A Systems Pharmacology-Based Study of the Molecular Mechanisms of San Cao Decoction for Treating Hypertension.
ABSTRACT: Traditional Chinese medicine (TCM) has a longstanding history and has gained widespread clinical applications. San Cao Decoction (SCD) is an experience prescription first formulated by Prof. Duzhou Liu. We previously demonstrated its antihypertensive effects; however, to systematically explain the underlying mechanisms of action, we employed a systems pharmacology approach for pharmacokinetic screening and target prediction by constructing protein-protein interaction networks of hypertension-related and putative SCD-related targets, and Database for Annotation, Visualization, and Integrated Discovery enrichment analysis. We identified 123 active compounds in SCD and 116 hypertension-related targets. Furthermore, the enrichment analysis of the drug-target network showed that SCD acts in a multidimensional manner to regulate PI3K-Akt-endothelial nitric oxide synthase signaling to maintain blood pressure. Our results highlighted the molecular mechanisms of antihypertensive actions of medicinal herbs at a systematic level.
Project description:ETHNOPHARMACOLOGICAL RELEVANCE:San-Cao Granule (SCG) has been used in patients with liver fibrosis for many years and has shown good effect. However, its mechanism of therapeutic action is not clear because of its complex chemical system. The purpose of our study is to establish a comprehensive and systemic method that can predict the mechanism of action of SCG in antihepatic fibrosis. MATERIALS AND METHODS:In this study, a "compound-target-disease" network was constructed by combining the SCG-specific and liver fibrosis-specific target proteins with protein-protein interactions, and network pharmacology was used to screen out the underlying targets and mechanisms of SCG for treatment of liver fibrosis. Then, some key molecules of the enriched pathway were chosen to verify the effects of SCG on liver fibrosis induced by thioacetamide (TAA). RESULTS:This systematic approach had successfully revealed that 16 targets related to 11 SCG compounds were closely associated with liver fibrosis therapy. The pathway-enrichment analysis of them showed that the TGF-?1/Smad signaling pathway is relatively important. Animal experiments also proved that SCG could significantly ameliorate liver fibrosis by inhibiting the TGF-?1/Smad pathway. CONCLUSION:SCG could alleviate liver fibrosis through the molecular mechanisms predicted by network pharmacology. Furthermore, network pharmacology could provide deep insight into the pharmacological mechanisms of Chinese herbal formulas.
Project description:Glycerol is an attractive renewable building block for the synthesis of polyglycerols, which find application in the cosmetic and pharmaceutical industries. The selective etherification of glycerol to higher oligomers was studied in the presence of CaO colloids and the data are compared with those obtained from NaOH and CaO. The materials were prepared by dispersing CaO, CaCO3 , or Ca(OH)2 onto a carbon nanofiber (CNF) support. Colloidal nanoparticles were subsequently dispensed from the CNF into the reaction mixture to give CaO colloids that have a higher activity than equimolar amounts of bulk CaO and NaOH. Optimization of the reaction conditions allowed us to obtain a product with Gardner color number <2, containing no acrolein and minimal cyclic byproducts. The differences in the CaO colloids originating from CNF and bulk CaO were probed using light scattering and conductivity measurements. The results confirmed that the higher activity of the colloids originating from CaO/CNF was due to their more rapid formation and smaller size compared with colloids from bulk CaO. We thus have developed a practical method for the synthesis of polyglycerols containing low amounts of Ca.
Project description:The genome of the ascomycete Neurospora crassa encodes CAO-1 and CAO-2, two members of the carotenoid cleavage oxygenase family that target double bonds in different substrates. Previous studies demonstrated the role of CAO-2 in cleaving the C40 carotene torulene, a key step in the synthesis of the C35 apocarotenoid pigment neurosporaxanthin. In this work, we investigated the activity of CAO-1, assuming that it may provide retinal, the chromophore of the NOP-1 rhodopsin, by cleaving β-carotene. For this purpose, we tested CAO-1 activity with carotenoid substrates that were, however, not converted. In contrast and consistent with its sequence similarity to family members that act on stilbenes, CAO-1 cleaved the interphenyl Cα-Cβ double bond of resveratrol and its derivative piceatannol. CAO-1 did not convert five other similar stilbenes, indicating a requirement for a minimal number of unmodified hydroxyl groups in the stilbene background. Confirming its biological function in converting stilbenes, adding resveratrol led to a pronounced increase in cao-1 mRNA levels, while light, a key regulator of carotenoid metabolism, did not alter them. Targeted Δcao-1 mutants were not impaired by the presence of resveratrol, a phytoalexin active against different fungi, which did not significantly affect the growth and development of wild-type Neurospora. However, under partial sorbose toxicity, the Δcao-1 colonies exhibited faster radial growth than control strains in the presence of resveratrol, suggesting a moderate toxic effect of resveratrol cleavage products.
