Baicalin Maintains Articular Cartilage Homeostasis and Alleviates Osteoarthritis by Activating FOXO1.

Baicalin has been acknowledged for its anti-inflammatory properties. However, its potential impact on osteoarthritis (OA) has not yet been explored. Therefore, our study aimed to examine the effects of Baicalin on OA, both in laboratory and animal models. To evaluate its efficacy, human chondrocytes affected by OA were treated with interleukin-1ß and/or Baicalin. The effects were then assessed through viability tests using the cell counting kit-8 (CCK-8) method and flow cytometry. In addition, we analyzed the expressions of various factors such as FOXO1, autophagy, apoptosis, and cartilage synthesis and breakdown to corroborate the effects of Baicalin. We also assessed the severity of OA through analysis of tissue samples. Our findings demonstrate that Baicalin effectively suppresses inflammatory cytokines and MMP-13 levels caused by collagenase-induced osteoarthritis, while simultaneously preserving the levels of Aggrecan and Col2. Furthermore, Baicalin has been shown to enhance autophagy. Through the use of FOXO1 inhibitors, lentivirus-mediated knockdown, and chromatin immunoprecipitation, we verified that Baicalin exerts its protective effects by activating FOXO1, which binds to the Beclin-1 promoter, thereby promoting autophagy. In conclusion, our results show that Baicalin has potential as a therapeutic agent for treating OA (Clinical Trial Registration number: 2023-61).

Qihuang Zhuyu formula alleviates coronary microthrombosis by inhibiting PI3K/Akt/αIIbß3-mediated platelet activation.

BACKGROUND: Coronary microembolism (CME) is commonly seen in the peri-procedural period of Percutaneous Coronary Intervention (PCI), where local platelet activation and endothelial cell inflammation crosstalk may lead to micro thrombus erosion and rupture, with serious consequences. Qihuang Zhuyu Formula (QHZYF) is a Chinese herbal compound with high efficacy against coronary artery disease, but its antiplatelet mechanism is unclear. HYPOTHESIS/PURPOSE: This study aimed to elucidate the effects and mechanisms of QHZYF on sodium laurate-induced CME using network pharmacology and in vitro and in vivo experiments. METHODS: We employed high-performance liquid chromatography mass spectrometry to identify the main components of QHZYF. Network pharmacology analysis, molecular docking and surface plasmon resonance (SPR) were utilized to predict the primary active components, potential therapeutic targets, and intervention pathways mediating the effects of QHZYF on platelet activation. Next, we pretreated a sodium laurate-induced minimally invasive CME rat model with QHZYF. In vivo experiments were performed to examine cardiac function in rats, to locate coronary arteries on heart sections to observe internal microthrombi, to extract rat Platelet-rich plasma (PRP) for adhesion assays and CD62p and PAC-1 (ITGB3/ITGA2B) flow assays, and to measure platelet-associated protein expression in PRP. In vitro clot retraction and Co-culture of HUVECs with PRP were performed and the gene pathway was validated through flow cytometry and immunofluorescence. RESULTS: Combining UPLC-Q-TOF/MS technology and database mining, 78 compounds were finally screened as the putative and representative compounds of QHZYF, with 75 crossover genes associated with CME. QHZYF prevents CME mainly by regulating key pathways of the inflammation and platelets, including Lipid and atherosclerosis, Fluid shear stress, platelet activation, and PI3K-Akt signaling pathways. Five molecules including Calyson, Oroxin A, Protosappanin A,Kaempferol and Geniposide were screened and subjected to molecular docking and SPR validation in combination with Lipinski rules (Rule of 5, Ro5). In vivo experiments showed that QHZYF not only improved myocardial injury but also inhibited formation of coronary microthrombi. QHZYF inhibited platelet activation by downregulating expression of CD62p receptor and platelet membrane protein αIIbß3 and reduced the release of von Willebrand Factor (vWF), Ca2+ particles and inflammatory factor IL-6. Further analysis revealed that QHZYF inhibited the activation of integrin αIIbß3, via modulating the PI3K/Akt pathways. In in vitro experiments, QHZYF independently inhibited platelet clot retraction. Upon LPS induction, the activation of platelet membrane protein ITGB3 was inhibited via the PI3K/Akt pathway, revealing an important mechanism for attenuating coronary microthrombosis. We performed mechanistic validation using PI3K inhibitor LY294002 and Akt inhibitor MK-2206 to show that QHZYF inhibited platelet membrane protein activation and inflammation to improved coronary microvessel embolism by regulating PI3K/Akt/αIIbß3 pathways, mainly by inhibiting PI3K and Akt phosphorylation. CONCLUSION: QHZYF interferes with coronary microthrombosis through inhibition of platelet adhesion, activation and inflammatory crosstalk, thus has potential in clinical anti-platelet applications. Calyson, Oroxin A, Protosappanin A, Kaempferol and Geniposide may be the major active ingredient groups of QHZYF that alleviate coronary microthrombosis.

