Action and therapeutic targets of myosin light chain kinase, an important cardiovascular signaling mechanism.

The global incidence of cardiac diseases is increasing, imposing a substantial socioeconomic burden on healthcare systems. The pathogenesis of cardiovascular disease is complex and not fully understood, and the physiological function of the heart is inextricably linked to well-regulated cardiac muscle movement. Myosin light chain kinase (MLCK) is essential for myocardial contraction and diastole, cardiac electrophysiological homeostasis, vasoconstriction of vascular nerves and blood pressure regulation. In this sense, MLCK appears to be an attractive therapeutic target for cardiac diseases. MLCK participates in myocardial cell movement and migration through diverse pathways, including regulation of calcium homeostasis, activation of myosin light chain phosphorylation, and stimulation of vascular smooth muscle cell contraction or relaxation. Recently, phosphorylation of myosin light chains has been shown to be closely associated with the activation of myocardial exercise signaling, and MLCK mediates systolic and diastolic functions of the heart through the interaction of myosin thick filaments and actin thin filaments. It works by upholding the integrity of the cytoskeleton, modifying the conformation of the myosin head, and modulating innervation. MLCK governs vasoconstriction and diastolic function and is associated with the activation of adrenergic and sympathetic nervous systems, extracellular transport, endothelial permeability, and the regulation of nitric oxide and angiotensin II. Additionally, MLCK plays a crucial role in the process of cardiac aging. Multiple natural products/phytochemicals and chemical compounds, such as quercetin, cyclosporin, and ML-7 hydrochloride, have been shown to regulate cardiomyocyte MLCK. The MLCK-modifying capacity of these compounds should be considered in designing novel therapeutic agents. This review summarizes the mechanism of action of MLCK in the cardiovascular system and the therapeutic potential of reported chemical compounds in cardiac diseases by modifying MLCK processes.

[Analysis on disease burden and direct medical cost of Xueshuan Xinmaining Tablets in patients with cerebral infarction and coronary heart disease].

The increasing burden of cardiovascular disease in China has become a major public health problem, and the prevention and treatment of cardiovascular disease is in urgent need. For the reality of integrated Chinese and Western medicine in the Chinese health care system, we can consider the service ability of traditional Chinese medicine. Xueshuan Xinmaining Tablet is a kind of Chinese patent medicine commonly used in the treatment of recovery stage of ischemic stroke and angina pectoris of coronary heart disease. Based on the data of hospitalized patients covered by national urban basic medical insurance of China Medical Insurance Research Association in 2013, this study evaluated the treatment cost and detailed composition of the cost for the patients with cerebral infarction and coronary heart disease treated by Xueshuan Xinmaining Tablets. At the same time, the differences in disease burden and direct medical expenses among Xueshuan Xinmaining Tablets group, Western medicine group and another commonly used Chinese patent medicine group were analyzed. Among the three groups of patients with cerebral infarction and coronary heart disease, the hospitalization rates caused by various causes(44.4% and 29.6%) and diseases(20.8% and 5.2%) in Xueshuan Xinmaining Tablets group were the lowest(all P<0.01), and the number of hospitalization times in half a year was highest in the common Chinese patent medicine group(all P<0.01). In patients with cerebral infarction, the median annual total outpatient expenses were 7 476.8, 7 601.8, 15 650.1 yuan respectively in Western medicine group, Xueshuan Xinmaining Tablets group and the common Chinese patent medicine group(P<0.01), and the median hospitalization expenses were 11 620.2, 14 988.9, 13 325.6 yuan respectively(P=0.058). In patients with coronary heart disease, the total outpatient expenses of the three groups were 6 831.4, 10 228.6, 13 132.4 yuan respectively(P<0.01), and the total hospitalization expenses were 13 354.7, 14 911.5, 15 725.3 yuan respectively(P=0.134). The results showed that in patients with cerebral infarction and coronary heart disease, the hospitalization rate was lowest in Xueshuan Xinmaining Tablets group, beneficial to the turnover of hospital beds and full use of hospital medical resources. The total annual outpatient cost of Xueshuan Xinmaining Tablets group was lower than that of common Chinese patent medicine group, beneficial to reduce the burden of disease.

