Investigation of the Active Compounds and Important Pathways of Huaiqihuang Granule for the Treatment of Immune Thrombocytopenia Using Network Pharmacology and Molecular Docking.

Materials and Methods: Compounds of HQHG were scanned by LC-MS/MS, and the target profiles of compounds were identified based on SwissTarget Prediction. ITP target proteins were collected from various databases. Then, KEGG pathway and GO enrichment analyses were performed to explore the signaling pathways related to HQHG for ITP. The PPI and drug-herbs-compounds-targets-pathways network were constructed using Cytoscape 3.7.2. Finally, Discovery studio software was used to confirm the key targets and active compounds from HQHG. Results: A total of 187 interacting targets of 19 potentially active compounds in HQHG and 3837 ITP-related targets were collected. Then, 187 intersection targets were obtained. A total of 20 key targets including EGFR, CASP3, TNF, STAT3, and ERBB2 were identified through PPI network analysis. These targets were mainly focused on the biological processes of positive regulation of protein phosphorylation, cellular response to organonitrogen compound, and cellular response to nitrogen compound. 20 possible pathways of HQHG in the treatment of ITP were identified through KEGG enrichment. EGFR, CASP3, TNF, and STAT3 are the four most important target proteins, while adenosine, caffeic acid, ferulic acid, quercetin-3ß-D-glucoside, rutin, scopoletin, and tianshic acid are the most important active compounds, which were validated by molecular docking simulation. Conclusion: This study demonstrated that HQHG produced relief effects against ITP by regulating multitargets and multipathways with multicompounds. And the combined data provide novel insight of drug developing for ITP.

Olfactory metacognition and memory in individuals with different subjective odor imagery abilities.

Imagery vividness is one of the key indicators to evaluate the ability to generate mental images. There is large inter-individual variability in olfactory imagery (OI) abilities, however, little is known about the underlying factors for individual OI abilities. Using a word cueing imagery paradigm and the trial-by-trial imagery vividness rating method, participants with high or low OI abilities (differentiated by the Vividness of Olfactory Imagery Questionnaire) completed two OI tasks with either shorter (2 s) or longer (8 s) image generation time. Participants' olfactory function, olfactory-related working memory and episodic recognition memory were measured using validated methods. Moreover, olfactory metacognition was assessed using the Odor Awareness Scale (OAS) and the Importance of Olfaction Questionnaire (IOQ). Compared to participants with high OI abilities, those with low OI abilities reported less vivid odor images during OI tasks. For participants with low OI abilities, the imagery vividness significantly improved as the image generation time increased. There was no difference regarding olfactory perception or olfactory-related memory performances between the high and the low OI ability groups. However, participants with higher OI abilities had significant higher scores on the OAS and the IOQ, indicating a superior olfactory-related metacognition. These results provide evidences supporting the underlying factors that related to variances of subjective ability of generating vivid odor mental images.

Global regulatory factor AaLaeA upregulates the production of antitumor substances in the endophytic fungus Alternaria alstroemeria.

The global regulatory factor LaeA has been shown to be involved in the biosynthesis of secondary metabolites in various fungi. In a previous work, we isolated an endophytic fungus from Artemisia annua, and its extract had a significant inhibitory effect on the A549 cancer cell line. Phylogenetic analysis further identified the strain as Alternaria alstroemeria. Overexpression of AalaeA gene resulted in significantly increased antitumor activity of this strain's extract. The 3-(4, 5- dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay results showed that the inhibition rate of the AalaeAOE29 mutant extract on A549 cancer cells was significantly higher than that of the WT extract, as the IC50 decreased from 195.0 to 107.4 µg/ml, and the total apoptosis rate was enhanced. Overexpression of the AalaeA gene significantly increased the contents of myricetin, geraniol, ergosterol, and 18 other antitumor compounds as determined by metabolomic analysis. Transcriptomic analysis revealed significant changes in 95 genes in the mutant strain, including polyketide synthases, nonribosomal peptide synthases, cytochrome P450s, glycosyltransferases, acetyl-CoA acetyltransferases, and others. These results suggested that AaLaeA mediated the antitumor activity of the metabolites in A. alstroemeria by regulating multiple metabolic pathways.

