Sodium nitroprusside improved the quality of Radix Saposhnikoviae through constructed physiological response under ecological stress.

The ecological significance of secondary metabolites is to improve the adaptive ability of plants. Secondary metabolites, usually medicinal ingredients, are triggered by unsuitable environment, thus the quality of medicinal materials under adversity being better. The quality of the cultivated was heavily declined due to its good conditions. Radix Saposhnikoviae, the dried root of Saposhnikovia divaricata (Turcz.) Schischk., is one of the most common botanicals in Asian countries, now basically comes from cultivation, resulting in the market price being only 1/10 to 1/3 of its wild counterpart, so improving the quality of cultivated Radix Saposhnikoviae is of urgency. Nitric oxide (NO) plays a crucial role in generating reactive oxygen species and modifying the secondary metabolism of plants. This study aims to enhance the quality of cultivated Radix Saposhnikoviae by supplementing exogenous NO. To achieve this, sodium nitroprusside (SNP) was utilized as an NO provider and applied to fresh roots of S. divaricata at concentrations of 0.03, 0.1, 0.5, and 1.0 mmol/L. This study measured parameters including the activities of antioxidant enzymes, secondary metabolite synthesis enzymes such as phenylalanine ammonia-lyase (PAL), 1-aminocyclopropane-1-carboxylic acid (ACC), and chalcone synthase (CHS), as well as the contents of NO, superoxide radicals (O2·-), hydrogen peroxide (H2O2), malondialdehyde (MDA), and four secondary metabolites. The quality of Radix Saposhnikoviae was evaluated with antipyretic, analgesic, anti-inflammatory effects, and inflammatory factors. As a result, the NO contents in the fresh roots were significantly increased under SNP, which led to a significant increase of O2·-, H2O2, and MDA. The activities of important antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD), were found to increase as well, with their peak levels observed on the 2nd and 3rd days. PAL, ACC, and CHS activities were also significantly enhanced, resulting in the increased secondary metabolite contents of Radix saposhnikoviae in all groups, especially the 0.5 mmol/L SNP. The four active ingredients, prim-O-glucosylcimifugin, cimifugin, 4'-O-ß-D-glucosyl-5-O-methylvisamminol, and sec-O-glucosylhamaudol, increased by 88.3%,325.0%, 55.4%, and 283.8%, respectively, on the 3rd day. The pharmaceutical effects of Radix Saposhnikoviae under 0.5 mmol/L SNP were significantly enhanced. Exogenous SNP can induce the physiological response of S. divaricata under adverse conditions and significantly improve the quality of Radix Saposhnikoviae.

High-throughput metabolomic method based on liquid chromatography: high resolution mass spectrometry with chemometrics for metabolic biomarkers and pathway analysis to reveal the protective effects of baicalin on thyroid cancer.

Cell metabonomics focuses on discovering metabolic biomarkers and pathway changes in cells from biological systems to obtain the cell properties and functional information under different conditions. Baicalin possesses various pharmacological activities, and plays a vital role in the oncology research field. However, the detailed mechanism of its action is still unclear. In this work, we employed ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) based non-targeted metabolomics method associated with chemometrics analysis to explore metabolic pathways and biomarkers for investigating the efficacy and pharmacological targets of baicalin against thyroid cancer cells. In addition, morphological observation, parameter calculation of cell proliferation and apoptosis were carried out, which assisted in elucidation of pharmacological activity of baicalin on the human thyroid cancer cells. The results showed that baicalin possesses an intense stimulative apoptosis and inhibits proliferation activity on SW579 human thyroid cancer cells, and partially reversed the cell metabolite abnormalities. A total of nineteen differentiated metabolites in SW579 cells were identified and deemed as potential biomarkers after the baicalin treatment, involving nine metabolic pathways, such as taurine and hypotaurine metabolism, pyrimidine metabolism, fructose and mannose metabolism, steroid hormone biosynthesis and sphingolipid metabolism. High-throughput non-targeted metabolomics provide an insight into specialized mechanism of baicalin against thyroid cancer and contributes to novel drug discovery and thyroid cancer management in clinical practice.

[Exogenous H2O2 regulated secondary metabolism of Scutellaria baicalensis and enhanced drug quality].

