Effects of Total Saponins from Dioscorea Nipponica Makino on Monosodium Urate-Induced M1-Polarized Macrophages through Arachidonic Acid Signaling Pathway: An in vitro Study / 中国结合医学杂志

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.

Analysis of the effect of midazolam on pain in a rat model of lumbar disc herniation based on the p38 MAPK signaling pathway / 中国骨伤

OBJECTIVE@#To investigate the effect of midazolam on pain in lumbar disc herniation model rats based on p38 MAPK signaling pathway.@*METHODS@#Fifty SPF-grade Sprague-Dawley healthy rats, half male and half female, were selected and randomly divided into normal group, model group, and low-dose, medium-dose, high-dose groups. Model group and low-dose, medium-dose, high-dose groups were initially modeled for lumbar disc herniation. Intraperitoneal injection of saline was performed in rats of normal and model groups; and in the low-dose, medium-dose, and high-dose groups, intraperitoneal injection of midazolam was performed with doses of 30, 60, and 90 mg/kg, respectively. Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), 5-hydroxytryptamine (5-HT), β-endorphin (β-EP), substance P (SP), neuropeptide Y (NPY) were detected in the serum of rats by enzyme-linked immunoassay. The expression of p38 MAPK and matrix metalloproteinase-3(MMP-3) protein were detected by Western blot in the tissues of rats of each group.@*RESULTS@#The levels of TNF-α, IL-1β and β-EP were higher and the level of 5-HT was lower in the model group than in the normal group(P<0.05);the levels of TNF-α, IL-1β and β-EP were lower and the level of 5-HT was higher in the low-dose, medium-dose and high-dose groups than in the model group(P<0.05). The levels of SP and NPY increased in the model group compared with the normal group (P<0.05) and the levels of SP and NPY decreased in the low-dose, medium-dose and high-dose groups compared with the model group (P<0.05). The expression of p38 MAPK and MMP-3 increased in the model group compared with the normal group (P<0.05); the expression of p38 MAPK and MMP-3 decreased in the low-dose, medium-dose and high-dose compared with the model group(P<0.05).@*CONCLUSION@#Midazolam may ameliorate the immune inflammatory response in rats with a model of lumbar disc herniation, possibly regulated through the p38MAPK signaling pathway.

Mechanism of Scutellariae Radix-Paeoniae Radix Rubra Combination of Different Proportions Against Hepatic Fibrosis in Rats / 中国实验方剂学杂志

ObjectiveTo observe the effects of Scutellariae Radix （SR）-Paeoniae Radix Rubra （PRR） combination of different proportions on the expression of the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear transcription factor κB （NF-κB） and phosphatidylinositol kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathways in liver tissues of rats with hepatic fibrosis and explore the mechanism against hepatic fibrosis. MethodSixty male SD rats of SPF grade were randomly divided into a normal group， a model group， a positive control （silymarin） group， and SR-PRR 1∶1， SR-PRR 1∶2， and SR-PRR 1∶4 groups， with 10 rats in each group. The hepatic fibrosis model was induced in rats except for those in the normal group by intraperitoneal injection of 40% tetrachloromethane （CCl4）-olive oil solution at 3 mL·kg-1， 5 mL·kg-1 for the first time， for 8 weeks， twice per week. After 4 weeks， rats were treated correspondingly at 10 mL·kg-1 by intragastric administration， and the body weight of rats in each group was weighed for 8 weeks. After administration， histopathological changes in the liver were observed. Serum alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， hyaluronic acid （HA）， laminin （LN）， albumin （ALB）， alkaline phosphatase （AKP）， and superoxide dismutase （SOD） activities， malondialdehyde （MDA）， and hydroxyproline （HYP） content in liver tissues were detected. The mRNA expression levels of TLR4， MyD88， NF-κB， PI3K， Akt， and mTOR in the liver of rats were detected by real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the model group， SR-PRR combination of different proportions could recover the body weight and improve the pathological injury of the liver. As revealed by enzyme linked immunosorbent assay （ELISA） results， compared with the normal group， the model group showed increased ALT， AST， HA， LN， AKP， MDA， and HYP levels to different degrees （P<0.05）. Compared with the model group， the groups with drug intervention showed decreased levels of ALT， AST， HA， LN， AKP， MDA， and HYP， potentiated SOD activity， and increased level of ALB （P<0.05）. As revealed by Real-time PCR results， compared with the normal group， the model group showed increased mRNA expression of TLR4， MyD88， NF-κB， PI3K， Akt， and mTOR （P<0.05）. Compared with the model group， the groups with drug intervention showed reduced mRNA expression of TLR4， MyD88， NF-κB， PI3K， Akt， and mTOR in the liver of rats （P<0.05）. ConclusionSR-PRR combination of different proportions can improve the histopathological injury in liver tissues caused by CCl4， with the optimal effect observed in the SR-PRR 1∶4 group. SR-PRR may inhibit the development of liver fibrosis by inhibiting the expression of TLR4/MyD88/NF-κB and PI3K/Akt/mTOR signaling pathways， thereby alleviating chemical-induced liver injury.

