[Mechanism of acteoside in prevention and treatment of gouty arthritis based on liver metabolomics].

This study aims to reveal the effect of acteoside on gouty arthritis(GA) in rats based on liver metabolomics. The ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to search for the potential biomarkers and metabolic pathways. SD rats were randomly assigned into blank, model, colchicine(0.3 mg·kg~(-1)), and high-, medium-, low-dose(200, 100, and 50 mg·kg~(-1), respectively) acteoside groups(n=7). The rats were administrated once a day for 7 continuous days. Monosodium urate(MSU) was used to induce GA model in rats during administration. The degree of joint swelling and pathological changes of synovial tissue in rats were observed, and the levels of interleukin(IL)-1ß, IL-18 and tumor necrosis factor(TNF)-α in the synovial tissue of rats were measured. UPLC-Q-TOF-MS was employed to collect rat liver data, and Progenesis QI and EZ info were used for data analysis. Human Metabolomics Database(HMDB) and Kyoto Encyclopedia of Genes and Genomes(KEGG) were employed to predict the potential biomarkers and metabolic pathways. The results showed that acteoside alleviated joint swelling, reduced synovial tissue damage, and lowered the levels of inflammatory cytokines in GA rats. A total of 19 common biomarkers were identified, 17 of which can be regulated by acteoside. Seven metabolic pathways were enriched, such as glycerophospholipid metabolism, linoleic acid metabolism, and taurine and hypotaurine metabolism, among which glycerophospholipid metabolism was strongly disturbed. The metabolomics analysis suggested that acteoside may down-regulate the expression of inflammatory cytokines and alleviate the symptoms of GA rats by regulating glycerophospholipid metabolism, linoleic acid metabolism, and taurine and hypotaurine metabolism. The findings provide a reference for future research and development of acteoside.

Effects of Total Saponins from Dioscorea Nipponica Makino on Monosodium Urate-Induced M1-Polarized Macrophages through Arachidonic Acid Signaling Pathway: An in vitro Study.

OBJECTIVE: To investigate and reveal the underlying mechanism of the effect of total saponins from Dioscoreae nipponica Makino (TSDN) on the arachidonic acid pathway in monosodium urate (MSU) crystal-induced M1-polarized macrophages. METHODS: M1 polarization of RAW264.7 cells were induced by 1 µ g/mL lipopolysaccharide (LPS). The methylthiazolyldiphenyl-tetrazolium bromide method was then used to screen the concentration of TSDN. MSU (500 µ g/mL) was used to induce the gouty arthritis model. Afterwards, 10 µ g/L TSDN and 8 µ mol/L celecoxib, which was used as a positive control, were added to the above LPS and MSU-induced cells for 24 h. The mRNA and protein expressions of cyclooxygenase (COX) 2, 5-lipoxygenase (5-LOX), microsomal prostaglandin E synthase derived eicosanoids (mPGES)-1, leukotriene B (LTB)4, cytochrome P450 (CYP) 4A, and prostaglandin E2 (PGE2) were tested by real-time polymerase chain reaction and Western blotting, respectively. The enzyme-linked immunosorbent assay was used to test the contents of M1 markers, including inducible nitric oxid synthase (NOS) 2, CD80, and CD86. RESULTS: TSDN inhibited the proliferation of M1 macrophages and decreased both the mRNA and protein expressions of COX2, 5-LOX, CYP4A, LTB4, and PGE2 (P<0.01) while increased the mRNA and protein expression of mPGES-1 (P<0.05 or P<0.01). TSDN could also significantly decrease the contents of NOS2, CD80, and CD86 (P<0.01). CONCLUSION: TSDN has an anti-inflammation effect on gouty arthritis in an in vitro model by regulating arachidonic acid signaling pathway.

Mechanism of Action of Shenerjiangzhi Formulation on Hyperlipidemia Induced by Consumption of a High-Fat Diet in Rats Using Network Pharmacology and Analyses of the Gut Microbiota.