Xinkeshu for coronary heart disease complicated with anxiety or depression: A meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: The incidence of coronary heart disease (CHD) complicated with anxiety or depression is increasing year by year. However, many anti-anxiety drugs or antidepressants have a certain degree of adverse reactions and are not easily accepted by patients. Xinkeshu (XKS), as a proprietary Chinese patent medicine with "psycho-cardiology" effect, is one of the commonly used drugs in the treatment of CHD complicated with anxiety or depression in China. AIM OF THE STUDY: To systematically evaluate the efficacy and safety of XKS for CHD complicated with anxiety or depression. METHODS: Nine different electronic databases were independently searched to include randomized controlled trials (RCTs) of XKS for CHD complicated with anxiety or depression published from inception to February 2022, and the methodological quality was evaluated using the bias risk assessment tool from Cochrane Handbook 5.0 and the modified Jadad scale. Meta-analysis was performed using RevMan 5.3 and Stata 16.0 software. The GRADE Profiler 3.6.1 and TSA 0.9.5.10 beta were adopted to evaluate the certainty and conclusiveness of the evidence. RESULTS: A total of 18 RCTs involving 1907 subjects were included. There were 956 subjects in the XKS group and 951 subjects in the control group. Baseline conditions were consistent and comparable between the groups. Compared with single-use western medicine (WM), XKS combined with WM significantly reduced scores of Hamilton Anxiety Scale (HAMA) [Mean difference (MD) = -7.60, 95% confidence interval (95% CI) (-10.37, -4.83), P < 0.000 01], Zung Self-rating Anxiety Scale (SAS) [MD = -10.05, 95% CI (-12.70, -7.41), P < 0.000 01], Hamilton Depression Scale (HAMD) [MD = -6.74, 95% CI (-11.58, -1.90), P = 0.006], and Zung Self-rating Depression Scale (SDS) [MD = -10.75, 95% CI (-17.05,-4.45), P = 0.000 8], as well as improved clinical effective rate [odds ratio (OR) = 4.24, 95% CI (2.47, 7.27), P < 0.000 01]. In terms of safety, 4 studies reported the adverse reactions in detail. The severity was mild and symptoms disappeared after treatment. CONCLUSION: Current evidence indicates that XKS may be effective and safe in the treatment of patients with CHD complicated with anxiety or depression. Since the quality of the literature included in this study was generally low, there is an urgent need for more RCTs with high quality, low bias risk and sufficient sample size to validate our conclusions.

Jiawei Yanghe Decoction suppresses breast cancer by regulating immune responses via JAK2/STAT3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiawei Yanghe Decoction (JWYHD) is a widely used traditional Chinese medicine prescription in the clinical setting for the treatment of autoimmune diseases. Many studies showed that JWYHD has anti-tumor activities in cell and animal models. However, the anti-breast cancer effects of JWYHD and the underlying mechanisms of action remain unknown. AIM OF STUDY: This study aimed to determine the anti-breast cancer effect and reveal the underlying mechanisms of action in vivo, in vitro and in silico. MATERIALS AND METHODS: Orthotopic xenograft breast cancer mouse model and inflammatory zebrafish model were used to observe the anti-tumor effect and immune cell regulation of JWYHD. Moreover, the anti-inflammatory effect of JWYHD were evaluated by the expression of RAW 264.7 cells. JWYHD active ingredients were obtained by UPLC-MS/MS and potential targets were screened by network pharmacology. The therapeutic targets and signaling pathways predicted by computer were assessed by Western blot, real-time PCR (RT-PCR), immunohistochemistry (IHC) staining, and Enzyme-linked immunosorbent assays (ELISA) to explore the therapeutic mechanism of JWYHD against breast cancer. At last, Colivelin and Stattic were used to explore the effect of JWYHD on JAK2/STAT3 pathway. RESULTS: JWYHD significantly decreased the tumor growth in a dose-dependent manner in the orthotopic xenograft breast cancer mouse model. Flow cytometry and IHC results indicated that JWYHD decreased the expressions of M2 macrophages and Treg while increasing M1 macrophages. Meanwhile, ELISA and Western blot results showed a decrease in IL-1ß, IL-6, TNFα, PTGS2 and VEGFα in tumor tissue of JWYHD groups. The results were also verified in LPS-induced RAW264.7 cells and zebrafish inflammatory models. TUNEL assay and IHC results showed that JWYHD significantly induced apoptosis. Seventy-two major compounds in JWYHD were identified by UPLC-MS/MS and Network pharmacology. It was found that the significant binding affinity of JWYHD to TNFα, PTGS2, EGFR, STAT3, VEGFα and their expressions were inhibited by JWYHD. IHC and Western blot analysis showed that JWYHD could decrease the expression of JAK2/STAT3 pathway. Furthermore, Colivelin could reverse the decrease effect of JWYHD in vitro. CONCLUSION: JWYHD exerts a significant anti-tumor effect mainly by inhibiting inflammation, activating immune responses and inducing apoptosis via the JAK2/STAT3 signaling pathway. Our findings provide strong pharmacological evidence for the clinical application of JWYHD in the management of breast cancer.

