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Ferulic acid (FA) alleviated mitochondrial dysfunction following hypoxia/reoxygenation (H/R). (A) ADP/ATP ratio. (B) JC-1 staining. The ratio of Red/Green fluorescence reflected change in the mitochondrial membrane potential. (C, D) Cells were analyzed by flow cytometry after being stained with DCFDA to detect ROS. Data were expressed as mean ± SEM (n = 3). *P < 0.05 and **P < 0.01 versus the control group. #P < 0.05 and ##P < 0.01 versus the H/R group.
Source publication
Ferulic acid protects against cardiac injury by scavenging free radicals. However, the role of mitophagy in ferulic acid-induced cardioprotection remains obscure. In the present study, H9c2 cells were exposed to hypoxia/reoxygenation and ferulic acid treatment during hypoxia. We illustrated the impact of ferulic acid on oxidative damage in H9c2 cel...
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Citations
... Ferulic acid decreases mitochondrial binding to lysosomes and downregulates the PINK1/Parkin pathway to protect cardiomyocytes from I/R injury [93]. Oxidative stress is one of the main risk factors for reperfusion injury, and aspirin eugenol ester (AEE) has been shown to reduce oxidative stress in human umbilical vein endothelial cells through the mitochondria-lysosome axis [94]. ...
Organelle damage is a significant contributor to myocardial ischemia/reperfusion (I/R) injury. This damage often leads to disruption of endoplasmic reticulum protein regulatory programs and dysfunction of mitochondrial energy metabolism. Mitochondria and endoplasmic reticulum are seamlessly connected through the mitochondrial-associated endoplasmic reticulum membrane (MAM), which serves as a crucial site for the exchange of organelles and metabolites. However, there is a lack of reports regarding the communication of information and metabolites between mitochondria and related organelles, which is a crucial factor in triggering myocardial I/R damage. To address this research gap, this review described the role of crosstalk between mitochondria and the correlative organelles such as endoplasmic reticulum, lysosomal and nuclei involved in reperfusion injury of the heart. In summary, this review aims to provide a comprehensive understanding of the crosstalk between organelles in myocardial I/R injury, with the ultimate goal of facilitating the development of targeted therapies based on this knowledge.
Graphical Abstract
... Ferulic acid (FA) is a ubiquitous polyphenol in the hydroxycinnamic acids group found in large quantities in cereals, cocoa and herbs [11]. Studies have pointed to FA's remarkable bioactive potential in conditions such as diabetes [12,13] and cardiovascular diseases [14,15]. Numerous animal studies have documented FA supplementation's ability to alleviate DM-associated manifestations, including its ability to counteract oxidative damage in tissue, decrease blood glucose and plasma insulin levels, and improve lipid profiles [12,13,[16][17][18][19][20][21]. ...
This study investigated the differences in health outcomes associated with ferulic acid (FA) supplementation in animals before the induction of diabetes with streptozotocin (STZ) treatment and post-STZ treatment. 18 male Wistar rats were equally distributed into three groups: groups 1 and 2 received FA (50 mg/kg body weight) supplementation one week before STZ treatment (60 mg/kg body weight, intraperitoneal) and one week after STZ treatment, respectively; group 3 received STZ without FA supplementation. FA supplementation was continued for 12 weeks after STZ treatment. The results indicated no difference in glucose and lipid profile with FA supplementation. However, FA supplementation reduced lipid and protein oxidative damage in the heart, liver and pancreas and increased glutathione in the pancreas. The results indicate that while oxidative damages were positively affected by FA, it was not sufficient to improve metabolic markers of diabetes.
