Regulatory mechanism of icariin in cardiovascular and neurological diseases.

Cardiovascular diseases (CVDs) and neurological diseases are widespread diseases with substantial rates of morbidity and mortality around the world. For the past few years, the preventive effects of Chinese herbal medicine on CVDs and neurological diseases have attracted a great deal of attention. Icariin (ICA), the main constituent of Epimedii Herba, is a flavonoid. It has been shown to provide neuroprotection, anti-tumor, anti-osteoporosis, and cardiovascular protection. The endothelial protection, anti-inflammatory, hypolipidemic, antioxidative stress, and anti-apoptosis properties of ICA can help stop the progression of CVDs and neurological diseases. Therefore, our review summarized the known mechanisms and related studies of ICA in the prevention and treatment of cardio-cerebrovascular diseases (CCVDs), to better understand its therapeutic potential.

Modified Linggui Zhugan Decoction protects against ventricular remodeling through ameliorating mitochondrial damage in post-myocardial infarction rats.

Introduction: Modified Linggui Zhugan Decoction (MLZD) is a Traditional Chinese Medicine prescription developed from Linggui Zhugan Decoction (LZD) that has been used for the clinical treatment of ischemic cardiovascular diseases. However, the cardioprotective mechanism of MLZD against post-myocardial infarction (MI) ventricular remodeling remains unclear. Methods: We explored the effects of MLZD on ventricular remodeling and their underlying mechanisms, respectively, in SD rats with MI models and in H9c2 cardiomyocytes with oxygen-glucose deprivation (OGD) models. The cardiac structure and function of rats were measured by echocardiography, HE staining, and Masson staining. Apoptosis, inflammation, mitochondrial structure and function, and sirtuin 3 (SIRT3) expression were additionally examined. Results: MLZD treatment significantly ameliorated cardiac structure and function, and thus reversed ventricular remodeling, compared with the control. Further research showed that MLZD ameliorated mitochondrial structural disruption, protected against mitochondrial dynamics disorder, restored impaired mitochondrial function, inhibited inflammation, and thus inhibited apoptosis. Moreover, the decreased expression level of SIRT3 was enhanced after MLZD treatment. The protective effects of MLZD on SIRT3 and mitochondria, nevertheless, were blocked by 3-TYP, a selective inhibitor of SIRT3. Discussion: These findings together revealed that MLZD could improve the ventricular remodeling of MI rats by ameliorating mitochondrial damage and its associated apoptosis, which might exert protective effects by targeting SIRT3.

Beneficial effects of cinnamon and its extracts in the management of cardiovascular diseases and diabetes.

Cardiovascular diseases (CVDs) and diabetes are the leading causes of death worldwide, which underlines the urgent necessity to develop new pharmacotherapies. Cinnamon has been an eminent component of spice and traditional Chinese medicine for thousands of years. Numerous lines of findings have elucidated that cinnamon has beneficial effects against CVDs in various ways, including endothelium protection, regulation of immune response, lowering blood lipids, antioxidative properties, anti-inflammatory properties, suppression of vascular smooth muscle cell (VSMC) growth and mobilization, repression of platelet activity and thrombosis and inhibition of angiogenesis. Furthermore, emerging evidence has established that cinnamon improves diabetes, a crucial risk factor for CVDs, by enhancing insulin sensitivity and insulin secretion; regulating the enzyme activity involved in glucose; regulating glucose metabolism in the liver, adipose tissue and muscle; ameliorating oxidative stress and inflammation to protect islet cells; and improving diabetes complications. In this review, we summarized the mechanisms by which cinnamon regulates CVDs and diabetes in order to provide a theoretical basis for the further clinical application of cinnamon.

Regulatory Mechanisms of Baicalin in Cardiovascular Diseases: A Review.

Cardiovascular diseases (CVDs) is the leading cause of high morbidity and mortality worldwide, which emphasizes the urgent necessity to develop new pharmacotherapies. In eastern countries, traditional Chinese medicine Scutellaria baicalensis Georgi has been used clinically for thousands of years. Baicalin is one of the main active ingredients extracted from Chinese herbal medicine S. baicalensis. Emerging evidence has established that baicalin improves chronic inflammation, immune imbalance, disturbances in lipid metabolism, apoptosis and oxidative stress. Thereby it offers beneficial roles against the initiation and progression of CVDs such as atherosclerosis, hypertension, myocardial infarction and reperfusion, and heart failure. In this review, we summarize the pharmacological features and relevant mechanisms by which baicalin regulates CVDs in the hope to reveal its application for CVDs prevention and/or therapy.

