Ferulic acid attenuates non-alcoholic steatohepatitis by reducing oxidative stress and inflammation through inhibition of the ROCK/NF-κB signaling pathways.

Ferulic acid (FA) is a natural polyphenol compound existing in many plants. The purpose of this study was to investigate the effect of FA on non-alcoholic steatohepatitis (NASH) induced by high-cholesterol and high-fat diet (HCHF) and its possible mechanism. Rats were fed HCHF for 12 weeks to establish NASH model. FA improved liver coefficients and had no effect on body weight changes. FA could reduce serum alanine transferase (ALT) and aspartate transferase (AST) activities. FA attenuated the increase of total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL) levels caused by NASH, improved the liver pathological damage induced by NASH, and inhibited the progression of liver fibrosis. FA prevented the production of reactive oxygen species (ROS) and the increase of malondialdehyde (MDA) levels, and attenuated the decrease in superoxide dismutase (SOD) activity. Meanwhile, FA significantly restored the levels of interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α (TNF-α). In addition, we also found that FA inhibited the activity of ROCK and the activation of NF-κB signaling pathway in the liver of NASH rats. Overall, FA has a hepatoprotective anti-oxidative stress and anti-inflammatory effects in NASH rats, and its mechanism may be related to the inhibition of ROCK/NF-κB signaling pathway.

Icotinib: efficacy in different solid tumors and gene mutations.

Icotinib is a first-generation inhibitor of epidermal growth factor receptor, which has been approved by the Chinese National Medical Products Administration, for the treatment of non-small cell lung cancer with epidermal growth factor receptor sensitive mutations. In addition, icotinib also shows moderate activity in other solid tumors driven by epidermal growth factor receptor, including non-small cell lung cancer with epidermal growth factor receptor rare non-resistant mutations, and esophageal cancer with epidermal growth factor receptor amplification or overexpression. This article reviews the efficacy of icotinib in different solid tumors with different epidermal growth factor receptor alterations.

Safranal, an active constituent of saffron, ameliorates myocardial ischemia via reduction of oxidative stress and regulation of Ca2+ homeostasis.

Safranal (SFR) is the major constituent of saffron. The purpose of this study was to observe the effect of SFR on myocardial ischemia induced by isoprenaline (ISO) and to explore its possible mechanism. The myocardial ischemia rat model was established by subcutaneous injection of ISO (85 mg/kg/d) on the 8th and 9th day of the experiment. Serum creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA) and superoxide dismutase (SOD) were measured, as were changes in calcium concentration, reactive oxygen species (ROS) and cardiac morphology of the myocardial tissue. The effects of SFR on cell contraction, Ca2+ transient and L-type Ca2+ current (ICa-L) in isolated rat myocardial cells were measured using the Ion Optix detection system and the whole-cell patch-clamp technique. SFR can decrease the activity of serum CK, LDH and MDA, and increase the activity of serum SOD, reduce intracellular calcium concentration and the manufacture of ROS. In addition, SFR can improve changes in heart morphology. SFR can significantly inhibit contraction, Ca2+ transients and ICa-L in isolated ventricular myocytes. SFR has a cardioprotective role in ISO-induced MI rats, and the underling mechanism is related to the inhibition of oxidative stress, myocardial contractility, ICa-L and the regulation of Ca2+ homeostasis.

Inhibitory effects of four active components in saffron on human ether-a-go-go-related gene (hERG) K+ currents.

The main active components of saffron are crocin, crocetin, picrocrocin, and safranal. There are many studies on their cardioprotective effects, but their cardiotoxicities have not been reported. The human ether-a-go-go-related gene (hERG) K+ channels are of considerable pharmaceutical interest as the target responsible for acquired long QT syndromes. The aim of this study is to explore the effects of crocin, crocetin, picrocrocin, and safranal on the K+ channels encoded by hERG. The interaction of these components with the rapid delayed rectification of K+ currents (IKr) were studied using the perforated patch recording technique. Crocin and picrocrocin had no significant effects on IKr, but crocetin and safranal inhibited hERG K+ currents in a concentration-dependent manner, with IC50 values of 36.35 µM and 37.86 µM, respectively. The maximum inhibitory effects were 37.74 ± 4.14% and 33.74 ± 4.81%, respectively, and the effects were reversible upon washout. The results demonstrate that crocetin and safranal significantly inhibit hERG K+ current, but crocin and picrocrocin do not. This suggests that crocetin and safranal may increase the risk of cardiac arrhythmias by inhibiting IKr.

