Volume 9,Issue 2,2017 Table of Contents

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  • 1  Plant Tissue Culture and Biosynthesis Provide a Fast Way to Produce Active Constituents of Traditional Chinese Medicines
    Chang-xiao Liu
    2017, 9(2):99-100. DOI: 10.1016/S1674-6384(17)60083-2
    [Abstract](684) [HTML](0) [PDF 207.84 K](784)
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    2  Discovery and Development of Artemisinin and Related Compounds
    Chang-xiao Liu
    2017, 9(2):101-114. DOI: 10.1016/S1674-6384(17)60084-4
    [Abstract](947) [HTML](0) [PDF 811.48 K](1073)
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    Artemisinin is isolated from the plant Artemisia annua, sweet wormwood, an herb employed in traditional Chinese medicine. Prof. You-you Tu discovered artemisinin in the 1960s, so she was awarded the 2015 Nobel Prize in Physiology or Medicine. Artemisinin and its semi-synthetic derivatives are a group of drugs that possess the most rapid action of all current drugs against Plasmodium falciparum malaria. In this review, the author investigated history on discovery of artemisinin, ethnopharmacology of Artemisia plants, chemistry and pharmacological activities of the relative compounds, and introduced Tu and other Chinese and world scientists’ contribution, development of artemisinin and the related compounds and registered and marketed artemisinin drugs in China, UK, and USA. The author also recalled the studies on the mechanism of action of artemisinins and artemisinin combination therapies and summed up the resistance issues. In Current Recommendations and the Global Plan for Insecticide Resistance Management in Malaria Vectors (GPIRM), that the WHO prevents the development and manages the spread of insecticide resistance is summarized in the technical basis for coordinated action against insecticide resistance: preserving the effectiveness of modern malaria vector control. Prof. Tu re-emphasized the artemisinin resistant on five principles to the WHO. She called on the world's scientists to pay attention to the study of drug resistance, and hopes scientists to contribute to break resistance of artemisinins.
    3  Production of Active Compounds in Medicinal Plants: From Plant Tissue Culture to Biosynthesis
    Juan Wang Jian-li Li Jing Li Jin-xin Li Shu-jie Liu Lu-qi Huang Wen-yuan Gao
    2017, 9(2):115-125. DOI: 10.1016/S1674-6384(17)60085-6
    [Abstract](671) [HTML](0) [PDF 403.14 K](1289)
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    Over past decades plant tissue culture has emerged as an alternative of whole plant cultivation in the production of valuable secondary metabolites. Adventitious roots culture of Panax ginseng and Echinacea purpure has reached the scale of 1?10 kL. Some molecular biological techniques, such as transgenic technology and genetic stability are increasingly used in the studies on plant tissue cultures. The studies on elicitors have deepened into the induction mechanism, including signal molecules, functional genes, and so on. More and more biological elicitors, such as A. niger and yeast are used to increase the active compounds in plant tissue cultures. We also discussed the application of synthetic biology in the studies on biosynthesis of artemisinin, paclitaxel, and tanshinon. The studies on active ingredients biosynthesis of medicinal plants provide unprecedented possibilities to achieve mass production of active ingredients. Plant tissue cultures can not only produce active ingredients but also as experimental materials for biosynthesis. In order to improve the contents of active compounds in medicinal plants, following aspects could be carried out gene interference or gene silencing, gene overexpression, combination with chemical synthesis, application of elicitors, and site-directed mutagenesis of the key enzymes.
    4  Research and Application of Adlay in Medicinal Field
    Fei Yu Jun Zhang Ya-zhuo Li Zhen-ying Zhao Chang-xiao Liu
    2017, 9(2):126-133. DOI: 10.1016/S1674-6384(17)60086-8
    [Abstract](1133) [HTML](0) [PDF 808.55 K](963)
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    The traditional Chinese medicine (TCM) adlay has been used as a dietary supplement to promote health and treat various ailments for thousands of years. The effective and safe ingredients of TCM could be used as sources for developing new drugs. This paper reviews the main research and application of adlay seed in medicinal field in the following aspects: botanical resource, ethnopharmacological function, chemical constituents, pharmacology and pharmacokinetics, safety evaluation and toxicity, and clinical application. We hope that the review could help researchers mine the scientific values of adlay seed, innovative drug design, provide the guidance for the application in clinical therapy, and enhance the academic level and clinical efficacy of adlay seed.
