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Yi X, Abas R, Raja Muhammad Rooshdi RAW, Yan J, Liu C, An J, Daut UN. Time-restricted feeding attenuated hypertension-induced cardiac remodeling by modulating autophagy levels in spontaneously hypertensive rats. Sci Rep 2025; 15:16973. [PMID: 40374761 PMCID: PMC12081920 DOI: 10.1038/s41598-025-01587-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Accepted: 05/07/2025] [Indexed: 05/18/2025] Open
Abstract
To investigate whether time-restricted feeding (TRF) can alleviate cardiac remodeling in spontaneously hypertensive rats (SHRs) by regulating autophagy levels. A 16-week TRF intervention was conducted on Wistar Kyoto (WKY) rats and SHRs, with dietary intake confined to the interval from 9:00 am to 5:00 pm each day. The study examined the impact of TRF on blood pressure (BP), cardiac morphology and function, and the expression levels of key proteins involved in autophagy and its associated signaling cascades. Transmission Electron Microscopy (TEM) was utilized to further evaluate autophagic changes in left ventricular (LV) tissues. TRF significantly mitigated systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) in SHRs. Additionally, TRF improved ejection fraction (EF) and diminished interventricular septal thickness at end-diastole (IVS-d). The study further revealed that TRF enhanced the expression of microtubule-associated protein-I light chain 3 (LC3-I), while reducing that of microtubule-associated protein-II light chain 3 (LC3-II). Moreover, TRF suppressed the expression levels of Beclin-1, phosphorylated phosphoinositide 3-kinase (p-PI3K), phosphorylated protein kinase B (p-AKT), and phosphorylated mechanistic target of rapamycin (p-mTOR) in the LV tissues. TEM analysis confirmed that TRF could inhibit autophagy levels in the LV tissues. TRF can attenuate cardiac remodeling in SHRs by regulating autophagy levels.
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Affiliation(s)
- Xin Yi
- Department of Internal Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia
- Department 1 of Cardiovasology, North China University of Science and Technology Affiliated Hospital, Tangshan City, 063000, Hebei Province, China
| | - Razif Abas
- Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia
| | | | - Jie Yan
- Department 1 of Cardiovasology, North China University of Science and Technology Affiliated Hospital, Tangshan City, 063000, Hebei Province, China
| | - Canzhang Liu
- Department 1 of Cardiovasology, North China University of Science and Technology Affiliated Hospital, Tangshan City, 063000, Hebei Province, China
| | - Jiaxu An
- Department of Internal Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia
| | - Ummi Nadira Daut
- Department of Internal Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.
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Khayatan D, Razavi SM, Arab ZN, Nasoori H, Fouladi A, Pasha AVK, Butler AE, Karav S, Momtaz S, Abdolghaffari AH, Sahebkar A. Targeting mTOR with curcumin: therapeutic implications for complex diseases. Inflammopharmacology 2025; 33:1583-1616. [PMID: 39955697 DOI: 10.1007/s10787-025-01643-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Accepted: 10/16/2024] [Indexed: 02/17/2025]
Abstract
The mammalian target of rapamycin (mTOR) is a crucial enzyme in regulating multiple signaling pathways in the body, including autophagy, proliferation and apoptosis. Disruption of these mTOR signaling pathways can lead to an array of abnormalities and trigger disease processes, examples being neurodegenerative conditions, cancer, obesity and diabetes. Under conditions of oxidative stress, mTOR can regulate apoptosis and autophagy, with tissue repair being favored under such circumstances. Moreover, the correlation between mTOR and other signaling pathways could play a pivotal role in the pathophysiology of numerous disorders. mTOR has a tight connection with NF-κB, Akt, PI3K, MAPK, GSK-3β, Nrf2/HO-1, JAK/STAT, CREB/BDNF, and ERK1/2 pathways, which together could play significant roles in the regulation of inflammation, apoptosis, cell survival, and oxidative stress in different body organs. Research suggests that inhibiting mTOR could be beneficial in treating metabolic, neurological and cardiovascular conditions, as well as potentially extending life expectancy. Therefore, identifying new chemicals and agents that can modulate the mTOR signaling pathway holds promise for treating and preventing these disorders. Curcumin is one such agent that has demonstrated regulatory effects on the mTOR pathway, making it an exciting alternative for reducing complications associated with complex diseases by targeting mTOR. This review aims to examine the potential of curcumin in modulating the mTOR signaling pathway and its therapeutic implications.
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Affiliation(s)
- Danial Khayatan
- Department of Toxicology & Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
- GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Seyed Mehrad Razavi
- Department of Toxicology & Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
- GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Zahra Najafi Arab
- Department of Toxicology & Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
- GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Hadis Nasoori
- Department of Toxicology & Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
- GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Abtin Fouladi
- GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Aytak Vahdat Khajeh Pasha
- Department of Toxicology & Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
- GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Alexandra E Butler
- Research Department, Royal College of Surgeons in Ireland, Bahrain, Adliya, Bahrain
| | - Sercan Karav
- Department of Molecular Biology and Genetics, Canakkale Onsekiz Mart University, Canakkale, 17100, Turkey
| | - Saeideh Momtaz
- GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
- Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran
- Department of Toxicology and Pharmacology, School of Pharmacy, and Toxicology and Diseases Group, Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
| | - Amir Hossein Abdolghaffari
- Department of Toxicology & Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
- GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
| | - Amirhossein Sahebkar
- Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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3
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Hao M, Zhang C, Wang T, Hu H. Pharmacological effects, formulations, and clinical research progress of curcumin. Front Pharmacol 2025; 16:1509045. [PMID: 40166470 PMCID: PMC11955698 DOI: 10.3389/fphar.2025.1509045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Accepted: 03/03/2025] [Indexed: 04/02/2025] Open
Abstract
Curcumin, a polyphenolic compound derived from the traditional Chinese medicine turmeric, which has a variety of pharmacological effects, including anti-cancer, anti-inflammatory, antioxidant, and antiviral properties. However, its clinical application is hindered by low solubility and bioavailability. To overcome these limitations, researchers have developed various formulations such as nanoformulations, solid dispersions, and microspheres. These advancements have led to improved therapeutic effects and have facilitated the progression of clinical research, primarily focusing on Phase I and Phase II trials for conditions like diabetes, obesity, and metabolic syndrome. In recent years, there has been a noticeable increase in Phase III and IV clinical trials, particularly concerning oral and dental diseases and arthritis. This article reviews recent literature from both domestic and international sources, providing a comprehensive overview of curcumin's research progress, including its pharmacological mechanisms, formulation developments, and clinical studies.
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Affiliation(s)
- Minghui Hao
- College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, China
| | - Chungang Zhang
- College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, China
- Department of Pharmacy, Changzhi Medical College, Changzhi, China
- Qimeng Co., LTD, Chifeng, China
| | - Ti Wang
- College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, China
| | - Heng Hu
- College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, China
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Patil N, Patil VS, Punase N, Mapare G, Bhatt S, Patil CR. Comparative Efficacy of β-Carotene and Losartan Against Isoproterenol-Induced Cardiac Fibrosis: An Experimental and Computational Studies. JOURNAL OF THE AMERICAN NUTRITION ASSOCIATION 2025:1-16. [PMID: 39927680 DOI: 10.1080/27697061.2025.2461217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 01/05/2025] [Accepted: 01/28/2025] [Indexed: 02/11/2025]
Abstract
OBJECTIVE β-carotene, a vitamin A precursor is reported to inhibit molecular pathways cardinal to pathogenesis of fibrotic tissue alterations and in this study, the effectiveness of 14 days oral administration of β-carotene (10, 20, and 40 mg/kg/day) in the cardiac fibrosis (CF) in rats was studied and explored the mechanisms through network pharmacology. METHODS CF was induced by isoproterenol (ISO) 6 mg/kg/SC from day 1 to day 7. Losartan (LOS) 10 mg/kg/day/p.o. served as the standard. Both β-carotene and LOS were administered from day 1 to 14. On the 15th day, ECG and blood pressure (systolic, diastolic and mean) were recorded in the anesthetized rats followed by their euthanasia. The extent of cardiac fibrosis in the isolated hearts was determined using heart coefficient, tissue levels of hydroxyproline, histological examination. The oxidative stress in cardiac tissue was estimated, as GSH, SOD, catalase, MDA and NO. β-carotene targeted proteins pathway, process, and functional enrichment analysis were explored through network pharmacology. RESULTS β-carotene dose-dependently mitigated the biochemical and histological changes induced by ISO in heart tissues. In ECG, it restored ST height, QT, and QRS intervals. Additionally, it normalized systolic, diastolic, and mean arterial pressures. The reduction in heart coefficient suggests β-carotene's potential to inhibit collagen deposition in heart tissue. β-carotene normalized oxidative stress markers, and hydroxyproline levels. All other biochemical parameters were restored to normal levels with β-carotene treatment. β-carotene 40 mg/kg dose showed comparable effect to that of LOS 10 mg/kg. β-carotene modulated IL-17, TNF, NF-kappa B, HIF-1, Sphingolipid, Relaxin, Adipocytokine, cAMP, Toll-like receptor, MAPK, PI3K-Akt, cGMP-PKG, VEGF, Ras, and PPAR signaling pathways. CONCLUSIONS β-carotene dose-dependently protects against ISO-induced CF in rats, with 40 mg/kg as an effective antifibrotic dose.