Mechanisms underlying the cardio-protection of total ginsenosides against myocardial ischemia in rats in vivo and in vitro: Possible involvement of L-type Ca2+ channels, contractility and Ca2+ homeostasis.

Here we aimed to observe the effects of total ginsenosides (TG) against isoproterenol (ISO) induced myocardial ischemia (MI) and to explore its underlying mechanisms based on L-type Ca2+ current (ICa-L), intracellular Ca2+ ([Ca2+]i) and contraction in isolated rat myocytes. Rat model of MI was induced by subcutaneously injection of ISO (85 mg/kg) for 2 consecutive days. J-point elevation, heart rate, serum levels of creatine kinase (CK) and lactated dehydrogenase (LDH), and heart morphology changes were observed. Influences of TG on ICa-L, [Ca2+]i and contraction in isolated rat myocytes were observed by the patch-clamp technique and IonOptix detection system. TG significantly reduced J-point elevation, heart rate, serum levels of CK and LDH, and improved heart pathologic morphology. TG decreased ICa-L in concentration-dependent manner with a half-maximal inhibitory concentration (IC50) of 31.65 µg/mL. TG (300 µg/mL) decreased ICa-L of normal and ischemic ventricular myocytes by 64.33 ± 1.28% and 61.29 ± 1.38% respectively. At 30 µg/mL, TG reduced Ca2+ transient by 21.67 ± 0.94% and cell shortening by 38.43 ± 6.49%. This study showed that TG displayed cardioprotective effects on ISO-induced MI rats and the underlying mechanisms may be related to inhibition of ICa-L, damping of [Ca2+]i and decrease of contractility.

Effects of total flavones from Acanthopanax senticosus on L-type calcium channels, calcium transient and contractility in rat ventricular myocytes.

Acanthopanax senticosus (Rupr. et Maxim.) Harms (AS), a traditional herbal medicine, has been widely used to treat ischemic heart disease. However, the underlying cellular mechanisms of its benefits to cardiac function remain unclear. The present study examined the effects of total flavones from AS (TFAS) on L-type Ca(2+) channel currents (ICa-L ) using the whole cell patch-clamp technique and on intracellular calcium ([Ca(2+) ]i ) handling and cell contractility in rat ventricular myocytes with the aid of a video-based edge-detection system. Exposure to TFAS resulted in a concentration- and voltage-dependent blockade of ICa-L , with the half-maximal inhibitory concentration (IC50 ) of 283.12 µg/mL and the maximal inhibitory effect of 36.49 ± 1.95%. Moreover, TFAS not only increased the maximum current in the current-voltage relationship but also shifted the activation and inactivation curves of ICa-L toward the hyperpolarizing direction. Meanwhile, TFAS significantly reduced amplitudes of myocyte shortening and [Ca(2+) ]i with an increase in the time to 10% of the peak (Tp) and a decrease in the time to 10% of the baseline (Tr). Thus, the cardioprotective effects of TFAS may be attributed mainly to the attenuation of [Ca(2+) ]i through the direct inhibition of ICa-L in rat ventricular myocytes and consequent negative effect on myocardial contractility.

Luteolin targets the AGE-RAGE signaling to mitigate inflammation and ferroptosis in chronic atrophic gastritis.

Chronic atrophic gastritis (CAG) is a chronic inflammatory disease and precancerous lesion in stomach cancer. Abnormal activation cellular ferroptosis further damages gastric tissue, which is susceptible to inflammation. Luteolin has powerful anti-inflammatory and regulatory potential for cellular ferroptosis. We aimed to clarify the involvement of luteolin in inflammation and ferroptosis during CAG. Luteolin targets were searched to identify intersecting genes in the chronic atrophic gastritis disease database. The AGE-RAGE pathway is a potential target of luteolin for the treatment of chronic atrophic gastritis and a binding site between luteolin and RAGE was predicted through a computer simulation of molecular docking. We established a CAG rat model using N-methyl-N-nitro-N-nitroguanidine. The therapeutic effect of luteolin on CAG was detected using western blotting, qPCR, hematoxylin and eosin staining, lipid oxidation (MDA), and Fe2+ assays. Luteolin inhibited the AGE-RAGE signaling pathway and reduced the inflammatory response in gastric tissues. Additionally, luteolin downregulated the concentration of (MDA) and Fe2+, and CAG downregulated the expression levels of ACSL4 and NOX1 and upregulated the expression levels of FIH1 and GPX4 ferroptosis-related proteins, thus inhibiting the ferroptosis of gastric tissue cells, which had a therapeutic effect on CAG.