Shenerjiangzhi formulation (SEJZ) is a new traditional Chinese medicine formulation (patent number: CN110680850A). SEJZ contains Eleutherococcus senticosus (Rupr. and Maxim.), Maxim (Araliaceae; E. senticosus radix and rhizome), Lonicera japonica Thunb (Caprifoliaceae; Lonicera japonica branch, stem), Crataegus pinnatifida Bunge (Rosaceae; Crataegus pinnatifida fruit), and Auricularia auricula. SEJZ has been designed to treat hyperlipidemia. Despite the therapeutic benefits of SEJZ, its underlying mechanism of action is not known. We explored the efficacy of SEJZ against hyperlipidemia by integrating network pharmacology and 16S rRNA gene sequencing and elucidated its mechanism of action. First, SEJZ targets were found through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and from the literature. Hyperlipidemia-related therapeutic targets were obtained from GeneCards, Online Mendelian Inheritance in Man, and DrugBank databases. Then, Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape were applied for the analyses and construction of a protein-protein interaction (PPI) network. The Kyoto Encyclopedia of Genes and Genomes database was employed to identify signaling pathways that were enriched. Second, the therapeutic effects of SEJZ against hyperlipidemia induced by consumption of a high-fat diet in rats were evaluated by measuring body weight changes and biochemical tests. SEJZ treatment was found to alleviate obesity and hyperlipidemia in rats. Finally, 16S rRNA gene sequencing showed that SEJZ could significantly increase the abundance of short-chain fatty acid-producing bacteria, restore the intestinal barrier, and maintain intestinal-flora homeostasis. Using PICRUSt2, six metabolic pathways were found to be consistent with the results of network pharmacology: "African trypanosomiasis", "amoebiasis", "arginine and proline metabolism", "calcium signaling pathway", "NOD-like receptor signaling pathway", and "tryptophan metabolism". These pathways might represent how SEJZ works against hyperlipidemia. Moreover, the "African trypanosomiasis pathway" had the highest association with core genes. These results aid understanding of how SEJZ works against dyslipidemia and provide a reference for further studies.

[Formation of neutrophil extracellular traps and their effects on autoimmune diseases].

Neutrophil extracellular traps(NETs) are networks of extracellular fibers primarily composed of DNA, histones, granular proteins, and cytoplasmic proteins and released to the outside of cells by neutrophils under the stimulation of bacteria, fungi, viruses, parasites, etc. NETs are generated in two forms, suicidal NETs and vital NETs, according to different stimuli. NETs have both anti-inflammatory and pro-inflammatory effects. On the one hand, they can play the anti-microbial role to resist inflammation by capturing, fixing, and killing invading pathogens, which is a special way for neutrophils to exert host defenses. On the other hand, in case of excessive formation or insufficient elimination, they can cause tissue damage directly, and also promote the release of inflammatory factors by recruiting other pro-inflammatory cells or proteins to further expand the inflammatory response, which is related to the pathologies of many diseases. In autoimmune diseases, NETs as important sources of autoantigens, can act as danger-associated molecular patterns( DAMPs) and activate the nucleotide-binding oligomerization domain leucine-rich repeats containing pyrin domain 3(NLRP3) inflammasome and complement system, thereby breaking self-tolerance and accelerating autoimmune inflammation. In addition, NETs can also activate other immune cells(such as B cells, antigen-presenting cells, and T cells) and regulate the acquired immune response. The present study reviewed the correlation of NETs with diseases such as systemic lupus erythematosus(SLE), rheumatoid arthritis(RA), and gouty arthritis(GA) to reveal the effect of dynamic balance between formation and clearance of NETs in autoimmune diseases and provide a theoretical basis for the investigation of underlying mechanisms and targeted therapies of traditional Chinese medicine.

Saposhnikoviae Radix Enhanced the Angiogenic and Anti-Inflammatory Effects of Huangqi Chifeng Tang in a Rat Model of Cerebral Infarction.

