Riboflavin ameliorates intestinal inflammation via immune modulation and alterations of gut microbiota homeostasis in DSS-colitis C57BL/6 mice.

While there have been advancements in understanding the direct and indirect impact of riboflavin (B2) on intestinal inflammation, the precise mechanisms are still unknown. This study focuses on evaluating the effects of riboflavin (B2) supplementation on a colitis mouse model induced with 3% dextran sodium sulphate (DSS). We administered three different doses of oral B2 (VB2L, VB2M, and VB2H) and assessed its impact on various physiological and biochemical parameters associated with colitis. Mice given any of the three doses exhibited relative improvement in the symptoms and intestinal damage. This was evidenced by the inhibition of the pro-inflammatory cytokines TNF-α, IL-1ß, and CALP, along with an increase in the anti-inflammatory cytokine IL-10. B2 supplementation also led to a restoration of oxidative homeostasis, as indicated by a decrease in myeloperoxidase (MPO) and malondialdehyde (MDA) levels and an increase in reduced glutathione (GSH) and catalase (CAT) activities. B2 intervention showed positive effects on intestinal barrier function, confirmed by increased expression of tight junction proteins (occludin and ZO-1). B2 was linked to an elevated relative abundance of Actinobacteriota, Desulfobacterota, and Verrucomicrobiota. Notably, Verrucomicrobiota showed a significant increase in the VB2H group, reaching 15.03% relative abundance. Akkermansia exhibited a negative correlation with colitis and might be linked to anti-inflammatory function. Additionally, a remarkable increase in n-butyric acid, i-butyric acid, and i-valeric acid was reported in the VB2H group. The ameliorating role of B2 in gut inflammation can be attributed to immune system modulation as well as alterations in the gut microbiota composition, along with elevated levels of fecal SCFAs.

Ultrasonic-ethanol pretreatment assisted aqueous enzymatic extraction of hemp seed oil with low Δ9-THC.

In this study, ultrasonic-ethanol pretreatment combined with AEE was developed for oil extraction from hemp seeds. The oil yield reached a maximum of 23.32 % at 200 W ultrasonic power and 30 min ultrasonic time, at this point, the degradation rate of Δ9-THC was 83.11 %. By determining the composition of hemp seed before and after pretreatment, it was shown that ultrasonic-ethanol pretreatment reduced the protein content of the raw material. An enzyme mixture consisting of pectinase and hemicellulase (1/1/1, w/w/w) was experimentally determined to be used, and the AEE extraction conditions were optimized using the Plackett-Burman design and the Box-Behnken. The optimal conditions were determined to be pH 5, total enzyme activity of 37,800 U/g, liquid-solid ratio of 10.4 mL/g, enzyme digestion temperature of 32 °C, enzymatic time of 189 min, and oil recovery of 88.38 %. The results of confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM) showed that the emulsion formed during ultrasonic ethanol pretreatment was not uniformly distributed, and the droplets appeared to be aggregated; and the irregular pores of hemp seed increased after pretreatment. The contents of Δ9-THC and CBN in the extracted oil samples were 9.58 mg/kg and 52.45 mg/kg, respectively. Compared with the oil extracted by Soxhlet extraction (SE), the oil extracted by this experimental method was of better quality and similar in fatty acid composition.

Exploration of the Potential Mechanism of Yujin Powder treating Dampness-heat Diarrhea by Integrating UPLC-MS/MS and Network Pharmacology Prediction.

BACKGROUND: Yujin powder (YJP) is a classic prescription for treating dampness-heat diarrhea (DHD) in Traditional Chinese Medicine (TCM), but the main functional active ingredients and the exact mechanisms have not been systematically studied. OBJECTIVES: This study aimed to preliminarily explore the potential mechanisms of YJP for treating DHD by integrating UPLC-MS/MS and network pharmacology methods. METHODS: Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technology was used to determine the ingredients of YJP. And then, the targets of these components were predicted and screened from TCMSP, SwissTargetPrediction databases. The disease targets related to DHD were obtained by using the databases of GeneCards, OMIM, DisGeNET, TTD, and DrugBank. The protein-protein interaction networks (PPI) of YJP-DHD were constructed using the STRING database and Origin 2022 software to identify the cross-targets by screening the core-acting targets and a network diagram by Cytoscape 3.8.2 software was also constructed. Metascape database was used for performing GO and KEGG enrichment anlysis on the core genes. Finally, molecular docking was used to verify the results with AutoDock 4.2.6, AutoDock Tools 1.5.6, PyMOL 2.4.0, and Open Babel 2.3.2 software. RESULTS: 597 components in YJP were detected, and 153 active components were obtained through database screening, among them the key active ingredients include coptisine, berberine, baicalein, etc. There were 362 targets treating DHD, among them the core targets included TNF, IL-6, ALB, etc. The enriched KEGG pathways mainly involve PI3K-Akt, TNF, MAPK, etc. Molecular docking results showed that coptisine, berberine, baicalein, etc., had a strong affinity with TNF, IL-6, and MAPK14. Therefore, TNF, IL-6, MAPK14, ALB, etc., are the key targets of the active ingredients of YJP coptisine, baicalein, and berberine, etc. They have the potential to regulate PI3K-Akt, MAPK, and TNF signalling pathways. The component-target-disease network diagram revealed that YJP treated DHD through the effects of anti-inflammation, anti-diarrhea, immunoregulation, and improving intestinal mucosal injury. CONCLUSION: It is demonstrated that YJP treats DHD mainly through the main active ingredients coptisine, berberine, baicalein, etc. comprehensively exerting the effects of anti-inflammation, anti-diarrhea, immunoregulation, and improving intestinal mucosal injury, which will provide evidence for further in-depth studying the mechanism of YJP treating DHD.

