Network pharmacology and experimental verification to explore the anti-superficial thrombophlebitis mechanism of Mailuo shutong pill.

ETHNOPHARMACOLOGICAL RELEVANCE: Mailuo shutong pill (MLST) has been widely used in clinical treatment of superficial thrombotic phlebitis (STP). Nevertheless, the major active components of MLST and the mechanism of synergistic action have not been reported. AIM OF THE STUDY: The present study aimed to evaluate the improving effects and the underlying mechanism of MLST on mannitol-induced STP in rabbits. MATERIAL AND METHODS: In this study, Ultrahigh-performance liquid chromatography electrospray ionization quadrupole-exactive orbitrap mass spectrometry (UHPLC-ESI-Q-Exactive-Orbitrap-MS) was used to analyze and identify the chemical composition of MLST and the prototype components absorbed into the blood. Then, according to the prototype components in serum, the targets and mechanisms of MLST were explored by applying network pharmacology. The rabbit model of STP was established by injecting 20% mannitol into bilateral auricular vein. The pathological changes of rabbit ear tissues, inflammatory factors, coagulation function and hemorheology were detected. In addition, molecular docking verified the interaction between the main active ingredient and the key target. Finally, the PI3K/AKT pathway and its regulated downstream pathways were verified by Western blot. RESULTS: A total of 96 MLST components and 53 prototypical components absorbed into the blood were successfully identified. Based on network pharmacology, PI3K/AKT pathway and 10 chemical components closely related to this pathway were obtained. Hematoxylin-eosin (HE) staining results indicated that MLST effectively improved of the pathological damage of ear tissues. MLST decreased levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and C-reactive protein (CRP). The expression of platelets (PLT) and fibrinogen concentration (FIB) was decreased, while prothrombin time (PT) and activated partial thromboplastin time (APTT) were prolonged. In addition, the plasma viscosity and whole blood viscosity in the MLST groups were significantly decreased. The more important discovery was that the expressions of P-PI3K, VEGF, P-AKT, P-IκB-α, P-NF-κB, NLRP3, ASC, Cleaved IL-1ß and Cleaved Caspase-1 were effectively reversed after treatment with MLST. CONCLUSIONS: This study comprehensively analyzed and characterized the chemical composition of MLST and the prototypical components absorbed into the blood. This study strongly confirmed the pharmacodynamic effect of MLST on STP. More importantly, this pharmacodynamic effect was achieved through inhibition of the PI3K/AKT pathway and its regulated NF-κB and NLRP3 pathways.

Pharmacokinetics, tissue distribution and excretion of six bioactive components from total glucosides picrorhizae rhizoma, as simultaneous determined by a UHPLC-MS/MS method.

Total glucosides picrorhizae rhizome (TGPR) is an innovative traditional Chinese medicine, which is a candidate drug for the treatment of nonalcoholic steatohepatitis (NASH). However, there is still lack of deep research on the behaviors of TGPR in vivo. In this study, a reliable, specific, and sensitive liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method has been constructed for simultaneous determination of picroside I, picroside II, vanillic acid, androsin, cinnamic acid and picroside IV, the major active constituents of TGPR, in rat various biological matrices (plasma, tissue, bile, urine and feces) using diphenhydramine hydrochloride and paeoniflorin as the internal standard. All biosamples were prepared using a simple protein precipitation with acetonitrile. Chromatographic separation was achieved on a waters UHPLC® HSS T3 (100×2.1 mm, 1.8 µm) column. The mobile phase consisted of methanol: acetonitrile1(1:1, V/V) and 0.5 mM ammonium formate in water, was employed to separate six components from endogenous interferences. The components were detected with a triple quadrupole mass spectrometer using positive and negative ion multiple reaction monitoring (MRM) mode. The newly developed method was successfully applied to investigate the pharmacokinetics, tissue distribution and excretion of six components in rats. The pharmacokinetic results indicated that the six components in TGPR could be quickly absorbed and slowly eliminated and their bioavailability were less than 12.37%, which implied the poor absorption after intragastric dosing. For tissue distribution, the six components in TGPR were detected in liver and only androsin could penetrate the blood-brain barrier. Meanwhile, the excretion study demonstrated that vanillic acid was mostly excreted as prototype drugs and the remaining five components might be widely metabolized in vivo as the metabolites, the unconverted form was excreted mainly by feces route. The pharmacokinetics, tissue distribution and excretion characteristics of six bioactive components in TGPR were firstly revealed, which will provide references for further clinical application of TGPR as an anti-NASH drug.

