European journal of pharmacology最新文献

{"title":"microRNA-18a-5p promotes vascular smooth muscle cell phenotypic switch by targeting Notch2 as therapeutic targets in vein grafts restenosis","authors":"Xu Zhan ,&nbsp;Chang-Ming Zhong ,&nbsp;Hao Tang ,&nbsp;Hansong Xiao ,&nbsp;Yongzheng Guo ,&nbsp;Cheng Zhang ,&nbsp;Can Qu ,&nbsp;Xiaowen Wang ,&nbsp;Chun Huang","doi":"10.1016/j.ejphar.2024.177097","DOIUrl":"10.1016/j.ejphar.2024.177097","url":null,"abstract":"<div><div>Vascular smooth muscle cells (VSMCs) phenotype switching plays a crucial role in vein graft restenosis following coronary artery bypass grafting (CABG) surgery. To discover novel clinically relevant therapeutic targets for vein graft restenosis after CABG, we therefore investigated whether miRNA-18a-5p mediated phenotype switching plays a critical role in the development of vein graft restenosis. We studied miRNA-18a-5p expression in plasma samples of patients with or without vein graft restenosis at 1, 3 and 5 years after coronary artery bypass graft surgery, and in normal vs. atherosclerotic human femoral artery samples, to prove its role in VSMC phenotype switching. We found that the expression of miRNA-18a-5p significantly increased in vein grafts restenosis rat model after bypass surgery at 7, 14, 28 days and human blood specimens with vein grafts failure after grafting surgery. Through gain- and loss-of-function approaches, we determined that miRNA-18a-5p affects VSMC proliferation, migration, differentiation, and contractility. Notch2 was found to be a direct target of miRNA-18a-5p, which is critical for VSMC phenotype switching. Finally, miRNA-18a-5p knockdown used miRNA sponge via AAV6 locally delivery in vivo, miRNA-18a-5p sponge gene transfer therapy reduced the neointimal area, neointimal thickness, and intimal/media area ratio in vein grafts compared with the controls and improved vein graft hemodynamics. miRNA-18a-5p is a critical modulator of VSMC phenotypic switch during development of vein graft restenosis by downregulating Notch2, therefore targeting miRNA-18a-5p may be a helpful strategy for the treatment of vein grafts restenosis or failure after CABG surgery.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"985 ","pages":"Article 177097"},"PeriodicalIF":4.2,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617509","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":"AdipoRon improves mitochondrial homeostasis and protects dopaminergic neurons through activation of the AMPK signaling pathway in the 6-OHDA-lesioned rats","authors":"Seyed Zanyar Athari ,&nbsp;Rana Keyhanmanesh ,&nbsp;Fereshteh Farajdokht ,&nbsp;Mohammad Karimipour ,&nbsp;Negin Azizifar ,&nbsp;Soraya Alimohammadi ,&nbsp;Gisou Mohaddes","doi":"10.1016/j.ejphar.2024.177111","DOIUrl":"10.1016/j.ejphar.2024.177111","url":null,"abstract":"<div><div>The progressive decline of dopaminergic neurons in Parkinson's disease (PD) has been linked to an imbalance in energy and the failure of mitochondrial function. AMP-activated protein kinase (AMPK), the major intracellular energy sensor, regulates energy balance, and damage to nigral dopaminergic neurons induced by 6-hydroxydopamine (6-OHDA) is exacerbated in the absence of AMPK activity. This study aimed to examine the potential therapeutic advantages of AdipoRon, an AMPK activator, on motor function and mitochondrial homeostasis in a 6-OHDA-induced PD model. Male Wistar rats were subjected to unilateral injection of 6-OHDA (10 μg) into the left medial forebrain bundle at two points, and after 7 days, they were treated with intranasal AdipoRon (0.1, 1, and 10 μg) or Levodopa (10 mg/kg, p. o.) for 21 successive days. Following the last treatment day, motor behavior was evaluated through the Murprogo's test, bar test, beam walking test, and apomorphine-induced rotation test. After euthanasia, the left substantia nigra (SN) was separated for evaluation of ATP, mitochondrial membrane potential (MMP), and protein expressions of AMPK, p-AMPK, and mitochondrial dynamics markers (Mfn-2 and Drp-1). Moreover, the number of tyrosine hydroxylase-positive (TH⁺) cells was quantified in the left substantia nigra. Intranasal AdipoRon effectively reversed muscle rigidity, akinesia, bradykinesia, and rotation caused by 6-OHDA. Moreover, AdipoRon increased the phospho-AMPK/AMPK ratio, mitigated mitochondrial dysfunction, and improved mitochondrial dynamics in the SN. Furthermore, AdipoRon increased the number of TH⁺ cells in the SN of PD animals. These findings suggest that AdipoRon could protect dopaminergic neurons by activating the AMPK pathway and improving mitochondrial dysfunction.