Huangqi Chifeng Tang (HQCFT), a traditional Chinese formula of three herbs, has been used to treat cerebral infarction (CI). Saposhnikoviae Radix (SR) was designed as a guiding drug for HQCFT to improve its angiogenic and anti-inflammatory effects. In this study, TTC staining was used to detect the area of CI. H&E staining was used to detect the histopathologic changes in the cerebral tissue. Western blotting was performed to detect the protein expression of NLRP3, caspase 1, IL-1ß, IL-6, TNF-α, MMP-9, VEGF, and VEGFR2 in cerebral tissue. Immunohistochemistry was used to detect the protein expression of MMP-9, VEGF, and VEGFR2. The contents of HIF-1α, NLRP3, caspase 1, IL-1ß, IL-6, and TNF-α in the serum were determined by ELISA. Our study showed that HQCFT and HQCFT-SR could improve the pathological condition and reduce the infarcted area of the brain tissue in a rat model. In addition, HQCFT and HQCFT-SR significantly decreased the expression levels and serum contents of NLRP3, caspase 1, IL-1ß, IL-6, and TNF-α; increased the expression levels of the VEGF and VEGFR2 proteins; and obviously reduced the serum content of HIF-1α. Importantly, the cytokines in brain tissue and serum from the HQCFT group exhibited better efficacy than those from the HQCFT-SR group. HQCFT exerted significant angiogenic and anti-inflammatory effects in rats subjected to middle cerebral artery occlusion (MCAO); these effects can be attributed to the guiding and enhancing effect of SR.

Anti-inflammation effects of the total saponin fraction from Dioscorea nipponica Makino on rats with gouty arthritis by influencing MAPK signalling pathway.

BACKGROUND: Dioscorea nipponica Makino is widely used in traditional Chinese medicine to treat gouty arthritis. METHODS: Sixty male Wistar rats were divided into six groups: the normal group, model group, colchicine group (COL) and three total saponin groups (RDN) (high dose [160 mg/kg], middle dose [80 mg/kg] and low dose [40 mg/kg]). HE staining was used to detect the histopathologic changes of the synovial tissue of joint. Immunohistochemical method was used to detect the protein expressions of P-38, p-P38, JNK, p-JNK, ERK1/2, p-ERK1/2, MEK1/2, p-MEK1/2, MKK4, p-MKK4, ICAM1, VCAM1, and PPARγ in the synovial tissue of joint. Realtime PCR and WB methods were used to detect the mRNA and protein expressions of PPARγ and AdipoR2 in the synovial tissue of joint. The contents of CXCL1 and ADP in the blood serum were measured by Elisa method. RESULTS: Our study showed that RDN could improve the situation of the synovial tissue, reduce the protein expressions of MKK4, p-MEK1/2, p-JNK, p-ERK1/2, ICAM1. They could also decrease the content of CXCL1 and increase the content of ADP in the blood serum. CONCLUSION: RDN has good effect of anti-inflammation. This is in part realized by influencing MAPK signalling pathway. It provides a new visual angle to reveal the mechanism of RDN to treat GA.

Enhancing effect of macroporous adsorption resin on gamma-aminobutyric acid production by Enterococcus faecium in whole-cell biotransformation system.

Gamma-aminobutyric acid (GABA) biosynthesis depended to a great extent on the biotransformation characterization of glutamate decarboxylase (GAD) and process conditions. In this paper, the enhancing effect of D101 macroporous adsorption resin (MAR) on the GABA production was investigated based on the whole-cell biotransformation characterization of Enterococcus faecium and adsorption characteristics of D101 MAR. The results indicated that the optimal pH for reaction activity of whole-cell GAD and pure GAD was 4.4 and 5.0, respectively, and the pH range retained at least 50% of GAD activity was from 4.8 to 5.6 and 4.0-4.8, respectively. No substrate inhibition effect was observed on both pure GAD and whole-cell GAD, and the maximum activity could be obtained when the initial L-glutamic acid (L-Glu) concentration exceeded 57.6 mmol/L and 96.0 mmol/L, respectively. Besides, GABA could significantly inhibit the activity of whole-cell GAD rather than pure GAD. When the initial GABA concentration of the reaction solution remained 100 mmol/L, 33.51 ± 9.11% of the whole-cell GAD activity was inhibited. D101 MAR exhibited excellent properties in stabilizing the pH of the conversion reaction system, supplementing free L-Glu and removing excess GABA. Comparison of the biotransformation only in acetate buffer, the GABA production, with 50 g/100 mL of D101 MAR, was significantly increased by 138.71 ± 5.73%. D101 MAR with pre-adsorbed L-Glu could significantly enhance the production of GABA by gradual replenishment of free L-Glu, removing GABA and maintaining the pH of the reaction system, which would eventually make the GABA production more economical and eco-friendly.

