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Anti-inflammatory mechanism of the non-volatile ingredients performance liquid chromatography-heated electron spray ionization-high resolution mass spectroscope and cell metabolomics

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Journal of Traditional chinese Medicine 2024年第2期44卷 260-267页

作者： JING Wenguang LIN Xiaoyu LI Chu ZHAO Xiaoliang CHENG Xianlong WANG Penglong WEI Feng MA Shuangcheng Institute of Control of chinese Traditional Medicine and Ethnic Medicine National Institutes for Food and Drug ControlBeijing 102629China School of Traditional chinese Medicine Beijing University of Chinese MedicineBeijing 102488China Beijing Key Laboratory of Traditional chinese Medicine Basic research on Prevention and Treatment of Major Diseases Experimental Research CenterChina Academy of Chinese Medical SciencesBeijing 100700China

OBJECTIVE:To explore the anti-inflammatory components and mechanism of the non-volatile ingredients of ***:High performance liquid chromatographyheated electron spray ionization-high resolution mass spectroscope(HPLC-HESI-HRMS)was used to analyze the chemical constituents of the non-volatile ingredients of *** anti-inflammatory activity of ingredients was evaluated using lipopolysaccharide(LPS)induced RAW264.7 cell inflammation model,and the antiinflammatory mechanism was investigated using multivariate statistical analysis of cell ***:The non-volatile ingredients of patchouli were characterized by HPLC-HESI-HRMS,and 36 flavonoids and 18 other components were *** ingredients of patchouli not only had a good protective effect on the LPS-induced inflammation model of RAW264.7 cells,but also regulated the expression levels of arginine,L-leucine,cholesterol,fructose and sorbitol by down-regulating arginine metabolism,aminoacyl-tRNA biosynthesis,polyol/sorbitol pathway,so as to reduce inflammation and reduce cell ***:The non-volatile ingredients of patchouli had good anti-inflammatory effect and exerted its curative effect by regulating endogenous metabolic pathway to reduce inflammatory response.

关键词： Pogostemon non-volatile ingredients anti-inflammatory cell metabolomics

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Small molecules for fat combustion: targeting obesity

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Acta Pharmaceutica Sinica B 2019年第2期9卷 220-236页

作者： Jingxin Liu Yitao Wang Ligen Lin State Key Laboratory of Quality research in chinese Medicine Institute of Chinese Medical Sciences University of Macao

Obesity is increasing in an alarming rate worldwide, which causes higher risks of some diseases, such as type 2 diabetes, cardiovascular diseases, and cancer. Current therapeutic approaches,either pancreatic lipase inhibitors or appetite suppressors, are generally of limited effectiveness. Brown adipose tissue(BAT) and beige cells dissipate fatty acids as heat to maintain body temperature, termed non-shivering thermogenesis; the activity and mass of BAT and beige cells are negatively correlated with overweight and obesity. The existence of BAT and beige cells in human adults provides an effective weight reduction therapy, a process likely to be amenable to pharmacological intervention. Herein, we combed through the physiology of thermogenesis and the role of BAT and beige cells in combating with obesity. We summarized the thermogenic regulators identified in the past decades, targeting G proteincoupled receptors, transient receptor potential channels, nuclear receptors and miscellaneous *** in clinical trials were also presented. The main purpose of this review is to provide a comprehensive and up-to-date knowledge from the biological importance of thermogenesis in energy homeostasis to the representative thermogenic regulators for treating obesity. Thermogenic regulatorsmight have a large potential for further investigations to be developed as lead compounds in fighting obesity.

关键词： Thermogenesis Brown adipose tissue Beige cells Obesity Uncoupling protein 1

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Flavonoid profiling of a traditional chinese medicine formula of Huangqin Tang using high performance liquid chromatography

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Acta Pharmaceutica Sinica B 2016年第2期6卷 148-157页

作者： Tao Li Shuaixing Zhuang Yiwei Wang Yanli Wang Weihao Wang Huihui Zhang Li Chen Dunfang Wang Zhongming Zhou Weipeng Yang Institute of chinese Materia Medica China Academy of Chinese Medical Sciences Experimental research Center China Academy of Chinese Medical Sciences China Food and Drug Administration

The quality control processes for herbal medicines have been problematic. Flavonoids are the major active components of Huangqin Tang(HQT, a traditional chinese medicine formula). In this study, we used a combinative method approach consisting of chromatographic fingerprinting(high performance liquid chromatography; HPLC), quantitative methods and a pharmacodynamic evaluation model to analyze the flavonoids of HQT obtained from different sources. Ten batches of HQT were analyzed by the HPLC fingerprinting method and 26 common peaks were detected, of which 23 peaks corresponded with the chemical profile of HQT. In addition, 11 major compounds were identified by LC–MS analysis(liquid chromatography–tandem mass spectrometer; LC–MS^n) and quantified by the HPLC quantitative method approach. The studied10 batches of HQT were found to be homogeneous in their composition with a similarity between 0.990 and1.000. The distribution of the 11 identified compounds was found to be very similar among the batches. Only slight pharmacodynamic differences were detected between the different batches, confirming the homogeneity of HQT. The results of this study prove that the combination of chromatographic fingerprinting and quantitative analysis can be readily used for comprehensive quality control of herbal medicines.

