Current molecular pharmacology最新文献

{"title":"The Role of Local Angiotensin II/Angiotensin Type 1 Receptor in Endometriosis: A Potential Target for New Treatment Approaches","authors":"Shirin Moazen, Mohammad-Hassan Arjmand","doi":"10.2174/0118761429315431240712100124","DOIUrl":"10.2174/0118761429315431240712100124","url":null,"abstract":"<p><p>Endometriosis is a chronic inflammatory disorder described by the presence of functional endometrial-like tissues at extra-uterine locations that are related to chronic pelvic pain and infertility. Multiple molecular mechanisms, including inflammation, reactive oxygen species (ROS) generation, fibrotic reactions, and angiogenesis, are involved in the pathogenesis of endometriosis; however, the exact cause of this disorder still remains a matter of discussion. Recently, it has been shown that the local renin-angiotensin system (RAS) has been expressed in different tissues, like the gynecological tract, and alterations in its expression are associated with multiple pathological conditions like endometriosis. Angiotensin II (Ang II), as a main peptide of the RAS through angiotensin type 1 receptor (AT1R), upregulates signal transduction pathways such as nuclear factor kappa B (NF-κB), mitogen activation protein kinase (MAPK), and transforming growth factor beta (TGF-β) to promote inflammation, oxidative stress, and fibrogenesis. Angiotensin receptor blockers (ARBs) control high blood pressure, which is increased by excessive AT1R activity. Recently, it has been recognized that ARBs have tissue protective effects because of their anti-inflammatory and antifibrotic effects. In this review, we focused on the role of local Ang II/AT1R axis activity in endometriosis pathogenesis and justified the use of ARB agents as a potential therapeutic strategy to improve endometriosis.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429315431"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upregulation of LncRNA WT1-AS Inhibits Tumor Growth and Promotes Autophagy in Gastric Cancer via Suppression of PI3K/Akt/mTOR Pathway.","authors":"Xiaobei Zhang, Meng Jin, Xiaoying Yao, Jilan Liu, Yonghong Yang, Jian Huang, Guiyuan Jin, Shiqi Liu, Baogui Zhang","doi":"10.2174/0118761429318398240918063450","DOIUrl":"10.2174/0118761429318398240918063450","url":null,"abstract":"<p><strong>Background: </strong>Increasing evidence has highlighted the involvement of the imbalance of long non-coding RNAs in the development of gastric cancer (GC), which is one of the most common malignancies in the world. This study aimed to determine the role of lncRNA WT1-AS in the progression of GC and explore its underlying mechanism.</p><p><strong>Methods: </strong>The expression of lncRNA WT1-AS in gastric cancer tissues was detected using RT-qPCR. We knocked down the expression of WT1-AS in GC cells or treated them with rapamycin or both. Then, transwell assay and scratch assay were carried out to determine the migration of GC cells, and flow cytometry was carried out to determine the cell cycle. The immunofluorescence technique was used to determine the autophagy, and a tumor formation experiment was carried out to determine tumor growth <i>in vivo</i>. The expression of factors related to the PI3K/Akt/mTOR pathway was also measured by Western Blotting.</p><p><strong>Results: </strong>In GC tissues and cells, lncRNA WT1-AS was underexpressed. Moreover, overexpression of lncRNA WT1-AS blocked the PI3K/Akt/mTOR pathway. Upregulation of lncRNA WT1-AS or inhibition of the PI3K/Akt/mTOR pathway suppressed cancer cell migration in vitro, leading to cell cycle arrest, and promoted autophagy while inhibiting tumor growth <i>in vivo</i>. It also reduced the expression levels of Ki-67, MMP2, MMP9, and VEGF. The WT1-AS+rapamycin group was the most prominent in all experiments.</p><p><strong>Conclusion: </strong>The upregulation of lncRNA WT1-AS could suppress the PI3K/Akt/mTOR pathway, which inhibits cell migration and cell cycle arrest while promoting autophagy in gastric cancer cells.