... Rat cardiomyocyte H9c2 cells are immortalized cells with a cardiac phenotype; H9c2 cells are the most commonly used cell type for isolated primary cardiomyocyte characteristics, they are easily accessible and cultured (Chou et al., 2010;Kuznetsov et al., 2015;Upadhyay et al., 2020;Hu et al., 2022), and they have been used as models in ischemia and reperfusion studies (Han et al., 2004;Wang et al., 2016;Shengm et al., 2019;Luo et al., 2020;Ma et al., 2020). Thus, we analyzed the expression of microRNAs following astaxanthin treatment in an anoxia-reoxygenation system for H9c2 cardiomyocytes to uncover targets of astaxanthin action and guide strategies for myocardial A/R protection. ...
Introduction: The protective effects of astaxanthin against myocardial ischemia-reperfusion injuries are well documented, although the mechanisms are not defined.
Methods: The anoxia-reoxygenation injury model was established after astaxanthin treated H9c2 cells for 24 h. Cell viability, lactate dehydrogenase, oxidative stress level and western blot were tested. Secondly, measured the effects of astaxanthin pretreatment on microRNA expression in a rat myocardial cell anoxia-reoxygenation injury model.
Results: After anoxia-reoxygenation injury, in a dose dependent manner, astaxanthin increased cell viability, superoxide dismutase and glutathione peroxidase activity, decreased lactate dehydrogenase and malondialdehyde levels, downregulated protein expression of caspase-3, caspase-8, nuclear factor erythroid-2-related factor 2 and heme oxygenase-1, and upregulated the Bcl-2/Bax ratio. High-throughput sequencing and qPCR showed that microRNAs rno-miR-125b-5p and rno-let-7c-1-3p were differentially expressed (|log2| ≥ 0.585, q < 0.1) between the normal, anoxia-reoxygenation, and astaxanthin (1.25 μM) groups. Kyoto Encyclopedia of Genes and Genomes and GO Gene ontology pathway enrichment analyses showed that TNF signaling, axon guidance, NF-κB signaling pathway, and other pathways displayed differentially expressed microRNA target genes associated with myocardial injuries.
Discussion: These results suggested that thetarget genes of rno-miR-125b-5p were enriched in inflammation and apoptosis-related signaling pathways. Also, the results imply that simultaneous targeting of these related signaling pathways could significantly prevent myocardial anoxia-reoxygenation injury in the presence of astaxanthin.
... Components of TYHX were identified by previous high-performance liquid chromatography (HPLC) studies, and five significant components were confirmed, including ferulic acid, ginsenoside Rb1, astragaloside IV, diosgenin, and catalpol [8]. These components of TYHX have great potential for therapy and prevention in multiple cardiovascular diseases, including antioxidant, antiapoptotic, and anti-inflammatory effects [26,27]. In addition, it can play a protective role for various cells (cardiomyocytes, sinoatrial node cells, and endothelial cells) under stress conditions [28][29][30]. ...
Background:
The transient outward potassium current (I to) and the ultrarapid delayed rectifier potassium current (I Kur) are major potassium currents involved in the repolarization process of sinoatrial node cells (SNCs).
Methods and results:
The SNCs of neonatal rats were divided into control, ischemia/reperfusion (I/R), I/R+blank serum, and Tongyang Huoxue recipe (TYHX) serum groups. I to and I Kur were recorded using the whole cell patch-clamp technique, and the current-voltage (I-V), steady-state activation (SSA), steady-state inactivation (SSI), and recovery from inactivation (RFI) curves were plotted, respectively. Compared to the control group, both the peak current density and the current density at the voltage of I to and I Kur decreased obviously in SNCs after simulated I/R, the SSA curves moved right, and the SSI curves moved left. After TYHX was added to the extracellular solution of SNCs, both the peak current density and the current density at the voltage of I to and I Kur increased significantly, the SSA curves moved left, and the SSI curves moved right with a significant difference of V 1/2. The recovery from the I Kur RFI curves was slightly restored, and the I to curves did not change.
Conclusions:
TYHX increases the peak current density, accelerates the activation, and decreases the inactivation of the I to and I Kur. This may be the mechanism of TYHX in shortening the action potential duration of repolarization, which accelerates spontaneous pulsation.