Mechanistic investigation of the ameliorative effect of liquiritin on hypoxia/reoxygenation­induced cardiomyocyte injury based on network pharmacology and in vitro validation.

Liquiritin (LIQ) is a flavonoid known for its cardioprotective properties, extracted from Glycyrrhiza uralensis Fisch. The purpose of the present study was to investigate the protective mechanism of LIQ against hypoxia/reoxygenation (H/R) injury through in vitro experiments, with the goal of enhancing its pharmacological effects. Initially, network pharmacology was employed to explore the targets and mechanisms of LIQ. Subsequently, an in vitro H/R model was established using H9c2 cells. Potential targets for LIQ and myocardial ischemia-reperfusion injury (MIRI) were identified through online databases. The STRING, Cytoscape and DAVID databases were used to extract intersecting targets and mechanisms. In vitro experiments were conducted to validate these findings, assessing cardiac enzymes, oxidative stress indicators, mitochondrial fluorescence, apoptotic fluorescence, inflammation and related protein expression. The network pharmacological analysis revealed that the protective effects of LIQ on MIRI involve oxidative stress, inflammation and apoptosis. The results of in vitro experimental validation demonstrated that LIQ significantly reduced the activities of lactated dehydrogenase and creatine kinase isoenzyme-MB (P<0.05 or 0.01), as well as the level of malondialdehyde (P<0.01). It also inhibited the production of reactive oxygen species (P<0.01), the release of inflammatory factors (P<0.05 or 0.01) and apoptosis (P<0.01). By contrast, the LIQ pre-treatment group exhibited a significant increase in mitochondrial membrane potential level (P<0.05 or 0.01) and the activities of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase (P<0.05 or 0.01). Furthermore, LIQ reduced the protein expressions of TNF-α receptor type 1 (TNFR1) and MMP9, along with the level of NF-κB phosphorylation (P<0.05 or 0.01). In conclusion, LIQ mitigated H/R-induced cardiomyocyte injury through mechanisms that may involve antioxidants, anti-apoptotic effects, protection against mitochondrial damage and suppression of inflammatory levels. These effects are achieved via inhibition of the TNFR1/NF-κB/MMP9 pathway.

Chemical Characteristics and Comparison of Schizonepetae Herba and Schizonepetae Herba Carbonisata by Combination of GC-MS and UHPLC-MS Strategies.

BACKGROUND: Schizonepetae Herba (SH, Jingjie) and Schizonepetae Herba Carbonisata (SHC, Jingjie Tan) are two different forms of the same herbal material, with SHC being the processed product of SH. The different clinical efficacies of SH and SHC may be caused by changes in their chemical compositions. Despite this, there have been few studies that have reported on the comparative identification of SH and SHC. Therefore, the aims of this experiment are to investigate the differential changes of non-volatile and volatile components before and after SH processing. OBJECTIVES: To establish combination strategies for identifying the chemical markers in SH and SHC using ultra-HPLC-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) and headspace gas chromatography-mass spectrometry (HS-GC-MS). METHODS: UHPLC-Q-TOF-MS and HS-GC-MS methods was utilized to comprehensively discriminate between SH and SHC. To identify chemical markers, principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) were performed on 14 batches of SH and SHC. RESULTS: A total of 71 non-volatile compounds and 81 volatile compounds were tentatively identified in SH and SHC. Among these, 14 non-volatile compounds and 18 volatile oils were found to be potential characteristic markers that can differentiate between SH and SHC. CONCLUSION: The present work provides valuable information for understanding the chemical differences between SH and SHC. The results obtained from this research may serve as a scientific foundation for comprehensively revealing the mechanisms involved in the carbonizing processing method of stir-frying SH. HIGHLIGHTS: The chemical changes that occur before and after carbonizing SH were investigated using integrated methods based on LC-MS and GC-MS, and chemical markers in SH and SHC were identified.

Liquiritin Protects Against Cardiac Fibrosis After Myocardial Infarction by Inhibiting CCL5 Expression and the NF-κB Signaling Pathway.