Molecular machinery and interplay of apoptosis and autophagy in coronary heart disease.

Coronary heart disease (CHD) is a common heart disease and the leading cause of cardiovascular death. Apoptosis and autophagy are two forms of programmed cell deaths which participate in the pathogenesis, development and prognosis of CHD. They are activated by several different pathways respectively and can interact with each other through the Beclin 1-Bcl-2/Bcl-xL complex, mTOR, TRAIL, TNF-α, ER stress and nucleus p53 pathways. Excessive apoptosis can promote myocardial ischemia, ischemia/reperfusion (I/R) injury, post-ischemia cardiac remodeling and coronary atherosclerosis except for VSMC-induced atherosclerosis progress. In contrast, activated autophagy protects heart from myocardial ischemia injury and post-ischemia cardiac remodeling, but can exert controversial effects on I/R injury and coronary atherosclerosis. Therefore, considering the pathological significance and mechanisms of apoptosis and autophagy underlying CHD, therapeutic implication of targeting apoptosis and autophagy is obvious. Fortunately, some therapeutic drugs and pharmacologic compounds involving mTOR inhibitor and AMPK activator have been reported to regulate apoptosis and autophagy. Although recent studies are limited and insufficient, they have pointed out the complex interplay between apoptosis and autophagy and further provided treatment concept for CHD by balancing the switch between the two responses.

[Explore molecular mechanism of Chinese herbs with promoting blood circulation and resolving phlegm effects on myocardial ischemia reperfusion injury based on correlation between microRNA and mtDNA].

A large number of basic and clinical studies have shown that the Chinese herbs with promoting blood circulation and resolving phlegm effects could prevent and treat myocardial ischemia-reperfusion injury(MIRI) by regulating lipid metabolism. But its mechanism is not yet clear. The studies show that mitochondrial DNA (mtDNA), microRNAs and lipid metabolism participate in the whole process of MIRI and affect the prognosis. mtDNA mutation is the primary factor to cause myocardial ischemia and reperfusion myocardial cell damage. microRNAs aggravate or reduce MIRI injury by down-regulating or up-regulating related genes expression, while miR-33, as a key regulator of cholesterol transport, regulates lipid metabolism through CROT, PGC-1α, AMPK and other genes located in the mitochondria. There are less studies on correlation between miR-33 and mtDNA, microRNAs. Therefore, further studies on the correlation between miR-33 and mtDNA, microRNAs, as well as the discussions on whether the traditional Chinese medicine (TCM) with promoting blood circulation and resolving phlegm effects could target miR-33 to regulate lipid metabolism and inducemt DNA mutations or deletions, would have important significance for the prevention and treatment of MIRI.

[Multi-index integrated evaluation method optimizes water-extraction and ethanol precipitation of Xuanbi'antong formula (XBF)].

To determine the process parameters of optimal water-extraction and ethanol precipitation method for Xuanbi'antong (XBF) extract, which is a clinically experience formula for coronary disease. Orthogonal test L9(34) was conducted for the study of XBF water-extraction and ethanol precipitation process. Extractum, salvianolic acid B, rhizoma coptidis alkaloid, paeoniflorin, puerarin, ginsenoside Rb1, ginsenosides and echinacoside were selected as marker components and multi-index comprehensive weighted score was used to select and verify optimal water-extraction and ethanol precipitation process. The optimal extraction process was as follows： XBF was added with 10 times distilled water, decocted for half an hour for 3 times. The best ethanol-precipitation process was established where the ethanol was added up to 70% and precipitated for 24 hours in 1.12 extract density (20 ℃). The optimized water-extraction and ethanol precipitation method is stable and reliable, and can provide reference for further development and utilization of the formula.

[Study on compatibility of Salviae Miltiorrhizae Radix et Rhizoma and Chuanxiong Rhizoma based on pharmacokinetics of effective components salvianolic acid B and ferulic acid in rat plasma].