[Determination of complexation ability of rhubarb with copper ions by ultra-high performance liquid chromatography].

Gandou decoction (GDD) is a traditional Chinese medicine prescription that has been widely used to treat copper metabolism disorders in China with remarkable clinical effect and lower toxicity. However, evaluation of the complexation ability of copper ions is challenging, which hinders screening and discovery of coordinate active ingredients in GDD. An analytical method is needed to determinate the complexation ability of chemical constituents with copper ions. In this study, a rapid and accurate method based on ultra-high performance liquid chromatography (UHPLC) was developed to determine the complexing ability of rhubarb with copper ions. First, the optimal coordination reaction conditions between active ingredients of rhubarb and copper ions were determined. The samples were separated using an Agilent Eclipse Plus C18 column (50 mm×2.1 mm, 1.8 µm) with 5 µL injection volumes. The mobile phase was gradient eluted with methanol and water containing 0.1% (v/v) phosphoric acid at a flow rate of 0.3 mL/min. The detection wavelength was 254 nm and the column temperature was 30 ℃. Under the optimized chromatographic conditions, the rhubarb constituents were effectively separated. Next, peak areas of rhubarb were calculated before and after the coordination reaction between copper ions. The complexing ability of active ingredients in rhubarb with copper ions was evaluated by calculating the rate of changes of their chromatographic peak areas. Finally, ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was used to identify the coordination active ingredients in rhubarb extract. Focusing on the coordination reaction conditions between active ingredients of rhubarb and copper ions revealed that the active ingredients of rhubarb and copper ions reached equilibrium by coordination reaction at pH 9 for 12 h. Methodological evaluation revealed the good stability and repeatability of the method. Under these conditions, 20 major components of rhubarb were identified by UPLC-Q-TOF-MS. According to the coordination rate of each component and copper ions, eight components with strong coordination were screened out (gallic acid 3-O-ß-D-(6'-O-galloyl)-glucopyranoside, aloe emodin-8-O-ß-D-glucoside, sennoside B, l-O-galloyl-2-O-cinnamoyl-glucoside, chysophanol-8-O-ß-D-(6″-O-acetyl)-glucoside, aloe-emodin, rhein and emodin). The respective complexation rates of the components were 62.50%, 29.94%, 70.58%, 32.77%, 34.61%, 26.07%, 28.73% and 31.78%. Compared with other reported methods, the presently developed method can be used to screen the active ingredients of traditional Chinese medicines that have complexing ability with copper ions, especially in complex mixture systems. This study describes an effective detection technology for evaluating and screening the complexing ability of other traditional Chinese medicines with metal ions.

Construction of hemp seed protein isolate-phosphatidylcholine stablized oleogel-in-water gel system and its effect on structural properties and oxidation stability.

Rice bran wax was added to hemp seed oil (HSO) to prepare oleogel, and hemp seed protein isolate (HPI)-phosphatidylcholine (PC) was used as the emulsifier to obtain an oleogel-in-water (Og/W) gel system. The effect of HPI concentration on the construction of gel system was studied. Microscopic observations found that the oil droplets were encapsulated by the emulsifier. X-ray diffraction and Fourier transform infrared spectroscopy analysis showed that the increase in HPI concentration promoted the interaction between PC and protein, but didn't affect the crystal structure of gel. Thermogravimetric analysis showed that when the HPI concentration was 8 %, the sample formed a dense gel network and had good thermal stability. At this time, the oil holding capacity of gel was 98.81 ± 0.08 %, and the gel hardness was 109.55 ± 1.74 g. After 30 days of storage, the retention rate of Δ9-THC reached 96.3 %, and the peroxide value was 4.98 mmol/kg.

