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In order to assure the safety and efficacy of the Chinese Medicines in Europe, the quality of TCM herbals should be guaranteed so that they can be freely imported in the European Union and other Western European Countries which are signatories of the European Pharmacopoeia Convention. Consequently, new Ph Eur TCM herbal drug Monographs should be elaborated, based on preexisting Monographs in the Chinese Pharmacopoeia (ChP) 2010. Such a program has been inaugurated in 2005 by the Ph Eur Groups of Experts 13 A and B (Phytochemistry). Since then good progress has been made, elaborating of about one third of the originally proposed 100 TCM herbals being identified as important monographs for the European Market. Taking into account the many challenges still laying ahead, the establishment of a specialized Working Party (WP) on TCM with specialists and experts from many EU Member States has been decided by the Ph Eur Commission in 2008 which is highly active ever since in the examination and elaboration of new TCM herbal drug monographs, primarily to assure the safety of the European patient and further to provide quality parameters extremely important for all registration and licensing procedures of the respective National Authorities all over Europe. This paper is a survey of results and difficulties obtained so far which has been encountered meanwhile in the elaboration process by the Ph Eur TCM WP of these monographs and will discuss these in detail. Moreover the role of Ph Eur TCM monographs in the European community is addressed.

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Artemisinin represents a showcase example not only for the activity of medicinal herbs deriving from traditional chinese medicine, but for phytotherapy in general. Its isolation from Sweet Wormwood (qinhao, Artemisia annua L.) represents the starting point for an unprecedent success story in the treatment of malaria worldwide. Beyond the therapeutic value against Plasmodium parasites, it turned out in recent years that the bioactivity of artemisinin is not restricted to malaria. We and others found that this sesquiterpenoid also exerts profound anticancer activity in vitro and in vivo. Artemisinin-type drugs exert multi-factorial cellular and molecular actions in cancer cells. Ferrous iron reacts with artemisinin, which leads to the formation of reactive oxygen species and ultimately to a plethora anticancer effects of artemisinins, e.g. expression of antioxidant response genes, cell cycle arrest (G1 as well as G2 phase arrests), DNA damage that is repaird by base excision repair, homogous recombination and non-homologous end-joining, as well as different modes of cell death (intrinsic and extrinsic apoptosis, autophagy, necrosis, necroptosis, oncosis, and ferroptosis). Furthermore, artemisinins inhibit neoangiogenesis in tumors. The signaling of major transcription factors (NF-κB, MYC/MAX, AP-1, CREBP, mTOR etc.) and signaling pathways are affected by artemisinins (e.g. Wnt/β-catenin pathway, AMPK pathway, metastatic pathways, nitric oxide signaling, and others). Several case reports on the compassionate use of artemisinins as well as clinical Phase I/II pilot studies indicate the clinical activity of artemisinins in veterinary and human cancer patients. Larger scale of Phase II and III clinical studies are required now to further develop artemisinin-type compounds as novel anticancer drugs. Abbreviations: ABCB6, ATP-binding Cassette Transporter B6; ABCG2, ATP Binding Cassette Transporter G2; AIF, Apoptosis Inducing Factor; AKT, V-Akt Murine Thymoma Viral Oncogene Homologue; AMPK, AMP-Activated Protein Kinase; Ang-1, Angiotensin 1; ARE, Arteether; ARM, Artemether; ARS, Artemisinin; ART, Artesunate; ATF4, Activating Transcription Factor 4; Bak, Bcl2 Antagonist/Killer 1; Bax, Bcl2-Associated X Protein, Pro-Apoptotic BH3-Only Bcl-2 Family Member; Bcl-2, B-cell CLL/lymphoma 