A study was made on the pharmacokinetic regularity of effective components salvianolic acid B and ferulic acid in Salviae Miltiorrhizae Radix et Rhizoma (SMRR) and Chuanxiong Rhizoma(CR) in rats, so as to discuss the compatibility mechanism of Salviae Miltiorrhizae Radix et Rhizoma and Chuanxiong Rhizoma. Rats were randomly divided into three groups and intravenously injected with 50 mg x kg(-1) salvianolic acid B for the single SMRR extracts group, 0.5 mg x kg(-1) ferulic acid for the single CR extracts group and 50 mg x kg(-1) salvianolic acid B + 0.5 mg x kg(-1) ferulic acid for the SMRR and CR combination group. The blood samples were collected at different time points and purified by liquid-liquid extraction with ethyl acetate. With chloramphenicol as internal standard (IS), UPLC was adopted to determine concentrations of salvianolic acid B and ferulic acid. The pharmacokinetic parameters of salvianolic acid B and ferulic acid were calculated with WinNonlin 6.2 software and analyzed by SPSS 19.0 statistical software. The UPLC analysis method was adopted to determine salvianolic acid B and ferulic acid in rat plasma, including linear equation, stability, repeatability, precision and recovery. The established sample processing and analysis methods were stable and reliable, with significant differences in major pharmacokinetic parameters, e.g., area under the curve (AUC), mean residence time (MRT) and terminal half-life (t(1/2)). According to the experimental results, the combined application of SMRR and CR can significantly impact the pharmacokinetic process of their effective components in rats and promote the wide distribution, shorten the action time and prolong the in vivo action time of salvianolic acid B and increase the blood drug concentration and accelerate the clearance of ferulic acid in vivo.

Two new flavonols from Cudrania cochinchinensis.

Two new flavonols, 6-p-hydroxybenzyl kaempferol (1) and 6-p-hydroxybenzyl quercetin (2), together with six known compounds were isolated from the roots of Cudrania cochinchinensis and their structures elucidated on the basis of spectroscopic methods. Their antioxidant capacities were evaluated by 1,1-diphenyl-2-picryl-hydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical-scavenging assays. The results suggested that compounds 2, 4, and 7 showed significant radical-scavenging activities.

Effects of COVID-19 on the cardiovascular system: A mendelian randomization study.

Infections with the coronavirus disease 2019 (COVID-19) and disorders of the heart and blood vessels are causally related. To ascertain the causal relationship between COVID-19 and cardiovascular disease (CVD), we carried out a Mendelian randomization (MR) study through a method known as inverse variance weighting (IVW). When analyzing multiple SNPs, MR can meta-aggregate the effects of multiple loci by using IVW meta-pooling method. The weighted median (WM) is the median of the distribution function obtained by ranking all individual SNP effect values according to their weights. WM yields robust estimates when at least 50% of the information originates from valid instrumental variables (IVs). Directed gene pleiotropy in the included IVs is permitted because MR-Egger does not require a regression straight line through the origin. For MR estimation, IVW, WM and MR-Egger were employed. Sensitivity analysis was conducted using funnel plots, Cochran's Q test, MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis. SNPs related to exposure to COVID-19 and CVD were compiled. CVD for COVID-19 infection, COVID-19 laboratory/self-reported negative, and other very severe respiratory diagnosis and population were randomly assigned using MR. The COVID-19 laboratory/self-reported negative results and other very severe respiratory confirmed cases versus MR analysis of CVD in the population (p â€‹> â€‹0.05); COVID-19 infection to CVD (p â€‹= â€‹0.033, OR â€‹= â€‹1.001, 95%CI: 1.000-1.001); and the MR-Egger results indicated that COVID-19 infection was associated with CVD risk. This MR study provides preliminary evidence for the validity of the causal link between COVID-19 infection and CVD.

CaMK II in Cardiovascular Diseases, Especially CaMK II-δ: Friends or Enemies.

Cardiovascular diseases (CVDs) tend to affect the young population and are associated with a significant economic burden and psychological distress to the society and families. The physiological and pathological processes underlying CVDs are complex. Ca2+/calmodulin-dependent kinase II (CaMK II), a protein kinase, has multiple biological functions. It participates in multiple pathological processes and plays a central role in the development of CVDs. Based on this, this paper analyzes the structural characteristics and distribution of CaMK II, the mechanism of action of CaMK II, and the relationship between CaMK II and CVDs, including ion channels, ischemia-reperfusion injury, arrhythmias, myocardial hypertrophy, cardiotoxicity, hypertension, and dilated cardiomyopathy. Given the different regulatory mechanisms of different isoforms of CaMK II, the clinical use of specific targeted inhibitors or novel compounds should be evaluated in future research to provide new directions.