Comparison of the Antioxidant Activities and Polysaccharide Characterization of Fresh and Dry Dendrobium officinale Kimura et Migo.

It is generally believed that fresh Dendrobium officinale (FDO) has more significant pharmacological activity than dried Dendrobium officinale (DDO); however, the difference has not been clearly shown. Our study compared their antioxidant properties both in vitro and in vivo, and the molecular weight arrangement and monosaccharide composition of the fresh Dendrobium officinale polysaccharides (FDOPs) and the dried Dendrobium officinale polysaccharides (DDOPs) were analyzed by HPLC-GPC and GC-MS. The results showed that the FDO and its polysaccharides had more significant effects on scavenging DPPH, ABTS, and hydroxyl radicals than the DDO. In addition, both the FDO and DDO significantly reduced lipid peroxidation levels and increased the SOD, T-AOC, CAT, and GSH levels in mice with acute liver damage caused by CCl4, while the FDO and its polysaccharides were more effective. Histopathological analysis further verified the protective effect of the Dendrobium polysaccharides on CCl4-induced liver injury. The determination of the polysaccharides revealed that the polysaccharide and mannose contents of the FDO were significantly higher than their dried counterparts, and the homogeneous arrangement of the polysaccharides in the FDO was degraded into three polysaccharide fragments of different molecular weights in the DDO. Overall, our data identified differences in the antioxidant activities of the FDO and DDO, as well as the reasons for these differences.

Application of magnetic immobilized enzyme of nano dialdehyde starch in deacidification of rice bran oil.

Glutaraldehyde is usually used as a cross-linking agent in the immobilization of enzymes, but this will have a negative effect on the enzyme. Dialdehyde starch can effectively replace glutaraldehyde as a cross-linking agent, but the large particle size of dialdehyde starch affects the performance of immobilized enzyme. In this study, dialdehyde starch nanoparticles (DSNP) were combined with modified Fe3O4 to obtain magnetic carrier (MDSNP), and Candida Antarctica lipase B (CALB) was crosslinked to the carrier to obtain magnetic immobilized enzyme (MDSNPCALB). The characterization results show that the functional groups of each material have obvious characteristic absorption peaks, strong diffraction peaks and typical crystal structures, high magnetism, no coercivity, relatively good dispersion and nano particle size. MDSNPCALB was added to degummed rice bran oil (RBO) and ethanolamine was used as an acyl receptor for acylation and deacidification. After repeated use for 10 times, MDSNPCALB remained highly active, indicating that MDSNPCALB can be effectively used for the deacidification of RBO.

Randomized clinical trial of radiofrequency-induced thermotherapy combined with transilluminated powered phlebectomy versus high ligation and stripping for the treatment of lower limb varicose veins.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of radiofrequency-induced thermotherapy (RFiTT) combined with transilluminated powered phlebectomy (TIPP) in the treatment of lower limb varicose veins (VVs) in comparison with high ligation and stripping (HLS) combined with TIPP. METHODS: The patients with lower limb VVs were randomly assigned to RFiTT combined with TIPP or HLS combined with TIPP. The primary end point was total closure rate of the great saphenous vein at 12 months. Secondary end points included Venous Clinical Severity Score and 14-item Chronic Venous Insufficiency Questionnaire score changes at 12 months and perioperative complications. RESULTS: The total closure rate of the great saphenous vein at 12 months was slightly lower in the RFiTT group (90.9% [90/99]) than in the HLS group (97.0% [98/101]) but not statistically significant (χ2 = 0.068; P = .08). Operation time, intraoperative blood loss, duration in hospital, duration in bed, and resumption of activities were statistically significantly better with RFiTT than with HLS. There were no significant differences between the groups in deep venous thrombosis, phlebitis, hematomas, pain, and infection. However, skin pigmentation and paresthesia were statistically significantly better with RFiTT than with HLS. At 12 months, both groups showed similar improvement from baseline in Venous Clinical Severity Score (1.28 ± 0.57 in the RFiTT group vs 1.33 ± 0.61 in the HLS group) and 14-item Chronic Venous Insufficiency Questionnaire score (67.32 ± 1.29 in the RFiTT group vs 67.45 ± 1.32 in the HLS group); however, neither group was superior to the other. CONCLUSIONS: RFiTT combined with TIPP is an effective treatment method for lower limb VVs and had a more satisfactory clinical outcome in surgical data, skin pigmentation, and paresthesia than HLS at the 12-month follow-up.

Highly efficient electrochemical gas reduction on a three-dimensional foam electrode: mechanism and application for the determination of hazardous mercury in complex matrix.