... We previously discussed that ferulic acid has protected cardiomyocytes by regulating mitophagy; however, the specific regulatory mechanism has not been elucidated. According to in vitro experiments [156], mitophagy is a selective form of autophagy that can become hyperactivated in hypoxic/reoxygenated H9C2 cells. Ferulic acid can prevent heart damage by scavenging free radicals and affecting oxidative injury. ...
Heart failure occurs because of various cardiovascular pathologies, such as coronary artery disease or cardiorenal syndrome, eventually reaching end-stage disease. Various factors contribute to cardiac structural or functional changes that result in systolic or diastolic dysfunction. Several studies have confirmed that the key factor in heart failure progression is myocardial cell death, and mitophagy is the major mechanism regulating myocardial cell death in heart failure. The clinical mechanisms of heart failure are well understood in practice. However, the essential role of mitophagic regulation in heart failure has only recently received widespread attention. Receptor-mediated mitophagy is involved in various mitochondrial processes like oxidative stress injury, energy metabolism disorders, and calcium homeostasis, which are also the main causes of heart failure. Understanding of the diverse regulatory mechanisms in mitophagy and the complexity of its pathophysiology in heart failure remains incomplete. Related studies have found that various natural medicinal plants and active ingredients, such as flavonoids and saponins, can regulate mitophagy to a certain extent, improve myocardial function, and protect myocardial cells. This review comprehensively covers the relevant mechanisms of different types of mitophagy in regulating heart failure pathology and controlling mitochondrial adaptability to stress injury. Further, it explores the relationship between mitophagy and cardiac ejection dysfunction. Natural medicinal plant-targeted regulation strategies and scientific evidence on mitophagy were provided to elucidate current and potential strategies to apply mitophagy-targeted therapy for heart failure.
... According to previous research studies, activating Parkin-dependent mitophagy could reduce injuries led by OxS and protect cells from different stimuli on cardiomyocytes, like CoCl 2 and hypoxia/reoxygenation (H/R) (Sun et al., 2016;Cao et al., 2020). At present, research studies have confirmed that various compounds possess cardioprotective effects via regulating mitophagy (Xu et al., 2019;Hu et al., 2020;Luo et al., 2020). ...
... Vanillic acid (4-hydroxy-3-methoxybenzoicacid (VA) Figure 1), a cinnamic acid derivative, exists widely in nature and is found abundantly in several Chinese herbal medicines like Picrorhiza scrophulariiflora Pennell, Atractylodes macrocephala, and Coptis chinensis. VA has a strong antioxidant effect and demonstrates therapeutic potential against CVDs, which could reduce the production of intracellular ROS and reduce myocardial cell damage caused by hypoxia and reoxygenation (Luo et al., 2020;Kaur et al., 2022). At present, research about VA effects on cardioprotective focuses on reducing apoptotic rate and lipid peroxidation (Stanely Mainzen Prince et al., 2011), but there is lack of research studies on effects for mediating mitophagy. ...
Vanillic acid, a phenolic compound mainly obtained from the foot of Picrorhiza scrophulariiflora Pennell, has been demonstrated to possess a cardiovascular-protective effect in previous studies. However, there is lack of research on vanillic acid protecting cardiomyocytes from oxidative stress injury by mediating mitophagy. In the present study, oxidative stress injury in the H9c2 cell line was induced by H2O2. Our results confirmed that vanillic acid mitigated apoptosis and injury triggered by oxidative stress, evidenced by the decline in production of reactive oxygen species and malondialdehyde and level of lactate dehydrogenase and the increase of superoxide dismutase and glutathione. The use of vanillic acid could also improve the polarization of mitochondrial membrane potential and decrease the cellular calcium level. After treatment by vanillic acid, impaired autophagy flux and mitophagy were improved, and the length of mitochondria was restored. Vanillic acid increased the expression of PINK1, Parkin, Mfn2, and the ratio of LC3-II/LC3-I and decreased the expression of p62. But, under the intervention of mitophagy inhibitor 3-MA, vanillic acid could not change the expression of PINK1/Parkin/Mfn2 and downstream genes to affect cell autophagy, mitophagy, and mitochondrial function. Our findings suggested that vanillic acid activated mitophagy to improve mitochondrial function, in which the PINK1/Parkin/Mfn2 pathway could be the potential regulatory mechanism.