Purpose: Despite significant advances in interventional treatment, myocardial infarction (MI) and subsequent cardiac fibrosis remain major causes of high mortality worldwide. Liquiritin (LQ) is a flavonoid extract from licorice that possesses a variety of pharmacological properties. However, to our knowledge, the effects of LQ on myocardial fibrosis after MI have not been reported in detail. The aim of our research was to explore the potential role and mechanism of LQ in MI-induced myocardial damage. Methods: The MI models were established by ligating the left anterior descending branch of the coronary artery. Next, rats were orally administered LQ once a day for 14 days. Biochemical assays, histopathological observations, ELISA, and Western blotting analyses were then conducted. Results: LQ improved the heart appearance and ECG, decreased cardiac weight index and reduced levels of cardiac-specific markers such as CK, CK-MB, LDH, cTnI and BNP. Meanwhile, LQ reduced myocardial infarct size and improved hemodynamic parameters such as LVEDP, LVSP and ±dp/dtmax. Moreover, H&E staining showed that LQ attenuated the pathological damage caused by MI. Masson staining showed that LQ alleviated myocardial cell disorder and fibrosis while reducing collagen deposition. LQ also decreased the levels of oxidative stress and inflammation. Western blotting demonstrated that LQ significantly down-regulated the expressions of Collagen I, Collagen III, TGF-ß1, MMP-9, α-SMA, CCL5, and p-NF-κB. Conclusion: LQ protected against myocardial fibrosis following MI by improving cardiac function, and attenuating oxidative damage and inflammatory response, which may be associated with inhibition of CCL5 expression and the NF-κB pathway.

Nephroprotective effect of magnesium isoglycyrrhizinate against arsenic trioxide-induced acute kidney damage in mice.

Magnesium isoglycyrrhizinate (MgIG) has anti-inflammatory, antioxidative, antiviral and anti-hepatotoxic effects. However, protective effects of MgIG against renal damage caused by arsenic trioxide (ATO) have not been reported. The present study aimed to clarify the protective function of MgIG on kidney damaged induced by ATO. Other than the control group and the group treated with MgIG alone, mice were injected intraperitoneally with ATO (5 mg/kg/day) for 7 days to establish a mouse model of kidney damage. On the 8th day, blood and kidney tissue were collected and the inflammatory factors and antioxidants levels in the kidney tissue and serum were measured. The expression of protein levels of caspase-3, Bcl-2, Bax, Toll-like receptor-4 (TLR4) and nuclear factor-κB (NF-κB) were determined via western blot analysis. In the renal tissue of mice, ATO exposure dramatically elevated markers of oxidative stress, apoptosis and inflammation. However, MgIG could also restore the activities of urea nitrogen and creatinine to normal levels, decrease the malondialdehyde level and reactive oxygen species formation and increase superoxide dismutase, catalase and glutathione activities. MgIG also ameliorated the morphological abnormalities generated by ATO, reduced inflammation and apoptosis and inhibited the TLR4/NF-κB signaling pathway. In conclusion, MgIG may mitigate ATO-induced kidney damage by decreasing apoptosis, oxidative stress and inflammation and its mechanism may be connected to the inhibition of TLR4/NF-κB signaling.

Protective mechanisms of 10-gingerol against myocardial ischemia may involve activation of JAK2/STAT3 pathway and regulation of Ca2+ homeostasis.

10-Gingerol (10-Gin), an active ingredient extracted from ginger, has been reported to have beneficial effects on the cardiovascular system. However, its protective effects on myocardial ischemia (MI) and the underlying cellular mechanisms are still unclear. To investigate the protection conferred by 10-Gin against MI injury and its potential mechanisms in cardiomyocytes via patch-clamp and molecular biology techniques. A rat MI model was established using the subcutaneous injection of isoproterenol (85 mg/kg) administered on two consecutive days. 10-Gin was pre-administered to rats for seven days to assess its cardio-protection. The patch-clamp and IonOptix Myocam detection techniques were used to investigated 10-Gin's effects on L-type Ca2+ channels (LTCCs), Ca2+ transients and cell contractility in isolated rat cardiomyocytes. 10-Gin administration alleviated MI injury, improved cardiac function and myocardial histopathology, reduced myocardial infarct area, downregulated oxidative stress and Ca2+ levels, and decreased the expression of apoptotic factors. Importantly, 10-Gin led to an increase in phosphorylated Janus kinase 2 and signal transducer and activator of transcription 3 (JAK2 and STAT3, respectively) expressions. Furthermore, 10-Gin inhibited LTCCs in a concentration-dependent manner with a half-maximal inhibitory concentration of 75.96 µM. Moreover, 10-Gin administration inhibited Ca2+ transients and cell contractility. Our results suggest that 10-Gin exerts cardioprotective effects on MI in vivo and in vitro in connection with the inhibition of oxidative stress and apoptosis via activation of the JAK2/STAT3 signalling pathway, and regulation of Ca2+ homeostasis by LTCCs.

