Abstract：Objective:To investigate the effect of alcohol extract of Magnoliae Officinalis Cortex, alcohol extract of Polygalae Radix and their compatibility on fecal metabolites of rats, analyze its potential metabolic pathways, and provide experimental basis for exploring the possible mechanism of Magnoliae Officinalis Cortex relieving gastrointestinal motility disorders induced by Polygalae Radix.Method:Forty male SD rats were randomly divided into the normal group, alcohol extract of Magnoliae Officinalis Cortex group(3.50 g·kg-1), alcohol extract of Polygalae Radix group(1.75 g·kg-1) and compatibility group (3.5 g·kg-1 of alcohol extract of Magnoliae Officinalis Cortex+ 1.75 g·kg-1 of alcohol extract of Polygalae Radix). Fecal samples were collected within 24 h after continuous gavage for 3 days.The fecal metabolites in each group was detected by ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometry(UPLC-Q-TOF-MS), mobile phase was acetonitrile-0.1%formic acid solution for gradient elution, data collection range was m/z 50-1 200 under positive and negative ion mode of electrospray ionization.The characteristic biomarkers and corresponding metabolic pathways were analyzed or screened by Progenesis QI v2.0, SIMCA-P 14.0, SPSS 20.0, MetaboAnalyst 4.0 and other softwares.Result:A total of 17 characteristic metabolic markers were screened out, including 5-formiminotetrahydrofolic acid, L-3-hydroxykynurenine, 7, 8-dihydropteroic acid, etc.The main related pathways included biosynthesis of unsaturated fatty acids, linoleic acid metabolism, vitamin B6 metabolism, etc.Conclusion:The mechanism of Magnoliae Officinalis Cortex relieving gastrointestinal motility disorders induced by Polygalae Radix may be related to purine metabolism, folate biosynthesis, tryptophan metabolism and primary bile acid biosynthesis.
Keywords：Magnoliae Officinalis Cortex;Polygalae Radix;compatibility;feces;metabolic markers;tryptophan metabolism;primary bile acids
Abstract：Objective:To investigate the regulatory effect of Sijunzi Tang(SJZT) and its single herbs(Ginseng Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma Praeparata cum Melle, Atractylodis Macrocephalae Rhizoma and Poria) on intestinal flora in spleen-deficient rats.Method:Normal rats were randomly divided into the blank group, model group, Zhengchangsheng granules group, SJZT group and each single herb group, rats were orally administered Sennae Folium decoction to induce diarrhea for ten consecutive days to establish a spleen-deficient model(distilled water for the blank group), then treated with the corresponding drugs for seven consecutive days(distilled water for the blank group and the model group). Fresh feces were collected on pre-modeling(0th day), post-modeling(11th day), and post-treatment(18th day). Short-chain fatty acids(SCFAs) in feces were acidified by sulphuric acid and extracted by diethyl ether, then determined by gas chromatography. The structural change(diversity and similarity) of intestinal flora in feces was analyzed by 16S rDNA-polymerase chain reaction(PCR)-denaturing gel gradient electrophoresis(DGGE) technique.Result:Compared with blank group, the contents of SCFAs as well as diversity and similarity indexes of intestinal flora in feces of all administered groups were significantly decreased on the 11th day(P<0.05, P<0.01), this indicated that the spleen-deficient model was successfully constructed. On the 18th day, compared with model group, the contents of SCFAs as well as diversity and similarity indexes of intestinal flora in feces of Atractylodis Macrocephalae Rhizoma group were significantly increased(P<0.01), these indexes in feces of SJZT group, Ginseng Radix et Rhizoma group and Poria group were significantly increased(P<0.05, P<0.01), while Glycyrrhizae Radix et Rhizoma Praeparata cum Melle group only increased diversity index of intestinal flora(P<0.05).Conclusion:Ginseng Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma and Poria are the single herbs responsible for the regulatory effect of SJZT on intestinal flora in spleen-deficient rats, and Atractylodis Macrocephalae Rhizoma may play a major role.
Abstract：Objective:To investigate the effect of Buyang Huanwu Tang in resisting lipopolysaccharide (LPS)-induced macrophage activation and autophagy through phosphatidylinositol 3-kinase/protein kinase B/mammalian rapamycin target protein (PI3K/Akt/mTOR) signaling pathway.Method:The cell counting kit-8 (CCK-8) method was used to screen out the optimal LPS concentration for inducing the activity of RAW264.7 macrophages. RAW264.7 macrophages were treated separately with PI3K blocker 3-methyladenine(3-MA) (5 mmol·L-1), Akt blocker MK2206 (5 μmol·L-1), mTOR blocker Rapamycin (10 μmol·L-1), Beclin1 blocker Spautin-1 (5 μmol·L-1), different doses of Buyang Huanwu Tang serum (5%, 10%, 20%) and the optimum concentration of LPS for 24 h. The concentrations of inflammatory factors interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in RAW264.7 macrophages were detected by enzyme-lined immunosorbent assay(ELISA). Western blot was used to detect the expression levels of phosphorylated PI3K, phosphorylated Akt, phosphorylated mTOR protein, microtubule light chain protein 3 (LC3), ubiquitin-binding protein 1 (p62) and Beclin-1. The autophagy flow of RAW264.7 cells was detected by transfection with autophagy double-labeled adenovirus.Result:Results of CCK-8 showed the highest cell viability when 10 mg·L-1 LPS was applied. The concentrations of IL-1β, IL-6 and TNF-α in the model group were significantly higher than those in the blank group (P<0.01). Compared with the model group, Rapamycin significantly increased IL-6 concentration (P<0.05), and other administration groups could decrease the levels of IL-1β, IL-6 and TNF-α (P<0.05, P<0.01). The expression levels of p-Akt, p-PI3K and p-mTOR in the model group were significantly lower (P<0.05), and LC3 and p62 protein expressions were significantly higher than those in the blank group (P<0.01). Compared with the model group, Rapamycin significantly decreased the expression of p-Akt protein, with no impact on the expressions of p-mTOR. However, Buyang Huanwu Tang and other blockers significantly increased p-Akt, p-PI3K and p-mTOR (P<0.05, P<0.01), while decreased the protein expressions of LC3 and p62 (P<0.05, P<0.01). There was no significant difference in the expression level of Beclin-1 protein in each group. Compared with the blank group, there were obvious autophagosome spots in the model group, and the autophagic flow was smooth. Compared with the model group, the formation of autophagic spots in 3-MA, Spautin-1 group and Buyang Huanwu Tang groups were significantly decreased or disappeared, and the size of autophagosome spots in MK2206 and Rapamycin groups was significantly reduced, but the autophagy activity was still strong.Conclusion:Buyang Huanwu Tang can resist LPS-induced macrophages activation and autophagy, inhibit macrophage inflammatory response, regulate PI3K/Akt/mTOR signaling pathway, and inhibit the excessive occurrence of autophagy.
