Volume 9,Issue 1,2017 Table of Contents

1 Quality Marker Concept Inspires the Quality Research of Traditional Chinese Medicines

De-an Guo

2017, 9(1):1-2. DOI: 10.1016/S1674-6384(17)60069-8

[Abstract](552) [HTML](0) [PDF 172.92 K](1684)

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2 A New Concept on Quality Marker for Quality Assessment and Process Control of Chinese Medicines

Chang-xiao Liu , Yi-yu Cheng , De-an Guo , Tie-jun Zhang , Ya-zhuo Li , Wen-bin Hou , Lu-qi Huang , Hai-yu Xu

2017, 9(1):3-13. DOI: 10.1016/S1674-6384(17)60070-4

[Abstract](751) [HTML](0) [PDF 625.25 K](2311)

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Chinese medicine (CM) is the most typical conventional therapy compared with any other traditional or alternative medicine systems. The active components of CMs are either primary or secondary metabolites generated by metabolic and biosynthetic enzymes in plants, protecting the plants from environmental stress. The characteristics of these metabolites are diverse, complicated and unique. In this paper, current approaches for quality assessment were extensively reviewed, a new concept of quality marker (Q-marker) was then proposed for CM quality assessment. Additionally, definition of the Q-marker, as well as the relevant methods, were discussed, on the basis of the biosynthetic pathways of secondary metabolites and source of biological active components. Study design of Q-marker is complex system for quality assessment and production process control of CM products with transitivity and traceability. Therefore, the system with characteristics of transmission and traceability is expected to be established for regulation of quality. Upon the concept which the transitivity and traceability in the quality assessment and production process control covered the entire process, such as raw materials, decoction slices, processing, extraction and production can be further enhanced. The transitivity and traceability will inevitably require close attention to “who, what, where, when, and why” details at each stage of Q-markers of CM production form raw materials to patent product. The establishing quality standards are enablers of many and various transitivity and traceability solutions, not a solution in them. It means that the transitivity and traceability system is readily link between products and across borders in quality. According to the thinking mode and methods of investigation on quality assessment of CM product, we focus on the entire process, in terms of safety and effectiveness and quality control. The standard preparation of CM or CM decoction is not only the basis for study of Q-marker, but also the basis for transmission and traceability of the quality of CM product.

3 LC-MS-based Metabolomics in Traditional Chinese Medicines Research: Personal Experiences

Qian Mao , Jin-di Xu , Ming Kong , Hong Shen , He Zhu , Shan-shan Zhou , Song-lin Li ,

2017, 9(1):14-21. DOI: 10.1016/S1674-6384(17)60071-6

[Abstract](1006) [HTML](0) [PDF 543.46 K](1773)

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LC-MS-based metabolomics has being widely used in traditional Chinese medicines (TCMs) research due to the great coverage of mass ranges, high sensitivity to detect metabolites, and no need of sample derivatization. Herein, we reviewed our research on the applications of LC-MS-based metabolomics in TCMs research over the past decade in the following aspects: herbal authentication, determination of herb harvest time, chemical transformation of herbs during post-harvest handlings (sulfur- fumigation and drying), discrimination of raw and processed herbs, chemical transformation of TCMs during preparation, screening endogenous toxic compounds in TCMs, unveiling synergistic mechanisms between small molecules (such as saponins) and polysaccharides in TCMs, revealing synergistic actions of TCMs with chemical drugs, which demonstrated that metabolomics is a superior strategy in TCMs research concerning the holistic perspectives.

4 A Review of Quality Assessment and Grading for Agarwood

Yang-yang Liu , Jian-he Wei , Zhi-hui Gao , Zheng Zhang , Jun-chen Lyu

2017, 9(1):22-30. DOI: 10.1016/S1674-6384(17)60072-8

[Abstract](1149) [HTML](0) [PDF 369.80 K](2383)

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Agarwood is an important non-timber forest product widely used in religious and cultural activities as perfume and fragrance and as traditional medicine in Asia. The high value of agarwood and the inflated consuming market have led to constant rising of the prices. In general, the price of the agarwood is determined according to its quality, which can be divided into different grades. But up to now, there is not any standard quality grading system which could be used overwhelmingly throughout the agarwood producing, commerce and consumption. Therefore, we reviewed agarwood in diversified grading indexes, systems and methods.

