinal plant that has been traditionally used in China to treat various ailments, such as rheumatism, cholera, dysentery, enteritis, beriberi, and scurvy. A variety of chemical constituents have been extracted from this genus, including terpenoids, phenolics, flavonoids, phenylpropanoids and their derivatives, benzoic acid derivatives, biphenyls, oxylipins, and alkaloids. The biological activity of some of these constituents has already been evaluated. Pharmacological investigations have demonstrated that the plants in the genus <i>Chaenomeles</i> exhibit anti-inflammatory, analgesic, antioxidant, antihyperglycemic, antihyperlipidemic, gastrointestinal protective, antitumor, immunomodulatory, antibacterial, antiviral, hepatoprotective, neuroprotective and other pharmacological activities. The objective of this review is to provide a comprehensive and up-to-date summary of the available information on the genus <i>Chaenomeles</i> to serve as a valuable reference for further investigations.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138556973","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

Targeting dysregulated lipid metabolism in the tumor microenvironment 靶向肿瘤微环境中脂质代谢失调。

IF 6.9 3区医学

Archives of Pharmacal Research Pub Date : 2023-12-07 DOI: 10.1007/s12272-023-01473-y

Do-Hee Kim, Na-Young Song, Hyungshin Yim

{"title":"Targeting dysregulated lipid metabolism in the tumor microenvironment","authors":"Do-Hee Kim, Na-Young Song, Hyungshin Yim","doi":"10.1007/s12272-023-01473-y","DOIUrl":"10.1007/s12272-023-01473-y","url":null,"abstract":"<div><p>The reprogramming of lipid metabolism and its association with oncogenic signaling pathways within the tumor microenvironment (TME) have emerged as significant hallmarks of cancer. Lipid metabolism is defined as a complex set of molecular processes including lipid uptake, synthesis, transport, and degradation. The dysregulation of lipid metabolism is affected by enzymes and signaling molecules directly or indirectly involved in the lipid metabolic process. Regulation of lipid metabolizing enzymes has been shown to modulate cancer development and to avoid resistance to anticancer drugs in tumors and the TME. Because of this, understanding the metabolic reprogramming associated with oncogenic progression is important to develop strategies for cancer treatment. Recent advances provide insight into fundamental mechanisms and the connections between altered lipid metabolism and tumorigenesis. In this review, we explore alterations to lipid metabolism and the pivotal factors driving lipid metabolic reprogramming, which exacerbate cancer progression. We also shed light on the latest insights and current therapeutic approaches based on small molecular inhibitors and phytochemicals targeting lipid metabolism for cancer treatment. Further investigations are worthwhile to fully understand the underlying mechanisms and the correlation between altered lipid metabolism and carcinogenesis.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10725365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138497686","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

Role of monocarboxylate transporter I/lactate dehydrogenase B-mediated lactate recycling in tamoxifen-resistant breast cancer cells 单羧酸转运体I/乳酸脱氢酶b介导的乳酸循环在他莫昔芬耐药乳腺癌细胞中的作用。

IF 6.9 3区医学

Archives of Pharmacal Research Pub Date : 2023-12-04 DOI: 10.1007/s12272-023-01474-x

Min Chang Choi, Sang Kyum Kim, Young Jae Choi, Yong June Choi, Suntae Kim, Kyung Hwan Jegal, Sung Chul Lim, Keon Wook Kang