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"985 ","pages":"Article 177111"},"PeriodicalIF":4.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615522","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":"Berberine ameliorates inflammation by inhibiting MrgprB2 receptor-mediated activation of mast cell in mice","authors":"Yun Huang ,&nbsp;Jian Zhang ,&nbsp;Huan You ,&nbsp;Fan Ye ,&nbsp;Yan Yang ,&nbsp;Chan Zhu ,&nbsp;Yu-Cui Jiang ,&nbsp;Zong-Xiang Tang","doi":"10.1016/j.ejphar.2024.177109","DOIUrl":"10.1016/j.ejphar.2024.177109","url":null,"abstract":"<div><h3>Background</h3><div>Berberine, an isoquinoline alkaloid, is known for anti-inflammatory activities. However, the research on the anti-inflammatory mechanism of berberine is not comprehensive. Recently, studies have shown that MrgprB2 (Mas-related G-protein-coupled receptor B2) in mice and MrgprX2 (Mas-related G-protein-coupled receptor X2) in humans play vital roles in inflammation. Therefore, this study aims to investigate whether the anti-inflammatory activity of berberine is related to MrgprB2 receptor.</div></div><div><h3>Methods</h3><div>The anti-inflammatory activity of BH (berberine hydrochloride) was evaluated by hindpaw edema analysis, pathological analysis and RT-qPCR. Transgenic mice (MrgprB2^−/− mice), HEK293T cell transfection, calcium imaging, electrophysiology, molecular docking and other methods were employed to investigate the potential relationship between the anti-inflammatory activity of BH and the MrgprB2 receptor.</div></div><div><h3>Results</h3><div>The results demonstrated that BH significantly alleviated C48/80 (compound 48/80)-induced local inflammation in vivo. This was evidenced by a decrease in paw edema, reduced infiltration of inflammatory cells, inhibition of mast cell activation, and down-regulation of inflammatory factors such as CXCL13 (CXC subfamily 13) and TNF-α (tumor necrosis factor-α). It was also found that knockout of MrgprB2 receptor could block the anti-inflammatory activity of BH in mice. Furthermore, calcium imaging revealed that BH effectively inhibited the activity of MrgprB2 receptor in overexpressed HEK293T cells in vitro. Additionally, it was observed that BH also inhibited MrgprB2-mediated voltage-dependent current changes in mouse peritoneal mast cells. Molecular docking results further indicated that BH had affinity with MrgprX2 protein.</div></div><div><h3>Conclusions</h3><div>The anti-inflammatory mechanism of BH may be partially attributed to the inhibition of MrgprB2 receptor-mediated mast cell activation.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"985 ","pages":"Article 177109"},"PeriodicalIF":4.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616267","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":"Unleashing the future: The revolutionary role of machine learning and artificial intelligence in drug discovery","authors":"Manoj Kumar Yadav ,&nbsp;Vandana Dahiya ,&nbsp;Manish Kumar Tripathi ,&nbsp;Navaneet Chaturvedi ,&nbsp;Mayank Rashmi ,&nbsp;Arabinda Ghosh ,&nbsp;V. Samuel Raj","doi":"10.1016/j.ejphar.2024.177103","DOIUrl":"10.1016/j.ejphar.2024.177103","url":null,"abstract":"<div><div>Drug discovery is a complex and multifaceted process aimed at identifying new therapeutic compounds with the potential to treat various diseases. Traditional methods of drug discovery are often time-consuming, expensive, and characterized by low success rates. Because of this, there is an urgent need to improve the drug development process using new technologies. The integration of the current state-of-art of artificial intelligence (AI) and machine learning (ML) approaches with conventional methods will enhance the efficiency and effectiveness of pharmaceutical research. This review highlights the transformative impact of AI and ML in drug discovery, discussing current applications, challenges, and future directions in harnessing these technologies to accelerate the development of innovative therapeutics. We have discussed the latest developments in AI and ML technologies to streamline several stages of drug discovery, from target identification and validation to lead optimization and preclinical studies.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"985 ","pages":"Article 177103"},"PeriodicalIF":4.