Huang Qin decoction increases SLC6A4 expression and blocks the NFκB-mediated NLRP3/Caspase1/GSDMD pathway to disrupt colitis-associated carcinogenesis.

Huang Qin decoction (HQD) is a traditional Chinese medicine formula for treating colitis, but the effects and molecular mechanism of action of HQD in colitis-associated carcinogenesis (CAC) are still unclear. Therefore, we aimed to determine the beneficial effects of HQD on CAC in mice and to reveal the underlying mechanism involved. AOM/DSS was used to induce CAC in mice, and the effects of HQD on tumorigenesis in mice were examined (with mesalazine serving as a positive control). Mesalazine or HQD treatment alleviated body weight loss and decreased the disease activity index in mice induced by AOM/DSS. Mesalazine or HQD treatment also suppressed the shortening of colon tissue length, the number of tumors, and the infiltration of inflammatory cells. The genes targeted by HQD were predicted and verified, followed by knockout experiments. Elevated SLC6A4 and inhibited serotonin production and inflammation were observed in HQD-treated mice. HQD inhibited the NFκB and NLRP3/caspase1/GSDMD pathways. The therapeutic effect of HQD was diminished in SLC6A4-deficient AOM/DSS mice. Additionally, the downregulation of SLC6A4 mitigated the inhibitory effect of HQD-containing serum on MODE-K cell pyroptosis. Our findings suggest that SLC6A4 is a pivotal regulator of HQD-alleviated CAC via its modulation of the NLRP3/caspase1/GSDMD pathway.

Evidence mapping and overview of systematic reviews of the effects of acupuncture therapies.

OBJECTIVE: To provide a route map regarding systematic reviews (SRs) of acupuncture therapies that will meet two goals: (1) to identify areas in which more or better evidence is required and (2) to identify acupuncture applications that, although proven effective, remain underused in practice, and thus warrant more effective knowledge dissemination. ELIGIBILITY CRITERIA: We included SRs that conducted meta-analyses (MAs) of randomised controlled trials (RCTs) for this overview. INFORMATION SOURCES: We searched for SRs without language restrictions from January 2015 to November 2020 in four Chinese electronic databases and Epistemonikos database. And we also searched for newly published RCTs that were eligible for selected best SRs in PubMed, Medline, Cochrane Central Register of Controlled Trials, Embase and four Chinese electronic databases from its lasted search dates to November 2020. SYNTHESIS OF RESULTS: We reanalysed the selected MAs if new primary studies were added. We used random-effect model to calculate the overall effect. RESULTS: Our search identified 120 SRs published in the last 5 years addressing acupuncture therapies across 12 therapeutic areas and 77 diseases and conditions. The SRs included 205 outcomes and involved 138 995 participants from 1402 RCTs. We constructed 77 evidence matrices, including 120 SRs and their included RCTs in the Epistemonikos database. Seventy-seven SRs represented the effect estimate of acupuncture therapies. Finally, we system summarised the areas of possible underutilisation of acupuncture therapies (high or moderate certainty evidence of large or moderate effects), and the areas of warranting additional investigation of acupuncture therapies (low or very low certainty evidence of moderate or large effects). CONCLUSION: The evidence maps and overview of SRs on acupuncture therapies identified both therapies with substantial benefits that may require more assertive evidence dissemination and promising acupuncture therapies that require further investigation.

Identification and First Report of Fusarium andiyazi Causing Sheath Rot of Zizania latifolia in China.

Zizania latifolia is a perennial plant native to East Asia. The swollen culm of Z. latifolia is a popular vegetable and traditional herbal medicine consumed in China and some other Asian countries. From 2019 to 2021, a sheath rot disease was found in Zhejiang Province of China. Symptoms mainly occurred in the leaf sheath showing as brown necrotic lesions surrounded by yellow halos. The pathogen fungal isolates were isolated from the affected sheaths. Ten representative isolates were selected for morphological and molecular identification by phylogenetic analyses of the translation elongation factor 1-α (TEF1) and the RNA polymerase II subunit beta (RPB2) gene regions. Based on the combined datasets, the fungal isolates were identified as Fusarium andiyazi. Koch's postulates were confirmed by pathogenicity test, re-isolation and re-identification of the fungal isolates. To the best of our knowledge, this is the first report of sheath rot caused by F. andiyazi in Z. latifolia in China.

