Volume 9,Issue 4,2017 Table of Contents

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  • 1  Determination of Quality Markers is Basis for Establishing Quality Standard and Control of Chinese Herbal Medicines
    Chang-xiao Liu
    2017, 9(4):299-300. DOI: 10.1016/S1674-6384(17)60108-4
    [Abstract](449) [HTML](0) [PDF 0.00 Byte](9)
    2  Gut Microbiota Brings a Novel Way to Illuminate Mechanisms of Natural Products in vivo
    Peng Guo Chong-ming Wu
    2017, 9(4):300-306. DOI: 10.1016/S1674-6384(17)60109-6
    [Abstract](620) [HTML](0) [PDF 0.00 Byte](13)
    Poor bioavailability and undefined major/direct targets are two major obstacles for herbal medicines and natural products (NPs) to elucidate their precise mechanisms in vivo. Gut microbiota is an important bridge between eukayotic body and environment, which can interact with a majority of medicines with poor bioavailability and mediate their in vivo pharmacological activities. There are two main modes through which gut microbiota may mediate the pharmacological effects of NPs. First, gut microbiota catabolizes the NPs in herbal medicines into secondary metabolites with higher bioavialability and/or higher activity, facilitating the NPs enter circulation and exert beneficial impact at the pathological spot. Second, herbal medicines and NPs can favorably shift the compositional structure of gut microbiota, thereby performing remote functions to diseased organs/tissues via the systemic impaction of gut microbiota. In this review, the potential pathways were summarized through which gut microbes facilitate the pharmacological functions of herbal medicines and NPs and highlight the significance of gut microbiota in clarifying the in vivo mechanisms of herbal medicines and NPs.
    3  Research on Quality Markers of Moutan Cortex: Quality Evaluation and Quality Standards of Moutan Cortex
    Zhi-qiang Wang Jie Shen Pei Li Shuang-shuang Liu Fan Yi Hai-bo Liu Fan-rong Wu Chun-nian He Fei-hu Chen Pei-gen Xiao
    2017, 9(4):307-320. DOI: 10.1016/S1674-6384(17)60110-2
    [Abstract](644) [HTML](0) [PDF 0.00 Byte](9)
    Objective To identify the quality markers of Moutan Cortex (MC) and establish the quality evaluation methods for multi-component assay and fingerprinting of MC. Methods The chemical constituents in MC were identified by HPLC-QTOF-MS. UPLC was employed for the multi-component assay and fingerprinting of MC. Furthermore, text mining was carried out to review the biosynthesis pathways and pharmacological and pharmacokinetic studies related to MC, and in silico target fishing was conducted to construct compound-target networks for MC. Results Sixteen compounds were clearly identified in MC and their structures were confirmed through comparison with literature data. In addition, the biosynthetic pathways and component specificities of the identified compounds were summarized and confirmed by text mining. Pharmacological activities, including traditional usage and modern pharmacological studies were summarized. A total of 282 targets from Homo sapiens were fished for 13 compounds. In addition, pharmacokinetic studies of different compounds were synopsized. Finally, multi-component assay and fingerprint of MC were established. Conclusion Eight major components are selected as quality markers of MC, such as oxypaeoniflorin, apiopaeonoside, albiflorin, paeonolide, paeoniflorin, 1,2,3,4,6- penta-O-galloyl-β-D-glucose, mudanpioside C and paeonol. These eight quality markers are successfully applied to the quality evaluation of MC, and could be useful in improving the current quality standards of MC.
    4  Tyrosinase Inhibitory Activity of Total Triterpenes and Poricoic Acid A Isolated from Poria cocos
    Shu-hua Hu Gao Zhou You-wei Wang
    2017, 9(4):321-328. DOI: 10.1016/S1674-6384(17)60111-4
    [Abstract](433) [HTML](0) [PDF 0.00 Byte](23)
    Objective With the improvement of people’s living standards, people’s requests for beauty are increasing. Skin whitening and lightening have become the pursuit of many women, and whitening and removing freckles have become the focus of scientific research. At present, widely used whitening agents, such as kojic acid, vitamin C, and its derivatives, have shortcomings such as poor stability and retarded effect. Therefore, safer and more effective whitening products from herbs are urgently needed. To explore the possibility of triterpenes as whitening active substance, the effects of total triterpenes of Poria (TTP) and poricoic acid A (PAA) on mushroom tyrosinase activities and B16 cells were investigated, and their mechanisms on mushroom tyrosinase were also studied. Methods Using arbutin and nicotinamide as reference substances, we determinated the inhibitory effects of TTP and PAA on mushroom tyrosinase and tyrosinase in B16 cells and then studied the inhibitory mechanism on mushroom tyrosinase. Results TTP and PAA exhibited good inhibitory effects on the activities of monophenolase and diphenolase in mushroom tyrosinase, as well as a certain inhibitory effect on tyrosinase in B16 cells. Conclusion TTP and PAA are potential whitening active ingredients.