Abstract：Objective:To observe the effect of Simiao Yongan Tang on the pathologic morphology of atherosclerosis (AS) vulnerable plaque and the permeability of vasa vasorum (VV), and to explore its intervention mechanism with VV as the target.Method:Healthy male ApoE-/-mice were randomly divided into model group, Simiao Yongan Tang group(11.7 mg·kg-1·d-1)and simvastatin group(2.6 mg·kg-1·d-1). High-fat diet supplemented with 1.1% L-methionine was given to induce the animal model, while C57BL/6 mice were used as the control group. The model was evaluated after 8 weeks of feeding. After successful modeling, continued drug intervention was given for 8 weeks, and the pathological changes of the mouse aorta were observed by oil red O staining. The expression levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) proteins in the outer membrane of aortic root plaques were observed by immunohistochemical staining.Result:The results of oil red O staining showed that as compared with the control group, the plaque area of the aortic wall was significantly increased in the model group (P<0.01). As compared with the model group, the plaque area of the aorta was significantly decreased in the simvastatin group (P<0.01), end the area of plaque in the aortic wall was reduced in Simiao Yongan Tang group (P<0.05). The results of immunohistochemical staining showed that as compared with the normal control group, the positive expression of MMP-9 in the aortic adventitia was significantly increased in the model group (P<0.01). As compared with the model group, the positive expression of MMP-9 was significantly decreased in simvastatin group and Simiao Yongan Tang group(P<0.01). As compared with the simvastatin group, the positive expression of MMP-9 was significantly decreased in Simiao Yongan Tang group (P<0.01).Conclusion:Simiao Yongan Tang can reduce the area of mouse aortic plaque, reduce the VV permeability of the outer plaque by regulating the expression of MMP-9 and TIMP-1, and stabilize the vulnerable plaque.
Abstract：Objective:To investigate the effect of Gancao Fuzitang on the proliferation of fibroblast-like synoviocytes (FLS) in synovial tissue of mice with adjuvant-induced arthritis (AA).Method:The 48 male Balb/c mice were randomly divided into 4 groups: normal control group, model group(arthritis induced through injection with adjuvant), Gancao Fuzitang group and triptolide group. The normal control group and the model control group were orally given physiological saline. After the successful modeling, the mice of the other two groups were treated with Gancao Fuzitang or triptolide orally for 18 days. Then the animals were euthanized, the paw edema of the animals was measured, and arthritic ankles were observed by histological examination. Tumor necrosis factor (TNF)-α was examined by immunoassays. The proliferation of synovial cells of foot joints was detected by immunohistochemical expressions of Vimentin. The expressions of Cyclin D1, proliferating cell nuclear antigen (PCNA), p53 and p21 were detected by Western blot.Result:Compared with the normal control group, the mice of synovial hyperplasia and bone erosion in model group were obvious. The joint swelling degree, TNF-α level and proliferation of FLS were increased (P<0.05). The expressions of Cyclin D1, PCNA were up-regulated(P<0.05), but the expressions of p53 and p21 were down-regulated(P<0.05). Compared with the model group, Gancao Fuzitang significantly alleviated joint swelling and injuries, reduced the level of TNF-α, cell cycles (Cyclin D1 and PCNA), and increased protein expressions of p53 and p21 (P<0.05).Conclusion:Gancao Fuzitang has a therapeutic effect on AA mice, and the mechanism might be associated with its anti-inflammatory effect and the effects in regulating Cyclin D1, PCNA, p53 and p21 expressions and inhibiting FLS proliferation.
Abstract：Rhei Radix et Rhizoma is a common medicine in clinic, which is widely used for a variety of diseases, such as constipation, jaundice, peptic ulcer, bacillary dysentery. In recent years, there have been many cases of clinical abuse and increasing number of adverse reactions about Rhei Radix et Rhizoma. Many reports concerned with its toxicity have drawn more and more attention at home and abroad. This review makes a brief summary on the toxicity research of Rhei Radix et Rhizoma in recent years in the aspects of hepatotoxicity, nephrotoxicity and its corresponding toxicity-controlling methods. Liver and kidney toxicity of Rhei Radix et Rhizoma was explained in various aspects, including liver and kidney biochemical indicators, apoptosis, mitochondrial function, gene and protein expression and signaling pathway. Besides, the attenuation methods of Rhei Radix et Rhizoma were summarized in aspects of processing and compatibility of traditional Chinese medicine. In conclusion, this study explains hepatotoxicity and nephrotoxicity of Rhei Radix et Rhizoma objectively, and explore relevant toxicological mechanisms, in order to provide proper reference for its further research and the safety of clinical use.
Keywords：Rhei Radix et Rhizoma;hepatotoxicity;nephrotoxicity;attenuation
Abstract：Objective:To observe the effect of long-term administration of emodin on the kidney toxicity of mice, explore its possible toxic mechanism, and provide some basis for clinical rational drug use and further research.Method:The 30 Kunming mice, half male and half female, were randomly divided into 3 groups: control group, emodin low dose group and emodin high dose groups (0.8, 1.6 g·kg-1), 10 mice in each group. Continuous intragastric administration was given for 11 weeks. During administration, the general situation of the mice was observed and recorded. After treatment, the serum urea nitrogen (BUN), creatinine (SCr), malondialdehyde (MDA), superoxide dismutase (SOD) tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) were detected. Kidney index was calculated and glutathione peroxidase (GSH-Px) and reduced glutathione/oxidized glutathione (GSH/GSSG) ratio were measured. The kidneys were taken for histopathological examination and the protein expression levels of transforming growth factor-β1(TGF-β1) and cysteine aspartic acid specific protease-3 (Caspase-3) were then detected by immunohistochemistry assay.Result:As compared with control group of the same sex, the weight of mice in the administration groups was decreased significantly, renal index was decreased while BUN and SCr levels were increased significantly (P<0.05, P<0.01); activity of SOD was decreased significantly (P<0.05, P<0.01); content of TNF-α was increased significantly (P<0.05, P <0.01), while the content of GSH-Px and the ratio of GSH/GSSG were decreased significantly in high emodin group(P<0.05), and the expression of Caspase-3 was increased significantly in high emodin group (P<0.05). Renal histopathology: tubule epithelial cells swelling, tubulointerstitial protein tube type, hyperemia and lymphocytic small focal hyperplasia were observed in emodin high dose group, but the performance above was not obvious in low dose group.Conclusion:The long-term administration of emodin at a large dose would show toxicity effect on mice kidney, and the toxicity was obvious at the dose of 1.6 g·kg-1·d-1, but there was no significant difference between the sexes. The mechanism of its potential toxicity may be related to the disorder of oxidation system, the injury of oxidative stress, the triggering of inflammatory reaction, and the apoptosis of cells.
Abstract：Objective:To study nephrotoxicity induced by long-term administration of different doses of aloe-emodin in mice, and explore its mechanism.Method:A total of 30 male and female Kunming mice were randomly divided into normal control group, and low-dose aloe-emodin group, high-dose aloe-emodin group (0.8, 1.6 g·kg-1). Every dose of group was administered intragastrically for 11 weeks, twice daily. effect of serum urea nitrogen (BUN), creatinine (SCr), superoxide dismutase (SOD), malondialdehyde (MDA), Glutathione (GSH/GSSG) and Glutathione Peroxidase (GSH-Px) levels were detected by biochemical kits according to manufacturer's instruction. Enzyme-linked immune assay was used to determine serum tumor necrosis factor (TNF)-α and interleukins(IL)-6 levels. Hematoxylin eosin(HE) staining was used to detect renal pathological changes in kidney tissues, and cysteine aspartic acid specific protease(Caspase)-3 and transforming growth factor(TGF)-β1 proteins were determined by immunohistochemistry.Result:According to results, compared with normal control group, the levels of BUN and SCr in serum with high-dose aloe-emodin were increased. The renal tubules in low-dose group were mildly injured, while renal tubules and glomeruli of high-dose group were moderately damaged. Compared with normal control group, the level of SOD was significant decreased (P<0.05), MDA was increased (P<0.05), the levels of GSH/GSSG in kidneys of high-dose groups were decreased (P<0.05). In high-dose group, the expression of Caspase-3 protein was increased in kidneys, especially in males (P<0.05). Compared with normal control group, the levels of TNF-α and IL-6 were increased, the expression of TGF-β1 protein in kidneys was increased in low-dose and high-dose groups (P<0.05).Conclusion:results show that 1.6 g·kg-1 aloe-emodin was administered intragastrically for 11 weeks, which had toxic effects on kidney in mice. The mechanism may be related to oxidative stress, apoptosis and TGF-β1 protein expression.