2; Bcl-xL, B-cell CLL/Lymphoma-x Long; BCR/ABL, Breakpoint Cluster Region/Abl Proto-Oncogene; Bid, BH3-Interacting Domain Death Agonist; Bim, Pro-Apoptotic Bcl2- Family Member; BSO, Buthionine Sulfoximine; C/EBP β, CCAAT/Enhancer Binding Protein β; CAM, Chorioallantoic Membrane; CD, Cluster of Differentiation; CDC25B; CDK, Cyclin-Dependent Kinase; CHOP/DDIT, DNA Damage-Inducible Transcript; CIP1/WAF1, CDK-Interacting Protein 1/Wild-Type p53-Activated Fragment 1; c-JUN, Jun Proto-Oncogene; COX2, Cyclooxygenase 2; CREB, Cyclic ATP Responsive Element Binding Protein; DHA, Dihydroartesunate; DNA-PK, DNA-Dependent Protein Kinase; DR5, Death Receptor 5; E2F1, E2F Transcription Factor 1; EA, Ethacrynic Acid; EGFR, Epidermal Growth Factor Receptor; EMT, Epithelial to Mesenchymal Transition; EndoG, Endonuclease G; ERK, Extracellular Signal-Regulated Kinase; FAK, Focal Adhesion Kinase; FAS, Fas Cell Surface Death Receptor; Flt-1, Fms- Related Tyrosine Kinase 1; GADD153, Growth Arrest and DNA Damage-Inducible 153; GRP78, Glucose-Regulated Protein; GSK3 β, Glycogen Synthase Kinase 3 β; HIF-1α, Hypoxia-Inducible Factor-1 α; HPV39, Human Papilloma Virus 39; HR, Homologous Repair; hTERT, Human Telomerase Reverse Transcriptase; hTR, Human Telomerase; HUVEC, Human Umbilical Vein Endothelial Cells; IFN, Interferon; IL, Interleukin; IκBβ, Inhibitor of Kappa B β; JNK, c-Jun N-Terminal Kinase; KDR/flk-1, Kinase Insert Domain Receptor; LC3, Microtubule- Associated Protein 1 Light Chain 3; MAPK, Nitogen-Activated Protein Kinase; MAX, MYC-Associated Factor X; Mcl-1, Myeloid Cell Leukemia 1; MDM2, Mouse Double Minute 2 Homologue; MEK, also known as MAPKK, Mitogen-Activated Protein Kinase Kinase; MMP, Matrix Metalloproteinase; MPNST, Malignant Peripheral Nerve Sheath Tumor; mTOR, Mammalian Target of Rapamycin; MYC, Avian Myelomastosis Viral Oncogene Homologue; NAC, N-Acetyl Cysteine; NFκB, Nuclear Factor Kappa B; NHEJ, Non-Homologous End-Joining; NO, Nitric Oxide; NOXA, Also Known As PMA/P1; Phorbol-12-Myristate-13-Acetate-Induced Protein 1; PARK7, Parkinson Disease Protein 7, Protein Deglycase DJ-1; PARP, Poly ADP Ribose Polymerase; PCNA, Proliferating Cell Nuclear Antigen; PGE2, Prostaglandine E2; PI3-K, Phospoinositide-3 Kinase; PMA, Phorbol-12-Myristate-13-Acetate; RAF, Ras-Associated Factor Proto-Oncogene; RAS, Rat Sarcoma Viral Oncogene Homologue; RKIP, Raf-1 Kinase Inhibitor Protein; ROS, Reactive Oxygen Species, SMAC/DIABLO, IAP-Binding Mitochondrial Protein; TCTP, Translationally Controlled Tumor Protein; TF, Transferrin; TFRC, Transferrin Receptor 1 Gene; TGB1, Triple Gene Block Protein β, TGF-beta, Tumor Growth Factor β, TIMP, Tissue Inhibitor of Metalloproteinase, TNF-α, Tumor Necrosis Factor α, TOPO2 A, DNA Topoisomerase 2 α, TRAIL, Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand, Treg, Regulatory T Cells, VDAC2, Voltage-Dependent Anion Channel 2, VEGF, Vascular Endothelial Growth Factor, VEGFR, Vascular Endothelial Growth Factor Receptor, XIAP, X-Linked Inhibitor of Apoptosis, YY1, Yin Yang 1

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Metabolomics, an omic science in systems biology, is the comprehensive profiling of metabolic changes occurring in living systems and has been widely used in the modern research of traditional Chinese medicine (TCM). TCM is a complex medical science, which reflects rich philosophical dialectical thought, puts the human body into a large system for observation and keeps human in a healthy status. For TCM aroused great interest in the whole world, herbs and Chinese medical formulae (CMF) as treatment methods have also been widely attention. Metabolomics represents a powerful way that provides a dynamic drawing of the phenotype of biological systems via the research of endogenous metabolites, and its methods are similar to those of TCM. This review summarizes the advantages of metabolomics, highlight the key role of biomarkers for drug discovery and development of TCM.

