Analysis of flavonoids and phenylethanoid glycosides in the Tibetan herb Lagotis brevituba Maxim based on UHPLC-LTQ-orbitrap-MS / 药学学报

Ultra high performance liquid chromatography tandem linear ion trap orbitrap mass spectrometry (UHPLC-LTQ-orbitrap-MS) was applied to analyze and identify flavonoids and phenylethanoid glycosides in the Tibetan herb Lagotis brevituba Maxim. A method of data-dependent scan coupling with dynamic exclusion was developed for analyzing flavonoids and phenylethanoid glycosides under positive and negative ion mode of electrospray ionization (ESI). The compounds of Lagotis brevituba Maxim. were systematically identified through exact molecular mass, fragmentation patterns, retention time and reported references. A total of 167 compounds were detected, of which 84 were flavonoids and 83 were phenylethanoid glycosides, which greatly enriched the number and types of flavonoids and phenylethanol glycosides in Lagotis genus medicinal plants. Baohuoside Ⅰ, 4 disaccharide O-glycoside flavonoids (composed of deoxyhexose and glucuronic acid), 9 C-glycoside flavonoids, 15 tetrasaccharide phenylethanoid glycosides and 5 phenylethanoid glycosides with substituents on the β-position of the phenylethyl group were identified in Lagotis genus medicinal plants for the first time. This study provides scientific support for elucidating the material basis and improving the quality control of Lagotis brevituba Maxim.

HIF-1: structure, biology and natural modulators / 中国天然药物

Hypoxia-inducible factor 1 (HIF-1), as a main transcriptional regulator of metabolic adaptation to changes in the oxygen environment, participates in many physiological and pathological processes in the body, and is closely related to the pathogenesis of many diseases. This review outlines the mechanisms of HIF-1 activation, its signaling pathways, natural inhibitors, and its roles in diseases. This article can provide new insights in the diagnosis and treatment of human diseases, and recent progress on the development of HIF-1 inhibitors.

Recent advances in surface-enhanced Raman scattering technique for pollutant detection in Chinese medicinal material / 中国中药杂志

Chinese medicinal material is the foundation of traditional Chinese medicine(TCM) industry. Its quality is not only closely related to the health of residents but also the key to the development of the TCM industry. Pesticide residues, heavy metals and mycotoxins are the major pollutants of Chinese medicinal materials. In recent years, quite a number of rapid detection methods for pollutants have been constructed. Among them, surface-enhanced Raman scattering(SERS), which has been widely used in food chemistry, environmental analysis, and other fields because of its speediness and non-destructiveness, shows its great potential in the pollutant detection in Chinese medicinal material. This paper firstly reviews the application of SERS for the detection of common pollutants in Chinese medicinal material. We then discussed the characteristics and advantages of SERS technique for pesticide detection, including the principle, SERS substrate design, specific recognition, etc. Finally, simultaneous detection of multiple pesticide residues in Chinese medicinal material was explored.

Nagilactone E increases PD-L1 expression through activation of c-Jun in lung cancer cells / 中国天然药物

Nagilactone E (NLE), a natural product with anticancer activities, is isolated from Podocarpus nagi. In this study, we reported that NLE increased programmed death ligand 1 (PD-L1) expressions at both protein and mRNA levels in human lung cancer cells, and enhanced its localization on the cell membrane. Mechanistically, NLE increased the phosphorylation and expression of c-Jun, and promoted the localization of c-Jun in the nucleus, while silencing of c-Jun by small interfering RNA (siRNA) reduced NLE-induced PD-L1. Further study showed that NLE activated the c-Jun N-terminal kinases (JNK), the upstream of c-Jun, and its inhibitor SP600125 reversed the NLE-increased PD-L1. Moreover, NLE-induced PD-L1 increased the binding intensity of PD-1 on the cell surface. In summary, NLE upregulates the expression of PD-L1 in lung cancer cells through the activation of JNK-c-Jun axis, which has the potential to combine with the PD-1/PD-L1 antibody therapies in lung cancer.

