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Wańczura P, Aebisher D, Iwański MA, Myśliwiec A, Dynarowicz K, Bartusik-Aebisher D. The Essence of Lipoproteins in Cardiovascular Health and Diseases Treated by Photodynamic Therapy. Biomedicines 2024; 12:961. [PMID: 38790923 PMCID: PMC11117957 DOI: 10.3390/biomedicines12050961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Revised: 04/22/2024] [Accepted: 04/24/2024] [Indexed: 05/26/2024] Open
Abstract
Lipids, together with lipoprotein particles, are the cause of atherosclerosis, which is a pathology of the cardiovascular system. In addition, it affects inflammatory processes and affects the vessels and heart. In pharmaceutical answer to this, statins are considered a first-stage treatment method to block cholesterol synthesis. Many times, additional drugs are also used with this method to lower lipid concentrations in order to achieve certain values of low-density lipoprotein (LDL) cholesterol. Recent advances in photodynamic therapy (PDT) as a new cancer treatment have gained the therapy much attention as a minimally invasive and highly selective method. Photodynamic therapy has been proven more effective than chemotherapy, radiotherapy, and immunotherapy alone in numerous studies. Consequently, photodynamic therapy research has expanded in many fields of medicine due to its increased therapeutic effects and reduced side effects. Currently, PDT is the most commonly used therapy for treating age-related macular degeneration, as well as inflammatory diseases, and skin infections. The effectiveness of photodynamic therapy against a number of pathogens has also been demonstrated in various studies. Also, PDT has been used in the treatment of cardiovascular diseases, such as atherosclerosis and hyperplasia of the arterial intima. This review evaluates the effectiveness and usefulness of photodynamic therapy in cardiovascular diseases. According to the analysis, photodynamic therapy is a promising approach for treating cardiovascular diseases and may lead to new clinical trials and management standards. Our review addresses the used therapeutic strategies and also describes new therapeutic strategies to reduce the cardiovascular burden that is induced by lipids.
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Affiliation(s)
- Piotr Wańczura
- Department of Cardiology, Medical College of the University of Rzeszów, 35-310 Rzeszów, Poland
| | - David Aebisher
- Department of Photomedicine and Physical Chemistry, Medical College of the University of Rzeszów, 35-310 Rzeszów, Poland
| | - Mateusz A Iwański
- English Division Science Club, Medical College of the University of Rzeszów, 35-310 Rzeszów, Poland
| | - Angelika Myśliwiec
- Center for Innovative Research in Medical and Natural Sciences, Medical College of the University of Rzeszów, 35-310 Rzeszów, Poland
| | - Klaudia Dynarowicz
- Center for Innovative Research in Medical and Natural Sciences, Medical College of the University of Rzeszów, 35-310 Rzeszów, Poland
| | - Dorota Bartusik-Aebisher
- Department of Biochemistry and General Chemistry, Medical College of the University of Rzeszów, 35-310 Rzeszów, Poland
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Li SH, Ma GL, Zhang SL, Yang YY, Liu HF, Luo A, Wen J, Cao ZZ, Jia YZ. Naringin exerts antiarrhythmic effects by inhibiting channel currents in mouse cardiomyocytes. J Electrocardiol 2023; 80:69-80. [PMID: 37262953 DOI: 10.1016/j.jelectrocard.2023.05.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 04/26/2023] [Accepted: 05/02/2023] [Indexed: 06/03/2023]
Abstract
INTRODUCTION Naringin, a flavonoid extracted from citrus plants, has a variety of biological effects. Studies have shown that increasing the consumption of flavonoid-rich foods can reduce the incidence of cardiac arrhythmia. Naringin has been reported to have beneficial cardiovascular effects and thus can be used to prevent cardiovascular diseases, but the electrophysiological mechanism through which it prevents arrhythmias has not been elucidated. This study was conducted to investigate the effect of naringin on the transmembrane ion channel currents in mouse ventricular myocytes and the antiarrhythmic effect of this compound on Langendorff-perfused mouse hearts. METHODS Action potentials (APs) and ionic currents were recorded in isolated ventricular myocytes using the whole-cell patch-clamp technique. Anemone toxin II (ATX II) and CaCl2 were used to induce early afterdepolarizations (EADs) and delayed afterdepolarizations (DADs), respectively. Electrocardiogram (ECG) recordings were conducted in Langendorff-perfused mouse hearts with a BL-420F biological signal acquisition and analysis system. RESULTS At the cellular level, naringin shortened the action potential duration (APD) of ventricular myocytes and decreased the maximum depolarization velocity (Vmax) of APs.Naringin inhibited the L-type calcium current (ICa.L) and ATX II enhanced the late sodium current (INa.L) in a concentration-dependent manner with IC50 values of 508.5 μmol/L (n = 9) and 311.6 μmol/L (n = 10), respectively. In addition, naringin also inhibited the peak sodium current (INa·P) and delayed the rectifier potassium current (IK) and the transient outward potassium current (Ito). Moreover, naringin reduced ATX II-induced APD prolongation and EADs and had a significant inhibitory effect on CaCl2-induced DADs as well. At the organ level, naringin reduced the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) induced by ATX II and shortened the duration of both in isolated hearts. CONCLUSION Naringin can inhibit the occurrence of EADs and DADs at the cellular level; furthermore, it can inhibit INa.L, ICa.L, INa·P, IK, and Ito in ventricular myocytes. Naringin also inhibits arrhythmias induced by ATX II in hearts. By investigating naringin with this electrophysiological method for the first time, we determined that this flavonoid may be a multichannel blocker with antiarrhythmic effects.