[Modulation effect of Acanthopanax senticosus polysaccharides through inflammatory cytokines in protecting immunological liver-injured mice].

The aim of this paper was to discuss the protective effect and mechanism of Acanthopanax senticosus polysaccharides( ASPs) on immunological liver injury caused by conanavalin A( Con A). BALB/c mice were randomly divided into seven groups: control group,model group( Con A),low-,medium-,and high-dose( 36. 25,72. 5,145 mg·kg~(-1)) ASPs groups,bifendate( 200 mg·kg~(-1),positive drug) group and pyrrolidinedithiocarbamate( PDTC,NF-κB inhibitor,200 mg·kg~(-1)) group. ASPs groups and bifendate group were given with corresponding drugs by ig administration once daily for 7 d. Control group,model group and PDTC group were given with normal saline by ig administration once daily for 7 d. After the last ig administration,PDTC was given in DTC group by iv administration( 200 mg·kg~(-1)); 0. 5 h after that,Con A( 20 mg·kg~(-1)) was injected via the tail vein to induce immunological liver injury in all the mice except normal control group. The mice were killed 8 h later and their liver tissues were collected for histopathological examination. The contents of nitric oxide( NO),superoxide dismutase( SOD),malondialdehyde( MDA),reduced glutathione( GSHPX),interleukin( IL-1ß) and tumor necrosis factor( TNF-α) in liver tissues were detected by kit assay. Western blot method was used to detect TNF-α,intercellular cell adhesion molecule-1( ICAM-1),inducible nitric oxide synthase( i NOS) and nuclear factor( NF-κB) protein expression in liver tissues. As compared with model group,ASPs not only could reduce the activity of MDA,NO,IL-1ß and TNF-α,but also increase the content of GSH-PX and SOD; at the same time,the protein expression levels of TNF-α,ICAM-1,i NOS and NF-κB were reduced in liver tissues; in addition,inflammatory cell infiltration was alleviated,hepatocyte cytoplasm was loose and swollen,and nuclear condensation and staining were improved. ASPs has a protective effect on immunological liver injury,and the mechanism may be associated with regulating secretion of inflammatory cytokines and the expression of adhesion factor through NF-κB signaling pathway.

Anti-inflammatory Effect of Total Saponin Fraction from Dioscorea nipponica Makino on Gouty Arthritis and Its Influence on NALP3 Inflammasome.

OBJECTIVE: To investigate the mechanism of Chinese herbal medicine Dioscorea nipponica for the treatment of monosodium urate crystals-induced gouty arthritis (GA) in rats. METHODS: Sixty male Wistar rats were divided into 6 groups: normal, model, indomethacin and three total saponin (900, 300 and 100 mg/kg) groups. The liver, kidney and serum levels of lysosomal enzymes, antioxidant capacities, and inflammatory factors were measured. In addition, the mRNA and protein levels of the NALP3 inflammasome components in the mononuclear cells of rats' peripheral blood were analyzed using real-time polymerase chain reaction and Western blotting methods, respectively. RESULTS: Total saponins groups could reduce the activities of ß-galactosidase, ß-N acetyl glucosamine enzyme, ß-glucuronidase, acid phosphatase, and malonaldehyde as well as the contents of TNF-α, IL-1ß and IL-8 (all P<0.05). They could also increase the activities of glutathione peroxidase and total superoxide dismutase (both P<0.05). Further studies showed that total saponins groups of high, middle and low doses could all increase the mRNA and protein levels of caspase-1, adapter apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and NALP3 in the mononuclear cells of peripheral blood (all P<0.05). CONCLUSION: Dioscorea nipponica may treat GA by regulating lysosomal enzymes, antioxidant capacities and the NALP3 inflammasome.

Acanthopanax senticosus Protects Structure and Function of Mesencephalic Mitochondria in A Mouse Model of Parkinson's Disease.

