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.

Beneficial effects of psyllium on the prevention and treatment of cardiometabolic diseases.

Cardiometabolic diseases are reaching epidemic proportions worldwide. Dietary fiber intake can improve the risk factors associated with CMD. Psyllium, especially its husk, is one of the most widely used dietary fiber supplements, which is often used to enrich cereals and other food products. Numerous pharmacological studies have investigated the active ingredients and therapeutic effects of psyllium and its extracts, including antioxidant, anti-tumor, antidiabetic, hypotensive, anti-inflammation, neuroprotection, antidiarrheal, and antiviral activities. In this review, we will summarize the available studies on the therapeutic potential and possible mechanisms of psyllium in treating CMDs, such as hyperlipidemia, diabetes mellitus, and its complications, hypertension, hyperuricemia and obesity, and its applications in food systems.

Yi-Xin-Shu capsule ameliorates cardiac hypertrophy by regulating RB/HDAC1/GATA4 signaling pathway based on proteomic and mass spectrometry image analysis.

BACKGROUND: Cardiac hypertrophy (CH) forms the main pathological basis of chronic heart failure (CHF). Mitigating and preventing CH is the key strategy for the treatment of ventricular remodeling in CHF. Yi-Xin-Shu capsule (YXS) has been commonly applied in the clinical treatment of CHF in Asian countries for several decades. However, the underlying mechanism of YXS has not been revealed yet. PURPOSE: To assess the efficiency of YXS in CH and identify its potential therapeutic targets for the managing of CH. METHOD: Ultrasonic cardiogram was used to evaluate the cardiac function of CH rats. Hematein Eosin (HE)-staining, Masson-staining and transmission electron microscope were used to measure the morphological changes, cardiac fibrosis degree and ultrastructure characteristics of cardiomyocytes, respectively. ELISA was used to detect the myocardial injury biomarkers. Then, the potential targets regulated by YXS were screened out via proteomic analysis and mass spectrometry image analysis. Finally, the targets were validated by real-time quantitative (RT-q) PCR, immunofluorescence, immunohistochemistry, and western-blotting methods. RESULTS: YXS improved the cardiac function of CH rats and attenuated the injuries in morphology and subcellular structure of cardiomyocytes. A core protein-protein interaction network was established on differentially expressed proteins (DEP) using proteomics analysis. GATA binding protein 4 (GATA4) was identified as the key target regulated by YXS. The results of mass spectrometry image analysis indicated that the expressions of histone deacetylase 1 (HDAC1) and retinoblastoma (RB) could also be regulated by YXS. Further valuative experiments showed that YXS may attenuate CH by regulating the RB/HDAC1/GATA4 signaling pathway. CONCLUSIONS: For the first time, this study discloses the precise mechanism investigation of the efficacy of YXS against CH. These data demonstrate that YXS may protect against CH by regulating the RB/HDAC1/GATA4 signaling pathway.

Role of puerarin in pathological cardiac remodeling: A review.

Pathological cardiac remodeling normally involves changes in structure, function, and energy metabolism of the heart induced by cardiac injury or load, terminally leading to heart failure. Cardiac remodeling plays an essential role in the progression of cardiovascular disease, thus increasingly identified as an important therapeutic target for heart failure of all pathogenesis. Puerarin, as a natural isoflavone mainly from Pueraria lobata （Willd.）Ohwi, has been developed as injections, eye drops, microemulsions, etc., and is widely used in the clinical treatment of cardiovascular diseases in eastern Asia countries. In recent years, a growing number of studies have shown that puerarin significantly inhibits myocardial hypertrophic growth, myocyte death, fetal gene expression, fibroblast proliferation and activation, improves energy metabolism, promotes post-infarction angiogenesis, and suppresses inflammation and oxidative stress, consequently attenuating or preventing cardiac remodeling in response to multiple stimuli ( e.g., pressure overload, MIRI, MI, Iso, and Ang II stimulation). This review summarized the roles and underlying molecular mechanisms of puerarin in cardiac remodeling induced by diverse etiologies, aiming to help develop novel therapeutic strategies to prevent or reverse pathological ventricular remodeling.