A Traditional Chinese Medicine Traceability System Based on Lightweight Blockchain.

BACKGROUND: Recently, the problem of traditional Chinese medicine (TCM) safety has attracted attention worldwide. To prevent the spread of counterfeit drugs, it is necessary to establish a drug traceability system. A traditional drug traceability system can record the whole circulation process of drugs, from planting, production, processing, and warehousing to use by hospitals and patients. Once counterfeit drugs are found, they can be traced back to the source. However, traditional drug traceability systems have some drawbacks, such as failure to prevent tampering and facilitation of sensitive disclosure. Blockchain (including Bitcoin and Ethernet Square) is an effective technology to address the problems of traditional drug traceability systems. However, some risks impact the reliability of blockchain, such as information explosion, sensitive information leakage, and poor scalability. OBJECTIVE: To avoid the risks associated with the application of blockchain, we propose a lightweight block chain framework. METHODS: In this framework, both horizontal and vertical segmentations are performed when designing the blocks, and effective strategies are provided for both segmentations. For horizontal segmentation operations, the header and body of the blockchain are separated and stored in the blockchain, and the body is stored in the InterPlanetary File System. For vertical segmentation operations, the blockchain is cut off according to time or size. For the addition of new blocks, miners only need to copy the latest part of the blockchain and append the tail and vertical segmentation of the block through the consensus mechanism. RESULTS: Our framework could greatly reduce the size of the blockchain and improve the verification efficiency. CONCLUSIONS: Experimental results have shown that the efficiency improves compared with ethernet when a new block is added to the blockchain and a search is conducted.

Electroacupuncture facilitates the integration of a grafted TrkC-modified mesenchymal stem cell-derived neural network into transected spinal cord in rats via increasing neurotrophin-3.

AIMS: This study was aimed to investigate whether electroacupuncture (EA) would increase the secretion of neurotrophin-3 (NT-3) from injured spinal cord tissue, and, if so, whether the increased NT-3 would promote the survival, differentiation, and migration of grafted tyrosine kinase C (TrkC)-modified mesenchymal stem cell (MSC)-derived neural network cells. We next sought to determine if the latter would integrate with the host spinal cord neural circuit to improve the neurological function of injured spinal cord. METHODS: After NT-3-modified Schwann cells (SCs) and TrkC-modified MSCs were co-cultured in a gelatin sponge scaffold for 14 days, the MSCs differentiated into neuron-like cells that formed a MSC-derived neural network (MN) implant. On this basis, we combined the MN implantation with EA in a rat model of spinal cord injury (SCI) and performed immunohistochemical staining, neural tracing, electrophysiology, and behavioral testing after 8 weeks. RESULTS: Electroacupuncture application enhanced the production of endogenous NT-3 in damaged spinal cord tissues. The increase in local NT-3 production promoted the survival, migration, and maintenance of the grafted MN, which expressed NT-3 high-affinity TrkC. The combination of MN implantation and EA application improved cortical motor-evoked potential relay and facilitated the locomotor performance of the paralyzed hindlimb compared with those of controls. These results suggest that the MN was better integrated into the host spinal cord neural network after EA treatment compared with control treatment. CONCLUSIONS: Electroacupuncture as an adjuvant therapy for TrkC-modified MSC-derived MN, acted by increasing the local production of NT-3, which accelerated neural network reconstruction and restoration of spinal cord function following SCI.

Synthetic Fluorinated l-Fucose Analogs Inhibit Proliferation of Cancer Cells and Primary Endothelial Cells.