Global regulatory factor VeA upregulates the production of antitumor substances in endophytic Fusarium solani.

A number of studies have demonstrated that endophytic fungi have the potential to produce antitumor active substances with novel structures and significant activities. In our previous studies, we isolated a Fusarium strain from the stem of the medicinal plant Nothapodytes pittosporoides (Oliv.). In this study, we identified this strain as Fusarium solani and found that its crude extract has significant antitumor activity against human alveolar adenocarcinoma cells (A549). We overexpressed the global regulatory factor VeA in F. solani (VeAOE), resulting in a significant increase in antitumor activity. The MTT assay results showed that the inhibition rate of the VeAOE mutant extract on A549 cancer cells was significantly higher than that of the WT extract, as the IC50 decreased from 369.22 to 285.89 µg/mL, and the apoptosis ratio was significantly increased by approximately 4.86-fold. In VeAOE, accumulation of alkaloids, terpenoids, carboxylic acid derivatives, phenols and flavonoid metabolites with potential antitumor activity was significantly increased compared with WT based on metabolomic analysis. Additionally, transcriptome analysis found that the expression patterns of 48 genes related to antitumor activity were significantly changed in VeAOE, mainly involving glycosyl hydrolases, the Zn(2)-Cys(6) class, cytochrome P450 monooxygenase, 3-isopropylmalate dehydratase, and polyketide synthases. These results suggested that VeA mediated the antitumor activity of the metabolites in F. solani HB1-J1 by regulating multiple metabolic pathways.

Overexpression of the global regulator FnVeA upregulates antitumor substances in endophytic Fusarium nematophilum.

The special niche of endophytic fungi promotes their potential to produce antitumor compounds with novel structure and significant bioactivity for screening of new antitumor drugs. In our previous studies, we isolated a Fusarium strain from the roots of the medicinal plant Nothapodytes pittosporoides and identified it as Fusarium nematophilum. We found that the crude extract of F. nematophilum had significant antitumor activity on A549 cancer cells, and overexpressing the global regulatory factor FnVeA (the VeA gene of the fungus F. nematophilum) resulted in a significant increase in the antitumor activity, which was approximately fivefold higher than wild strain for relative inhibition rate. In FnVeAOE, the accumulation of indole, alkene, alkaloid, steroid, and flavonoid metabolites with potential antitumor activity was significantly upregulated compared with wild type via metabolomic analysis. Moreover, the transcriptome analysis showed that 134 differential genes were considered to be closely related to the biosynthesis of antitumor substances, of which 59 differential genes were considered as candidate key genes, and related to tryptophan dimethylallyltransferase, cytochrome P450 monooxygenase, polyketide synthases, and transcription factors. Taken together, we suggest that FnVeA may regulate the biosynthesis of antitumor substances by mediating the expression of genes related to secondary metabolic pathways in F. nematophilum.

Cloning and Functional Characterization of Two Germacrene A Oxidases Isolated from Xanthium sibiricum.

Sesquiterpene lactones (STLs) from the cocklebur Xanthium sibiricum exhibit significant anti-tumor activity. Although germacrene A oxidase (GAO), which catalyzes the production of Germacrene A acid (GAA) from germacrene A, an important precursor of germacrene-type STLs, has been reported, the remaining GAOs corresponding to various STLs' biosynthesis pathways remain unidentified. In this study, 68,199 unigenes were studied in a de novo transcriptome assembly of X. sibiricum fruits. By comparison with previously published GAO sequences, two candidate X. sibiricum GAO gene sequences, XsGAO1 (1467 bp) and XsGAO2 (1527 bp), were identified, cloned, and predicted to encode 488 and 508 amino acids, respectively. Their protein structure, motifs, sequence similarity, and phylogenetic position were similar to those of other GAO proteins. They were most strongly expressed in fruits, according to a quantitative real-time polymerase chain reaction (qRT-PCR), and both XsGAO proteins were localized in the mitochondria of tobacco leaf epidermal cells. The two XsGAO genes were cloned into the expression vector for eukaryotic expression in Saccharomyces cerevisiae, and the enzyme reaction products were detected by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) methods. The results indicated that both XsGAO1 and XsGAO2 catalyzed the two-step conversion of germacrene A (GA) to GAA, meaning they are unlike classical GAO enzymes, which catalyze a three-step conversion of GA to GAA. This cloning and functional study of two GAO genes from X. sibiricum provides a useful basis for further elucidation of the STL biosynthesis pathway in X. sibiricum.