Effect of Tai Chi vs Aerobic Exercise on Blood Pressure in Patients With Prehypertension: A Randomized Clinical Trial.

Importance: Prehypertension increases the risk of developing hypertension and other cardiovascular diseases. Early and effective intervention for patients with prehypertension is highly important. Objective: To assess the efficacy of Tai Chi vs aerobic exercise in patients with prehypertension. Design, Setting, and Participants: This prospective, single-blinded randomized clinical trial was conducted between July 25, 2019, and January 24, 2022, at 2 tertiary public hospitals in China. Participants included 342 adults aged 18 to 65 years with prehypertension, defined as systolic blood pressure (SBP) of 120 to 139 mm Hg and/or diastolic BP (DBP) of 80 to 89 mm Hg. Interventions: Participants were randomized in a 1:1 ratio to a Tai Chi group (n = 173) or an aerobic exercise group (n = 169). Both groups performed four 60-minute supervised sessions per week for 12 months. Main Outcomes and Measures: The primary outcome was SBP at 12 months obtained in the office setting. Secondary outcomes included SBP at 6 months and DBP at 6 and 12 months obtained in the office setting and 24-hour ambulatory BP at 12 months. Results: Of the 1189 patients screened, 342 (mean [SD] age, 49.3 [11.9] years; 166 men [48.5%] and 176 women [51.5%]) were randomized to 1 of 2 intervention groups: 173 to Tai Chi and 169 to aerobic exercise. At 12 months, the change in office SBP was significantly different between groups by -2.40 (95% CI, -4.39 to -0.41) mm Hg (P = .02), with a mean (SD) change of -7.01 (10.12) mm Hg in the Tai Chi group vs -4.61 (8.47) mm Hg in the aerobic exercise group. The analysis of office SBP at 6 months yielded similar results (-2.31 [95% CI, -3.94 to -0.67] mm Hg; P = .006). Additionally, 24-hour ambulatory SBP (-2.16 [95% CI, -3.84 to -0.47] mm Hg; P = .01) and nighttime ambulatory SBP (-4.08 [95% CI, -6.59 to -1.57] mm Hg; P = .002) were significantly reduced in the Tai Chi group compared with the aerobic exercise group. Conclusions and Relevance: In this study including patients with prehypertension, a 12-month Tai Chi intervention was more effective than aerobic exercise in reducing SBP. These findings suggest that Tai Chi may help promote the prevention of cardiovascular disease in populations with prehypertension. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1900024368.

Three new germacrane-type sesquiterpenes with NGF-potentiating activity from Valeriana officinalis var. latiofolia.

Three new germacrane-type sesquiterpenoids, volvalerenal F (1), volvalerenal G (2) and volvalerenic acid D (3), along with five known compounds 4-8, were isolated from the CHCl3 soluble partition of the ethanol extract of Valeriana officinalis var. latiofolia. The structures of the new compounds were determined on the basis of spectroscopic evidence, including their 1D- and 2D-NMR spectra, as well as mass spectrometry. The eight germacrane-type sesquiterpenoids showed nerve growth factor (NGF) potentiating activity, which mediates the neurite outgrowth in PC 12D cells. This study intends to reveal the chemical basis of the use of V. officinalis var. latiofolia as a dietary supplement.

[Chemical constituents of Cudrania cochinchinensis].

OBJECTIVE: To study the chemical constituents of Cudrania cochinchinensis. METHODS: Compounds were isolated and purified by silica gel column, sephadex LH-20 chromatography and recrystallization. Their structures were elucidated by physicochemical properties and spectral data. RESULTS: Thirteen compounds were isolated from the 70% ethanol extract of the root of Cudrania cochinchinensis and identified as beta-sitosterol (1), butyrospermol (2), butyrospermol acetate (3), (+) syringarenol (4), 1, 3, 6-trihydroxy-7-methoxy xanthone (5), 1, 3, 6, 7-tetrahydroxy-8-prenylxanthone (6), kaempferol (7), dihydrokaempferol (8), umbelliferone (9),4-hydroxybenzyl ethyl ether (10), 2,4-dihydroxybenzaldehyde (11), 4-hydrox-ybenzaldehyde (12) and vanillin (13). CONCLUSION: Compounds 2 - 6, 10 - 13 are isolated from Cudrania cochinchinensis for the first time.