    5  Decomposition and Reformulation of Banxia Baizhu Tianma Decoction: A Vasodilatory Approach
    Chu Shan Tan Yean Chun Loh Yung Sing Ch’ng Mariam Ahmad Mohd. Zaini Asmawi Mun Fei Yam
    2017, 9(2):134-146. DOI: 10.1016/S1674-6384(17)60087-X
    [Abstract](925) [HTML](0) [PDF 0.00 Byte](3)
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    Objective To decompose and reformulate Banxia Baizhu Tianma Decoction (BBT) in order to optimize its ratio for vasodilatory effect. The fingerprints of these six component herbs were also studied via Tri-step FTIR analysis. Methods The herbal components of BBT were extracted separately with different solvents, such as 95% ethanol, 50% ethanol, and distilled water. The vasodilatory effect of the extracts was studied using the in vitro pre-contracted aortic ring model. Among these extracts, the water extracts of Pinellia ternata [PT(W)] and Citri reticulatae [CR(W)], 50% ethanol extracts of Gastrodia elata [GE(50)] and Glycyrrhiza uralensis [GU(50)], and 95% ethanol extracts of Atractylodes macrocephala [AM(E)], and Poria cocos [PC(E)] were selected for the orthogonal stimulus-response compatibility group study due to their high effectiveness in vasodilation. Results The best combination ratio (G2) was GE(50), GU(50), AM(E), PC(E), CR(W), and PT(W) at EC0, EC5, EC5, EC5, EC5, and EC5, with EC50 of (0.06 ± 0.01) mg/mL. Comparison between the vasodilatory effects of extracts derived from G2 and BBT were also studied. From the results, the 50% ethanol extract following G2 ratio was found to be most potent extract with the highest vasodilatory effect compared with other extracts derived from G2 or BBT, with EC50 of (0.05 ± 0.005) mg/mL. Conclusion The optimum ratio and appropriate extraction method for the new BBT formulae are obtained. G2 is determined as the best formulae with the highest potency in producing the vasodilatory effect on isolated rat aortic rings. The results obtained suggest that 50% ethanol is found to be the best solvent to extract the vasoactive compounds of G2 in order to exhibit the highest efficacy of vasodilatory effect.
    6  UPLC-Q-TOF/MS-based Metabolic Profiles of Bioactive Components in Rehmannia glutinosa and Cornus officinalis Herb Pair by Rat Intestinal Bacteria
    Jin-hua Tao Min Zhao Yong Ling Shu Jiang Wen-qian Qiu
    2017, 9(2):147-152. DOI: 10.1016/S1674-6384(17)60088-1
    [Abstract](1192) [HTML](0) [PDF 0.00 Byte](5)
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    Objective To investigate the metabolic routes and metabolites of Rehmannia glutinosa and Cornus officinalis herb pair produced by gut microbiome from rats. Methods A rapid and sensitive ultra-performance liquid chromatography/quadrupole-time-of- flight mass spectrometry (UPLC-Q-TOF/MS) technique combined with MetabolynxTM software was established and successfully applied to identify the metabolites of the main bioactive components in the herb pair extract by rat intestinal bacteria. Results Four parent compounds (loganin, morroniside, catalpol, and acteoside) and their eight corresponding metabolites were detected and tentatively identified by the characteristics of their protonated ions. Hydrogenated and demethylated loganetin, dehydroxylated morronisid aglycone, caffeic acid, and its methylated product were the main metabolites. These metabolites suggested that the glycosides were firstly hydrolyzed to their aglycones by hydrolytic enzymes of the enteric microbial flora and subsequently to the other metabolites through hydrogenation, (de)-methylation, and de-hydroxylation. Conclusion The results may be helpful for the further investigation of the pharmacokinetic study of R. glutinosa and C. officinalis herb pair in vivo.