Protective Effects of 6-Gingerol on Cardiotoxicity Induced by Arsenic Trioxide Through AMPK/SIRT1/PGC-1α Signaling Pathway.

Background and Objective: Arsenic trioxide (As2O3) induced cardiotoxicity to limit the clinical applications of the effective anticancer agent. 6-Gingerol (6G) is the main active ingredient of ginger, a food with many health benefits. The present study aims to investigate the potential pharmacological mechanisms of 6G on As2O3-induced myocardial injury. Methods and Results: Fifty KunMing mice were divided into five groups (n = 10) receiving: 1) physiological saline; 2) 6G (20 mg/kg) alone; 3) As2O3 (5 mg/kg); 4) 6G (10 mg/kg) and As2O3 (5 mg/kg); 5) 6G (20 mg/kg) and As2O3 (5 mg/kg). 6G was given orally and As2O3 was given intraperitoneally once per day for seven consecutive days. Biochemical, histopathological, transmission electron microscopy, ELISA, and western blotting analyses were then performed. Based on the resultant data, As2O3 was found to induce cardiotoxicity in mice. 6G significantly ameliorated As2O3-induced heart injury, histopathological changes, oxidative stress, myocardial mitochondrial damage, inflammation, and cardiomyocyte apoptosis, while reversed As2O3-induced inhibition of the AMPK/SIRT1/PGC-1α pathway. Conclusion: Our experimental results reveal that 6G effectively counteracts As2O3-induced cardiotoxicity including oxidative stress, inflammation and apoptosis, which might be attributed to its activation action on AMPK/SIRT1/PGC-1α signaling pathway.

Protective effects and possible mechanism of 6-gingerol against arsenic trioxide-induced nephrotoxicity based on network pharmacological analysis and experimental validation.

BACKGROUND AND OBJECTIVE: Nephrotoxicity induced by the chemotherapeutic drug arsenic trioxide (ATO) is often overlooked, and the underlying mechanisms remain poorly understood. Based on network pharmacology and experimental validation, this study investigates the protection of 6-gingerol (6G) against ATO-induced nephrotoxicity and the potential mechanisms. METHODS: We screened and collected 6G and disease-related targets and then imported the interaction targets into a String database to construct protein-protein interaction (PPI) networks. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Mice were injected intraperitoneally with ATO (5 mg/kg) for seven days to induce nephrotoxicity, and then the histological morphology of the kidneys, biochemical indices of serum and tissues, and associated protein expressions were observed. RESULTS: The network pharmacology results revealed that the effects of 6G against nephrotoxicity are closely related to apoptosis, and the MAPKs pathway was screened for validation. In animal experiments, 6G improved the histopathological morphology of the kidneys, reduced the levels of renal function markers, enhanced antioxidant activity, and decreased the levels of inflammation. Furthermore, 6G reduced apoptotic cells in kidney tissues, decreased the levels of Bax and c-Caspase-3, and increased the level of Bcl-2. The results of immunohistochemistry and western blotting revealed that 6G significantly inhibited the expressions of p-p38, p-ERK, and p-JNK. CONCLUSION: The results comprehensively demonstrate the protective effects of 6G against ATO-induced nephrotoxicity. The effects are related to anti-oxidant, anti-inflammatory, and anti-apoptotic properties, possibly through inhibition of the MAPKs pathway.

Protective effect of baicalin against arsenic trioxide-induced acute hepatic injury in mice through JAK2/STAT3 signaling pathway.