Tongxinluo capsule as supplementation and cardiovascular endpoint events in patients with coronary heart disease: A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Tongxinluo Capsule(TXLC) is a well-known traditional Chinese medicine prescription with effects of tonifying Qi and activating blood based on the Chinese herbal medicine theory that has been recommended as routine adjuvant treatment in patients with coronary heart disease (CHD) in China. AIM OF THE STUDY: This meta-analysis aimed to evaluate the efficacy and safety of TXLC as supplementation in the prevention of adverse cardiovascular events in patients with CHD. MATERIALS AND METHODS: We performed a literature search in Pubmed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), Wan Fang Database, and Chinese Biomedical Database (CBM) from their inceptions to March 2020. Only randomized controlled trials (RCTs) that assessed supplementation with TXLC or placebo and with adverse cardiovascular outcomes, were included in this meta-analysis. Primary end points were myocardial infarction (MI), target vessel revascularization (TVR) or in-stent restenosis (ISR), and cardiovascular death. Secondary end points included cerebrovascular accidents, heart failure (HF), and unscheduled readmission for cardiovascular diseases (CVDs). Adverse drug events were also evaluated. Trial sequential analysis (TSA) was conducted to reduce random errors introduced by possible insufficient sample size. RESULTS: Eleven RCTs involving 1505 patients were analyzed. The mean(SD) age of included patients were 59.03(9.7) years. Treatment duration varied from 2 months to 12 months. Compared with placebo, TXLC supplementation showed significant effects on reducing the risk of MI (RR = 0.44, [95% CI, 0.24-0.80]), TVR or ISR (RR = 0.43, [95% CI, 0.31-0.58]), cerebrovascular accidents(RR = 0.17, [95% CI, 0.06-0.46]), HF (RR = 0.41, [95% CI, 0.21-0.79]), and unscheduled readmission for CVDs (RR = 0.72, [95% CI], P = 0.04), but did not have associations with incidence of cardiovascular death (RR = 0.53, [95% CI, 0.15-1.91]). Subgroups of trials with 2-month (MI: RR = 0.44, [95% CI, 0.13-1.53]; cardiovascular death: RR = 0.30, [95% CI, 0.01-7.67]; cerebrovascular accidents: RR = 0.04, [95% CI, 0.01-0.26]; unscheduled readmission for CVDs: RR = 0.43, [95% CI, 0.20-0.94]) and 12-month (MI: RR = 0.42, [95% CI, 0.20-0.89]; TVR or ISR: RR = 0.42, [95% CI, 0.31-0.58]; HF: RR = 0.34, [95% CI, 0.14-0.78]; unscheduled readmission for CVDs: RR = 0.85, [95% CI, 0.59-1.22]) intervention period were analyzed. The adverse drug reactions were mild with no significant difference between TXLC and placebo. CONCLUSIONS: This meta-analysis indicated that TXLC supplementation had beneficial effects on the prevention of cardiovascular adverse events, especially in TVR or ISR after coronary revascularization and may possibly lower the incidence of first or recurrent MI and HF within 12 months in patients with CHD, while insufficient sample size implied that these results lacked certain stability. And the effects of TXLC on cardiovascular mortality, cerebrovascular events, and unscheduled readmission for CVDs could not be confirmed due to insufficient cases. Clinical trials with large-sample sizes and extended follow-up time are of interest in the future researches.

Roles and mechanisms of puerarin on cardiovascular disease：A review.

Cardiovascular diseases (CVDs) are now the leading cause of mortality and morbidity worldwide，resulting in a large global economic burden. Recently, complementary and alternative medicine, such as traditional Chinese medicine (TCM) have received great attention. Puerarin (Pue) is an isoflavone isolated from the roots of Pueraria lobata (Willd.) Ohwi (also named "Ge gen" in China), and is a versatile TCM herb used for the treatment of fever, diarrhea, diabetes mellitus CVDs and cerebrovascular diseases. Numerous lines ofin vitro studies, as well as in vivo animal experiments have established that Pue offers beneficial roles against the progression of atherosclerosis, ischemic heart diseases, heart failure hypertension and arrhythmia by inhibiting pathological processes, such as the mitigation of endothelium injury, protection against inflammation, the disturbance of lipid metabolism, protection against ischemic reperfusion injury, anti-myocardial remodeling and other effects. Here, we provide a systematic overview of the pharmacological actions and molecular targets of Pue in cardiovascular disease prevention and treatment, to provide insights into the therapeutic potential of Pue in treating cardiovascular diseases.