For the first time a nickel foam electrode (NFE) is applied in the field of electrochemical vapor generation (EVG) to carry out the electrochemical vapor phase conversion of mercury. Systematical electrochemical and morphological research has demonstrated that the specific surface area of the NFE was several times larger than that of the metal/non-metal electrode with the same geometric size. At the same time, the 3D porous channel composed of multi-layer nickel wire ensures the full contact between reactant and interface. The evident enhancement of spectral signals on a Ni electrode (283%), compared with Pt (27%) and graphite (109%), confirmed that the NFE effectively enhances the yield of mercury reduction. The NFE exhibits low limit of detection (0.017 µg L-1) and a wide linear range (0.2-20 µg L-1) with recoveries of actual samples in the range 87.8-117% towards Hg2+. Although the NFE has no advantage in electronic transmission and catalytic performance, its excellent stability, especially anti-interference and other characteristics, is sufficient for the analysis of hazardous mercury in complex matrix including certified reference materials and real samples.

Rapid extraction of arsenic species from traditional Chinese herbal by dual-frequency ultrasound-assisted enzymatic digestion prior to spectral analysis.

Considering the huge difference of biological toxicity, it is extremely significant to recognize the exact content of arsenic species in actual samples. In this paper, a novel pretreatment technique for the efficient extraction of arsenic species from herbal samples is developed by dual-frequency ultrasound-assisted enzymatic digestion (DUED). The preservation of arsenic original form, reduction of the actual analysis time, environmental friendliness and free-interference in subsequent detection make this method over the traditional method such as wet digestion, ashing and some solvent extraction technologies. The combination of DUED and atomic fluorescence spectrometry realize the speciation analysis of arsenic in traditional Chinese medicine. The optimizations of experimental parameters have been achieved, and the potential mechanism is discussed. The experimental data showed that cellulase is suitable for the digestion of herbal matrix than α-amylase and papain. Ultrasound can significantly increase the rate of enzymatic hydrolysis of biological molecules, especially under dual-frequency ultrasound irradiation. The highest relative extraction efficiency can be obtained by combining 40 kHz ultrasonic bath (UB) with 20 kHz ultrasonic probe (UP). Two certified reference materials [CRMs, GBW(E)090066 and GBW(E)090067] and four practical herbs were used to evaluate the accuracy and practicability of the method. Inorganic arsenic, including trivalent arsenic and pentavalent arsenic, was the main species in the four herbal samples.

Exploration the active compounds of Astragali Radix in treatment of adriamycin nephropathy by network pharmacology combined with transcriptomic approach.

PURPOSE: This paper aimed to study the active compounds of Astragali Radix (AR) in the treatment of adriamycin nephropathy (AN) by a combination of network pharmacology and transcriptomics. METHODS: The chemical compounds of AR were screened out by text mining and database searching. Pharm Mapper was used to predict the targets of these chemical compounds. Potential targets of AN were screened by integrating the data from network pharmacology with known transcriptomics analysis results of kidney tissue. Compound-active target-potential target interactions networks were constructed so as to illustrate the relationship between compounds and targets, and obtain the chemical compounds directly related to potential targets of AN. The formula of compound contribution index (CI) based on algorithm was used to screen the active compounds of AR in the treatment of AN. In addition, we established an adriamycin-induced cell damage model with MPC5 cell, and used MTT assay, trypan blue dyeing and western blot analyses to validate the pharmacodynamic effect of the active compounds. RESULTS: 27 chemical compounds and 376 targets in AR were obtained by network pharmacology. Through Compound-active target-potential target interactions networks analysis, 22 compounds and 9 active targets as well as 130 potential targets were linked through 282 edges. The CI of every chemical compounds was further calculated by formula, the first four chemical compounds, including astragaloside IV, formononetin, quercetin and calycosin, whose cumulative contribution rate reached 87.28%, were considered to be active compounds. The results of MTT and trypan blue staining indicate that four active compounds had the significant protective effect on adriamycin-induced cell damage with MPC5 cell. Western blot result showed that four active compounds could significantly increase the expression of podocin protein in MPC5 cell. CONCLUSION: The active compounds of AR in the treatment of AN were successfully identified by using a network pharmacology and transcriptomics approach. This approach is expected to be beneficial to the study of the pharmacodynamic material basis of traditional Chinese medicine (TCM) in treating specific diseases.

Metabolomics coupled with integrative pharmacology reveal the protective effect of FangjiHuangqi Decoction against adriamycin-induced rat nephropathy model.