Rhizobacterial compositions and their relationships with soil properties and medicinal bioactive ingredients in Cinnamomum migao.

Introduction: Rhizobacterial communities and their metabolites can affect plant growth, development, and stress resistance, as well as the biosynthesis and accumulation of bioactive compounds in medicinal plants. This relationship has been well-characterized in many medicinal herbs, although much less commonly in medicinal trees. Methods: Here, we analyzed the composition and structure of Cinnamomum migao rhizobacterial communities across nine growing regions in Yunnan, Guizhou and Guangxi, China, as well as differences in soil properties and fruit bioactive compounds. Results: Results showed that the C. migao rhizobacterial communities exhibited high species richness, but location-specific differences in structure. Site-specific differences in soil properties and bioactive compounds were also observed. Furthermore, rhizobacterial community compositions were correlated with both soil properties and fruit bioactive compounds, metabolism-related functions were most common in C. migao rhizobacteria. Discussion: Several bacterial genera, including Acidothermus, Acidibacter, Bryobacter, Candidatus_Solibacter, and Acidimicrobiales, potentially promote the biosynthesis and accumulation of 1,8-cineole, cypressene, limonene, and α-terpineol, Nitrospira and Alphaproteobacteria may play an inhibitory role. Finally, our results emphasized the critical role that soil pH and nitrogen levels play in driving rhizobacterial community structure, and specific functional bacteria can also counteract with soil properties, Acidibacter and Nitrospira can affect soil pH and nitrogen effectiveness. Overall, this study provides additional insight into the complex correlation of rhizosphere microorganisms with bioactive ingredients and soil properties of medicinal plants.

Shouhui Tongbian Capsules induce regression of inflammation to improve intestinal barrier in mice with constipation by targeted binding to Prkaa1: With no obvious toxicity.

Constipation arising from the poor bowel movement is a rife enteric health problem. Shouhui Tongbian Capsule (SHTB) is a traditional Chinese medicine (TCM) which effectively improve the symptoms of constipation. However, the mechanism has not been fully evaluated. The purpose of this study was to evaluate the effect of SHTB on the symptoms and intestinal barrier of mice with constipation. Our data showed that SHTB effectively improved the constipation induced by diphenoxylate, which was confirmed by shorter first defecation time, higher internal propulsion rate and fecal water content. Additionally, SHTB improved the intestinal barrier function, which was manifested by inhibiting the leakage of Evans blue in intestinal tissues and increasing the expression of occludin and ZO-1. SHTB inhibited NLRP3 inflammasome signaling pathway and TLR4/NF-κB signaling pathway, reduced the number of proinflammatory cell subsets and increased the number of immunosuppressive cell subsets to relieve inflammation. The photochemically induced reaction coupling system combined with cellular thermal shift assay and central carbon metabolomics technology confirmed that SHTB activated AMPKα through targeted binding to Prkaa1 to regulate Glycolysis/Gluconeogenesis and Pentose Phosphate Pathway, and finally inhibited intestinal inflammation. Finally, no obvious toxicity related to SHTB was found in a repeated drug administration toxicity test for consecutive 13 weeks. Collectively, we reported SHTB as a TCM targeting Prkaa1 for anti-inflammation to improve intestinal barrier in mice with constipation. These findings broaden our knowledge of Prkaa1 as a druggable target protein for inflammation inhibition, and open a new avenue to novel therapy strategy for constipation injury.

Different Arbuscular Mycorrhizal Fungi Established by Two Inoculation Methods Improve Growth and Drought Resistance of Cinnamomum Migao Seedlings Differently.