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Affiliation(s)
- Niharika Patil
- Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, India
| | - Vishal S Patil
- Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, India
| | - Nandeeni Punase
- Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, India
| | - Ghanshyam Mapare
- Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, India
| | - Shvetank Bhatt
- School of Health Sciences and Technology, Vishwanath Karad MIT World Peace University, Kothrud, Pune, India
| | - Chandragouda R Patil
- Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, India
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Bader Eddin L, Nagoor Meeran MF, Kumar Jha N, Goyal SN, Ojha S. Isoproterenol mechanisms in inducing myocardial fibrosis and its application as an experimental model for the evaluation of therapeutic potential of phytochemicals and pharmaceuticals. Animal Model Exp Med 2025; 8:67-91. [PMID: 39690876 PMCID: PMC11798751 DOI: 10.1002/ame2.12496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Accepted: 08/14/2024] [Indexed: 12/19/2024] Open
Abstract
Cardiac injury initiates repair mechanisms and results in cardiac remodeling and fibrosis, which appears to be a leading cause of cardiovascular diseases. Cardiac fibrosis is characterized by the accumulation of extracellular matrix proteins, mainly collagen in the cardiac interstitium. Many experimental studies have demonstrated that fibrotic injury in the heart is reversible; therefore, it is vital to understand different molecular mechanisms that are involved in the initiation, progression, and resolution of cardiac fibrosis to enable the development of antifibrotic agents. Of the many experimental models, one of the recent models that has gained renewed interest is isoproterenol (ISP)-induced cardiac fibrosis. ISP is a synthetic catecholamine, sympathomimetic, and nonselective β-adrenergic receptor agonist. The overstimulated and sustained activation of β-adrenergic receptors has been reported to induce biochemical and physiological alterations and ultimately result in cardiac remodeling. ISP has been used for decades to induce acute myocardial infarction. However, the use of low doses and chronic administration of ISP have been shown to induce cardiac fibrosis; this practice has increased in recent years. Intraperitoneal or subcutaneous ISP has been widely used in preclinical studies to induce cardiac remodeling manifested by fibrosis and hypertrophy. The induced oxidative stress with subsequent perturbations in cellular signaling cascades through triggering the release of free radicals is considered the initiating mechanism of myocardial fibrosis. ISP is consistently used to induce fibrosis in laboratory animals and in cardiomyocytes isolated from animals. In recent years, numerous phytochemicals and synthetic molecules have been evaluated in ISP-induced cardiac fibrosis. The present review exclusively provides a comprehensive summary of the pathological biochemical, histological, and molecular mechanisms of ISP in inducing cardiac fibrosis and hypertrophy. It also summarizes the application of this experimental model in the therapeutic evaluation of natural as well as synthetic compounds to demonstrate their potential in mitigating myocardial fibrosis and hypertrophy.
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Affiliation(s)
- Lujain Bader Eddin
- Department of Pharmacology and Therapeutics, College of Medicine and Health SciencesUAE UniversityAl AinUnited Arab Emirates
| | - Mohamed Fizur Nagoor Meeran
- Department of Pharmacology and Therapeutics, College of Medicine and Health SciencesUAE UniversityAl AinUnited Arab Emirates
| | - Niraj Kumar Jha
- School of Bioengineering & BiosciencesLovely Professional UniversityPhagwaraIndia
- Centre for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Saveetha UniversityChennaiIndia
| | - Samer N. Goyal
- Shri Vile Parle Kelvani Mandal's Institute of PharmacyDhuleMaharashtraIndia
| | - Shreesh Ojha
- Department of Pharmacology and Therapeutics, College of Medicine and Health SciencesUAE UniversityAl AinUnited Arab Emirates
- Zayed Bin Sultan Center for Health SciencesUnited Arab Emirates UniversityAl AinUnited Arab Emirates
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6
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Ding JY, Meng TT, Du RL, Song XB, Li YX, Gao J, Ji R, He QY. Bibliometrics of trends in global research on the roles of stem cells in myocardial fibrosis therapy. World J Stem Cells 2024; 16:1086-1105. [PMID: 39734477 PMCID: PMC11669986 DOI: 10.4252/wjsc.v16.i12.1086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Revised: 10/05/2024] [Accepted: 11/11/2024] [Indexed: 12/13/2024] Open
Abstract
BACKGROUND Myocardial fibrosis, a condition linked to several cardiovascular diseases, is associated with a poor prognosis. Stem cell therapy has emerged as a potential treatment option and the application of stem cell therapy has been studied extensively. However, a comprehensive bibliometric analysis of these studies has yet to be conducted. AIM To map thematic trends, analyze research hotspots, and project future directions of stem cell-based myocardial fibrosis therapy. METHODS We conducted a bibliometric and visual analysis of studies in the Web of Science Core Collection using VOSviewer and Microsoft Excel. The dataset included 1510 articles published between 2001 and 2024. Countries, organizations, authors, references, keywords, and co-citation networks were examined to identify evolving research trends. RESULTS Our findings revealed a steady increase in the number of publications, with a projected increase to over 200 publications annually by 2030. Initial research focused on stem cell-based therapy, particularly for myocardial infarction and heart failure. More recently, there has been a shift toward cell-free therapy, involving extracellular vesicles, exosomes, and microRNAs. Key research topics include angiogenesis, inflammation, apoptosis, autophagy, and oxidative stress. CONCLUSION This analysis highlights the evolution of stem cell therapies for myocardial fibrosis, with emerging interest in cell-free approaches. These results are expected to guide future scientific exploration and decision-making.
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Affiliation(s)
- Jing-Yi Ding
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Tian-Tian Meng
- Department of Rehabilitation, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing 100071, China
| | - Ruo-Lin Du
- Department of Emergency Medicine, South Branch of Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Xin-Bin Song
- Department of Intensive Care Unit, Zhumadian Hospital of Traditional Chinese Medicine, Zhumadian 463000, Henan Province, China
| | - Yi-Xiang Li
- Department of Chinese Medicine, The Third People's Hospital of Henan Province, Zhengzhou 450000 Henan Province, China
| | - Jing Gao
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Ran Ji
- Department of Intensive Care Unit, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Qing-Yong He
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
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7
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Ruan Y, Luo H, Tang J, Ji M, Yu D, Yu Q, Cao Z, Mai Y, Zhang B, Chen Y, Liu J, Liao W. Curcumin inhibits oxidative stress and autophagy in C17.2 neural stem cell through ERK1/2 signaling pathways. Aging Med (Milton) 2024; 7:559-570. [PMID: 39507234 PMCID: PMC11535172 DOI: 10.1002/agm2.12361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Accepted: 09/25/2024] [Indexed: 11/08/2024] Open
Abstract
Objectives This study investigates curcumin's neuroprotective role and its potential in promoting neurogenesis in progenitor cells within the brain. Notably, curcumin's antioxidant properties have been implicated in Alzheimer's disease treatment. However, the association between curcumin's antioxidative effects and its impact on neural stem cells (NSCs) remains to be elucidated. Methods C17.2 neural stem cells were utilized as a model to simulate oxidative stress, induced by hydrogen peroxide (H2O2). We quantified the levels of superoxide dismutase (SOD), malondialdehyde (MDA), and intracellular reactive oxygen species (ROS), alongside the gene expression of SOD1 and SOD2, to assess intracellular oxidative stress. Additionally, Western blot analysis was conducted to measure the expressions of LC3-II, Beclin-1, and phosphorylated ERK (p-ERK), thereby evaluating autophagy and ERK signaling pathway activation. Results Treatment with curcumin resulted in a reduction of MDA and ROS levels, suggesting a protective effect on NSCs against oxidative damage induced by H2O2. Furthermore, a decrease in the relative expressions of LC3-II, Beclin-1, and p-ERK was observed post-curcumin treatment. Conclusions The findings suggest that curcumin may confer protection against oxidative stress by attenuating autophagy and deactivating the ERK1/2 signaling pathways, which could contribute to therapeutic strategies for Alzheimer's disease.