Abstract：Objective:To observe effect of long-term administration of rhein on the kidney toxicity of mice, and explore its possible toxic mechanism, in order to provide some basis for rational clinical drug use and further research.Method:The 30 Kunming mice (half male and half female) were randomly divided into 3 groups: control group, low-dose rhein group and high-dose rhein group (0.175, 0.35 g·kg-1), with 10 mice in each group. The intragastric administration lasted for 60 days. During administration, general situations of the mice were observed and recorded. Serum urea nitrogen (BUN), creatinine (SCr), malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were detected after drug withdrawal. Kidney index was calculated, and glutathione peroxidase (GSH-Px) and reduced glutathione/oxidized glutathione (GSH/GSSG) ratio were measured. The kidneys were collected and histopathologically examined, and the protein expressions of transforming growth factor beta (TGF-β1) and cysteine aspartic acid specific protease-3 (Caspase-3) were detected by immunohistochemistry.Result:Compared with the control group of the same sex, BUN and SCr of the administration group increased significantly(P<0.05, P<0.01). In the high-dose group, the activity of SOD decreased significantly(P<0.05, P<0.01), while the expressions of TNF-α and Caspase-3 increased significantly(P<0.05). In the male group, the renal index was significantly decreased(P<0.05, P<0.01), the GSH-Px content in the male high-dose group was significantly decreased(P<0.05), whereas the expression of TGF-β1 was increased(P<0.05). The histopathological changes of kidney were observed by hematoxylin-eosin (HE) staining. In the high-dose group, protein tubules were found in renal tubule lumen, glomerular and interstitial capillary congestion, tubule epithelial cell swelling and small focal proliferation of lymphocytes, and the pathological changes were more serious in male mice. The above performances in the low-dose group was less significant than those in the high-dose group.Conclusion:The toxicity of rhein in the kidney of mice was obvious at the dose of 0.35 g·kg-1·d-1, and the toxicity in male organism is more obvious. The mechanism of its potential toxicity may cause the imbalance of glutathione antioxidant system, induce excessive oxidation, trigger inflammatory reaction, activate the expression of Caspase-3, and then induce apoptosis.
Abstract：Objective:To observe the effect of combination of Tanreqing injection(Tanreqing) and imipenem-cilastatin on extensively-drug resistant Pseudomonas aeruginosa (XDPA), and study the mechanism of the combination.Method:The minimum inhibitory concentrations (MICs) of Tanreqing and imipenem-cilastatin against planktonic XDPA strain isolated in clinic were determined by the broth microdilution method. The checkerboard method was used to evaluate the combination effect. The bacterial metabolic activity in mature biofilm was studied by microtiter-plate test. The destructive effect of combination drugs on dynamic biofilm was observed by using BioFlux system, and viable cells were examined by confocal laser scanning microscope (CLSM) after treatment. The scanning electron microscopy (SEM) was used for observing Pseudomonas aeruginosa and length measurement.Result:The MIC values of imipenem-cilastatin and Tanreqing were 512 mg·L-1 and more than 16 500 mg·L-1. The checkerboard analysis showed that Tanreqing could enhance the sensitivity of imipenem-cilastatin, while the combination drugs synergistically inhibited the growth of bacteria. Compared with the control group or the imipenem-cilastatin individual group, the combined drugs significantly reduced the amount of living bacteria in the biofilm (P<0.05, P<0.01). BioFlux results showed that the combination drugs destructed the biofilm structure and reduced the area coverage (P<0.05) by comparing with the control group or the single drug group. The results of fluorescent staining showed that the combination drug significantly inhibited the metabolic activity of bacteria in dynamic biofilm. Tanreqing inhibited bacterial division to achieve the antibacterial effect.Conclusion:Tanreqing and imipenem-cilastatin synergistically inhibit the bacterial growth in planktonic and biofilm states, and destruct biofilms.
Abstract：Objective:To study the protective effect of tetramethylpyrazine (TMP) on PC12 cells induced by tert-butyl hydroperoxide (t-BHP) and the regulatory mechanism on signaling pathway of phosphatidylinositol-3-kinases (PI3K)/kinase B (Akt)/mammalian target of rapamycin(mTOR).Method:PC12 cells cultured in vitro were treated with t-BHP (200 μmol·L-1) for 6 h to establish a model of oxidative damage in PC12 cells. The experiment was divided into blank group, model group (200 μmol·L-1t-BHP), TMP group. PC12 cells were pretreated with TMP(25, 50, 100 μmol·L-1) for 12 h, and then treated with t-BHP for 6 h. The cell viability was detected by cell counting kit-8(CCK-8) method, and lactate dehydrogenase (LDH) leakage, malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, reactive oxygen species (ROS) and glutathione peroxidase (GSH-Px) activity were detected by enzyme-linked immunosorbent assay (ELISA). Apoptosis was observed by annexin V-FITC/PI double staining. B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), total protein kinase B (Akt), and phosphorylated protein kinase B (p-Akt), mTOR and p-mTOR expressions were detected by Western blot.Result:The cell viability of PC12 cells treated with 200 μmol·L-1 t-BHP decreased to about 50%after 6 h. This condition was suitable for the establishment of oxidative damage model. Compared with the model group, TMP (25, 50, 100 μmol·L-1) pretreatment for 12 h significantly increased the survival rate of PC12 cells (P<0.05, P<0.01), decreased the release of LDH and MDA (P<0.05, P<0.01), significantly reduced the ROS content in PC12 cells (P<0.01), significantly increased the activity of SOD, GSH-Px (P<0.05, P<0.01), and inhibited the cell apoptosis. Western blot showed that compared with the model group, the protein expressions of p-Akt and p-mTOR in TMP (50 μmol·L-1) pretreatment group increased significantly (P<0.01), and the Bcl-2/Bax ratio increased significantly. Treatment with LY294002 (PI3K protein inhibitor) also attenuated these changes.Conclusion:Ligustrazine protects PC12 cell injury induced by t-BHP by activating PI3K/Akt/mTOR signaling pathway.
Keywords：tetramethylpyrazine;neuroprotection;PC12 cell;tert-buty hydroperoxide(t-BHP);phosphatidylinositol-3-kinases (PI3K)/kinase B (Akt)/mammalian target of rapamycin(mTOR)
Abstract：Objective:Compare the effects of 3 administration methods (tracheal perfusion, tail vein injection and aerosol inhalation) with bleomycin (BLM) in inducing pulmonary fibrosis in rats, in order to find out the optimal administration methods.Method:Eighty sprague-dawley (SD) male rats with SPF were randomly divided into aerosol inhalation blank group, single tracheal perfusion group(10 mg·kg-1), multiple tracheal perfusion group(5 mg·kg-1), single intravenous injection group(150 mg·kg-1), multiple intravenous injection group(50 mg·kg-1), single aerosol inhalation group (30 min)and multiple aerosol inhalation group(30 min). The mortality and body weight of rats in each group were observed at 7 d, 14 d and 28 d after the administration. And 28 days later after the administration, the lung coefficients of rats in each group were observed, paraffin sections were prepared, hematoxylin-eosin staining (HE) and Masson staining were performed, and the contents of hydroxyproline (HYP) and plasminogen activator inhibitor-1 (PAI-1) in lung tissues were detected by enzyme-linked immunosorbent assay (ELISA), so as to evaluate the alveoli inflammation and pulmonary fibrosis of rats in each group.Result:Compared with the aerosol inhalation blank group, the rats in the trachea perfusion group had the highest mortality among the drug treatment groups. The pulmonary coefficients of rats in the multiple intravenous injection group and the multiple inhalation group were significantly higher than those in the blank group(P<0.05, P<0.01). The multiple inhalation group was higher than the other model group and the single atomization model group. The results of HE and Masson staining showed thickening of pulmonary septum and higher degree of pulmonary interstitial fibrosis in tracheal perfusion group, intravenous injection group and multiple inhalation group. The degree of pulmonary fibrosis in the multiple inhalation group was more obvious than that in other groups. The results of ELISA showed that the levels of HYP and PAI-1 in lung tissues of rats in aerosol inhalation group and tracheal perfusion group were significantly higher than those in control group(P<0.05). The multiple inhalation group and the single atomization inhalation group were significantly higher than other modules.Conclusion:Bleomycin was inhaled repeatedly to establish pulmonary fibrosis model. The pathological injury and physiological indexes of the model rats were relatively stable, which conforms with the evolution process of pulmonary fibrosis.