Therapeutic Effect of Huangqi Chifengtang on Cerebral Infarction Rat Model and Its Effect on Expression of ZO-1， Claudin-5， P-gp and MRP1 Protein in Brain Tissue / 中国实验方剂学杂志

ObjectiveTo explore the therapeutic effect and mechanism of Huangqi Chifengtang on middle cerebral artery embolism（MCAO） rat model. MethodThe 90 SPF male rats were randomly divided into sham operation group， model group， high， medium and low dose groups of Huangqi Chifengtang （8.10，4.05，2.025 g·kg-1） and positive drug group （Naoxintong 0.32 g·kg-1）. MCAO rat model was established and intervened with Huangqi Chifengtang， and the neurological scores of each group were scored. The area of cerebral infarction was calculated by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Serum interleukin-6 （IL-6） and interleukin-1β（IL-1β） were detected by enzyme-linked immunosorbent assay （ELISA），The contents of matrix metalloproteinase-9（MMP-9）， vascular endothelial growth factor（VEGF） and vascular endothelial growth factor receptor 2 （VEGFR2）， the pathological changes of brain tissue in each group were observed by hematoxylin eosin （HE） staining. Western blot was used to detect zonule atresia protein-1（ZO-1）， tight junction protein-5（Claudin-5） and P-glycoprotein （P-gp） and multidrug resistance protein 1（MRP1）. ResultCompared with the sham operation group， the neurological function score and cerebral infarction rate of the model group were significantly increased（P<0.01）， and the levels of IL-6， IL-1β and MMP-9 in serum were significantly increased（P<0.01）， the levels of ZO-1 and Claudin-5 protein expression decreased significantly（P<0.01）， and the levels of P-gp and MRP1 protein expression increased significantly（P<0.01）. Compared with the model group， the neurological function score of rats in each administration group decreased significantly at 14 days （P<0.05，P<0.01）， the pathological changes of brain tissue effectively improved， the rate of cerebral infarction significantly reduced （P<0.01）， and the expression level of IL-6， IL-1β and MMP-9 in serum decreased significantly （P<0.05，P<0.01）， the content of VEGFR2 increased significantly （P<0.01）， and the content of VEGF increased significantly in high， medium dose and positive drug groups （P<0.05，P<0.01）. Although it decreased in low dose group， there was no significant difference. The levels of ZO-1 and Claudin-5 protein expression in brain tissue of high dose group and positive drug group increased significantly （P<0.05，P<0.01）， the level of MRP1 and P-gp protein expression decreased significantly （P<0.05）. ConclusionHuangqi Chifengtang can play a therapeutic role in rats with cerebral infarction by improving the pathological changes of brain tissue， reducing inflammatory reaction， promote angiogenesis and regulating the function of blood-brain barrier（BBB）.