Fucosylation is one of the most prevalent modifications on N- and O-glycans of glycoproteins, and it plays an important role in various cellular processes and diseases. Small molecule inhibitors of fucosylation have shown promise as therapeutic agents for sickle cell disease, arthritis, and cancer. We describe here the design and synthesis of a panel of fluorinated l-fucose analogs bearing fluorine atoms at the C2 and/or C6 positions of l-fucose as metabolic fucosylation inhibitors. Preliminary study of their effects on cell proliferation revealed that the 6,6-difluoro-l-fucose (3) and 6,6,6-trifluoro-l-fucose (6) showed significant inhibitory activity against proliferation of human colon cancer cells and human umbilical vein endothelial cells. In contrast, the previously reported 2-deoxy-2-fluoro-l-fucose (1) had no apparent effects on proliferations of all the cell lines tested. To understand the mechanism of cell proliferation inhibition by the fluorinated l-fucose analogs, we performed chemoenzymatic synthesis of the corresponding GDP-fluorinated l-fucose analogs and tested their inhibitory activities against the mammalian α1,6-fucosyltransferase (FUT8). Interestingly, the corresponding GDP derivatives of 6,6-difluoro-l-fucose (3) and 6,6,6-trifluoro-l-fucose (6), which are the stronger proliferation inhibitors, showed much weaker inhibitory activity against FUT8 than that of the 2-deoxy-2-fluoro-l-fucose (1). These results suggest that FUT8 is not the major target of the 6-fluorinated fucose analogs (3 and 6). Instead, other factors, such as the key enzymes involved in the de novo GDP-fucose biosynthetic pathway and/or other fucosyltransferases involved in the biosynthesis of tumor-associated glyco-epitopes are most likely the targets of the fluorinated l-fucose analogs to achieve cell proliferation inhibition. To our knowledge, this is the first comparative study of various fluorinated l-fucose analogs for suppressing the proliferation of human cancer and primary endothelial cells required for angiogenesis.

An evidence mapping and analysis of registered COVID-19 clinical trials in China.

BACKGROUND: This article aims to summarize the key characteristics of registered trials of 2019 novel coronavirus (COVID-19), in terms of their spatial and temporal distributions, types of design and interventions, and patient characteristics among others. METHODS: A comprehensive search of the registered COVID-19 trials has been performed on platforms including ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (WHO ICTRP), Chinese Clinical Trials Registry (CHiCTR), Australian Clinical Trials Registry, Britain's National Research Register (BNRR), Current Control Trials (CCT), and Glaxo Smith Kline Register. Trials registered at the first 8 weeks of the COVID-19 outbreak are included, without language restrictions. For each study, the registration information, study design, and administrator information are collected and summarized. RESULTS: A total of 220 registered trials were evaluated as of February 27, 2020. Hospital-initiated trials were the majority and account for 80% of the sample. Among the trials, pilot studies and phase 4 trials are more common and represent 35% and 19.1% of the sample, respectively. The median sample size of the registered trials is 100, with interquartile range 60-240. Further, 45.9% of the trials mentioned information on a data monitoring committee. 54.5% of the trials did not specify the disease severity among patients they intend to recruit. Four types of interventions are most common in the experimental groups across the registered studies: antiviral drugs, Traditional Chinese Medicine (TCM), biological agents, and hormone drugs. Among them, the TCM and biological agents are frequently used in pilot study and correspond to a variety of primary endpoints. In contrast, trials with antiviral drugs have more targeted primary outcomes such as "COVID-19 nucleic acid test" and "28-day mortality." CONCLUSIONS: We provide an evidence mapping and analysis of registered COVID-19 clinical trials in China. In particular, it is critical for ongoing and future studies to refine their research hypothesis and better identify their intervention therapies and the corresponding primary outcomes. It is also imperative for multiple public health divisions and research institutions to work together for integrative clinical data capture and sharing, with a common objective of improving future studies that evaluate COVID-19 interventions.

C, N, and P stoichiometry and their interaction with different plant communities and soils in subtropical riparian wetlands.

Ecological stoichiometry represents the balance of nutrient elements under ecological interactions, which are crucial for biogeochemical cycles in ecosystems. Little is known about carbon (C), nitrogen (N), and phosphorus (P) ecological stoichiometry in aboveground biomass, roots, and soil, especially in the subtropical riparian wetlands. Here, eight dominate plant communities in riparian wetlands were chosen, and C, N, and P contents, and C:N:P ratios of aboveground biomass, roots, and soil were investigated. The results demonstrated that plant community had remarkable effects on the C:N:P stoichiometry in aboveground biomass, roots, and soil, which varied widely. C, N, and P concentrations in aboveground biomass were mostly higher than that in roots, while no significant difference was detected in C:N:P ratios. Moreover, there were higher soil C, N, and P contents in Cannabis indica plant communities; while lower soil N:P ratios suggested that riparian wetlands were more susceptible to N limitation, rather than P. Pearson correlation analysis and redundancy analysis (RDA) showed that there were strong associations among C, N, and P contents, and C:N:P ratios in aboveground biomass, roots, and soil, indicating that C, N, and P ecological stoichiometry of aboveground biomass were regulated by soil C, N, and P contents through the roots. In addition, the contents of C and N, and N and P exhibited a strong relationship according to linear regression. These findings suggested that the interactions among the C, N, and P stoichiometry were existed in the plant-soil system.