Impact of the COVID-19 pandemic lockdown on hospitalizations for cerebrovascular disease and related in-hospital mortality in China: A nationwide observational study.

BACKGROUND AND PURPOSE: The aim of this nationwide study was to assess the impact of the COVID-19 pandemic on cerebrovascular disease hospitalization rates, out-of-pocket rates, and in-hospital case fatality rates. METHODS: All hospitalizations for cerebrovascular disease from 1599 hospitals from 2019 to 2020 were selected using the International Classification of Diseases, 10th revision, in the Hospital Quality Monitoring System (HQMS). We defined 2019 as the pre-pandemic group and 2020 as the post-pandemic group. Multivariate analyses were done to assess the association between the pandemic and patient outcomes and out-of-pocket rate with odds ratios (OR) and 95% CIs presented. RESULTS: In total, 9 640 788 patients with the cerebrovascular disease were recruited (mean age was 65.7[SE.0.004] years, and 55.7% were male), and data is available for 5145358 patients in 2019 (pre-epidemic) and 4495430 patients in 2020(post-pandemic), indicating a 12.6% decrease. Out-of-pocket rate increase of 9.3% (2020 vs 2019: 34.1%% vs 31.2% [absolute difference, 2.9% {95% CI, 1.3% to 4.5%}, odd ratio {OR}, 1.1{95% CI, 1.0 to 1.1}]. The epidemic has led to an 18.0% increase in in-hospital mortality (2020 vs 2019: 1.1%% vs 0.9% [absolute difference, 0.2% {95% CI, 0.1% to 0.2%}, odd ratio {OR}, 1.1{95% CI, 1.1 to 1.2}]. The epidemic has led to significantly increased in-hospital mortality for patients with stroke but had no significant impact on other cerebrovascular diseases. CONCLUSIONS: During the COVID-19 pandemic lockdown, patients hospitalized for stroke fell by 12.6%, and there were substantial increases in out-of-pocket rates (9.3%) and in-hospital case fatality rates (18.0%).

Screening of an FDA-approved compound library identifies apigenin for the treatment of myocardial injury.

Apigenin is the active ingredient in Ludangshen. Although previous studies reported the cardioprotective actions of apigenin against doxorubicin (Dox)-induced cardiomyopathy, the underlying mechanisms remain incompletely understood. Since apigenin beneficially regulates various aspects of mitochondrial function and dynamics, we asked whether apigenin improves heart function in mice with Dox-induced cardiomyopathy by regulating the mitochondrial unfolded protein response (UPRmt). Co-administration of apigenin significantly restored heart function, reduced myocardial swelling, inhibited cardiac inflammation, increased cardiac transcription of UPRmt-related genes, and promoted cardiomyocyte survival in Dox-treated mice. In turn, blockade of UPRmt abolished the mito- and cytoprotective effects of apigenin, evidenced by decreased ATP production, suppressed mitochondrial antioxidant capacity, and increased apoptosis, in Dox-treated, cultured HL-1 cardiomyocytes. Furthermore, apigenin treatment prevented Dox-induced downregulation of Sirt1 and Atf5 expression, and the beneficial effects of apigenin were completely nullified in Sirt1 knockout (KO) mice or after siRNA-mediated Sirt1 knockdown in vitro. We thus provide novel evidence for a promotive effect of apigenin on UPRmt via regulation of the Sirt1/Atf5 pathway. Our findings uncover that apigenin seems to be an effective therapeutic agent to alleviate Dox-mediated cardiotoxicity.

Epac, a positive or negative signaling molecule in cardiovascular diseases.