Cucurbitacin B suppresses metastasis mediated by reactive oxygen species (ROS) via focal adhesion kinase (FAK) in breast cancer MDA-MB-231 cells / 中国天然药物

Metastasis is responsible for the majority of cancer-related deaths and prevention of metastasis remains a big challenge for cancer therapy. Cucurbitacin B (Cuc B) is a natural triterpenoid with potent anticancer activities while its effect on metastasis remains unclear. In the present study, the inhibitory effect and mechanisms of Cuc B on metastasis were investigated in MDA-MB-231 breast cancer cells. The cells were treated with or without Cuc B, and the cytotoxicity was determined by MTT assay. The effect of Cuc B on metastasis was evaluated with wound healing, transwell, and adhesion assays. Furthermore, the adhesion of cancer cells to endothelial cells was determined. The protein expression was determined by Western blotting. Cuc B (< 100 nmol·L) showed no obvious cytotoxicity to MDA-MB-231 cells, but significantly inhibited migration, invasion, and adhesion to Matrigel, fibronectin, type I collagen, and endothelial cells. Cuc B dramatically inhibited the phosphorylation of focal adhesion kinase (FAK) and paxillin in dose- and time-dependent manners. Furthermore, Cuc B induced intracellular reactive oxygen species (ROS) generation, which could be reduced by N-acetyl-l-cysteine (NAC). In addition, NAC pretreatment could reverse Cuc B-induced suppression of migration and adhesion, expression of FAK, but showed no effect on paxillin expression. In summary, Cuc B suppressed ROS-dependent metastasis through FAK pathway in breast cancer MDA-MB-231 cells, demonstrating novel mechanisms for the anticancer effects of Cuc B.

Cucurbitacin B suppresses metastasis mediated by reactive oxygen species (ROS) via focal adhesion kinase (FAK) in breast cancer MDA-MB-231 cells / 中国天然药物

Metastasis is responsible for the majority of cancer-related deaths and prevention of metastasis remains a big challenge for cancer therapy. Cucurbitacin B (Cuc B) is a natural triterpenoid with potent anticancer activities while its effect on metastasis remains unclear. In the present study, the inhibitory effect and mechanisms of Cuc B on metastasis were investigated in MDA-MB-231 breast cancer cells. The cells were treated with or without Cuc B, and the cytotoxicity was determined by MTT assay. The effect of Cuc B on metastasis was evaluated with wound healing, transwell, and adhesion assays. Furthermore, the adhesion of cancer cells to endothelial cells was determined. The protein expression was determined by Western blotting. Cuc B (< 100 nmol·L) showed no obvious cytotoxicity to MDA-MB-231 cells, but significantly inhibited migration, invasion, and adhesion to Matrigel, fibronectin, type I collagen, and endothelial cells. Cuc B dramatically inhibited the phosphorylation of focal adhesion kinase (FAK) and paxillin in dose- and time-dependent manners. Furthermore, Cuc B induced intracellular reactive oxygen species (ROS) generation, which could be reduced by N-acetyl-l-cysteine (NAC). In addition, NAC pretreatment could reverse Cuc B-induced suppression of migration and adhesion, expression of FAK, but showed no effect on paxillin expression. In summary, Cuc B suppressed ROS-dependent metastasis through FAK pathway in breast cancer MDA-MB-231 cells, demonstrating novel mechanisms for the anticancer effects of Cuc B.