    5  Variation of Sweet Chemicals in Different Ripening Stages of Wolfberry Fruits
    Dan Qian Jian Yang Li-ping Kang Rui-feng Ji Lu-qi Huang
    2017, 9(4):329-334. DOI: 10.1016/S1674-6384(17)60112-6
    [Abstract](425) [HTML](0) [PDF 0.00 Byte](15)
    Objective To evaluate the variation of sweet chemicals (sugars and betaine) in fruits of six species in genus Lycium L. i.e. Lycium truncatum, L. cylindricum, L. dasystemum, L. dasystemum var. rubricaulium, L. chinense, and L. barbarum harvested at three different ripening stages. Methods A simple and effective method based on UPLC-ELSD was developed for the simultaneous determination of two monosaccharides (glucose and fructose), two disaccharides (sucrose and maltose), one sugar alcohol (xylitol), and betaine in wolfberry fruits (goji berries) of genus Lycium L. Results The six species of wolfberry fruits harvested at the three different ripening stages were evaluated in sugars and betaine contents. Fructose and glucose were the predominant sugars in mature wolfberry fruits. Fructose, glucose, and betaine, as well as total sugar contents, increased continually over the ripening process. L. truncatum and L. dasystemum had higher contents of sugars and betaine than the other species. Conclusion UPLC-ELSD is a simple, reliable and effective method for analysis of the sweet chemicals in wolfberries. Wolfberry fruits at the different ripening stages were significant different in sweetness. L. truncatum and L. dasystemum could be the potential sources of wolfberry fruit sources.
    6  Protective Effect of Salvianolic Acid A on Brain Endothelial Cells after Treatment with Deprivation and Reperfusion of Oxygen-glucose
    Si-qi Feng Jian-liang Geng Run-bin Sun Jing-qiu Huang Zhao-yi Tan Cai-xia Yan Ji-ye AA Guang-ji Wang
    2017, 9(4):335-343. DOI: 10.1016/S1674-6384(17)60113-8
    [Abstract](448) [HTML](0) [PDF 0.00 Byte](15)
    Objective Salvianolic acid A (SAA) has a significant protective effect on ischemia/reperfusion injury of brain. However, it is not clear for SAA to exert its cerebral protection by targeting at the microvascular endothelial cells of blood brain barrier (BBB). Our previous study demonstrated that SAA could hardly pass through the BBB. This present study was therefore designed to investigate the protective effect of SAA on brain microvascular endothelial cells (BMECs) induced by deprivation and reperfusion with oxygen-glucose. Methods Rat BMECs were treated with oxygen glucose deprivation (OGD), followed by reperfusion (OGD/R). Cell viability was assessed by MTT and the content of reactive oxygen species (ROS) in cells after OGD/R in the absence or presence of SAA. GC-MS based metabolomic platform was applied to evaluate the regulation of SAA on the cellular metabolic perturbation induced by OGD/R. Results OGD/R significantly increased the production of intracellular reactive oxygen species (ROS), and decreased the activity of cells. SAA significantly reduced ROS and improve the cell viability. Metabolomic study revealed distinct perturbation of metabolic pathways of energy metabolism in the BMEC induced by OGD/R, while SAA significantly regulated the perturbed metabolism involved in energy metabolism pathways, especially for intermediates in TCA cycle. Conclusion SAA shows protective effects on BMECs involved in central nervous system.