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Affiliation(s)
- Yuting Ruan
- Department of Rehabilitation, The Second Affiliated HospitalGuangzhou Medical UniversityGuangzhouGuangdongChina
| | - Haoyu Luo
- Department of Neurology, The Second Affiliated HospitalGuangzhou Medical UniversityGuangzhouGuangdongChina
| | - Jingyi Tang
- Department of NeurologySun Yat‐sen Memorial Hospital of Sun Yat‐sen UniversityGuangdongChina
| | - Mengyao Ji
- Department of Neurology, The Second Affiliated HospitalGuangzhou Medical UniversityGuangzhouGuangdongChina
| | - Dapeng Yu
- Department of Rehabilitation, The Second Affiliated HospitalGuangzhou Medical UniversityGuangzhouGuangdongChina
| | - Qun Yu
- Department of Neurology, The Second Affiliated HospitalGuangzhou Medical UniversityGuangzhouGuangdongChina
| | - Zhiyu Cao
- Department of NeurologySun Yat‐sen Memorial Hospital of Sun Yat‐sen UniversityGuangdongChina
| | - Yingren Mai
- Department of Neurology, The Second Affiliated HospitalGuangzhou Medical UniversityGuangzhouGuangdongChina
| | - Bei Zhang
- Department of NeurologyThe First Affiliated Hospital of Guangdong Pharmaceutical UniversityGuangzhouChina
| | - Yan Chen
- Department of Rehabilitation, The Second Affiliated HospitalGuangzhou Medical UniversityGuangzhouGuangdongChina
| | - Jun Liu
- Department of Neurology, The Second Affiliated HospitalGuangzhou Medical UniversityGuangzhouGuangdongChina
| | - Wang Liao
- Department of Neurology, The Second Affiliated HospitalGuangzhou Medical UniversityGuangzhouGuangdongChina
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Cai M, Wu P, Ni W, Huang D, Wang X. mTORC1 hyperactivation and resultant suppression of macroautophagy contribute to the induction of cardiomyocyte necroptosis by catecholamine surges. Physiol Rep 2024; 12:e15966. [PMID: 38444056 PMCID: PMC10915131 DOI: 10.14814/phy2.15966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 02/17/2024] [Accepted: 02/26/2024] [Indexed: 03/07/2024] Open
Abstract
Previous studies revealed a controversial role of mechanistic target of rapamycin complex 1 (mTORC1) and mTORC1-regulated macroautophagy in isoproterenol (ISO)-induced cardiac injury. Here we investigated the role of mTORC1 and potential underlying mechanisms in ISO-induced cardiomyocyte necrosis. Two consecutive daily injections of ISO (85 mg/kg, s.c.) or vehicle control (CTL) were administered to C57BL/6J mice with or without rapamycin (RAP, 5 mg/kg, i.p.) pretreatment. Western blot analyses showed that myocardial mTORC1 signaling and the RIPK1-RIPK3-MLKL necroptotic pathway were activated, mRNA expression analyses revealed downregulation of representative TFEB target genes, and Evan's blue dye uptake assays detected increased cardiomyocyte necrosis in ISO-treated mice. However, RAP pretreatment prevented or significantly attenuated the ISO-induced cardiomyocyte necrosis, myocardial inflammation, downregulation of TFEB target genes, and activation of the RIPK1-RIPK3-MLKL pathway. LC3-II flux assays confirmed the impairment of myocardial autophagic flux in the ISO-treated mice. In cultured neonatal rat cardiomyocytes, mTORC1 signaling was also activated by ISO, and inhibition of mTORC1 by RAP attenuated ISO-induced cytotoxicity. These findings suggest that mTORC1 hyperactivation and resultant suppression of macroautophagy play a major role in the induction of cardiomyocyte necroptosis by catecholamine surges, identifying mTORC1 inhibition as a potential strategy to treat heart diseases with catecholamine surges.
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Affiliation(s)
- Mingqi Cai
- Heart CenterShanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina
- Division of Basic Biomedical SciencesSanford School of Medicine of the University of South DakotaVermillionSouth DakotaUSA
| | - Penglong Wu
- Division of Basic Biomedical SciencesSanford School of Medicine of the University of South DakotaVermillionSouth DakotaUSA
- Department of Cardiology, Xiamen Cardiovascular Hospital of Xiamen University, School of MedicineXiamen UniversityXiamenChina
| | - Wei Ni
- Department of Cardiology, Xiamen Cardiovascular Hospital of Xiamen University, School of MedicineXiamen UniversityXiamenChina
| | - Dong Huang
- Heart CenterShanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina
| | - Xuejun Wang
- Division of Basic Biomedical SciencesSanford School of Medicine of the University of South DakotaVermillionSouth DakotaUSA
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9
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Ahmed A, Abdel-Rahman D, Hantash EM. Role of canagliflozin in ameliorating isoprenaline induced cardiomyocyte oxidative stress via the heme oxygenase-1 mediated pathway. Biotech Histochem 2023; 98:593-605. [PMID: 37779487 DOI: 10.1080/10520295.2023.2262390] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/03/2023] Open
Abstract
Canagliflozin (CZ) is commonly prescribed for management of type-2 diabetes mellitus (T2DM); it also can reduce the risk of myocardial infarction. We used 80 albino Wistar rats to investigate the cardioprotective potential of CZ against oxidative stress caused by administration of isoprenaline (ISO). We found that ISO stimulates production of reactive oxygen species and that CZ administration caused up-regulation of antioxidants and down-regulation of oxidants due to nuclear factor erythroid-2 related factor-2, as well as by enhancement of the heme oxygenase-1 mediated cascade. CZ monotherapy may play a cardioprotective role in diabetic patients. CZ possesses strong antioxidant potential that ameliorates cardiac damage induced by ISO administration.
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Affiliation(s)
- Ahmed Ahmed
- Anatomy and Embryology Department, College of Medicine, Tanta University, Tanta, Egypt
- Biomedical Sciences Department, College of Medicine, Gulf Medical University, Ajman, United Arab Emirates
| | - Dina Abdel-Rahman
- Department of Pathology, College of Medicine, Beni-Suef University, Beni-Suef, Egypt
| | - Ehab M Hantash
- Anatomy and Embryology Department, College of Medicine, Tanta University, Tanta, Egypt
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10
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Hareeri RH, Alam AM, Bagher AM, Alamoudi AJ, Aldurdunji MM, Shaik RA, Eid BG, Ashour OM. Protective Effects of 2-Methoxyestradiol on Acute Isoproterenol-Induced Cardiac Injury in Rats. Saudi Pharm J 2023; 31:101787. [PMID: 37766820 PMCID: PMC10520946 DOI: 10.1016/j.jsps.2023.101787] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 09/08/2023] [Indexed: 09/29/2023] Open
Abstract
Myocardial injury (MI) is an important pathological driver of mortality worldwide., and arises as a result of imbalances between myocardial oxygen demand and supply. In MI, oxidative stress often leads to inflammatory changes and apoptosis. Current therapies for MI are known to cause various adverse effects. Consequently, the development of new therapeutic agents with a reduced adverse event profile is necessary. In this regard, 2-methoxyestradiol (2ME), the metabolic end-product of oestradiol, possesses anti-inflammatory and antioxidant properties. The aim of this research is to assess the impact of 2ME on cardiac injury caused by isoproterenol (ISO) in rats. Animals were separated into six groups; controls, and those receiving 2ME (1 mg/kg), ISO (85 mg/kg), ISO + 2ME (0.25 mg/kg), ISO + 2ME (0.5 mg/kg), and ISO + 2ME (1 mg/kg). 2ME significantly attenuated ISO-induced changes in electrocardiographic changes and the cardiac histological pattern. This compound also decreased lactate dehydrogenase activity, creatine kinase myocardial band and troponin levels. The ability of 2ME to act as an antioxidant was shown by a decrease in malondialdehyde concentration, and the restoration of glutathione levels and superoxide dismutase activity. Additionally, 2ME antagonized inflammation and cardiac cell apoptosis, a process determined to be mediated, at least partially, by suppression of Gal-3/TLR4/MyD88/NF-κB signaling pathway. 2ME offers protection against acute ISO-induced MI in rats and offers a novel therapeutic management option.