With the development of the society, the number of people who got the nephrotic syndrome (NS) is going up roughly. Therefore, finding a better way to treat NS is becoming a major global public health issue. As we all know, traditional Chinese medicine (TCM), especially Fangji Huangqi Decoction (FHD), has a long history and has good curative effects on NS. However, the mechanism of FHD treating NS has not been clearly elucidated. To address this problem, a feasible system was developed by metabolomics and integrative pharmacology approach. To study the mechanisms of Chinese medical formula FHD treating NS based on metabolomics and integrative pharmacology. In this study, a NMR based metabolomics approach coupled with biochemical assay and Western Blot had been employed to study the protective effect of FHD against adriamycin-induced nephropathy using rat model. And we proposed a integrative pharmacology-based method, which combined chemical ingredients database building, target identification and network analysis. These were aimed to decipher the mechanisms of action for the FHD in NS treatment. Multivariate analysis revealed that 13 of 16 perturbed metabolites could be reversed by FHD, and the MetaboAnalyst analysis revealed that the anti-nephrotic syndrome effect of FHD was probably related with regulation of alanine, aspartate and glutamate metabolism, citrate cycle, pyruvate metabolism, cysteine and methionine metabolism and glyoxylate and dicarboxylate metabolism. The integrative pharmacology analysis revealed 93 potential targets for FHD, and suggested that the protective effect of FHD on the nephrotic syndrome was probably related with the regulation of immune, and energy metabolic and fatty acid metabolic. In addition, both the metabolomics and the integrative pharmacology are focus together on the alanine, aspartate and glutamate metabolism pathway. These metabolites changes and the core targets changes, as well as the metabolite-target pathway network provide insights into the mechanisms of FHD treating nephrotic syndrome, and further studies are needed to validate the bioactive compounds responsible for the anti-nephrotic syndrome effect of FHD.

Comparison of dexmedetomidine and sufentanil as adjuvants to local anesthetic for epidural labor analgesia: a randomized controlled trial.

BACKGROUND: The epidural dexmedetomidine combined with ropivacaine has been successfully used for labor analgesia. We compared the effects of dexmedetomidine and sufentanil as adjuvants to local anesthetic for epidural labor analgesia. METHODS: Eighty nulliparous women were enrolled in the double-blind study and randomly divided into two groups. Group D received 0.5 µg/mL dexmedetomidine with 0.1% ropivacaine for epidural labor analgesia, and group S (control group) received 0.5 µg/mL sufentanil with 0.1% ropivacaine for labor analgesia. Hemodynamic parameters were monitored. Pain was assessed using a visual analog scale. The onset of epidural analgesia, duration of stages of labor, Ramsay Sedation Scale, blood loss, neonatal Apgar scores, umbilical artery blood pH and adverse effects, such as respiratory depression, nausea, vomiting, pruritus, and bradycardia, were recorded. RESULTS: Compared with the control group, visual analog scale values after cervical dilation >3 cm were lower in group D (P<0.05) and first-stage labor duration was shorter in group D (378.5±52.6 vs 406.5±58.2, P<0.05). Ramsay Sedation Scale values were higher in group D compared to the control group (2.8±0.6 vs 2.4±0.5, P<0.05). No significant differences in side effects were observed between the groups. CONCLUSION: Dexmedetomidine is superior to sufentanil in analgesic effect and duration in first-stage labor during epidural analgesia when combined with 0.1% ropivacaine (www.chictr.org.cn, registration ChiCTR-OPC-16008548).

Study on Improvement Effects of Liqi Sanjie Granule on Liver-qi Stagnation Model Rats / 中国药房

OBJECTIVE： To investigate the improvement effects of Liqi sanjie granule on liver-qi stagnation model rats. METHODS： According to the weight， totally 80 rats were randomly divided into blank control group （normal saline）， model control group （normal saline）， Xiaoyao pill control group （positive control a， 750 mg/kg ，calculated by crude drug）， Xiaojin pill control group （positive control b， 200 mg/kg， calculated by pill weight）， Liqi sanjie pill control group （prototype control， 1 957 mg， calculated by crude drug） and Liqi sanjie granule low-dose， medium-dose and high-dose groups （978.5， 1 957， 3 914 mg/kg， calculated by crude drug）， with 10 rats in each group. Each group was given medicine 20 mL/kg intragastrically once a day， for consecutive 21 d. 1 h after per medication， liver-qi stagnation model was established in those groups by binding method except for blank control group. The syrup preference of rats was determined by designing syrup preference test. Rattail suspension test was adopted to determine the hanging immobility time and struggling times of mice. Open-field behavior test was used to determine total behavior score so as to judge the extent of liver-qi stagnation and effect of the drug in rats. RESULTS： Compared with blank control group， hanging immobility time of model control group was significantly prolonged， the syrup preference and the total behavior score of open field test were decreased significantly， with statistical significance （P＜0.05 or P＜0.01）. Compared with model control group， the struggling times of rats were increased significantly in Xiaojin pill control group， Liqi sanjie pill control group and Liqi sanjie granule medium-dose group （P＜0.05 or P＜0.01）； the hanging immobility time of Xiaoyao pill control group， Xiaojin pill control group， Liqi sanjie pill control group， Liqi sanjie granule low-dose and medium-dose groups were shortened significantly； syrup preference and total behavior score of open-field behavior test were increased significantly （P＜0.05 or P＜0.01）. Compared with Liqi sanjie pill control group， the struggling times of rats were decreased significantly and hanging immobility time were prolonged significantly only in Liqi sanjie granule high-dose group （P＜0.05 or P＜0.01）； there was no statistical significance in above indexes of rats in Liqi sanjie granule low-dose and medium-dose groups （P＞0.05）. CONCLUSIONS： Liqi sanjie granule can significantly improve liver-qi stagnation caused by binding method， and the effects of low-dose and medium-dose Liqi sanjie granule are similar to those of Liqi sanjie pill.