Project description:Ca(x)Zn(1-x)O alloys are potential candidates to achieve wide band-gap, which might significantly promote the band gap engineering and heterojunction design. We performed a crystal structure search for CaO-ZnO system under pressure, using an ab initio evolutionary algorithm implemented in the USPEX code. Four stable ordered Ca(x)Zn(1-x)O structures are found in the pressure range of 8.7-60?GPa. We further constructed the pressure vs. composition phase diagram of CaO-ZnO alloys based on the detailed enthalpy calculations. With the increase in Ca concentration, the CaO-ZnO alloy first undergoes a hexagonal to monoclinic transition, and then transforms back to a hexagonal phase. At Above 9?GPa, there is no cubic structure in the alloys, in contrast to the insostructural components (B1-B1). The band gap of the Ca(x)Zn(1-x)O alloy shows an almost linear increase as a function of the Ca concentration. We also investigated the variation regularity of the band gap under pressure.
Project description:Emission of hazardous trace elements, especially arsenic from fossil fuel combustion, have become a major concern. Under an oxidizing atmosphere, most of the arsenic converts to gaseous As₂O₃. CaO has been proven effective in capturing As₂O₃. In this study, the mechanisms of As₂O₃ adsorption on CaO surface under O₂ atmosphere were investigated by density functional theory (DFT) calculation. Stable physisorption and chemisorption structures and related reaction paths are determined; arsenite (AsO₃3-) is proven to be the form of adsorption products. Under the O₂ atmosphere, the adsorption product is arsenate (AsO₄3-), while tricalcium orthoarsenate (Ca₃As₂O₈) and dicalcium pyroarsenate (Ca₂As₂O₇) are formed according to different adsorption structures.
Project description:This research investigated the production of biodiesel from soybean oil (transesterification process) using pure calcium oxide and calcium oxide obtained from eggshell as heterogeneous catalysts. Uncalcined eggshell and calcined eggshell catalysts produced were analysed using XRF and XRD spectrometers. The processing parameters considered during the transesterification of the soybean were methanol/oil mole ratio, catalyst concentration and reaction time and their effects on biodiesel yield were evaluated. Reaction temperature of 60?°C and stirring rate of 450?rpm (revolution per minute) were kept constant. As a result of calcination, XRF analysis revealed an increase in CaO percentage composition of eggshell catalyst from 96% to 97%. Also, the biodiesel yields obtained revealed similar performance patterns for both the calcined eggshell catalyst and the pure CaO catalyst.
Project description:No reduction in either coronary mortality or sudden cardiac death (SCD) has been demonstrated in overviews of randomized trials of treatment of hypertension with diuretics.An overview was conducted of coronary mortality and SCD in randomized controlled antihypertensive trials in which an epithelial sodium channel (ENaC) inhibitor/ hydrochlorthiazide (HCTZ) combination was used. Secondarily, an analogous overview in which thiazide diuretic was used alone was performed. Randomized trials that used an ENaC inhibitor/ HCTZ combination (or, alternatively, thiazide diuretic alone) were identified from previous meta-analyses, searches of PubMed, search of the Cochrane Clinical Trials database, and review of publications that addressed the consequences of treating hypertension. Trials in which participants were randomized to either an ENaC inhibitor combined with a thiazide diuretic (or to a thiazide diuretic alone) or to control treatment for at least one year and in which coronary mortality was reported were included. Numbers of events in individual trials were abstracted independently by 2 authors.Significant reductions in both coronary mortality and SCD were observed in the overview of trials in which elderly patients received an ENaC inhibitor/ HCTZ combination. The odds ratio (OR) for coronary mortality was 0.59 (95% confidence interval [CI] 0.44, 0.78) and for SCD was 0.60 (95% CI 0.38, 0.94). In contrast, an overview of the trials using thiazide diuretics alone showed no significant reductions of either coronary mortality (OR 0.94; 95% CI 0.81, 1.09) or SCD (OR 1.27; 95% CI 0.93, 1.75).Use of an ENaC inhibitor combined with HCTZ for treatment of hypertension in the elderly results in favorable effects on coronary mortality and SCD.