关键词： Radix Scutellariae Flavonoids HPLC fingerprinting analysis Multiple-component quantitative analysis Paw edema Carrageenin Antipyretic Anti-inflammatory

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Neocryptotanshinone inhibits lipopolysaccharide-induced inflammation in RAW264.7 macrophages by suppression of NF-κB and iNOS signaling pathways

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Acta Pharmaceutica Sinica B 2015年第4期5卷 323-329页

作者： Chuanhong Wu Wenwen Zhao Xuenong Zhang Xiuping Chen State Key Laboratory of Quality research in chinese Medicine Institute of Chinese Medical SciencesUniversity of Macao

Neocryptotanshinone(NCTS) is a natural product isolated from traditional chinese herb Salvia miltiorrhiza Bunge. In this study, we investigated its anti-inflammatory effects in lipopolysaccharide(LPS)-stimulated mouse macrophage(RAW264.7) cells. MTT results showed that NCTS partly reversed LPS-induced cytotoxicity. Real-time PCR results showed that NCTS suppressed LPS-induced mRNA expression of inflammatory cytokines, including tumor necrosis factor α(TNFα), interleukin-6(IL-6) and interleukin-1β(IL-1β). Moreover, NCTS could decrease LPS-induced nitric oxide(NO)production. Western blotting results showed that NCTS could down-regulate LPS-induced expression of inducible nitric oxide synthase(iNOS), p-IκBα, p-IKKβ and p-NF-κB p65 without affecting cyclooxygenase-2(COX-2). In addition, NCTS inhibited LPS-induced p-NF-κB p65 nuclear *** conclusion, these data demonstrated that NCTS showed anti-inflammatory effect by suppression of NF-κB and iNOS signaling pathways.

关键词： Neocryptotanshinone Inflammation NF-κB Inducible nitric oxide synthase

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Cucurbitacin B suppresses metastasis mediated by reactive oxygen species(ROS) via focal adhesion kinase(FAK) in breast cancer MDA-MB-231 cells

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chinese Journal of Natural Medicines 2018年第1期16卷 10-19页

作者： LUO Wei-Wei ZHAO Wen-Wen LU Jin-Jian WANG Yi-Tao CHEN Xiu-Ping State Key Laboratory of Quality research in chinese Medicine Institute of Chinese Medical Science University of Macao

Metastasis is responsible for the majority of cancer-related deaths and prevention of metastasis remains a big challenge for cancer therapy. Cucurbitacin B(Cuc B) is a natural triterpenoid with potent anticancer activities while its effect on metastasis remains unclear. In the present study, the inhibitory effect and mechanisms of Cuc B on metastasis were investigated in MDA-MB-231 breast cancer cells. The cells were treated with or without Cuc B, and the cytotoxicity was determined by MTT assay. The effect of Cuc B on metastasis was evaluated with wound healing, transwell, and adhesion assays. Furthermore, the adhesion of cancer cells to endothelial cells was determined. The protein expression was determined by Western blotting. Cuc B(< 100 nmol·L~^(-1)) showed no obvious cytotoxicity to MDA-MB-231 cells, but significantly inhibited migration, invasion, and adhesion to Matrigel, fibronectin, type I collagen, and endothelial cells. Cuc B dramatically inhibited the phosphorylation of focal adhesion kinase(FAK) and paxillin in dose-and time-dependent manners. Furthermore, Cuc B induced intracellular reactive oxygen species(ROS) generation, which could be reduced by N-acetyl-l-cysteine(NAC). In addition, NAC pretreatment could reverse Cuc B-induced suppression of migration and adhesion, expression of FAK, but showed no effect on paxillin expression. In summary, Cuc B suppressed ROS-dependent metastasis through FAK pathway in breast cancer MDA-MB-231 cells, demonstrating novel mechanisms for the anticancer effects of Cuc B.