OBJECTIVE: To investigate the neuro-protective effects of Acanthopanax senticosus Harms (EAS) on mesencephalic mitochondria and the mechanism of action, using a mouse model of Parkinson's disease (PD). METHODS: The chemical fingerprint analysis of the extract of Acanthopanax senticosus Harms (EAS) was performed using the ultra performance liquid chromatograph and time of flight mass spectrometry. Thirty mice were randomly divided into the control group, the MPTP model group, and the EAS treated group with MPTP (MPTP+EAS group, 10 in each group). The MPTP model group and the MPTP+EAS group received MPTP-HCl (30 mg/kg i.p) once a day for 5 days. The control group received an equal volume of saline (20 mL/kg i.p) once a day for 5 days. Induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride daily (MPTP-HCl, 30 mg/kg) for 5 days, the PD mice were treated with EAS at 45.5 mg/kg daily for 20 days. The behavioral testing of mice was carried out using the pole-climbing test. The integrity and functions of neurons were examined in mesencephalic mitochondria in a PD mouse model, including nicotinamide adenine dinucleotide dehydrogenase ubiquinone flavoprotein 2 (NDUFV2), mitochondrially encoded nicotinamide adenine dinucleotide dehydrogenase 1 (MT-ND1), succinate dehydrogenase complex subunit A (SDHA), and succinate dehydrogenase cytochrome b560 subunit (SDHC). RESULTS: After treatment with EAS, the behavioral changes induced by MPTP were attenuated significantly (P<0.05). EAS protected the mesencephalic mitochondria from swelling and attenuated the decreases in their membrane potential (both P<0.05), which was supported by an ultra-structural level analysis. The changes in reactive oxygen species (ROS), malonic dialdehyde (MDA), oxidative phosphorylation (OXPHOS) system 4 subunits levels and PD-related proteins expressions (parkin, Pink1, DJ-1, α-synuclein, and Lrrk2) reverted to near normal levels (all P<0.05), based on the results of immune-histological and Western blotting observations. CONCLUSIONS: The neuro-protective effects of EAS are linked to protecting mice against MPTP-induced mitochondrial dysfunction and structural damage. Therefore, EAS is a promising candidate for the prevention or treatment of mitochondrial neurodegenerative disorders, such as PD.

[Inhibitory effect of Scutellariae Radix on hepatic fibrosis based on urinary metabonomic].

Urinary metabolomics combined with histological progression were utilized to evaluate the therapeutic effect of Scutellariae Radix decoction and baicalin on hepatic fibrosis (HF) and explore their mechanisms, intervention targets and metabolic pathways. HF rat model was established through subcutaneous injection of CCl4 for 8 weeks. Meanwhile, different doses of Scutellariae Radix decoction and baicalin were administered. Histomorphology of liver tissue was observed and scored by HE and Masson. Urinary metabonomic analysis based on UPLC-Q-TOF-MS was made for the changes of urinary potential biomarkers among different groups at different time points of HF. Finally, it was found that Scutellariae Radix decoction could improve HF by regulating L-tryptophan, 3-methyldioxyindole, 5-hydroxyindoleacetylglycine, kynurenic acid, 4-(2-amino-3-hydroxyphenyl)-2,4-dioxobutanoic acid, methylmalonic acid and L-leucine. However, baicalin could improve HF by regulating L-tryptophan, 3-methyldioxyindole, 5-hydroxyindoleacetylglycine, 4-(2-amino-3-hydroxyphenyl)-2,4-dioxobutanoic acid, kynurenic acid, and methylmalonic acid. These metabolites involved in tryptophan metabolism and valine, leucine and isoleucine degradation pathways. These results indicated that Scutellariae Radix had the multi-target and multi-pathway characteristics in the treatment of HF. Additionally, low-dose Scutellariae Radix decoction and baicalin are showed better efficacies, with no statistically significant difference between them in histomorphology.

[Liver metabonomics of acute gouty arthritis treated by Diosocorea nipponica].

