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Radix Scrophulariae Extracts Exert Effect on Hyperthyroidism via MST1/Hippo Signaling Pathway

Chinese Journal of Integrative Medicine 2023年第11期29卷 998-1006页

作者： ZHANG Ning YE Tao LU Xu LI Zi-hui LI Ling Department of Pharmacy The First Affiliated Hospital of Guizhou University of Traditional Chinese MedicineGuiyang(50001)China Department of Chinese Medicine Rehabilitation The First Affiliated Hospital of Guizhou University of Traditional Chinese MedicineGuiyang(50001)China College of Pharmacy Guizhou University of Traditional Chinese MedicineGuiyang(550025)China College of Life and Health Dalian UniversityDalianLiaoning Province(116622)China

Objective:To explore the mechanism of Radix Scrophulariae(RS)extracts in the treatment of hyperthyroidism rats by regulating proliferation,apoptosis,and autophagy of thyroid cell through the mammalian sterile 20-like kinase 1(MST1)/Hippo pathway.Methods:Twenty-four rats were randomly divided into 4 groups according to a random number table:control,model group,RS,and RS+Hippo inhibitor(XMU-MP-1)groups(n=6 per group).Rats were gavaged with levothyroxine sodium tablet suspension(LST,8μg/kg)for 21 days except for the control group.Afterwards,rats in the RS group were gavaged with RS extracts at the dose of 1,350 mg/kg,and rats in the RS+XMU-MP-1 group were gavaged with 1,350 mg/kg RS extracts and 1 mg/kg XMU-MP-1.After 15 days of administration,thyroid gland was taken for gross observation,and histopathological changes were observed by hematoxylin-eosin staining.The structure of Golgi secretory vesicles in thyroid tissues was observed by transmission electron microscopy.The expression of thyrotropin receptor(TSH-R)was observed by immunohistochemistry.Terminal-deoxynucleoitidyl transferase mediated nick end labeling assay was used to detect cell apoptosis in thyroid tissues.Real-time quantity primer chain reaction and Western blot were used to detect the expressions of MST1,p-large tumor suppressor gene 1(LATS1),p-Yes1 associated transcriptional regulator(YAP),proliferating cell nuclear antigen(PCNA),G_(1)/S-specific cyclin-D1(Cyclin D1),B-cell lymphoma-2(Bcl-2),Caspase-3,microtubule-associated proeins light chain 3Ⅱ/Ⅰ(LC3-Ⅱ/Ⅰ),and recombinant human autophagy related 5(ATG5).Thyroxine(T4)level was detected by enzyme-linked immunosorbent assay.Results:The thyroid volume of rats in the model group was significantly increased compared to the normal control group(P<0.01),and pathological changes such as uneven size of follicular epithelial cells,disorderly arrangement,and irregular morphology occurred.The secretion of small vesicles by Golgi apparatus was reduced,and the expressions of receptor protein TSH-R and T4 were s

关键词： Radix inhibited Scr

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Systems-Based Interactome Analysis for Hematopoiesis Effect of Angelicae sinensis Radix: Regulated Network of Cell Proliferation towards Hemopoiesis

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Chinese Journal of Integrative Medicine 2019年第12期25卷 939-947页

作者： ZHENG Guang ZHANG He YANG Yun SUN Ying-li ZHANG Yan-jing CHEN Ju-ping HAO Ting LU Cheng GUO Hong-tao ZHANG Ge FAN Dan-ping HE Xiao-juan LU Ai-ping Information Science and Engineering School Lanzhou UniversityLanzhou(730000)China School of Biology Lanzhou UniversityLanzhou(730000)China Institute of Basic Research in Chinese Medicine China Academy of Chinese Medical SciencesBeijing(100700)China Department of Rheumatism the First Affiliated Hospital of Henan University of Traditional Chinese MedicineZhengzhou(450000)China School of Chinese Medicine Hong Kong Baptist UniversityKowloon TongKowloonHong Kong SARChina

Objective: To explore the molecular-level mechanism on the hematopoiesis effect of Angelicae sinensis Radix(ASR) with systems-based interactome analysis. Methods: This systems-based interactome analysis was designed to enforce the workflow of "ASR(herb)→compound→target protein→internal protein actions→ending regulated protein for hematopoiesis". This workflow was deployed with restrictions on regulated proteins expresses in bone marrow and anemia disease and futher validated with experiments. Results: The hematopoiesis mechanism of ASR might be accomplished through regulating pathways of cell proliferation towards hemopoiesis with cross-talking agents of spleen tyrosine kinase(SYK), Janus kinase 2(JAK2), and interleukin-2-inducible T-cell kinase(ITK). The hematopoietic function of ASR was also validated by colonyforming assay performed on mice bone marrow cells. As a result, SYK, JAK2 and ITK were activated. Conclusion: This study provides a new approach to systematically study and predict the therapeutic mechanism for ASR based on interactome analysis towards biological process with experimental validations.