Drought stress is one of the greatest obstacles affecting field crop productivity in arid and semi-arid regions, and its severity and frequency are expected to increase due to human-induced changes to the environment and climate. Drought has led to rocky desertification in Karst regions. Cinnamomum migao is a unique, fast-growing medicinal plant of Southwest China that only thrives in Karst regions. Arbuscular mycorrhizal fungi (AMF) symbiosis alleviates drought stress in plants; however, establishment and function of the symbiotic interaction between AMF host plant in relation to the inoculation method remain unclear. Therefore, we conducted an experiment to investigate the effects of AMF species (Glomus etunicatum and Funneliformis mosseae) and two inoculation methods (seed vs. seedling inoculation) under drought stress on C. migao seedlings, and quantified mycorrhizal colonization, AMF spore density, root vigor, relative water content, C. migao growth, antioxidant enzyme activities, and osmotic adjustment. Inoculation with AMF (G. etunicatum and F. mosseae) positively affected the growth and root vigor of Cinnamomum migao under drought stress, regardless of the inoculation method. Additionally, both AMF species markedly upregulated antioxidant enzyme activities and osmotic adjustment substances, regardless of the inoculation method. Our results showed that the collective stimulatory effect of G. etunicatum is more efficient than that of F. mosseae. AMF application could promote afforestation with C. migao to prevent rocky desertification in Karst regions where water is the greatest limiting factor on plant growth and yield.

Ligand fishing with cellular membrane-coated cellulose filter paper: a new method for screening of potential active compounds from natural products.

Ligand fishing is a widely used approach for screening active compounds from natural products. Recently, cell membrane (CM) as affinity ligand has been applied in ligand fishing, including cell membrane chromatography (CMC) and CM-coated magnetic bead. However, these methods possess many weaknesses, including complicated preparation processes and time-consuming operation. In this study, cheap and easily available cellulose filter paper (CFP) was selected as carrier of CM and used to fabricate a novel CM-coated CFP (CMCFP) for the first time. The type of CFP was optimized according to the amount of immobilized protein, and the immobilization of CM onto CFP by the insertion and self-fusion process was verified by confocal imaging. The CMCFP exhibited good selectivity and stability and was used for fishing potentially active compounds from extracts of Angelica dahurica. Three potentially active compounds, including bergapten, pabulenol, and imperatorin, were fished out and identified. The traditional Chinese medicine systems pharmacology database and analysis platform was used to build an active compound-target protein network, and accordingly, the gamma-aminobutyric acid receptor subunit alpha-1 (GABRA1) was deduced as potential target of CM for the active compounds of Angelica dahurica. Molecular docking was performed to evaluate the interaction between active compounds and GABRA1, and bergapten was speculated as a new potentially active compound. Compared with other methods, the fishing assay based on CMCFP was more effective, simpler, and cheaper.

Exploring pharmacological mechanisms of Xueshuan-Xinmai-Ning tablets acting on coronary heart disease based on drug target-disease gene interaction network.

BACKGROUND: Xueshuan-Xinmai-Ning Tablet (XXNT), a commercially available patent drug, has been extensively used in the treatment of coronary heart disease (CHD) with a satisfying therapeutic efficacy. The aim of this study was to explore the underlying pharmacological mechanisms of XXNT acting on CHD. STUDY DESIGN: An integrative pharmacology-based investigation was performed. METHOD: Putative targets of composite compounds contained in XXNT were predicted using the Drug Target Prediction Tool in the Computation Platform for Integrative Pharmacology of Traditional Chinese Medicine (TCMIP, www.tcmip.cn) and MedChem Studio. Then, an interaction network of XXNT putative targets-known CHD-related genes was constructed, and candidate XXNT targets related to its therapeutic effects on CHD were identified by calculating three major network topological features. Functional enrichment analysis was performed to investigate the specific functions and pathways involved by the candidate XXNT targets acting on CHD, which were further validated by in vitro experiments. RESULTS: A total of 742 putative targets hit 126 chemical components contained in XXNT were predicted. Following the construction of XXNT putative target-known CHD-related gene network, and the network topological feature calculation, we identified 51 candidate XXNT targets related to its therapeutic effects on CHD. Functionally, these candidate XXNT targets were significantly associated with various cardiovascular system-related pathways, sedation-related pathways, inflammatory and immune-related pathways and endocrine/metabolic system-related pathways. More importantly, the in vitro experiment validation confirmed the regulatory effects of XXNT in SRC, VEGF and VEGFR-1, which play roles in VEGF signaling pathway, based on the endothelial injury cell model. CONCLUSION: Our findings reveal that XXNT may attenuate the major pathological changes of CHD through regulating its candidate targets, which might be involved into the signal transductions in nervous-endocrine-immune-cardiovascular-metabolic system.