Mechanism of Total Saponins from Dioscoreae Nipponicae Rhizoma to Treat Gouty Arthritis by Regulating M1/M2 Polarization of Macrophages / 中国实验方剂学杂志

Objective:To illustrate the effect of M1/M2 polarization of macrophages on gouty arthritis models induced with monosodium urate and reveal the molecular mechanism of total saponins from Dioscoreae Nipponicae Rhizoma to treat gouty arthritis. Method:A total of 72 male SD rats were randomly divided into four groups： normal group， model group， total saponin group （160 mg·kg^-1）， celecoxib group （43.3 mg·kg^-1）， with 18 rats in each group. Gouty arthritis models were induced by injecting monosodium urate into ankle joints bilaterally. Histopathology changes of ankle joints were observed by hematoxylin-eosin（HE） staining. Immunohistochemistry method was used to detect the protein expression change of CD68， interleukin-4（IL-4）， inducible nitric oxide synthase （iNOS） and transforming growth factor-<italic>β</italic>₁（TGF-<italic>β</italic>₁）. Result:HE staining results showed that the inflammation of the model group was most obvious on the third day after modeling， and the disease was in the acute stage. On day 5， the inflammation was alleviated， and on day 8， the inflammation was still present but close to normal. The total saponin group and celecoxib group could improve the pathological changes of synovial tissue， and the effect of total saponin group was more obvious. Immunohistochemical results were as follows. Compared with the normal group. The expression of CD68 and iNOS in the model group increased on the 3rd，5th and 8th day of administration （<italic>P</italic><0.01）. Compared with the model group， the total saponins group could reduce the expression of CD68 and iNOS （<italic>P</italic><0.05，<italic>P</italic><0.01）on the 3rd day of administration， and significantly reduced them expression on the 5th and 8th days （<italic>P</italic><0.01）. Compared with the normal group， IL-4 and TGF-<italic>β</italic>₁ expression were increased in the model group when the drug was given for three days（<italic>P</italic><0.01）. Total saponin group could enhance IL-4 expression（<italic>P</italic><0.05）and decreased the TGF-<italic>β</italic>₁ expression（<italic>P</italic><0.01）. Compared with normal group， the expression of IL-4 in the model group decreased on the 5th and 8th day of administration （<italic>P</italic><0.01）， and the expression of TGF-<italic>β</italic>₁ in the model group decreased on the 5th day of administration（<italic>P</italic><0.01）. Compared with the model group， the total saponins group could increase the expression of IL-4 and TGF-<italic>β</italic>₁ at 5 d and 8 d after administration （<italic>P</italic><0.01）. Conclusion:Total saponins from Dioscoreae Nipponicae Rhizoma has the potential effect to treat gouty arthritis by regulating M1/M2 polarization.

Formation of neutrophil extracellular traps and their effects on autoimmune diseases / 中国中药杂志

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.

Tracing origin and review of modern research on meridian guide theory of traditional Chinese medicine / 中草药

Meridian guide theory of traditional Chinese medicine (TCM) is an experience summary of pharmacologists in past dynasties, which develops together with the meridian theory, and plays a pivotal role in guiding the rational clinical application. In recent years, many researchers have been devoted to the study of meridian guide theory and have obtained some substantive progress. Based on the idea of tracing origin and seeking innovation, the theoretical origin and modern research are taken as the thread, the emergence is summarized and analyzed; And the construction and application of meridian guide theory, as well as research progress in the past five years are reviewed in this paper, with a view to provide positive help for the standardized use of meridian guide medicine, and also provide reference for the further study of the effect of meridian guide medicine.

Anti-inflammatory Effect of Total Saponin Fraction from Dioscorea nipponica Makino on Gouty Arthritis and Its Influence on NALP3 Inflammasome / 中国结合医学杂志

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 β-galactosidase, β-N acetyl glucosamine enzyme, β-glucuronidase, acid phosphatase, and malonaldehyde as well as the contents of TNF-α, IL-1β 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.