Baicalin (BA) is a kind of flavonoid that is isolated from Scutellaria baicalensis Georgi, which has been verified to have hepatoprotective effects in some diseases. However, the role of BA in acute hepatic injury induced by arsenic trioxide (ATO) remains unclear. The aim of this study was to investigate the protective action of BA on acute hepatic injury induced by ATO and to probe its possible mechanism. Mice were pretreated with BA (50, 100 mg/kg) by gavage. After 7 h, ATO (7.5 mg/kg) was injected intraperitoneally to induce liver injury. After 7 days of treatment, serum and hepatic specimens were collected and assayed to evaluate the hepatoprotective effect of BA. Pathological sections and the liver function index indicated that ATO caused significant liver injury. The fluorescence of reactive oxygen species and oxidative stress indicators showed that ATO also increased oxidative stress. The inflammatory markers in ATO-induced mice also increased significantly. Staining of the terminal deoxynucleotidyl transferase dUTP nick end labeling and apoptotic factor assay showed that apoptosis increased. However, with BA pretreatment, these changes were significantly weakened. In addition, BA treatment promoted the expression of proteins related to the JAK2/STAT3 signaling pathway. The results suggest that BA can ameliorate acute ATO-induced hepatic injury in mice, which is related to the inhibition of oxidative stress, thereby reducing inflammation and apoptosis. The mechanism of this protection is potentially related to the JAK2/STAT3 signaling pathway.

Evaluation of the relationship between polymorphisms in CYP2C19 and the single-dose pharmacokinetics of omeprazole in healthy Chinese volunteers: A multicenter study.

The aim of this study was to evaluate the relationship between polymorphisms in CYP2C19 and the single-dose pharmacokinetics (PKs) of omeprazole in healthy Chinese volunteers. A 20 mg single dose of omeprazole (Losec) enteric-coated capsules or tablets was orally administered to 656 healthy subjects from eight subcenters. The polymorphic alleles of CYP2C19*2, *3, and *17 were determined by Sanger sequencing and Agena mass array. Plasma concentrations of omeprazole were determined by high-performance liquid-chromatography tandem mass spectrometry. PK parameters of area under the concentration versus time curve (AUC)0-t , AUC from zero to infinity (AUC0-∞ ), maximum plasma concentration (Cmax ), and terminal half-life (t1/2 ) were significantly influenced by CYP2C19 phenotype (all p < 0.001) and diplotype (all p < 0.001), and the same results were obtained in the subgroup analysis of the effects of diet and dosage form. The polymorphisms of CYP2C19*2(rs4244285; all PK parameters p < 0.001) and *3(rs4986893; pCmax  = 0.020, and the p values of other PK parameters were less than 0.001) were significantly associated with the PKs of omeprazole. For CYP2C19*17 (rs12248560), only t1/2 showed a significant correlation (p = 0.032), whereas other PK parameters did not. The present study demonstrated that the Pks of omeprazole is greatly influenced by CYP2C19.

Gentianella acuta mitigates cardiovascular damage and inflammation in diet-induced hypercholesterolaemic rats.

Gentianella acuta (G. acuta) has been widely used as a traditional medicine by Chinese Mongolian populations for the treatment of heart diseases and has also been tested in modern pharmacological experiments. However, the effects of G. acuta on cardiovascular damage and inflammation under conditions of hypercholesterolaemia remain unclear. The present study investigated the effects and mechanisms of the water extract of G. acuta on cardiovascular damage and inflammation caused by a high-cholesterol diet. Male Sprague-Dawley rats were fed a high-cholesterol diet for 4 weeks to establish the hypercholesterolaemia rat model, and they were administered physiological saline or 1.2 g/kg of G. acuta by gavage starting from the 15th day. After the last administration, the blood, heart and thoracic aorta samples were collected and examined. It was revealed that G. acuta treatment could ameliorate cardiomyocyte disorder and thoracic aortic vessel wall damage, reduce serum lipid levels and inflammatory factors and improve heart function. Compared with the Model group, the serum levels of triglycerides, total cholesterol, low-density lipoprotein and tumour necrosis factor-α were decreased, and the high-density lipoprotein and interleukin-10 levels were increased in the Model-G group. Moreover, in both the heart and thoracic aorta, G. acuta reduced the expression and phosphorylation of inhibitor of nuclear factor kappa-B kinase ß (IKKß), inhibitor of NF-κB-α (IκBα) and p-nuclear factor kappa-B (NF-κB). Therefore, G. acuta may exert an inhibitory effect on the IKK/IκB/NF-κB signalling pathway to protect the heart and thoracic aorta in hypercholesterolaemic rats.