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The interest of Western medicine in Traditional Chinese Medicine (TCM) as a source of drug leads/new drugs to treat diseases without available efficient therapies has been dramatically augmented in the last decades by the extensive work and the outstanding findings achieved within this kind of medicine. The practice of TCM over thousands of years has equipped scientists with substantial experience with hundreds of plants that led to the discovery of artemisinin (qinghaosu), which is extracted from the medicinal plant Artemisia annua L. (qinghao). The unexpected success of artemisinin in combating malaria has drawn strong attention from the scientific community towards TCM. Artemisinin was discovered by Youyou Tu in 1972. Since then, several novel pharmacological activities based on the well-known properties of the sesquiterpene lactone structure with the oxepane ring and an endoperoxide bridge have been unravelled. Beyond malaria, artemisinin and its derivatives (artemisinins) exert profound activities towards other protozoans (Leishmania, Trypanosoma, amoebas, Neospora caninum, and Eimeria tenella), trematodes (Schistosoma, liver flukes), and viruses (human cytomegalovirus, hepatitis B and C viruses). Less clear is the effect against bacteria and fungi. Based on the promising results of artemisinin and the first generation derivatives (artesunate, artemether, arteether), novel drug development strategies have been pursued. These included the synthesis of acetal- and non-acetal-type artemisinin dimeric molecules as well as developing nanotechnological approaches, e.g. artemisinin-based liposomes, niosomes, micelles, solid lipid nanocarriers, nanostructured lipid carriers, nanoparticles, fullerenes and nanotubes. The current review presents an overview on different aspects of artemisinins, including sources, chemistry, biological/pharmacological properties, types of infectious pathogens that are susceptible to artemisinins in vitro and in vivo, in addition to the advancement in their drug delivery systems utilizing pharmaceutical technology. It would be expected that different therapeutic strategies based on the second and third generation artemisinin derivatives and artemisinin-based drug technologies would be available in the near future to treat specific infectious diseases. Abbreviations: ARM: Artemether; ARM-LNP: Artemether-loaded lipid nanoparticles; ART: Artemisinin; ACT: Artemisinin-based combination therapies; AC-PL: Artemisinin-curcumin-loaded PEGylated liposomes; ADPs: Artemisinin dimer piperazine derivatives; A-CL: Artemisinin-loaded conventional liposomes, artemisinin-curcumin-loaded; AST: Artesunate; BBB: Blood-brain barrier; AC-CL: Conventional liposomes; A-PL: artemisinin-loaded PEGylated liposomes; DHA: Dihydroartemisinin; %EE: Entrapment efficiency; GNO: Ground nut oil; kDNA: Kinetoplast; LNs: Lipid nanospheres; NPs: Liposomal nanoparticles; MRT: Mean residence times; MPEG: Methoxy polyethylene glycol; NP: Nanoparticle; NLC: Nanostructured lipid carrier; NCEs: New chemical entities; PSM: Plant secondary metabolites; SNL: Solid lipid nanovectors; TCM: Traditional Chinese Medicine; TR: Transferrin; TNBC: Triple negative breast cancer; VM: Vasculogenic mimicry Received 12 January 2016; Accept 3 May 2016

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Background: Edible bird nest (EBN) is a natural food product rich in glycoprotein such as sialic acid, which has been reported to improve brain functions. The EBN is widely consumed due to its higher nutritional contents and antioxidant status; however, an interaction of EBN on brain cell metabolic activity and viability are still unclear. Objective: The objectives of this study were to identify the effect of sialic acid from EBN on the cell viability and to determine the appropriate concentration of sialic acid on cognitive performance in mice. Materials and Methods: The viability of pheochromocytoma and neuroblastoma cell lines were tested using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. For in vivo study, 7-week-old female BALB/c mice were randomly assigned into four treatment groups and were treated with sialic acid for 21 days. At day 22, all mice were tested on cognitive performance by Y-maze test. Results: Treatment concentration of sialic acid extract and sialic acid standard at 60 μg/mL (0.6 ppm) increased cell viability and showed no cytotoxicity effects in pheochromocytoma and neuroblastoma cell lines. In addition, an administration of higher dose of sialic acid at 0.6 ppm in animals improved Y-maze test performance, which they showed significantly higher number of entries and time spent in the novel arm. Conclusion: Thus, the current study shows that the sialic acid extract at 0.6 ppm improved brain cognitive performance in mice associated with an increased viability of pheochromocytoma and neuroblastoma cell lines.