Qiliqiangxin prevents right ventricular remodeling by inhibiting apoptosis and improving metabolism reprogramming with pulmonary arterial hypertension.

Pathological remodeling of the right ventricular (RV) contributes to the mortality of pulmonary arterial hypertension (PAH) patients, and RV myocardial apoptosis and metabolism play decisive roles in RV remodeling. Qiliqiangxin (QLQX), a traditional Chinese medicine, has a cardio-protective effective on left ventricular remodeling. However, whether QLQX can decrease RV myocardial apoptosis, improve metabolism, and attenuate RV remodeling remain uncertain. This study investigated the effects of QLQX on RV remodeling, myocardial mitochondria, apoptosis, and metabolism reprogramming. RV remodeling was induced by intraperitoneal injection of Monocrotaline (MCT). We first discovered that QLQX improved hemodynamic parameters and inhibited MCT-induced RVH. Next, QLQX significantly attenuated RV remodeling which covered RV myocardial fibrosis, and RV capillary density. Furthermore, we uncovered that QLQX attenuated RV myocardial apoptosis. We also confirmed that QLQX reversed metabolic shift toward glycolysis which decreased the uptake of glucose showed by fluorodeoxyglucose F 18 positron emission tomography (18FDG-PET). Mechanistically, QLQX optimized mitochondrial function by ameliorating structural abnormality of mitochondria, reducing the release of cytochrome c from mitochondria, and upregulating the expression of SOD2. Mitochondria-dependent apoptosis and mitochondria-associated metabolism were involved in QLQX regulation of RV. Moreover, our study showed that PINK1/Parkin 2 pathway was involved in improving mitochondrial function. We concluded that QLQX could inhibit PAH-induced RV remodeling by decreasing mitochondria associated apoptotic pathway and reversing mitochondrial related metabolic shift. The PINK1/Parkin mitophagy pathway may play a key role in mitochondria protection.

Guanxinshutong Alleviates Atherosclerosis by Suppressing Oxidative Stress and Proinflammation in ApoE-/- Mice.

Atherosclerosis (AS) is a chronic progressive disease related to dyslipidemia, inflammation, and oxidative stress. Guanxinshutong capsule (GXST), a traditional Chinese medicine, has been widely used in treating coronary atherosclerotic heart disease, while its mechanism actions on AS are still not to be well addressed. Our present study is aimed to examine the effect of GXST on AS and elucidate the multitarget mechanisms of GXST on AS. Network pharmacology analysis was employed to screen the multitarget mechanisms of GXST on AS. ApoE-/- mice were used to validate these effects. Circulating lipid profile and oxidative stress-related factors were measured by the Elisa kit. Furthermore, the aortic trunk and aortic root were excised for oil red O staining, histopathological and immunohistochemical analysis. We first discovered that GXST was clued to exert synergistically antiatherosclerosis properties including lipid-lowering, anti-inflammation, and antioxidation through the computational prediction based on a network pharmacology simulation. Next, the validation experiments in atherosclerosis mice provided evidence that GXST significantly reduced atherosclerotic lesions, increased collagen deposition, and attenuated LV remodeling to some extent. Mechanistically, GXST modulated lipid profile, downregulated the level of inflammatory cytokines and NF-κBp65. GXST also reduced the activity of oxidative parameter MDA and upregulated the activities of antioxidant enzymes (SOD and GSH) compared with the AS model group. In conclusion, GXST intervention might attenuate atherosclerosis by mechanisms involving reducing lipid deposition, modulating oxidative stress and inflammatory responses, but a larger controlled trial is necessary for confirmation.

Bao Yuan decoction and Tao Hong Si Wu decoction improve lung structural remodeling in a rat model of myocardial infarction: Possible involvement of suppression of inflammation and fibrosis and regulation of the TGF-ß1/Smad3 and NF-κB pathways.