Salvia miltiorrhiza (SM) Injection Ameliorates Iron Overload-Associated Cardiac Dysfunction by Regulating the Expression of DMT1, TfR1, and FP1 in Rats.

Previous studies have found that Salvia miltiorrhiza (SM) injection have a protective effect on the iron overloaded (IO) heart. However, the mechanisms are not completely known. In the present study, we investigated the underlying mechanisms based on the iron transport-related proteins. The rats were randomly divided into five groups: control, IO group, low-dose SM group, high-dose SM group, and deferoxamine control group. Iron dextran was injected to establish the IO model. After 14 days of treatment, cardiac histological changes were observed by hematoxylin and eosin (H&E) staining. Iron uptake-related proteins divalent metal transporter-1 (DMT-1), transferrin receptor-1 (TfR-1), and iron export-related proteins ferroportin1 (FP1) in the heart were detected by Western blotting. The results showed that SM injection decreased cardiac iron deposition, ameliorated cardiac function, and inhibited cardiac oxidation. Most important of all, SM injection downregulated the expression of DMT-1 and TfR-1 and upregulated FP1 protein levels compared with the IO group. Our results indicated that reducing cardiac iron uptake and increasing iron excretion may be one of the important mechanisms of SM injection reducing cardiac iron deposition and improving cardiac function under the conditions of IO.

Investigation of the ameliorative effects of baicalin against arsenic trioxide-induced cardiac toxicity in mice.

Baicalin (BA), a kind of flavonoids compound, comes from Scutellaria baicalensis Georgi (a kind of perennial herb) and has beneficial effects on the cardiovascular system through anti-oxidant, anti-inflammation, and anti-apoptosis actions. However, the therapeutic effects and latent mechanisms of BA on arsenic trioxide (ATO)-induced cardiac toxicity has not been reported. The present research was performed to explore the effects and mechanisms of BA on ATO-induced heart toxicity. Male Kunming mice were treated with ATO (7.5 mg/kg) to induce cardiac toxicity. After the mice received ATO, BA (50 and 100 mg/kg) was administered for estimating its cardioprotective effects. Statistical data demonstrated that BA treatment alleviated electrocardiogram abnormalities and pathological injury caused by ATO. BA could also lead to recovery of CK and LDH activities to normal range and cause a decrease in MDA levels and ROS generation, augmentation of SOD, CAT, and GSH activities. We also found that BA caused a reduction in the expression of proinflammatory cytokines, such as TNF-α and IL-6. Moreover, BA attenuated ATO-induced apoptosis by promoting the expression of Bcl-2 and suppressing the expression of Bax and caspase-3. TUNEL test result demonstrated BA caused impediment of ATO-induced apoptosis. Furthermore, BA treatment suppressed the high expression of TLR4, NF-κB and P-NF-κB caused by ATO. In conclusion, these results indicate that BA may alleviate ATO-induced cardiac toxicity by restraining oxidative stress, apoptosis, and inflammation, and its mechanism would be associated with the inhibition of the TLR4/NF-κB signaling pathway.

Cardioprotective effects of glycyrrhizic acid involve inhibition of calcium influx via L-type calcium channels and myocardial contraction in rats.

Glycyrrhizic acid (GA) is one of the main active components in licorice and has often been reported to have cardioprotective effects. However, the underlying cellular mechanisms remain unclear. The aim of this study is to verify the protective effects of GA against isoproterenol (ISO)-induced myocardial ischemia injury in rats. Another aim is to explore the cellular mechanisms based on the L-type Ca2+ channel, myocardial cell contraction, and intracellular Ca2+ ([Ca2+]i) transient. The results show that GA reduced the ST segment elevation, decreased the heart rate, prevented ISO-induced QT-interval shortening, improved heart morphology, and decreased the activity of CK and LDH. GA blocked ICa-L in a dose-dependent manner. The concentration for 50% of the maximal effect (EC50) of GA was 145.54 µg/mL, and the maximal inhibition was 47.43 ± 0.75% at 1000 µg/mL. However, GA did not affect the dynamical properties of the Ca2+ channel. GA reversibly reduced the amplitude of cell contraction in a dose-dependent manner and slowed down its deflection and recovery, as well as the [Ca2+]i transient. The data demonstrate that GA inhibits L-type Ca2+ channels, decreases the [Ca2+]i transient, and shows a negative cardiac inotropic effect in the ventricular myocardial cells of adult rats. It also protects the myocardia from ischemia injury induced by ISO.