5 Distribution of Metabolites in Root Barks of Seven Tree Peony Cultivars for Quality Assessment Using NMR-based Metabolomics

Pei Wang , Ze-ming Rong , Cui-xia Ma , Xin-feng Zhao , Chao-ni Xiao , Xiao-hui Zheng

2017, 9(1):31-41. DOI: 10.1016/S1674-6384(17)60073-X

[Abstract](1220) [HTML](0) [PDF 516.71 K](2344)

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Objective To determine the distribution of metabolites in the root barks of different tree peony cultivars for quality assessment. Methods Seven tree peony phenotypic cultivars with different colors were systematically analyzed using NMR-based metabolomics. Results A total of 16 metabolites from their methanol extracts were simultaneously identified and quantified, including one primary metabolite (sucrose) and 15 secondary ones (acetophenones, phenolics, monoterpene glycosides, flavonoids, and unsaturated fatty acids). The quantitative data indicated that sucrose (90-180 mg/g) and acetophenones (15-100 mg/g), and non-phenolics, monoterpene glycosides, flavonoids, and unsaturated fatty acids (2-15 mg/g) were the major metabolites in these tree peony cultivars. The significantly increasing levels of paeonoside with bioactivity were observed in “Xiangyu”, “Wujinyaohui”, “Roufurong”, “Yaohuang”, “Zhaofen”, “Doul?”, and “Yingrihong” in order. Opposite trends in the levels of paeonoside and paeonol were observed in “Xiangyu” and “Yingrihong”, suggesting that the changes of the secondary metabolites in plants were influenced by primary metabolites, such as sucrose/glucose, and the different physiological processes occurred in different tree peony cultivars. Conclusion “Yingrihong” with red flower has the highest medicine quality whereas “Xiangyu” with white flower has the worst one based on the content of paeonoside.

6 Simultaneous Determination of Seven Components in Gamboge and Its Processed Products Using a Single Reference Standard

Min Xu , Hong-sheng Tan , Wen-wei Fu , Ling-yun Pan , Yue-xun Tang , Shen-da Huang , Yan-feng Xiu

2017, 9(1):42-49. DOI: 10.1016/S1674-6384(17)60074-1

[Abstract](1191) [HTML](0) [PDF 443.21 K](1929)

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Objective To establish a quality control method for simultaneous determination of multiple components in gamboge. Methods A single reference standard for the determination of multiple components (SSDMC) with HPLC was proposed. Seven major components of gamboge including gambogenic acid (S), β-morellic acid (C1), 2R-30-hydroxygambogic acid (C2), isogambogenic acid (C3), gambogellic acid (C4), 2R-gambogic acid (C5), and 2S-gambogic acid (C6) were simultaneously analyzed using gambogenic acid as reference standard. The credibility and feasibility of SSDMC method were validated with respect to linearity, limits of detection and quantification, precision, stability, repeatability, accuracy, ruggedness, and robustness. The relative conversion factors (RCFs) of S and C1-6 were calculated. Twelve batches of gamboge including crude and processed products were successfully analyzed by applying the SSDMC and traditional external standard (ES) methods. Results The SSDMC method was credible and feasible. The RCFs of S and C1-6 were 1.000, 0.913, 0.864, 1.064, 0.777, 0.921, and 0.919, respectively. No significant difference was observed in the contents of the seven components between SSDMC and ES methods. The heat-processing technique caused a reduction in the seven components. Conclusion SSDMC is a simple, reliable, and effective method for the analysis of the complex multiple components in gamboge, and it is also a practical and economical approach.