Electroacupuncture Facilitates the Integration of Neural Stem Cell-Derived Neural Network with Transected Rat Spinal Cord.

The hostile environment of an injured spinal cord makes it challenging to achieve higher viability in a grafted tissue-engineered neural network used to reconstruct the spinal cord circuit. Here, we investigate whether cell survival and synaptic transmission within an NT-3 and TRKC gene-overexpressing neural stem cell-derived neural network scaffold (NN) transplanted into transected spinal cord could be promoted by electroacupuncture (EA) through improving the microenvironment. Our results showed that EA facilitated the cell survival, neuronal differentiation, and synapse formation of a transplanted NN. Pseudorabies virus tracing demonstrated that EA strengthened synaptic integration of the transplanted NN with the host neural circuit. The combination therapy also promoted axonal regeneration, spinal conductivity, and functional recovery. The findings highlight EA as a potential and safe supplementary therapeutic strategy to reinforce the survival and synaptogenesis of a transplanted NN as a neuronal relay to bridge the two severed ends of an injured spinal cord.

Topotecan induces apoptosis via ASCT2 mediated oxidative stress in gastric cancer.

BACKGROUND: Topotecan (TPT) is a Topo I inhibitor and shows obvious anti-cancer effects on gastric cancer. Cancer cells reprogram their metabolic pathways to increase nutrients uptake, which has already been a hallmark of cancer. But the effect of TPT on metabolism in gastric cancer remains unknown. PURPOSE: To investigate the effect of TPT on metabolism in gastric cancer. METHODS: ATP production was measured by ATP Assay kit. Glucose and glutamine uptake were measured by Glucose (HK) Assay Kit and Glutamine/Glutamate Determination Kit respectively. To detect glutathione (GSH) concentration and reactive oxygen species (ROS) generation, GSH and GSSG Assay Kit and ROS Assay Kit were adopted. Apoptosis rates, mitochondrial membrane potential (MMP) were determined by flow cytometry and protein levels were analyzed by immumohistochemical staining and western blotting. RESULTS: TPT increased ATP production. TPT promoted glucose uptake possibly via up-regulation of hexokinase 2 (HK2) or glucose transporter 1 (GLUT1) expression, while decreased glutamine uptake by down-regulation of ASCT2 expression. ASCT2 inhibitor GPNA and ASCT2 knockdown significantly suppressed the growth of gastric cancer cells. Inhibition of ASCT2 reduced glutamine uptake which led to decreased production of GSH and increased ROS level. ASCT2 knockdown induced apoptosis via the mitochondrial pathway and weakened anti-cancer effect of TPT. CONCLUSION: TPT inhibits glutamine uptake via down-regulation of ASCT2 which causes oxidative stress and induces apoptosis through the mitochondrial pathway. Moreover, TPT inhibits proliferation partially via ASCT2. These observations reveal a previously undescribed mechanism of ASCT2 regulated gastric cancer proliferation and demonstrate ASCT2 is a potential anti-cancer target of TPT.

Electrochemical Oxidation of l-selenomethionine and Se-methylseleno-l-cysteine at a Thiol-Compound-Modified Gold Electrode: Its Application in a Flow-Through Voltammetric Sensor.

A flow-electrolytic cell that consists of a bare gold wire or of different thiol-compound-modified gold electrodes (such as 2,4-thiazolidinedione, 2-mercapto-5-thiazoline, 2-mercaptothiazoline, l-cysteine, thioglycolic acid) was designed to be used in a voltammetric detector to identify l-selenomethionine and Se-methylseleno-l-cysteine using high-performance liquid chromatography. Both l-selenomethionine and Se-methylseleno-l-cysteine are more efficiently electrochemically oxidized on a thiol/gold than on a bare gold electrode. For the DC mode, and for measurements with suitable experimental parameters, a linear concentration from 10 to 1600 ng·mL-1 was found. The limits of quantification for l-selenomethionine and Se-methylseleno-l-cysteine were below 10 ng·mL-1. The method can be applied to the quantitative determination of l-selenomethionine and Se-methylseleno-l-cysteine in commercial selenium-containing supplement products. Findings using high-performance liquid chromatography with a flow-through voltammetric detector and ultraviolet detector are comparable.

