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| Death receptor-mediated signaling pathway of ginsenoside in relieving MC apoptosis. FasL, Fas ligand; FADD, Fas-associated death domain protein; DISC, death-induced signal complex; tBid, truncated Bid; cyt-C, cytochrome C.
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Ischemic heart disease has a high mortality, and the recommended therapy is reperfusion. Nevertheless, the restoration of blood flow to ischemic tissue leads to further damage, namely, myocardial ischemia/reperfusion injury (MIRI). Apoptosis is an essential pathogenic factor in MIRI, and ginsenosides are effective in inhibiting apoptosis and allevi...
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Acute myocardial infarction (MI) is the leading cause of death worldwide. Exogenous delivery of nitric oxide (NO) to the infarcted myocardium has proven to be an effective strategy for treating MI due to the multiple physiological functions of NO. However, reperfusion of blood flow to the ischemic tissues is accompanied by the overproduction of tox...
Citations
... Actually, the regulatory action of lncRNA Snhg1 on cell viability has also been demonstrated in multiple disorders, such as cancers, Parkinson's disease, and hypoxic injury [38][39][40]. Besides, apoptosis is a significant feature of MIRI and is considered an essential pathogenic factor in MIRI [3,41]. Apoptosis causes cardiomyocyte loss and myocardium remolding and aggravates inflammatory response [3]. ...
... Apoptosis causes cardiomyocyte loss and myocardium remolding and aggravates inflammatory response [3]. Therefore, inhibiting myocardial cell apoptosis is critical for limiting MIRI progression [41]. This research demonstrated that enforced lncRNA Snhg1 restrained myocardial cell apoptosis in H/R-stimulated HL-1 cells and I/R mice model. ...
Background
Myocardial ischemia-reperfusion injury (MIRI) is caused by reperfusion after ischemic heart disease. LncRNA Snhg1 regulates the progression of various diseases. N6-methyladenosine (m⁶A) is the frequent RNA modification and plays a critical role in MIRI. However, it is unclear whether lncRNA Snhg1 regulates MIRI progression and whether the lncRNA Snhg1 was modified by m⁶A methylation.
Methods
Mouse cardiomyocytes HL-1 cells were utilized to construct the hypoxia/reoxygenation (H/R) injury model. HL-1 cell viability was evaluated utilizing CCK-8 method. Cell apoptosis, mitochondrial reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were quantitated utilizing flow cytometry. RNA immunoprecipitation and dual-luciferase reporter assays were applied to measure the m⁶A methylation and the interactions between lncRNA Snhg1 and targeted miRNA or target miRNAs and its target gene. The I/R mouse model was constructed with adenovirus expressing lncRNA Snhg1. HE and TUNEL staining were used to evaluate myocardial tissue damage and apoptosis.
Results
LncRNA Snhg1 was down-regulated after H/R injury, and overexpressed lncRNA Snhg1 suppressed H/R-stimulated cell apoptosis, mitochondrial ROS level and polarization. Besides, lncRNA Snhg1 could target miR-361-5p, and miR-361-5p targeted OPA1. Overexpressed lncRNA Snhg1 suppressed H/R-stimulated cell apoptosis, mitochondrial ROS level and polarization though the miR-361-5p/OPA1 axis. Furthermore, WTAP induced lncRNA Snhg1 m⁶A modification in H/R-stimulated HL-1 cells. Moreover, enforced lncRNA Snhg1 repressed I/R-stimulated myocardial tissue damage and apoptosis and regulated the miR-361-5p and OPA1 levels.
Conclusion
WTAP-mediated m⁶A modification of lncRNA Snhg1 regulated MIRI progression through modulating myocardial apoptosis, mitochondrial ROS production, and mitochondrial polarization via miR-361-5p/OPA1 axis, providing the evidence for lncRNA as the prospective target for alleviating MIRI progression.
... Owing to the intricate nature of I/RI disease, its exact pathophysiology has not been fully understood. However, it has been reported that inhibiting cell death pathways could potentially reduce nearly half of the ultimate infarct size [2,3] . The underlying pathophysiology of I/RI includes oxidative stress (due to excessive production of ROS [4] ), abnormal increase in calcium, mitochondrial malfunction, and an inflammatory response that eventually triggers cell death signaling like necrosis, apoptosis, and necroptosis [2,5,6] . ...
... However, it has been reported that inhibiting cell death pathways could potentially reduce nearly half of the ultimate infarct size [2,3] . The underlying pathophysiology of I/RI includes oxidative stress (due to excessive production of ROS [4] ), abnormal increase in calcium, mitochondrial malfunction, and an inflammatory response that eventually triggers cell death signaling like necrosis, apoptosis, and necroptosis [2,5,6] . Hence, finding appropriate treatment for I/RI disease, as one of the most important medical problems, would be a lifesaver. ...