7 Analysis on Isozyme and Diterpene Lactones Variability during Ontogenesis of Andrographis paniculata

Jun-li Gao , Yan-hua Shao , Xiao-ping Lai , Ping Ding

2017, 9(1):50-57. DOI: 10.1016/S1674-6384(17)60075-3

[Abstract](469) [HTML](0) [PDF 513.91 K](1628)

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Objective To understand the relationship between isozyme activities and diterpene lactone biosynthesis of Andrographis paniculata. Methods Plants were collected during ontogeny from seeding to seed maturity, and separated into leaves and stems for determination. Morphological and yield parameters were used to describe plant growing states. Isozyme changes were tested by polyacrylamide gel electrophoresis. HPLC was used to develop the fingerprints as well as to determine the diterpene lactone content. Results Significant increases were observed in the activities of isozymes, such as aspartate aminotransferase (AST), malate dehydrogenase (MDH), peroxidase (POD), and catalase (CAT), around the early stage of bud in leaves, and the activities of these four kinds of isozymes increased gradually as time progressed in stems. The content changes of diterpene lactones in leaves and stem were various. In the leaves, andrographolide (1) was recorded the highest [(23.63 ± 1.06) mg/g] at the early stage of bud, whereas deoxyandrographolide (2) was the lowest [(6.78 ± 0.27) mg/g] at this period and it reached the highest level at the seeding stage [(26.05 ± 1.04) mg/g]. Dehydroandrographolide (3) and neoandrographolide (4) fluctuated during growing stages. Meanwhile, the HPLC fingerprint showed that the content changes of two unknown compounds were related to that of dehydroandrographolide in leaves. In stems, andrographolide had increased gradually until the bud stage [(8.26 ± 0.33) mg/g], and other three diterpene lactones showed a trend of fluctuation. The yield of total diterpene lactones in aerial part reached the highest at the first flowering stage (806.71 mg/plant). Conclusion These results lay the foundation for the future research on the relationship of isozymes and diterpene lactones, and for determining the most favorable time for harvesting A. paniculata.

8 2-(2-Phenylethyl)chromones from Endophytic Fungal Strain Botryosphaeria rhodina A13 from Aquilaria sinensis

Yao Zhang , Hong-xin Liu , Wen-shan Li , Mei-hua Tao , Qing-ling Pan , Zhang-hua Sun , Wei Ye , Hao-hua Li , Wei-min Zhang

2017, 9(1):58-62. DOI: 10.1016/S1674-6384(17)60076-5

[Abstract](588) [HTML](0) [PDF 505.87 K](1719)

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Objective To study the characteristic 2-(2-phenylethyl)chromone components of endophytic fungal strain of Aquilaria sinensis by solid culture. Methods The compounds were isolated by various chromatographic methods such as silica gel, reverse-phase silica gel, Sephadex-LH20 column chromatography as well as crystallization. Results Seven 2-(2-phenylethyl)chromone analogues were isolated from the solid culture of Botryosphaeria rhodina A13. Their structures were established by spectral data as well as physicochemical properties, and identified as 6-hydroxy-7-methoxy-2-(2-phenylethyl)chromone (1), 6,7-dimethoxy-2-(2-phenylethyl) chromone (2), (5S,6R,7S,8R)-2-(2-phenylethyl)-5,6,7,8-tetrahydrchromone (3), 6- hydroxy-2-(2-phenylethyl)chromone (4), 4′-hydroxy-2-(2-phenylethyl)chromone (5), 6-methoxy-2-phenethyl-4H-chromen-4-one (6), and 6-methoxy-2-(4′-methoxy- phenethyl)-4H-chromen-4-one (7). Conclusion All of the compounds are isolated for the first time from the genus Botryosphaeria. This research opens up a new vista to produce the characteristic components of agarwood by endophytic fungi.

9 Antifungal Activity of Aspidin BB from Dryopteris fragrans against Trichophyton rubrum Involved Inhibition of Ergosterol Biosynthesis

Shi-hao Yang , Wen-hao Chen , Feng Shan , Xiao-zhou Jia , Rong-rong Deng , Chu-ping Tang , Zhi-bin Shen

2017, 9(1):63-68. DOI: 10.1016/S1674-6384(17)60077-7

[Abstract](890) [HTML](0) [PDF 303.43 K](1777)