Identification and quantification of oleanane triterpenoid saponins and potential analgesic and anti-inflammatory activities from the roots and rhizomes of Panax stipuleanatus.

BACKGROUND: Panax stipuleanatus represents a folk medicine for treatment of inflammation. However, lack of experimental data does not confirm its function. This article aims to investigate the analgesic and anti-inflammatory activities of triterpenoid saponins isolated from P. stipuleanatus. METHODS: The chemical characterization of P. stipuleanatus allowed the identification and quantitation of two major compounds. Analgesic effects of triterpenoid saponins were evaluated in two models of thermal- and chemical-stimulated acute pain. Anti-inflammatory effects of triterpenoid saponins were also evaluated using four models of acetic acid-induced vascular permeability, xylene-induced ear edema, carrageenan-induced paw edema, and cotton pellet-induced granuloma in mice. RESULTS: Two triterpenoid saponins of stipuleanosides R1 (SP-R1) and R2 (SP-R2) were isolated and identified from P. stipuleanatus. The results showed that SP-R1 and SP-R2 significantly increased the latency time to thermal pain in the hot plate test and reduced the writhing response in the acetic acid-induced writhing test. SP-R1 and SP-R2 caused a significant decrease in vascular permeability, ear edema, paw edema, and granuloma formation in inflammatory models. Further studies showed that the levels of inflammatory mediators, nitric oxide, malondialdehyde, tumor necrosis factor-α, and interleukin 6 in paw tissues were downregulated by SP-R1 and SP-R2. In addition, the rational harvest of three- to five-year-old P. stipuleanatus was preferable to obtain a higher level of triterpenoid saponins. SP-R2 showed the highest content in P. stipuleanatus, which had potential as a chemical marker for quality control of P. stipuleanatus. CONCLUSION: This study provides important basic information about utilization of P. stipuleanatus resources for production of active triterpenoid saponins.

Effects of Supplemental Lighting on Potassium Transport and Fruit Coloring of Tomatoes Grown in Hydroponics.

Supplemental blue/red lighting accelerated fruit coloring and promoted lycopene synthesis in tomato fruits. Potassium (K) is the most enriched cation in tomato fruits, and its fertigation improved tomato yield and fruit color. However, the effects of supplemental lighting on K uptake and transport by tomatoes and whether supplemental lighting accelerates fruit coloring through enhancing K uptake and transport are still unclear. We investigated the effects of supplemental light-emitting diode (LED) lighting (SL; 100% red, 100% blue; 75% red combined 25% blue) on K uptake in roots and transport in the fruits as well as the fruit coloring of tomatoes (Micro-Tom) grown in an experimental greenhouse in hydroponics. The use of red SL or red combined blue SL enhanced K uptake and K accumulation as well as carotenoid (phytoene, lycopene, γ-carotene, and ß-carotene) content in fruits by increasing photosynthesis, plant growth, and fruit weight. The genes related to ethylene signaling were upregulated by red SL. Quantitative real-time PCR (qRT-PCR) results showed that K transporter genes (SlHAKs) are differentially expressed during fruit development and ripening. The highest-expressed gene was SlHAK10 when fruit reached breaker and ripening. SlHAK3 and SlHAK19 were highly expressed at breaker, and SlHAK18 was highly expressed at ripening. These might be related to the formation of tomato fruit ripening and quality. SlHAK4, SlHAK6, SlHAK8, and SlHAK9 were significantly downregulated with fruit ripening and induced by low K. The expression level of SlHAK6, SlHAK10, SlHAK15, and SlHAK19 were significantly increased by blue SL or red combined blue SL during breaker and ripening. Blue SL or red combined blue SL increased content of phytoene, ß-carotene, α-carotene, and γ-carotene and accelerated fruit coloring by enhancing K uptake in roots and transport in fruits during fruit ripening. This was consistent with the expression level of SlHAK6, SlHAK10, SlHAK15, and SlHAK19 during fruit development and ripening. The key genes of photoreceptors, light signaling transcript factors as well as abscisic acid (ABA) transduction induced by blue SL or red combined blue SL were consistent with the upregulated genes of SlHAK6, SlHAK10, SlHAK15, and SlHAK19 under blue SL and red combined blue SL. The K transport in tomato fruits might be mediated by light signaling and ABA signaling transduction. These results provide valuable information for fruit quality control and the light regulating mechanism of K transport and fruit coloring in tomatoes.