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.

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.

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.

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.

[Effects of Qili Qiangxin Capsule on Lung Structural Remodeling in Heart Failure Rats after Myocardial Infarction and Its Mechanism].

Objective To observe the effect of Qili Qiangxin Capsule (QQC) in improving lung struc- tural remodeling on heart failure (HF) rats after myocardial infarction (Ml) and to study its possible mecha- nism. Methods The proximal left anterior descending branch of coronary artery was ligated using a terylene suture to establish acute myocardial infarction (AMI) rat model. After successful AMI modeling rats were ran- domly divided into the model group (intragastrically administered with distilled water at 1 mL/100 g, n =13) and the QQC group (intragastrically administered with QQC at the daily dose of 1 g/kg, n =9). And the sham-opera- tion group (intragastrically administered with distilled water at 1 mL/100 g, n =10) was also set up. After four weeks intervention heart functions of rats were detected using echocardiography. The pathological changes of lung structures were observed by HE and Masson staining method. Protein expressions of lung α-SMA, Collagen I, TGF-ß1, and p-Smad3 of the lung tissue were detected by immunohistochemistry and Western blot. Re- sults Compared with the sham-operation group, ejection fraction (EF) and fraction shortening (FS) decreased (P <0. 05) , protein expressions of lung left ventricular internal diastolic diameter (LVIDd), left ventric- ular internal systolic diameter (LVIDs), end diastolic volume (EDV), end systolic volume (ESV), α-smooth muscle actin (a-SMA), Collagen I, tumor growth factor-ß1 (TGF-ß1), and p-Smad3 increased (P <0.05) in the model group. The muscularized small arteries ratio and collagen area of the lung tissue increased in the model group (P <0. 05). Compared with the model group, EF and FS increased (P <0. 05), protein expressions of LVIDs, ESV, α-SMA, Collagen I, TGF-ß, , and p-Smad3 decreased (P <0.05) in the QQC group. The muscular- ized small arteries ratio and collagen area of the lung tissue decreased in the QQC group (P <0. 05). Conclusion QQC could improve lung structural remodeling degree of HF rats after MI, and its possible mechanism might be achieved by regulating TGF-beta,/Smad3 signaling pathways.

Beneficial Effects of Qili Qiangxin Capsule on Lung Structural Remodeling in Ischemic Heart Failure via TGF-ß1/Smad3 Pathway.

Qili qiangxin (QL) capsule is a traditional Chinese medicine that is widely used for the treatment of patients with chronic heart failure (CHF) of all etiologies, although the exact mechanisms of action remain unclear. CHF leads to pulmonary vascular remodelling and thickening of the alveolar-capillary barrier that may be important mechanisms in the poor clinical outcome in patients with end-stage heart failure. We examined whether QL could improve lung injury in ischemic CHF by reducing lung remodeling. Rats with myocardial infarct received QL (1.0 g/kg/day) for 4 weeks. Echocardiographic and morphometric measurements were obtained followed by echocardiography, histological staining, and immunohistochemical analysis of lung sections. CHF caused significant lung structural remodeling evidenced by collagen deposition and thickening of the alveolar septa after myocardial infarct that were greatly improved by QL. Lung weight increased after infarct with no evidence of pulmonary edema and was normalized by QL. QL also reduced lung transforming growth factor-ß1 (TGF-ß1), p-Smad3, tumor necrosis factor-α (TNF-α), and Toll-like receptor-4 (TLR4) expression. Thus, QL reduces lung remodeling associated with CHF, mainly by suppressing the TGF-ß1/Smad3 signaling pathway. The mechanism may also involve inhibition of TLR4 intracellular signaling.

Effects of Qili Qiangxin Capsule on AQP2, V2R, and AT1R in Rats with Chronic Heart Failure.