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616815","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":"The role for ω-3 polyunsaturated and short chain fatty acids in hypertension: An updated view on the interaction with gut microbiota","authors":"Gabriele Brosolo ,&nbsp;Andrea Da Porto ,&nbsp;Stefano Marcante ,&nbsp;Filippo Capilupi ,&nbsp;Nicole Bertin ,&nbsp;Cinzia Vivarelli ,&nbsp;Luca Bulfone ,&nbsp;Antonio Vacca ,&nbsp;Cristiana Catena ,&nbsp;Leonardo A. Sechi","doi":"10.1016/j.ejphar.2024.177107","DOIUrl":"10.1016/j.ejphar.2024.177107","url":null,"abstract":"<div><div>As of 2024, arterial hypertension is still considered the leading modifiable cardiovascular risk factor and, due to high rates of undertreatment and poor blood pressure control, the major contributor to human morbidity and mortality. Development of new treatment options and better interventions in lifestyle correction have become a priority of experimental and clinical research. In the last decades, dietary supplementation of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) and generation of gut microbiota-derived short chain fatty acids (SCFAs) have surged as potential and promising interventions for hypertension and cardiovascular prevention. ω-3 PUFAs are considered “essential” fatty acids that can be obtained only from dietary sources. Although previous intervention trials were not consistent in reporting a significant benefit of ω-3 PUFAs, the recent REDUCE-IT trial has provided robust evidence in support of their role in cardiovascular prevention. Recent studies have also identified the intestinal microbiota as a potential player in the pathophysiology and progression of hypertension. Although this might occur through many pathways, generation of SCFAs that is highly dependent on dietary fiber intake is primarily involved, providing an additional target for the development of novel therapeutic strategies. For these reasons, some scientific societies currently recommend dietary supplementation of ω-3 PUFAs and fiber-containing foods in patients with hypertension. In this narrative review, we summarize the results of studies that examined the effects of ω-3 PUFAs and SCFAs on blood pressure, highlighting the mechanisms of action on the vascular system and their possible impact on hypertension, hypertension-related organ damage and, ultimately, cardiovascular outcomes.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"985 ","pages":"Article 177107"},"PeriodicalIF":4.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616648","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":"The involvement and possible targeting of cardiolipins degradation and disturbed linoleic acid metabolism in cardiac atrophy under cancer cachexia","authors":"Yue-ping Wang ,&nbsp;Rui-qin Zhang ,&nbsp;Nan Li ,&nbsp;Qiong-sen Wang ,&nbsp;Ke Yu ,&nbsp;Meng Fan ,&nbsp;Xiong-wen Zhang ,&nbsp;Li-xing Feng ,&nbsp;Xuan Liu","doi":"10.1016/j.ejphar.2024.177108","DOIUrl":"10.1016/j.ejphar.2024.177108","url":null,"abstract":"<div><div>Cardiac atrophy is one of the critical characteristics of cancer cachexia though its mechanisms had not been fully clarified. In the present study, to study the mechanisms of cardiac atrophy in cancer cachexia and search for possible drug targets, cancer cachexia mice bearing C26 colon tumor cells and cultured H9c2 cardiomyocytes induced with simulated cancer cachexia injuries were used as <em>in vivo</em> and <em>in vitro</em> model, respectively. Results of both spatial metabolomics and LC-MS non-targeted metabolomics analysis of heart tissues suggested the disturbance of glycerophospholipid and fatty acid metabolism in the cancer cachexia hearts. Results of lipidomic analysis confirmed that the fatty acid composition of glycerophospholipids changed and the levels of linoleic acid (LA)-rich cardiolipins (CLs) significantly decreased. GC-MS analysis of fatty acids profile confirmed that the level of LA significantly increased and the ratio value of ω-6/ω-3 polyunsaturated fatty acids (PUFA) also increased in the cancer cachexia hearts. In H9c2 cardiomyocytes induced by simulated cancer cachexia injuries, degradation of CLs were also observed. Furthermore, SS-31, a tetrapeptide targeting CLs, could protect the H9c2 cardiomyocytes under simulated cancer cachexia injury by ameliorating the degradation of CLs, inhibiting apoptosis and attenuating the decrease in cell size. Collectively, these results have provided new insights into the cardiac atrophy in cancer cachexia, in which degradation of glycerophospholipids such as CLs and increase in LA and AA-related oxylipins might be important contributing factors and possible therapy targets.