    7  Identification of WRKY Transcription Factors Related to Saikosaponin Biosynthesis in Adventitious Roots of Bupleurum chinense
    Su-rui Wu Ke Gao Xuan Liu Jiao Xu Jian-he Wei Chun Sui
    2017, 9(2):153-160. DOI: 10.1016/S1674-6384(17)60089-3
    [Abstract](946) [HTML](0) [PDF 0.00 Byte](8)
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    Objective To identify the genes of WRKY transcription factors (TFs) from roots of Bupleurum chinense and genes that potentially regulate saikosaponin (SS) biosynthesis. Methods Firstly, the subfamily cluster analysis was mainly based on Arabidopsis thaliana WRKYs for 27 putative WRKY TFs selected from previous transcriptome sequencing data. Secondly, qPCR was used to screen such genes of WRKY TFs that could be induced by NaCl and PEG6000 in adventitious roots of B. chinense. Meanwhile, saikosaponins (SSs) in treated adventitious roots were determined by HPLC. The roots were collected at 0, 2, 4, 8, 12, 24, 48, and 72 h after treatments, and 120 h only for PEG. Finally, the tissue-specific expression was analyzed on screened genes by qPCR. Results The 27 genes were grouped into three categories: There were nine in Group I, 15 in Group II, and two in Group III. Four genes of WRKYTFs, BCWRKY6, BCWRKY16, BCWRKY32, and BCWRKY35 were obviously induced by NaCl in adventitious roots of B. chinense, while only BCWRKY32 was induced by PEG. The content of SSs increased at different levels in NaCl and PEG6000 treatment. Three genes including BCWRKY6, BCWRKY32, and BCWRKY35, expressed most in roots, were similar to the accumulation pattern of SS. Conclusion The three WRKY genes, BCWRKY6, BCWRKY32, and BCWRKY35, may be involved in the biosynthesis of SS.
    8  Efficacy of Traditional Chinese Medicines in Preventing Oxaliplatin-induced Peripheral Neurotoxicity in Cancer Patients: A Network Meta-analysis
    Xiao-chen Wei Li-qin Zhu Hui Wang Chun-ge Wang Qi Deng Xin Li
    2017, 9(2):161-168. DOI: 10.1016/S1674-6384(17)60090-X
    [Abstract](971) [HTML](0) [PDF 0.00 Byte](12)
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    Objective Oxaliplatin-induced peripheral neurotoxicity (OIPN) is the main limitation for its continuation in cancer patients. Traditional Chinese medicines (TCMs) have been used to prevent OIPN in China and have been demonstrated to be effective. However, due to the lack of direct comparison among TCMs, it remains unclear that which TCM is the best for OIPN prevention. Consequently, the present study aimed to compare the relative efficacies of TCMs to find out the best TCM by applying a network meta-analysis. Methods Studies were identified by searching PubMed, EMbase, Cochrane Libraries, CNKI, WanFang, and WeiPu database from January 1990 to May 2016. Randomized controlled trials (RCTs) that evaluated the efficacy of TCMs in preventing OIPN in cancer patients were included. Statistical analysis was performed with ADDIS 1.16.6. Results Twenty-five RCTs (1572 patients) involving five TCMs were included. The results of network meta-analyses showed that compared with oxaliplatin-based chemotherapy alone, the combination with Huangqi Injection (HQI), Shenmai Injection (SMI), Shenfu Injection (SFI), Buyang Huanwu Decoction (BHD), and Huangqi Guizhi Wuwu Decoction (HGWD) could decrease the overall OIPN incidence and the severe OIPN incidence in cancer patients. In addition, probability ranking results showed the order of efficacy in preventing overall OIPN incidence was HQI > HGWD > SFI = SMI > BHD, while the order of efficacy in preventing severe OIPN incidence was HQI > HGWD > BHD > SFI = SMI. Conclusion All five TCMs are effective neuroprotective agents against OIPN. Among these TCMs, HQI and HGWD were superior to others in clinical efficacy. Moreover, Astragalus membranaceus might be a more promising herb for the OIPN prevention. However, more direct head-to-head RCTs with high quality and large sample size are still needed to further confirm the conclusion.