Abstract：Objective:To observe the effect of Changji′an prescription on intestinal permeability in diarrhea-predominant irritable bowel syndrome (IBS-D) rats and explore its mechanism for treatment of IBS-D.Method:Male SD neonatal rats were randomly divided into five groups: normal group, model group, pinaverium bromide group(0.018 g·kg-1), high-dose(33.48 g·kg-1) and low-dose (16.74 g·kg-1)Changji′an prescription groups. Except for the normal group, the IBS-D model was established by the combination of maternal and infant separation+ acetic acid stimulation+ restraint stress. After drug treatment, the ultrastructure of rat intestinal mucosa was observed by using transmission electron microscopy and the plasma D-lactate level was detected by enzyme-linked immunosorbent assay (ELISA). The expression levels of tight junction proteins Occludin and Claudin-1 were detected by Western blot. The mRNA expression levels of Occludin, Claudin-1 and zonula occluden(ZO)-1 were detected by real time polymerase chain reaction (Real-time PCR).Result:As compared with the normal group, the intestinal mucosal epithelial cells were damaged in IBS-D model group, and the microvilli arrangement was sparse and tight junction was widened, and some were not obvious, and the plasma D-lactate level in IBS-D rats was increased significantly (P<0.05), and the mRNA and protein expression levels of Occludin and Claudin-1 in the colon were decreased and the mRNA expression of ZO-1 was also decreased (P<0.05). After drug treatment, as compared with the model group, all drug-administered groups can repair intestinal mucosal cell damage. Plasma D-lactate level in pinaverium bromide group and high-dose Changji′an prescription group was significantly decreased (P<0.05) while D-lactate level in the low-dose group Changji′an prescription group had a tendency to decrease with no statistical difference. The mRNA and protein expression levels of Occludin and Claudin-1 and the mRNA expression of ZO-1 in the colon of rats in each administration group were higher than those in the model group (P<0.05).Conclusion:The therapeutic effect of Changji′an prescription on IBS-D may be achieved by improving the intestinal permeability.
Abstract：Objective:To compare the contents of alkaloids from fine and ultrafine powder of Dendrobium nobile stem in rat plasma, and investigate the effect of D. nobile stem with different particle sizes on gene expression of intestinal transporters.Method:Rats were randomly divided into the blank group, fine powder group of D. nobile stem(0.25 g·kg-1) and ultrafine powder group of D. nobile stem(0.25 g·kg-1). The rats were gavaged every 6 h for 5 days.The samples of rat plasma and small intestine were collected.The plasma samples were detected with UPLC-MS.The chromatography separation was performed on a Hypersil Gold C18 column(2.1 mm×150 mm, 1.9 μm) with acetonitrile-0.1%formic acid solution as mobile phase for gradient elution.Electrospray ionization (ESI) was applied and operated in positive ion mode.The mRNA expression of multidrug resistance protein 1(MDR1), oligopeptide transporter protein 1(PEPT1), organic cation transporter protein 2(OCT2), breast cancer resistance protein 1(BCRP1), monocarboxylate transport protein 1(MCT1) and multidrug resistance related protein 2(MRP2) in small intestine were quantified by real time fluorescence quantitative polymerase chain reaction.Result:After intragastric administration of fine and ultrafine powder of D. nobile stem, dendrobine, mubironine B and dendramine could be detected in rat plasma.The contents of dendrobine and dendramine in the ultrafine powder group were significantly higher than that in the fine powder group(P<0.05). Compared with the blank group, gene expression of BCRP1 was significantly inhibited by fine and ultrafine powder of D. nobile stem(P<0.05), and the expression in the ultrafine powder group was lower than that in the fine powder group(P<0.05). The gene expression of MDR1 was up-regulated by fine powder of D. nobile stem(P<0.05).Conclusion:Compared with the fine powder group of D. nobile stem, the plasma concentrations of dendrobine and dendramine in the ultrafine powder group are significantly increased, it may be related to the intestinal transporters of MDR1 and BCRP1.These results can provide experimental basis for selecting particle size of D. nobile stem.
Keywords：Dendrobium nobile stem;fine powder;ultrafine powder;intestinal transporters;alkaloids;multidrug resistance protein;breast cancer resistance protein
Abstract：Objective:To observe the efficacy of Duhuo Xuduan Tang in treating patients with liver and kidney Yin-deficiency type of lumbar disc herniation, and explore the changes of metabolomics in serum.Method:Totally 68 cases of non-emergency lumbar disc herniation admitted to the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from January 2017 to September 2018 were randomly divided into observation group (38 cases) and routine group (30 cases). All of patients in both groups rest in bed after reduction maneuver. The observation group was orally treated with Duhuo Xuduan Tang, 150 mL/time, 2 times/d, and the control group was orally given ibuprofen, 300 mg/time, and vitamin B1, 10 mg/time, 2 times/d. The drugs were administered for 5 days a week and then stopped for 2 days. Both groups were treated continuously for 4 weeks. Before and after treatment, the visual analogue scale (VAS), the Japanese Orthopaedic Association assessment treatment (JOA) score and the clinical efficacy were observed. The serum metabolomics changes of two groups before and after treatment were compared by ultra-high liquid chromatography-mass spectrometry.Result:Compared with before treatment, the VAS scores of two groups were lower, while the JOA scores were increased (P<0.01). Compared with the routine group after treatment, the clinical efficacy of observation group was significantly improved (P<0.01), and the VAS score decreased and the JOA score increased (P<0.01). The contents of citric acid, lysine, pyruvic acid and β-cryptoxanthin in serum were increased (P<0.01).Conclusion:Duhuo Xuduan Tang has a clear curative effect in treating lumbar disc herniation with liver and kidney Yin deficiency. The mechanism may be related to the enhancement of energy metabolism, anti-oxidation and anti-inflammation.
Abstract：Objective:To explore the clinical efficacy of Yangjing Zhongyu Tang in treating kidney-Yin deficiency due to repeated implantation failure (RIF).Method:Totally 70 patients with kidney yin deficiency due to repeated implantation failure (RIF) who received the periodic Frozen thawed embyo (FET) after in vitro fertilization (IVF) embryo cryopreservation were selected from the Integrative Medicine Reproductive and Genetics Center of Affiliated Hospital of Shandong University of Traditional Chinese Medicine(TCM). They were randomly divided into observation group and control group, with 35 cases in each group. All patients were received long protocol controlled ovarian hyperstimulation. Observation group was given Yangjing Zhongyu Tang from the 5th day to the 14th day of the menstrual cycle 1 month before transplantation, and continued to take it on the 5th day of the menstrual cycle in the month of the transplantation. Control group did not given TCM. After treatment, TCM syndrome scores, endometrial thickness, typing, uterine artery pulsation index (PI) and resistance index (RI) of HCG, endometrial secretion leukemia inhibitory factor (LIF), blood vessels endothelial growth factor (VEGF), interleukin-1β (IL-1β) and monocyte chemoattractant protein-1 (MCP-1), number of eggs obtained, fertilization rate and embryo transfer results were observed.Result:After treatment, the scores of TCM syndromes in observation group were significantly improved, with statistically significant difference (P<0.05). There was no significant difference in endometrial thickness between two groups after treatment. The type of endometrium in observation group was significantly higher than that of control group (P<0.05). There was no significant difference in PI between two groups. The RI value of observation group was significantly lower than that of control group (P<0.05). VEGF, IL-1β and LIF of observation group were higher than those of control group, and the MCP-1 was lower than that of control group (P<0.05). There was no significant difference in the number of eggs obtained and the fertilization rate between two groups. The clinical pregnancy rate of observation group was significantly higher than that of control group (P<0.05).Conclusion:Yangjing Zhongyu Tang can significantly alleviate the clinical symptoms of patients with kidney-Yin deficiency due to RIF, effectively improve the type A endometrial morphology of RIF patients, reduce the uterine artery blood flow resistance, optimize endometrial implantation, and significantly improve the clinical pregnancy rate.