    7  Amelioration of Tripterygium wilfordii Polycoride on TNBS/Ethanol-induced Ulcerative Colitis via Inhibiting Lipid Peroxidation and Its Downstream Inflammatory Meditors
    Yi-jun Zhou Dan-ping Qin Yao-dong Wang Qiang Yang Chun-li Zhang Qun Dai
    2017, 9(4):344-352. DOI: 10.1016/S1674-6384(17)60114-X
    [Abstract](438) [HTML](0) [PDF 0.00 Byte](7)
    Objective To study the protective effect of Tripterygium wilfordii polycoride (TWP) against TNBS/ethanol-induced ulcerative colitis (UC) rat model. Methods TNBS and ethanol enema were adopted to build TNBS/ethanol-induced UC rat model. Ninety male Wistar rats were divided into six groups: normal, model, low-, medium-, high-dose TWP and azathioprine (AZA) groups, each for 15 rats. All rats were administered by corresponding medicine for 14 d. After 14 d, corresponding colon tissues underwent general and microscopic evaluation. Blood samples were taken from heart and serum was separated by centrifugation. MDA, SOD, GSH, IL-1β and TNF-α levels in serum were tested by ELISA. Colonic samples underwent RT-PCR and Western blotting analysis. Results DAI, general and microscopic evaluation all showed that TWP could promote colonic mucosa healing and such effect was equal to AZA. ELISA results about lipid peroxidation indicated that TWP could decrease MDA level and increase SOD and GSH levels in a dose-dependent manner. TWP with high dose could strongly decrease the MDA level and increase the SOD and GSH levels (P < 0.01). ELISA results about inflammatory cytokines indicated that TWP could inhibit the expression of IL-1β and TNF-α in a dose-dependent manner. Western blotting analysis and RT-PCR all indicated that no matter in mRNA level or protein level, TWP could inhibit the expression of NF-κB, TNF-α, IL-1β, and IFN-γ in a dose-dependent manner. The inhibitory effect of AZA towards NF-κB was slightly weaker than TWP with high dose (P > 0.05), whereas slightly stronger towards terminal inflammatory cytokines (P > 0.05). Conclusion TWP could significantly lower the infiltration of inflammatory cells under microscope, eventually led to mucosa healing, the mechanism of which was to inhibit lipid peroxidation, then further inhibit NF-κB activation, eventually lower the expression of inflammatory meditors locally and systemically.
    8  Synergistic Antimicrobial Activity of Berberine Hydrochloride, Baicalein and Borneol against Candida albicans
    Yan Liu Yu Zhao Da-liang Guo Wen-wei Liu Yu-xuan Liu
    2017, 9(4):353-357. DOI: 10.1016/S1674-6384(17)60115-1
    [Abstract](449) [HTML](0) [PDF 0.00 Byte](11)
    Objective To determine the synergistic effects of berberine hydrochloride, baicalein, and borneol in different combinations on Candida albicans. Methods The broth microdilution method was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the three agents, and the checkerboard method was simultaneously used to determine the MIC and fractional inhibitory concentration index (FICI) of the combination of three antimicrobial agents to study their extracorporeal effects. Results Berberine hydrochloride was the most potent inhibitor of C. albicans (MIC and MBC of 0.160 and 0.640 mg/mL), followed by borneol (MIC and MBC of 0.320 and 0.640 mg/mL) and baicalein (MIC and MBC of 1.28 and 20.48 mg/mL). Moreover, the antifungal effect of the combination was significantly stronger than that tested alone. Further in vivo study showed that the mortality rate of tainted mice reduced over 50% compared with the control group. Conclusion The results of experiments in vitro and in vivo indicate the synergistic effect of the combination of three antimicrobial agents on C. albicans, which can make reference for the future clinical treatment.
    9  Anti-inflammatory and Anti-oxidant Effects of Licorice Flavonoids on Ulcerative Colitis in Mouse Model
    Dong-yu Liu Li Gao Juan Zhang Xiao-wei Huo Hui Ni Li Cao
    2017, 9(4):358-368. DOI: 10.1016/S1674-6384(17)60116-3
    [Abstract](1950) [HTML](0) [PDF 0.00 Byte](12)
    Licorice (Glycyrrhizae Radix or Liquiritiae Radix) is traditionally used to treat various diseases including inflammation and gastric ulcers. Licorice is rich in flavonoid compounds and possesses anti-inflammatory activities. To investigate the protective effects of licorice flavonoids (LFs) in both acetic acid-induced and dextran sulphate sodium (DSS)-induced ulcerative colitis (UC) mouse model and its underlying mechanism. Acute UC was induced by intra-rectal acetic acid (4% v/v) after pretreatment with LFs (100, 200, and 400 mg/kg, p.o.), 0.9% saline (20 mL/kg, p.o.) or Sulfasalazine (SASP) (600 mg/kg, p.o.) for 10 d. Quantitative analysis of chemical components of LFs was also conducted by HPLC. Our results showed that pre-treatment with LFs significantly reduced the wet weight/length ratio of colon, percentage of affected area, macroscopic and histological damage scores in acid-induced UC mice. LFs also significantly decreased the oxidative stress and pro-inflammatory cytokines, upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and downregulated nuclear transcription factor kappa B (NF-κB) pathway. At last, LFs also showed obvious antiulcer effect on the DSS-induced UC model. The major components of LFs were licochalcone A, glabrone, licoflavone, and licoflavone B. This study demonstrates that the protective effect of LFs may at least in part be due to its anti-oxidant activity through Nrf2 pathway and anti-inflammatory activity through NF-κB pathway.