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Affiliation(s)
- Shi-Han Li
- Institute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China
| | - Guo-Lan Ma
- Institute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China
| | - Shuang-Lin Zhang
- Institute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China
| | - Yan-Yan Yang
- Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan 430065, China
| | - Han-Feng Liu
- Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan 430065, China
| | - Antao Luo
- Institute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China
| | - Jie Wen
- Institute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China
| | - Zhen-Zhen Cao
- Institute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China.
| | - Yu-Zhong Jia
- Institute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China
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Gunata M, Parlakpinar H. Experimental heart failure models in small animals. Heart Fail Rev 2023; 28:533-554. [PMID: 36504404 DOI: 10.1007/s10741-022-10286-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/08/2022] [Indexed: 12/14/2022]
Abstract
Heart failure (HF) is one of the most critical health and economic burdens worldwide, and its prevalence is continuously increasing. HF is a disease that occurs due to a pathological change arising from the function or structure of the heart tissue and usually progresses. Numerous experimental HF models have been created to elucidate the pathophysiological mechanisms that cause HF. An understanding of the pathophysiology of HF is essential for the development of novel efficient therapies. During the past few decades, animal models have provided new insights into the complex pathogenesis of HF. Success in the pathophysiology and treatment of HF has been achieved by using animal models of HF. The development of new in vivo models is critical for evaluating treatments such as gene therapy, mechanical devices, and new surgical approaches. However, each animal model has advantages and limitations, and none of these models is suitable for studying all aspects of HF. Therefore, the researchers have to choose an appropriate experimental model that will fully reflect HF. Despite some limitations, these animal models provided a significant advance in the etiology and pathogenesis of HF. Also, experimental HF models have led to the development of new treatments. In this review, we discussed widely used experimental HF models that continue to provide critical information for HF patients and facilitate the development of new treatment strategies.
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Affiliation(s)
- Mehmet Gunata
- Department of Medical Pharmacology, Faculty of Medicine, Inonu University, Malatya, 44280, Türkiye
| | - Hakan Parlakpinar
- Department of Medical Pharmacology, Faculty of Medicine, Inonu University, Malatya, 44280, Türkiye.
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Kamisah Y, Che Hassan HH. Therapeutic Use and Molecular Aspects of Ivabradine in Cardiac Remodeling: A Review. Int J Mol Sci 2023; 24:ijms24032801. [PMID: 36769115 PMCID: PMC9917668 DOI: 10.3390/ijms24032801] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2022] [Revised: 01/24/2023] [Accepted: 01/31/2023] [Indexed: 02/05/2023] Open
Abstract
Cardiac remodeling can cause ventricular dysfunction and progress to heart failure, a cardiovascular disease that claims many lives globally. Ivabradine, a funny channel (If) inhibitor, is used in patients with chronic heart failure as an adjunct to other heart failure medications. This review aims to gather updated information regarding the therapeutic use and mechanism of action of ivabradine in heart failure. The drug reduces elevated resting heart rate, which is linked to increased morbidity and mortality in patients with heart failure. Its use is associated with improved cardiac function, structure, and quality of life in the patients. Ivabradine exerts several pleiotropic effects, including an antiremodeling property, which are independent of its principal heart-rate-reducing effects. Its suppressive effects on cardiac remodeling have been demonstrated in animal models of cardiac remodeling and heart failure. It reduces myocardial fibrosis, apoptosis, inflammation, and oxidative stress as well as increases autophagy in the animals. It also modulates myocardial calcium homeostasis, neurohumoral systems, and energy metabolism. However, its role in improving heart failure remains unclear. Therefore, elucidating its molecular mechanisms is imperative and would aid in the design of future studies.