关键词： Cucurbitacin B Metastasis ROS FAK Breast Cancer

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Approach to lattice-related/content-specific spectral ranges of near-infrared diffuse reflectance spectroscopy of cefazolin sodium and the construction of a quantitative model for the determination of cefazolin sodium content in different crystal forms

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Science China Chemistry 2013年第6期56卷 789-798页

作者： LIU YanYun FENG YanChun JIA YanHua HU ChangQin National institutes for Food and Drug Control Hubei Institute for Food and Drug Control Institute of Medicinal Biotechnology Chinese Academy of Medical Science and Peking Union Medical College

Cefazolin sodium can form both α- and β-form crystals. It also can form dehydrated crystalline and amorphous products through different production processes. Because different polymorphic medicines usually have different physical and chemical properties, it is critical to emphasize the crystallization control of polymorphic medicines. Near-infrared （NIR） analysis, which incorporates a combination of NIR spectroscopic techniques and multivariate chemometric methods, is considered a powerful tool for the determination of the crystallinity of polymorphic drugs. The selection of optimal spectral ranges that correlate with the lattice specificity and content specificity is crucial to obtaining a specific NIR model. In the present work, near-infrared （NIR） spectra of cefazolin sodium with different crystal forms created through different processes were studied. The results suggest that wavelengths within the range of 9102.7-8597.5 cm-1 is related to the specificity of the cefazolin sodium crystal lattice and that the range of 6001.6-5496.4 cm i is associated with the quantitative content of cefazolin sodium. The two ab- sorptions are caused by the second overtone of the C-H stretching band （3nC-H） and the first overtone of C-H stretching band （2uC-H）, respectively. Using these results, we established a suitable method of constructing a universal quantitative model by using mixed samples in different crystal forms as a calibration set, selecting a content-specific range （6001.6-5496.4 cm-l）, and adding lattice-related spectral ranges where appropriate. This may provide a framework for the construction of prediction models for polymorphic medicines.

关键词： cefazolin sodium crystal form near-infrared spectroscopy crystal-specific model universal model

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Cytocompatibility and Hemolysis of AZ31B Magnesium Alloy with Si-containing Coating

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Journal of Materials Science & Technology 2015年第8期31卷 845-851页

作者： Qiang Wang Lili Tan Ke Yang School of Stomatology China Medical University Institute of Metal research Chinese Academy of Sciences

In the present study, a Si-containing coating was fabricated on AZ31B Mg alloy. Cytocompatibility of the coated alloy was evaluated by both indirect and direct contact methods, respectively. Effects of a number of incubation variables on the sensitivity and reproducibility of the hemolysis test were also examined by using positively and negatively responding biomaterials. Cytocompatibility testing results indicated that cell condition, cell adherence, cell proliferation and extracellular matrix secretion of the coated alloy were improved compared with those of the uncoated alloy for different extraction and co-culture time. The hemolysis test suggested that hemolysis testing conditions were critical to determine the hemolysis of the alloy. It was also found that 1 day in vitro degradation of the uncoated AZ31B alloy had no destructive effect on erythrocyte. As for the coated AZ31B alloy at any time point, the hemolysis rate was much lower than 5%, the safe value for biomaterials. These in vitro experimental results indicate that the Si-containing coating is effective to improve the cytocompatibility and hemolysis behaviors of AZ31B alloy during its degradation.

关键词： Magnesium alloys Biodegradable Cytocompatibility Hemolysis

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Cytotoxic Effects of Biodegradation of Pure Mg and MAO-Mg on Tumor Cells of MG63 and KB

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Journal of Materials Science & Technology 2014年第5期30卷 487-492页

作者： Qiang Wang1a Shi Jin Xiao Lin Yang Zhang Ling Ren Ke Yang School of Stomatology China Medical University Institute of Metal research Chinese Academy of Sciences

Magnesium （Mg） based metals possess unique features of biodegradation that can be used for different purposes. In this study, two tumor cells, MG63 and KB, were cultured directly on a pure Mg with and without MAO coating to evaluate their cytotoxic effects on the tumor cells. It was found that both MG63 cells and KB cells adhered better on the surface of the coated Mg samples than those on the pure Mg samples. However, the survivals of two kinds of tumor cells were obviously inhibited on both Mg samples with and without coating, compared with that on the pure titanium. In addition, the survival of MG63 cells was more susceptive to the Mg degradation compared with the KB cells. Thus, the application of such effect should take account of that the degradation of Mg based metal may result in different cytotoxic effect on different cells.