    10  Metabolomic Analysis of Biochemical Changes in Urine of Osteoarthritis Rat and Interventional Effects of Bushen-Huoxue Herb Couple
    Hua Yin Ling Wang Qing-lin Li Jian-hua Zhang Lin Zhang Xuan Wang
    2017, 9(4):369-375. DOI: 10.1016/S1674-6384(17)60117-5
    [Abstract](343) [HTML](0) [PDF 0.00 Byte](15)
    Objective Osteoarthritis (OA) is a kind of degenerative arthritis, involving degradation of joints, including articular cartilage and subchondral bone. Bushen-Huoxue Herb Couple (BHHC) is a Chinese herb pair with invigorating the kidney and promoting blood circulation. In our study, a Gas Chromatography-Mass Spectrometer (GC-MS) based metabolomics was developed to achieve a systematic observation of the progression of OA and evaluate the efficacy of BHHC in OA rats. Methods Forty Sprague-Dawley rats (half males and half females) were randomly divided into five groups, including normal group, OA model group, sham-operated group, BHHC group, positive medicine (PM) group after anterior cruciate ligament reconstruction and meniscectomy on rats. Urine samples for analysis were collected on week 0, 2, 4, 6, 8, 10, 12, and 14 during the experiment. Results The histological results showed that BHHC had a strong action of repairment and reconstruction of joint damage. By combining with partial least squares discriminant analysis (PLS-DA), 14 biomarkers were identified in urine samples. The biomarkers were mainly involved 10 metabolism pathways, such as tricarboxylic acid cycle metabolism, acid amino metabolism, tryptophan metabolism, lipid metabolism and phenylalanine metabolism. Using these potential biomarkers as a screening index, it indicated that BHHC could reverse the pathological process of OA through regulating amino acid metabolism, lipid metabolism, nucleotide metabolism and energy metabolism. Conclusions This study demonstrates that a metabolomics is a useful tool for identifying potential OA biomarkers and investigating the underlying mechanisms of Traditional Chinese Medicine in OA treatment.
    11  Determination and Pharmacokinetic Study of Nitidine Chloride in Rat Plasma after Intragastrical Administration by LC-ESI-MS/MS Method
    Dong-mei Wang Jing-fan Zhou Xiao-bin Zhong Jie Feng
    2017, 9(4):376-380. DOI: 10.1016/S1674-6384(17)60118-7
    [Abstract](379) [HTML](0) [PDF 0.00 Byte](10)
    Objective To study the pharmacokinetics of nitidine chloride (NC) in rat plasma after intragastrical (i.g.) administration. Methods A liquid chromatography-electrospray ionization-mass/mass sprectrometry (LC-ESI-MS/MS) was used and carbamazepine was used as an intermal standard (I.S.). The rat plasma samples were deproteinized with acetonitrile and the resultant supernatant was assayed on an analytical DiamonsilTM ODS C18 column (2.1 mm × 150 mm) equipped with a C18 guard column (4 mm × 20 mm) with a mobile phase of acetonitrile–10 mM ammonium acetate buffer–formic acid (35: 65: 0.2, v/v/v) at the flow rate of 0.25 mL/min. The LC–MS was carried out on a triple-quadrupole mass spectrometry equipped with an ESI and positive selected-ion monitoring. Target ions were monitored at [M - Cl]+ m/z 348.2 for NC and [M + H]+ m/z 237.2 for I.S., respectively. Results The simple one step deproteinize and rapid analysis method were successfully used in pharmacokinetic study on NC after i.g. administration. The linear relationship was good over the range of 2.5 – 1000.0 ng/ml (r2 = 0.999 2) in rat plasma. The lower limit of quantification and detection were 2.5 and 1.6 ng/ml, respectively. The extraction recovery was in the range of 86.54 – 98.60%. The intra- and inter-day precisions (relative standard deviation) were less than 6.00%, with accuracies deviation between 89.40 to 95.57%. A two-compartment pharmacokinetic open model was proposed and validated to explain the apparent biphasic disposition of NC in rat plasma after i.g. administration. Conclusion This study was successfully applied to a pharmacokinetic study of NC in rats plasma following i.g. administration and could be used for preclinical and clinical pharmacokinetic evaluation of NC.