To explore the prevention and protection effect of Diosocorea nipponica (DNM)) on acute gouty arthritis (AGA) rats based on liver metabonomics, and find potential biomarkers and related pathways. AGA model rats were induced by monosodium urate crystal suspension. UPLC-TOF-MS coupled with pattern recognition technique was employed to find out the potential biomarkers and related metabolic pathways. Eleven common potential biomarkers were identified. Among the potential intervention targets in normal rats given by DNM, 4 biomarkers were up-regulated, and the other 4 targets were down regulated. Among the potential intervention targets in AGA rats given by DNM, 5 metabolites were up-regulated by MSU and 5 metabolites were down regulated. The abnormal expression levels of adenosine monophosphate, 5-methyltetrahydrofolic acid, oxidized glutathione, hypoxanthine, docosahexaenoic acid, glutathione, uridine diphosphate glucose and inosine could be corrected by DNM extract. Three pathways were founded with greatest correlation, including purine metabolism, starch and sucrose metabolism and glutathione metabolism. Therefore, it could be inferred that D. nipponica has the effect for anti-acute gouty arthritis by intervening endogenous metabolites from the liver under physiological condition and acute gouty arthritis condition.

Influence of the total saponin fraction from Dioscorea nipponica Makino on TLR2/4-IL1R receptor singnal pathway in rats of gouty arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Dioscorea nipponica Makino have been extensively used in traditional medicine for the treatment of arthritic diseases, particularly gouty arthritis (GA). MATERIALS AND METHODS: Sixty male Wistar rats were divided into six groups: the normal group, model group, colchicine group (COL) and three total saponin groups (RDN) (high dose [160mg/kg], middle dose [80mg/kg] and low dose [40mg/kg]). The mRNA and protein expression levels of TLR2, TLR4, IRAK1, TRAF6, TAK1, IKKα, IκBα and NF-κB in the synovial tissue of joint were detected by realtime PCR and WB methods respectively. The contents of IL-1ß, IL-6 and TNF-α in the blood serum were measured by Elisa method. The activation of NF-κB was measured by EMSA method. RESULTS: Our study showed that RDN decreased both the mRNA and protein expressions of TLR2, TLR4, IRAK1, TRAF6, TAK1, IKKα, IκBα and NF-κB of the synovial tissue of joint of rats induced with monosodium urate crystal (MSU). They could also reduce the levels of IL-1ß, IL-6 and TNF-α in the blood serum. Further, EMSA results showed that RDN reduced the DNA binding ability of NF-κB p65 of model group. CONCLUSION: RDN has the effect of anti-inflammation in MSU-induced GA model. This is realised by influencing an important inflammatory signal pathway which is called TLR2/4-IL1R receptor signal pathway. It highlights the potential utility of RDN for the management of GA.

Green tea polyphenols induce cell death in breast cancer MCF-7 cells through induction of cell cycle arrest and mitochondrial-mediated apoptosis.

In order to study the molecular mechanisms of green tea polyphenols (GTPs) in treatment or prevention of breast cancer, the cytotoxic effects of GTPs on five human cell lines (MCF-7, A549, Hela, PC3, and HepG2 cells) were determined and the antitumor mechanisms of GTPs in MCF-7 cells were analyzed. The results showed that GTPs exhibited a broad spectrum of inhibition against the detected cancer cell lines, particularly the MCF-7 cells. Studies on the mechanisms revealed that the main modes of cell death induced by GTPs were cell cycle arrest and mitochondrial-mediated apoptosis. Flow cytometric analysis showed that GTPs mediated cell cycle arrest at both G1/M and G2/M transitions. GTP dose dependently led to apoptosis of MCF-7 cells via the mitochondrial pathways, as evidenced by induction of chromatin condensation, reduction of mitochondrial membrane potential (ΔΨm), improvement in the generation of reactive oxygen species (ROS), induction of DNA fragmentation, and activations of caspase-3 and caspase-9 in the present paper.

[Effect of Baichanting Compound on Dopamine Contents in Parkinson's Disease Model Mice].