The increasing demand of Chinese materia medica could not be supplied by wild resource, and the cultivated medicinal materials become popular, which led to decreased quality of many medicinal materials due to the difference of the circumstance between the wild and the cultivated. How to improve quality becomes key points of Chinese medicine resource. The leaves of Scutellaria baicalensis were sprayed with H2O2, the activities of superoxide dismutase (SOD) and catalase (CAT) changed little, but there had been a marked decrease of peroxidase (POD) and ascorbic oxidase (APX), which showed that the antioxidase system declined. Meanwhile, H2O2, as enhanced the expression of phenylalnine ammonialyase (PAL) and ß-glucuronidase (GUS) as well as activity of PAL, promoted the biosynthesis and biotransformation of flavonoids. At the day 2 after treated, H2O2 of 0.004 µmol·L⁻¹ the contents of the baicalin and the wogonoside decreased slightly, but the contents of the baicalein and the wogonin increased significantly, the baicalein from 0.094% to 0.324%, the wogonin from 0.060% to 0.110%, i. e. increased 246% and 83.3%, respectively.

Chemical metabolomics for investigating the protective effectiveness of Acanthopanax senticosus Harms leaf against acute promyelocytic leukemia.

Recent advances in the study of high-throughput metabolomics combined with high-resolution mass spectrometry have accelerated our understanding of the efficacy, mechanisms, and application of natural products. In this study, we have used chemical metabolomics to investigate and discover small molecule metabolites for the potential mechanism of Acanthopanax senticosus Harms leaf (ASL) against acute promyelocytic leukemia (APL). Based on high-throughput metabolomics, the underlying biomarker was found by combining chromatography coupled with quadrupole time-of-flight mass spectrometry with multivariate data analysis. The protective effect of ASL was dissected using biochemical indicators, pathology sections, immunohistochemistry, and multivariate analysis. Furthermore, 13 potential biomarkers associated with the pathway of sugar metabolism, amino-acid metabolism, nucleotide metabolism, and the metabolism of arachidonic acid were identified from serum samples. This study would help to understand chemical metabolomics for investigating the anti-APL effectiveness of ASL.

Feeble Antipyretic, Analgesic, and Anti-inflammatory Activities were Found with Regular Dose 4'-O-ß-D-Glucosyl-5-O-Methylvisamminol, One of the Conventional Marker Compounds for Quality Evaluation of Radix Saposhnikoviae.

INTRODUCTION: 4'-O-ß-D-glucosyl-5-O-methylvisamminol (GML) is a conventional marker compound for quality control of Radix Saposhnikoviae. Despite that, neither pharmacodynamic or pharmacokinetic information is available with regard to GML. As such, the aim of thisstudy was to assess the conventional evaluation indices for the quality of Radix Saposhnikoviae. MATERIALS AND METHODS: Pyretic animal model, hot plate test, and ear edema model were established to evaluate and compare the antipyretic, analgesic, and anti-inflammatory effect of the chromone derivativescimifugin, prime-O-glucosylcimifugin (PGCN), and GML in Radix Saposhnikoviae. High performance liquid chromatography separation and analysis was used to obtain pharmacokinetic parameters. Simulated gastric fluid and simulated intestinal fluid was used to investigate the metabolite profiles of PGCN and GML in gastrointestinal tract. RESULTS: Cimifugin exerted a marked dose-dependent antipyretic, analgesic, and anti-inflammatory effect, whereas the effects of PGCN were relatively lower. GML had feeble pharmacodynamic effects. Pharmacokinetic study showed that only cimifugin was detected in the plasma sample of cimifugin and PGCN-treated animals, with drug concentration in the former much higher than the latter. No components were traced in the plasma samples from GML-treated rats. Stability study showed that PGCN and GML was predominantly biotransformed into cimifugin and 5-O-methyvisammiol, respectively. The latter was proven to be extremely unstable in liver tissue homogenate and plasma. CONCLUSIONS: A feeble antipyretic, analgesic, and anti-inflammatory activities was observed when GML was orally delivered. Given that Radix Saposhnikoviae extract is generally administered orally, we speculate that this compound might be a nonpharmacolagically active agent in real usage. Thus, it might be unscientific to evaluate the quality of Radix Saposhnikoviae based on the content of GML. SUMMARY: GML-derived cimifugin, which represents the potential pharma codynamic component of Radix Saposhnikoviae chromones, in plasma was almost nil in contrast to cimifugin and PGCN. And thus, feeble antipyretic, analgesic, and anti-inflammatory activities were found with GML. Abbreviations used: AUC:area under concentration-time curve, DNP:2,4-Dinitrophenol, HPLC:high performance liquid chromatography, HPLC-MS:high performance liquid chromatography- mass spectrography, GML:4'-O-ß-D-glucosyl-5-O-methylvisamminol, MVL:5-O-methyvisammiol, PGCN:prime-O-glucosylcimifugin, SGF:alkaline phosphatase. SIF:simulated intestinal fluid.