Zhenwu decoction ameliorates cardiac hypertrophy through activating sGC (soluble guanylate cyclase) - cGMP (cyclic guanosine monophosphate) - PKG (protein kinase G) pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhenwu Decoction (ZWD) is a traditional Chinese medicine (TCM) formula which has wide scope of indications related to Yang deficiency and dampness retention in TCM syndrome. Cardiac hypertrophy can induce similar symptoms and signs to the clinical features of Yang deficiency and dampness retention syndrome. ZWD can increase the left ventricular ejection fraction, reduce cardiac hypertrophy of patients with chronic heart failure. However, its underlying pharmacological mechanism remains unclear. AIM OF THE STUDY: The study aimed to confirm the protective effects of ZWD on cardiac hypertrophy and explore the underlying mechanisms. MATERIALS AND METHODS: The potential targets and pathways of ZWD in cardiac hypertrophy were highlighted by network pharmacology and validated by mechanistic and functional studies. RESULTS: Our network pharmacology analysis suggests that the protective effects of ZWD on cardiac hypertrophy are related to cyclic guanosine monophosphate (cGMP) - protein kinase G (PKG) pathway. Subsequent animal studies showed that ZWD significantly ameliorated cardiac function decline, cardiac hypertrophy, cardiac fibrosis and cardiomyocyte apoptosis. To explore the underlying mechanisms of action, we performed Western blotting, immunohistochemical analysis, and detection of inflammatory response and oxidative stress. Our results showed that ZWD activated the soluble guanylate cyclase (sGC) - cGMP - PKG signaling pathway. The sGC inhibitor ODQ that blocks the sGC-cGMP-PKG signaling pathway in zebrafish abolished the protective effects of ZWD, suggesting sGC-cGMP-PKG is the main signaling pathway mediates the protective effect of ZWD in cardiac hypertrophy. In addition, three major ingredients from ZWD, poricoic acid C, hederagenin and dehydrotumulosic acid, showed a high binding energy with prototype sGC. CONCLUSION: ZWD reduces oxidative stress and inflammation and exerts cardioprotective effects by activating the sGC-cGMP-PKG signaling pathway.

Qihuang Zhuyu Formula Attenuates Atherosclerosis via Targeting PPARγ to Regulate Cholesterol Efflux and Endothelial Cell Inflammation.

At present, due to the limitations of drug therapy targets for atherosclerosis, some patients fail to achieve satisfactory efficacy. Cholesterol efflux dysfunction and endothelial cell inflammation are considered to be important factors in the development of atherosclerosis. Peroxisome proliferator-activated receptor gamma (PPARγ), a promising therapeutic target for atherosclerosis, plays a dual role in regulating cholesterol efflux and endothelial cell inflammation. However, the use of PPARγ agonist in clinical practice is greatly limited as it could lead to water and sodium retention and hence result in congestive heart failure. Qihuang Zhuyu Formula (QHZYF) is a hospital preparation of Jiangsu Province Hospital of Chinese Medicine which has definite effect in the treatment of atherosclerosis, but its pharmacological mechanism has not been clear. In this study, we successfully predicted that QHZYF might regulate cholesterol efflux and endothelial inflammation via targeting PPARγ-mediated PPARγ/LXRα/ABCA1-ABCG1 and PPARγ/NF-κB p65 pathways by using UPLC-Q-TOF/MS, network pharmacology, bioinformatics analysis, and molecular docking technology. Subsequently, we confirmed in vivo that QHZYF could attenuate atherosclerosis in ApoE-/- mice and regulate the expression levels of related molecules in PPARγ/LXRα/ABCA1-ABCG1 and PPARγ/NF-κB p65 pathways of ApoE-/- mice and C57BL/6 wild-type mice. Finally, in in vitro experiments, we found that QHZYF could reduce lipid content and increase cholesterol efflux rate of RAW 264.7 cells, inhibit the inflammatory response of HUVECs, and regulate the expression levels of related molecules in the two pathways. In addition, the above effects of QHZYF were significantly weakened after PPARγ knockdown in the two kinds of cells. In conclusion, our study revealed that QHZYF attenuates atherosclerosis via targeting PPARγ-mediated PPARγ/LXRα/ABCA1-ABCG1 and PPARγ/NF-κB p65 pathways to regulate cholesterol efflux and endothelial cell inflammation. More importantly, our study offers a promising complementary and alternative therapy which is expected to make up for the limitation of current drug treatment methods and provide a valuable reference for new drugs development in the future.