Hypaconitine inhibits TGF-β1-induced epithelial-mesenchymal transition and suppresses adhesion, migration, and invasion of lung cancer A549 cells / 中国天然药物

Epithelial-mesenchymal transition (EMT) has been implicated in tumor invasion and metastasis and provides novel strategies for cancer therapy. Hypaconitine (HpA), a diester-diterpenoid alkaloid isolated from the root of the Aconitum species, exhibits anti-inflammatory, analgesic, and especially, cardiotoxic activities. Here, we reported the anti-metastatic potentials of HpA in transforming growth factor-β1 (TGF-β1)-induced EMT in lung cancer A549 cells. The cytotoxic effect of HpA was determined by MTT assay. A549 cells were treated with TGF-β1 with or without HpA co-treatment, and the morphological alterations were observed with a microscopy. The expression of E-cadherin, N-cadherin, and NF-κB was determined by both Western blotting and immunofluorescence analyses. The adhesion, migration, and invasion were detected with Matrigel, wound-healing, and transwell assays, respectively. The expression of Snail was determined by Western blotting. The expression of NF-κB p65, IκBα, and p-IκBα in nuclear and cytosolic extracts was assessed by Western blotting. The results showed that low concentration of HpA (<16 μmol·L) had no obvious cytotoxicity to A549 cells. Morphologically, TGF-β1 treatment induced spindle-shaped alteration in the cells. The upregulation of N-cadherin, NF-κB, and Snail and the downregulation of E-cadherin were detected after TGF-β1 treatment. The adhesion, migration and invasion abilities were also increased by TGF-β1. Besides, TGF-β1 induced expression of Snail in a time-dependent manner. Furthermore, TGF-β1 induced nuclear translocation of NF-κB p65. All these alterations were dramatically inhibited by HpA co-treatment. In addition, the NF-κB inhibitor PDTC showed similar inhibitory effect. In conclusion, these results showed that HpA inhibited TGF-β1-induced EMT in A549 cells, which was possibly mediated by the inactivation of the NF-κB signaling pathway, providing an evidence for anti-cancer effect of HpA.

Anticancer carbazole alkaloids and coumarins from Clausena plants: A review / 中国天然药物

Pharmaceutical research has focused on the discovery and development of anticancer drugs. Clinical application of chemotherapy drugs is limited due to their severe side effects. In this regard, new naturally occurring anticancer drugs have gained increasing attention because of their potential effectiveness and safety. Fruits and vegetables are promising sources of anticancer remedy. Clausena (family Rutaceae) is a genus of flowering plants and includes several kinds of edible fruits and vegetables. Phytochemical and pharmacological studies show that carbazole alkaloids and coumarins from Clausena plants exhibit anticancer activity. This review summarizes research progresses made in the anticancer properties of plants belonging to Clausena; in particular, compounds with direct cytotoxicity, cell cycle arrest, apoptosis induction, and immune potentiation effects are discussed. This review reveals the potential use of plants from Clausena in preventing and treating cancer and provides a basis for development of relevant therapeutic agents.

Analysis of difficult problems on European Union laws and regulations of traditional herbal medicinal products / 中国中药杂志

Registration of Chinese patent medicine in European Union (EU) is of great significance to the internationalization of traditional Chinese medicine as EU market acts as an important position in the global botanical market. In retrospect, the domestic studies on EU regulations of traditional herbal medicinal products have been conducted for more than 10 years, but there is still some cognitive bias and lack of research. In this paper, a review of the relevant research progress and the main misunderstanding problems about Directive 2004/24/EC, like the centralized and decentralized supervision system of traditional herbal medicinal products in the EU, marketing authorization procedures for traditional herbal medicinal products, Community Herbal Monograph and List Entries, would be systematically analyzed, so as to provide reference for the registration of Chinese patent medicine in EU.