Modulation effect of Acanthopanax senticosus polysaccharides through inflammatory cytokines in protecting immunological liver-injured mice / 中国中药杂志

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-1β) 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-1β 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.

Effect of Crude Epimedii Folium and Processed Epimedii Folium on Kidney Yang Deficiency Edema Model Rats / 中国实验方剂学杂志

Objective: To compare the effects between crude and processed Epimedii Folium on the rats of kidney-Yang deficiency and edema, in order to discuss the mechanism. Method: The rat model of kidney-Yang edema was duplicated with hydrocortisone and doxorubicin hydrochloride. At day 1 and day 8 of modeling, the rats were injected with doxorubicin hydrochloride (3.5 mg·kg-1) via tail vein, while being intraperitoneally injected with hydrocortisone (3.75 mg·kg-1·d-1) for 15 days.After modeling,the rats were divided into model group,crude Epimedii Folium group(204.86 mg·kg-1)and processed Epimedii Folium group(204.86 mg·kg-1), and a normal control group was set up additionally.Rats in each treatment group were given the corresponding drugs,and those in normal and model groups were given the same volume of normal saline by gavage for continuous 14 days.At the end of the administration,24 h urine was measured by rat metabolic cage method; 24 h urinary protein was detected by ultraviolet spectrophotometry; the content of plasma albumin (ALB) and total serum protein (TP) were measured by an automatic biochemical analyzer; and the content of adenosine monophosphate was measured by enzyme-linked immunosorbent assay(ELISA). Cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), triiodothyronine (T3), thyroxine (T4), serum creatinine (SCr), serum urea(BUN), estradiol (E2), testosterone (T) indicator content were determined by enzyme-linked immunosorbent assay(ELISA). Kidney tissues were collected to make pathological section by htoxylin eosin(HE) staining. Result: Compared with the normal group, all the indicators of appearance, biochemistry and pathological section in the model group indicated kidney Yang deficiency edema in the rats (PP2, T indicators to varying degrees(PPP2, T (PPP3, T4 and anal temperature (PPConclusion: Both crude Epimedii Folium group and processed Epimedii Folium group have certain effect in treating kidney Yang deficiency edema, and the possible mechanism is to alleviate glomerular podocyte injury induced by doxorubicin. Their emphasis in the treatment of kidney Yang deficiency edema is different. Crude Epimedii Folium has a cold property, and can treat kidney Yang deficiency edema by strengthening renal excretion function of rats with kidney Yang deficiency edema. Processed Epimedii Folium is processed with sheep oil to produce icariin and other substances, and its property changed from cold to warm, with a focus on alleviating the kidney Yang deficiency status of rats with kidney Yang deficiency edema.

Analysis of Effect of Chaihu Longgu Mulitang on Intestinal Microflora Diversity of Schizophrenic Rats Based on 16S rRNA Technique / 中国实验方剂学杂志

Objective:To explore the effect of Chaihu Longgu Mulitang on intestinal microflora diversity of schizophrenic model rats, and further reveal its therapeutic characteristics and mechanisms based on the 16S rRNA technique. Method:Except the normal group, male SD rats were intraperitoneally injected dizocilpine maleate with daily dose of 0.1 mg·kg-1.After the success of the model, Chaihu Longgu Mulitang high, middle and low dose groups were converted into the human clinical upper limit daily, and the experimental rats were given Chaihu Longgu Mulitang with doses of 11.2, 5.6, 2.8 g·kg-1, respectively. And the positive drug group was treated with 0.4 mg·kg-1 of risperidone tablets.The normal group and model group was treated with water.The rats were continuous administrated 14 days with dosing volume of 10 mL·kg-1, the contents in caecum of rats were taken after anesthesia.Illumina MiSeq was used as the sequencing platform, the number of operational taxonomic units(OTUs), richness and diversity indexes, diversity of alpha and beta, differential phylum and genus of intestinal flora in V4 zone of 16S rRNA were comprehensively analyzed and evaluated. Result:Chaihu Longgu Mulitang could improve the number of OTUs, richness and diversity indexes of intestinal flora, imbalance of alpha and beta diversity of schizophrenic model rats.And this formula had a callback effect on 5 differential phyla of bacteria(Bacteroidetes, Acidobacteria, Proteobacteria, Firmicutes and TM7) and 20 genera of bacteria in schizophrenic model rats. Conclusion:Chaihu Longgu Mulitang plays an therapeutic effect on diversity of abnormal microflora in schizophrenic model rats, and this paper reveals the pathological mechanism of intestinal microflora in the state of schizophrenia by 16S rRNA technique.