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Safflower, Carthamus tinctorius L., is an annual oilseed crop that is cultivated on small plots all over the world. The seed oil content ranges from 20% to 45%; the oil is high in linoleic acid, an unsaturated fatty acid that aids in lowering the blood cholesterol level. Thus, safflower has long been used as medical plant in many countries, especially in China and India. However, for industrial purposes, it has long been neglected because of the low seed yield or oil content, until its physical role was revealed. In recent years, research works carried out in many countries mostly focused on improving the seed or oil yield. In this review, after illustrating the fatty acid composition of safflower seed oil as well as the genetic characteristics of safflower and their relationships with agronomic traits, a brief analysis of the current worldwide situation and future prospects of safflower utilization are presented.

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Herbal medicines may benefit from metabolomics studies, and applying metabolomics may provide answers about which herbal interventions may be effective for individuals, which metabolic processes are triggered, and the subsequent chemical pathways of activity. Physalis pubescens L (PPL) is an herbal fruit for one year living plant and has been developed into healthy function’s food. However, the mechanisms of health functions are still unclear. To comprehensively and holistically assess its anti-fatigue and antioxidant effects, a novel integrative metabolomics approach was applied. In this study, we present metabolomics analysis applying ultra performance liquid chromatography coupled to quadrupole with time-of-flight mass spectrometry (UPLC-Q/TOF-MS) to determine metabolite alterations after oral administration PPL to rats. Fifteen metabolites in urine were identified as potential biomarkers. Pattern analysis of the UPLC-Q/TOF-MS data disclosed that PPL could relieve fatigue rats by ameliorating the disturbance in amino acids metabolism and energy metabolism, alleviating the oxidative stress from reactive oxygen species and the inflammatory damage, and recovering the destructed regulation. Based on these results, we demonstrated that PPL is a promising source of natural anti-fatigue and antioxidants material for use in functional foods and medicines.

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Acupuncture, as a healing art in traditional Chinese medicine, has been widely used to treat various diseases. In the history of acupuncture anesthesia, in the past decades, mechanisms of acupuncture analgesia has been widely investigated, and in recent years, acupuncture protection on organ functions has attracted great interest. This review summarized the research progress on mechanisms of acupuncture for analgesia and its protection against organ function injury in anesthesia, and its perspective of analgesia, immunomodulation, neuroendocrine regulation and multiple organ protection. The current evidence supports that acupuncture analgesia and its organ protection in anesthesia is associated with the integration of neuroendocrine-immune networks in the level of neurotransmitters, cytokines, hormones, neuronal ensembles, lymphocytes, and endocrine cells. Although the mechanisms of acupuncture analgesia and its organ protection are still not completely understood, basic as well as clinic researches on the mechanisms and applications of acupuncture and related techniques are being carried out.

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Direct analysis in real time (DART) possesses the merits of analyzing sample in its native status with minimal or even no sample pretreatment. In this review, we summarized the recent applications of DART in the field of herbal medicine analysis such as compound detection, species identification, metabolites profiling and initial quantification. DART with the characters of hyper-rapid, easy-hyphenated offers a new research tool for herbal medicines to complete the experimental process in a very simple but still reliable way. It is anticipated that more wide and deep applications of DART in herbal medicine analysis, as rapid quantification, high-throughput active compounds screening, rapid species identification, and fast illegal additives screening will be promising and foreseeable in the near future.

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Herbal medicines, including traditional Chinese medicines (TCMs), have been used in Eastern countries for treating diseases such as cancer for thousands of years. With the growing knowledge of tumorigenesis and cancer therapy, some natural compounds have been developed as clinical anticancer drugs. In addition, many compounds and TCMs have been characterized as complementary and alternative treatments, with synergetic effects on enhancing the efficacy or reducing the side effects of the therapeutics. In this review, we summarized the recent studies focusing on the combination of natural compounds or TCM decoction with chemotherapeutics. The detailed mechanisms of action of the combinations and the application of analytical methods on TCM development are also discussed.