Abstract：Objective:To observe the effect of Yiqi Huoxue Tongmai method in treating lower extremity atherosclerotic disease (LEAD) and on hemodynamic index and vascular endothelial function.Method:One hundred and five patients were randomly divided into control group (52 cases) and observation group (53 cases) by random number table. Patients in control group were treated for controlling blood sugar, blood fat, blood pressure and given aspirin enteric-coated tablets, 100 mg/day, cilostazol tablets, 100 mg/day, 2 times/day. In addition to the therapy of control group, patients in observation group were given modified Danggui Sini Tang and Buyang Huanwu Tang for oral and washout, 1 dose/day. The treatment course lasted for 12 weeks. Before and after treatment, ankle brachial index (ABI) was detected. And intimal thickness of shallow femoral shallower, arteriae tibialis posterior and arteriae dorsalis pedis, hardening degree, patch size and degree of stenosis were detected by color Doppler ultrasound diagnostic apparatus. Qi deficiency and blood stasis syndrome were scored. And levels of the whole blood viscosity, plasma viscosity, erythrocyte sedimentation rate (ESR), D-dimer (D-D), fibrinogen (FIB), erythrocyte electrophoresis, fasting blood glucose (FPG), glycosylated hemoglobin (HbA1c), serum 25-hydroxyvitamin D3 ( [25(OH)D3] ), endothelin (ET), nitric oxide (NO) and homocysteine (Hcy) were detected.Result:By the rank sum test, the clinical effect in observation group was better than that in control group (Z=2.371, P<0.05). After treatment, ABI in observation group was higher than that in control group (P<0.01), scores of Qi deficiency and blood stasis were lower than those in control group (P<0.01). Scores of intimal thickness of shallow femoral shallower, arteriae tibialis posterior and arteriae dorsalis pedis, hardening degree, patch size and degree of stenosis and the total score in observation group were lower than those in control group (P<0.01). And levels of the whole blood viscosity, ESR, D-D, FIB, erythrocyte electrophoresis were better than those in control group (P<0.01), while levels of HbA1c, ET and Hcy were lower than those in control group (P<0.01), and levels of [25(OH)D3] and NO were higher than those in control group (P<0.01).Conclusion:Modified Danggui Sini Tang and Buyang Huanwu Tang can ameliorate hemodynamics and vascular endothelial function, improve ABI, relieve arteriosclerosis and narrow degrees, and alleviate clinical symptoms.
Keywords：diabetes;atherosclerotic lesions of lower extremity;Qi deficiency and blood stasis syndrome;Danggui Sini Tang;Buyang Huanwu Tang;hemodynamics;endothelial function
Abstract：Objective:To observe influence of dialectical addition and subtraction of Shengmaiyin combined with Xuefu Zhuyu Tang on fibrinolytic activity and coagulation active factor of patients with non-small cell lung cancer at hypercoagulable state.Method:One hundred and eighty patients were randomly divided into control group (58 cases) and observation group (60 cases) by random number table. Patients in control group got low molecular weight heparins calcium injection by subcutaneous injection for 3 weeks, 1.0 mL (5 000 AXa unit)/time, 1 time/day, and oral aspirin enteric-coated tablets, 100 mg/time, 1 time/day. Patients in observation group got dialectical addition and subtraction of Shengmaiyin combined with Xuefu Zhuyu Tang, 1 dose/day. A course of treatment was 8 weeks. And activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), platelet (PLT), fibrinogen (FIB), D-dimer (D-D), plasma tissue plasminogen activator (t-PA), plasminogen activator inhibitor in plasma-1 (PAI-1), von willebrand factor (vWF), P-selectin, basic fibroblast growth factor (bFGF), transforming growth factor (TGF), vascular endothelial growth factor (VEGF) were detected. And before and after treatment, scores of Qi deficiency and blood stasis syndrome and hemorheological indices were detected.Result:After treatment, APTT, PT and TT in observation group were longer than those in control group. Levels of PLT, D-D and PAI-1 were lower than those in control group (P<0.01), level of t-PA was higher than that in control group (P<0.01). And levels of vWF, P-selectin, bFGF, TGF and VEGF were lower than those in control group (P<0.05, P<0.01). And improvement of hemorheological indexes the such as the whole blood viscosity (high shear and low shear), plasma viscosity and platelet aggregation rate were better than those in control group (P<0.01). And scores of symptoms of Qi deficiency were lower than those in control group (P<0.01), and except for 'zhengji’, scores of symptoms of blood stasis were lower than those in lower than those in control group (P<0.01).Conclusion:Dialectical addition and subtraction of Shengmaiyin combined with Xuefu Zhuyu Tang can ameliorate hypercoagulable state of NSCLC, relieve clinical symptoms, and can regulate fibrinolytic activity and coagulation activity factors, so it can mitigate dangers caused by deep venous thrombosis of NSCLC.
Abstract：Objective:Nuclear magnetic resonance hydrogen spectrum(1H-NMR) was adopted to investigate the effect of dry-cold environment and diet on urine and plasma metabolites of rats, in order to find possible biomarkers and their related metabolic pathways.Method:The dry-cold environment and diet were used as a stressors to intervene rats for 3 weeks, urine and plasma samples were collected.1H-NMR combined with multivariate data analysis were used to identify relevant metabolic markers and analyze their metabolic pathways.Result:The dry-cold environment and diet resulted in significant changes of 23 metabolites in urine and 15 metabolites in plasma; these metabolites were closely related to changes of various metabolic pathways, namely the tricarboxylic acid(TCA) cycle, pyruvate metabolism, glycolysis or gluconeogenesis, valine, leucine and isoleucine biosynthesis, glycine, serine and threonine metabolism, histidine metabolism; glyoxylic acid and dicarboxylic acid metabolism, alanine, aspartic acid and glutamate metabolism.Conclusion:Dry-cold environment and diet conditions can lead to the changes of various metabolic pathways in the body.The metabolomics based on 1H-NMR has the advantage of explaining the pathophysiological dynamics and overall changes of the body, which is of great significance for exploring the pathogenesis of non-deterministic disease factors.