Intestinal Microflora Diversity of Rats Treated with Scutellariae Radix Based on Theory of “Insight into Abdomen” / 中国实验方剂学杂志

Objective: To explore the effect of Scutellariae Radix on the diversity of intestinal flora in rats under physiological conditions, in order to determine the property of Scutellariae Radix property. Method: 16S rRNA high-throughput gene sequencing technique was used to detect the cecum solutes of rats treated with Scutellariae Radix (10 g·kg-1). The number, richness and diversity index of the intestinal flora taxon (OTUs) and the differential phylum and genus were comprehensively analyzed. The network visualization was used to find the correlation between differential phylum and genus. Result: Based on the Illumina Miseq platform, compared with the blank group, the number of OTUs and the index of richness and diversity of the intestinal flora of the rats treated with Scutellariae Radix decreased. Bacteroidetes and Spirochaetes were significantly up-regulated(PPPPPRuminococcus, Paraprevotella, Prevotella and Oscillospira. Conclusion: Scutellariae Radix can reduce the diversity of intestinal flora and inhibit the metabolism of the body, so its property is cold.

Study on Radix Scrophulariae for the treatment of hyperthyroidism rat model of yin deficiency based on urine metabonomics / 药学学报

The Chinese herbal Radix Scrophulariae is the main medicine for nourishing yin and reducing fire. It can be used to treat hyperthyroidism due to yin deficiency and fire hyperactivity, but its mechanism is not clear. The present study was aimed to explore the mechanism of Radix Scrophulariae treatment of hyperthyroidism due to yin deficiency and fire hyperactivity. The urine metabolomic approach was conducted using the method of UPLC-TOF-MS. The results showed that Radix Scrophulariae has good therapeutic effects on hyperthyroidism rat model of yin deficiency. After treatment with Radix Scrophulariae, through metabolic profiling and protocol analysis, 6 potential metabolic markers may be closely related with the treatment mechanism of Radix Scrophulariae on this disease, including proline betaine, estrone, thymidine, 5-hydroxyindoleacetic acid, cyclic AMP and L-dopa. The strongest metabolic pathways were associated with tryptophan metabolism, pyrimidine metabolism, tyrosine metabolism, purine metabolism and steroid hormone biosynthesis. The urine metabolomic approach can be applied to clarify the therapeutic mechanism of Radix Scrophulariae on hyperthyroidism rat of yin deficiency, and provide the theoretical basis for the clinical practice of Radix Scrophulariae on nourishing yin to reduce pathogenic fire.

Inhibitory effect of Scutellariae Radix on hepatic fibrosis based on urinary metabonomic / 中国中药杂志

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.

Acanthopanax senticosus Protects Structure and Function of Mesencephalic Mitochondria in A Mouse Model of Parkinson's Disease / 中国结合医学杂志

<p><b>OBJECTIVE</b>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).</p><p><b>METHODS</b>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).</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Liver metabonomics of acute gouty arthritis treated by Diosocorea nipponica / 中国中药杂志

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.