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"985 ","pages":"Article 177108"},"PeriodicalIF":4.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616728","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":"Phenyllactic acid modulates the gut microbiota, enhances intestinal health, and alleviates physical frailty in aging mice","authors":"Dayoung Kim ,&nbsp;Han Xu ,&nbsp;Ouyang Li ,&nbsp;Mengjuan Xue ,&nbsp;Zhijun Bao ,&nbsp;Fan Yang","doi":"10.1016/j.ejphar.2024.177105","DOIUrl":"10.1016/j.ejphar.2024.177105","url":null,"abstract":"<div><div>Phenyllactic acid (PLA) is a natural antibiotic-like compound derived from certain foods and probiotics. PLA levels have been associated with age-related sarcopenia and provide benefits to metabolic health when derived from probiotics. However, the specific regulatory effects of PLA in aging remain largely unexplored. In this study, aging mice were administered PLA via gavage, followed by fecal 16S rRNA sequencing, measurements of targeted metabolites, glucose metabolism monitoring, and physical performance assessments. Our results indicate that PLA administration significantly altered gut microbiota composition, increased the abundance of short-chain fatty acids (SCFAs) and succinate producing microbiota, and enhanced gut integrity in aging mice. Furthermore, PLA treatment raised fasting blood glucose levels and improved physical activity. Mechanistically, PLA intake elevated the levels of circulating SCFAs and succinate, promoting glycogen metabolic homeostasis and maintaining skeletal muscle oxidative capacity. This study provides evidence that PLA modulates the gut microbiota in aging mice, supports intestinal health, promotes glucose homeostasis, and enhances physical activity.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"985 ","pages":"Article 177105"},"PeriodicalIF":4.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616720","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":"The power of three: Retatrutide's role in modern obesity and diabetes therapy","authors":"Toufik Abdul-Rahman ,&nbsp;Poulami Roy ,&nbsp;Fatma Kamal Ahmed ,&nbsp;Jann Ludwig Mueller-Gomez ,&nbsp;Sarmistha Sarkar ,&nbsp;Neil Garg ,&nbsp;Victor Oluwafemi Femi-Lawal ,&nbsp;Andrew Awuah Wireko ,&nbsp;Hala Ibrahim Thaalibi ,&nbsp;Muhammad Usman Hashmi ,&nbsp;Andrew Sefenu Dzebu ,&nbsp;Sewar Basheer Banimusa ,&nbsp;Aayushi Sood","doi":"10.1016/j.ejphar.2024.177095","DOIUrl":"10.1016/j.ejphar.2024.177095","url":null,"abstract":"<div><div>The increasing prevalence of obesity and type 2 diabetes mellitus has resulted in a significant challenge to public health throughout the globe. It required the development of novel therapeutic approaches. Retatrutide is a groundbreaking triple agonist that targets glucagon receptors, gastric inhibitory polypeptide, and glucagon-like peptide-1. Retatrutide's complex mechanism of action involves a synergistic interaction among these receptors, resulting in increased insulin secretion, improved glucose homeostasis, and refined appetite modulation. Clinical trials in phases 1 to 3 have demonstrated significant efficacy, highlighted by significant reductions in body weight and favorable glycemic control outcomes. Additionally, retatrutide shows promise in mitigating cardiovascular risk factors and addressing metabolic dysfunction-associated steatotic liver disease. However, careful attention is required to delineate its long-term safety profile, explore its potential in special populations, unravel its adjunctive therapeutic roles, and elucidate its mechanisms in pediatric cohorts. As a transformative therapeutic modality, retatrutide represents a beacon of hope, signifying transformative changes in the management landscape of obesity and type 2 diabetes mellitus (T2DM), and warranting continued exploration and refinement in clinical practice. This narrative review examines the therapeutic potential of retatrutide in the management of obesity and T2DM.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"985 ","pages":"Article 177095"},"PeriodicalIF":4.