关键词： Angelicae sinensis Radix interactome cell proliferation hemopoiesis regulation cross-talking agents

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Hematopoietic effect of small molecular fraction of Polygoni multiflori Radix Praeparata in cyclophosphamide-induced anemia mice

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Chinese Journal of Natural Medicines 2019年第7期17卷 535-544页

作者： ZHU Li-Li FAN Luo-Di HU Ming-Hua MA Fang-Li QI Jin Jiangsu Key Laboratory of TCM Evaluation and Translational Research China Pharmaceutical University Nanjing 210009 China Infinitus Chinese Herbal Immunity Research Centre Infinitus (China) Company Limited. Guangzhou 510663 China

The aim of this study is to investigate the protective effects of a small molecular fraction(SMF) of Polygoni multiflori Radix Praeparata(PMRP) in a cyclophosphamide(CTX) induced anemia mouse model. Small molecular fraction of PMRP was prepared and identified by high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(HPLC-Q-TOF-MS). In pharmacology, we examined the peripheral hemogram and thymus and spleen index. The content of granulocyte-macrophage colony-stimulating factor(GM-CSF) in serum was mensurated by enzyme-linked immunosorbent assay(ELISA);The level of superoxide dismutase(SOD), catalase(CAT), total antioxidant capacity(T-AOC), and malondialdehyde(MDA) in serum and spleen tissue homogenate were detected, and glutathione peroxidase(GSH-PX) was assayed in spleen. The results show that SMF can significantly accelerate the recovery of peripheral hemogram, increase the activity of antioxidant enzymes and GM-CSF in serum and spleen. SMF also increases the number of spleen cells, improves bone marrow pathology. In conclusion, the SMF of PMRP promoted the recovery of hematopoietic function in a CTX-induced anemia mouse, which can support SMF to be used as an adjunct to chemotherapy to counteract its side effects.

关键词： Polygoni multiflori Radix Praeparata Small molecular fraction Cyclophosphamide Hemopoiesis

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Metabolomics analysis and rapid identification of changes in chemical ingredients in crude and processed Astragali Radix by UPLC-QTOF-MS combined with novel informatics UNIFI platform

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Chinese Journal of Natural Medicines 2018年第9期16卷 714-720页

作者： LIU Peng-Peng SHAN Guo-Shun ZHANG Fan CHEN Jiang-Ning JIA Tian-Zhu School of Pharmacy Liaoning University of Traditional Chinese Medicine

Astragali Radix, the root of Astragalus membranaceus(Fisch.) Bge. var. mongholicus(Bge.) Hsiao or Astragalus membranaceus(Fisch.) Bge., is widely used as a tonic decoction pieces in the clinic of traditional Chinese medicine(TCM). Astragali Radix has various processed products with varying pharmacological actions. There is no modern scientific evidence to explain the differences in pharmacological activities and related mechanisms. In the present study, we explore the changes in chemical components in Astragali Radix after processing, by ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry(UPLC-QTOF-MS) combined with novel informatics UNIFI platform and multivariate statistical analysis. Our results showed that the crude and various processed products could be clearly separated in PCA scores plot and 15 significant markers could be used to distinguish crude and various processed products by OPLS-DA in UNIFI platform. In conclusion, the present study provided a basis of chemical components for revealing connotation of different processing techniques on Astragali Radix.