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":"17 1","pages":"e18761429318398"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142735377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thymol and Carvacrol as Potential Tocolytic and Anti-inflammatory Agents in Pregnant Rat Uterus.","authors":"Victor Manuel Muñoz-Pérez, Aurora Pérez-Sánchez, Andrés Salas-Casas A, Mario I Ortíz","doi":"10.2174/0118761429342128241231163610","DOIUrl":"10.2174/0118761429342128241231163610","url":null,"abstract":"<p><strong>Introduction: </strong>This work aimed to evaluate the anti-inflammatory and myorelaxant effect of thymol (TM) and carvacrol (CAR) in the pregnant rat uterus. Both compounds exhibit considerable antimicrobial, antispasmodic, and anti-inflammatory effects and due to these properties, they were studied in this in vitro model of premature birth induced by infection.</p><p><strong>Method: </strong>All uterine tissues were studied in uterine contraction tests to determine the inhibitory effect of TM, CAR (10, 56, 100, 150, and 230 μM), and nifedipine (a calcium channel antagonist) on phasic and tonic contraction induced by electro- and pharmacomechanical stimuli. The quantitative determination of cyclic adenosine monophosphate (cAMP) induced by TM and CAR in the uterine lysate was carried out by ELISA. For the determination of the anti-inflammatory effect of TM, the pro-inflammatory cytokine, interleukin (IL)-1β, in uterine samples stimulated with lipopolysaccharide (LPS) was measured. Forskolin (FSK) was used as a positive control to evaluate the cAMP and cytokine levels. TM, CAR, and nifedipine inhibited the uterine contractions at the highest concentration level, however, nifedipine was the most equipotent (p<0.05). In addition, TM and CAR did not increase the intracellular cAMP production in comparison with FSK (p<0.05). However, both compounds were able to decrease the LPS-induced production in a concentration-dependent manner that was considered statistically significant (p>0.05).</p><p><strong>Results: </strong>Finally, both the anti-inflammatory and uterine relaxing effects induced by TM and CAR were neither associated with the increase in cAMP levels nor with the production of IL-1β in pregnant rat uterine samples. Therefore, TM and CAR can be considered as alternative adjuvants for the treatment of infection-induced preterm labor. Before the in vitro experiments, an in-silico analysis was conducted using the Expaisy online server to evaluate the biological effects of thymol on uterine contraction.</p><p><strong>Conclusion: </strong>It is crucial to know the interaction and identification of genes encoding the Voltage-dependent L-type calcium channel subunit alpha-1C proteins, because of the functional relationship it may have in the inhibition of the uterine contraction. These properties place TM as a potentially safe and effective adjuvant agent in cases of preterm birth, an area of pharmacological treatment that requires urgent improvement.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429342128"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting of Lysosomes as a Therapeutic Target in Cancer.","authors":"Biyu Liu, Chengsheng Yang, Jiayi Liu, Minzhi Peng, Junquan Mao, Sanyuan Tang, Weiguo Huang","doi":"10.2174/0118761429354659250320051057","DOIUrl":"10.2174/0118761429354659250320051057","url":null,"abstract":"<p><p>Lysosomes are important intracellular organelles involved in degradation metabolism, maintenance of homeostasis, cell survival and programmed death regulation, and play an important role in immunity. Some studies have shown that lysosomes are closely linked to tumor development. Lysosomes in tumor cells increase in size and activity to adapt to rapid proliferation. Cancer cells provide strong support for their unrestricted growth and proliferation by precisely regulating the number, composition and functional activities of lysosomes and also create favorable conditions for malignant behaviors such as survival, migration, invasion, and metastatic spread of cancer cells.