Qili qiangxin capsule (QL), a traditional Chinese herbal compound, has been proved to be effective and safe for the treatment of chronic heart failure (CHF). Upregulation of aquaporin-2 (AQP2) accounts for the water retention in CHF. The aim of the present study was to evaluate the effects of QL on the expression of AQP2 in rats with CHF induced by acute myocardial infarction and to investigate the underlying mechanisms. The urine output of all rats was quantified and collected every day at the first week and the 4th week after administration of QL or Valsartan. The expression of AQP2, vasopressin type 2 receptor (V2R), and angiotensin II type 1 receptor (AT1R) were examined after treatment for 4 weeks. Urinary output increased significantly after administration of QL. Importantly, the protein expression of AQP2 and AQP2 phosphorylated at serine 256 (pS256-AQP2) was downregulated after administration of QL and Valsartan to CHF rats. Furthermore, QL reduced plasma arginine vasopressin (AVP) and angiotensin II (AngII) level and downregulated V2R and AT1R protein expression. Thus, QL exerts its diuretic effect and improves cardiac function in CHF rats by reversing the increases in both AQP2 and pS256-AQP2 expression. The possible mechanisms may involve inhibition of V2R and AT1R.

Effect of two Chinese medicinal compounds, blood-activating and water-draining medicine, on tumor necrosis factor α and nuclear factor κ B expressions in rats with intracerebral hemorrhage.

OBJECTIVE: To investigate the effect of blood-activating Chinese medicinal compounds and water-draining Chinese medicinal compounds on tumor necrosis factor alpha (TNF-α) and nuclear factor kappaB (NF-κ B) expressions in rats with intracerebral hemorrhage (ICH) at the acute stage, and to monitor their therapeutic effect and mechanism of action on inflammation and cerebral edema. METHODS: A rat model of cerebral hemorrhage was achieved by injecting autologous arterial blood into the caudate nucleus. A total of 168 rats were randomly divided into 4 groups: blood-activating medicine group (n=42), water-draining medicine group (n=42), sham operated group (n=42), and the model group (n=42). A series of brain samples were obtained at days 1, 3 and 5 after ICH from rats in all groups. Protein expression levels of TNF-α and NF-κ B were measured by immunohistochemical staining and gene expression levels of TNF-α and NF-κ B were measured by real-time fluorescent PCR. RESULTS: Compared to the sham operated group, protein expression levels of TNF-α and NF-κ B in the model group significantly increased (P<0.01). Protein and gene expressions of TNF-α from the blood-activating medicine group and water-draining medicine group significantly decreased when compared to those in the model group P<0.05). Meanwhile, compared to the model group, the expression of NF-κ B in the blood-activating medicine group significantly decreased (P<0.05), while expression of NF-κ B in the water-draining medicine group did not differ (P>0.05). CONCLUSIONS: Blood-activating Chinese medicinal compounds and water-draining Chinese medicinal compounds can alleviate inflammation of peripheral tissue and cerebral edema. However, the blood-activating Chinese medicinal compounds were more effective than the water-draining Chinese medicinal compounds. The possible effective mechanism may be by means of inhibiting the activation of NF-κ B so as to suppress the transcription of target genes including gene expression of TNF-α.

The Effects of Velvet Antler of Deer on Cardiac Functions of Rats with Heart Failure following Myocardial Infarction.

Velvet antler of deer (VAD) is a commonly-used kidney-Yang supplementing traditional Chinese medication. According to the heart-kidney-related theory, heart Yang originates in kidney Yang and heart failure due to heart Yang deficiency can be treated by tonifying kidney Yang. In this study, we investigated therapeutic effects of VAD on cardiac functions in rats with heart failure following myocardial infarction. Forty-eight male Wistar rats were subjected either to left coronary artery ligation (N = 36) or to sham operation (N = 12). One week after the surgery, rats with heart failure received daily treatment of double-distilled water, captopril or VAD by gavage for consecutively four weeks, while sham-operated animals were given double-distilled water. Ultrasonic echocardiography was adopted to examine cardiac structural and functional parameters and serum brain natriuretic peptide (BNP) concentration was measured using radioimmunoassay. We found that VAD partially reversed changes in cardiac functional parameters and serum BNP levels in rats with heart failure. These results provide further evidence for the heart-kidney-related theory and suggest that VAD might be a potentially alternative and complementary medicine for the treatment of heart failure.