Polysaccharide enhances Radix Saposhnikoviae efficacy through inhibiting chromones decomposition in intestinal tract.

Vegetative but not reproductive stage of Saposhnikovia divaricate (Turxz.) schischk possesses pharmacological activities. However, our recent study showed that reproductive S. divaricate supplemented with polysaccharide showed evidently elevated pharmacological activities and increased cimifugin content in rat serum. The aims of present study were to assess the influence of polysaccharides on the chromones pharmacological activities in Radix Saposhnikoviae (RS), the dried root of vegetative stage of S. divaricate, and to explore the underlying mechanisms. Only cimifugin was detected in the plasma of chromone treated animals and RS polysaccharide significantly increased the plasma content of cimifugin. It was shown that neither cimifugin absorption nor glycoside components transformation in simulated digestive fluid was affected by RS polysaccharide. However, a significant promotion of transformation of cimifugin to more stable prime-O-glucosylcimifugin (PGCN) by RS polysaccharide, and a protective effect of polysaccharide on chromone components were observed in small intestine solutions. Meanwhile, RS polysaccharide produced a significant elevation of cimifugin and PGCN concentration in vivo. Based on these findings, we concluded that RS polysaccharide could greatly increase the content of cimifugin, which might be related to its degradation-proof effect on cimifugin, via transforming cimifugin to comparatively more stable PGCN and spatial structure protection.

[Regulation on Female-male Flower Ratio of Monoecious Plant Schisandra chinensis Based on Reactive Oxygen Species (ROS)].

OBJECTIVE: To study the effect of reactive oxygen species on female-male flower ratio of Schisandra chinensis in order to improve the yield. METHODS: Spraying different concentration solution of H2O2, paraquat and sodium dithionite on the leaves of Schisandra chinensis before fruit bud initiation. RESULTS: Exogenous sodium dithionite (O2- carrier) increased the female-male flower ratio greatly from 7.6% to 42.3%. H2O2 and paraquat (OH- carrier) had little effect. CONCLUSION: The regulation effects vary according to different ROS. Exogenous sodium dithionite has the best effect.

[Overview of traditional Chinese medicine quality evaluation method based on overall research].

The establishment of quality evaluation of traditional Chinese medicine system that not only accords with Chinese medicine function characteristics but also is recognized as international medical circles, is an arduous task in urgent need of solving the current modernization of traditional Chinese medicine in the process of internationalization. It is difficult to evaluate atraditional Chinese medicine by detection of single active components in traditional Chinesemedicinewiththe western medicine quality controlmethod due to the overall effects of traditional Chinese drugs, the components of the overall diversity, targets, and the complexity of the interaction between components of unpredictable make the Long-term since, domestic and foreign scholars continue to explore and put forward a series of quality evaluation of traditional Chinese medicine to promote the development of traditional Chinese medicine. This article summarized the related academic ideas and developments to, providea new thought and perspective for the quality control of traditional Chinese medicine.

[Progress of serum pharmacochemistry of traditional Chinese medicine and further development of its theory and method].

Serum pharmacochemistry of traditional Chinese medicine (TCM) is designed to screen the efficacy material base of TCMs from the constituents absorbed into the blood after oral administration. The theory and method is in accordance with the effect characteristics of TCMs, and reflects the interaction between the body and the drugs, has become an effective pathway for researching the efficacy material base of TCMs which has been recognized and used widely. In the paper, the previous research contents and methods of the serum pharmacochemistry of TCM were reviewed, and on the basis of the further validity of the special administration form of the TCM formula and the corresponding property to TCM syndrome, the new strategy of serum pharmacochemistry of TCM integrating the metabonomics technologies was put forward. According to the strategy, we take the biological characters of TCM syndrome as a research starting point, taking TCM formula as object, using the metabolic biomarkers of syndromes or disease to evaluate the therapeutic effect of formula and screen the compounds of TCMs in serum which are highly correlated with the metabolic biomarkers through the correlation analysis, and by further biological validation to finally confirm the efficacy material basis of TCMs. Integrating with the systems biology technologies, the theory and method of serum pharmacochemistry of TCM will further develop, and open a new chapter in the interpretation of the theory of TCM.

[Effect of salicylic acid on photosynthesis, physio-biochemistry and quality of Panax ginseng under full sun shine in spring].