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Affiliation(s)
- Rawan H. Hareeri
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Abdulrahman M. Alam
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Amina M. Bagher
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Abdulmohsin J. Alamoudi
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mohammed M. Aldurdunji
- Department of Clinical Pharmacy, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Rasheed A. Shaik
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Basma G. Eid
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Osama M. Ashour
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
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Zhang L, Zhang H, Xie X, Tie R, Shang X, Zhao Q, Xu J, Jin L, Zhang J, Ye P. Empagliflozin ameliorates diabetic cardiomyopathy via regulated branched-chain amino acid metabolism and mTOR/p-ULK1 signaling pathway-mediated autophagy. Diabetol Metab Syndr 2023; 15:93. [PMID: 37149696 PMCID: PMC10163822 DOI: 10.1186/s13098-023-01061-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Accepted: 04/14/2023] [Indexed: 05/08/2023] Open
Abstract
BACKGROUND Empagliflozin, a sodium-glucose co-transporter 2 inhibitor (SGLT2i), has been reported to significantly reduce the risk of heart failure in multiple clinical studies. However, the underlying mechanisms remain elusive. This study aimed to investigate the effect of empagliflozin on branched-chain amino acid (BCAA) metabolism in diabetic cardiomyopathy. METHODS Thirty male 8-week KK Cg-Ay/J mice were used to study diabetic cardiomyopathy; here, 15 were used as the model group, and the remaining 15 were administered empagliflozin (3.75 mg/kg/day) by gavage daily for 16 weeks. The control group consisted of fifteen male 8-week C57BL/6J mice, whose blood glucose and body weight were measured simultaneously with the diabetic mice until 16 weeks without additional intervention. Echocardiography and histopathology were performed to evaluate cardiac structure and function. Proteomic sequencing and biogenic analysis were performed on mouse hearts. Parallel Reaction Monitoring and western blotting were performed to validate the expression levels of differentially expressed proteins. RESULTS The results showed that empagliflozin improved ventricular dilatation and ejection fraction reduction in diabetic hearts, as well as the elevation of myocardial injury biomarkers hs-cTnT and NT-proBNP. At the same time, empagliflozin alleviates myocardial inflammatory infiltration, calcification foci deposition, and fibrosis caused by diabetes. The results of the proteomics assay showed that empagliflozin could improve the metabolism of various substances, especially promoting the BCAA metabolism of diabetic hearts by up-regulating PP2Cm. Furthermore, empagliflozin could affect the mTOR/p-ULK1 signaling pathway by reducing the concentration of BCAA in diabetic hearts. When mTOR/p-ULK1 protein was inhibited, ULK1, the autophagy initiation molecule, increased. Moreover, autophagy substrate p62 and autophagy marker LC3B were significantly reduced, indicating that the autophagy activity of diabetes inhibition was reactivated. CONCLUSIONS Empagliflozin may attenuate diabetic cardiomyopathy-related myocardial injury by promoting the catabolism of BCAA and inhibiting mTOR/p-ULK1 to enhance autophagy. These findings suggest that empagliflozin could be a potential candidate drug against BCAA increase and could be used for other cardiovascular diseases with a metabolic disorder of BCAA.
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Affiliation(s)
- Lin Zhang
- Medical School of Chinese PLA, Department of Geriatric Cardiology, The Second Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Heming Zhang
- Department of Anesthesiology, The 963 Hospital of the PLA Joint Logistics Support Force, Jiamusi, China
- Department of Anesthesiology, The Second Affiliated Hospital of Air Force Medical University, Xi'an, China
| | - Xiuzhu Xie
- Medical School of Chinese PLA, Department of Geriatric Cardiology, The Second Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Ruping Tie
- Medical School of Chinese PLA, Department of Geriatric Cardiology, The Second Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Xiaolin Shang
- Department of Pharmacy, Medical Support Center of Chinese PLA General Hospital, Beijing, China
| | - Qianqian Zhao
- Medical School of Chinese PLA, Department of Cardiology, The Sixth Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Junjie Xu
- Health Service Department of the Guard Bureau of the General Office of the Central Committee of the Communist Party of China, Beijing, China
| | - Liyuan Jin
- Department of Geriatric Cardiology, The Second Medical Centre, Chinese PLA General Hospital, Beijing, China.
| | - Jinying Zhang
- Department of Basic Medicine, Medical School of Chinese PLA, Chinese PLA General Hospital, Beijing, China.
| | - Ping Ye
- Department of Geriatric Cardiology, The Second Medical Centre, Chinese PLA General Hospital, Beijing, China.
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Curcumin Alleviates D-Galactose-Induced Cardiomyocyte Senescence by Promoting Autophagy via the SIRT1/AMPK/mTOR Pathway. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:2990843. [PMID: 35880107 PMCID: PMC9308546 DOI: 10.1155/2022/2990843] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Accepted: 06/24/2022] [Indexed: 11/17/2022]
Abstract
Oxidative stress and impaired autophagy are the hallmarks of cardiac aging. However, there are no specific drugs available to prevent cardiac aging. Curcumin is a natural polyphenolic drug with antioxidant, antiaging, and autophagy-promoting effects. Here, we describe the preventive role of Curcumin in cardiac aging through the induction of autophagy and the restoration of autophagy via the SIRT1/AMPK/mTOR pathway. The number of cells positive for senescence-associated β-galactosidase, P53, P16, and intracellular ROS increased significantly in senescent cardiomyocytes, stimulated using D-galactose. Curcumin reversed this effect in a dose-dependent manner. Curcumin-induced autophagy increased the expression of SIRT1and phosphorylated AMPK and decreased phosphorylated mTOR in a dose-dependent manner. SIRT1-siRNA-mediated knockdown inhibited the antioxidation, antiaging, the promotion of autophagy, and the SIRT1/AMPK/mTOR pathway activation effect of curcumin. Therefore, curcumin could be an effective anticardiac aging drug.
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Resveratrol and Curcumin for Chagas Disease Treatment—A Systematic Review. Pharmaceuticals (Basel) 2022; 15:ph15050609. [PMID: 35631435 PMCID: PMC9143057 DOI: 10.3390/ph15050609] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Revised: 05/03/2022] [Accepted: 05/09/2022] [Indexed: 02/08/2023] Open
Abstract
Chagas disease (CD) is a neglected protozoan infection caused by Trypanosoma cruzi, which affects about 7 million people worldwide. There are two available drugs in therapeutics, however, they lack effectiveness for the chronic stage—characterized mainly by cardiac (i.e., cardiomyopathy) and digestive manifestations (i.e., megaesophagus, megacolon). Due to the involvement of the immuno-inflammatory pathways in the disease’s progress, compounds exhibiting antioxidant and anti-inflammatory activity seem to be effective for controlling some clinical manifestations, mainly in the chronic phase. Resveratrol (RVT) and curcumin (CUR) are natural compounds with potent antioxidant and anti-inflammatory properties and their cardioprotective effect have been proposed to have benefits to treat CD. Such effects could decrease or block the progression of the disease’s severity. The purpose of this systematic review is to analyze the effectiveness of RVT and CUR in animal and clinical research for the treatment of CD. The study was performed according to PRISMA guidelines and it was registered on PROSPERO (CDR42021293495). The results did not find any clinical study, and the animal research was analyzed according to the SYRCLES risk of bias tools and ARRIVE 2.0 guidelines. We found 9 eligible reports in this study. We also discuss the potential RVT and CUR derivatives for the treatment of CD as well.