OBJECTIVE: To observe the effect of Baichanting Compound (BC) on dopamine (DA) in striatum of Parkinson's disease (PD) mice, and to screen the optimal component proportion. METHODS: The PD model was established in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced C57BL/6 mice. By using uniform design, they were intervened by three extracts of BC in different proportions [Acanthopanax senticosus extract (X1): white peony root extract (X2): Uncaria rhynchophylla extract (X3) = 30.00: 34.92: 82.50, 48.00: 19.98: 72.19, 18.00: 44.88: 61.88, 36.00: 29.94: 51.56, 54.00: 15.00: 41.25, 24.00: 39.90: 30.94, 42.00: 24.96: 20.63). Equal volume of 5% carboxymethylcellulose sodium was administered to mice in the model group and the normal group by gastrogavage. All medication was lasted for 20 successive days. The dopamine (DA) content was determined by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS). Except 10 in the normal group, 20 PD model mice were screened and divided into the model group and the BC group (with the optimal proportion) according to random digit table. BC extract in optimal proportion was administered to mice in the BC group by gastrogavage, while equal volume of 5% carboxymethylcellulose sodium was administered to mice in the model group and the normal group by gastrogavage. All medication was lasted for 20 successive days. Praxiology was observed in each group. DA content in striatum was also detected. Results Compared with the normal group, the DA content in striatum decreased significantly in the model group (P < 0.01), suggesting a successful PD modeling. Compared with the model group, the DA content in striatum increased significantly in 1 and 2 groups (P<0.05). According to results of quadratic polynomial stepwise regression statistics, the regression equation obtained was: Y = 0.265 + 0.026 X 2 - 0.056 X 3 + 0.334 x 10(-3) x X1 x X3 + 0.691 x 10(-3) X X3(2). X3 extract was the main factor influencing the effectiveness (P < 0.01). The optimal proportion of BC was predicted by the regression equation: X1 = 54.00 mg/(kg x d), X2 = 44.88 mg/(kg x d), the X3 = 82.50 mg/(kg x d). The pole climbing time was shortened, times of autonomic activities increased, DA content was elevated, all with statistical difference in BC groups (P < 0.01, P < 0.05). CONCLUSION: BC could increase DA content in PD model mice with the optimal proportion as 54.00: 44.88: 82.50.

Transgenic plants expressing the AaIT/GNA fusion protein show increased resistance and toxicity to both chewing and sucking pests.

The adoption of pest-resistant transgenic plants to reduce yield losses and decrease pesticide use has been successful. To achieve the goal of controlling both chewing and sucking pests in a given transgenic plant, we generated transgenic tobacco, Arabidopsis, and rice plants expressing the fusion protein, AaIT/GNA, in which an insecticidal scorpion venom neurotoxin (Androctonus australis toxin, AaIT) is fused to snowdrop lectin (Galanthus nivalis agglutinin, GNA). Compared with transgenic tobacco and Arabidopsis plants expressing AaIT or GNA, transgenic plants expressing AaIT/GNA exhibited increased resistance and toxicity to one chewing pest, the cotton bollworm, Helicoverpa armigera. Transgenic tobacco and rice plants expressing AaIT/GNA showed increased resistance and toxicity to two sucking pests, the whitefly, Bemisia tabaci, and the rice brown planthopper, Nilaparvata lugens, respectively. Moreover, in the field, transgenic rice plants expressing AaIT/GNA exhibited a significant improvement in grain yield when infested with N. lugens. This study shows that expressing the AaIT/GNA fusion protein in transgenic plants can be a useful approach for controlling pests, particularly sucking pests which are not susceptible to the toxin in Bt crops.

Microarray Expression Analysis for the Paradoxical Roles of Acanthopanax senticosus Harms in Treating α-Synucleinopathies.

α-Synuclein is a key player in the pathogenesis of neurodegenerative disorders with Lewy bodies. Our previous studies have also showed that Acanthopanax senticosus harms (AS) could significantly suppress α-synuclein overexpression and toxicity. Identifying the RNAs related to α-synucleinopathies may facilitate understanding the pathogenesis of the diseases and the safe application of AS in the clinic. Microarray expression profiling of long non-coding RNAs (lncRNAs) and mRNAs was undertaken in control non-transgenic and human α-synuclein transgenic mice. The effects of AS on central nervous system (CNS) in pathology and physiology were investigated based on the lncRNA/mRNA targets analysis. In total, 341 lncRNAs and 279 mRNAs were differentially expressed by α-synuclein stimulus, among which 29 lncRNAs and 25 mRNAs were involved in the anti-α-synucleinopathies mechanism of AS. However, the levels of 19/29 lncRNAs and 12/25 mRNAs in AS group were similar to those in α-synuclein group, which may cause potential neurotoxicity analogous to α-synuclein. This study demonstrated that some of lncRNAs/mRNAs were involved in α-synuclein related pathophysiology, and AS produced the bidirectional effects on CNS under pathological and physiological conditions.