Bacterial diversity in phosphorus immobilization of the South China Sea.

Marine bacteria play indispensable roles in the phosphorus (P) cycle, primarily responsible for P assimilation and remineralization. The aim of this study was to determine diversity of marine aerobic bacteria from the South China Sea capable of P immobilization. Highly efficient P immobilized genera reached 87.72% of all genera, which were mainly distributed in epipelagic seawater zone and semi-deep sediment zone. Accumulated P in extracellular polymeric substances (EPS) accounted for about 70% of immobilized P of representative bacteria. The sum of bioavailable P (non-apatite inorganic phosphorus, organic phosphorus) amounted to more than 90% of total P in representative bacteria, and orthophosphate monoester was identified as the only extracellular P species. Marine bacteria which participated in P cycle were general, not specific genus. EPS of marine bacteria played an important role in P immobilization, and accumulated P species were bioavailable. Our results may provide a better insight for understanding roles of marine bacteria in P cycle.

[Distribution of Moxibustion-induced Thermosensitive Acupoints of Yangming Meridians in Patients with Perennial Allergic Rhinitis].

OBJECTIVE: To examine the distribution of heat-sensitive acupoints below the elbow and knee joints of the Yangming Meridians in patients with perennial allergic rhinitis (PAR)．. METHODS: A total of 27 PAR volunteers 16－55 years in age were recruited in the present study. In a quiet room, the patient was ordered to take a recumbent or sitting position, and the operator held an ignited moxa-stick to make a circling (about 2 min), sparrow-pecking (2 min) and forwards-backwards moving (1 min) moxibustion perpendicularly over the skin (about 3 cm away) along the running course of the Large Intestine Meridian of Hand Yangming below the elbow joints and the Stomach Meridian of Foot Yangming below the knee joints on both sides. The procedures were repeated again and again until the moxibustion sensation disappeared. The patient was asked to carefully perceive the heat diffusion, diathermic, extending, athermal (cool and itching) feelings, at the heated loci. If one or more of the feelings appeared, it was considered as the thermosensitive phenomenon and that spot was marked as the "thermosensitive spot" or "thermosensitive acupoint"．. RESULTS: In those 27 PAR patients, the thermosensitive response was found at Quchi (LI 11), Shousanli (LI 10), Hegu (LI 4), Sanjian (LI 3), and Zusanli (ST 36), constituting 59.25% (16/27), 85.18% (23/27), 44.44% (12/27), 55.55% (15/27), and 11.11% (3/27), respectively, being 92.59% in total. Of the 27 patients, 2, 2, 9, 8, 5 and 1 cases had 0, 1, 2, 3, 4 and 5 thermosenitive acupoints appeared, accounting for 7.41%, 7.41%, 33.33%, 29.63%, 18.52% and 3.70%, respectively. CONCLUSION: There is a certain occurrence rate of the thermosensitive acupoints below the elbow and knee joints of the Yangming Meridians in PAR patients, which may provide a target-point for treating PAR.

[Changes of transport sugar content in different organs of Rehmannia glutinosa].

Raffinose series oligosaccharides are the transport and storage sugars of many plants, Rehmannia glutinosa is one of the commonly used Chinese herbal medicines, medicinal parts ist he roots. Root and tuber of R. glutinosa contains stachyose, raffinose and other oligosaccharides, but the study about the process of growth and development of other organs in the non-structural changes in sugar content is rare.In this study, leaves, stems and roots of R. glutinosa were used as materials to analyze the diurnal variation and the changes of sugar content of sucrose, raffinose and stachyose in different organs of R. glutinosa. The results showed that the content of sucrose in R. glutinosa leaves gradually increased from seedling stage.However, the content of stachyose did not change much at the early stage of growth, and the stachyose rapidly increased at the later stage of growth. The raffinose content gradually decreased throughout the growing season, young leaves of R. glutinosa have higher ability to sucrose synthesis than mature leaves, while mature leaf has higher raffinose and stachyose synthesis ability than young leaves. Sucrose and stachyose content in stem gradually increased, while there was little change in raffinose content. The content of raffinose and stachyose in root increased rapidly from the beginning of fast growing period, while the content of sucrose did not change much. The content of sucrose in leaves of R. glutinosa did not change much at day and night, while the daily changes of raffinose and stachyose contents were very obvious. The contents of raffinose and stachyose in daytime were higher than those at night. The content of raffinose in root and stem was not changed much, but the change of stachyose in root, stem and leaf was very obvious, especially in stem and leaf. In summary, the leaf is the main synthetic organ of raffinose, leaves, stems and roots are stachyose synthesis organ. Sucrose, raffinose and stachyose are the major transport forms of carbohydrates in R. glutinosa.