[Expert consensus on clinical application of GBE50 Dispersible Tablets for ischemic cardiovascular and cerebrovascular diseases].

Ginkgo biloba Extract( GBE50) Dispersible Tablets is a new standardized prescription,which is widely used in the treatment of ischemic cardiovascular and cerebrovascular diseases. However,there are still many problems in its clinical application.Rational and safe use of GBE50 Dispersible Tablets is pivotal to the medication safety and clinical prognosis of patients. This consensus has been jointly formulated by clinical experts of traditional Chinese medicine and western medicine in cardiovascular and cerebrovascular diseases and followed the Manual for the Clinical Experts Consensus of Chinese Patent Medicine published by the China Association of Chinese Medicine. The present study identified clinical problems based on clinical investigation,searched the research papers according to PICO clinical problems,carried out evidence evaluation,classification,and recommendation by GRADE system,and reached the expert consensus with nominal group technique. The consensus combines evidence with expert experience. Sufficient evidence of clinical problems corresponds to " recommendations",while insufficient evidence to " suggestions". Safety issues of GBE50 Dispersible Tablets,such as indications,usage and dosage,and medication for special populations,are defined to improve clinical efficacy,promote rational medication,and reduce drug risks. This consensus needs to be revised based on emerging clinical issues and evidencebased updates in practical applications in the future.

Tetramethylpyrazine alleviates diabetes-induced high platelet response and endothelial adhesion via inhibiting NLRP3 inflammasome activation.

BACKGROUND: The inflammatory state of diabetes promotes high platelet response and endothelial adhesion, which are the main risk factors for cardiovascular events. Tetramethylpyrazine (TMP) is an amide alkaloid isolated from the traditional Chinese medicine Rhizoma Ligustici Chuanxiong, which has been widely used in the clinical treatment of ischemic cardiovascular disease. PURPOSE: This study aimed to investigate whether TMP could alleviate diabetes-induced high platelet response and endothelial adhesion and the underlying mechanisms. METHODS: Type 2 diabetes mellitus (T2DM) rat model was established by high-fat feeding combined with low dose of streptozotocin. Rats in the TMP treatment group were administered with TMP (100 or 200 mg/kg) for 21 days. Cultured human umbilical vein endothelial cells (HUVECs) were stimulated with glucose (5.5 mM) to induce endothelial activation. The NOD-like receptor protein 3 (NLRP3) over- and low-expressing cell models were established via transfection of NLRP3 lentivirus plasmid into HUVECs. INF39 (25 mg/kg), a chemical inhibitor of NLRP3 inflammasome, was used to explore the role of NLRP3 in T2DM associated high platelet response and endothelial adhesion. RESULTS: TMP effectively improved the prothrombotic phenotypes and inhibited the expression of vascular inflammatory factors and adhesion molecules in T2DM rats. TMP inhibited NLRP3 inflammasome and reduced the adhesion of HUVECs to platelets and monocytes in vitro. Over-expression of NLRP3 blocked the effect of TMP on HUVECs activation and adhesion, while TMP had no effect on NLRP3 low-expressing HUVECs. The NLRP3 inhibitor INF39 produced similar effects of TMP on diabetes-induced high platelet response, endothelial adhesion and vascular inflammation. CONCLUSION: TMP ameliorates diabetes-induced high platelet response and endothelial adhesion via inhibiting NLRP3 inflammasome activation in T2DM rats, which provide a new basis for the clinical prevention and treatment of diabetes-associated cardiovascular events.

[Meta-analysis for clinical efficacy of traditional Chinese medicine in treating resistant hypertension].