Application of a sensitive and specific LC-ESI-MS/MS method for the simultaneous quantification of twelve bioactive components in dog plasma for an intravenous pharmacokinetic study of Yiqifumai Injection in beagle dogs.

Yiqifumai Injection is a lyophilized powder preparation widely used to treat coronary heart disease. However, its in vivo bioactive components and pharmacokinetic behavior remain unknown. Therefore a sensitive and specific LC-MS/MS was developed and validated for the simultaneous quantification of eight saponins and four lignans in beagle dog plasma. The plasma samples were pretreated by protein precipitation with methanol-acetonitrile (1:1, v/v). Chromatographic separation of all the 12 analytes and estazolam (internal standard, IS) was successfully accomplished on an Ultimate® XB-C8 column (100 × 2.1 mm, 3 µm) with a gradient elution system. The total running time was 8 min with a flow rate of 0.40 mL/min. Acquisition of mass spectrometric data was performed via positive electrospray ionization in multiple reaction monitoring mode. The assay was fully validated in terms of selectivity, linear range, lower limit of quantitation, precision, accuracy, matrix effect, recovery and stability. This validated method was successfully applied to the pharmacokinetics of 12 bioactive components after intravenous administration of Yiqifumai Injection to beagle dogs at a dose of 0.541 g/kg.

Research on Q-markers of Qiliqiangxin capsule for chronic heart failure treatment based on pharmacokinetics and pharmacodynamics association.

BACKGROUND: Qiliqiangxin capsule (QLQX), composed of 11 herbs, is an effective traditional Chinese medicine (TCM) that has been widely used for treatment of chronic heart failure (CHF) in China. In the Chinese pharmacopoeia (Ch.P.) only astragaloside was described as the marker component to control the quality of QLQX, which could not reflect the overall effectiveness. PURPOSE: The aim of this work was to investigate the quality markers (Q-markers) of QLQX based on the association of the pharmacodynamics (PD) of inhibitory effect on activated renin-angiotensin-aldosterone system (RAAS) and the pharmacokinetics (PK) of bioactive compounds according to the Q-marker theory. METHODS: The contents of astragaloside, calycosin-7-glucoside, sinapine, ginsenoside Rb1, ginsenoside Rb2, ginsenoside Rg1, salvianolic acid A, salvianolic acid B, danshensu, rosmarinic acid, formononetin, aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine and benzoylhypacoitine were determined by an HPLC-MS/MS method both in QLQX preparation and in the plasma of CHF rats administered intragastrically with QLQX. The effect of lowering angiotensin II (Ang II) production by QLQX was assayed by ELISA. The association between PK and PD was explored and the bioactive compounds with higher content in vitro and better exposure in vivo, which were closely related to the inhibitory effect on the activated RAAS, were identified as Q-markers of QLQX for CHF treatment. RESULTS: The contents of 17 constituents were in the order of salvianolic acid B > danshensu > ginsenoside Rb1 > sinapine > benzoylmesaconine > astragaloside > benzoylhypacoitine > ginsenoside Rb2 > salvianolic acid A > ginsenoside Rg1 > calycosin-7-glucoside > rosmarinic acid > formononetin > benzoylaconine > hypaconitine > aconitine > mesaconitine in QLQX preparation. PK and PD association study of 14 bioactive compounds of QLQX showed the maximum effect (Emax) of astragaloside, calycosin-7-glucoside, sinapine and ginsenoside Rg1 and their peak concentration (Cmax) appeared at the same time; while the time of Emax of ginsenoside Rb1, ginsenoside Rb2, salvianolic acid A, salvianolic acid B, danshensu, rosmarinic acid, formononetin, benzoylaconine, benzoylmesaconine and benzoylhypacoitine was delayed from the time of their Cmax. CONCLUSIONS: Astragaloside, calycosin-7-glucoside, sinapine and ginsenoside Rg1 are suitable as the Q-markers of QLQX for CHF treatment, which have higher content in vitro, finer exposure in vivo and a direct correlation with the inhibitory effect on activated RAAS.