[Study on potential effect of Dioscorea nipponica in intervening peripheral system of rats based on metabonomic analysis].

To study the potential effect of Dioscorea nipponica(DN) in intervening peripheral system of rats based on metabolomic analysis. The identification of the potential intervention targets of DN in peripheral system may facilitate its safe application and therapeutic potential exploitation. Totally 20 male SD rats were randomly divided into the blank group and the DN-treated groups, with 10 rates in each group. The DN-treated group was orally administrated with DN extracts once a day for 5 days, with the dose of 80 mg x kg(-1) (equivalent to 15 g crude drug in human), and the blank group was given equal volume of saline once a day for 5 days. Heart, liver, spleen, lung, and kidney tissues and serum samples were collected from each rat 24 h later after the last administration. The ultra-performance liquid chromatography/quadrupole time-of-flight-mass spectrometry based metabolomics was used to investigate the effect of DN in intervening peripheral system of rats. After the treatment with DN, 5 modulated metabolites in heart tissue, 6 in liver tissue, 5 in spleen tissue, 3 in lung tissue, 5 in kidney tissue and 6 in serum sample were identified and considered as the potential intervention targets of DN. Effect of DN in regulating some endogenous metabolites was beneficial for protecting peripheral system, while that in other endogenous metabolites produced potential toxicity to peripheral system. The metabolomic analysis revealed the coexistence of protective and toxic effects of DN on peripheral system, which may be a practical guidance for its safe application and beneficial to the expansion of its application scope.

[Effect of total saponins from rhizoma dioscoreae nipponicae on the expression of SDF1 and HCIKB kinase in rIK-1beta induced fibroblast-like synoviocytes].

OBJECTIVE: To study the effect of total saponins from Rhizoma Dioscoreae nipponicae (RDN) on the expression of stroma cell derived factor 1 (SDF1) and IKB kinase (IKK) in rIL-1beta induced fibroblast-like synoviocytes (FLS). METHODS: FLS were primarily cultured and the 3rd generation log phase growth FLS were divided into the normal control group, the model group, and the medication group. 10 microg/L rIL-1beta was used to induce the proliferation of FLS in the model group.10 microg/L rIL-1beta and 100 microg/L RDN were administered to co-incubate FLS in the medication group. No treatment was given to FLS in the normal control group. Expression levels of SDF1 and IkapaB kinase proteins (p-IKK) were detected using Western blot. RESULTS: Expression levels of SDF1 and p-IKK increased significantly higher in the model group than in the normal control group (P<0.01). Compared with the model group, expression levels of SDF-1 and p-IKK significantly decreased in the medication group (P <0.01). CONCLUSIONS: Total saponins from RDN could inhibit the activation of both SDF1 and p-IKK. It might further regulate the expression of IKB kinase by regulating the expression of SDF1.

Metabonomic Study of the Effects of Acanthopanax senticosus on Peripheral System of Rats.

Acanthopanax senticosus is extensively used to treat various nervous and cerebrovascular diseases in traditional medicinal systems in China and Russia. Ultrahigh-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry coupled with pattern recognition methods was used to investigate the effects of A. senticosus on the peripheral system in rats. The analysis of possible pathways influenced by A. senticosus was performed with MetaboAnalyst and Cytoscape software. After treatment with A. senticosus, 21 modulated metabolites in heart tissue, 20 in liver tissue, 14 in spleen tissue, 17 in lung tissue, 16 in kidney tissue, and 12 in a serum sample were identified and considered potential biomarkers of A. senticosus treatments. The regulation of some endogenous metabolites by A. senticosus could be beneficial for the treatment of several peripheral system diseases, such as hypertension, cancer, and oxidative stress, etc. However, there were also some upregulated endogenous metabolites producing potential toxicity to the peripheral system. A metabonomic analysis revealed that protection and toxicity coexisted in the effects of A. senticosus on the peripheral system, which may be a practical guide for its safe use and beneficial to the expansion of its application.