Evaluating a Cobalt-Tetraphenylporphyrin Complex, Functionalized with a Reduced Graphene Oxide Nanocomposite, for Improved Tooth Whitening.

OBJECTIVES: To study using cobalt-tetraphenylporphyrin/reduced graphene oxide (CoTPP/RGO), a nanocomposite highly catalytic both for oxidizing and for reducing hydrogen peroxide (H2 O2 ), to whiten teeth. METHODS: Dyes (D&C Red 34, Orange No. 4), tea, and betel nuts (Areca catechu) were used to stain the tooth specimens for three days and subsequently bleached using H2 O2 alone, H2 O2 plus CoTPP, or H2 O2 plus CoTPP/RGO for 0.5-70 hours. The process was photographed using an electronic chromometer and a camera. Color change was assessed after each session. The results of bleaching teeth with and without photoirradiation were compared. RESULTS: CoTPP/RGO increased the tooth-whitening efficacy of H2 O2 for specimens stained with dyes, tea, and betel nuts. Using lamps (photoactivation) (wavelengths: 254 nm and 310 nm) to catalyze the H2 O2 bleaching agent reduced the bleaching treatment time. CLINICAL SIGNIFICANCE: First, the Co/TPP/RGO complex allows improved tooth bleaching and shorter treatment times. Second, because the Co/TPP/RGO complex bleached D&C Red 34 at a similar rate and to a similar degree as tea and other natural agents stain teeth, it is a convenient staining agent for studying many vital aspects of tooth bleaching. (J Esthet Restor Dent 28:321-329, 2016).

Refractory hypercalcaemia secondary to parathyroid carcinoma: response to high-dose denosumab.

OBJECTIVE: Hypercalcaemia is an important cause of increased morbidity and mortality in patients with parathyroid carcinoma. Surgical resection is the mainstay of treatment but, equally, managing hypercalcaemia is of paramount importance. At present, few therapies have been shown to be effective in the most severe cases. This report describes the efficacy of denosumab in a patient with parathyroid carcinoma when conventional therapies had been shown to be relatively ineffective.SUBJECT, METHODS AND RESULTS: A 50-year-old man presented with symptomatic hypercalcaemia 1 year after the surgery for his parathyroid carcinoma. Investigations revealed raised serum calcium and parathyroid hormone concentrations consistent with the recurrence of the disease. Imaging failed to localise any surgically remediable foci. Medical management with loop diuretics, calcimimetics and bisphosphonates failed to provide a sustained response. Denosumab, as a monthly injection, led to a gradual decrement in his peak calcium concentrations with the values now persistently below 3 mmol/l. CONCLUSIONS: Denosumab, a fully human MAB that binds to the 'receptor activator of nuclear factor κB ligand (RANKL)', was shown to have a profound effect in modulating malignant hypercalcaemia. This medication should be considered as an effective option in patients with refractory hypercalcaemia secondary to parathyroid carcinoma.

Trichodermaerin, a new diterpenoid lactone from the marine fungus Trichoderma erinaceum associated with the sea star Acanthaster planci.

Trichodermaerin (1), a novel diterpenoid lactone, together with the known compound, harziandione (2) were isolated from the culture broth of the fungus Trichoderma erinaceum associated with the sea star Acanthaster planci. Their structures were determined by analysis of the NMR and MS data. 1 was the Baeyer-Villiger monooxygenase catalyzed oxidation product of 2. Compound 2 did not show cytotoxic activities against various cancer cell lines.

In Vitro Screening for Antihepatic Steatosis Active Components within Coptidis Rhizoma Alkaloids Extract Using Liver Cell Extraction with HPLC Analysis and a Free Fatty Acid-Induced Hepatic Steatosis HepG2 Cell Assay.