Determination of quality markers of Xuezhiling tablet for hyperlipidemia treatment.

BACKGROUND: The massive number of ingredients in traditional Chinese medicines (TCMs) makes quality control very difficult. The concept of quality markers (Q-marker) was recently proposed to evaluate the quality of TCMs. Xuezhiling tablets (XZL) are widely used for the treatment of hyperlipidemia in China owing to its noticeable effectiveness and mild adverse effects, but there are no proper Q-markers for this Chinese patent medicine. PURPOSE: The aim of the present study was to determine the Q-markers of XZL against hyperlipidemia through an integration of investigations on its lipid-lowering effect, metabolomics, content determination and pharmacokinetics. METHODS: XZL was prepared in accordance with the method described in the Chinese pharmacopoeia (Ch.P.). Hyperlipidemia was induced in rats through the administration of a high-fat diet (HFD). The hypolipidemic effect of XZL was investigated through the detection of the blood levels of total glyceride (TG), total cholesterol (TC), and low density lipoprotein cholesterol (LDL-C). A metabolomics study was conducted to analyze the overall effects of XZL on the regulation of lipid metabolism. The main bioactive compounds of XZL were identified and determined in the XZL preparation and the medicated plasma of hyperlipidemic rats. RESULTS: XZL lowered the levels of TG, TC, and LDL-C through alterations of metabolic patterns. 2,3,5,4'-Tetrahydroxystilbene-2-O-ß-D-glucopyranoside (THSG), chrysophanol-1-O-ß-glucopyranosyl-(1→3)-O-ß-D-glucopyranosy1-(1→6)-O-ß-D-glucopyranosyl-(1→6)-O-ß-D-glucopyranoside (SHJ), cassiaside, rubrofusarin gentiobioside, aurantio-obtusin, chryso-obtusin, and obtusinfolin were identified and determined both in the preparation and the blood of hyperlipidemic rats. CONCLUSION: SHJ, obtusinfolin, THSG, rubrofusarin gentiobioside, and aurantio-obtusin, which are more abundant in the preparation, leading to greater exposure in vivo, were suitable Q-markers to guarantee the medicinal quality of XZL and ensure the clinical effectiveness on hyperlipidemia.

Identifying potential quality markers of Xin-Su-Ning capsules acting on arrhythmia by integrating UHPLC-LTQ-Orbitrap, ADME prediction and network target analysis.

BACKGROUND: Quality marker (Q-markers) has been proposed as a novel concept for quality evaluation and standard elaboration of traditional Chinese medicine (TCM). Xin-Su-Ning capsule (XSNC) has been extensively used for the treatment of arrhythmia with the satisfactory therapeutic effects in clinics. However, it is lack of reliable and effective Q-markers of this prescription. PURPOSE: To identify potential Q-markers of XSNC against arrhythmia. STUDY DESIGN: An integrative pharmacology-based investigation was performed. METHODS: Ultra-high-pressure liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap) was performed to identify the preliminary chemical profile of XSNC in a rapid and high-throughput manner. Then, in silico Absorption-Distribution-Metabolism-Excretion (ADME) models were utilized to screen candidate active chemical compounds characterized by drug-likeness features. In addition, drug target-disease gene interaction network was constructed, and network features were calculated to identify key candidate targets and the potential Q-markers of XSNC against arrhythmia. RESULTS: A total of 41 chemical compounds with good drug-likeness and more chances to be absorbed into body were identified as the candidate bioactive chemical compounds which might offer contributions to the therapeutic effects of XSNC against arrhythmia in vivo. Following the prediction of 921 XSNC putative targets and the construction of XSNC putative target-known therapeutic target of arrhythmia interaction network, 315 hub nodes with high connectivity were selected. Functionally, the hub nodes were involved into modulation of cardiac sympatho-vagal balance, regulation of energy production and metabolism, as well as angiogenesis and vascular circulation during the development and progression of arrhythmia. Moreover, 63 major hubs with network topological importance were chosen as XSNC candidate targets against arrhythmia. Furthermore, berberine, palmatine, scopoletin, liquiritigenin, naringenin, formononetin, nobiletin, tangeretin, 5-demethylnobiletin, kushenol E and kurarinone hitting the corresponding XSNC candidate targets were screened out to be the potential Q-markers of XSNC against arrhythmia. CONCLUSION: Our integrative pharmacology-based approach combining UHPLC-LTQ-Orbitrap, in silico ADME prediction and network target analysis may be efficient to identify potential Q-markers of TCM prescriptions. Our data showed that berberine, palmatine, scopoletin, liquiritigenin, naringenin, formononetin, nobiletin, tangeretin, 5-demethylnobiletin, kushenol E and kurarinone might function as candidate markers for qualitative evaluation of XSNC.