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Objectives Aspidin BB, a typical phloroglucinol derivative from Dryopteris fragrans, possesses significant antifungal property. This study aimed to investigate potential mechanism of antifungal activity of Aspidin BB against Trichophyton rubrum which is the most common pathogens responsible for chronic dermatophytosis. Methods The minimum inhibitory concentration (MIC) of Aspidin BB against strains was determined by broth microdilution. The effects of Aspidin BB on ergosterol biosynthesis were investigated by content determination based on UPLC method. Besides, the effects of drugs on squalene epoxidase (SE) in T. rubrum cell membrane were analyzed. Results MIC value of Aspidin BB against T. rubrum was 25.0 μg/mL. Aspidin BB reduced ergosterol content significantly, but no notable effect on squalene epoxidase activity. Conclusion The results suggested that Aspidin BB inhibited ergosterol biosynthesis. However, it was not squalene epoxidase but other components may sever as possible targets in ergosterol biosynthesis pathway.

10 Bioactive Study on Mixtures of Epimedin C and Icariin Monomers with Invariant Molarity to Zebrafish Osteoporosis Model

Mi Huang , Jing Feng , Ping Xia , Zai-xuan Zhong , Shun-ping He , Yu-qin Shu , Jiang-yan He , Ying Wang

2017, 9(1):69-73. DOI: 10.1016/S1674-6384(17)60078-9

[Abstract](977) [HTML](0) [PDF 374.00 K](1659)

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Objective To evaluate the anti-osteoporosis effect of the mixtures of epimedin C and icariin monomers with invariant molarity on zebrafish osteoporosis model. Methods The zebrafishes, fertilized 4 d ago, were exposed in 11 groups of nutrient solutions with prednisolone (25 μmol/L) as well as epimedin C and icariin (15 μmol/L) of various contents. The ratio of epimedin C and icariin in the 11groups were as follows: A (10:0), B (9:1), C (8:2), D (7:3), E (6:4), F (5:5), G (4:6), H (3:7), I (2:8), J (1:9), and K (0:10). Meanwhile, a negative control group with prednisolone (25 μmol/L) was prepare as S. The selected zebrafish fetus was put into the 24-hole culture plate, and ensure every 5 zebrafishes in 1 hole and 2 holes as a group. They were placed in incubator at 28.5 oC, and the daily changes of fluid were investigated until they were put to death on day 8 and then fixed. After dyeing with alizarin red, the segmental venter of zebrafish skulls was observed and quantitative analysis of dyed area was conducted. Results Compared with the negative control group S, the integrated optical density (IOD) values of cranial dyed area in all groups increased significantly (P < 0.05); Compared with group S, the IOD value of cranial dyed area in mixtures of epimedium monomers increased significantly (P < 0.05). The mixtures of epimedium monomers were all effective in facilitating zebrafish cranial mineralization and preventing prednisolone from inducing osteoporosis. According to mixtures of A-K groups, zebrafish cranial mineralization gradually decreased with gradually reduced content of epimedin C, with significant difference among groups (P < 0.05). Conclusion The higher the content of epimedin C in mixtures with invariant molarity is, the more active the anti-osteoporosis effect of epimedinC to zebrafish osteoporosis model is.

11 Developmental Toxicity and Potential Teratogenicity of Compound Danshen Tablet, Angong Niuhuang Pill, and Lidan Paishi Tablet in Zebrafish Embryos

Jie-feng Chen , Tong Liu , Dan-ping Huang , Qi-di He , Zuan-guang Chen , Mei-cun Yao

2017, 9(1):74-79. DOI: 10.1016/S1674-6384(17)60079-0

[Abstract](1045) [HTML](0) [PDF 314.00 K](2338)

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Objective Herbal medicines containing toxic herbs or minerals such as Compound Danshen Tablet (CDT), Angong Niuhuang Pill (ANP), and Lidan Paishi Tablet (LPT) are avoided or used with caution for pregnant women because of potential teratogenicity. To understand their mechanism, they were chosen as model subjects for the research. Methods Zebrafish embryos were used to evaluate their potential teratogenic risk in vitro. Results All of them showed teratogenic and lethal effects in zebrafish embryos, with the EC50 values at 351, 793, and 220 μg/mL, and LC50 values at 417, 596, and 380 μg/mL, respectively. CDT and LPT, displaying week potential teratogenicity as their teratogenicity indexes were greater than 1, induced tail malformation and cardiac edema mainly in zebrafish embryos, respectively. Conclusion The results provide the significant guidance of clinical safety of medication.