Background:
Simvastatin (SIM) has anti-inflammatory and antioxidant properties against cardiac ischemia/reperfusion injury (I/RI). However, it suffers from low bioavailability and a short half-life. Nanoniosomes are novel drug delivery systems that may increase SIM effectiveness. The present research evaluates the impact of SIM-loaded nanoniosomes on the oxygen-glucose deprivation/reperfusion (OGD/R) injury model of H9c2 cells.
Methods:
Cells were seeded based on five groups: (1) control; (2) OGD/R; (3) OGD/R receiving SIM; (4) OGD/R receiving nanoniosomes; and (5) OGD/R receiving SIM loaded nanoniosomes. OGD/R injury of the H9c2 cells was treated with SIM or SIM loaded nanoniosomes. Cell viability, two inflammatory factors, necroptosis factors, along with HMGB1 and Nrf2 gene expressions were assessed.
Results:
The cells treated with SIM loaded nanoniosomes showed a significant elevation in the cell viability and a reduction in HMGB1, Nrf2, TNF-α, IL-1β, RIPK1, and ROCK1 expression levels compared to the OGD/R and SIM groups.
Conclusion:
Based on our findings, nanoniosomes could safely serve as a drug delivery system to counterbalance the disadvantages of SIM, resulting in improved aqueous solubility and stability.
... The anti-apoptosis effect of EPG partly accounted for its rescue activity on MI rats ( Fig. 3A and B). Similar to our present study, ginsenosides and ginsenoside Rg1 [48], which is up to 9.62% in EPG, had been proven to inhibit myocardial cell apoptosis against I/R injury. STIM1 activates TRPC1 via its C-terminal polybasic domain, which is distinct from its ORAI1-activating domain; and knockdown of STIM1 dramatically reduces TRPC1-mediated SOCE and Ca 2þ current [7]. ...
Background
Caveolin-1, the scaffolding protein of cholesterol-rich invaginations, plays an important role in store-operated Ca²⁺ influx and its phosphorylation at Tyr14 (p-caveolin-1) is vital to mobilize protection against myocardial ischemia (MI) injury. SOCE, comprising STIM1, ORAI1 and TRPC1, contributes to intracellular Ca²⁺ ([Ca²⁺]i) accumulation in cardiomyocytes. The purified extract of steamed Panax ginseng (EPG) attenuated [Ca²⁺]i overload against MI injury. Thus, the aim of this study was to investigate the possibility of EPG affecting p-caveolin-1 to further mediate SOCE/[Ca²⁺]i against MI injury in neonatal rat cardiomyocytes and a rat model.
Methods
PP2, an inhibitor of p-caveolin-1, was used. Cell viability, [Ca²⁺]i concentration were analyzed in cardiomyocytes. In rats, myocardial infarct size, pathological damages, apoptosis and cardiac fibrosis were evaluated, p-caveolin-1 and STIM1 were detected by immunofluorescence, and the levels of caveolin-1, STIM1, ORAI1 and TRPC1 were determined by RT-PCR and Western blot. And, release of LDH, cTnI and BNP was measured.
Results
EPG, ginsenosides accounting for 57.96%, suppressed release of LDH, cTnI and BNP, and protected cardiomyocytes by inhibiting Ca²⁺ influx. And, EPG significantly relieved myocardial infarct size, cardiac apoptosis, fibrosis, and ultrastructure abnormality. Moreover, EPG negatively regulated SOCE via increasing p-caveolin-1 protein, decreasing ORAI1 mRNA and protein levels of ORAI1, TRPC1 and STIM1. More importantly, inhibition of the p-caveolin-1 significantly suppressed all of the above cardioprotection of EPG.
Conclusions
Caveolin-1 phosphorylation is involved in the protective effects of EPG against MI injury via increasing p-caveolin-1 to negatively regulate SOCE/[Ca²⁺]i.
... Apoptosis is a regulated form of programmed cell death; it is characterized by cell shrinkage, condensation of cytoplasm, nuclear shrinkage, and formation of apoptotic bodies [94]. Apoptosis is an important pathological mechanism involved in the entire MIRI process; it aggravates myocardial injury and leads to myocardial dysfunction [95]. ...