Cardiovascular disease (CVD) is one of the leading causes of death and disability, and has always been a hotspot in clinical and scientific research. The illness brings a heavy economic burden and causes psychological pressure on society and families. The pathogenesis of CVD is complex and has not yet been fully elucidated. Mitochondria provide energy for cardiovascular function. cAMP signaling is closely related to the mechanism of action of mitochondria. Epac, an important effector of cAMP, is involved in a variety of physiopathological mechanisms of CVD. Epac acts on a variety of pathways, including ion level regulation, cardiac hypertrophy, cardiac fibrosis, cardiomyocyte apoptosis, and angiogenesis. In this article, we systematically discuss the mechanism of action of Epac in CVDs to provide (i) ideas for the treatment of CVDs such as arrhythmia and heart failure and (ii) a basis for studying biological pathways and carrying out targeted drug research. Although some of the studied mechanisms are inconsistent, they also illustrate the complexity and importance of the effects of Epac.

Huoxue Qingre decoction used for treatment of coronary heart disease network analysis and metabolomic evaluation.

Objective: Network pharmacology provides new methods and references for the research of traditional Chinese medicine, but some problems remain, such as single evaluation components and index methods, imperfect relevant databases, unscientific prediction results, and lack of verification of results. Herein, we used a modified network pharmacology research method to explore the potential network analysis mechanism of Huoxue Qingre decoction in the treatment of coronary heart disease and utilized clinical trials for assessment. Methods: Based on literature research, the targets corresponding to the drug were obtained with the assistance of the TCMSP database and Swiss Target Prediction, and the target proteins were corrected using the UniProt database. The targets related to coronary heart disease was obtained through the GeneCards database. A protein-protein interaction network diagram was constructed, and a "component-intersection target" network diagram was drawn based on Cytoscape 3.6.2 software. The mapped targets were imported into the DAVID bioinformatics platform, which underwent Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and the network pharmacology prediction results were evaluated through clinical trials. Results: We obtained 151 compounds related to Huoxue Qingre decoction, 286 genes after evaluation and deduplication, and 426 genes related to coronary heart disease. Finally, 81 common target genes were obtained with 32 pathways according to the KEGG pathway enrichment analysis. The validation results of the clinical trials showed that a total of 98 differential metabolites were found in the treatment of coronary heart disease with Huoxue Qingre decoction, involving a total of 16 metabolic pathways. Compared with the network pharmacology prediction results, it was found that only the pathways in cancer (hsa05200) were the common pathways in the top 32 signaling pathways predicted by network pharmacology. The expanded network pharmacology prediction results revealed that the sphingolipid signaling pathway (hsa04071) and prostate cancer pathway (hsa05215) matched the predicted metabolic pathways, with differential metabolites of N-oleoyl-D-sphingomyelin and 1-methyl-6-phenyl-1h-imidazole[4,5-b]pyridine-2-amine. Conclusion: Through the network analysis and metabolomic evaluation, there may be three signaling pathways that involve the Huoxue Qingre decoction in the treatment of coronary heart disease: pathways in cancer (hsa05200), sphingolipid signaling pathway (hsa04071), and prostate cancer pathway (hsa05215).

Mitochondrial Damage in Myocardial Ischemia/Reperfusion Injury and Application of Natural Plant Products.

Ischemic heart disease (IHD) is currently one of the leading causes of death among cardiovascular diseases worldwide. In addition, blood reflow and reperfusion paradoxically also lead to further death of cardiomyocytes and increase the infarct size. Multiple evidences indicated that mitochondrial function and structural disorders were the basic driving force of IHD. We summed up the latest evidence of the basic associations and underlying mechanisms of mitochondrial damage in the event of ischemia/reperfusion (I/R) injury. This review then reviewed natural plant products (NPPs) which have been demonstrated to mitochondria-targeted therapeutic effects during I/R injury and the potential pathways involved. We realized that NPPs mainly maintained the integrality of mitochondria membrane and ameliorated dysfunction, such as improving abnormal mitochondrial calcium handling and inhibiting oxidative stress, so as to protect cardiomyocytes during I/R injury. This information will improve our knowledge of mitochondrial biology and I/R-induced injury's pathogenesis and exhibit that NPPs hold promise for translation into potential therapies that target mitochondria.

Protective effects of natural products against myocardial ischemia/reperfusion: Mitochondria-targeted therapeutics.