Study on Long-term Toxicity of Liqi Sanjie Extractum in Rats with Intragastric Administration / 中国药房

OBJECTIVE： To study the long-term toxicity of Liqi sanjie extractum in rats after intragastric administration， and to provide reference for safety evaluation before clinical practice. METHODS： A total of 160 rats were randomly divided into control group （normal saline） and Liqi sanjie extractum low-dose， medium-dose and high-dose groups （7.828 0， 15.656 0， 31.312 0 g/kg， calculated by crude drug）， with 40 rats in each group. They were given relevant medicine intragastrically once a day from Monday to Saturday. The experimental period was 120 days， and the recovery period was 30 days after the end of the experiment. General information of rats was observed， and body weight and feed consumption of rats were measured once a week. At the 61st day of administration， the end of administration and the end of recovery period， 10， 20 and 10 rats were collected from each group to observe their hematology， blood biochemistry， organ coefficient and histopathology changes. RESULTS： From 61st day to 120th day of administration， the rats of Liqi sanjie extractum high-dose group had hair loss and erection， and recovered after withdrawal of medicine. During medication， the body weight of mice in Liqi sanjie extractum low-dose and medium-dose groups increased faster than control group， while the body weight of rats in Liqi sanjie extractum high-dose group increased slower than control group. Compared with control group， the feed consumption of Liqi sanjie extractum low-dose group increased， while those of Liqi sanjie extractum medium-dose and high-dose groups decreased； the rats were recovered after drug withdrawal. On the 61st day of administration and after the end of administration， some hematological indexes， blood biochemical indexes and organ coefficients of rats in administration group were significantly different from those of control group （P＜0.05 or P＜0.01）. The hematology， blood biochemistry and organ coefficients of rats were basically recovered after the end of the recovery period. The number of erythrocyte， hematocrit， standard deviation of erythrocyte width， albumin， globulin ratio and potassium K+ levels in Liqi sanjie extractum low-dose group were significantly lower than those in control group （P＜0.05 or P＜0.01）. The absolute value of intermediate cells in blood of rats in Liqi sanjie extractum medium-dose group was significantly higher than that of control group （P＜0.05）， and the mean hemoglobin concentration， K+ and uterine coefficient in blood were significantly lower than those of control group （P＜0.05）. The number of white blood cells， absolute value of lymphocyte， absolute value of intermediate cells， the percentage of intermediate cells， prothrombin time and spleen coefficient in Liqi sanjie extractum high-dose group were significantly higher than those in the control group （P＜0.05 or P＜0.01）. Mean hemoglobin concentration， granulocyte percentage， albumin， alkaline phosphatase and K+ were significantly lower than those in the control group （P＜0.05 or P＜0.01）. No abnormalities in systemic autopsy and histopathology were noticed in rats. CONCLUSIONS： Long-term intragastric administration of Liqi sanjie extractum can cause certain toxic reactions in rats， and low dose of Liqi sanjie extractum causes less and lighter toxic reactions which can be automatically recovered after drug withdrawal. It can provide reference for the determination of clinical safe dose.