    9  Screening of Eleven Commonly Used Traditional Chinese Medicines for Inhibitory Effects on Human Cytochrome P450 Enzymes
    Lin-hu Ye Ling-ti Kong Bing-xin Xiao Qian Wang Xiao-xi He Xin-min Liu Qi Chang
    2017, 9(2):169-175. DOI: 10.1016/S1674-6384(17)60091-1
    [Abstract](1064) [HTML](0) [PDF 0.00 Byte](9)
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    Objective Traditional Chinese medicines (TCMs) as natural therapeutic agents have been widely used and received great attention over the world. However, the information on them to cause herb-drug interactions mediated by cytochrome P450 (CYP) enzymes is limited. The present study aims to evaluate the inhibitory effects of 11 commonly used TCMs, including Nelumbinis Folium, Ginseng Radix et Rhizoma, Ziziphi Spinosae Semen, Chrysanthemi Flos, Lonicera Japonica Flos, Lycii Fructus, Cassiae Semen, Poria, Crataegi Fructus, Schisandrae Chinensis Fructus, and Polygonati Rhizoma, on the five human major CYP isoenzymes 2C19, 2D6, 3A4, 2E1, and 2C9. Methods An in vitro cocktail method was used. Results The aqueous extracts of all tested TCMs were found no significant inhibitory effect, with IC50 values higher than 100 μg/mL. While, the ethanolic extracts of some herbs showed more potent inhibition. These herbs include Nelumbinis Folium with IC50 values of 12.05 and 61.43 μg/mL on CYP2D6 and CYP2E1, Schisandrae Chinensis Fructus with IC50 values of 64.42 and 47.24 μg/mL on CYP2C19 and CYP3A4, and Chrysanthemi Flos with IC50 values of 45.25 μg/mL on CYP2C9, respectively. Conclusion Co-administration of these TCMs and their products with conventional medicines should be paid much attention to, and their potential inhibitory effects on CYP enzyme activities need to be further investigated.
    10  Anti-inflammatory Effects of Saxifrage Cream in Hapten-induced Chronic Dermatitis-eczema in Mice
    Jun Yang Yong-Ai Xiong Shi-Ji Xiao Ying-Shu Xu
    2017, 9(2):176-182. DOI: 10.1016/S1674-6384(17)60092-3
    [Abstract](1039) [HTML](0) [PDF 0.00 Byte](8)
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    Objective Chronic dermatitis-eczema is a kind of inflammatory skin disease characterized by pruritic and eczematous skin lesions. In the present study, we investigated the anti-allergic effect of Saxifrage cream on eczema-like skin lesions induced by 2,4-dinitrochlorobenzene (DNCB) in mice. Methods KM mice were randomly divided into eight groups: normal group (Norm), model group (DNCB), positive group 1 (Dexamethasone cream, DEX), positive group 2 (Chinese herbal medicine Paeonol cream, PA), Saxifrage cream groups (equivalent to crude herb 1.25, 2.50, 5.00 g/g, S1, S2, S4), and negative group (Norm + S4). Except for the normal control group and negative control group, right ears of mice in other groups were repeatedly induced with 0.5% DNCB for four times for 3 d and previously sensitized with 7% DNCB to induce eczema. Then mice in different groups were treated by DEX, PA, S1, S2, and S4, respectively. After mice were sacrificed, weight difference of two ears, immune organ change, and pathological change of right ear were used to assess the effects of the drugs. Results Compared with model group, DEX, PA, S2, and S4 could significantly lower mice ear thickness and swelling degree, and improve eczema skin symptoms. Meanwhile, the index of thymus and spleen in treatment groups were significantly reduced (P < 0.05). What’s more, the histological analysis demonstrated that thickening of the skin lesions were significantly reduced in DEX, S2, and S4-treated group, and the levels of IL-4 and IL-6 in serum could be reduced by DEX, S2, and S4. Conclusion Saxifrage cream has a protective function against DNCB-induced eczematous. The mechanism might be related to alleviate eczematous inflammatory reaction.
    11  Inhibition of Yuyihe Powder on Tumor Growth in Mice Models of Sarcoma 180
    Jun-ling Li Shi-li Wang Jin-xiang Han Hai Xu Xiao-bin Xu Jun-ying Xue
    2017, 9(2):183-187. DOI: 10.1016/S1674-6384(17)60093-5
    [Abstract](1063) [HTML](0) [PDF 0.00 Byte](12)
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    Objective To explore the antitumor effect of Yuyihe Powder (Yu Yi He San, YYHS) and its antitumor mechanism. Methods After treatment, tumor weight, immune apparatus weight, the life span of transplanted animals, spleen lymphocyte proliferation assays, and IL-2 concentration in mouse serum were recorded or detected. Results YYHS showed strong antitumor ability. Compared with control group, mid-dose YYHS (1.0 g/kg) could inhibit the tumor growth, prolong the life span of S180-bearing mice to some extent, significantly increase the thymic and splenic indices of S180 mice, and strongly promote the secretion of IL-2 in blood; The inhibitory rate on tumor growth and life prolongation rate were 37.1% and 38.37%, respectively. Conclusion YYHS could not only significantly inhibit the growth of S180 cells, but also markedly prolong the survival time of S180 bearing mice. The mechanism of antitumor effect could obviously enhance immunologic function of the S180 bearing mice to inhibit the growth of S180 cells.