Keywords：dry-cold environment;diet;metabolomics;nuclear magnetic resonance hydrogen spectrum(1H-NMR);tricarboxylic acid cycle;amino acids;metabolic pathways
Abstract：Objective:To prepare self-emulsifying carrier system which was suitable for three Chinese medicinal ingredients(baicalein, berberine and allicin), and investigate transdermal absorption effect in vitro of these three self-emulsifying preparations.Method:The optimum formulation and dosage were screened by the saturated solubility method, pseudo-ternary phase diagram method and orthogonal experiment.Transdermal absorption test in vitro was carried out with excised rats skin and Franz diffusion cell.The cumulative penetration amounts of baicalein, berberine and allicin in the identical self-emulsifying system were determined by HPLC and compared with baicalein powder, berberine powder and allicin powder, respectively.Result:The optimum formulation was ethyl oleate-cremophor RH40-polyethylene glycol(PEG)400.The self-emulsifying preparation had a suitable particle size with a relatively regular spherical shape.At 10 h of transdermal absorption, the transdermal rates of baicalein, berberine and allicin in identical self-emulsifying system were 6.898 6, 7.600 4, 190.040 μg·cm-2·h-1, the cumulative penetration amounts of them were 71.38, 85.54, 1 795.16 μg·cm-2, respectively.Conclusion:The self-emulsifying carrier system is prepared successfully, which can be used by different kinds of Chinese medicinal ingredients, and the transdermal absorption effect in vitro of these self-emulsifying preparations is good, which can provide experimental basis for the preparation and transdermal absorption of self-emulsifying preparation of Chinese herbal compound.
Abstract：Objective:To elucidate the characteristics of bidirectional regulation of raw and steamed products of Rhei Radix et Rhizoma and their active components, in order to provide scientific basis for clinical rational use of this decoction pieces.Method:Mice were randomly divided into the blank group(distilled water, 10 mL·kg-1), raw rhubarb group(1.62 g·kg-1), steamed rhubarb group(0.972 g·kg-1), raw rhubarb anthraquinone group(0.22 g·kg-1), steamed rhubarb anthraquinone group(0.19 g·kg-1), raw rhubarb tannin group(0.17 g·kg-1) and steamed rhubarb tannin group(0.027 g·kg-1). Each group was divided into 3 batches of 10 mice. Mice in each group were given the corresponding dose by continuous gavage for 7 days, the diarrhea index(EI) of mice in each group was recorded every day. The serum levels of motilin(MTL), vasoactive intestinal peptide(VIP) and epinephrine(EPI) were measured on day 1, 3, 7.Result:Compared with the blank group, EI of the rhubarb group increased significantly on the 3rd day(P<0.05), EI of the steamed rhubarb group was relatively stable during 7 days of administration, EI of the raw and steamed rhubarb anthraquinone groups decreased significantly on the 7th day of administration(P<0.01), EI of the raw rhubarb tannin group increased significantly on the 3rd day(P<0.01), and EI of the steamed rhubarb tannin group was significantly decreased on the 7th day(P<0.01). Compared with the blank group, the levels of MTL, VIP and EPI in the raw and steamed rhubarb anthraquinone and tannin groups decreased on the 1st day of administration, on the 3rd day of administration, the MTL level in the steamed rhubarb anthraquinone group increased significantly(P<0.05); the VIP levels of the steamed rhubarb anthraquinone group, the raw rhubarb tannin group and the steamed rhubarb tannin group increased significantly(P<0.01), the EPI level of the steamed rhubarb anthraquinone group was significantly increased(P<0.01), on the 7th day of administration, the MTL levels of the raw and steamed rhubarb tannin groups increased to the level in the blank group, the VIP level of the raw rhubarb anthraquinone group increased significantly(P<0.01), the EPI levels of raw and steamed rhubarb anthraquinone and tannin groups were further decreased significantly(P<0.01).Conclusion:The combined anthraquinone and hydrolyzable tannin in rhubarb can promote gastrointestinal motility and diarrhea. The effect of astringent intestines is caused by the monomer tannin produced by digestion and decomposition of condensed tannin, which may be one of the mechanisms of bidirectional regulation of rhubarb decoction pieces.
Abstract：Objective:To establish the HPLC fingerprint of raw products, rice-processed products and honey-processed products of Codonopsis Radix from Shanxi, and establish determination of their chemical constituents, which was used to analyze the changes of types and contents of chemical constituents in Codonopsis Radix from Shanxi before and after processing.Method:Agilent ZORBAX SB-C18 column(4.6 mm×250 mm, 5 μm) was adopted, the separation process was carried out using a binary gradient elution system composed of 0.5% phosphoric acid aqueous solution and acetonitrile, the column temperature was 30 ℃ and the detection wavelength was 220 nm.Result:Compared with the corresponding reference fingerprint, the similarities of HPLC fingerprint of 10 batches of raw products and processed products were >0.90.In raw products, rice-processed products and honey-processed products of Codonopsis Radix from Shanxi, the contents of lobetyolin were (0.33±0.049), (0.24±0.034), (0.18±0.047) mg·g-1, the contents of atractylenolide Ⅲ were (0.20±0.046), (0.40±0.046), (0.31±0.060) mg·g-1, the contents of 5-hydroxymethylfurfural(5-HMF) were (0.74±0.16), (1.45±0.19), (1.54±0.12) mg·g-1, respectively.Conclusion:Different processing methods have little effect on types of chemical constituents in Codonopsis Radix from Shanxi, but have great effect on the contents of some chemical constituents.
Keywords：Codonopsis Radix from Shanxi;processed products;fingerprint;similarity;lobetyolin;atractylenolide Ⅲ;5-hydroxymethylfurfural
Abstract：Objective:To design and synthesize series of rotundic acid derivatives by introducing aromatic ester groups with rotundic acid as the parent nucleus, test their anti-tumor activity in vitro, investigate the structure-activity relationship of rotundic acid derivatives in inhibiting tumor cell proliferation, and obtain the novel rotundic acid derivatives with high anti-tumor activity.Method:Compounds 1-8 were synthesized with rotundic acid as the initial raw material through the 28-etherification, 3β and 23di-aromatic esterification eaction. The anti-tumor activities in vitro were evaluated by MTT assay against A375 (human malignant melanoma cells), HeLa (human cervical cancer cells), SPC-A1 (human lung adenocarcinoma cells), and HepG2 (human liver cancer cells).Result:Compounds 2-8 were new compounds. Their structures were identified by melting point (MP), high resolution electrospray ionization tandem mass spectrometry (HR-ESI-MS), 1H nuclear magnetic resonance (1H-NMR) and 13C nuclear magnetic resonance (13C-NMR). MTT results showed that compounds 3, 5 and 8 exhibited significant anti-tumor activity, especially compound 5 was found to have the best inhibition activity on HeLa, A375, HepG2 and SPC-A1 with IC50 values of (5.25±1.08), (5.99±0.88), (3.31±1.89), (5.74±1.78) μmol·L-1, 1.92, 3.22, 3.79, 3.72 times of that of rotundic acid, respectively.Conclusion:Compound 5 has significant anti-tumor activity with great significance for further research and development of new anti-tumor medicines.