To systematically evaluate the efficacy and safety of traditional Chinese medicine in treating patients with resistant hypertension. CNKI, Wanfang, VIP, CBM, PubMed, Web of Science, Cochrane Library, EMbase and other databases were retrieved by computers to screen out the randomized controlled trial of traditional Chinese medicine in treating resistant hypertension. Cochrane Handbook was used to evaluate the quality of the included literature, RevMan 5.3 and Stata 12.0 was used for Meta-analysis. Finally, 11 literatures meeting the criteria were included, involving 1 023 patients. The results of Meta-analysis showed that the combined therapy of standard triple antihypertensive regimen with traditional Chinese medicine could further reduce systolic blood pressure of patients with resistant hypertension(MD=-16.69, 95%CI[-22.21,-11.16], P<0.000 01), reduce diastolic blood pressure(MD=-7.51, 95%CI[-8.26,-6.76], P<0.000 01), improve the effective rate of anti-hypertension(OR=5.16, 95%CI[3.01, 8.84], P<0.000 01), improve the up-to-standard rate of blood pressure(OR=3.01, 95%CI[1.49, 6.09], P=0.002), and improve the effectiveness of clinical symptoms(OR=4.48, 95%CI[2.31, 8.68], P<0.000 01), with no significant effect on creatinine level(MD=-2.51, 95%CI[-6.91, 1.89], P=0.26). The results of this study indicated that the combined therapy of standard triple antihypertensive regimen with traditional Chinese medicine could further improve the clinical efficacy in patients with resistant hypertension with a good safety, but more high-quality clinical studies are still needed to verify this conclusion.

Total flavone of Abelmoschl manihot L. medic exhibits protective effect against hind-limb ischemia in rat model.

Total flavones of Abelmoschus manihot L. Medic (TFA) is the major active component isolated from Chinese herb Abelmoschus manihot L. Medic. TFA has shown neuroprotective effect against cerebral ischemia injury in rats and rabbits. However, the effects of TFA on hind-limb ischemia and the underlying mechanisms remain unclear. Therefore, in the present study, we used a rat hind-limb ischemia model to investigate protective effect of TFA against limb ischemia injury. The rat model of hind-limb ischemia was established. Treatment groups received TFA at two different doses (160 and 40mg/kg) daily for 10 days. Sham operated control group and model group received saline. At the end the rats were sacrificed, hindlimb tissues were stained with Haematoxylin-Eosin and Masson's trichrome. RNA and protein were extracted from tissues for PCR and Western blot analysis. The results showed that TFA reduced lower limb ischemic injury, recovered tissue volume and diminished fibrosis and muscle degeneration. Mechanistically, we showed that TFA increased the expression of anti-apoptotic factor such as Bcl-2 and survivin, decreased the expression of pro-apoptotic factor such as Caspase 3, Bax and Bak and inhibited the activation of caspase 3 and 9. In summary, this study proves new evidence that TFA protects hind-limb against ischemia injury by inhibiting apoptosis and could be a promising therapeutic agent for acute lower extremity ischemia.

Effect of Kangshuanyihao Formula on the Inflammatory Reaction and SIRT1/TLR4/NF-κB Signaling Pathway in Endothelial Injury.

Endothelial injury plays an important role in atherosclerosis (AS). Kangshuanyihao formula uses therapeutic principles from Chinese medicine to supplement Qi, thereby promoting blood circulation, and remove blood stasis. The mechanism by which the formula inhibits endothelial injury was examined in a rat model of 1,25-dihydroxyvitamin D3 (VD3) intraperitoneal injection and high-fat-induced endothelial injury. Rats were randomly divided into the model, high-dose, middle-dose, low-dose, positive drug (rosuvastatin), and combination (positive drug + middle-dose) groups; 10 Sprague-Dawley rats served as the blank group. The aortic endothelium was stained with hematoxylin and eosin and the levels of blood lipids and inflammation markers (mRNA and protein) were measured. Endothelial injury, lipid levels, and inflammation were increased in the model. Kangshuanyihao formula reduced endothelial injury, improved lipid levels, and downregulated inflammation, as shown by significant reduction of the protein levels of SIRT1, TLR4, and NF-κB and mRNA levels of SIRT1, TLR4, NF-κB, IL-1ß, IL-6, and IL-12. Thus, we conclude that Kangshuanyihao formula can inhibit the inflammatory reaction in the rat model of high-fat-induced endothelial injury after intraperitoneal injection of VD3. This mechanism may be attributed to regulating the SIRT1/TLR4/NF-κB signaling pathway.

Identification of Chemical Composition of Leaves and Flowers from Paeonia rockii by UHPLC-Q-Exactive Orbitrap HRMS.