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Objective: The present study aims to optimize the extraction conditions of polysaccharides and flavonoids from a polyherbal preparation consisting of three kinds of Chinese medicinal herbs, Codonopsis pilosula, Crataegus pinnatifida, and Lycium barbarum, and evaluation of its immunomodulatory activity in immunosuppressed mice. Materials and Methods: An orthogonal design (L₉ [3]⁴) was constructed to achieve the optimal extraction conditions. The immunomodulatory action of the polyherbal preparation was studied at three doses of 10, 20, and 40 mL/kg/day orally by measuring splenocyte proliferation in mice model of cyclophosphamide-induced immunosuppression. Results: The chosen parameters, including the ratio of solvent-to-raw material, duration of extraction, and extraction times, were the fundamental variables that influenced the extract yields. The highest yield of total polysaccharides content was 54.3 mg/mL when the ratio of solvent-to-raw material, duration of extraction, and number of extractions were 12:1, 1.5 h, and 3, respectively. The maximum extraction yield of the flavonoids was 3.5 mg/mL when the ratio of solvent-to-raw material was 12:1, the extraction time was 2 h, and the number of extractions was 3. The prescription screening showed that the impact of the polyherbal preparation on the splenocyte proliferation capacity was more pronounced than its disassembled components. Oral administration of the polyherbal preparation could significantly increase the concanavalin A-stimulated mouse spleen cells proliferation in a dose-dependent manner. Conclusion: These findings suggested that the polyherbal preparation possesses potential for augmenting the immune activity due to the polysaccharide and flavonoid content in these herbal medicines.

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Genus Alpinia consists of over 250 species, which are widely distributed in south and southeast Asia. Many plants of genus Alpinia have been used for thousands of years to treat digestive system diseases and as anti-inflammatory drugs. Phytochemical research on this genus has led to the isolation of different kinds of diarylheptanoids, terpenes triterpenoids, phenylbutanoids, lignans, and flavonoids. Experimental evidences revealed that both the crude extracts and pure constituents isolated from the genus Alpinia exhibit a wide range of bioactivities such as anti-cancer, anti-oxidant, anti-bacterial, anti-viral, cardiovascular, and digestive system protective effects. Here, we summarize the phytochemistry and pharmacology investigation of the genus Alpinia, which can provide reference for further research and drug development.

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Turmeric, derived from the rhizomes of Curcuma longa L. (Zingiberaceae), is one of the most popular herbal medicines. Its main bioactive constituents include curcuminoids, sesquiterpenes, and terpecurcumins. It exhibits antitumor, anti-inflammatory, antioxidant, antibacterial, and antiviral activities. With the rapid development of analytical technologies, remarkable progress has been made in studies of turmeric. This review article summarizes research advances in chemical analysis and quality control of turmeric from 2009 to 2018.

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Pharmacopoeial standards for crude drugs are established based on analysis of authenticated specimens which should be representative of the quality of material traditionally specified in systems of traditional medicine from species’ geographical origin. This reflects the ‘geo-authentic’ material that corresponds to traditional ecological and medical knowledge. In cases where specimens are obtained from cultivation outside of the species origin, this ‘authenticated’ material will not be ‘geo-authentic’. There is a growing trend for the protection of ‘geographical indication’ (GI) botanicals in the context of intellectual property rights. GI botanicals are named after a geographical area, indicating production within a particular area, quality and characteristics dependent on natural, historical and cultural factors. However, with the globalization of systems of traditional medicine such as Ayurvedic medicine and traditional Chinese medicine, Asian species are being introduced to cultivation outside of their geographical origins particularly in the EU and US. In contrast to the Chinese concept of ‘daodi’ and European concepts of ‘provenance’ or ‘terroir’ is the competing trend for ‘locally grown’ herbs, i.e. cultivated closer to where they will be used. Reasons include concerns about quality control, contamination from polluted air, soil and water in some source countries, climate change, supply chain security and traceability, costs of production and price pressure. This review looks at selected agronomic experiments aiming to discern differences between geo-authentic medicinal herbs vs. introduced crops and whether the global market cares to make a distinction or pay a price premium for articles with designations of geographical origin of specified quality. Abbreviations: AO, Appellation of Origin, GI, geographical indication; PDO, protected designation of origin; PGI, protected geographical indication; MAP, medicinal and aromatic plant; TCM, traditional Chinese medicine; TEK, traditional ecological knowledge; TSG, traditional speciality guaranteed.

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Four new dicaffeoylspermidine derivatives, lycibarbarspermidines P-S (1-4), were isolated from the fruit of Lycium barbarum (wolfberry). The structures were determined by extensive spectroscopic (HRESIMS, 1D NMR, and 2D NMR) analyses and chemical methods. Dicaffeoylspermidine derivatives are a kind of major bioactive and characteristic constituents in wolfberry, and the discovery of 1 -4 added new members of this family.