Abstract：Objective:Through the analysis of the characteristics and main chemical components of Ginseng Radix et Rhizoma, the correlation between the characteristics and components of Ginseng Radix et Rhizoma was explored, and a new evaluation standard of Ginseng Radix et Rhizoma grade was established to provide a more comprehensive and scientific basis for the quality evaluation of Ginseng Radix et Rhizoma.Method:The appearance characteristics of 48 batches of Ginseng Radix et Rhizoma samples were quantitatively measured. The contents of 9 kinds of Ginseng Radix et Rhizoma were determined. The results of correlation analysis, principal component analysis and cluster analysis were used to classify ginseng medicinal materials according to the analysis results, and the grade evaluation criteria were constructed.Result:First-class ginseng medicinal materials: diameter of main root>1.72 cm, length of reed head>2.61 cm, weight of single branch>14.15 g, content of ginsenoside Rb1>0.612 1%, content of ginsenoside Re>0.385 8%, content of ginsenoside Rg1>0.320 8%, no scar, impurities, moth, mildew. Second-class ginseng medicinal materials: the diameter of main root is 1.55-1.72 cm, the length of reed head is 1.74-2.61 cm, the weight of single branch is 10.24-14.15 g, the content of ginsenoside Rb1 is 0.496 8%-0.612 1%, the content of ginsenoside Re is 0.323 3%-0.385 8%, the content of ginsenoside Rg1 is 0.263 6%-0.320 8%, and there are no scars, impurities, worms and mildew. Third-class ginseng medicinal materials: main root diameter 1.29-1.55 cm, reed head length 1.34-1.74 cm, single branch weight 6.90-10.24 g, ginsenoside Rb1 content 0.389 5%-0.496 8%, ginsenoside Re content 0.235 2%-0.323 3%, ginsenoside Rg1 content 0.217 1%-0.263 6%, no impurities, worms, mildew. Fourth-class ginseng medicinal materials: diameter of main root<1.29 cm, length of reed head<1.34 cm, weight of single branch<6.90 g, content of ginsenoside Rb1<0.389 5%, the content of ginsenoside Re<0.235 2%, content of ginsenoside Rg1<0.217 1%, without impurities, worms and mildew.Conclusion:The appearance indexes of ginseng medicinal materials were divided according to the standards of taproot diameter, reed head length and single ginseng weight, and the content of ginsenoside Rg1, Re, Rb1 was used as the internal quality evaluation index. Ginseng commercial specifications were divided into four grades, which integrated the appearance and internal indicators, and had more scientific and comprehensive characteristics, which could be used as the basis for the classification of Ginseng Radix et Rhizoma medicinal materials.
Keywords：Ginseng Radix et Rhizoma;medicinal materials;intrinsic index components;appearance characteristics;grade evaluation
Abstract：Objective:To analyze and identify the non-medicinal parts in Zanthoxylum nitidum husk by HPLC-LTQ/Orbitrap-MS, and study the antioxidant activity, in order to provide the scientific basis for further research and development of Z. nitidum.Method:Data is collected by HPLC-LTQ/Orbitrap-MS, and high-resolution MS and MS2 spectra of mass spectrogram of chromatographic peaks were analyzed and compared with the literature database. The structure of each chromatographic peak was calculated and confirmed. The anti-oxidative activity of the Z. nitidum husk was studied by DPPH scavenging free radical ability and ABTS free radical scavenging ability.Result:Twenty-five alkaloids were identified from Z. nitidum husk. The main constituents were isoquinoline alkaloids (nitidine, liriodenine, magnocurarine), pyrrolidine alkaloid (allocryptopine, oxymatrine, oxysophocarpine), quinoline alkaloid (magnoflorine, nitidine chloride), and organic amine alkaloids (γ-sanshool). Antioxygenic activity was studied by DPPH scavenging free radical ability and ABTS free radical scavenging ability. The results showed that they were within the measured concentration range, the antioxidant activity increased with the rise of the sample concentration, a good dose dependence was presented.Conclusion:In this paper, the chemical constituents and the activity Z. nitidum husk were studied. Studies have shown a variety of alkaloids, with a good antioxidant activity. This study provides a reference for further research and development of Z. nitidum.
Abstract：Objective:To isolate and identify the chemical constituents from 95%ethanol extracts from stems of Zanthoxylum bungeanum.Method:The stems (25 kg) were extracted with 95%ethanol under reflux for three times and then filtrated, and the combined filtrates were concentrated under vacuum to get the extracts. After suspension with water, the extracts were extracted with petroleum ether, dichloromethane, ethyl acetate and n-butanol successively, and five corresponding parts were obtained. The parts of petroleum ether, dichloromethane, ethyl acetate were separated in a similar way to get pure compounds. By the method the subjects were first chromatographed on silica gel column respectively, then the selected sub-fractions were further separated by Sephadex LH-20, and finally purified on preparation HPLC to get the monomer compound. The n-butanol part was first treated with macroporous resin D101, and then the sub-fractions were further purified by almost the same method as mentioned above. The structures of these compounds were determined by spectrum technology as IR, MS, 1H-NMR, 13C-NMR.Result:Ten compounds were isolated from Z. bungeanum stems and identified as follows: (+ )-magnoflorine(1), (-)-marmesin(2), (-)-columbianetin(3), (-)-decursinol(4), lupeol(5), α-amyrin(6), β-amyrin(7), δ-amyrin(8), quercetin(9), rutin(10). Among them, 1 was alkaloid, 2, 3, 4 were coumarin, 5, 6, 7, 8 were triterpenoid, 9, 10 were flavonoids.Conclusion:Compounds 1-8 were isolated from this plant for the first time.
Abstract：Objective:To build a gray-level matching template by using the gray level information of the microscopic image of the transverse section of Chinese medicinal materials, in order to realize the automatic recognition of the images of Chinese medicinal materials independent of scale and orientation.Method:By using the embedding method of polyethylene glycol (PEG), the transverse slices of 19 kinds of common rhizomatous medicinal materials were obtained. The images of the slices were taken by digital microscopic imaging technology, and the mosaic grayscale images were obtained by image registration, noise removal and boundary location. The center of the structure of the materials in the images was selected to establish the polar coordinate system, so as to divide grids from the radial and angular directions. By counting the gray information in each grid, the gray information digital matrix that can characterize the microscopic identification characteristics of the materials was obtained. Images in an appropriate sample size was used to train the matrix for generalization of the matrix. The covariance coefficients between the matrix of positive or negative verification sample and the template matrix were calculated to set the best identification parameters. For each medicinal material, 80 fan-shaped images were prepared, including 70% of training samples, 15% of validation samples and 15% of test samples, and single template and template set were tested with test samples.Result:In the test of 240 images including non-template-set medicinal materials, the correct recognition rate of single-template test was 90.1%, and that of template-set test was 92.5%.Conclusion:This method can well characterize the microscopic identification characteristics of Chinese medicinal materials, with a strong anti-interference ability and less subjective-errors, acquire sample images easily, and provide technical support for the digitization of morphological quality control of Chinese medicinal materials.
Abstract：Integrated pharmacological approach was used to predict the target genes and signal pathways of Xiaoer Fupi granules in the treatment of functional dyspepsia(FD), and the possible mechanism was discussed. The disease target information was collected by the DISEASES and UniProt databases, integrated pharmacological platform of traditional Chinese medicine(TCM-IP) was used to predict chemical composition, target, protein gene ontology(GO) function and Kyoto encyclopedia of genes and genomes(KEGG) pathway, and the networks of candidate target and TCMs-chemical components-core targets-key pathways were constructed. A total of 2 882 potential targets and 96 candidate target pathways were predicted, and β-1, 4-galactosyltransferase(β-1, 4-GalT) subtypes(B4GALT4, B4GALT2, B4GALT1) and phosphorylated protein kinase C subtype D(PRKCD), adenylate cyclase 2(ADCY2) and other targets were predicted. Some pathways were enriched, such as nervous system, endocrine system, thyroid hormone signaling pathway, long-term depression and other pathways related to FD. It was predicted that Xiaoer Fupi granules for treating FD by regulating gastrointestinal hormones, anti-depression, and regulating nerves and endocrine system. This study provides a basis for the precise clinical application and positioning of Xiaoer Fupi granules, and helps to clarify the mechanism of this drug.
Keywords：Xiaoer Fupi granules;integrated pharmacology;functional dyspepsia;precise medicine;Shenling Baizhusan;gastrointestinal hormones;endocrine system
Abstract：Herbgenomics is an interdisciplinary subject between traditional Chinese medicine(TCM) and genomics.It is a comprehensive discipline covering multi-omics research in both medicinal organisms of TCM and the relationship of TCM to human body.It has been widely used in the research fields of medicinal model organisms, synthetic biology of TCM, identification of TCM molecules and breeding of medicinal plant cultivars, pharmacokinetics, and the study on the geoherbalism and medicinal of TCM.With the release of important documents, such as the Law of the People's Republic of China on TCM and the Outline of TCM Development Strategy(2016—2030), the Chinese medicine industry has entered a new and high-level development opportunity and the herbgenomic research area has got a landmark achievement.The training of well-rounded students and researchers is a key point for the development of TCM industry and the reform of medical colleges and universities.Therefore, the establishment of herbgenomics is particularly important for the modernization of TCM.At present, many colleges and universities have set up the course of Herbgenomics among graduate students and undergraduates, and initially formed a distinctive herbal genomics talent training system.This paper introduces the herbgenomics from the progress of the research, the development of teaching courses, the background of the textbook, the main content and key technologies of the discipline and the prospect of discipline construction, in order to provide theoretical basis and methodological support for the discipline construction, personal training and scientific research of herbgenomics.