\u0000Lysosomes play a central role in tumor progression, and in recent years, lysosomes have become an important target for anticancer strategies aimed at interfering with their function or modulating related signaling pathways to inhibit tumors. Current anti-cancer strategies include the following five aspects: (1) targeting tumor cell energy metabolism and lysosomes to inhibit growth; (2) inhibiting lysosomal histone proteases to block degradation metabolism; (3) destabilizing lysosomal membranes to trigger tumor cell death; (4) modulating lysosomal calcium signaling to affect tumor cell function; and (5) interfering with the mTOR signaling pathway to inhibit tumor growth and proliferation. These lysosome-targeted anticancer strategies offer broad prospects and potential for the development of novel anticancer drugs and therapies and are expected to bring more effective and safer therapeutic options for cancer patients.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429354659"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Mitochondrial Targeting Drug SkQ1 Attenuates the Progression of Post- Traumatic Osteoarthritis through Suppression of Mitochondrial Oxidative Stress.","authors":"Zhen-Ya Zhi, Peng-Cheng Wang","doi":"10.2174/0118761429383749250312082958","DOIUrl":"10.2174/0118761429383749250312082958","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Post-traumatic osteoarthritis (PTOA) constitutes a distinct subtype of osteoarthritis (OA). Despite extensive research, no effective pharmacological intervention has been established to prevent or halt the progression of PTOA. Current therapeutic approaches are primarily limited to symptomatic management and pain relief. SkQ1, a novel mitochondria-targeted antioxidant, has emerged as a promising therapeutic agent due to its dual capacity to scavenge excessive intracellular reactive oxygen species (ROS) and modulate inflammatory responses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study aimed to investigate the therapeutic potential of SkQ1 in the early stages of PTOA and elucidate its underlying molecular mechanisms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Chondrocytes were cultured under varying concentrations of SkQ1 to evaluate its cytotoxicity. Additionally, an in vitro oxidative stress model was established to assess the antioxidant effects of SkQ1 across different concentration levels, from which the optimal concentration for PTOA treatment was determined. The rat PTOA model was established through medial meniscal tear (MMT) surgery, followed by intra-articular administration of SkQ1 postoperatively. The gait characteristics of rats in each group were assessed biweekly following surgery. Outcome measures were evaluated at 2 and 6 weeks postoperatively, including pathological evaluation of knee cartilage, ROS levels, markers of oxidative damage, such as malondialdehyde (MDA) and 8-hydroxy-deoxyguanosine (8-OHdG), mitochondrial membrane potential, mitochondrial DNA copy number, and apoptosis-related cytokines.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In vitro, lower concentrations of SkQ1 (500 nM) exhibited superior antioxidant efficacy while minimizing cytotoxicity. The results indicated that SkQ1 administration significantly enhanced knee joint functionality and mitigated articular cartilage degeneration in both the acute and subacute phases of PTOA by inhibiting oxidative stress pathways. In a rat model of PTOA, SkQ1 not only alleviated gait abnormalities, but also substantially reduced levels of oxidative stress biomarkers, including ROS, MDA, and 8-OHdG. Furthermore, SkQ1 effectively preserved mitochondrial membrane potential and increased mitochondrial DNA copy number. Mechanistically, SkQ1 inhibited the release of cytochrome C (Cyt-C) and apoptosis-inducing factor (AIF) and downregulated key components of the mitochondria-mediated apoptotic pathway, such as Bax, Bak, cleaved caspase-3, and cleaved caspase-9.