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Affiliation(s)
- Yusof Kamisah
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
- Correspondence:
| | - Hamat H. Che Hassan
- Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
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Liu M, Li Z, Ouyang Y, Chen M, Guo X, Mazhar M, Kang J, Zhou H, Wu Q, Yang S. Material basis and integrative pharmacology of danshen decoction in the treatment of cardiovascular diseases. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 108:154503. [PMID: 36332387 DOI: 10.1016/j.phymed.2022.154503] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 10/03/2022] [Accepted: 10/11/2022] [Indexed: 06/16/2023]
Abstract
BACKGROUND Cardiovascular diseases (CVDs) are among the primary and predominant threats to human health with increasing incidence. Danshen Decoction (DSD) as an adjuvant therapy can benefit CVDs patients by improving clinical efficacy. PURPOSE The purpose of this study was to identify the active components and potential pharmacological mechanisms of DSD by combining mass spectrometry with a network pharmacology strategy and to review the use of DSD in the treatment of CVDs. METHOD First, the composition of DSD was analyzed by ultrahigh-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS). Second, the network pharmacology method was used to elucidate the underlying material basis and possible pharmacological mechanism of DSD for the treatment of CVDs. Finally, clinical and experimental studies on DSD in the past ten years were retrieved from the PubMed and CNKI database, and the content of these studies was used to summarize the latest progress in DSD treatment of CVDs. OUTCOME A total of 35 compounds were found in DSD by manual identification from the analysis of MS, which may be the material basis for the therapeutic effect of DSD. After taking the intersection of 2086 targets related to CVDs, these 35 compounds are considered to play a role in the treatment of CVDs through 210 targets including signal transducer and activator of transcription 3 (STAT3), sarcoma (SRC) and phosphoinositide-3-kinase regulatory subunit (PIK3R), and a total of 168 signaling pathways were involved in the regulation of CVDs by DSD, including PI3K-AKT signaling pathway, Alzheimer disease, and Rap1 signaling pathway. A total of 29 clinical studies using DSD in the treatment of CVDs were included in the literature review, and these studies showed the positive significance of DSD as adjuvant therapy, while 14 experimental studies included in the literature review also demonstrated the effectiveness of DSD in the treatment of CVDs. CONCLUSION DSD plays a role in the treatment of CVDs through a variety of active ingredients. Large-scale clinical research and more in-depth experimental research will help to further reveal the mechanism of DSD in the treatment of CVDs.
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Affiliation(s)
- Mengnan Liu
- Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, PR China; Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou 646000, PR China; National Traditional Chinese Medicine Clinical Research Base and Department of Cardiovascular Medicine, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, PR China
| | - Ziyi Li
- School of Clinical Medicine, Southwest Medical University, Luzhou 646000, PR China
| | - Yue Ouyang
- Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, PR China
| | - Mingtai Chen
- Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, PR China; Department of Cardiovascular Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen 518000, PR China
| | - Xin Guo
- Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, PR China
| | - Maryam Mazhar
- Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou 646000, PR China
| | - Junli Kang
- School of Clinical Medicine, Southwest Medical University, Luzhou 646000, PR China
| | - Hua Zhou
- Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, State Key Laboratory of Dampness Syndrome of Chinese Medicine, Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou 510000, PR China.
| | - Qibiao Wu
- Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, PR China.
| | - Sijin Yang
- Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, PR China; Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou 646000, PR China; National Traditional Chinese Medicine Clinical Research Base and Department of Cardiovascular Medicine, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, PR China.