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14
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Curcumin Inhibits the Proliferation of Renal Cancer 786-O Cells through MTOR Signaling Pathway and Its Mechanism. JOURNAL OF HEALTHCARE ENGINEERING 2022; 2022:1842389. [PMID: 35399832 PMCID: PMC8986413 DOI: 10.1155/2022/1842389] [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: 02/17/2022] [Revised: 03/10/2022] [Accepted: 03/16/2022] [Indexed: 12/14/2022]
Abstract
Objectives. The mechanism of curcumin inhibiting renal cancer 786-O cells proliferation through MTOR signaling pathway was investigated. Methods. Human renal cancer 786-O cells were cultured with curcumin for 48 h. The OD values were measured by the MTT method, and the growth inhibition rate of 786-O cells was calculated. The cell cycle distribution and apoptosis rate were detected by flow cytometry (FCM). Transwell chamber was introduced to detect cell invasion ability. Cell migration ability was detected by the cell scratch test. The protein expression was assessed by Western blot. Results. With curcumin concentration increasing, the expressions of MMP2, MMP9, MTOR, and p-MTOR proteins and the number of cells in the S phase decreased gradually, while number of cells in G1 and G2/M phases and cells apoptosis rate increased continuously. With the increasing of concentration and time, growth of 786-O cells in each treatment group was inhibited to varying degrees. The higher the inhibition rate was, the cells migration and transmembrane cells proportion decreased significantly. Conclusions. Curcumin inhibits the proliferation, migration, and invasion and induces apoptosis of renal cancer 786-O cells by blocking the MTOR signaling pathway. It may be related to the downregulation of MMP2 and MMP9 proteins.
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Lee JH, Kim DH, Kim M, Jung KH, Lee KH. Mitochondrial ROS-Mediated Metabolic and Cytotoxic Effects of Isoproterenol on Cardiomyocytes Are p53-Dependent and Reversed by Curcumin. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27041346. [PMID: 35209134 PMCID: PMC8877017 DOI: 10.3390/molecules27041346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 02/04/2022] [Accepted: 02/14/2022] [Indexed: 11/16/2022]
Abstract
Acute β-adrenergic stimulation contributes to heart failure. Here, we investigated the role of p53 in isoproterenol (ISO)-mediated metabolic and oxidative stress effects on cardiomyocytes and explored the direct protective effects offered by the antioxidant nutraceutical curcumin. Differentiated H9C2 rat cardiomyocytes treated with ISO were assayed for glucose uptake, lactate release, and mitochondrial reactive oxygen species (ROS) generation. Survival was assessed by sulforhodamine B assays. Cardiomyocytes showed significantly decreased glucose uptake and lactate release, as well as increased cellular toxicity by ISO treatment. This was accompanied by marked dose-dependent increases of mitochondria-derived ROS. Scavenging with N-acetyl-L-cysteine (NAC) effectively lowered ROS levels, which completely recovered glycolytic metabolism and survival suppressed by ISO. Mechanistically, ISO reduced extracellular-signal-regulated kinase (ERK) activation, whereas it upregulated p53 expression in an ROS-dependent manner. Silencing of p53 with siRNA blocked the ability of ISO to stimulate mitochondrial ROS and suppress glucose uptake, and partially recovered cell survival. Finally, curcumin completely reversed the metabolic and ROS-stimulating effects of ISO. Furthermore, curcumin improved survival of cardiomyocytes exposed to ISO. Thus, ISO suppresses cardiomyocyte glycolytic metabolism and survival by stimulating mitochondrial ROS in a p53-dependent manner. Furthermore, curcumin can efficiently rescue cardiomyocytes from these adverse effects.
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Affiliation(s)
- Jin Hee Lee
- Department of Nuclear Medicine, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea; (J.H.L.); (D.H.K.); (M.K.)
- Samsung Advanced Institute for Health and Sciences and Technology, Sungkyunkwan University School of Medicine, Seoul 06351, Korea
| | - Da Hae Kim
- Department of Nuclear Medicine, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea; (J.H.L.); (D.H.K.); (M.K.)
| | - MinA Kim
- Department of Nuclear Medicine, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea; (J.H.L.); (D.H.K.); (M.K.)
- Samsung Advanced Institute for Health and Sciences and Technology, Sungkyunkwan University School of Medicine, Seoul 06351, Korea
| | - Kyung-Ho Jung
- Department of Nuclear Medicine, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea; (J.H.L.); (D.H.K.); (M.K.)
- Samsung Advanced Institute for Health and Sciences and Technology, Sungkyunkwan University School of Medicine, Seoul 06351, Korea
- Correspondence: (K.-H.J.); (K.-H.L.); Tel.: +82-2-3410-2649 (K.-H.J.); +82-2-3410-2630 (K.-H.L.); Fax: +82-2-3410-2639 (K.-H.J. & K.-H.L.)
| | - Kyung-Han Lee
- Department of Nuclear Medicine, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea; (J.H.L.); (D.H.K.); (M.K.)
- Samsung Advanced Institute for Health and Sciences and Technology, Sungkyunkwan University School of Medicine, Seoul 06351, Korea
- Correspondence: (K.-H.J.); (K.-H.L.); Tel.: +82-2-3410-2649 (K.-H.J.); +82-2-3410-2630 (K.-H.L.); Fax: +82-2-3410-2639 (K.-H.J. & K.-H.L.)
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Alotaibi BS, Ijaz M, Buabeid M, Kharaba ZJ, Yaseen HS, Murtaza G. Therapeutic Effects and Safe Uses of Plant-Derived Polyphenolic Compounds in Cardiovascular Diseases: A Review. Drug Des Devel Ther 2021; 15:4713-4732. [PMID: 34848944 PMCID: PMC8619826 DOI: 10.2147/dddt.s327238] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Accepted: 09/12/2021] [Indexed: 12/29/2022] Open
Abstract
Polyphenols have long been recognized as health-promoting entities, including beneficial effects on cardiovascular disease, but their reputation has been boosted recently following a number of encouraging clinical studies in multiple chronic pathologies, that seem to validate efficacy. Health benefits of polyphenols have been linked to their well-established powerful antioxidant activity. This review aims to provide comprehensive and up-to-date knowledge on the current therapeutic status of polyphenols having sufficient heed towards the treatment of cardiovascular diseases. Furthermore, data about the safety profile of highly efficacious polyphenols has also been investigated to further enhance their role in cardiac abnormalities. Evidence is presented to support the action of phenolic derivatives against cardiovascular pathologies by following receptors and signaling pathways which ultimately cause changes in endogenous antioxidant, antiplatelet, vasodilatory, and anti-inflammatory activities. In addition, in vitro antioxidant and pre-clinical and clinical experiments on anti-inflammatory as well as immunomodulatory attributes of polyphenols have revealed their role as cardioprotective agents. However, an obvious shortage of in vivo studies related to dose selection and toxicity of polyphenols makes these compounds a suitable target for clinical investigations. Further studies are needed for the development of safe and potent herbal products against cardiovascular diseases. The novelty of this review is to provide comprehensive knowledge on polyphenols safety and their health claims. It will help researchers to identify those moieties which likely exert protective and therapeutic effects towards cardiovascular diseases.
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Affiliation(s)
- Badriyah Shadid Alotaibi
- Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Munazza Ijaz
- Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Pakistan
| | - Manal Buabeid
- Medical and Bio-Allied Health Sciences Research Centre, Ajman University, Ajman, United Arab Emirates
- Department of Clinical Sciences, Ajman University, Ajman, 346, United Arab Emirates
| | - Zelal Jaber Kharaba
- Department of Clinical Sciences, College of Pharmacy, Al-Ain University of Science and Technology, Abu Dhabi, United Arab Emirates
| | - Hafiza Sidra Yaseen
- Department of Pharmacy, COMSATS University Islamabad, Lahore Campus, Lahore, 54000, Pakistan
| | - Ghulam Murtaza
- Department of Pharmacy, COMSATS University Islamabad, Lahore Campus, Lahore, 54000, Pakistan
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Sadoughi F, Hallajzadeh J, Mirsafaei L, Asemi Z, Zahedi M, Mansournia MA, Yousefi B. Cardiac fibrosis and curcumin: a novel perspective on this natural medicine. Mol Biol Rep 2021; 48:7597-7608. [PMID: 34648140 DOI: 10.1007/s11033-021-06768-1] [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: 05/22/2021] [Accepted: 09/10/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND According to WHO statistics, cardiovascular disease are the leading causes of death in the world. One of the main factors which is causing heart failure, systolic and diastolic dysfunction, and arrythmias is a condition named cardiac fibrosis. This condition is defined by the accumulation of fibroblast-produced ECM in myocardium layer of the heart. OBJECTIVE Accordingly, the current review aims to depict the role of curcumin in the regulation of different signaling pathways that are involved in cardiac fibrosis. RESULTS A great number of cellular and molecular mechanisms such as oxidative stress, inflammation, and mechanical stress are acknowledged to be involved in cardiac fibrosis. Despite the available therapeutic procedures which are designed to target these mechanisms in order to prevent cardiac fibrosis, still, effective therapeutic methods are needed. Curcumin is a natural Chinese medicine which currently has been declared to have therapeutic properties such as anti-oxidant and immunomodulatory activities. In this review, we have gathered several experimental studies in order to represent diverse impacts of this turmeric derivative on pathogenic factors of cardiac fibrosis. CONCLUSION Curcumin might open new avenues in the field of cardiovascular treatment.