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The findings suggested that SkQ1 exerts its therapeutic effects via multiple mechanisms, including the reduction of ROS accumulation, mitigation of oxidative damage, preservation of mitochondrial function, and inhibition of apoptotic pathways. These diverse actions position SkQ1 as a promising disease-modifying agent for PTOA treatment, potentially offering benefits that extend beyond ","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429383749"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to: An Essential Role of c-Fos in Notch1-mediated Promotion of Proliferation of KSHV-Infected SH-SY5Y Cells.","authors":"Huiling Xu, Jinghong Huang, Lixia Yao, Wenyi Gu, Aynisahan Ruzi, Yufei Ding, Ying Li, Weihua Liang, Jinfang Jiang, Zemin Pan, Dongdong Cao, Naiming Zhou, Dongmei Li, Jinli Zhang","doi":"10.2174/187446721701241105144436","DOIUrl":"https://doi.org/10.2174/187446721701241105144436","url":null,"abstract":"<p><p>In the online version of the article, a change was made in the author's position. The affiliation of Dongmei Li and Jinli Zhang in the online version of the article titled \"An Essential Role of c-Fos in Notch1-mediated Promotion of Proliferation of KSHV-Infected SH-SY5Y Cells\" has been updated in \"Current Molecular Pharmacology,\" 2024; 17: e18761429264583 [1]. The original article can be found online at: https://www.eurekaselect.com/article/137219 Original: Huiling Xu1,2,#, Jinghong Huang1,#, Lixia Yao1,#, Wenyi Gu3, Aynisahan Ruzi4, Yufei Ding5, Ying Li6, Weihua Liang1, Jinfang Jiang1, Zemin Pan1, Dongdong Cao1, Naiming Zhou6,7,*, Dongmei Li1,# and Jinli Zhang1,# * Address correspondence to this author at the Institute of Biochemistry, College of Life Sciences, Zijingang Campus, Zhejiang University, Hangzhou, Zhejiang 310058, China; Tel: 86-13588743854; E-mail: zhounaiming@zju.edu.cn #This author has contributed equally to this work Corrected: Huiling Xu1,2,#, Jinghong Huang1,#, Lixia Yao1,#, Wenyi Gu3, Aynisahan Ruzi4, Yufei Ding5, Ying Li6, Weihua Liang1, Jinfang Jiang1, Zemin Pan1, Dongdong Cao1, Naiming Zhou6,7,*, Dongmei Li1,#,* and Jinli Zhang1,#,* * Address correspondence to these authors at the Institute of Biochemistry, College of Life Sciences, Zijingang Campus, Zhejiang University, Hangzhou, Zhejiang 310058, China. Department of Biochemistry and Molecular Biology/Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine 59 North 2nd Road, Shihezi, Xinjiang, 832002 China. Department of Biochemistry and Molecular Biology/Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine 59 North 2nd Road, Shihezi, Xinjiang, 832002 China. Tel: +86-13588743854; E-mail: zhounaiming@zju.edu.cn Tel: +86-993-2057882; E-mail: lidong_abc@126.com, lidongmei@shzu.edu.cn Tel: +86-993-2057882; E-mail: jinli1998@126.com #These authors have contributed equally to this work.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":"17 ","pages":"e051124236081"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to: Bedaquiline in Drug-Resistant Tuberculosis: A Mini-Review.","authors":"Baljinder Singh, Charan Singh","doi":"10.2174/187446721701240911110426","DOIUrl":"https://doi.org/10.2174/187446721701240911110426","url":null,"abstract":"<p><p>In the online version of the article, a change was made in the list of author's and affiliation section. The affiliation of Charan Singh in the online version of the article titled \"Bedaquiline in Drug-Resistant Tuberculosis: A Mini-Review\" has been updated in \"Current Molecular Pharmacology,\" 2023; 16: e210422203904 [1]. The original article can be found online at: https://www.eurekaselect.com/article/122759 Original: Baljinder Singh1 1Department of Pharmaceutics, UIPS, Panjab University, Chandigarh 160014, India Corrected: 1Department of Pharmaceutics, UIPS, Punjab University, Chandigarh 160014, India 2Department of Pharmaceutics, ISF College of Pharmacy, Moga, Punjab, 142001, India 3Department of Pharmaceutical Sciences, School of Sciences, Hemvati Nandan Bahuguna Garhwal University (A Central University), Srinagar, Uttarakhand, 246174, India Funding: Original: None. Corrected: The financial support provided by the Science and Engineering Research Board (SERB), Department of Science and Technology (DST), Government of India, under the Research Grant File No. EEQ/2020/000616.