    12  Chemical Constituents from Mycelia and Spores of Fungus Cordyceps cicadae
    Jia-hui Wang Zhong-liang Zhang Yu-qin Wang Min Yang Chun-hua Wang Xu-wen Li Yue-wei Guo
    2017, 9(2):188-192. DOI: 10.1016/S1674-6384(17)60094-7
    [Abstract](1097) [HTML](0) [PDF 0.00 Byte](6)
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    Objective To isolate and identify the chemical constituents from mycelia and spores of the fungus Cordyceps cicadae, respectively. Methods The chemical constituents were isolated and purified by repeated silica gel, Sephadex LH-20, and reversed phase HPLC. The structures of these compounds were elucidated on the basis of extensive spectroscopic analysis, including 1D and 2D NMR. Results Nine known sterols such as ergosterol (1), ergosterol peroxide (2), 9,11-dehydroergosterol peroxide (3), 3β,5α,9α- trihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (4), 3β,5α,9α,14α-tetrahydroxy-(22E, 24R)-ergosta-7,22-dien-6-one (5), 5α,6α-epoxy-(22E,24R)-ergosta-8(14),22-diene- 3β,7α-diol (6), 3β,5α,6β-(22E,24R)-ergosta-7,22-dien-3,5,6-triol (7), 3β,5α,6α-6- methoxyergosta-(22E,24R)-7,22-diene-3,5-diol (8), 4-hydroxy-17R-methylincisterol (9), together with a resorcinol derivative, 5-n-nonadecylresorcinol (10), a cyclo- desipeptide, beauvericin (11), and a nucleoside, N6-(2-hydroxyethyl)adenosine (12) were successively isolated from the cultivated C. cicadae mycelia and spores. Conclusion Compounds 3?10 are reported for the first time from the title sample, beauvericin exhibits significant cytotoxicity against human leukemia cell line and human lung cancer cell line.
    13  Triterpenoids from Whole Plants of Phyllanthus urinaria
    Ye Wu Shuang-shuang Xie Zheng-xi Hu Zhao-di Wu Yi Guo Jin-wen Zhang Jian-ping Wang Yong-bo Xue Yong-hui Zhang
    2017, 9(2):193-196. DOI: 10.1016/S1674-6384(17)60095-9
    [Abstract](1191) [HTML](0) [PDF 0.00 Byte](12)
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    Objective To study the chemical constituents of whole plant of Phyllanthus urinaria and their biological activity. Methods The chemical constituents were isolated and purified by repeated column chromatography over silica gel, Rp-C18 (reverse phase), MCI, and Sephadex LH-20, as well as semi-preparative HPLC. NMR spectroscopic analyses were used for the structure identification. In this case, the inhibitory rate of NO production of the isolated triterpenoids was evaluated. Results Seven triterpenoids, identified as 28-norlup-20(29)-ene-3,17β-diol (1), betulin (2), β-betulinic acid (3), 3-oxo- friedelan-28-oic acid (4), oleanolic acid (5), 3R-E-coumaroyltaraxerol (6), and 3R-Z- coumaroyltaraxerol (7), were isolated and identified from the whole plants of P. urinaria. Compounds 1?5 exerted inhibitory effects against NO production in LPS-induced RAW 264.7 mouse macrophages with the inhibitory rate of NO production ranging from 4.0% to 27.8% at the concentration of 25 μmol/L. Conclusion To the best of our knowledge, this is the first report of compounds 1?4, 6, and 7 from the family Euphorbiaceae. Compounds 1?5 exhibited inhibitory effects against NO production in LPS-induced RAW 264.7 mouse macrophages.

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