{"title":"Role of monocarboxylate transporter I/lactate dehydrogenase B-mediated lactate recycling in tamoxifen-resistant breast cancer cells","authors":"Min Chang Choi, Sang Kyum Kim, Young Jae Choi, Yong June Choi, Suntae Kim, Kyung Hwan Jegal, Sung Chul Lim, Keon Wook Kang","doi":"10.1007/s12272-023-01474-x","DOIUrl":"10.1007/s12272-023-01474-x","url":null,"abstract":"<div><p>Although tamoxifen (TAM) is widely used in patients with estrogen receptor-positive breast cancer, the development of tamoxifen resistance is common. The previous finding suggests that the development of tamoxifen resistance is driven by epiregulin or hypoxia-inducible factor-1α-dependent glycolysis activation. Nonetheless, the mechanisms responsible for cancer cell survival and growth in a lactic acid-rich environment remain elusive. We found that the growth and survival of tamoxifen-resistant MCF-7 cells (TAMR-MCF-7) depend on glycolysis rather than oxidative phosphorylation. The levels of the glycolytic enzymes were higher in TAMR-MCF-7 cells than in parental MCF-7 cells, whereas the mitochondrial number and complex I level were decreased. Importantly, TAMR-MCF-7 cells were more resistant to low glucose and high lactate growth conditions. Isotope tracing analysis using <sup>13</sup>C-lactate confirmed that lactate conversion to pyruvate was enhanced in TAMR-MCF-7 cells. We identified monocarboxylate transporter1 (MCT1) and lactate dehydrogenase B (LDHB) as important mediators of lactate influx and its conversion to pyruvate, respectively. Consistently, AR-C155858 (MCT1 inhibitor) inhibited the proliferation, migration, spheroid formation, and in vivo tumor growth of TAMR-MCF-7 cells. Our findings suggest that TAMR-MCF-7 cells depend on glycolysis and glutaminolysis for energy and support that targeting MCT1- and LDHB-dependent lactate recycling may be a promising strategy to treat patients with TAM-resistant breast cancer.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138476652","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

Selumetinib overcomes gefitinib primary and acquired resistance by regulating MIG6/STAT3 in NSCLC Selumetinib通过调节MIG6/STAT3在NSCLC中克服吉非替尼的原发性和获得性耐药。

IF 6.9 3区医学

Archives of Pharmacal Research Pub Date : 2023-11-30 DOI: 10.1007/s12272-023-01471-0

Xiaoping Song, Lina Wang, Wei Tang, Luyao Yuan, Qingchao Liu, Jing Li, Daidi Fan

{"title":"Selumetinib overcomes gefitinib primary and acquired resistance by regulating MIG6/STAT3 in NSCLC","authors":"Xiaoping Song, Lina Wang, Wei Tang, Luyao Yuan, Qingchao Liu, Jing Li, Daidi Fan","doi":"10.1007/s12272-023-01471-0","DOIUrl":"10.1007/s12272-023-01471-0","url":null,"abstract":"<div><p>Gefitinib, as the first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has achieved great advances in the treatment of non-small cell lung cancer (NSCLC), but drug resistance will inevitably occur. Therefore, exploring the resistance mechanism of gefitinib and developing new combination treatment strategies are of great importance. In our study, the results showed that selumetinib (AZD6244) synergistically inhibited the proliferation of NSCLC with gefitinib. Selumetinib also enhanced gefitinib-induced apoptosis and migration inhibition ability in gefitinib-resistant lung cancer cell lines. Subsequently, the negative regulation between MIG6 and STAT3 was observed and verified through the STRING database and western blotting assays. Sustained activation of STAT3 was significantly downregulated when co-treatment with selumetinib in gefitinib-resistant cells. However, the downregulation of p-STAT3, resulting from the combination of selumetinib and gefitinib was counteracted by the deletion of MIG6, suggesting that selumetinib enhanced gefitinib sensitivity by regulating MIG6/STAT3 in NSCLC. In contrast, p-STAT3 was further inhibited after treatment with gefitinib and selumetinib when MIG6 was overexpressed. Furthermore, the combined administration of selumetinib and gefitinib effectively promoted the sensitivity of lung cancer xenografts to gefitinib in vivo, and the tumor inhibition rate reached 81.49%, while the tumor inhibition rate of the gefitinib monotherapy group was only 31.95%. Overall, MIG6/STAT3 negative regulation plays an important role in the sustained activation of STAT3 and the resistance to EGFR-TKIs. Our study also suggests that EGFR-TKIs combined with MEK1/2 inhibitors, such as selumetinib, may be beneficial to those NSCLC patients who develop a primary or acquired resistance to EGFR-TKIs, providing theoretical support for combining TKIs and selumetinib in clinical cancer treatment.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138457485","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