The Paeonia genus, an important source of crude drugs, has been extensively used in traditional Chinese medicine (TCM) to treat cardiovascular and female-related diseases. Although many peony species have been investigated, the study of Paeonia rockii is still quite limited, especially its chemical composition. Here, an advanced ultra-high-performance liquid chromatography (UHPLC) analytical technique combined with Q-Exactive Orbitrap hybrid quadrupole-Orbitrap mass spectrometry utilizing high-resolution full MS and MS/MS scan modes was applied to screen and identify the chemical constituents of this species. As a result, a total of 46 compounds were characterized, including 11 monoterpene glycosides, five phenolic acids, six tannins and 24 flavonoids. Among them, 16 compounds were reported for the first time in Paeonia rockii.

Chinese Herbal Medicine for Aspirin Resistance: A Systematic Review and Meta-Analysis.

OBJECTIVES: To assess the effectiveness and safety of Chinese herbal medicine (CHM) for the treatment of aspirin resistance (AR). METHODS: A comprehensive research of seven electronic databases was performed for comparative studies evaluating CHM for AR. Two authors independently extracted data and assessed the methodological quality of the included trials using the Cochrane risk of bias tool. Data wasere synthesized by using RevMan 5.3 software. (PROSPERO Registration #CRD42015020182). RESULTS: 18 randomized controlled trials (RCTs) involving 1,460 patients were included. 15 RCTs reported significant difference in the reduction of platelet aggregation rate (PAR) induced by adenosine diphosphate (ADP) (P<0.05), and 11 reported significant effect of CHM plus aspirin to reduce PAR induced by arachidonic acid (AA) (P<0.05) compared with aspirin 100mg/d treatment. The pooling data of 3 RCTs showed the thromboxane B2 (TXB2) in patients with CHM plus aspirin versus aspirin were significantly reduced (Random Effect model (RE), Standard Deviation (SD) = -95.93, 95% Confidential Interval (CI)[-118.25,-73.61], P<0.00001). Subgroup analysis showed that TXB2 (Fixed Effect model (FE), SD = -89.23, 95%CI[-121.96,-56.49], P<0.00001) had significant difference in Tongxinluo capsule plus aspirin versus aspirin. 2 RCTs reported the clinical effective rate, and the meta-analysis result showed a significant difference in intervention and control group (FE, Relative Risk (RR) = 1.67, 95%CI[1.15, 2.42], P = 0.007<0.05). In 4 trials, CHM plus aspirin had better effects of reducing the reoccurrence of cerebral infarction than aspirin (FE, RR = 0.24, 95%CI [0.11, 0.49], P<0.0001). And one trial showed that CHM plus aspirin could decrease the National Institutes of Health Stroke Scale (NHISS) score (P<0.05) and increase the Barthel Index (BI) score (P<0.05). 4 trials stated that there were no adverse effects occurred in intervention group, and analysis showed significant difference of CHM or CHM plus aspirin in reducing the occurrence of adverse events (FE, RR = 0.22, 95%CI[0.13, 0.39], P<0.00001). 5 trials claimed that the CHM monotherapy and CHM adjunctive therapy for AR did not add the risk of bleeding (FE, RR = 0.50, 95%CI[0.20, 1.22], P = 0.13>0.05). CONCLUSIONS: CHM may be effective and safe as an alternative and collaborative therapy for AR. However, the current evidence and potential promising findings should be interpreted with caution due to poor and varying methodological quality of included studies and the heterogeneity of interventions. Thus, further exploration of this strategy with adequately powered RCTs is warranted.

[Content determination of twelve major components in Tibetan medicine Zuozhu Daxi by UPLC].

A quantitative analytical method of ultra-high performance liquid chromatography (UPLC) was developed for simultaneously determining twelve components in Tibetan medicine Zuozhu Daxi. SIMPCA 12.0 software was used a principal component analysis PCA) and partial small squares analysis (PLSD-DA) on the twelve components in 10 batches from four pharmaceutical factories. Acquity UPLC BEH C15 column (2.1 mm x 100 mm, 1.7 µm) was adopted at the column temperature of 35 °C and eluted with acetonitrile (A) -0.05% phosphate acid solution (B) as the mobile phase with a flow rate of 0. 3 mL · min(-1). The injection volume was 1 µL. The detection wavelengths were set at 210 nm for alantolactone, isoalantolactone and oleanolic; 260 nm for trychnine and brucine; 288 nm for protopine; 306 nm for protopine, resveratrol and piperine; 370 nm for quercetin and isorhamnetin. The results showed a good separation among index components, with a good linearity relationship (R2 = 0.999 6) within the selected concentration range. The average sample recovery rates ranged between 99.44%-101.8%, with RSD between 0.37%-1.7%, indicating the method is rapid and accurate with a good repeatability and stability. The PCA and PLSD-DA analysis on the sample determination results revealed a great difference among samples from different pharmaceutical factories. The twelve components included in this study contributed significantly to the quantitative determination of intrinsic quality of Zuozhu Daxi. The UPLC established for to the quantitative determination of the twelve components can provide scientific basis for the comprehensive quality evaluation of Zuozhu Daxi.