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Zhang X, Zhang Y, Sun A, Ge J. The effects of nicotinamide adenine dinucleotide in cardiovascular diseases: Molecular mechanisms, roles and therapeutic potential. Genes Dis 2022; 9:959-972. [PMID: 35685463 PMCID: PMC9170600 DOI: 10.1016/j.gendis.2021.04.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 03/29/2021] [Accepted: 04/02/2021] [Indexed: 12/23/2022] Open
Abstract
Recently, cardiovascular diseases (CVDs) were identified as the leading cause of mortality, imposing a heavy burden on health care systems and the social economy. Nicotinamide adenine dinucleotide (NAD+), as a pivotal co-substrate for a range of different enzymes, is involved in many signal transduction pathways activated in CVDs. Emerging evidence has shown that NAD+ can exert remediating effects on CVDs by regulating metabolism, maintaining redox homeostasis and modulating the immune response. In fact, NAD+ might delay ageing through sirtuin and non-sirtuin pathways and thus contribute to interventions for age-related diseases such as CVDs. Considering that robust clinical studies of NAD+ are ongoing, we discuss current challenges and the future translational potential of NAD+ based on existing studies and our understanding. Despite some remaining gaps in its clinical application, NAD+ has been shown to have broad prospects and pan-effects, making it a suitable prophylactic drug for CVDs.
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Affiliation(s)
- Xiaokai Zhang
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, PR China
| | - Yang Zhang
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, PR China
| | - Aijun Sun
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, PR China.,Institute of Biomedical Sciences, Fudan University, Shanghai 200032, PR China
| | - Junbo Ge
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, PR China.,Institute of Biomedical Sciences, Fudan University, Shanghai 200032, PR China
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Heidary Moghaddam R, Samimi Z, Asgary S, Mohammadi P, Hozeifi S, Hoseinzadeh-Chahkandak F, Xu S, Farzaei MH. Natural AMPK Activators in Cardiovascular Disease Prevention. Front Pharmacol 2022; 12:738420. [PMID: 35046800 PMCID: PMC8762275 DOI: 10.3389/fphar.2021.738420] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Accepted: 11/03/2021] [Indexed: 12/11/2022] Open
Abstract
Cardiovascular diseases (CVD), as a life-threatening global disease, is receiving worldwide attention. Seeking novel therapeutic strategies and agents is of utmost importance to curb CVD. AMP-activated protein kinase (AMPK) activators derived from natural products are promising agents for cardiovascular drug development owning to regulatory effects on physiological processes and diverse cardiometabolic disorders. In the past decade, different therapeutic agents from natural products and herbal medicines have been explored as good templates of AMPK activators. Hereby, we overviewed the role of AMPK signaling in the cardiovascular system, as well as evidence implicating AMPK activators as potential therapeutic tools. In the present review, efforts have been made to compile and update relevant information from both preclinical and clinical studies, which investigated the role of natural products as AMPK activators in cardiovascular therapeutics.
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Affiliation(s)
- Reza Heidary Moghaddam
- Clinical Research Development Center, Imam Ali and Taleghani Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Zeinab Samimi
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Sedigheh Asgary
- Isfahan Cardiovascular Research Center, Cardiovascular Research Institute,.Isfahan University of Medical Sciences, Isfahan, Iran
| | - Pantea Mohammadi
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Soroush Hozeifi
- School of Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | | | - Suowen Xu
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Mohammad Hosein Farzaei
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.,Medical Technology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
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Ferulic Acid Alleviates Oxidative Stress-Induced Cardiomyocyte Injury by the Regulation of miR-499-5p/ p21 Signal Cascade. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:1921457. [PMID: 34917156 PMCID: PMC8670946 DOI: 10.1155/2021/1921457] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Accepted: 11/17/2021] [Indexed: 11/18/2022]
Abstract
Objective To investigate the protective effects and regulatory mechanisms of ferulic acid on oxidative stress-induced cardiomyocyte injury. Methods We established a cardiomyocyte oxidative stress cell model by H2O2 treatment and a mouse heart injury model by isoprenaline infusion of male C57BL/6 mice. Ferulic acid was applied to treat oxidative stress-induced cardiomyocyte injury. DHE staining was used to detect ROS production. DNA fragmentation, TUNEL assay, and cleaved caspase-3 were used to analyze cell apoptosis. Real-time PCR and Western blotting were used to analyze miRNA and protein levels to investigate the regulatory mechanisms of ferulic acid on oxidative stress-induced cardiomyocyte injury. Results Ferulic acid pretreatment significantly inhibited H2O2- and isoprenaline-induced oxidative stress and cell apoptosis by promoting miR-499-5p expression and inhibiting p21 expression. MiR-499-5p inhibition reversed the protective effects of ferulic acid. Further study found that ferulic acid could also attenuate isoprenaline-induced mouse heart fibrosis and cell apoptosis by reducing oxidative stress, inflammation, and apoptosis in vivo. Conclusions We proved that ferulic acid protects cardiomyocytes from oxidative stress-induced injury by regulating the miR-499-5p/p21signaling pathway, which provides insight into the clinical application of ferulic acid in the treatment of cardiovascular diseases.