Pro-angiogenic activity of notoginsenoside R1 in human umbilical vein endothelial cells in vitro and in a chemical-induced blood vessel loss model of zebrafish in vivo / 中国结合医学杂志

<p><b>OBJECTIVE</b>This study aimed at investigating whether notoginsenoside R1 (R1), a unique saponin found in Panax notoginseng could promote angiogenic activity on human umbilical vein endothelial cells (HUVECs) and elucidate their potential molecular mechanisms. In addition, vascular restorative activities of R1 was assessed in a chemically-induced blood vessel loss model in zebrafish.</p><p><b>METHODS</b>The in vitro angiogenic effect of R1 was compared with other previously reported angiogenic saponins Rg1 and Re. The HUVECs proliferation in the presence of R1 was determined by cell proliferation kit II (XTT) assay. R1, Rg1 and Re-induced HUVECs invasion across polycarbonate membrane was stained with Hoechst-33342 and quantified microscopically. Tube formation assay using matrigelcoated wells was performed to evaluate the pro-angiogenic actions of R1. In order to understand the mechanism underlying the pro-angiogenic effect, various pathway inhibitors such as SU5416, wortmannin (wort) or L-Nω-nitro- L-arginine methyl ester hydrochloride (L-NAME), SH-6 were used to probe the possible involvement of signaling pathway in the R1 mediated HUVECs proliferation. In in vivo assays, zebrafish embryos at 21 hpf were pre-treated with vascular endothelial growth factor (VEGF) receptor kinase inhibitor II (VRI) for 3 h only and subsequently post-treated with R1 for 48 h, respectively. The intersegmental vessels (ISVs) in zebrafish were assessed for the restorative effect of R1 on defective blood vessels.</p><p><b>RESULTS</b>R1 could stimulate the proliferation of HUVECs. In the chemoinvasion assay, R1 significantly increased the number of cross-membrane HUVECs. In addition, R1 markedly enhanced the tube formation ability of HUVECs. The proliferative effects of these saponins on HUVECs were effectively blocked by the addition of SU5416 (a VEGF-KDR/Flk-1 inhibitor). Similarly, pre-treatment with wort [a phosphatidylinositol 3-kinase (PI3K)-kinase inhibitor], L-NAME [an endothelial nitric oxide synthase (eNOS) inhibitor] or SH-6 (an Akt pathway inhibitor) significantly abrogated the R1 induced proliferation of HUVECs. In chemicallyinduced blood vessel loss model in zebrafish, R1 significantly rescue the damaged ISVs.</p><p><b>CONCLUSION</b>R1, similar to Rg1 and Re, had been showed pro-angiogenic action, possibly via the activation of the VEGF-KDR/Flk-1 and PI3K-Akt-eNOS signaling pathways. Our findings also shed light on intriguing pro-angiogenic effect of R1 under deficient angiogenesis condition in a pharmacologic-induced blood vessels loss model in zebrafish. The present study in vivo and in vitro provided scientific evidence to explain the ethnomedical use of Panax notoginseng in the treatment of cardiovascular diseases, traumatic injuries and wound healing.</p>

Overview of Taiwan's indigenous ethnopharmacology in the perspective of traditional knowledge protection / 中国结合医学杂志

Ethnopharmacology, the study of ethnic use of drugs, opens up the crucial gateway to understanding and promoting traditional medicine in the new age. Taiwan is a unique region where traditional medicine and herbal therapeutics have been benefiting its people of multiple races for centuries. This article overviews Taiwan's indigenous traditional medicine and the emerging status of ethnopharmacology study, and outlines the global scenario of the inheritance and development of traditional medicine. In such a scope of knowledge protection, this article particularly highlights the challenges with bioprospecting and biopiracy, and summarizes the current measures for protection of traditional knowledge in Taiwan. Finally, based upon these analyses, we propose rational strategies for promoting Taiwan's ethnopharmacology, from multiple angles of resource, economy, policy and law. We conclude that four measures, namely (1) protecting the natural environment of biodiversity, (2) avoiding unnecessary conflicts caused by bioprospecting and biopiracy, (3) strengthening the international collaboration, and (4) upgrading the legal system of traditional intelligence, would be the right paths for Taiwan to protect its invaluable heritage of traditional medicine and the knowledge of ethnopharmacology therein.