A high-throughput method was developed and applied to screen for the active antihepatic steatosis components within Coptidis Rhizoma Alkaloids Extract (CAE). This method was a combination of two previously described assays: HepG2 cell extraction with HPLC analysis and a free fatty acid-induced (FFA) hepatic steatosis HepG2 cell assay. Two alkaloids within CAE, berberine and coptisine, were identified by HepG2 cell extraction with HPLC analysis as high affinity components for HepG2. These alkaloids were also determined to be active and potent compounds capable of lowering triglyceride (TG) accumulation in the FFA-induced hepatic steatosis HepG2 cell assay. This remarkable inhibition of TG accumulation (P < 0.01) by berberine and coptisine occurred at concentrations of 0.2 µ g/mL and 5.0 µ g/mL, respectively. At these concentrations, the effect seen was similar to that of a CAE at 100.0 µ g/mL. Another five alkaloids within CAE, palmatine, epiberberine, jateorhizine, columbamine, and magnoline, were found to have a lower affinity for cellular components from HepG2 cells and a lower inhibition of TG accumulation. The finding of two potent and active compounds within CAE indicates that the screening method we developed is a feasible, rapid, and useful tool for studying traditional Chinese medicines (TCMs) in treating hepatic steatosis.

Photoelectron spectroscopy and the electronic structure of the uranyl tetrachloride dianion: UO2C(4(2-).

The uranyl tetrachloride dianion (UO(2)Cl(4)(2-)) is observed in the gas phase using electrospray ionization and investigated by photoelectron spectroscopy and relativistic quantum chemical calculations. Photoelectron spectra of UO(2)Cl(4)(2-) are obtained at various photon energies and congested spectral features are observed. The free UO(2)Cl(4)(2-) dianion is found to be highly stable with an adiabatic electron binding energy of 2.40 eV. Ab initio calculations are carried out and used to interpret the photoelectron spectra and elucidate the electronic structure of UO(2)Cl(4)(2-). The calculations show that the frontier molecular orbitals in UO(2)Cl(4)(2-) are dominated by the ligand Cl 3p orbitals, while the U-O bonding orbitals are much more stable. The electronic structure of UO(2)Cl(4)(2-) is compared with that of the recently reported UO(2)F(4)(2-) [P. D. Dau, J. Su, H. T. Liu, J. B. Liu, D. L. Huang, J. Li, and L. S. Wang, Chem. Sci. 3 1137 (2012)]. The electron binding energy of UO(2)Cl(4)(2-) is found to be 1.3 eV greater than that of UO(2)F(4)(2-). The differences in the electronic stability and electronic structure between UO(2)Cl(4)(2-) and UO(2)F(4)(2-) are discussed.

Control of hypertension in rats using volatile components of leaves of Taxus chinensis var. mairei.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Taxus chinensis var. mairei (Taxaceae) is used traditionally to fill pillows in some rural areas of China. Its volatile substances have been speculated to be capable of improving sleep quality, making blood pressure stable, and having diuretic capacity as recorded in Ancient Chinese Materia Medica. Using animal models and new technologies, we confirmed the hypotensive potential of volatile components from leaves of Taxus chinensis var. mairei (VCLT). MATERIALS AND METHODS: VCLT was obtained by supercritical CO(2) extraction equipment from Taxus chinensis var. mairei fresh leaves. Hypertensive rats were pre-induced by intraperitoneal (i,p.) injection of Nω-Nitro-l-Ariginine (l-NNA) for 15 days (15mg/kg, twice a day), then divided into 5 groups and subjected to the following treatments. l-NNA group (group 1) receiving l-NNA alone (15mg/kg, i.p., twice per day for 6 weeks); in addition to receiving l-NNA same as group 1, Hydrochlorothiazide (HDZ) group (group 2) receiving HDZ (orally administration, 5mg/kg, once per day for 6 weeks); VCLT groups (groups 3-5), including VCLT1, VCLT2, VCLT3. The VCLT rats were housed in an enclosed cage (2 rats/0.064m(3)). VCLT was mixed well and sprayed on fresh leaves surface of Taxus chinensis var. mairei (100ml/kg) with three dosages: 167g/kg (VCLT1), 233g/kg (VCLT2) and 333g/kg (VCLT3), respectively. Systolic Blood Pressure (SBP), plasma nitric oxide (NO), plasma angiotensin II, postprandial blood glucose, fasting blood glucose and blood lipids were determined. RESULTS: VCLT prevented the increase of SBP and plasma angiotensin II in l-NNA treated rats. Although VCLT does not significantly reduce blood triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C), it decreases total cholesterol (TC) while increasing plasma NO levels in a dose-dependent manner. CONCLUSION: VCLT can be used as a natural and supplementary reagents for the treatment of hypertension.