Human milk oligosaccharides 3′-sialyllactose and 6′-sialyllactose attenuate LPS-induced lung injury by inhibiting STAT1 and NF-κB signaling pathways 母乳低聚糖3'-唾液乳糖和6'-唾液乳糖通过抑制STAT1和NF-κB信号通路来减轻LPS诱导的肺损伤。

IF 6.9 3区医学

Archives of Pharmacal Research Pub Date : 2023-11-09 DOI: 10.1007/s12272-023-01470-1

Yujin Jin, Hyesu Jeon, Thuy Le Lam Nguyen, Lila Kim, Kyung-Sun Heo

{"title":"Human milk oligosaccharides 3′-sialyllactose and 6′-sialyllactose attenuate LPS-induced lung injury by inhibiting STAT1 and NF-κB signaling pathways","authors":"Yujin Jin, Hyesu Jeon, Thuy Le Lam Nguyen, Lila Kim, Kyung-Sun Heo","doi":"10.1007/s12272-023-01470-1","DOIUrl":"10.1007/s12272-023-01470-1","url":null,"abstract":"<div><p>Acute lung injury (ALI) is the leading cause of respiratory diseases induced by uncontrolled inflammation and cell death. Lipopolysaccharide (LPS) is a major trigger of ALI in the progression through macrophage differentiation and the accelerated release of pro-inflammatory cytokines. The present study aimed to investigate the protective effects of human milk oligosaccharides, specifically 3′-sialyllactose (3′-SL) and 6′-sialyllactose (6′-SL), on LPS-induced ALI and elucidate their underlying signaling pathways. The inhibitory effects of 3′-SL and 6′-SL on inflammation were evaluated using LPS-treated RAW 264.7 macrophages. To establish the ALI model, mice were treated with 10 mg/kg LPS for 24 h. Histological changes in the lung tissues were assessed using hematoxylin and eosin staining and immunofluorescence. LPS causes thickening of the alveolar wall infiltration of immune cells in lung tissues and increased serum levels of TNF-α, IL-1β, and GM-CSF. However, these effects were significantly alleviated by 100 mg/kg of 3′-SL and 6′-SL. Consistent with the inhibitory effects of 3′-SL and 6′-SL on LPS-induced pro-inflammatory cytokine secretion in serum, 3′-SL and 6′-SL suppressed mRNA expression of TNF-α, IL-1β, MCP-1, iNOS, and COX2 in LPS-induced RAW 264.7 cells. Mechanistically, 3′-SL and 6′-SL abolished LPS-mediated phosphorylation of NF-κB and STAT1. Interestingly, fludarabine treatment, a STAT1 inhibitor, did not affect LPS-mediated NF-κB phosphorylation. In summary, 3′-SL and 6′-SL protect LPS-induced macrophage activation and ALI through the STAT1 and NF-κB signaling pathways. </p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71520305","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

Death-associated protein kinase 1 phosphorylates MDM2 and inhibits its protein stability and function 死亡相关蛋白激酶1磷酸化MDM2并抑制其蛋白质稳定性和功能。

IF 6.9 3区医学

Archives of Pharmacal Research Pub Date : 2023-10-07 DOI: 10.1007/s12272-023-01469-8

Mi Zhang, Xindong Shui, Xiaoqing Zheng, Jong Eun Lee, Yingxue Mei, Ruomeng Li, Yuan Tian, Xiuzhi Zheng, Quling Wang, Long Wang, Dongmei Chen, Tao Zhang, Byeong Mo Kim, Jungho Kim, Tae Ho Lee