Molecular diversity analysis of Tetradium ruticarpum (WuZhuYu) in China based on inter-primer binding site (iPBS) markers and inter-simple sequence repeat (ISSR) markers.

"Wu zhu yu", which is obtained from the dried unripe fruits of Tetradium ruticarpum (A. Jussieu) T. G. Hartley, has been used as a traditional Chinese medicine for treatment of headaches, abdominal colic, and hypertension for thousands of years. The present study was designed to assess the molecular genetic diversity among 25 collected accessions of T. ruticarpum (Wu zhu yu in Chinese) from different areas of China, based on inter-primer binding site (iPBS) markers and inter-simple sequence repeat (ISSR) markers. Thirteen ISSR primers generated 151 amplification bands, of which 130 were polymorphic. Out of 165 bands that were amplified using 10 iPBS primers, 152 were polymorphic. The iPBS markers displayed a higher proportion of polymorphic loci (PPL = 92.5%) than the ISSR markers (PPL = 84.9%). The results showed that T. ruticarpum possessed high loci polymorphism and genetic differentiation occurred in this plant. The combined data of iPBS and ISSR markers scored on 25 accessions produced five clusters that approximately matched the geographic distribution of the species. The results indicated that both iPBS and ISSR markers were reliable and effective tools for analyzing the genetic diversity in T. ruticarpum.

Antihyperglycemic, antihyperlipidemic and antioxidant effects of standard ethanol extract of Bombax ceiba leaves in high-fat-diet- and streptozotocin-induced Type 2 diabetic rats.

The present study aimed at exploring the therapeutic potential of standard extract of Bombax ceiba L. leaves (BCE) in type 2 diabetic mellitus (T2DM). Oral administration of BCE at doses of 70, 140, and 280 mg·kg-1, to the normal rats and the high-fat-diet- and streptozotocin-induced T2DM rats were carried out. Effects of BCE on blood glucose, body weight, and a range of serum biochemical parameters were tested, and histopathological observation of pancreatic tissues was also performed. HPLC-ESI-Q/TOF-MS/MS analysis indicated that the chemical composition of BCE mainly contained mangiferin, isoorientin, vitexin, isomangiferin, isovitexin, quercetin hexoside, 2'-trans-O-cumaroyl mangiferin, and nigricanside. BCE caused a significant decrease in the concentrations of fasting blood glucose, glycosylated hemoglobin, total cholesterol, triglyceride, low density lipoprotein-cholesterol, serum insulin, and malondialdehyde, and increases in oral glucose tolerance, high density lipoprotein-cholesterol, and superoxide dismutase in the T2DM model rats. Moreover, considerable pancreatic ß-cells protection effect and stimulation of insulin secretion from the remaining pancreatic ß-cells could be observed after BCE treatment. The results indicated that BCE exhibited an excellent hypoglycemic activity, and alleviated dyslipidemia which is associated with T2DM. Antioxidant activity and protecting pancreatic ß-cells are the possible mechanisms involved in anti-diabetic activity of BCE.

[Morphological and cytohistological observations of seed germination and protocorm development of Bletilla striata].