[Effects of herbs capable of activating blood circulation or inducing diuresis on the expressions of tumor necrosis factor-alpha, nuclear factor-kappaB, and aquaporin-4 in rats with intracerebral hemorrhage].

OBJECTIVE: To investigate the effects of herbs capable of activating blood circulation or inducing diuresis on the expressions of tumor necrosis factor-alpha (TNF-alpha), nuclear factor-kappaB (NF-kappaB), and aquaporin-4 (AQP-4) in rats with intracerebral hemorrhage (ICH), and to study their possible mechanisms. METHODS: The ICH rat model was established by injecting autologous arterial blood into the right caudate nucleus. The 168 male rats were randomly divided into four groups, the sham-operative group, the model group, the blood activating group, and the diuresis inducing group, 42 in each group. Chinese compound decoction (consisting of 0.2 g rhubarb, 0.02 g leech, and 0.3 g notoginseng in each milliliter decoction) was given to rats in the blood activating group by gastrogavage at the dose of 10 mL/kg, once daily. Chinese compound decoction (consisting of 0.2 g poria, 0.2 g water plantain tuber, and 0.2 g acori graninei in each milliliter decoction) was given to rats in the diuresis inducing group by gastrogavage at the dose of 10 mL/kg, once daily. 4.0 mL/kg normal saline was given to rats in the model group and the sham-operative group by gastrogavage, once daily. A series of brain samples were obtained on the 1st, 3rd, and 5th day, respectively. The mRNA and protein expressions of TNFalpha, NF-kappaB p65, and AQP-4 were determined by immunohistochemical staining and Real-time fluorescent quantitative PCR respectively. RESULTS: After ICH, TNF-alpha, NF-KB, and AQP-4 protein positive cells in the brain tissue and their protein and mRNA expressions significantly increased in rats of the model group at each time point when compared with the sham-operative group (P < 0.01, P < 0.05). The gene and protein expressions of TNF-alpha and AQP-4 significantly decreased in the blood activating group and the diuresis inducing group at each time point when compared with the model group (PP < 0.05). The expression of NF-kappaB p65 in the blood activating group obviously decreased when compared with the model group (P < 0.05), but there was no statistical difference in the NF-KB expression when compared with the diuresis inducing group (P > 0.05). Compared with the model group, the water content of the brain tissue decreased to some degree in the blood activating group and the diuresis inducing group at each time point. There was statistical difference between the blood activating group and the diuresis inducing group (P < 0.05). CONCLUSIONS: Chinese herbs capable of activating blood circulation or inducing diuresis could inhibit the release of TNF-alpha, down-regulate the expression of AQP-4, and alleviate the brain edema around hematoma. But the action strength and the effect links were different.

Management of SAH with traditional Chinese medicine in China.

China lacks large scale authorized epidemiological study results in allusion to subarachnoid hemorrhage (SAH) within recent 15 years since MONICA (multinational monitoring of trends and determinants in cardiovascular disease) study revealed SAH situation in China in 2000. The main cause of SAH in China is aneurysm which takes up 30-50%, while over 90% aneurysm locates at Willis circle. Early surgery for SAH after aneurysm rupture is the dominant procedure to deal with SAH in China. Moreover, calcium antagonists rank the absolute leading position for cerebral vascular spasm (CVS) among medication-based treatment options. However, traditional Chinese medicine such as Salvia miltiorrhiza, Acanthopanax senticosus, Ginkgo biloba, Pueraria lobata, Liguisticum chuanxiong, cow bezoar, Diospyros kaki and Gynostemma pentaphyllum have been proven beneficial in CVS prevention and treatment, while Salvia miltiorrhiza and TCM soup have unique effects on bleeding absorption. In addition, aescine and some TCM soup might relieve strong headache after SAH. In general, TCM integrated with western medicine have shown unique advantages in the current treatment of SAH in China. However, it is a pity that China still lacks larger scale randomized controlled trials and research on SAH treatment focusing on TCM and the related mechanism of TCM on SAH still need to be investigated further.