{"title":"Death-associated protein kinase 1 phosphorylates MDM2 and inhibits its protein stability and function","authors":"Mi Zhang, Xindong Shui, Xiaoqing Zheng, Jong Eun Lee, Yingxue Mei, Ruomeng Li, Yuan Tian, Xiuzhi Zheng, Quling Wang, Long Wang, Dongmei Chen, Tao Zhang, Byeong Mo Kim, Jungho Kim, Tae Ho Lee","doi":"10.1007/s12272-023-01469-8","DOIUrl":"10.1007/s12272-023-01469-8","url":null,"abstract":"<div><p>Breast cancer is one of the major malignancies in women, and most related deaths are due to recurrence, drug resistance, and metastasis. The expression of the mouse double minute 2 (MDM2) oncogene is upregulated in breast cancer; however, its regulatory mechanism has yet to be fully elucidated. Herein, we identified the tumor suppressor death-associated protein kinase 1 (DAPK1) as a novel MDM2 regulator by unbiased peptide library screening. DAPK1 is directly bound to MDM2 and phosphorylates it at Thr419. DAPK1-mediated MDM2 phosphorylation promoted its protein degradation via the ubiquitin–proteasome pathway, resulting in upregulated p53 expression. DAPK1 overexpression, but not its kinase activity-deficient form, decreased colony formation and increased doxorubicin-induced cell death; however, DAPK1 knockdown produced the opposite effects in human breast cancer cells. In a xenograft tumorigenesis assay, DAPK1 overexpression significantly reduced tumor formation, whereas inhibition of DAPK1 kinase activity reduced its antitumorigenic effect. Finally, DAPK1 expression was negatively correlated with MDM2 levels in human breast cancer tissues. Thus, these results suggest that DAPK1-mediated MDM2 phosphorylation and its protein degradation may contribute to its antitumorigenic function in breast cancer.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2023-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41112401","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

2-Geranyl-1-methoxyerythrabyssin II alleviates lipid accumulation and inflammation in hepatocytes through AMPK activation and AKT inhibition 2-杰拉尔基-1-甲氧基赤藓霉素II通过AMPK激活和AKT抑制减轻肝细胞中的脂质积聚和炎症。

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2023-10-02 DOI: 10.1007/s12272-023-01464-z

Yiyuan Xi, Soeun Kim, Thi Thanh Thuy Nguyen, Phil Jun Lee, Jujia Zheng, Zhuofeng Lin, Namki Cho

{"title":"2-Geranyl-1-methoxyerythrabyssin II alleviates lipid accumulation and inflammation in hepatocytes through AMPK activation and AKT inhibition","authors":"Yiyuan Xi, Soeun Kim, Thi Thanh Thuy Nguyen, Phil Jun Lee, Jujia Zheng, Zhuofeng Lin, Namki Cho","doi":"10.1007/s12272-023-01464-z","DOIUrl":"10.1007/s12272-023-01464-z","url":null,"abstract":"<div><p>A growing proportion of the global adult and pediatric populations are currently affected by nonalcoholic steatohepatitis (NASH), leading to rising rates of liver fibrosis and hepatocellular carcinoma without effective pharmacotherapy. Here, we investigated whether 2-geranyl-1-methoxyerythrabyssin II (GMET), isolated from <i>Lespedeza bicolor</i>, could alleviate lipid accumulation and inflammatory responses in a NASH model. GMET exhibited potent in vitro and in vivo effects against lipid accumulation and attenuated inflammatory responses without cytotoxicity. Mechanistically, GMET inhibits acetyl-CoA carboxylase (ACC), sterol regulatory element-binding proteins-1c (SREBP1), and mammalian target of rapamycin (mTOR), and activates PPARα by activating AMP-activated kinase (AMPK), leading to the alleviation of lipid accumulation. In addition, GMET suppresses the NF-κB pathway by activating AMPK and inhibiting the activated protein kinase B (AKT)/IκB-kinase (IKK) pathway, leading to the inhibition of the inflammatory response in hepatocytes. All these protective effects of GMET on lipid accumulation and inflammation in vivo and in vitro were largely abolished by co-treatment with dorsomorphin, an AMPK inhibitor. In conclusion, GMET alleviated lipid accumulation and inflammation to preserve normal hepatocyte function in steatohepatitis. Thus, GMET is a novel potential multi-targeting compound to improve steatohepatitis.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41092977","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

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