Current topics on cancer biology and research strategies for anti-cancer traditional Chinese medicine / 中国中药杂志

Cancer, an abnormal cell proliferation resulted from multi-factors,has the highest morbidity and mortality among all the serious diseases. Considerable progress has been made in cancer biology in recent years. Tumor immunology, cancer stem cells (CSCs), autophagy, and epithelial-mesenchymal transition (EMT) have become hot topics of interests in this area. Detailed dissection of these biological processes will provide novel directions, targets, and strategies for the pharmacological evaluation, mechanism elucidation, and new drug development of traditional Chinese medicine.

Recent advances in natural product induced DNA damage response in cancer cells / 中国中药杂志

The DNA structures could be altered or even damaged by exogeous or endogenous factors during cell proliferation. Failure of effective and timely repair will lead to cell cycle arrest or apoptosis. By taking the advantage of the quick proliferation of cancer cells, DNA damage induction, cell cycle arrest and apoptosis promotion have become important strategies for ant-cancer chemotherapy. Previous reports showed that an array of natural compounds inhibit cancer cell proliferation by inducing DNA damage, which have therapeutic potentials for anti-cancer drug research and development.

Lobelia chinensis: chemical constituents and anticancer activity perspective / 中国天然药物

Research has demonstrated that many chemical constituents dominated by piperidine alkaloids and flavonoids, such as lobelanidine, lobeline, and lobelanine, have been obtained from Lobelia chinensis Lour. Experimental studies and clinical applications have also indicated that L. chinensis possesses a number of pharmacological activities (e.g., diuretic, choleretic, breathing excitement, anti-venom, anti-bacterial, and anticancer). This paper focuses on the properties, chemical constituents, and anticancer activity of L. chinensis to clarify the connection among them, and identify the active anticancer compounds. This work serves as the foundation for further research and development of L. chinensis.

Mechanism study on preventive and curative effects of buyang huanwu decoction in Qi deficiency and blood stasis diseases based on network analysis / 中国中药杂志

In this study, researchers adopted the network analysis method to study Buyang Huanwu decoction at three levels, namely chemical ingredients, targets and diseases, and discovered the potential effect of Buyang Huanwu decoction in cancer treatment. Besides, they analyzed the "target-target" network of Buyang Huanwu decoction based on diseases, calculated four network indexes, namely node centrality, closeness centrality, betweenness centrality and eigenvector centrality for a comprehensive evaluation on the importance and significance of each target in the network. Afterwards, key targets of Buyang Huanwu decoction were excavated to obtain two important targets--COX-2 and PPAR-gamma, which may be important targets involved in the qi deficiency and blood stasis diseases. Meanwhile, the two targets were the basis to build the core network of "chemical component-target-disease" of Buyang Huanwu decoction, which provided reference for further studies on the effect of Buyang Huanwu decoction in treating qi deficiency and blood stasis diseases. According to the study, the network analysis method was helpful to excavate potential targets Buyang Huanwu decoction in treating qi deficiency and blood stasis diseases, and could provide methodological reference for revealing the mechanism of Buyang Huanwu decoction at multiple levels, with a guiding significance for interpreting mechanisms of traditional Chinese medicinal formulae and developing new drugs.

Development of quality traceability system of traditional Chinese medicine / 中国中药杂志

The development of Chinese medicine is directly related to the quality and safety issues, It has drawn great attention of people. Chinese traditional medicine quality issue involves two aspects of traditional Chinese medicine itself and human. In order to prevent man-made or illegal factors led to the decrease of the quality of the traditional Chinese medicine (TCM) or security risk, it needs to establish a feasible system to guarantee, in which the construction and development of traditional Chinese medicine quality traceability system is an important direction of the development of the traditional Chinese medicine in the future. This paper first reviews the development of quality traceability system status and critical retrospective techniques, then introduced current development status of quality traceability system of traditional Chinese medicine( QTS-TCM), pointing out the characteristics of QTS-TCM, and finally given the current research findings of QTS-TCM.