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Zhou Y, Khan H, Xiao J, Cheang WS. Effects of Arachidonic Acid Metabolites on Cardiovascular Health and Disease. Int J Mol Sci 2021; 22:12029. [PMID: 34769460 PMCID: PMC8584625 DOI: 10.3390/ijms222112029] [Citation(s) in RCA: 91] [Impact Index Per Article: 22.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 10/29/2021] [Accepted: 11/04/2021] [Indexed: 02/06/2023] Open
Abstract
Arachidonic acid (AA) is an essential fatty acid that is released by phospholipids in cell membranes and metabolized by cyclooxygenase (COX), cytochrome P450 (CYP) enzymes, and lipid oxygenase (LOX) pathways to regulate complex cardiovascular function under physiological and pathological conditions. Various AA metabolites include prostaglandins, prostacyclin, thromboxanes, hydroxyeicosatetraenoic acids, leukotrienes, lipoxins, and epoxyeicosatrienoic acids. The AA metabolites play important and differential roles in the modulation of vascular tone, and cardiovascular complications including atherosclerosis, hypertension, and myocardial infarction upon actions to different receptors and vascular beds. This article reviews the roles of AA metabolism in cardiovascular health and disease as well as their potential therapeutic implication.
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Affiliation(s)
- Yan Zhou
- Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Avenida da Universidade, Taipa, Macau 999078, China;
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University, Mardan 23200, Pakistan;
| | - Jianbo Xiao
- Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, University of Vigo, 36310 Vigo, Spain;
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China
| | - Wai San Cheang
- Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Avenida da Universidade, Taipa, Macau 999078, China;
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Liu Y, Zhang H, Dai X, Zhu R, Chen B, Xia B, Ye Z, Zhao D, Gao S, Orekhov AN, Zhang D, Wang L, Guo S. A comprehensive review on the phytochemistry, pharmacokinetics, and antidiabetic effect of Ginseng. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2021; 92:153717. [PMID: 34583224 DOI: 10.1016/j.phymed.2021.153717] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 08/08/2021] [Accepted: 08/15/2021] [Indexed: 06/13/2023]
Abstract
BACKGROUND Radix Ginseng, one of the well-known medicinal herbs, has been used in the management of diabetes and its complications for more than 1000 years. PURPOSE The aim of this review is devoted to summarize the phytochemistry and pharmacokinetics of Ginseng, and provide evidence for the antidiabetic effects of Ginseng and its ingredients as well as the underlying mechanisms involved. METHODS For the purpose of this review, the following databases were consulted: the PubMed Database (https://pubmed.ncbi.nlm.nih.gov), Chinese National Knowledge Infrastructure (http://www.cnki.net), National Science and Technology Library (http://www.nstl.gov.cn/), Wanfang Data (http://www.wanfangdata.com.cn/) and the Web of Science Database (http://apps.webofknowledge.com/). RESULTS Ginseng exhibits glucose-lowering effects in different diabetic animal models. In addition, Ginseng may prevent the development of diabetic complications, including liver, pancreas, adipose tissue, skeletal muscle, nephropathy, cardiomyopathy, retinopathy, atherosclerosis and others. The main ingredients of Ginseng include ginsenosides and polysaccharides. The underlying mechanisms whereby this herb exerts antidiabetic activities may be attributed to the regulation of multiple signaling pathways, including IRS1/PI3K/AKT, LKB1/AMPK/FoxO1, AGEs/RAGE, MAPK/ERK, NF-κB, PPARδ/STAT3, cAMP/PKA/CERB and HIF-1α/VEGF, etc. The pharmacokinetic profiles of ginsenosides provide valuable information on therapeutic efficacy of Ginseng in diabetes. Although Ginseng is well-tolerated, dietary consumption of this herb should follow the doctors' advice. CONCLUSION Ginseng may offer an alternative strategy in protection against diabetes and its complications through the regulations of the multi-targets via various signaling pathways. Efforts to understand the underlying mechanisms with strictly-controlled animal models, combined with well-designed clinical trials and pharmacokinetic evaluation, will be important subjects of the further investigations and weigh in translational value of this herb in diabetes management.