Antioxidant activities of aqueous leaf extracts of Toona sinensis on free radical-induced endothelial cell damage.

ETHNOPHARMACOLOGICAL RELEVANCE: In Taiwan, Toona sinensis (Toona sinensis) is well known as a traditional Chinese medicine, while the underlying pharmacological mechanisms of this drug are still a matter of debate. MATERIALS AND METHODS: The purpose of this study was to evaluate the protective effects of non-cytotoxic concentrations of aqueous leaf extracts of Toona sinensis (TS extracts; 50-100 µg/mL) and gallic acid (5 µg/mL), a major component of these extracts, against AAPH-induced oxidative cell damage in human umbilical vein endothelial cells (ECs). RESULTS: Exposure of ECs to AAPH (15 mM) decreased cell viability from 100% to 43%. However, ECs were pre-incubated with TS extracts prior to AAPH induction resulted in increased resistance to oxidative stress and cell viability in a dose-dependent manner. An increase in ECs-derived PGI(2) and IL-1 ß in response to AAPH exposure was positively correlated with cytotoxicity and negatively with TS extracts concentrations. In addition, gallic acid also suppressed PGI(2) and IL-1 ß production in AAPH-induced ECs. Notably, TS extracts/gallic acid treatment significantly inhibited ROS generation, MDA formation, SOD/catalase activity, and Bax/Bcl-2 dysregulation in AAPH-stimulated ECs. Pretreatment of ECs with TS extracts/gallic acid also suppressed AAPH-induced cell surface expression and secretion of VCAM-1, ICAM-1 and E-selectin, which was associated with abridged adhesion of U937 leukocytes to ECs. Moreover, TS extracts/gallic acid treatment significantly inhibited the AAPH-mediated up regulation of PAI-1 and down regulation of t-PA in ECs, which may decrease fibrinolytic activity. CONCLUSIONS: Therefore, Toona sinensis may possess antioxidant properties that protect endothelial cells from oxidative stress. Our results also support the traditional use of Toona sinensis in the treatment of free radical-related diseases and atherosclerosis.

Toona sinensis (leaf extracts) inhibit vascular endothelial growth factor (VEGF)-induced angiogenesis in vascular endothelial cells.

AIM OF THE STUDY: Toona sinensis is well known as a traditional Chinese medicine; also, it has been shown to exhibit anticancer and anti-inflammatory effects. This study was aimed at evaluating the anti-angiogenesis effect of the aqueous extracts of Toona sinensis (TS extracts) or gallic acid, a major component of TS extracts, against both VEGF-induced EA.hy 926 and human umbilical vein endothelial cells (HUVECs). MATERIALS AND METHODS: Anti-proliferative activity of TS extracts or gallic acid, was determined against EA.hy 926 and HUVECs by trypan blue exclusion method. Invasion, tube formation and chick chorioallantoic membrane assay were carried out to determine the in vitro and in vivo anti-angiogenic effects. RESULTS: Non-cytotoxic concentration of TS extracts (50-100µg/mL) and gallic acid (5µg/mL) inhibited the proliferation of VEGF-stimulated EA.hy 926 and HUVECs. Inhibitory effects of TS extracts and gallic acid on angiogenesis were assessed by VEGF-induced migration/invasion and capillary-like tube formation by EA.hy 926 and HUVECs. Additionally, gelatin zymography assays showed that TS extracts and gallic acid suppressed the activity of metalloproteinase (MMP)-9 and MMP-2 activated by VEGF. In vivo, TS extracts and gallic acid strongly suppressed neovessel formation in the chorioallantoic membrane of chick embryos. Flow cytometry analyses and Western blot demonstrated that treatment with TS extracts and gallic acid induced G(0)/G(1) arrest in VEGF-stimulated EA.hy 926 cells via a reduction in the amounts of cyclin D1, cyclin E, CDK4, hyperphosphorylated retinoblastoma protein (pRb), VEGFR-2, and eNOS. CONCLUSIONS: These results support an anti-angiogenic activity of Toona sinensis that may contribute critically to its cancer and inflammation chemopreventive potentials.