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":"17 ","pages":"e110924233920"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adipose Tissue Dysfunction Following Trauma and Hypoxia Increases the Risk of Post-Surgical Adhesion: Potential for Therapeutic Interventions","authors":"Rozita Khodashahi, Mahmoud Tavakkoli, Gorgon A Ferns, Leyla Feyzmohammadi, Amir Hossein Mirzaei, Mohsen Aliakbarian, Mohammad-Hassan Arjmand","doi":"10.2174/0118761429308567240806111848","DOIUrl":"10.2174/0118761429308567240806111848","url":null,"abstract":"<p><p>Post-surgical adhesion is a medical challenge, especially following abdominal and pelvic surgeries. This refers to the formation of fibrotic scars that form from connective tissue in the gynecological tract or abdominal cavity. Dysfunctional adipose tissue (AT) by surgical injuries and hypoxia increases the risk of post-surgical adhesion through different molecular mechanisms. Damage-associated molecular patterns (DAMPs) and Hypoxia-induced factor 1 alpha (HIF-1α) produced during surgery trauma and hypoxia induce AT dysfunction to promote inflammation, oxidative stress, metabolic alterations, and profibrotic pathways, which contribute to post-surgical adhesions. HIF-1α and DAMPs can be considered therapeutic targets to prevent AT dysfunction and diminish the formation of adhesions in obese patients undergoing abdominal or pelvic surgeries.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429308567"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141984174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mass Spectrometry in Covalent Drug Discovery.","authors":"Chang Liu, Xiujuan Wen","doi":"10.2174/0118761429319065240605104628","DOIUrl":"https://doi.org/10.2174/0118761429319065240605104628","url":null,"abstract":"","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":"17 1","pages":"e18761429319065"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aloe-Emodin Relieves Myocardial Intracellular Calcium Homeostasis Imbalance Induced by High-Fat Diet <i>via</i> Protein Arginine Methyltransferase/ Ca²⁺/Calmodulin- Dependent Protein Kinase II Signaling Pathway in Rats.","authors":"Wen Li, Juan Hu, Ye Yuan, Zhimin Du, Jia Wang, Yilian Yang, Bing Shao, Jiapan Wang, Mingxiu Zhang, Chunlei Duan, Zhen Chen, Wenjie Liao, Xueqi He","doi":"10.2174/0118761429364907250319054353","DOIUrl":"10.2174/0118761429364907250319054353","url":null,"abstract":"<p><strong>Background: </strong>Chronic high-fat diets (HFDs) lead to an imbalance of calcium homeostasis in cardiomyocytes, which contributes to the development of myocardial ischemia-reperfusion injury, dilated cardiomyopathy, and other cardiovascular diseases. Aloe-emodin (AE) is an anthraquinone component isolated from aloe, rhubarb, and cassia seed, having cardiovascular protective, hepatoprotective, anti-inflammatory, and other pharmacological effects.</p><p><strong>Objective: </strong>This study aimed to explore the specific role of AE in obesity/hyperlipidemia-induced myocardial intracellular calcium homeostasis imbalance.</p><p><strong>Methods: </strong>Wistar rats (male, 220 ± 20 g) were fed HFD for four weeks and AE (100 mg/kg) was administrated for six weeks after confirmation of the HFD model. Serum lipids, reactive oxygen species levels, malondialdehyde levels, and superoxide dismutase levels were measured by commercial biochemical kits. Electrocardiograms of rats were recorded with the BL-420F biological function experimental system. Calcium transients and resting intracellular Ca2+ concentrations were determined by the Langendorff-perfused heart model. Protein levels of Ca2+/calmodulin-dependent protein kinase II (CaMKII), protein arginine methyltransferase 1 (PRMT1), and cardiac Ca2+ handling proteins were evaluated by western blot analysis.</p><p><strong>Results: </strong>HFD-induced hearts exhibited a reduced amplitude of Ca2+ transients and increased resting levels of [Ca2+] in the heart; AE treatment significantly improved these parameters. Furthermore, the HFD-induced heart showed downregulation of PRMT1, upregulation of CaMKII, and abnormalities in the levels of Ca2+ handling proteins. All these deleterious changes were significantly suppressed by the AE treatment. Moreover, AE treatment prevented palmitic acid (PA)-induced calcium overload in H9C2 cells; this effect was reduced by the application of an inhibitor of PRMT1.</p><p><strong>Conclusion: </strong>Taken together, this study demonstrates that AE could alleviate HFD/PA-induced myocardial intracellular calcium homeostasis imbalance via the PRMT1/CaMKII signaling pathway.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429364907"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}