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Affiliation(s)
- Yage Liu
- Diabetes Research Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Hao Zhang
- Diabetes Research Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Xuan Dai
- Diabetes Research Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Ruyuan Zhu
- Diabetes Research Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Beibei Chen
- Diabetes Research Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Bingke Xia
- Diabetes Research Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Zimengwei Ye
- Diabetes Research Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Dandan Zhao
- Diabetes Research Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Sihua Gao
- Diabetes Research Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Alexander N Orekhov
- Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow 125315, Russia
| | - Dongwei Zhang
- Diabetes Research Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
| | - Lili Wang
- Department of TCM Pharmacology, School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100029, China.
| | - Shuzhen Guo
- Department of Scientific Research Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
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Olgar Y, Durak A, Degirmenci S, Tuncay E, Billur D, Ozdemir S, Turan B. Ticagrelor alleviates high-carbohydrate intake induced altered electrical activity of ventricular cardiomyocytes by regulating sarcoplasmic reticulum-mitochondria miscommunication. Mol Cell Biochem 2021; 476:3827-3844. [PMID: 34114148 DOI: 10.1007/s11010-021-04205-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 06/03/2021] [Indexed: 12/17/2022]
Abstract
Metabolic syndrome (MetS) is associated with additional cardiovascular risk in mammalians while there are relationships between hyperglycemia-associated cardiovascular dysfunction and increased platelet P2Y12 receptor activation. Although P2Y12 receptor antagonist ticagrelor (Tica) plays roles in reduction of cardiovascular events, its beneficial mechanism remains poorly understood. Therefore, we aimed to clarify whether Tica can exert a direct protective effect in ventricular cardiomyocytes from high-carbohydrate diet-induced MetS rats, at least, through affecting sarcoplasmic reticulum (SR)-mitochondria (Mit) miscommunication. Tica treatment of MetS rats (150 mg/kg/day for 15 days) significantly reversed the altered parameters of action potentials by reversing sarcolemmal ionic currents carried by voltage-dependent Na+ and K+ channels, and Na+/Ca2+-exchanger in the cells, expressed P2Y12 receptors. The increased basal-cytosolic Ca2+ level and depressed SR Ca2+ load were also reversed in Tica-treated cells, at most, though recoveries in the phosphorylation levels of ryanodine receptors and phospholamban. Moreover, there were marked recoveries in Mit structure and function (including increases in both autophagosomes and fragmentations) together with recoveries in Mit proteins and the factors associated with Ca2+ transfer between SR-Mit. There were further significant recoveries in markers of both ER stress and oxidative stress. Taken into consideration the Tica-induced prevention of ER stress and mitochondrial dysfunction, our data provided an important document on the pleiotropic effects of Tica in the electrical activity of the cardiomyocytes from MetS rats. This protective effect seems through recoveries in SR-Mit miscommunication besides modulation of different sarcolemmal ion-channel activities, independent of P2Y12 receptor antagonism.
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Affiliation(s)
- Yusuf Olgar
- Faculty of Medicine, Department of Biophysics, Ankara University, Ankara, Turkey
| | - Aysegul Durak
- Faculty of Medicine, Department of Biophysics, Ankara University, Ankara, Turkey
| | - Sinan Degirmenci
- Faculty of Medicine, Department of Biophysics, Ankara University, Ankara, Turkey
| | - Erkan Tuncay
- Faculty of Medicine, Department of Biophysics, Ankara University, Ankara, Turkey
| | - Deniz Billur
- Faculty of Medicine, Department of Histology and Embryology, Ankara University, Ankara, Turkey
| | - Semir Ozdemir
- Faculty of Medicine, Department of Biophysics, Akdeniz University, Antalya, Turkey.
| | - Belma Turan
- Faculty of Medicine, Department of Biophysics, Ankara University, Ankara, Turkey.
- Faculty of Medicine, Department of Biophysics, Lokman Hekim University, Ankara, Turkey.
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