Patients with ischemic heart disease receiving reperfusion therapy still need to face left ventricular remodeling and heart failure after myocardial infarction. Reperfusion itself paradoxically leads to further cardiomyocyte death and systolic dysfunction. Ischemia/reperfusion (I/R) injury can eliminate the benefits of reperfusion therapy in patients and causes secondary myocardial injury. Mitochondrial dysfunction and structural disorder are the basic driving force of I/R injury. We summarized the basic relationship and potential mechanisms of mitochondrial injury in the development of I/R injury. Subsequently, this review summarized the natural products (NPs) that have been proven to targeting mitochondrial therapeutic effects during I/R injury in recent years and related cellular signal transduction pathways. We found that these NPs mainly protected the structural integrity of mitochondria and improve dysfunction, such as reducing mitochondrial division and fusion abnormalities, improving mitochondrial Ca2+ overload and inhibiting reactive oxygen species overproduction, thereby playing a role in protecting cardiomyocytes during I/R injury. This data would deepen the understanding of I/R-induced mitochondrial pathological process and suggested that NPs are expected to be transformed into potential therapies targeting mitochondria.

Pharmacological properties of total flavonoids in Scutellaria baicalensis for the treatment of cardiovascular diseases.

BACKGROUND: Scutellaria baicalensis, a medicinal herb belonging to the Lamiaceae family, has been recorded in the Chinese, European, and British Pharmacopoeias. The medicinal properties of this plant are attributed to the total flavonoids of Scutellaria baicalensis (TFSB), particularly the main component, baicalin. This study provides a systematic and comprehensive list of the identified TFSB components and their chemical structures. The quality control process, pharmacokinetics, clinical application, and safety of Scutellaria baicalensis are discussed, and its pharmacological effect on cardiovascular diseases (CVDs) is detailed. Finally, the future research trends and prospects of this medicinal plant are provided. METHODS: The Chinese and English papers related to TFSB were collected from the PubMed and CNKI databases using the relevant keywords. To highlight the pharmacological mechanism, clinical application, and safety of TFSB, the collected articles were screened and classified based on their research content. RESULTS: TFSB contains at least 100 different kinds of flavonoids, of which baicalin, baicalein, wogonin, wogonoside, scutellarin, and scutellarein are the main active ingredients. The preparation process of TFSB is relatively well established, and the extraction rate can be significantly increased by enzymatic pretreatment and ultrasonication. The low oral availability of TFSB may be effectively enhanced using nanoformulations. The available pharmacokinetic data show that flavonoid glycosides and aglycones with the same parent nucleus may be converted to structures that are conducive to absorption in vivo. Moreover, TFSB can protect against CVDs by inhibiting apoptosis, regulating oxidative stress response, participating in inflammatory response, protecting against myocardial fibrosis, inhibiting myocardial hypertrophy, and regulating blood vessels. In terms of clinical application and animal safety, the available studies show that TFSB can be applied in a wide range of clinical treatments and is safe to use is animals. CONCLUSION: This article systematically reviews the therapeutic effect and underlying pharmacological mechanism of TFSB against CVDs. The available studies clearly suggest that TFSB has great potential for the treatment of CVDs and is worthy of in-depth research and development.

Relevance of Ferroptosis to Cardiotoxicity Caused by Anthracyclines: Mechanisms to Target Treatments.

Anthracyclines (ANTs) are a class of anticancer drugs widely used in oncology. However, the clinical application of ANTs is limited by their cardiotoxicity. The mechanisms underlying ANTs-induced cardiotoxicity (AIC) are complicated and involve oxidative stress, inflammation, topoisomerase 2ß inhibition, pyroptosis, immunometabolism, autophagy, apoptosis, ferroptosis, etc. Ferroptosis is a new form of regulated cell death (RCD) proposed in 2012, characterized by iron-dependent accumulation of reactive oxygen species (ROS) and lipid peroxidation. An increasing number of studies have found that ferroptosis plays a vital role in the development of AIC. Therefore, we aimed to elaborate on ferroptosis in AIC, especially by doxorubicin (DOX). We first summarize the mechanisms of ferroptosis in terms of oxidation and anti-oxidation systems. Then, we discuss the mechanisms related to ferroptosis caused by DOX, particularly from the perspective of iron metabolism of cardiomyocytes. We also present our research on the prevention and treatment of AIC based on ferroptosis. Finally, we enumerate our views on the development of drugs targeting ferroptosis in this emerging field.