In order to search for a new pathway to improve the yield of ginseng through growing at the full sun shine accompanied by salicylic acid (SA), the net photosynthetic rate (P(n)), superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), malondialdehyde (MDA) in Panax ginseng leaves, and the content of ginsenosides in roots were compared under various concentrations of SA and full sun shine with the traditional shade shed. Under the full sun shine, 0.05, 0.2 mmol x L(-1) SA increased net photosynthetic rate to a great extent. Under the cloudy day, the average net photosynthetic rate increased by 127.8% and 155.0% over the traditional shade shed, 13.9% and 27.5% over the treatment without SA respectively; under the clear day, 23.5% and 30.4% over the traditional shade shed, 8.6% and 14.6% over the treatment without SA, particularly obvious in the morning and late afternoon. With such concentration, SA increased activities of SOD, CAT, POD, and decreased the contents of the MDA. This difference resulted from different light intensity, rise of light saturation point, and fall of compensation point. Full sun shine decreased ginsenosides contents, but with SA, the ginsenosides regained, the content of Rg1 and Re, Rb1, total six types of ginsenosides in SA 0.2 mmol x L(-1) group were higher than those in the control group (P < 0.05) and other groups. The application of 0.2 mmol x L(-1) SA under full sun shine during a short time has little threat to the P. ginseng in spring, and could enhance the resistance to the adversity, which would improve the yield of ginseng heavily.

[Effect of improving light intensity on physio-biochemistry of Panax ginseng].

OBJECTIVE: To provide the basis for improving ginseng production by exploring the difference of physio-biochemistry of Panax ginseng after increasing light intensity. METHODS: Activities of superoxide dismutase( SOD), hydrogen peroxidase (CAT), and peroxydase (POD), as well as contents of malondialdehyde (MDA), chlorophyll a and b under full-light condition were compared with those in the shade in spring and autumn. RESULTS: Activity of three kinds of enzymes in the anti-oxidation system (SOD,CAT and POD) were 27.52%, 41.96% and 37.7% higher than the shade group, respectively. The content of MDA was 11.23% lower. There had no obvious difference on the content of chlorophyll a, but chlorophyll b was decreased slightly. CONCLUSION: Increasing the light intensity properly can improve the activities of enzyme protection system, and lower the content of MDA, which indicates that the increasing of light will provide a theoretic guide for high-production technique of Panax ginseng.

[On formation factors of major producing areas for Chinese materia medica and planting regionalization].

After China's foundations, the diminution in wild medicinal plants, social progress, and improvement of science and technology level promoted the cultivation development of the traditional Chinese medicine, the traditional Chinese medicine from cultivation will become the principal source of future commodity. The broad of wide distribution, diversity of environment, and the difference of cultivation benefit formed major producing areas. According to the ecological factors and social and economic development of major producing areas, major producing areas could be divided into quality oriented, yield oriented, benefit oriented, humanity oriented, special environment oriented, and integrated factors oriented, based on the quality and the yield of the Chinese medicine, and economic benefit. The results could provides scientific guidance for the choice of a new optimum growing areas.

[Study on suitability regionalization producing area of vulnerable species Acanthopanax senticosus based on TCMGIS].

OBJECTIVE: To determine the suitable regions of Acanthopanax senticosus and provide the basis for its resource census, reservation, wild nature and cultivation. METHODS: The traditional Chinese medicine geographic information system (TCMGIS) was used to select the suitable producing areas. RESULTS: The ecological environments of 269 counties in 11 province or directly governed city region were suitable for Acanthopanax senticosus. They were located in Xiaoxing'anling, Changbai Mountain, Daxing' anling, Yanshan Mountains, Taihang Mountains and Qinling, among which Heilongjiang accounted for 49.3% and Inner Mongolia reached 22.4%, Jilin reached 16.5%, Liaoning reached 4.3%, the total of Hebei, Beijing, Henan, Shanxi, Sichuan and Gansu was 7.4%.

[Studies on the method for the processing roots of cultivated Saposhnikovia divaricata].

OBJECTIVE: To establishing a standard processing method for cultivated Saposhnikovia divaricata. METHOD: Crude drug was dried at different temperature, and the contents of prim-O-glucosyl-cimifugin,cimifugin,4'-O-beta-glucosyl-5-O-methylvisamminol, sec-O-glucosyl-hamaudol in the processed crude drug were determined by HPLC. RESULT: Of the contents of the four compounds, the sample that heated by 45 degrees C was at the best level. Prim-O-glucosggl-cinmifugin was 0.636%, cimifugin was 0.043%, 5-O-methtlvsamminol was 0.598%, sec-O-glu-cosyl-hamaudol was 1.85%, and total content was 1.302%. CONCLUSION: The best drying temperature for processing is 45 degrees C.