Application research of hot-melt extrusion in preparation of solid dispersion / 药学学报

Hot-melt extrusion (HME) is mainly used to enhance the dissolution rate and bioavailability of poorly water soluble drugs. It has many advantages, such as simple process, continuous operation, high efficiency, on-line monitoring and so on. HME provides an innovative approach, which has been concerned by pharmaceutical workers, for preparation of solid dispersion abroad. This article reviews recent advances on preparation of solid dispersion by HME in preparation processing, carrier materials and quality evaluation in order to further promote and apply HME in preparation of solid dispersion.

Inspirations from natural products based drug research and development for Chinese medicine research--analysis of natural products recoded in TTD / 药学学报

Natural product is an important source of new drug research and development (R&D). Traditional Chinese medicine (TCM) innovation is the key step for its modernization and internationalization. However, due to the complexity of TCM, there are many difficulties and confusions in this process. Target-based drug discovery is the mainstream model and method of R&D. TTD, short for therapeutic target database, is developed by National University of Singapore. Besides a large amount of information on drug targets, the database also contains considerable information related to natural products. This paper briefly introduces the TTD, analyzes the natural products derived drugs/compounds recorded in TTD, which we think might provide some inspiration for the innovation of TCM.

Globalization of acupuncture technology innovation: a quantitative analysis based on acupuncture patents in the U.S.A / 中国针灸

The structure of international flow of acupuncture knowledge was explored in this article so as to promote the globalization of acupuncture technology innovation. Statistical methods were adopted to reveal geographical distribution of acupuncture patents in the U.S.A. and the influencing factors of cumulative advantage of acupuncture techniques as well as innovation value of application of acupuncture patents. Social network analysis was also utilized to establish a global innovation network of acupuncture technology. The result shows that the cumulative strength on acupuncture technology correlates with the patent retention period. The innovative value of acupuncture invention correlates with the frequency of patent citation. And the U. S. A. and Canada seize central positions in the global acupuncture information and technology delivery system.

Study on the induction of skin transplantation tolerance against rejection in mice by third-party dendritic cells loaded with donor's antigens / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate whether the third-party dendritic cells (DC) incubated with donor's antigens possess the similar immune functions with donor derived immature DC.</p><p><b>METHODS</b>Female C57 BL/6, BALB/c and Kunming mice were used as skin transplant donors, recipients and third-party, respectively. Forty BALB/c mice were randomly divided into A (normal control), B (cyclophosphamide administration), C (CTX and donor derived immature DC), D (CTX and third-party immature DC), E (CTX and third-party DC loaded with donor's antigens) groups, with 8 mice in each group. The mice in group B, C, D and E were given CTX (200 mg/Kg) 4 days before operation, while those in group A were given equivalent amount of normal saline(NS). Then in group C, D and E, DC at a dose of 1 x 10(7)/ml were intraperitoneally injected with 2 days before grafting and 12 days after operation, but the mice in group A and B were given NS in the same manner. Mean survival time (MST) of skin grafts was recorded, and biopsies of grafts on 5 and 10 post-operation days (POD) were harvested for histologic examination.</p><p><b>RESULTS</b>Compared with group A [(16.1 +/- 3.5)d], MST of skin grafts in group C [(38.3 +/- 7.7) d] and E [(34.9 +/- 7.7) d] were significantly prolonged ( P < 0.01), while no obvious difference was observed between group C and E( P > 0.05), but there was statistically significant difference in MST between group D [(23.7 +/- 2.7) d] and E ( P < 0.05). In addition, clear epithelial structure and infiltration of inflammatory cells were observed in specimens from both groups C and E.</p><p><b>CONCLUSION</b>Both donor derived immature DC and third-party DC loaded with donor's antigens can partly induce donor specific transplantation tolerance.</p>