Identification of quality markers of Yuanhu Zhitong tablets based on integrative pharmacology and data mining.

BACKGROUND: The quality evaluation of traditional Chinese medicine (TCM) formulations is needed to guarantee the safety and efficacy. In our laboratory, we established interaction rules between chemical quality control and biological activity evaluations to study Yuanhu Zhitong tablets (YZTs). Moreover, a quality marker (Q-marker) has recently been proposed as a new concept in the quality control of TCM. However, no appropriate methods are available for the identification of Q-markers from the complex TCM systems. PURPOSE: We aimed to use an integrative pharmacological (IP) approach to further identify Q-markers from YZTs through the integration of multidisciplinary knowledge. In addition, data mining was used to determine the correlation between multiple constituents of this TCM and its bioactivity to improve quality control. METHODS: The IP approach was used to identify the active constituents of YZTs and elucidate the molecular mechanisms by integrating chemical and biosynthetic analyses, drug metabolism, and network pharmacology. Data mining methods including grey relational analysis (GRA) and least squares support vector machine (LS-SVM) regression techniques, were used to establish the correlations among the constituents and efficacy, and dose efficacy in multiple dimensions. RESULTS: Seven constituents (tetrahydropalmatine, α-allocryptopine, protopine, corydaline, imperatorin, isoimperatorin, and byakangelicin) were identified as Q-markers of YZT using IP based on their high abundance, specific presence in the individual herbal constituents and the product, appropriate drug-like properties, and critical contribution to the bioactivity of the mixture of YZT constituents. Moreover, three Q-markers (protopine, α-allocryptopine, and corydaline) were highly correlated with the multiple bioactivities of the YZTs, as found using data mining. Finally, three constituents (tetrahydropalmatine, corydaline, and imperatorin) were chosen as minimum combinations that both distinguished the authentic components from false products and indicated the intensity of bioactivity to improve the quality control of YZTs. CONCLUSIONS: Tetrahydropalmatine, imperatorin, and corydaline could be used as minimum combinations to effectively control the quality of YZTs.

A network pharmacology-based strategy deciphers the underlying molecular mechanisms of Qixuehe Capsule in the treatment of menstrual disorders.

BACKGROUND: QiXueHe Capsule (QXHC) is a Chinese patent drug that is extensively used for the treatment of menstrual disorders. However, its underlying pharmacological mechanisms have not been fully elucidated. METHODS: A list of QXHC putative targets were predicted using MetaDrug. An interaction network using links between QXHC putative targets and the known therapeutic targets of menstrual disorders was constructed. QXHC candidate targets were also identified via calculating the topological feature values of nodes in the network. Additionally, molecular docking simulation was performed to determine the binding efficiency of QXHC compound-putative target pairs. RESULTS: A total of 1022 putative targets were predicted for 311 chemical components containing in QXHC. Following the calculation of topological features of QXHC putative target-known therapeutic target of menstrual disorder network, 66 QXHC candidate targets for the treatment of menstrual disorders were identified. Functionally, QXHC candidate targets were significantly associated with several biological pathways, such as VEGF and Chemokine signaling pathways, Alanine/aspartate/glutamate metabolism, Long-term depression and T/B cell receptor signaling pathway. Moreover, molecular docking simulation demonstrated that there were 20 pairs of QXHC chemical component-candidate target had the strong binding free energy. CONCLUSIONS: This novel and scientific network pharmacology-based study holistically deciphers that the pharmacological mechanisms of QXHC in the treatment of menstrual disorders may be associated with its involvement into hemopoiesis, analgesia, nutrients absorption and metabolism, mood regulation, as well as immune modulation.