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Following the spirit of Central Committee about the Opinions on Promoting the Inheritance, Innovation, and Development of Traditional Chinese Medicine, Academician Chen Kai-Xian, from Shanghai University of Traditional Chinese Medicine, made a wonderful report on the development of traditional Chinese medicine (TCM) and global medicine. The report deeply elaborated on five aspects: the characteristics and advantages of TCM, the challenges faced by contemporary medicine, the status and role of TCM in the contemporary era, the inheritance and innovation of TCM, and the cooperation and development of “Belt and Road.”

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Backgroud: Acupuncture is common used for Bell’s palsy in clinic, however, recent systematic reviews all shows that there is no sufficient evidence to support the effectiveness of acupuncture for Bell’s palsy because ofthe poor quality and heterogeneity. It’s urgently necessary to develop a guideline of acupuncture for Bell’s palsy based on principles of evidence-based medicine to optimize acupuncture treating, standardize outcomes evaluating and to improve the quality of acupuncture for patients with Bell’s palsy under general circumstances. Objective: To improve the accuracy of diagnosing and managing Bell’s palsy, optimize acupuncture treating and outcomes evaluating for patients with Bell’s palsy, and to improve the quality of acupuncture for patients with Bell’s palsy in most instances. Methods: This guideline was developed using an explicit and transparent a priori protocol based on supporting evidences and experts’ consensus. The guideline developing Group followed the protocol through all stages of the development process: proposed clinical questions, searched clinical evidences, evaluated levels of evidences, developed recommendations, peer reviewed and consummated, and finally formed the draft of this guideline. Results: (1)The guideline development group made a Grade A recommendation that ①With a course of Bell’s palsy within 3 months, the patients with mild facial palsy may be treated with any one of acupuncture, western drugs, or acupuncture combing with western drugs, whereas the patients with severe facial palsy may be treated with acupuncture or acupuncture combing with western drugs. With a course of more than 3 months, acupuncture is more suitable. ②Acupuncture should be applied as early as possible for Bell’s palsy. ③The principle of selecting acupoints for Bell’s palsy is to select local points, points of corresponding meridians and those according to differentiation. Generally, the points of yangming meridians are the main ones. ④The various methods of acupuncture and moxibustion are adopted for Bell’s palsy, including filiform needling, moxibustion, electro-acupuncture, etc. Two or more methods are usually used together in clinical practice. (2) The development group formed expert consensus on the principles of acupuncture treatment for Bell’ palsy. Bell’s palsy is suitably treated according to the stages, differentiation and symptoms. Abbreviations: EBM: evidence-based medicine; GDG: The guideline developing Group; AHCPR: US Department of Health Care and Policy Research; SIGN: Scottish Intercollegiate Guidelines Working network; CT: computed tomography; MRI: magnetic resonance imaging

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Traditional Chinese medicine (TCM) has been widely used in many oriental countries for thousands of years and played an indispensable role in the prevention and treatment of diseases, especially the complicated and chronic ones. It is a very complex mixture containing hundreds or thousands of different components. Pharmacokinetic study on active constituents in TCM preparations is a good way for us to explain and predict a variety of events related to the efficacy and toxicity of TCM. In the drug discovery phases, pharmacokinetics is a key to guide medicinal chemists in the optimization process of a chemical series and to assist pharmacologists to design in vivo studies. To explore the potentially bioactive components in TCM, it is necessary to further study the in vivo pharmacokinetic characteristics of multiple absorbed components and find out the optical time-course behavior to providing more substantial research for new leads in drug discovery. Pharmacokinetics screening method could provide a reliable means of prospecting natural products in the search for new leads in drug discovery. This review summarizes the research progress of PK on TCM in the search for suitable lead compounds in recent years.