关键词： Magnesium ahoy Degradation Cytotoxic effect Tumor cell

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Myocardial Infarction Detection and Localization with Electrocardiogram Based on Convolutional Neural Network

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chinese Journal of Electronics 2021年第5期30卷 833-842页

作者： LIU Jikui WANG Ruxin WEN Bo LIU Zengding MIAO Fen LI Ye Shenzhen institutes of Advanced Technology Chinese Academy of Sciences Shenzhen College of Advanced Technology University of Chinese Academy of Sciences

Electrocardiogram(ECG) is widely used in Myocardial infarction(MI) diagnosis. The automatic diagnosis of MI based on the 12-lead ECG needs to consider not only the waveform change features in multi-resolution time series, but also the spatial correlation information between the leads. To this end, this work proposed multiscale spatiotemporal feature extraction method based on Convolutional neural network(CNN) for MI automatic diagnosis. First, the 12-lead ECG is first transformed into an ECG image through wavelet decomposition and 3-dimensional space reconstruction. The MI-CNN model is then constructed to identify MI using 41368 ECG ***, we develop the LL-CNN model, which is utilized only after the ECG signal is identified as an MI event by the MI-CNN model, to localize MI by employing transfer learning to overcome the limited data problem. The proposed method has achieved an accuracy of 99.51% on MI detection, and a macro-F1 of 99.14% on MI ***, the features visualization shows that U-wave has significant diagnostic value for MI. The proposed method significantly improves the performance of MI detection and localization compared with other methods. It is promising to be used for MI monitoring and diagnosis.

关键词： medical signal processing waveform change features convolutional neural network feature extraction multiscale spatiotemporal feature extraction method electrocardiogram MI automatic diagnosis ECG signal myocardial infarction detection MI-CNN model electrocardiography myocardial infarction diagnosis learning (artificial intelligence) medical signal detection MI detection MI localization ECG image multiresolution time series wavelet transforms wavelet decomposition LL-CNN model

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Biphasic firing response of nucleus accumbens neurons elicited by THPB-18 and its correlation with DA receptor subtypes

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Acta Pharmacologica Sinica 2004年第12期25卷 31-39页

作者： Yu FU2,3,4, Zi-tao ZHU2,5, Xing-zu ZHU2, Guo-zhang JIN2,6 2State KeyLaboratory of Drug research,Shanghai Institute ofMateria Medica, Shanghai institutes for BiologicalSciences, chineseAcademy of Sciences, Graduate Schoolof the chinese Academy of Sciences, Shanghai 201203, ChinaNow in Department of Pharmacology and Toxicology, Univer-sity of Texas medical Branch, USA.Now in Department of Physiology & Pharmacology, OregonHealth Sciences University, USA,5Now in Department of Physiology & Pharmacology, OregonHealth Sciences University, USA, State Key Laboratory of Drug research Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 201203 China

AIM: To investigate the possibility whether THPB-18 (l-12-shloroscoulerine) possesses the D1 agonist-D2 antago- nist action on meso-accumbens-mPFC DA system. METHODS: Single unit spontaneous firing activity was re- corded in the nucleus accumbens (NAc) neurons of na?ve and unilateral-6-hydroxydopamine (6-OHDA)-lesioned Sprague-Dawley rats. The effects of drugs applied intravenously or iontophoretically were determined by the change of firing rates. RESULTS: Under normal conditions, the systemic administration of THPB-18 produced a decrease-increase biphasic firing pattern in the NAc neurons during cumulative doses. High dose of THPB-18 was capable of reversing the inhibition induced by both D2 agonist LY171555 and D1/D2 agonist APO on NAc firing activity. Spiperone pretreatment could not block the high dose of THPB-18-induced firing rate increase, which was reversed by the D1 selective antagonist SCH23390. The tested NAc neurons were effectively inhibited by iontophoretically applied THPB-18 in 90 % of 6-OHDA-lesioned rats, while THPB-18 caused variable effects on the firing of NAc neurons in the neurons of unlesioned rats. The inhibitory effect of THPB-18 was blocked by iontophoretic application of SCH23390, but not D2 antagonist spiperone. CONCLUSION: Similar to l-stepholidine, THPB-18 also possesses the “D1 agonistic-D2 antagonistic” dual action on the VTA-NAc DA system.4Now in Department of Pharmacology and Toxicology, Univer-sity of Texas medical Branch, USA.5Now in Department of Physiology & Pharmacology, OregonHealth Sciences University, USA,4Now in Department of Pharmacology and Toxicology, Univer-sity of Texas medical Branch, USA.5Now in Department of Physiology & Pharmacology, OregonHealth Sciences University, USA,5Now in Department of Physiology & Pharmacology, OregonHealth Sciences University, USA,

关键词： berberine dopamine D1 receptors dopamine D2 receptors nucleus accumbens

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