In order to investigate the mechanism of growth for Bletilla striata, which could be applied for rapid propagation, morphological and cytohistological of seed germination and protocorm development in vitro culture were observed using paraffin section techniques. In this study, we have found that the development of B. striata goes through four stages： embryo, protocorm, rhizome and pseudobulb. The end away from embryo suspensor is able to differentiate green buds after the seed of B. striata swelling, growing point. At the same time, the other end of embryo grows many white villous roots, with the green bud differentiating into cotyledon, the embryo breaking through seed coat and being protocorm. The shoot apical meristem of protocorm consists of tunica, corpus and leaf primordium, whose developmental flowing tunica-corpus theory. After more vascular bundle appeared from the leaf primordium, B. striata grows into the stage of rhizome. While in the stage of rhizome, the root primordium of tissue culture seedlings are differentia initially that derived from rhizome vascular bundle, belonging to internal origin. Subsequently, the pseudobulb forms by the inner meristem growing into mature parenchymatous tissue and the rhizome enlargement gradually.

[Identification of six species of medicinal Diospyros plants based on leaf macro- and micro-morphology].

To establish a method for the identification of five species and one variety of medicinal plants from Diospyros, their leaf veins, epidermis, anatomic and powder characters were observed and compared with macro-morphological and microscopic methods. The results indicated the differences of secondary and tertiary veins among those Diospyros species. The single cell non-glandular hair and glandular hair exist in most species' epidermis while stone cells were only found in the leaf powders of two species. Through the study, the main differences of leaf macro- and micro-morphology of these species were obtained and practical keys were also established, which can provide scientific base not only for identification of these species during their vegetative stages, but also for accuracy authentication of the source of Kaki Folium.

Chemical Constituents of Pyrrosia calvata.

A novel flavanone glycoside, 3',5',5,7-tetrahydroxy-6-C-ß-D-glucopyranosyl-flavanone (1), along with 16 known compounds, (R/S)-eriodictyol-8-C-ß-D-glucopyranoside (2), quercetin-3-O-α-L-rhamnosyl (1''' --> 3''')-ß-D-glucopyranoside (3), hemipholin (4), 4ß-carboxymethyl-(-)-epicatechin methyl ester (5), kaempferol (6), quercetin (7), mangiferin (8), chlorogenic acid (9), 1,5-O-dicaffeoylquinic acid (10), 3,5-O-dicaffeoylquinic acid (11), 3-O-caffeoylquinic acid methyl ester (12), 1-O-caffeoyl glycoside (13), 4-O-ß-D-glucopyranosyl-caffeic acid (14), 3'-O-methyleplcatechin-7-O-ß-D-glucopyranoside (15), hop-22(29)-en-30-ol (16) and diploptene (17), were isolated from the whole plant of Pyrrosia calvata (Backer) Ching. Among them, compounds 2, 3, 4, 10, 11, 13 and 14 were isolated from the family Polypodiaceae for the first time, and compound 5 has not been recorded previously from the genus Pyrrosia.

[Herbal textural research on species of Xanthii Fructus].

Xanthii Fructus is a traditional medicine for the treatment of nasal diseases in clinic, mainly come from the burs of Xanthium sibiricum with a worldwide distribution. By sorting and studying literature of Chinese medicine and comparing different figures recorded with the morphological description of several species from Xanthium (Asteraceae) in the Flora of China, combining the biological investigation in resource survey, the article pointed out that the burs or the whole herbs of X. mongolicum, as well as X. sibiricum, has been used by the traditional Chinese medicine in ancient time. It provides a reference for further studies in the future.

Ilexgenin A inhibits endoplasmic reticulum stress and ameliorates endothelial dysfunction via suppression of TXNIP/NLRP3 inflammasome activation in an AMPK dependent manner.