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Toad venom, called as ChanSu in China, is a widely used traditional Chinese medicine (TCM) whose active components are mainly bufadienolides. ChanSu could exhibit cardiotonic, anti-microbial, anti-inflammatory and, most importantly, anti-cancer effects. In the present review, reports about the in vitro, in vivo and clinical anti-cancer effects of ChanSu or its representative component, bufalin, were summarized. And, reported anti-cancer mechanisms of cardenolides, structure analogues of bufadienolides, were also introduced. Based on the results got from research of ChanSu/bufalin and the results from cardenolides, possible signal network related to the anti-cancer effects of ChanSu/bufalin was predicted. Furthermore, future potential use of ChanSu in anti-cancer therapy was discussed. Abbreviations: TCM, traditional Chinese medicine; MAPK, mitogen-activated protein kinase; AP-1, activator protein-1; JNK, c-Jun N-terminal protein kinase; PAK, p21-activated kinase; CK2, casein kinase 2; PARP, poly ADP-ribose polymerase; COX-2, cyclooxygenase-2; VEGFR, vascular endothelial growth factor receptor; EGFR, epidermal growth factor receptor; NF-KB, nuclear factor-KB; ERK, extracellular signal-regulated kinase; ROS, reactive oxygen species; Hsp27, heat shock protein 27; TNF, tumor necrosis factor; BECN, Beclin; ATG8, autophagy related 8; Bid, BH3 interacting domain death agonist; AMPK, adenosine monophosphate kinase; mTOR, mammalian target of rapamycin; 4EBP1, eukaryotic translation initiation factor 4E binding protein 1; p70S6K1, ribosomal protein S6 kinase, 70kDa, polypeptide 1; ER, endoplasmic reticulum; AKT, protein kinase B; MMP, matrix metalloproteinase; TIMP, tissue inhibitors of metalloproteinase; TJs, tight junctions; GSK3p, glycogen synthase kinase 3 beta; FAK, focal adhesion kinase; Rho A, ras homolog gene family, member A; MEKK3, MAPK/ ERK kinase 3; MKK7, mitogen-activated protein kinase kinase 7; uPA, urokinase plasminogen activator; ER-a, estrogen receptor-a; TRAIL, TNF-related apoptosis-inducing ligand; STAT3, signal transducer and activator of transcription 3; Mcl-1, myeloid cell leukemia sequence 1; BNPs, bufalin-loaded mPEG-PLGA-PLL-cRGD nanoparticles; Bax, B-cell lymphoma 2-associated X protein; TACE, transcatheter arterial chemoembolization; THM, traditional herbal medicine; ORR, objective response rate; PI3K, phosphoinositide-3-kinase; Bu-BCS-NPs, bufalin encapsulating nanoparticles.

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Objective: In this study, the hepatotoxic components of Polygoni multiflori Radix and Polygoni multiflori Radix Praeparata (known as Heshouwu [HSW] and Zhiheshouwu [ZHSW] in China, respectively) were screened, isolated, and identified. Materials and Methods: The ethanol extracts of HSW and ZHSW were separated into 80 fractions according to their polarity in the preparation liquid phase. Chang liver cell line was used to screen the toxic components of HSW and ZHSW in vitro. The obtained toxic mixture was further collected, isolated, and identified to confirm the hepatotoxic compounds of HSW and ZHSW. Results: The identifid hepatotoxic compounds include 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside, emodin, physcion-8-O-β-d-glucoside, physcion, and citreorosein, the fist two among them were the main components of HSW and ZHSW. After processing of HSW, the contents of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside and emodin in ZHSW were signifiantly decreased. Conclusions: The traditional processing with herb has signifiant effects on the components, especially the toxic components, in the extract of HSW and is an effective method to reduce its toxicity.

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Background: Artemisinin dimer oxime – dimer molecule synthesized from artemisinin possesses high bioavailability and marked in vitro anticancer activities against solid tumor-derived cell lines, endothelial cell proliferation, migration, and angiogenic processes. Numerous murine models have been developed to study human cancer. The most widely used models are the human tumor xenograft mouse model. Materials and Methods: In this study, human tumor cells (NCI-H640, 1 × 10⁷ in 100 μL) are implanted subcutaneously, or 1 × 10⁷ in 50 μL in the thoracic cavity, in athymic nude mice (nu/nu). The implanted cells were allowed to grow for 10 days before initiation of drug treatment (dimer oxime and topotecan, ip). Tumor volume and thoracic/body weight ratio were recorded. Results: We successfully established subcutaneous and thoracic xenografts with human nonsmall cell lung cancer cell line xenografts in athymic nude mice in only 10 days. Using these models, we attempted treatment of xenografts with topotecan – a known anticancer drug and artemisinin dimer oxime or combination of these two drugs. Combination therapy showed a significant reduction in tumor volume and tumor/body weight. Treatments with combination of topotecan and dimer oxime resulted in the reduced mortality rates in comparison with untreated mice. Conclusions: Xenograft tumor models are useful for preclinical screening of new pharmacophores. From this preliminary study, it appears that combination of dimer oxime and topotecan may be used as chemotherapeutic agents against nonsmall cell lung cancer. Further studies are needed to evaluate other combination treatment regimens as well as the mechanism(s) of action.