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Affiliation(s)
- Fatemeh Sadoughi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran
| | - Jamal Hallajzadeh
- Department of Biochemistry and Nutrition, Medicinal Plants Research Center, Maragheh University of Medical Sciences, Maragheh, Iran.
| | - Liaosadat Mirsafaei
- Department of Cardiology, Ramsar Campus, Mazandaran University of Medical Sciences, Sari, Iran
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran
| | - Mahdi Zahedi
- Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgān, Iran.
| | - Mohammad Ali Mansournia
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Bahman Yousefi
- Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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Zeng J, Wang L, Zhao J, Zheng Z, Peng J, Zhang W, Wen T, Nie J, Ding L, Yi D. MiR-100-5p regulates cardiac hypertrophy through activation of autophagy by targeting mTOR. Hum Cell 2021; 34:1388-1397. [PMID: 34138410 DOI: 10.1007/s13577-021-00566-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 06/07/2021] [Indexed: 01/12/2023]
Abstract
Autophagy has been proved to play a vital role in cardiac hypertrophy. The present study was designed to investigate the relationship between miR-100-5p and autophagy in the development of cardiac hypertrophy. Here, miR-100-5p expression was detected in abdominal aortic coarctation (AAC)-induced cardiac hypertrophy rats and Angiotensin II (Ang II)-stimulated cardiomyocytes. In vitro and in vivo experiments were performed to explore the function of miR-100-5p on autophagy and cardiac hypertrophy. We also investigated the mechanism of miR-100-5p on autophagy with dual-luciferase reporter assays, RNA immunoprecipitation (RIP), quantitative real-time PCR (qRT-PCR), western blot, immunofluorescence, and transmission electron microscopy (TEM). The results showed that miR-100-5p was highly expressed in hypertrophic hearts and Ang II-induced cardiomyocytes. Overexpression of miR-100-5p promoted the expression of cardiac hypertrophy markers ANP, BNP and β-MHC and cell surface area, while those were suppressed by miR-100-5p inhibitor. Knockdown of miR-100-5p by antagomiR significantly improves cardiac function and attenuate cardiac hypertrophy in vivo. Mechanistic investigation has found that miR-100-5p promote autophagy by targeting mTOR. Inhibition of autophagy by 3-methyladenine (3-MA) or mTOR overexpression could reverse the function of miR-100-5p in cardiac hypertrophy. These results elucidate that miR-100-5p promoted the pathogenesis of cardiac hypertrophy through autophagy activation by targeting mTOR.
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Affiliation(s)
- Junyi Zeng
- Department of Cardiology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, China.
- Jiangxi Hypertension Research Institute, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, China.
| | - Liang Wang
- Department of Cardiology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, China
| | - Jianqing Zhao
- Department of Cardiology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, China
| | - Zeqi Zheng
- Department of Cardiology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, China
- Jiangxi Hypertension Research Institute, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, China
| | - Jingtian Peng
- Department of Cardiology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, China
| | - Wan Zhang
- Jiangxi Hypertension Research Institute, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, China
| | - Tong Wen
- Department of Cardiology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, China
| | - Jungang Nie
- Department of Cardiology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, China
| | - Lu Ding
- Jiangxi Hypertension Research Institute, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, China
| | - Dasong Yi
- Department of Cardiology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, China
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Huang SL, Huang ZC, Zhang CJ, Xie J, Lei SS, Wu YQ, Fan PZ. LncRNA SNHG5 promotes the glycolysis and proliferation of breast cancer cell through regulating BACH1 via targeting miR-299. Breast Cancer 2021; 29:65-76. [PMID: 34351577 PMCID: PMC8732815 DOI: 10.1007/s12282-021-01281-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2020] [Accepted: 08/01/2021] [Indexed: 12/24/2022]
Abstract
Background Breast cancer (BC) is one of the most common malignant tumors in women. Accumulating studies have been reported that long non-coding RNA (lncRNA) SNHG5 is highly expressed in BC. However, the specific molecular mechanism of SNHG5 in BC is unclear. Methods Gene and protein expressions in BC cell were detected by qRT-PCR and western blotting. The proliferation and cell cycle were measured using colony formation assay and flow cytometry analysis, separately. The glucose consumption and lactate production were determined by using the glucose assay kit and lactate assay kit. A dual-luciferase reporter assay was performed to measure the interaction between miR-299 and SNHG5 or BACH1. Results SNHG5 and BACH1 expressions were increased in BC cell while miR-299 level was decreased. SNHG5 increased BACH1 expression by directly targeting miR-299. SNHG5 silencing or miR-299 overexpression suppressed the proliferation of BC cell, arrested the cell cycle in the G1 cell phase, and decreased the glucose consumption and lactate production of BC cell. However, inhibition of miR-299 or overexpression of BACH1 could reverse the inhibitory effects of sh-SNHG5 on cell proliferation and glycolysis in BC. Conclusion SNHG5 promoted the BC cell growth and glycolysis through up-regulating BACH1 expression via targeting miR-299. These findings may improve the diagnostic and therapeutic approaches to BC.
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Affiliation(s)
- Shu-Lin Huang
- Department of Breast and Thyroid Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, No. 61, Jiefang West Road, Changsha, 410005, Hunan Province, People's Republic of China
| | - Zhong-Cheng Huang
- Department of General Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, Hunan Province, People's Republic of China
| | - Chao-Jie Zhang
- Department of Breast and Thyroid Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, No. 61, Jiefang West Road, Changsha, 410005, Hunan Province, People's Republic of China
| | - Jing Xie
- Department of Breast and Thyroid Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, No. 61, Jiefang West Road, Changsha, 410005, Hunan Province, People's Republic of China
| | - Shan-Shan Lei
- Department of Breast and Thyroid Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, No. 61, Jiefang West Road, Changsha, 410005, Hunan Province, People's Republic of China
| | - Ya-Qin Wu
- Department of Breast and Thyroid Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, No. 61, Jiefang West Road, Changsha, 410005, Hunan Province, People's Republic of China
| | - Pei-Zhi Fan
- Department of Breast and Thyroid Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, No. 61, Jiefang West Road, Changsha, 410005, Hunan Province, People's Republic of China.
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Zhang L, Tan J, Liu YP, Liu X, Luo M. Curcumin relieves the arecoline-induced fibrosis of oral mucosal fibroblasts via inhibiting HIF-1α/TGF-β/CTGF signaling pathway: an in vitro study. Toxicol Res (Camb) 2021; 10:631-638. [PMID: 34141177 DOI: 10.1093/toxres/tfab046] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 04/19/2021] [Accepted: 04/27/2021] [Indexed: 11/14/2022] Open
Abstract
Oral submacosal fibrosis (OSF) has been recognized as one of the oral potentially malignant disorders. Areca nut chewing is implicated in this pathological fibrosis. The current treatments for OSF have failed to achieve the desired curative effect. Here, we propose that curcumin has excellent therapeutic effect on OSF and explore its specific mechanism. Transwell assay was performed to detected cell migration. Flow cytometry was used to measured apoptosis. And MTT assay was performed to test cell viability. Gene and protein levels were detected by quantitative real-time polymerase chain reaction (qPCR) and western blotting. Our results displayed that curcumin treatment reduced fibrosis-related molecules (collagen type I alpha 1, collagen type III alpha 1, tissue inhibitor of metalloprotease 2) in arecoline-treated oral mucosal fibroblasts and elevated matrix metalloproteinase 2 expression. Additionally, curcumin could suppress cell proliferation and migration, and enhance the apoptosis of arecoline-treated normal oral mucosal fibroblasts. Most importantly, the hypoxia-inducible factor-1α (HIF-1α), transforming growth factor-β (TGF-β) and connective tissue growth factor (CTGF) expressions in arecoline-treated normal oral mucosal fibroblasts were reduced after exposure to curcumin, whereas the activation of HIF-1α/TGF-β/CTGF axis reversed curcumin's effect on improving fibrosis of arecoline-treated normal oral mucosal fibroblasts. Therefore, curcumin alleviated oral submucosal fibrosis via inhibiting HIF-1α/TGF-β/CTGF axis. In summary, curcumin effectively inhibited the migration and proliferation and promoted apoptosis in arecoline-induced normal oral mucosal fibroblasts by inactivating HIF-1α/TGF-β/CTGF pathway. And curcumin might be a potential therapeutic drug for OSF treatment.