Ilexgenin A is a natural triterpenoid with beneficial effects on lipid disorders. This study aimed to investigate the effects of ilexgenin A on endothelial homeostasis and its mechanisms. Palmitate (PA) stimulation induced endoplasmic reticulum stress (ER stress) and subsequent thioredoxin-interacting protein (TXNIP)/NLRP3 inflammasome activation in endothelial cells, leading to endothelial dysfunction. Ilexgenin A enhanced LKB1-dependent AMPK activity and improved ER stress by suppression of ROS-associated TXNIP induction. However, these effects were blocked by knockdown of AMPKα, indicating AMPK is essential for its action in suppression of ER stress. Meanwhile, ilexgenin A inhibited NLRP3 inflammasome activation by down-regulation of NLRP3 and cleaved caspase-1 induction, and thereby reduced IL-1ß secretion. It also inhibited inflammation and apoptosis exposed to PA insult. Consistent with these results in endothelial cells, ilexgenin A attenuated ER stress and restored the loss of eNOS activity in vascular endothelium, and thereby improved endothelium-dependent vasodilation in rat aorta. A further analysis in high-fat fed mice showed that oral administration of ilexgenin A blocked ER stress/NLRP3 activation with reduced ROS generation and increased NO production in vascular endothelium, well confirming the beneficial effect of ilexgenin A on endothelial homeostasis in vivo. Taken together, these results show ER stress-associated TXNIP/NLRP3 inflammasome activation was responsible for endothelial dysfunction and ilexgenin A ameliorated endothelial dysfunction by suppressing ER-stress and TXNIP/NLRP3 inflammasome activation with a regulation of AMPK. This finding suggests that the application of ilexgenin A is useful in the management of cardiovascular diseases in obesity.

Serum uric acid is neuroprotective in Chinese patients with acute ischemic stroke treated with intravenous recombinant tissue plasminogen activator.

BACKGROUND: Exogenous uric acid (UA) is a neuroprotective antioxidant that reinforces the benefits of intravenous recombinant tissue plasminogen activator thrombolysis in animal thromboembolic stroke. However, whether serum uric acid (SUA) also increases the benefits of thrombolysis in Chinese patients with acute ischemic stroke (AIS) has yet to be fully defined. METHODS: A total of 216 consecutive AIS patients of Chinese origin treated with intravenous thrombolysis were enrolled in a prospective stroke registry. Demographic and clinical characteristics, conventional risk factors, important laboratory data, and neurologic course were prospectively recorded. Functional outcomes were assessed with the modified Rankin Scale (mRS) score on day 90 by telephone calls. Receiver operating characteristic curves and binary logistic regression models were used to examine the performance of SUA in predicting excellent outcomes (mRS, 0-1). RESULTS: SUA levels were significantly higher in patients with excellent outcomes than those in patients with poor outcomes (331.46 ± 103.39 versus 277.69 ± 105.62, P = .008). SUA had a modest power for predicting excellent outcomes as suggested by area under the curve of .665 ± .052, P = .003. In multivariate models, increased SUA levels (adjusted odds ratio, 1.005; 95% confidence interval, 1.002-1.009; P = .033) were associated with excellent outcomes independently of the effect of possible confounders. Spearman correlation tests indicated that there was an inverse correlation between SUA levels and stroke severity. CONCLUSIONS: Increased SUA levels are associated with excellent outcomes in Chinese patients with AIS treated with intravenous thrombolysis, giving additional support to administration of exogenous UA as an adjuvant to thrombolysis.

Cause and control of Radix Ophiopogonis browning during storage.

In the storage of Radix Ophiopogonis, browning often happens to cause potential risk with regard to safety. Previously few reports investigate the browning of Radix Ophiopogonis. In this research, the causes and mechanisms of the browning of Radix Ophiopogonis were preliminarily elucidated. Content determination by high-performance liquid chromatography (HPLC) and spectrophotometry, enzyme activity determination by colorimetry, and morphological observation by electron microscopy were performed in the present study. Uniform design and three-dimensional response surfaces were applied to investigate the relationship between browning and storage factors. The cortex cell wall of browned Radix Ophiopogonis was ruptured. Compared with the normal Radix Ophiopogonis, cellulase and polyphenol oxidase enzymes were activated, the levels of 5-hydroxymethylfurfural (5-HMF), total sugars, and reducing sugars were increased, while the levels of polysaccharides and methylophiopogonanone A were decreased in browned Radix Ophiopogonis. The relationship between the storage factors and degree of browning (Y) could be described by following correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3. Accompanied with browning under storage conditions, the chemical composition of Radix Ophiopogonis was altered. Following the activation of cellulase, the rupture of the cortex cell wall and the outflow of cell substances flowed out, which caused the Radix Ophiopogonis tissue to become soft and sticky. The main causes of the browning were the production of 5-HMF, the activation of polyphenol oxidase, Maillard reactions and enzymatic browning. Browning could be effectively prevented when the air relative humidity (HR), temperature, and moisture content were under 25% RH, 12 °C and 18%, respectively.