Chronic heart failure (CHF) leads to pulmonary structural remodeling, which may be a key factor for poor clinical outcomes in patients with end-stage heart failure, and few effective therapeutic options are presently available. The aim of the current study was to explore the mechanism of action and pulmonary-protective effects of treatment with Bao Yuan decoction combined with Tao Hong Si Wu decoction (BYTH) on lung structural remodeling in rats with ischemic heart failure. In a model of myocardial infarction (MI) induced by ligation of the left anterior descending (LAD) artery, rats were treated with BYTH. Heart function and morphometry were measured followed by echocardiography, histological staining, and immunohistochemical analysis of lung sections. The levels of transforming growth factor-ß1 (TGF-ß1), type I collagen, phosphorylated-Smad3 (p-Smad3), tumor necrosis factor-α (TNF-α), toll-like receptor 4 (TLR4), active nuclear factor κB (NF-κB) and alpha smooth muscle actin (α-SMA) were detected using Western blotting. Lung weight increased after an infarct with no evidence of pulmonary edema and returned to normal as a result of BYTH. In addition, BYTH treatment reduced levels of type I collagen, TGF-ß1, and α-SMA expression and decreased the phosphorylation of Smad3 in the lungs of rats after MI. BYTH treatment also reduced the elevated levels of lung inflammatory mediators such as TNF-α, TLR4, and NF-κB. Results suggested that BYTH could effectively improve lung structural remodeling after MI because of its anti-inflammatory and anti-fibrotic action, which may be mediated by suppression of the TGF-ß1/Smad3 and NF-κB signaling pathways.

Qiliqiangxin Attenuates Cardiac Remodeling via Inhibition of TGF-ß1/Smad3 and NF-κB Signaling Pathways in a Rat Model of Myocardial Infarction.

BACKGROUND/AIMS: Qiliqiangxin (QL), a traditional Chinese medicine, has been demonstrated to be effective and safe for the treatment of chronic heart failure. Left ventricular (LV) remodeling causes depressed cardiac performance and is an independent determinant of morbidity and mortality after myocardial infarction (MI). Our previous studies have shown that QL exhibits cardiac protective effects against heart failure after MI. The objective of this study was to explore the effects of QL on myocardial fibrosis in rats with MI and to investigate the underlying mechanism of these effects. METHODS: A rat model of acute myocardial infarction was induced by ligating the left anterior descending coronary artery. The rats were treated with QL (1.0 g/kg/day) for 4 weeks after surgery. Echocardiography and histology examination were performed to evaluate heart function and fibrosis, respectively. Protein levels of transforming growth factor-ß1 (TGF-ß1), phosphorylated Smad3 (p-Smad3), phosphorylated Smad7 (p-Smad7), collagen I (Col- I), alpha smooth muscle actin (a-SMA), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), nuclear factor κB (NF-κB), and phosphorylated inhibitor of kappa B alpha (p-IκBα) were measured by western blot analysis. RESULTS: QL treatment ameliorated adverse cardiac remodeling 8 weeks after AMI, including better preservation of cardiac function, decreased inflammation, and reduced fibrosis. In addition, QL treatment reduced Col-I, a-SMA, TGF-ß1, and p-Smad3 expression levels but increased p-Smad7 levels in postmyocardial infarct rat hearts. QL administration also reduced the elevated levels of cardiac inflammation mediators, such as TNF-α and IL-6, as well as NF-κB and p-IκBα expression. CONCLUSIONS: QL therapy exerted protective effects against cardiac remodeling potentially by inhibiting TGF-ß1/Smad3 and NF-κB signaling pathways, thereby preserving cardiac function, as well as reducing myocardial inflammation and fibrosis.

Synthesis and antibacterial activity of novel 3-O-carbamoyl derivatives of clarithromycin and 11,12-cyclic carbonate azithromycin.

Two series of novel 3-O-carbamoyl derivatives of clarithromycin and 11,12-cyclic carbonate azithromycin were designed, synthesized and evaluated for their in vitro antibacterial activities. Compounds 4j and 4k were the most potent activity against erythromycin-susceptible Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae, which were comparable to those of clarithromycin and azithromycin. Compounds 4d, 4h and 4i showed potent activity against erythromycin-resistant S. pneumoniae encoded by the mef gene and compounds 4h and 4i displayed greatly improved activity against erythromycin-resistant S. pneumoniae encoded by the erm gene. Compound 7c exhibited improved activity against erythromycin-resistant S. pneumoniae encoded by the erm and mef genes.