Study on the Dose-time-effect Relationship of Tibetan Medicine Rannasangpei in Cerebral Ischemia-reperfusion Injury Model Rats with Intragastric Administration / 中国药房

OBJECTIVE： To study the dose-time-effect relationship of Tibetan medicine Rannasangpei in cerebral ischemic- reperfusion injury model rats with intragastric administration. METHODS： The rats were randomly divided into sham operation group （normal saline， 10 mL/kg）， model control group （normal saline， 10 mL/kg）， positive control group （nimodipine， 30      mg/kg）， Rannasangpei different dose groups （0.52， 1.04， 2.08， 4.17， 8.33， 16.67， 33.34， 66.68， 133.36， 266.72 and 533.44    mg/kg）， with 18 rats in each group. Each group was given relevant medicine intragastrically once； 25 min after intragastric administration， cerebral ischemic-reperfusion injury model was established with suture-occluded method in those groups except for sham operation group. 24， 48， 72 h after cerebral ischemia， neuroethology of rats were graded in each group. The rate of cerebral infraction was detected to evaluate the optimal effective time， the optimal dose （Dmax） and maximal effect （the rate of minimum cerebral infraction， Emax） of Ratnasampil at different periods of cerebral ischemia. Dose-time-effect relationship of Rannasangpei dose with the rate of cerebral infraction was fitted with Thermo Kinetica 5.1 software. The area under curve （AUClast） and retention dose （MRTlast） of dose-effect curve were calculated， and detect the levels of SOD and MDA. RESULTS： Compared with sham operation group， the neurobehavior of model group was significantly abnormal （P＜0.05 or P＜0.01）， and the rate of cerebral infarction was significantly increased （P＜0.01）； the level of SOD was decreased significantly （P＜0.01， 48 h）， and the level MDA was increased significantly （P＜0.05， 48 h）. Compared with model control group， there was no significant change in neurobehavioral abnormalities in the nimodipine group （P＞0.05）， and the rate of cerebral infraction was decreased significantly （P＜0.01， 24， 48 h）. The level of SOD in rats were increased significantly （P＜0.01， 48 h）， while the level MDA decreased significantly （P＜0.05， 48 h）. Rannasangpei 2.08-33.34 mg/kg could significantly improved neurobehavioral abnormalities （P＜0.05， 24 h）； 24 h after cerebral ischemia， the rate of cerebral infraction was decreased significantly in Rannasangpei 4.17-133.36 mg/kg group （the lowest is 33.34 mg/kg group， P＜0.05 or P＜0.01）. The level of SOD in rats were increased significantly in 33.34-533.44 mg/kg groups （P＜0.05）. the level MDA was decreased significantly in 0.52-2.08， 8.33， 33.34， 266.72 and 533.44 mg/kg groups （P＜0.05）. Dmax was 33.34 mg/kg， Emax was 3.02％， AUClast was 5 141.76 mg/kg and MRTlast was 329.161 mg/kg. 48 h after cerebral ischemia， the rate of cerebral infraction was decreased significantly in Rannasangpei 2.08-133.36 mg/kg groups （the lowest is 66.68 mg/kg group， P＜0.05 or P＜0.01）， while the level of SOD was increased significantly in 1.04-533.44（except for 4.17）mg/kg groups （P＜0.05）. The level of MDA was decreased significantly in 16.67-66.68， 533.44 mg/kg groups （P＜0.05）， Dmax was 66.68 mg/kg， Emax was 2.13％， AUClast was    5 219.36 mg/kg and MRTlast was 340.521 mg/kg. 72 h after cerebral ischemia， the rate of cerebral infraction and the level of MDA had no significant decreased in Rannasangpei groups （P＞0.05）， and the levels of SOD had no significant increase （except for 0.52 mg/kg group， P＞0.05）. CONCLUSIONS： The optimal effective time of Rannasangpei for the treatment of cerebral ischemia-reperfusion injury in rats is 48 h， and the Dmax is 66.68 mg/kg. The improvement mechanism may be related to increase the level of SOD and decrease the level of MDA.

Introduction of 169 Single-flavored Drugs Included in The Ayurvedic Pharmacopoeia of Indian / 中国药房

OBJECTIVE： To analyze the characteristics of 169 single-flavored drugs in The Ayurvedic Pharmacopoeia of Indian， and to provide reference for China to expand new drug sources and study new indications. METHODS： Sanskrit drug names， botanical names （family names）， Chinese medicine names， medicinal parts， therapeutic uses in Ayurveda， distributions in India， distributions or cultivations （introductions） in other countries and regions， the main treatments of other countries and regions were introduced comprehensively， so as to analyze the distribution， family names characteristics， medicinal part and indication characteristics of 169 single-flavored drugs. RESULTS： Totally 169 single-flavored drugs were mostly distributed in tropical and subtropical regions. There were 116 single-flavored drugs distributed throughout India （including introduction or cultivation） and medicinal； while 51 single-flavored drugs were only distributed in India； 21 single-flavored drugs were distributed and used in China； 10 single-flavored drugs have a distribution in China but have not been used； only one single-flavored drug had been used in China but had no distribution. Yunnan， Guangdong， Guangxi， Fujian were provinces （districs） where Ayurveda single-flavored drug was planted and used more frequently. Sri Lanka， Vietnam and Malaysia were countries where Ayurveda single-flavored drug was planted and used more frequently. The original plants of the 169 single-flavored drugs were derived from Euphorbiaceae and Dipterocarpaceae， Umbelliferae and Morus， etc. More roots and rhizomes were used. The types of commonly treatment diseases were digestive diseases， respiratory diseases， “symptoms， signs， and clinical and laboratory abnormalities， which cannot be classified elsewhere”， skin and subcutaneous tissue diseases， genitourinary system diseases， blood diseases， etc. The diseases with characteristic diagnosis and treatment were caused by imbalance of body wind， intermittent heat， imbalance of mucin and imbalances of three diseases. CONCLUSIONS： 169 single-flavored drugs in this paper are distributed in tropical and subtropical regions， and are often used to treat digestive diseases. This study can provide reference for the introduction and cultivation of Ayurveda single-flavored drug and for the development of new drug sources and new uses in China.