Abstract：Pharmaceutics of Traditional Chinese Medicine(TCM) is a comprehensive applied discipline integrating theory with practice, and it is a main core course of the undergraduate major of TCM with the characteristics of combining inheritance with innovation, theory with practice, integration with specialty. According to the characteristics of this curriculum and the current research situation of teaching model, this paper proposes to construct the " Fang-Zheng-Ji-Dao" characteristic teaching model of Pharmaceutics of TCM, and the construction, implementation strategies and methods of the model were elaborated in order to provide new ideas and methods for the innovation of the teaching model of Pharmaceutics of TCM.
Keywords：Pharmaceutics of Traditional Chinese Medicine(TCM);" Fang-Zheng-Ji-Dao ";characteristic teaching model;multimedia;production-learning-research;theory of TCM
Abstract：The chemical constituents of plants from the genus Sorbus are mainly flavonoids, biphenyls, terpenoids and organic acids.Pharmacological researches proved that the chemical components isolated from Sorbus plants has antitussive, relieving asthma, antibacterial and antioxidant effect.Moreover, the Sorbus plants were used as landscape trees.There is a bright developing prospect about Sorbus plants.In this review, we give an overview of the significant progress and the latest findings made in Sorbus plants, such as the stress response, chemical compositions, pharmacological activities and the propagation technology.The results including as following: ①more evidences are needed for species identification of Sorbus, ②the researches about Sorbus plants is focused on only a few species(S. alnifolia, S. amabilis, S. pohuashanensis, S. tianschanica, S. aucuparin), ③the existing researches centre upon chemical composition analysis and propagation and cultivation; the formation and mechanism of active components are rarely reported.Thus, the research of Sorbus plants is still in the early period, and this review paper will provide theoretical basis and reference for further research of Sorbus plants.
Abstract：Schisandrae Chinensis Fructus is dry, mature fruits of magnolia plant Schisandra chinensis. In recent years, domestic and foreign scholars have made a lot of studies on active constituents of S. chinensis and pharmacological activities. This article systematically organizes the active constituents and pharmacological activities of S. chinensis. It was found that fruit, seeds, roots, stems and leaves of S. chinensis and other medicinal parts mainly contained lignans, volatile oils, triterpenoids, polysaccharides and flavonoids. And lignans were the main characteristic active ingredients of S. chinensis, triterpenoids, polysaccharides and volatile oils were the secondary active ingredients, and the activity of flavonoids had rarely been reported. According to the pharmacological study of S. chinensis, S. chinensis lignans had certain effects on the central nervous system, cardiovascular system, liver, kidney and reproductive system, with anti-oxidation, anti-tumor, anti-bacterial and anti-HIV effects. Other chemical components also had good pharmacological activities, but were less studied than lignans. With dual functions in medicine and food, it was widely used as a health product and medicine. This article systematically summarized the active constituents and pharmacological activities of S. chinensis, and provided an important reference and basis for the further development of the health product and medicine of S. chinensis in the future.
Abstract：The surface and interface, as the transition region between two phases, belongs to the category of physical chemistry.At present, it is widely used in materials and other scientific fields.Meanwhile, this property also plays an important role in pharmaceutical research.The interface layer involved in the progress of pharmaceutical preparations is connected with the two-phase or three-phase between gas, liquid and solid closely.The interface effect will affect the final shaping of pharmaceutical preparations and the dissolution and absorption of drugs in the human body.In this paper, the surface and interface characteristics(specific surface area, surfacial and interfacial tension and surface Gibbs free energy) were compared, and the application of interface phenomena(wetting, solubilization and emulsification) in pharmaceutical research were introduced.From the points of view of the progress control of pharmaceutical preparations and the effectiveness of their products, the article expounds the important role of properties of surface and interface in the field of pharmaceutical preparations.Therefore, it is necessary to pay attention to the properties of surface and interface, one of the key physical properties of drugs, and to apply them in the pharmaceutical research.
Abstract：Diarrhea-predominant irritable bowel syndrome (IBS-D) is not only a biological mental disorder, but also a kind of chronic functional bowel disease induced by many factors. The pathogenesis of IBS-D is related to visceral sensory abnormalities, intestinal dynamics abnormalities, intestinal mucosal micro-inflammatory reactions, heredity, dietary intolerance and other factors. The visceral hypersensitivity is one of the main pathophysiology, and refers to an unknown cause of intestinal hypersensitivity to cold, bad mood and other stimuli. However, its mechanism remains unclear. The pathogenesis of IBS-D is closely related to the disturbance of brain and intestinal interaction. IBS-D patients often suffer from anxiety, depression and other psychiatric symptoms due to repeated illness, but long-term chronic mental stress can induce and aggravate IBS-D visceral hypersensitivity. Brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tyrosine kinase B (TrkB) are hotspots in studies about brain-gut axis. BDNF is a highly expressed cytokine in the central nervous system and gastrointestinal tract, and can promote the development of the nervous system, maintain the normal function of mature nerve cells and regulate the gastrointestinal motility and visceral sensitivity. Intestinal microbiota is the key link of brain-gut interaction. Mental disorders are closely related to intestinal symptoms caused by changes in intestinal microbial environment. Repeated mental stimulation can lead to changes in intestinal flora; on the other hand, changes in intestinal flora structure are closely related to the development of the nervous system and the function of the brain. With intestinal microbiota as the study object, this article mainly discusses the effect of intestinal microbiota in regulating visceral hypersensitivity of IBS-D based on brain-gut axis (BDNF/TrkB signaling pathway).
Keywords：diarrhea-predominant irritable bowel syndrome;brain-gut axis;intestinal microbiota;visceral hypersensitivity;bidirectional communication
Abstract：This paper compared and analyzed the relevant records of Chinese medicine pharmacy in the Han, Tang and Song dynasties, and summarized the changes of the dosage forms, preparation techniques and administration methods of Chinese medicine with the development of history.In this study, three classic medical works in the Han, Tang and Song dynasties, including Treatise on Febrile Diseases Caused by Cold, Valuable Prescriptions for Emergency and Formularies of the Bureau of People's Welfare Pharmacies, were taken as the research objects, and the development of the dosage forms, auxiliary materials, preparation technology and medication theory were summarized and explored by the ways of content analysis, comparative analysis and case analysis.The comparison showed that in the development process, the dosage forms gradually increased, but the liquid dosage forms gradually decreased, the solid dosage forms gradually increased.Not only the dosage forms varied in the number, types of excipients used more and more, but the level of preparation had been constantly improved while the methods of taking became more detailed.This evolution of dosage forms and pharmaceutical technologies in Chinese history is worth learning and thinking about it.Through exploring the traditional Chinese medicine(TCM) technologies and theories in the Han, Tang and Song dynasties, we can contribute to the inheritance of traditional preparations and it can provide the basis for the development of modern preparations with TCM characteristics.
Keywords：Treatise on Febrile Diseases Caused by Cold;Valuable Prescriptions for Emergency;Formularies of the Bureau of People's Welfare Pharmacies;preparations of traditional Chinese medicine;excipients;preparation process;medication time