Review Recent Advances in Natural Plant-based Treatment of Myocardial Ischemia-reperfusion Injury Peixun Yang 1,3,4, Minxuan Liu 2,3,4, Xiaoxue Fan 3,4, Xinzhuang Zhang 3,4, Liang Cao 3,4, Zhenzhong Wang 3,4, and Wei Xiao 3,4, * 1 Kanion School of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Avenue Qixia District, Nanjing 210046, China 2 School of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Avenue Qixia District, Nanjing 210046, China 3 National Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangning Industrial City, Economic and Technological Development Zone of Lianyungang, Lianyungang 222001, China 4 Jiangsu Kanion Pharmaceutical Co Ltd, Jiangning Industrial City, Economic and Technological Development Zone of Lianyungang, Lianyungang 222001, China * Correspondence: xw_kanion@163.com ( Wei Xiao) Received: 23 March 2023 Accepted: 10 May 2023 Abstract: Cardiovascular disease (CDV) is the primary cause of death in the world, and myocardial ischemia (MI) is one of the high-risk CVDs. The myocardial blood supply must be restored as soon as possible to reduce the mortality risk, however, reperfusion itself paradoxically leads to further death of cardiomyocytes and increases the infarct size; this is known as myocardial ischemia/reperfusion injury (MIRI). The pathological mechanism of MIRI is complex, and current research mainly focuses on oxidative stress, dysfunctional mitochondrial energy metabolism, Ca 2+ overload, endoplasmic reticulum stress (ERs) and the inflammatory response. This review briefly summarizes the mechanism of MIRI, and natural plant product (NPP) components proven to ameliorate MIRI and their related signaling pathways. NPPs can alleviate MIRI by regulating oxidative stress, inflammation, ERs, Ca 2+ overload and mitochondrial function maintenance. This review will deepen our understanding of how NPPs reduce MIRI and the future value of NPPs in cardio-protection.
... IHD occurring due to blocked coronary arteries has become one of the leading causes of morbidity and mortality in the world [5,18]. Reperfusion therapy is a double-edged sword that can restore the coronary blood flow to prevent the ischemic cardiomyocytes from injury but can also result in extra damage to the cardiomyocytes, which is called MI/RI [19,20]. Clinical symptoms of MI/RI include reperfusion arrhythmias, heart failure, and even sudden cardiac death [21]. ...
Inflammation is the primary pathological process of myocardial ischemia/reperfusion injury (MI/RI). 7-Hydroxyflavone (HF), a natural flavonoid with a variety of bioactivities, plays a crucial role in various biological processes. However, its cardioprotective effects and the underlying mechanisms of MI/RI have not been investigated. This study aimed to explore whether pretreatment with HF could attenuate MI/RI-induced inflammation in rats and investigate its potential mechanisms. The results showed that pretreatment with HF could significantly improve the anatomic data and electrocardiograph parameters, reduce the myocardial infarct size, decrease markers of myocardial injury (aspartate transaminase, creatine kinase, lactate dehydrogenase, and cardiac troponin I), inhibit inflammatory cytokines (IL-1β, IL-6, and TNF-α), suppress oxidative stress, and recover the architecture of the cardiomyocytes. The cardioprotective effect of HF was connected with the regulation of the MAPK/NF-κB signaling pathway. What is more, molecular docking was carried out to prove that HF could be stably combined with p38, ERK1/2, JNK, and NF-κB. In summary, this is a novel study demonstrating the cardioprotective effects of HF against MI/RI in vivo. Consequently, these results demonstrate that HF can be considered a promising potential therapy for MI/RI.
Myocardial ischemia/reperfusion (I/R) injury is the leading cause of death worldwide. Ginsenoside Rd (GRd) has cardioprotective properties but its efficacy and mechanism of action in myocardial I/R injury have not been clarified. This study investigated GRd as a potent therapeutic agent for myocardial I/R injury. Oxygen-glucose deprivation and reperfusion (OGD/R) and left anterior descending (LAD) coronary artery ligation were used to establish a myocardial I/R injury model in vitro and in vivo. In vivo, GRd significantly reduced the myocardial infarct size and markers of myocardial injury and improved the cardiac function in myocardial I/R injury mice. In vitro, GRd enhanced cell viability and protected the H9c2 rat cardiomyoblast cell line from OGD-induced injury GRd. The network pharmacology analysis predicted 48 potential targets of GRd for the treatment of myocardial I/R injury. GO and KEGG enrichment analysis indicated that the cardioprotective effects of GRd were closely related to inflammation and apoptosis mediated by the PI3K/Akt signaling pathway. Furthermore, GRd alleviated inflammation and cardiomyocyte apoptosis in vivo and inhibited OGD/R-induced apoptosis and inflammation in cardiomyocytes. GRd also increased PI3K and Akt phosphorylation, suggesting activation of the PI3K/Akt pathway, whereas LY294002, a PI3K inhibitor, blocked the GRd-induced inhibition of OGD/R-induced apoptosis and inflammation in H9c2 cells. The therapeutic effect of GRd in vivo and in vitro against myocardial I/R injury was primarily dependent on PI3K/Akt pathway activation to inhibit inflammation and cardiomyocyte apoptosis. This study provides new evidence for the use of GRd as a cardiovascular drug.