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Affiliation(s)
| | - Jin Tan
- Department of Stomatology, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan Province 410007, P.R. China
| | - Yi-Ping Liu
- Department of Stomatology, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan Province 410007, P.R. China
| | - Xun Liu
- Department of Stomatology, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan Province 410007, P.R. China
| | - Mang Luo
- Department of Stomatology, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan Province 410007, P.R. China
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Liu BY, Li L, Liu GL, Ding W, Chang WG, Xu T, Ji XY, Zheng XX, Zhang J, Wang JX. Baicalein attenuates cardiac hypertrophy in mice via suppressing oxidative stress and activating autophagy in cardiomyocytes. Acta Pharmacol Sin 2021; 42:701-714. [PMID: 32796955 PMCID: PMC8115069 DOI: 10.1038/s41401-020-0496-1] [Citation(s) in RCA: 85] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Accepted: 07/29/2020] [Indexed: 12/19/2022]
Abstract
Baicalein is a natural flavonoid extracted from the root of Scutellaria baicalensis that exhibits a variety of pharmacological activities. In this study, we investigated the molecular mechanisms underlying the protective effect of baicalein against cardiac hypertrophy in vivo and in vitro. Cardiac hypertrophy was induced in mice by injection of isoproterenol (ISO, 30 mg·kg-1·d-1) for 15 days. The mice received caudal vein injection of baicalein (25 mg/kg) on 3rd, 6th, 9th, 12th, and 15th days. We showed that baicalein administration significantly attenuated ISO-induced cardiac hypertrophy and restored cardiac function. The protective effect of baicalein against cardiac hypertrophy was also observed in neonatal rat cardiomyocytes treated with ISO (10 μM). In cardiomyocytes, ISO treatment markedly increased reactive oxygen species (ROS) and inhibited autophagy, which were greatly alleviated by pretreatment with baicalein (30 μM). We found that baicalein pretreatment increased the expression of catalase and the mitophagy receptor FUN14 domain containing 1 (FUNDC1) to clear ROS and promote autophagy, thus attenuated ISO-induced cardiac hypertrophy. Furthermore, we revealed that baicalein bound to the transcription factor FOXO3a directly, promoting its transcription activity, and transactivated catalase and FUNDC1. In summary, our data provide new evidence for baicalein and FOXO3a in the regulation of ISO-induced cardiac hypertrophy. Baicalein has great potential for the treatment of cardiac hypertrophy.
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Affiliation(s)
- Bing-Yan Liu
- School of Basic Medicine, Qingdao University, Qingdao, 266021, China
- Institute for Translational Medicine, Qingdao University, Qingdao, 266011, China
| | - Ling Li
- School of Basic Medicine, Qingdao University, Qingdao, 266021, China
| | - Gao-Li Liu
- Department of Cardiovascular Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Wei Ding
- Department of General Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266011, China
| | - Wen-Guang Chang
- Institute for Translational Medicine, Qingdao University, Qingdao, 266011, China
| | - Tao Xu
- Institute for Translational Medicine, Qingdao University, Qingdao, 266011, China
| | - Xiao-Yu Ji
- School of Basic Medicine, Qingdao University, Qingdao, 266021, China
- Institute for Translational Medicine, Qingdao University, Qingdao, 266011, China
| | - Xian-Xin Zheng
- School of Basic Medicine, Qingdao University, Qingdao, 266021, China
- Institute for Translational Medicine, Qingdao University, Qingdao, 266011, China
| | - Jing Zhang
- School of Basic Medicine, Qingdao University, Qingdao, 266021, China
- Institute for Translational Medicine, Qingdao University, Qingdao, 266011, China
| | - Jian-Xun Wang
- School of Basic Medicine, Qingdao University, Qingdao, 266021, China.
- Institute for Translational Medicine, Qingdao University, Qingdao, 266011, China.
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22
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Yang C, Zhao K, Zhang J, Wu X, Sun W, Kong X, Shi J. Comprehensive Analysis of the Transcriptome-Wide m6A Methylome of Heart via MeRIP After Birth: Day 0 vs. Day 7. Front Cardiovasc Med 2021; 8:633631. [PMID: 33829047 PMCID: PMC8019948 DOI: 10.3389/fcvm.2021.633631] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Accepted: 02/23/2021] [Indexed: 12/12/2022] Open
Abstract
Aim: To systematically classify the profile of the RNA m6A modification landscape of neonatal heart regeneration. Materials and Methods: Cardiomyocyte proliferation markers were detected via immunostaining. The expression of m6A modification regulators was detected using quantitative real-time PCR (qPCR) and Western blotting. Genome-wide profiling of methylation-modified transcripts was conducted with methylation-modified RNA immunoprecipitation sequencing (m6A-RIP-seq) and RNA sequencing (RNA-seq). The Gene Expression Omnibus database (GEO) dataset was used to verify the hub genes. Results: METTL3 and the level of m6A modification in total RNA was lower in P7 rat hearts than in P0 ones. In all, 1,637 methylation peaks were differentially expressed using m6A-RIP-seq, with 84 upregulated and 1,553 downregulated. Furthermore, conjoint analyses of m6A-RIP-seq, RNA-seq, and GEO data generated eight potential hub genes with differentially expressed hypermethylated or hypomethylated m6A levels. Conclusion: Our data provided novel information on m6A modification changes between Day 0 and Day 7 cardiomyocytes, which identified that increased METTL3 expression may enhance the proliferative capacity of neonatal cardiomyocytes, providing a theoretical basis for future clinical studies on the direct regulation of m6A in the proliferative capacity of cardiomyocytes.
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Affiliation(s)
- Chuanxi Yang
- Department of Cardiology, Medical School of Southeast University, Nanjing, China
| | - Kun Zhao
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jing Zhang
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiaoguang Wu
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Wei Sun
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiangqing Kong
- Department of Cardiology, Medical School of Southeast University, Nanjing, China.,Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jing Shi
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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23
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Molecules and Mechanisms to Overcome Oxidative Stress Inducing Cardiovascular Disease in Cancer Patients. Life (Basel) 2021; 11:life11020105. [PMID: 33573162 PMCID: PMC7911715 DOI: 10.3390/life11020105] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 01/18/2021] [Accepted: 01/27/2021] [Indexed: 02/06/2023] Open
Abstract
Reactive oxygen species (ROS) are molecules involved in signal transduction pathways with both beneficial and detrimental effects on human cells. ROS are generated by many cellular processes including mitochondrial respiration, metabolism and enzymatic activities. In physiological conditions, ROS levels are well-balanced by antioxidative detoxification systems. In contrast, in pathological conditions such as cardiovascular, neurological and cancer diseases, ROS production exceeds the antioxidative detoxification capacity of cells, leading to cellular damages and death. In this review, we will first describe the biology and mechanisms of ROS mediated oxidative stress in cardiovascular disease. Second, we will review the role of oxidative stress mediated by oncological treatments in inducing cardiovascular disease. Lastly, we will discuss the strategies that potentially counteract the oxidative stress in order to fight the onset and progression of cardiovascular disease, including that induced by oncological treatments.