Intervention of Epimedium 95％ethanol elution section in potential biomarkers in urine of rats based on metabonomics / 中国药理学与毒理学杂志

OBJECTIVE To observe the effect of Epimedium 95％ethanol elution section (E95EE) on endogenous metabolism in the urine of normal rats using methods of metabonomics, and to study whether differential expressions of biomarkers can influence different systems of the body along with various body-fluids-cycle distribution. METHODS SD rats were randomly divided into blank control group and E95EE group(10 rats per group). The rats of E95EE group were ig administered with E95EE 17.1 g · L-1, once daily, for 20 d, while those of normal control group were ig given an equal volume of saline. On the day of the final E95EE administration, the urine of 12 h was collected for analysis by UPLC-TOF/MS. RESULTS This study identified nine differential endogenous metabolites (3-sn-phos-phatidate, 5, 10-methenyltetrahydrofolate, l-1-phosphatidylethanolamine, 1-acyl-glycerone 3-phosphate, N-formimidoyl-l-glutamate, keto-oxaloacetate, sulfurous acid, formyl-N-acetyl-5-methoxykynurenamin and N-acetyl-5-hydroxytryptamine) and six primary metabolic pathways [glycerophospholipid metabolism, vitamin A (retinol) metabolism, histidine degradation, tryptophan metabolism, acetyl-CoA biosynthesis from citrate, glycolysis and gluconeogenesis]. The possible role of protection of E95EE discovered in the nervous and cardiovascular systems was displayed by the decreased level of 3-sn-phosphatidate and an increased level of N-formimidoyl-l-glutamate. However, the possible toxicity of E95EE on neoplastic prevention was achieved by reducing the level of l-1-phosphatidylethanolamine and 5,10-methenyl tetra-hydrofolate. CONCLUSION E95EE can produce both protection and toxicity on nervous, cardiovascular and immune systems, as well as on tumor-associated diseases. The mechanisms may be related to metabolic pathways of triglycerides, vitamin A, tryptophane and histidines.

Inhibitory effects of tamoxifen on thyroid papillary carcinoma / 中国现代普通外科进展

Objective:To explore the effects of tamoxifen on proliferation,migration and invasion of human thyroid papillary carcinoma BCPAP cells.Methods:Human thyroid papillary carcinoma BCPAP cells were treated with various concentrations of tamoxifen for 24 hours,respectively,CCK8 assay was used to detect the change of proliferation level;It can be divided into four groups:negative group,10 μmol/L TAM group and 20 μmol/L TAM group.Wound healing test was used to detect the change of migration ability and Transwell assay was used to detect the change of invasion ability.The protein levels of bcl-2 and C-myc in the BCPAP cells treated with various concentrations of tamoxifen were detected by Western blot.Results:CCK8 assay,wound healing test and Transwell assay showed that tamoxifen had induced a dose-dependent decrease in the proliferation,migration and invasion of human thyroid papillary carcinoma BCPAP cells.Furthermore,western blot demonstrated that the tamoxifen decreased the expression of bcl-2 and C-myc in BAPAP cells.Conclusions Tamoxifen can inhibit proliferation,migration and invasion of human thyroid papillary carcinoma BCPAP cells.We speculated that the inhibition of proliferation maybe related to down-regulation of bcl-2 and C-myc expression.

Effect of Baichanting Compound on Dopamine Contents in Parkinson's Disease Model Mice / 中国中西医结合杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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).</p><p><b>CONCLUSION</b>BC could increase DA content in PD model mice with the optimal proportion as 54.00: 44.88: 82.50.</p>

Advance in treatment of hyperuricemia by Chinese medicine based on uric acid transporterome / 中国中药杂志

With the development of the quality of life, the morbidity of hyperuricemia is increasing year by year. At the same time, it appears that this disease attacks the young people currently. As the study of pathogenesis of hyperuricemia advanced, a series of uric acid transporters were found during this process. Meanwhile, the definition of transporterome was proposed. They were divided into three groups according to the functions: reabsorption proteins, excretion proteins and skeleton proteins. At moment, the drugs for hyperuricmia mainly include uric acid composition inhibitors and uric acid excretion promoters. Since the excretion of uric acid plays a leading role during the process of attack of hyperurecimia, it makes sense to explore Chinese medicines with clear mechanism targeting the transporterome. Therefore, this paper would focus on transporterome and summarize the mechanisms of Chinese medicines in treating hyperuricemia.