    12  Protective Effects and Underlying Mechanisms of Compound Herba Houttuyniae in db/db Mice
    Yun Fang Hai-ying Wang
    2017, 9(4):381-387. DOI: 10.1016/S1674-6384(17)60119-9
    [Abstract](437) [HTML](0) [PDF 0.00 Byte](10)
    Objective Houttuynia cordata Thunb and Fructus Arctii are two traditional Chinese medicine (TCM) compounds widely used for reducing heat and toxins in the body. In addition, Fructus Arctii has been used in clinical therapy for diabetic nephropathy. On the basis of the TCM theory of heat in diabetes mellitus and the clinical efficacy of Fructus Arctii, the two compounds were used to develop a formula named Compound Herba Houttuyniae. This study evaluated the renoprotective effects of different Compound Herba Houttuyniae extracts and assessed their mechanisms through the Janus kinase/signal transducer and activator of transcription (JAK/STAT)–suppressors of cytokine signaling (SOCS)-1 pathway. Methods The normal group comprised db/m mice (n = 8); db/db mice were randomly divided into six groups according to the applied treatment method: model group (no treatment), AG490 group, petroleum ether extract (PEE) group, ethyl acetate extract (EAE) group, N-butanol extract (NE) group, and water extract (WE) group (n = 6 in each group). The general status, biochemical indicators, and renal histological changes in the mice were evaluated, and the JAK/STAT–SOCS-1 pathway was assessed. Results The NE and WE groups showed a decrease in 24-h urinary protein and albumin levels as well as serum uric acid and fibronectin levels but showed no changes in fasting plasma glucose and hemoglobin A1c levels. The protein expression of JAK2, STAT3, P-JAK2, and P-STAT3 and the gene expression of JAK2 and STAT3 in kidney tissues were significantly increased (P < 0.05) in the model group. Compared with the model group, the expression of P-JAK2 and P-STAT3 was downregulated in the extract treatment groups. The expression of SOCS-1 was increased in the NE and WE groups (P < 0.05). However, the expression of JAK2, STAT3, JAK2mRNA, and STAT3mRNA in the treatment groups did not show any significant differences. Conclusion Compound Herba Houttuyniae showed renoprotective effects in db/db mice, and the strongest effects were observed in the WE and NE groups. The underlying mechanism for these effects might involve the regulation of the JAK/STAT–SOCS-1 pathway.
    13  Simultaneous Determination of 10 Anthraquinones in Rhubarb Based on HPLC-Q-HR/MS
    Su-xiang Feng Meng-meng Li Di Zhao Xian-he Li Lei Zhang Zhe Wang Ning-ning Gao
    2017, 9(4):388-395. DOI: 10.1016/S1674-6384(17)60120-5
    [Abstract](450) [HTML](0) [PDF 0.00 Byte](12)
    Objective To develop a simple, sensitive, and precise method for simultaneous determination of 10 anthraquinones in Rhubarb. Methods HPLC-Q-HR/MS was employed for simultaneous quantification of free anthraquinones (aloe-emodin, emodin, chrysophanol, physcion, and rhein) and their glycosides. Chromatographic analysis was performed on an XBridgeTM C18 column (2.1 mm × 150 mm, 5 μm) with mobile phases consisting of 3 mmol/L ammonium acetate (A) and methanol (B) at a flow rate of 0.3 mL/min. Results All calibration curves exhibited good linear relationship (R2 > 0.999). The limits of detection (LOD) and quantification (LOQ) were in the range of 0.39-2.97 ng/mL and 0.56-8.90 ng/mL, respectively. The overall intra- and inter-day precisions of analytes presented as relative standard deviations (RSDs) were less than 2.79%. Relative recoveries varied between 97.83% and 104.28%. The validated method was applied to assess the quality of Rhubarb collected from different regions of China. Results showed that chrysophanol and rhein-8-O-β-D-glucoside was the largest portion of free anthraquinones and anthraquinone glycosides in Rhubarb, respectively. The total content of anthraquinones was higher in Rhubarbs from Sichuan, Qinghai, Yunnan, and Gansu provinces than that in those from Shandong and Henan provinces, while no significant variability existed in different regions of the same province. Conclusion HPLC-Q-HR/MS method is accurate and reliable for simultaneous quantification of above free anthraquinones and their glycosides in Rhubarb and can be applied to standardize the quality of Rhubarb and its quality control in different regions.

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