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616735","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":"Exendin-4, a glucagon-like peptide-1 receptor agonist, regulates ductus arteriosus by vasodilation and anti-remodeling through the PKA pathway","authors":"Yi-Ching Liu ,&nbsp;Yu-Hsin Tseng ,&nbsp;Yen-Hsien Wu ,&nbsp;Lorraine Tong ,&nbsp;Siao-Ping Tsai ,&nbsp;Shang-En Huang ,&nbsp;Bin-Nan Wu ,&nbsp;Shih-Hsing Lo ,&nbsp;I-Chen Chen ,&nbsp;Zen-Kong Dai ,&nbsp;Jwu-Lai Yeh ,&nbsp;Jong-Hau Hsu","doi":"10.1016/j.ejphar.2024.177106","DOIUrl":"10.1016/j.ejphar.2024.177106","url":null,"abstract":"<div><div>The mechanisms of ductus arteriosus (DA) closure involve vasoconstriction and vascular remodeling. Previous findings indicate that the glucagon-like peptide-1 receptor agonist (GLP-1RA) exhibits antihypertensive and anti-remodeling effects in the pulmonary circulation. However, its role in the DA remains unknown. This study aimed to investigate whether exendin-4 (Ex-4), a GLP-1RA, can regulate DA patency and elucidate its mechanisms. After confirming the presence of GLP-1R in neonatal rat DA tissue <em>in vivo</em>, the effects of Ex-4 on DA patency in neonatal rats were sequentially examined. Two hours after birth, we observed spontaneous closure of the DA in control rats. In contrast, Ex-4 prevented the closure of DA, accompanied by reduced intimal thickening. Ex-4 attenuated oxygen-induced vasoconstriction in isolated DA rings <em>ex vivo</em>. This effect was diminished in the presence of H89, a PKA inhibitor. <em>In vitro</em>, Ex-4 inhibited platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of DA smooth muscle cells. Additionally, Ex-4 inhibited PDGF-BB-induced reactive oxygen species (ROS) production, calcium mobilization, and signal transduction of MAPK and Akt pathways. Furthermore, Ex-4 preserved the nuclear expression of Nrf2 attenuated by PDGF-BB. Similarly, all these <em>in vitro</em> effects of Ex-4 were blunted by H89. In conclusion, Ex-4 maintains postnatal DA patency through vasodilatation and anti-remodeling via the PKA pathway. The GLP-1R/PKA pathway emerges as a promising target of DA patency in clinical management.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"985 ","pages":"Article 177106"},"PeriodicalIF":4.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617485","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":"Potential mechanism of perillaldehyde in the treatment of nonalcoholic fatty liver disease based on network pharmacology and molecular docking","authors":"Qian-qian Niu ,&nbsp;Yu-ting Xi ,&nbsp;Chun-rui Zhang ,&nbsp;Xi-yue Li ,&nbsp;Cheng-zhi Li ,&nbsp;Hui-dan Wang ,&nbsp;Peng Li ,&nbsp;Ya-ling Yin","doi":"10.1016/j.ejphar.2024.177092","DOIUrl":"10.1016/j.ejphar.2024.177092","url":null,"abstract":"<div><div>Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic metabolic liver diseases worldwide. Perillaldehyde (4-propyl-1-en-2-ylcyclohexene-1-aldehyde, PA) is a terpenoid compound extracted from Perilla, which has effective pharmacological activities such as anti-inflammatory, antidepressant, and anticancer. This study aimed to explore the pharmacological effects of PA in intervening with NAFLD and reveal its potential mechanisms. Firstly, we identified the core targets of PA intervention therapy for NAFLD through network pharmacology and molecular docking techniques. After that, in vitro animal experiments such as H&amp;E and Masson staining, immunofluorescence, immunohistochemistry, and Western blot were conducted to validate the results network effectively pharmacology predicted. Network pharmacology analysis suggested that PPAR-α may be the core target of PA intervention in NAFLD. H&amp;E and Masson staining showed that after low-dose (50 mg/kg) PA administration, there was a noticeable improvement in fat deposition in the livers of NAFLD mice, and liver tissue fibrosis was alleviated. Immunohistochemical and immunofluorescence analysis showed that low dose (50 mg/kg) PA could reduce hepatocyte apoptosis, decrease the content of pro-apoptosis protein Bax, and increase the expression of anti-apoptosis protein Bcl-2 in NAFLD mice. Western blot results confirmed that low-dose (50 mg/kg) PA could increase the expression of PPAR-α and inhibit the expression of NF-κB in NAFLD mice. Our study indicated that PA could enhance the activity of PPAR-α and reduce the level of NF-κB in NAFLD mice, which may positively affect the prevention of NAFLD.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"985 ","pages":"Article 177092"},"PeriodicalIF":4.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603698","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}