World Journal of Traditional Chinese Medicine

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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

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.

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

In recent years, more and more poison incidents of Chinese Materia Medica (CMM) were reported by China and other countries, which made people to doubt about the safety of CMM, especially for the toxic CMM. In this review, the toxicity of CMM and the toxicity classification of CMM were introduced. And traditional TCM theory and methods particularly used for control and attenuation of CMM’s toxicity were described in detail. The traditional processing technology and CMM drug combination were most important detoxifying measures used in CMM formulation and clinical practice. Finally, some factors that have influence on occurrence of CMM’s toxicity were discussed such as different species, producing technology and so on.

The pathophysiological characteristics of Phlegm-stasis Cementation Syndrome in Coronary Heart Disease (CHD) has been summarized in this article. According to epidemiological investigations, phlegm-stasis cementation syndrome has become a dominant syndrome in CHD along with the improvement in living and dietary condition. The interaction between blood stasis and phlegm turbidity that is called Phlegmstasis Cementation Syndrome exists in CHD and other diseases. The bridge linked blood stasis and phlegm turbidity lies in the adversely effects of lipid metabolism disorder on platelet activation, vascular function and hemorheology indexes. Lipid metabolism disorder also can induce persistent inflammation including monocyte/macrophage activation and oxidative stress. Inflammation also is an important stimulating factor for atherosclerosis and the biology that underlies the complications of CHD, which belonged to the concept of “toxin” in Traditional Chinese medicines (TCM). On the other hand, the important function of inflammatory process on abnormal hemorheology, platelet activation and vascular dysfunction can be used to elucidate the basic pathogenetic condition of the toxin inducing blood stasis in TCM. Therefore, it is this pathological process that can be used to address the basic pathogenetic theory of phlegm turbidity inducing the symptom of toxin and blood stasis, and subsequently phlegm-stasis cementation in TCM. We deduced that lipid metabolic disturbance, inflammation activation, vascular dyfunction and hemorheological disorders could be as pathophysiological characteristics of Phlegm-stasis cementation syndrome.

Objective: To demonstrate that acupuncture has an instant effect in equilibrating the imbalanced electrical conductivity of Yuan-Source acupoints after intervention on the Luo-Connecting acupoint (one-side) of the same channel. Methods: The experiment was designed as a randomized blinded control trial, with 56 volunteers. Reactive Electrical Permeable Points (REPP – mostly Yuan points) were measured in terms of electrical conductivity. Patients with a split-meridian (difference between left and right measurement) were randomly included in the control or experimental group. After five minutes of needle insertion in a Luo acupoint, the needle was removed and REPP were re-measured twice within a five minutes interval. Results: From the 56 volunteers, 32 had a valid Split-Meridian Difference (SMD > 20 μA) and were included in the study. The results indicate that after the third measurement (15 minutes – M3), 100% of the experimental group had SMD < 20 μA and 55% was with a SMD = 0 μA. In contrast, for the control group, 92% remained with a SMD > 20 μA, at M3, when compared with the initial measurement (M1). Results obtained between the experimental and control group are significantly different (p < 0.001). Conclusions: The present exploratory work indicates that there is evidence of instant body response to acupuncture that can be detected by changes in the electro-conductivity of specific acupoints.

Objective: This study is aimed to investigate the clinical significance of regulating effect of Jianpi Bushen Granule (JBG) combined with Western medicine on the level of serum acetylcholine receptor antibodies (AchRAb) in myasthenia gravis (MG) patients, so as to offer a theoretical basis of the targeted therapy with AchRAb. Methods: We detected the level of anti-AchRAb with enzyme linked immunosorbent assay (ELISA) in the sera from 60 cases of MG patients (randomly divided into the trial group 30 cases, control group 30) for before and after treatment 6 months, and the clinical evaluation carried out by the Quantitative score of myasthenia gravis (QMG) for before and after treatment 3,6 months. Results: (1) Comparison of the level of serum AchRAb:All included MG patients, the positive rate of serum AchRAb was about 81.67% (49/60), and the trial group was 83.33% (25/30), the control group was 90% (27/30), and the serum AchRAb levels of the trial group (0.994 ± 0.417) was lower than that of the contral group (1.068 ± 0.358), but there was no significant difference between the two groups before treatment (P > 0.05). After 6 months of treatment, the serum AchRAb levels of the trial group (0.721 ± 0.280) was also significantly lower than that of the contral group (0.907 ± 0.387), and the serum AchRAb levels was decreased dramatically compared with the same group before treatment, there was significant difference between the two groups (P < 0.05). (2)Comparison of QMG scoring:QMG scoring was decreased dramatically in the trial group compared with that of the control group after treatment, there was significant difference (P < 0.05), moreover, the total effective rate in the trial group (50%,86.67%)was significantly higher than those in the control groups (23.33%, 40%) after 3,6 months treatment (P < 0.05). There was also significant difference in the clinical evaluation by the QMG between the two groups before and after treatment. (3) Adverse reactions: no obvious adverse reactions appeared among the two groups. Conclusions: JBG combined with Western medicine therapy on MG by regulating the level of patients’ serum AchRAb shows definite effects, and it is worthy of further studying. Abbreviations:< JBG: Jianpi Bushen Granule; AchRAb: acetylcholine receptor antibodiesin; MG: myasthenia gravis; ELISA: enzyme linked immunosorbent assay; QMG: Quantitative score of myasthenia gravis; AchR: acetylcholine receptor; N₂AchRab: nicotinic acetylcholine receptor; TCM: Traditional Chinese Medicine; MuSK: muscle-specific kinase; NMJ: neuromuscular junction

Online since 28^th Sep 2017.