... The classical mitophagy pathway is the PTEN-induced putative kinase 1 (PINK1)/Parkin pathway. Inhibition of the PINK1/Parkin pathway has been shown to reduce mitophagy levels and injury induced by IS [11,12]. ...
... The protein-protein interaction (PPI) analysis revealed an interaction between NAF-1 and Parkin (Fig. 2d). Previous studies found that Parkin is closely related to mitophagy [11,12], therefore, we hypothesized that NAF-1 might regulate mitophagy through the PINK1/Parkin pathway. ...
Ischemic stroke (IS) has a high mortality and disability rate worldwide. NAF-1 is involved in the occurrence and development of nervous system diseases, but its involvement in the pathophysiology of IS is unclear. In this study, we investigated the role of NAF-1 in IS. Middle cerebral artery occlusion and reperfusion in Sprague-Dawley rats was used as an in vivo model of IS. Moreover, oxygen-glucose deprivation and reoxygenation of PC12 cells was used for in vitro study. Intracellular NAF-1 protein expression was influenced by LV-NAF-1 or siRNA. Quantitative real-time PCR and western blot analysis showed that NAF-1 was significantly downregulated following IS. Overexpression of NAF-1 reduced mitophagy in PC12 cells, and it alleviated tissue damage in vivo in rats and cell injury in vitro. In contrast, knockdown of NAF-1 increased mitophagy and worsened cell damage. These findings suggest that NAF-1 may have potential as a therapeutic target for IS.
... cinnamic acid, 3-phenyl-2-propenoic acid) that has a very high structural similarity to vanillin and is divided into two structural fractions; namely, the cis and trans structures. 9 Ferulic acid has antioxidant, [10][11][12] antithrombotic, 9,13 hypolipidemic, 14,15 hypoglycemic, 16,17 antidepressant, 18 anti-inflammatory, 19 and anticancer 20 activity/effects. Owing to its strong bioactivity, ferulic acid is often used as a preservative and preserving agent added to foods in the food industry, thus contributing to the extension of the shelf life of foods and ensuring their quality. ...
BACKGROUND
Vanillin is an important flavoring and aromatic ingredient found mainly in the pods of the tropical plant vanilla and is widely used in the food industry. Attempts have been made to produce vanillin from ferulic acid esters in agricultural residues of wheat bran.
RESULTS
The results showed that a strain with high tolerance to the substrate ferulic acid was isolated and screened from soil and identified as belonging to the genus Bacillus (Bacillus megaterium). The concentration of vanillin produced by this strain was 0.048 g L⁻¹, and the molar conversion of vanillin was 12.25%. The production of vanillin was optimized by orthogonal experiments. Beef pastes 6.0 g L⁻¹, soybean meal 5.0 g L⁻¹, magnesium sulfate heptahydrate 1.0 g L⁻¹, iron(II) sulfate heptahydrate 1.0 g L⁻¹, calcium chloride 1.0 g L⁻¹, dipotassium hydrogen phosphate trihydrate 1.0 g L⁻¹; fermentation culture conditions were pH 7.0, inoculum level 5%, loading volume 20%, ferulic acid 1.0 g L⁻¹, fermentation culture temperature 35 °C. The concentration of vanillin obtained was 0.218 g L⁻¹. Finally, transcriptomic analysis of the strain samples before and after the optimization of the fermentation conditions was carried out to study the effect of the optimization of the fermentation conditions on the concentration of vanillin produced by the strain.
CONCLUSION
This study provides a theoretical basis for further improving the yield of vanillin and gradually realizing efficient industrial production. © 2022 Society of Chemical Industry.