Metabolomics coupled with system pharmacology reveal the protective effect of total flavonoids of Astragali Radix against adriamycin-induced rat nephropathy model.

Astragali Radix (AR) has been used in the traditional Chinese medicine (TCM) in the treatment of various renal diseases for many years. In this study, a NMR based metabolomic approach coupled with biochemical assay and histopathological inspection had been employed to study the protective effect of total flavonoids (TFA) in AR against adriamycin-induced nephropathy using rats model. Multivariate analysis revealed that 11 of perturbed metabolites could be reversed by TFA, and the MetaboAnalyst analysis revealed that the anti-nephrotic syndrome effect of TFA was probably related with regulation of alanine, aspartate and glutamate metabolism, citrate cycle, pyruvate metabolism, cysteine and methionine metabolism and glyoxylate and dicarboxylate metabolism. The regulatory effects on the gene expression (ACE, nephrin, podocin) suggested that the anti-nephrotic syndrome effect of TFA was also related with the protection of renal filtration function and regulation of blood pressure. The system pharmacology analysis revealed 43 potential targets for TFA, and suggested that the protective effect of TFA on the nephrotic syndrome was probably related with the regulation of immune and renin-angiotensin system. These metabolic changes and the associated pathways, as well as the compound-target-disease network provide insights into the mechanisms of TFA for the treatment of nephrotic syndrome, and further studies are needed to validate the bioactive compounds responsible for the anti-nephrotic syndrome effect of TFA.

Research progress on pharmacological action of notoginsenoside R1 / 中国药理学通报

Sanqi in Chinese herbal medicine is the root and rhi-zoma of Panax notoginseng (Burk.)F.H.Chen. As the effects of strengthening with tonics, promoting blood circulation to re-move blood stasis,relieving swelling and pain and hemostasia,it is widely used as a tonic medicine in the traditional Chinese medicine. The main active constituents of Sanqi are panax noto-ginseng saponins,including ginsenoside Rg1,Rb1 and notogin-senoside R1. Notoginsenoside R1 is one of the unique monomer compositions of panax notoginseng,which is often used as an in-gredient indicator in new drug research and development.In cur-rent years, the scientists have been conducted tremendous fun-damental studies to research the pharmacological activities of no-toginsenoside R1, to reveal its protective effects on the cardio-vascular system,central nervous system as well as to many other aspects. It is hoped that the relevant study about the pharmaco-logical action of notoginsenoside R1 would help its further clini-cal application. This paper mainly reviews the research on the pharmacological mechanism of notoginsenoside R1 in recent years.

Sensitive determination of Se(IV) and tSe in rice and water samples using L-cysteine modified carbon paste electrode-based electrolytic hydride generation and atomic fluorescence spectrometry analysis.

This work illustrates an accurate method for determination of Se by electrolytic hydride generation technique based on a novel carbon paste electrode for sample introduction combined with atomic fluorescence spectral analysis. The studies show that Se(IV) can be converted efficiently to SeH2 on an L-cysteine modified carbon paste electrode (CMCPE), which has never been reported before. Significantly, generation from Se(IV) implies that the use of carbon paste electrode-based electron-induced hydride generation system to achieve efficiency is almost 90% to that obtained by chemical hydride generation, and the response obtained from CMCPE is 2 and 3 times of that from the Pb and graphite electrode, respectively. Results also display that the lifetime and the stability of the CMCPE is superior to that of L-cysteine ornamented graphite electrode fabricated by covalently bonding. Under the optimal conditions, a low concentration limit of detection 0.065µgL-1 of Se(IV) is achieved. The repeatability denoted as % RSD is 2.2% for 1.0µgL-1 Se(IV). The utility of the studied method is compared with certified reference materials as well as several edible samples. The advantages and limitations of this method, compared with existing techniques, are also discussed.