Astragaloside IV prevents lipopolysaccharide-induced injury in H9C2 cardiomyocytes.

This study aimed to investigate the protective effects of astragaloside IV (AS IV) on lipopolysaccharide (LPS)-induced injury in H9C2 cardiomyocytes. H9C2 Cardiomyocytes were cultured with LPS (10 µg·mL(-1)) for 4 h and treated with AS IV at 50, 100, and 150 µmol·L(-1) for various durations. Cell viability was determined by MTT. The content of released TNF-α and IL-6 from cardiomyocytes were evaluated by enzyme-linked immunosorbent assay (ELISA). The levels of superoxidase dismutase (SOD), malondialdehyde (MDA), lactate dehydrogenase (LDH), and creatine phosphate kinase (CK) were measured by using commercial available kits. The mRNA and protein expression levels of NF-κB p65 were measured by RT-PCR and Western blotting, respectively. And the NF-κB p65 activity was measured by ELISA. Our results demonstrated that AS IV at 50, 100, and 150 µmol·L(-1) markedly inhibited the release of TNF-α and IL-6 and decreased NF-κB expression, compared with the model group. Moreover, the improved SOD activity and decreased MDA, LDH and CK levels were detected after AS IV treatment. In summary, AS IV could increase the activities of antioxidant enzymes, inhibite lipid peroxidation, and down-regulate the inflammatory mediators involved in the inflammatory responses. These results demonstrated that AS IV could prevent LPS-induced injury in cardiomyocytes.

Astragaloside IV stimulates angiogenesis and increases nitric oxide accumulation via JAK2/STAT3 and ERK1/2 pathway.

Astragaloside IV (AS-IV), one of the major active constituents of Astragalus membranaceus in Traditional Chinese Medicine, has been widely used to treat ischemic diseases. However, the potential mechanism is this action is unclear. In this study, we tested the hypothesis that AS-IV might promote angiogenesis through multiple signaling pathways. Our data indicate that AS-IV treatment promotes umbilical vein endothelial cells (HUVEC) proliferation, migration, and tube formation. AS-IV treatment also activates JAK2/STAT3 and ERK1/2 signaling pathways, and up-regulates endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) production. AS-IV-induced angiogenesis in HUVECs is significantly blocked by specific kinase inhibitors. Our study indicated that AS-IV is a key regulator of NO and angiogenesis through the JAK2/STAT3 and ERK1/2 pathways, which provides a mechanistic basis for the potential use of this compound in the treatment of clinical ischemic diseases.

[Effect of clinical pathways based on integrative medicine for patients with chronic heart failure: a multi-center research].

OBJECTIVE: To assess a multi-center study effectiveness of clinical pathways based on integrative medicine (IM) for chronic heart failure (CHF) patients. METHODS: A combined method of historical control study and clinical study on concurrent control was used. After the standard management for clinical pathways was carried out in four hospitals at home, the effects on hospitalization days, medical expenses, clinical efficacy, patient satisfaction, and quality of life were assessed. RESULTS: Results of non-concurrent historical control study showed that: the hospital stay was significantly shorter in the pathways group than in the retrospective group (12.59 days vs 18.44 days), and the total cost of hospitalization was significantly reduced in the pathways group (yen 9 051.90 vs yen 11 978.40), showing statistical difference (P < 0.01). Moreover, the effect on the heart function was better in the pathways group than in the retrospective group (the markedly effective rate: 45.60% vs 21.90%; the total effective rate: 96.80% vs 86.10%), showing statistical difference (P < 0.01). Results of clinical study on concurrent control showed that the hospital stay was significantly shorter in the pathways group than in the control group (11.19 days vs 13.21 days), showing statistical difference (P < 0.05). The average total cost of hospitalization was significantly lower in the pathways group than in the control group (yen 8 656.80 vs yen 11 609.70), showing statistical difference (P < 0.01). As for clinical efficacy of Chinese medical syndrome, the total effective rate was higher in the pathways group than in the control group (97.10% vs 93.62%), showing statistical difference (P < 0.05). The markedly effective rate of heart function was better in the pathways group than in the control group, showing statistical difference (49.30% vs 38.30%, P < 0.05). The overall satisfaction was higher in the pathways group than in the conventional group (P < 0.01). There was no statistical difference in the mortality within 3 months after discharge from hospital, and the readmission rate due to heart failure between the two groups (P > 0.05). But there was statistical difference in the quality of life (P < 0.05). CONCLUSION: The pathway could shorten the hospitalization time, decrease the cost of hospitalization, improve the clinical efficacy, improve patients' quality of life and satisfaction, therefore, it could be spread nationwide.