... The multiple ther-apeutic effects of FA were owed to its biological activities, such as scavenging free radicals, anti-oxidation, anti-platelet aggregation, neuroprotection, and strengthening immune function (Barone et al., 2009;Mancuso and Santangelo, 2014). Furthermore, FA also was found to against myocardial ischemia/reperfusion (I/R) injury via inhibiting mitophagy which is dependent on PINK1/ Parkin (Luo et al., 2020a). In melanoma cells, FA was observed to be combined with 2-methoxyestradiol to induce cell death by inhibiting Hsp60 and Hsp90 (Kamm et al., 2019). ...
Acute lung injury (ALI) is mainly mediated by the damage of pulmonary microvascular endothelial cells (PMVECs). LPS is one of the pathogenic factors leading to microcirculatory abnormalities of ALI. Ferulic acid (FA) exhibits therapeutic effects against various diseases. During lipopolysaccharide-induced acute respiratory distress syndrome, FA, when given beforehand, could depress inflammation and oxidative stress. However, the concrete role and underlying mechanism of FA in ALI have not been well characterized. Ten μg/mL Lipopolysaccharide (LPS) was used to treat rat PMVECs for 24 hr. qRT-PCR was used to detect the level of miR-17 and phosphatase and tensin homolog deleted on chromosome ten (PTEN). Western blot was used to analyze the associated proteins in the PI3K/Akt pathway, and the apoptosis-related proteins. Flow cytometric analysis was performed to detect the apoptosis of PMVECs. MTT assay was constructed to detect the cell viability. Luciferase assay was conducted to detect the target gene of miR-17 and PTEN. A cell model for in vitro studying the role of FA in ALI was established using PMVECs. Our data demonstrate that FA up-regulates miR-17 and declines apoptosis induced by LPS. FA inhibits apoptosis mediated by up-regulating miR-17. Furthermore, we found miR-17 targeted PTEN negatively. FA inhibits cleaved caspase-3 and Bax expression through the PI3K/Akt pathway mediated by up-regulating miR-17. Over-expression of PTEN could contribute to the similar expression trend of the PI3K/Akt signal pathway protein compared to miR-17 inhibitor transfected cells. FA inhibits PMVECs apoptosis induced by LPS via miR-17/PTEN to further regulate the activation of the PI3K/Akt pathway in ALI. We anticipate that our data will provoke additional studies for ALI clinical therapy.
... Ferulic acid has been shown to drastically reduce cardiac function in mice with myocardial infarction, decrease the area of myocardial infarction, ameliorate pathology, and exert myocardial protection . Ferulic acid could reduce the NF-κB/NLRP3 inflammasome axis by decreasing pro-inflammatory cytokines (TNF-α and IL-1β), mRNA expression of NLRP3 inflammasomes, Caspase-1, and NF-κB (Doss et al. 2016;Mahmoud et al. 2019;Luo et al. 2020a). ...
Inflammatory infiltration has been implicated in the pathogenesis of cardiovascular diseases (CVDs). The NLRP3 inflammasome is involved in the development of several types of CVDs, including myocardial infarction, myocardial ischemia–reperfusion damage, heart failure, atrial fibrillation, and hypertension. Inhibiting the activity of NLRP3 inflammasome can inhibit the progress of CVDs. However, there is no NLRP3 inflammasome inhibitor in clinic, and it is very important to find a safe and effective NLRP3 inhibitor. Phenols and terpenoids are naturally natural products that have many anti-inflammatory effects in CVDs by modulating the NLRP3 inflammatory pathway. Thus, 20 natural products from phenols and terpenoids for the treatment of cardiovascular disease based on the inhibition of NLRP3 inflammasome were summarized and screened. Docking results showed salvianolic acid B and ellagic acid in phenols, and oridonin and triptolide in terpenoids had a better binding activity with NLRP3, which can provide theoretical support for finding novel NLRP3 inflammasome inhibitors or lead compounds in the future.