12 Anti-flu Effect of Compound Yizhihao Granule and Its Effective Components

Hua Huang , Hua Yao , Lin-lin Wang , Li-jun Si , Qiao-li Yang , Zheng-yi Gu

2017, 9(1):80-85. DOI: 10.1016/S1674-6384(17)60080-7

[Abstract](1002) [HTML](0) [PDF 0.00 Byte](15)

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Objective To research the anti-influenza effect of active ingredients in Compound Yizhihao Granule (CYG). Methods The cytotoxicity and cytopathic effects (CPE) were observed under the phase-contrast microscope, besides 50% toxicity concentration (TC50) and 50% inhibitory concentration (IC50) were also calculated using Reed-Muench method, then the antiviral activity in vitro according to Selection Index (SI = TC50/IC50 ) was evaluated. In PR8 virus-infected mice, survival time, death rate, and lung index were observed in order to evaluate the protective effect. Besides, the effective ingredients were determined using HPLC method, and their contents were calculated by external standard method. Results CYG could inhibit the influenza virus-induced CPE, with IC50 of 4.6 mg/mL (equal to herbal extracts 262.2 μg/mL), and no direct cytotoxic effect at this concentration. PR8-infected mice were ig given CYG, the lung index and mortality were significantly reduced, and survival time was obviously prolonged. HPLC analysis indicated CYG contained many kinds of antivirus active components, including rupestonic acid, epigoitrin, and adenosine. Conclusion CYG is an effective natural anti-influenza medicine. Its antiviral effect should be the synergic effect of a variety of antiviral active ingredients.

13 Chemical Constituents from Pericarpium Citri Reticulatae

Man-qin Fu , Geng-sheng Xiao , Ji-jun Wu , Yu-long Chen , Bo Zou , Ke-jing An , Yu-juan Xu

2017, 9(1):86-91. DOI: 10.1016/S1674-6384(17)60081-9

[Abstract](955) [HTML](0) [PDF 0.00 Byte](11)

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Objective To study the chemical constituents from Pericarpium Citri Reticulatae (Citrus reticulata). Methods The chemical constituents were isolated and purified by silica gel column, Sephadex LH-20, and ODS column chromatography. The structures were identified by spectral data. Results Nineteen compounds were isolated and identified as 4′,5,6,7-tetramethoxyflavone (1), 3,3′,4′,5,6,7,8-heptmethoxyflavone (2), sinensetin (3), 5-O-demethylnobiletin (4), tangeretin (5), nobiletin (6), apigenin (7), 5-O- desmethyltangeretin (8), 5,7-dihydroxy-3,3′,4′,6-tetramethoxyflavone (9), pachypodol (10), 4′,5,6,7-tetramethoxyflavanone (11), 3′,4′,5,7,8-pentamethoxyflavanone (12), agestricin C (13), scoparone (14), isoscopoletin (15), hesperidin (16), didymin (17), methylhesperidine (18), and naringin (19). Conclusion Compounds 9-15 are obtained from this plant for the first time.

14 Anti-mutagenicity of Swertiamarin and Its Metabolite in Incubated System of Human Intestinal Flora

Cheng-wang Tian , , Ya-ting Cheng , Tie-jun Zhang , , Xiu-wei Yang

2017, 9(1):92-95. DOI: 10.1016/S1674-6384(17)60082-0

[Abstract](928) [HTML](0) [PDF 0.00 Byte](9)

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Objective To study the biotransformation regulation and pharmacological effect of swertiamarin and its metabolite in incubated system of human intestinal flora. Methods Incubated system of human intestinal flora was utilized to research the intestinal metabolism of swertiamarin. Furthermore, mutagenic test and anti-mutagenic test were carried out to research the activity relationship of swertiamarin and its metabolite. Results Gentianine was found in the metabolites of swertiamarin. The pharmacological experiment indicated that swertiamarin and its metabolite both had good anti- mutagenic effect. Conclusion Swertiamarin is partly metabolized to gentianine after oral administration. They show similar anti-mutagenicity effects.

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