Purpose
The present study aimed to investigate the cardioprotective potential of soluble guanylate cyclase (sGC) and its 1 subunit on myocardial ischemia/reperfusion injury (MIRI), as well as the potential mechanism.
Methods
SD rats were subjected to left coronary artery ischemia/reperfusion, and H9C2 cells were cultured in an Anaero Pack anaerobic bag to induce a MIRI model. Myocardial infarction area, myocardial tissue morphology and myocardial tissue ultrastructure were observed by TTC, HE and transmission electron microscopy, respectively. Myocardial tissues of each group were examined by colorimetric assay for CAT, GSH-Px and SOD, TUNEL staining for apoptosis, ELISA for cGMP, and Western blot for protein expression of Capase3, sGCα1, PGC-1α and UCP2.
Results
In vivo, sGC exerted cardioprotective effects, as shown by a reduced myocardial infarct size. sGC also reduced oxidative stress and apoptosis in myocardial cells, which was associated with the activation of PGC-1α and UCP2. The protein expression of sGCα1 changes with the activity of sGC. In vitro, sGCα1 inhibited oxidative stress and apoptosis in H9C2 cells by activating the PGC-1α/UCP2 pathway.
Conclusion
Our results suggest that sGC and its α1 subunit exert cardioprotective effects by inhibiting oxidative stress and cell apoptosis during MIRI and reveal a potential mechanism involving the PGC-1α/UCP2 pathway.
Myocardial ischemia/reperfusion injury (MIRI) is the principal cause of death and occurs after prolonged blockage of the coronary arteries. Diabetes represents one of the main factors aggravating myocardial injury. Restoring blood flow is the first intervention against a heart attack, although reperfusion process could cause additional damage, such as the overproduction of reacting oxygen species (ROS). In recent years, açaí berry has gained international attention as a functional food due to its antioxidant and anti-inflammatory proprieties; not only, this fruit has shown glucose-lowering effects. Therefore, this study was designed to evaluate the cardioprotective effects of açaí berry on the inflammatory and oxidative response associated with diabetic MIRI. Diabetes was induced in rats by a single intravenous inoculation of streptozotocin (60 mg/kg) and allowed to develop for 60 days. MIRI was induced by occlusion of the left anterior descending coronary artery for 30 minutes followed by 2 hours of reperfusion. Açaí (200mg/kg) was administered 5 minutes before the end of ischemia and 1 hours after reperfusion. In this study, we clearly demonstrated that açaí treatment was able to reduce biomarkers of myocardial damage, infarct size and apoptotic process. Moreover, açaí administrations reduced inflammatory and oxidative response, modulating Nf-kB and Nrf2 pathways. These results suggest that açai berry supplementation could represent a useful strategy for pathological events associated to MIRI.
Heart diseases have a high incidence and mortality rate, and seriously affect people's quality of life. Mitochondria provide energy for the heart to function properly. The process of various heart diseases is closely related to mitochondrial dysfunction. Panax ginseng (P. ginseng), as a traditional Chinese medicine, is widely used to treat various cardiovascular diseases. Many studies have confirmed that P. ginseng and ginsenosides can regulate and improve mitochondrial dysfunction. Therefore, the role of mitochondria in various heart diseases and the protective effect of P. ginseng on heart diseases by regulating mitochondrial function were reviewed in this paper, aiming to gain new understanding of the mechanisms, and promote the clinical application of P. ginseng.
Myocardial ischemia has a high incidence and mortality rate, and reperfusion is currently the standard intervention. However, reperfusion may lead to further myocardial damage, known as myocardial ischemia/reperfusion injury (MIRI). There are currently no effective clinical treatments for MIRI. The PI3K/Akt signaling pathway is involved in cardiovascular health and disease and plays an important role in reducing myocardial infarct size and restoring cardiac function after MIRI. Activation of the PI3K/Akt pathway provides myocardial protection through synergistic upregulation of antioxidant, anti-inflammatory, and autophagy activities and inhibition of mitochondrial dysfunction and cardiomyocyte apoptosis. Many studies have shown that PI3K/Akt has a significant protective effect against MIRI. Here, we reviewed the molecular regulation of PI3K/Akt in MIRI and summarized the molecular mechanism by which PI3K/Akt affects MIRI, the effects of ischemic preconditioning and ischemic postconditioning, and the role of related drugs or activators targeting PI3K/Akt in MIRI, providing novel insights for the formulation of myocardial protection strategies. This review provides evidence of the role of PI3K/Akt activation in MIRI and supports its use as a therapeutic target.