Project description:OBJECTIVES:Jian Ling Decoction (JLD) is often prescribed to improve hypertension-related symptoms in China. However, this treatment has not been systematically reviewed for its efficacy against essential hypertension (EH). This review aims to assess the current clinical evidence of JLD in the treatment of EH. DESIGN:Seven electronic databases, including the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, the Chinese National Knowledge Infrastructure (CNKI), the Chinese Scientific Journal Database (VIP), the Chinese Biomedical Literature Database (CBM) and the Wanfang Database, were searched up to March 2014. Randomised control trials (RCTs) comparing JLD or combined with antihypertensive drugs versus antihypertensive drugs were included. We assessed the methodological quality, extracted the valid data and conducted the meta-analysis according to criteria from the Cochrane group. The primary outcome was categorical or continuous blood pressure (BP), and the secondary outcome was quality of life (QOL). RESULTS:Ten trials (655 patients) with unclear-to-high risk of bias were identified. Meta-analysis showed that JLD used alone showed no BP reduction effect; however, improvement on QOL was found in the JLD group compared to antihypertensive drugs. A significant reduction in systolic and diastolic BP was observed for JLD plus antihypertensive drugs when compared with antihypertensive drugs alone. No serious adverse effects were reported. CONCLUSIONS:Owing to insufficient clinical data, it is difficult to draw a definite conclusion regarding the effectiveness and safety of JLD for EH, and better trials are needed.
Project description:Novel MgO/CaO nanocomposite (MgO/CaO NRs) was synthesized by the hydrothermal method using diatomite porous frustules as a substrate under the microwave irradiation. The composite appeared as well crystalline rod-like nanoparticles with 52.3 nm as average particle size and 112.8 m2/g as BET surface area. The synthetic MgO/CaO NRs were addressed as a novel adsorbent for promising removal of levofloxacin (LVX) as pharmaceutical residuals. The adsorption studies revealed effective uptake of levofloxacin by MgO/CaO NRs with theoretical qmax of 106.7 mg/g and the equilibrium time of 720 min considering the best pH value (pH 7). The equilibrium studies highly fitted with the Langmuir model of monolayer adsorption considering the values of Chi-squared (?2) and determination coefficient. The estimated adsorption energy from Dubinin-Radushkevich (0.2 kJ/mol) signifies physisorption mechanisms that might be coulombic attractive forces considering the kinetic studies. The thermodynamic addressing for the reactions verified their spontaneous and exothermic nature within a temperature range from 303 to 333 K. Additionally, the prepared MgO/CaO NRs show significant recyclability properties to be used in realistic remediation process and its uptake capacity is higher than several studied adsorbents in literature.
Project description:Objective: San-Cao granule (SCG), a traditional Chinese herb formula, has been used for treating autoimmune hepatitis (AIH) in our clinics for a long time. However, its active ingredients and mechanisms of action were still unknown due to its complicated chemical compositions. In the present study, the pharmacological study of SCG on acute liver injury induced by Concanavalin A (Con A) was performed to provide a scientific evidence for SCG against liver injury. Methods: In order to screen active components and predicate mechanisms of action, an "ingredients-target-disease" interaction network was constructed by network pharmacology. Then, the pharmacological study was performed to evaluate the therapeutic effect and the underlying mechanisms of SCG on Con A-induced liver injury in mice. Results: This research demonstrated the pharmacological effect of SCG on Con A-induced liver injury, which was through improving the liver function, relieving the pathological changes of liver tissue, decreasing the level of pro-inflammatory cytokines, and thus balancing the pro- and anti-inflammatory cytokines. And the anti-inflammatory of SCG may advantage over the ursodeoxycholic acid (UDCA). Network pharmacology analysis revealed that the pharmacological effect of SCG might be related to its active ingredients of taraxanthin, dihydrotanshinone I, isotanshinone I, ?-sitosterol, 3?-acetyl-20,25-epoxydammarane-24?, and ?-7-stigmastenol. The hepatoprotective effect of SCG was reflected by suppressing Con A-induced apoptosis which was mediated by TRAIL and FASL. Conclusion: The combination of network pharmacology and experimental data has revealed the anti-apoptotic effect of SCG against Con A-induced liver injury.