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Background: It is widely accepted that the causes and mechanisms of abortion are very complicated. In China, Scutellariae Radix (SR) (Scutellaria baicalensis Georgi) is widely used as a traditional Chinese herbal medicine with anti-abortion effects. However, the chemical components and pharmacologic profiles of SR have not been elucidated. The network pharmacology approach can provide a system-level perspective to explore the components, targets, and mechanism of herbal medicines. Thus, this approach was employed to identify the absorbable compounds, potential targets, and signaling pathways associated with SR. Materials and Methods: In this study, we used the Lipinski rule and an oral bioavailability of >30% to identify the bioactive compounds in SR. Targets of the anti-abortion activity of SR were obtained from the PharmMapper website server database. The Search Tool for the Retrieval of Interacting Genes and DAVID databases were utilized to perform protein–protein interaction analysis and pathway enrichment analysis, respectively. Finally, Cytoscape software was used to visualize the active compound–target–Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway network of SR. Results: In total, 286 chemical compounds were identified in SR; of these, 27 compounds could be absorbed into the blood, and 10 compounds that had a high docking score with their corresponding targets were determined. These potentially active compounds of SR regulated 142 targets and clearly affected 29 KEGG pathways. From these targets, a total of 11 targets, which were expressed in the breast and female reproductive system, were associated with the anti-abortion effects of SR: EGFR, HRAS, HSP90AA1, ESR1, PRKACA, SRC, GSK3B, JAK2, IGF1R, CDK2, and AR. In the KEGG pathway analysis, five pathways were related to the anti-abortion effect of SR, including the estrogen signaling pathway, the prolactin signaling pathway, progesterone-mediated oocyte maturation, and oocyte meiosis. Conclusions: The network pharmacology approach used in our study attempted to explain the mechanism of the anti-abortion effects of SR and has provided an alternative approach for the investigation of the effects of this complex compound.

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Aristolochic acid (AA) is a group of structurally related nitrophenanthrene carboxylic acids found in many plants that are widely used by many cultures as traditional herbal medicines. AA is a causative agent for Chinese herbs nephropathy, a term replaced later by AA nephropathy. Evidence indicates that AA is nephrotoxic, genotoxic, and carcinogenic in humans; and it also induces tumors in the forestomach, kidney, renal pelvis, urinary bladder, and lung of rats and mice. Therefore, plants containing AA have been classified as carcinogenic to humans (Group 1) by the International Agency for Research on Cancer. In our laboratories, we have conducted a series of genotoxicity and toxicogenomic studies in the rats exposed to AA of 0.1–10 mg/kg for 12 weeks. Our results demonstrated that AA treatments induced DNA adducts and mutations in the kidney, liver, and spleen of rats, as well as significant alteration of gene expression in both its target and nontarget tissues. AA treatments altered mutagenesis- or carcinogenesis-related microRNA expression in rat kidney and resulted in significant changes in protein expression profiling. We also applied benchmark dose (BMD) modeling to the 3-month AA-induced genotoxicity data. The obtained BMDL₁₀(the lower 95% confidence interval of the BMD₁₀that is a 10% increase over the background level) for AA-induced mutations in the kidney of rats was about 7 μg/kg body weight per day. This review constitutes an overview of our investigations on AA-induced genotoxicity and toxicogenomic changes including gene expression, microRNA expression, and proteomics; and presents updated information focused on AA-induced genotoxicity in rodents.

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Radix achyranthis bidentatae (RAB), a member of the Amaranthaceae family, has been widely used in Traditional Chinese Medicine for 1000s of years. Increasing interest in RAB-derived medicinal has led to the discovery of additional triterpenoid saponins, phytoecdysones, polysaccharides, and many other compounds, as well as investigations into their pharmacology. A large number of pharmacological studies have shown RAB and its active components possess a range of pharmacological activities, including anti-tumor, anti-fertility, anti-senile, and anti-inflammatory effects. This review is an up-to-date summary and synthesis of the uses of RAB from phytochemical and pharmacological perspectives.

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