[Effects of seed priming on physiology of seed germination and seeding growth of Marsdenia tenacissima under NaCl stress].

To offer the reference and method for salt damage in the cultivation of Marsdenia tenacissima, the seeds of M. tenacissima collected from Maguan city ( Yunnan province) were taken as the test materials to study the effects of different priming materials on improving germination and growth under high-level salt stress condition. Four different treatments, which were GA3, KNO3-KH2PO4, PEG-6000, NaCl, combined with ANOVA were applied to test the performance of germination energy, germination percentage, germination index, MDA, SOD, and CAT. The results showed that the seed germination was obviously inhibited under salt stress and the soaked seeds with different priming materials could alleviate the damage of salt stress. Under these treatments, the activities of SOD, CAT the content of soluble protein significantly increased. While the content of MDA significantly decreased. The maximum index was obtained when treated with 1.20% KNO3-KH2PO4, the germination percentage increased from 52.67% to 87.33% and the activity of SOD increased from 138.01 to 219.44 respectively. Comparing with the treatment of 1.20% KNO3-KH2PO4, the germination percentage of treating with 300 mg x L(-1) GA3 increased from 52.67% to 80.67%, while the activity of SOD increased from 138.01 to 444.61.

[FTIR fingerprint spectrograms of traditional Chinese medicine Marsdenia tenacissima].

In this paper, Fourier transform infrared spectroscopy fingerprint analysis of Marsdenia tenacissima samples was used to develop a reliable method of tracing the geographical origins. Forty-eight samples from four provinces of China were analyzed by FTIR. We analyzed and characterized the fingerprints in both the full spectrum peaks and characteristic peaks, then the principal component analysis and the cluster analysis were carried out. The results of fingerprint analysis, correlation analysis, principal component analysis and cluster analysis can identify the geographic origins correctly, which verified and supplemented each other; the identification results and the actual location showed a high degree of consistency, namely the lower the space distance, the greater the similarity of different samples. These results revealed the obvious superiority and practical value in comparison to the more tedious and time-consuming wet chemistry method normally used. Using appropriate metrology methods can trace the geographical source correctly. The M. tenacissima materials from the region of Maguan should be considered as genuine medicinal materials taking into account the good quality.

Phytochemical and pharmacological studies on Radix Angelica sinensis.

The roots of Angelica sinensis (RAS), are a Chinese herbal medicine traditionally used in prescriptions for replenishing blood, treating abnormal menstruation, and other women's diseases. It has also been widely marketed as health food for women's care in Asia, and as a dietary supplement in Europe and America. RAS is well-known for its hematopoietic, antioxidant, and immunoregulatory activities. RAS also possesses anti-cancer, memory, radioprotective, and neuroprotective effects. Phytochemical investigations on this plant led to organic acids, phthalides, polysaccharides, and other metabolites. Based on recent animal studies and clinical trials, RAS has been used in the treatment of gynecologic diseases, cardio-cerebrovascular disease, nervous system diseases, and nephrotic syndrome. In this review, the recent phytochemical and pharmacological studies, drug-drug interactions, clinical applications, and toxicity of RAS are summarized.

Identification of the absorbed constituents after oral administration of Yuanhu Zhitong prescription extract and its pharmacokinetic study by rapid resolution liquid chromatography/quadrupole time-of-flight.