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24
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Liao CL, Liu Y, Huang MZ, Liu HY, Ye ZL, Su Q. Myocardial ischemia reperfusion injury is alleviated by curcumin-peptide hydrogel via upregulating autophagy and protecting mitochondrial function. Stem Cell Res Ther 2021; 12:89. [PMID: 33509263 PMCID: PMC7842017 DOI: 10.1186/s13287-020-02101-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Accepted: 12/14/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Ischemia-reperfusion injury (IRI) is an important factor limiting the success of cardiac reperfusion therapy. Curcumin has a significant cardioprotective effect against IRI, can inhibit ventricular remodeling induced by pressure load or MI, and improve cardiac function. However, the poor water solubility and low bioavailability of curcumin restrict its clinical application. METHODS In this study, we prepared and evaluated a curcumin-hydrogel (cur-hydrogel) to reduce cardiomyocyte apoptosis and reactive oxygen species formation induced by hypoxia-reoxygenation injury, promote autophagy, and reduce mitochondrial damage by maintaining the phosphorylation of Cx43. RESULTS Meanwhile, cur-hydrogel can restore cardiac function, inhibit myocardial collagen deposition and apoptosis, and activate JAK2/STAT3 pathway to alleviate myocardial ischemia-reperfusion injury in rats. CONCLUSIONS The purpose of this study is to elucidate the protective effects of cur-hydrogel on myocardial ischemia-reperfusion injury by regulating apoptosis, autophagy, and mitochondrial injury in vitro and in vivo, which lays a new theoretical and experimental foundation for the prevention and reduction of IRI.
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Affiliation(s)
- Chi-Lin Liao
- Department of Cardiology, People's Hospital of Baise, Baise, 533000, People's Republic of China
| | - Yang Liu
- Department of Cardiology, The Second People's Hospital of Nanning City, The Third Affiliated Hospital of Guangxi Medical University, Nanning, 530031, People's Republic of China
| | - Meng-Zhao Huang
- Department of Cardiology, People's Hospital of Baise, Baise, 533000, People's Republic of China
| | - Hua-Yong Liu
- Department of Cardiology, People's Hospital of Baise, Baise, 533000, People's Republic of China
| | - Zi-Liang Ye
- Department of Cardiology, Affiliated Hospital of Guilin Medical University, No. 15, Lequn Road, Xiufeng District, Guilin, 541001, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Qiang Su
- Department of Cardiology, Affiliated Hospital of Guilin Medical University, No. 15, Lequn Road, Xiufeng District, Guilin, 541001, Guangxi Zhuang Autonomous Region, People's Republic of China.
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Senesi P, Luzi L, Terruzzi I. Adipokines, Myokines, and Cardiokines: The Role of Nutritional Interventions. Int J Mol Sci 2020; 21:ijms21218372. [PMID: 33171610 PMCID: PMC7664629 DOI: 10.3390/ijms21218372] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 11/02/2020] [Accepted: 11/03/2020] [Indexed: 02/06/2023] Open
Abstract
It is now established that adipose tissue, skeletal muscle, and heart are endocrine organs and secrete in normal and in pathological conditions several molecules, called, respectively, adipokines, myokines, and cardiokines. These secretory proteins constitute a closed network that plays a crucial role in obesity and above all in cardiac diseases associated with obesity. In particular, the interaction between adipokines, myokines, and cardiokines is mainly involved in inflammatory and oxidative damage characterized obesity condition. Identifying new therapeutic agents or treatment having a positive action on the expression of these molecules could have a key positive effect on the management of obesity and its cardiac complications. Results from recent studies indicate that several nutritional interventions, including nutraceutical supplements, could represent new therapeutic agents on the adipo-myo-cardiokines network. This review focuses the biological action on the main adipokines, myokines and cardiokines involved in obesity and cardiovascular diseases and describe the principal nutraceutical approaches able to regulate leptin, adiponectin, apelin, irisin, natriuretic peptides, and follistatin-like 1 expression.
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Affiliation(s)
- Pamela Senesi
- Department of Biomedical Sciences for Health, Università degli Studi di Milano, 20131 Milan, Italy; (P.S.); (L.L.)
- Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, 20138 Milan, Italy
| | - Livio Luzi
- Department of Biomedical Sciences for Health, Università degli Studi di Milano, 20131 Milan, Italy; (P.S.); (L.L.)
- Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, 20138 Milan, Italy
| | - Ileana Terruzzi
- Department of Biomedical Sciences for Health, Università degli Studi di Milano, 20131 Milan, Italy; (P.S.); (L.L.)
- Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, 20138 Milan, Italy
- Correspondence:
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26
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Tai X, Shen Y, Zhao H, Wang Z, Guan W, Kang X, Guo W. [Anti-scarring effect of rapamycin following filtering surgery in rabbit eyes]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2020; 40:1346-1352. [PMID: 32990236 DOI: 10.12122/j.issn.1673-4254.2020.09.19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
OBJECTIVE To study the effect of rapamycin on scar formation in rabbit eyes following filtering operation and explore the possible mechanism. METHODS Ninety-six healthy adult rabbits were subjected to trabeculectomy of the left eye and subsequently randomly divided into 4 groups (n=24) for treatment with castor oil (control) or rapamycin (1%, 3%, or 5%) eye drops of the operated eyes 4 times a day. The morphology and function of the filtering blebs of the rabbits were compared at 7, 14, 21 and 28 days after the operation; at each of the time points, 6 rabbits from each group were euthanized for detection of expressions of proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA) in the tissues in the surgical area using immunohistochemistry. Cultured rabbit subconjunctival fibroblasts (RTFSs) were treated with different concentrations of rapamycin (0.06, 0.25, 1, and 4 mg/L) and the cell apoptosis was detected using flow cytometry. RESULTS In the first, second and third weeks after the operation, the rate of functional follicle formation was significantly higher in the 3 rapamycin groups than in the control group (P < 0.05), and the number of α- SMA-positive fibroblasts decreased over time in the 3 rapamycin groups. In cultured RTFSs, treatment with rapamycin at different concentrations resulted in increased apoptosis of the cells, and rapamycin above 0.25 mg/L significantly increased the cell apoptosis in a dose-dependent manner. CONCLUSIONS Rapamycin can inhibit hyperplasia of the filtering passage tissue, helps to preserve the functional filtering blebs and prolong their life span, and induces apoptosis of RTFS.
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Affiliation(s)
- Xue Tai
- Center of Myopia, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China
| | - Ying Shen
- Center of Myopia, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China
| | - Haixia Zhao
- Center of Myopia, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China
| | - Zhaoge Wang
- Center of Myopia, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China
| | - Wenying Guan
- Center of Myopia, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China
| | - Xin Kang
- Center of Myopia, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China
| | - Wenqi Guo
- Department of Emergency Medicine, Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010030, China
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27
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Role of Autophagy on Heavy Metal-Induced Renal Damage and the Protective Effects of Curcumin in Autophagy and Kidney Preservation. ACTA ACUST UNITED AC 2019; 55:medicina55070360. [PMID: 31295875 PMCID: PMC6681384 DOI: 10.3390/medicina55070360] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Revised: 06/28/2019] [Accepted: 07/08/2019] [Indexed: 12/16/2022]
Abstract
Curcumin is a hydrophobic polyphenol compound extracted from the rhizome of turmeric. The protective effect of curcumin on kidney damage in multiple experimental models has been widely described. Its protective effect is mainly associated with its antioxidant and anti-inflammatory properties, as well as with mitochondrial function maintenance. On the other hand, occupational or environmental exposure to heavy metals is a serious public health problem. For a long time, heavy metals-induced nephrotoxicity was mainly associated with reactive oxygen species overproduction and loss of endogenous antioxidant activity. However, recent studies have shown that in addition to oxidative stress, heavy metals also suppress the autophagy flux, enhancing cell damage. Thus, natural compounds with the ability to modulate and restore autophagy flux represent a promising new therapeutic strategy. Furthermore, it has been reported in other renal damage models that curcumin’s nephroprotective effects are related to its ability to regulate autophagic flow. The data indicate that curcumin modulates autophagy by classic signaling pathways (suppression of protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and/or by stimulation of adenosine monophosphate-activated protein kinase (AMPK) and extracellular signal-dependent kinase (ERK) pathways). Moreover, it allows lysosomal function preservation, which is crucial for the later stage of autophagy. However, future studies of autophagy modulation by curcumin in heavy metals-induced autophagy flux impairment are still needed.
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