Effects of salvianolic acid and notoginseng triterpenes on angiogenesis in EA-hy926 cells in vitro.

AIM: To investigate the different effects of salvianolic acid and notoginseng triterpenes on proliferation, angiogenesis and expression of vascular endothelial growth factor in EA-hy926 cells in vitro. METHODS: EA-hy926 cells were cultured in vitro. Salvianolic acid and notoginseng triterpenes at concentrations of 0.4, 0.8 and 1.2 mg·L(-1) were used to culture EA-hy926 cells. EA-hy926 cells in a blank control group were grown in culture solution only. Viability of cells was assessed by CCK-8, and after treated for 12 h, capillary-like structures were examined. After 24 h culture, the expression of VEGF was detected by real-time PCR. RESULTS: Salvianolic acid at 0.4, 0.8 mg·L(-1), the same as notoginseng triterpenes, increased VEGF content in EA-hy926 cells. Expression of VEGF protein in the salvianolic acid at 1.2 mg·L(-1) group, was up-regulated as compared with notoginseng triterpenes group (P < 0.05). CONCLUSION: Salvianolic acid and notoginseng triterpenes can promote EA-hy926 cell proliferation, angiogenesis and expression of VEGF protein. This analysis also provided evidence that salvianolic acid had the better effects as compared with notoginseng triterpenes.

Genetic and pharmacological inhibition of Rheb1-mTORC1 signaling exerts cardioprotection against adverse cardiac remodeling in mice.

A previous study indicated that Rheb1 is required for mammalian target of TOR complex 1 (mTORC1) signaling in the brain. However, the function of Rheb1 in the heart is still elusive. In the present study, we deleted Rheb1 specifically in cardiomyocytes and found that reduced Rheb1 levels conferred cardioprotection against pathologic remodeling in myocardial infarction (MI) and pressure overload (transverse aortic constriction) mouse models. Cardiomyocyte apoptosis was reduced and mTORC1 activity was suppressed in cardiomyocyte Rheb1-deletion mice, suggesting that Rheb1 regulates mTORC1 activation in myocardium. Furthermore, we demonstrated that astragaloside IV (As-IV) could inhibit mTORC1, and As-IV treatment displayed similar protection against MI and transverse aortic constriction as Rheb1 genetic inhibition. This study indicates that Rheb1 is essential for mTORC1 activation in cardiomyocytes and suggests that targeting Rheb1-mTORC1 signaling, such as by As-IV treatment, may be an effective therapeutic method for treating patients with adverse cardiac remodeling after MI and hypertrophy.

Clinical pathways based on integrative medicine in chinese hospitals improve treatment outcomes for patients with acute myocardial infarction: a multicentre, nonrandomized historically controlled trial.

Objective. To determine the impact of an integrative medicine clinical pathways (CPs) on the length of in-hospital stay and on outcomes for patients with acute myocardial infarction (AMI). Methods. A multicenter nonrandomized controlled trial enrolling 197 consecutive patients with AMI at eight urban TCM hospitals was conducted between 1 January 2010 and 31 October 2010. These patients were enrolled in the interventional group after the CPs had been implemented. The control group included 405 patients with AMI from eight hospitals; these patients were treated between 1 January 2008 and 31 December 2009, before the CPs were implemented. Outcome measures were the length of hospital stay costs of medical care, and major cardiovascular events (MACEs) during hospitalization. Results. Compared with the control group, the patients in intervention group had a shorter length of hospital stay (9.2 ± 4.2 days versus 12.7 ± 8.6 days, P < 0.05), and reduced healthcare costs in hospital (46365.7 ± 18266.9 versus 52866.0 ± 35404.4, P < 0.05). There were statistically significant differences in MACE between the two groups during the hospitalization period (2.5% versus 6.9%, P = 0.03). Conclusion. These data suggest that the development and implementation of the clinical pathways based in Integrative Medicine could further improve quality of care and outcome for patients with AMI.