Yuanhu Zhitong prescription (YZP) is well known for its analgesic effect. However, its multiple bioactive components in vivo remain unclear. In this paper, a rapid resolution liquid chromatography/quadrupole time-of-flight (RRLC-ESI-Q/TOF) was employed to identify the bioactive components and partial metabolites after oral administration of YZP extracts. Meanwhile, a RRLC-ESI-Q/TOF method was established and validated for the simultaneous quantification of protopine, α-allocryptopine, tetrahydropalmatine, corydaline, tetrahyberberine and byakangelicin in rat plasma and applied for their pharmacokinetic research. The results showed that twenty-one bioactive components of YZP were absorbed into the blood circulation and seventeen components were detected in cerebrospinal fluid (CSF). Moreover, the kinetic profiles of six analytes were obtained and the results suggested that the six analytes peaked between 3.5 and 5.0h and Cmax ranged from 214.6 to 858.3. The works could provide key information for identification of bioactive constituents and understanding the metabolism as well as pharmacological actions for YZP.

A computational drug-target network for yuanhu zhitong prescription.

Yuanhu Zhitong prescription (YZP) is a typical and relatively simple traditional Chinese medicine (TCM), widely used in the clinical treatment of headache, gastralgia, and dysmenorrhea. However, the underlying molecular mechanism of action of YZP is not clear. In this study, based on the previous chemical and metabolite analysis, a complex approach including the prediction of the structure of metabolite, high-throughput in silico screening, and network reconstruction and analysis was developed to obtain a computational drug-target network for YZP. This was followed by a functional and pathway analysis by ClueGO to determine some of the pharmacologic activities. Further, two new pharmacologic actions, antidepressant and antianxiety, of YZP were validated by animal experiments using zebrafish and mice models. The forced swimming test and the tail suspension test demonstrated that YZP at the doses of 4 mg/kg and 8 mg/kg had better antidepressive activity when compared with the control group. The anxiolytic activity experiment showed that YZP at the doses of 100 mg/L, 150 mg/L, and 200 mg/L had significant decrease in diving compared to controls. These results not only shed light on the better understanding of the molecular mechanisms of YZP for curing diseases, but also provide some evidence for exploring the classic TCM formulas for new clinical application.

Drug metabolism and pharmacokinetics of nanodrugs from Chinese medicines and natural products.

Over the past few years, nanoscale Chinese medicine has become one of focuses in modern Chinese medicine research. There is an increasing need for a more systematic study on the basic issues involved in traditional Chinese medicine and a more active participation of researchers in the application area of nanoscale traditional Chinese drugs. In this review, author analyzed the current applications of nanotechnology in research and development of drugs from natural products and herbal medicines involving traditional Chinese medicines, and also discussed the bio-medicinal evaluation issues on ADME including bio-distribution and metabolism of nanodrugs. Author noted that great challenges faced in nanodrugs from herb drugs and natural products are the follows: (1) the first challenge is to prepare nanodrug delivery system and quantitatively evaluate the therapeutic effects and safety; (2) the second challenge is to clarify the concrete metabolism course; and (3) the third challenge is to study the pharmacokinetics of nanodrugs.

Herb-drug interactions involving drug metabolizing enzymes and transporters.

Herbal medicines and their active ingredients are widely used worldwide, and they have become an important part of clinical medicine. The combined use of herbs and drugs has increased the possibility of pharmacokinetic and pharmacodynamic interactions. Clinical studies have demonstrated that the combined use of herbs and drugs can enhance or attenuate the drug efficacy and toxicity. The herb-drug combinations may reduce a drug efficacy and lead to treatment failure when long-term administration. Case reports detailing serious clinical adverse reactions have promoted studies on the interactions between herbs and drugs. This review highlights recent knowledge to discuss herb-drug interactions involving metabolizing enzymes and drug transporters. Drug transporters are widely present in body and play an important role in the absorption, distribution, excretion and metabolism, efficacy, and toxicity of drugs. Investigation of transporters has developed rapidly since 1990s, the effects of many transporters on the pharmacokinetics of drugs and herb-drug interactions have been reported. Some concepts on drug transporters issued experimentally and clinically drug-drug and herb-drug interactions have applied in many studies. Methodology studies are very important for understanding the mechanism, considerations and evaluation of experiments and clinical studies on drug metabolizing enzymes and transporters in drug-drug interactions.