关键词： Astragali Radix Processing UPLC-QTOF-MS UNIFI Multivariate statistical analysis Metabolomics

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Spectrum-effect relationship between HPLC fingerprints and bioactive components of Radix Hedysari on increasing the peak bone mass of rat

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Journal of Pharmaceutical Analysis 2019年第4期9卷 266-273页

作者： Xin-Yue Chen San-Hu Gou Zhi-Qiang Shi Zhi-Yuan Xue Shi-Lan Feng School of Pharmacy Lanzhou University

The traditional Chinese medicine of Radix Hedysari plays an important role in invigorating gas for ascending, benefiting blood for promoting production of fluid, and promoting circulation for removing obstruction in collaterals, which is consistent with the principle of treatment for osteoporosis. This study is designed to investigate the bioactive components on increasing peak bone mass (PBM) by exploring the spectrum-effect relationship between chromatography fingerprints and effect. Multiple indicators are selected to evaluate the pharmacological activity. In fingerprints, 21 common peaks are obtained, five of which are identified. Furthermore, gray relational analysis (GRA) is a quantitative method of gray system theory and is used to describe the correlation degree of common peaks and pharmacological activities with relational value. 21 components are then divided into three different regions, of which ononin and calycosin play an extremely significant role in increasing PBM. In addition, factor analysis and hierarchical cluster analysis (HCA) are used to screen the optimal producing area for Radix Hedysari. This provides a comprehensive and efficient method to improve the quality evaluation of Radix Hedysari, confirming the bioactive components for PBM-enhancement and further develop its medicinal value.

关键词： Factor analysis Gray relational analysis Hierarchical cluster analysis Peak bone mass Radix Hedysari Spectrum-effect relationship

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Chemical profiles and metabolite study of raw and processed Polygoni Multiflori Radix in rats by UPLC-LTQ-Orbitrap MS^n spectrometry

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Chinese Journal of Natural Medicines 2018年第5期16卷 375-400页

作者： HUANG Juan ZHANG Ju-Ping BAI Jun-Qi WEI Mei-Jin ZHANG Jing HUANG Zhi-Hai QU Guang-Hang XU Wen QIU Xiao-Hui The 2nd Clinical College of Guangzhou University of Chinese Medicine Guangdong Provincial Hospital of Chinese Medicine Guangzhou 510006 China Shanghai Huayu Pharmaceutical Limited Company Shanghai 200000 China

The raw and processed roots of Plygonum multiflorum Thunb(PM) are used to treat different diseases in clinical practice. In order to clarify the influence of processing, a comparative study of chemical substance analysis was carried out. As the xenobiotics with a high enough exposure in target organs being considered as the potential effective or toxicity components, an in vivo study was also implemented to characterize the constitutes and metabolites, and meanwhile, the factor of compatibility with black bean were also considered. As a result, a total of 148 compounds were detected in PM extracts and more than 40 compounds were only detected in the processed products, which were probably new components produced during the steaming process. In in vivo study, 7 prototype components and 66 metabolites were detected or tentatively identified, 24 of which were reported for the first time. Our results indicated that processing greatly changed the chemical composition of PM and influenced the disposition of the compounds in vivo. To the best of our knowledge, this was the first global comparative study of raw and processed PM. These results expanded our knowledge about the influence of processing of PM and provided the essential data for further efficacy or toxicity studies.

关键词： Polygoni Multiflori Radix Processing Chemical profiles In vivo metabolite study

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A hepatoprotection study of Radix Bupleuri on acetaminophen-induced liver injury based on CYP450 inhibition

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Chinese Journal of Natural Medicines 2019年第7期17卷 517-524页

作者： WANG Yu-Xin DU Yi LIU Xia-Fei YANG Fang-Xiu WU Xiao TAN Li LU Yi-Hong ZHANG Jing-Wei ZHOU Fang WANG Guang-Ji Key Lab of Drug Metabolism and Pharmacokinetics China Pharmaceutical University Nanjing 210009 China Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical University Xuzhou 221004 China Jiangsu Institute for Food and Drug Control Nanjing 210019 China

We investigated the potential hepatoprotective effect of Radix Bupleuri(RB) by inducing acute liver injury(ALI) in an animal model using acetaminophen(APAP) after pretreatment with RB aqueous extract for three consecutive days. Compared to those of the APAP group, the biochemical and histological results of the RB pretreatment group showed lower serum aspartate transaminase(AST) and alanine transaminase(ALT) levels as well as less liver damage. Pharmacokinetic study of the toxicity related marker acetaminophen-cysteine(APC) revealed a lower exposure level in rats, suggesting that RB alleviated APAP-induced liver damage by preventing glutathione(GSH) depletion. The results of cocktail approach showed significant inhibition of CYP2 E1 and CYP3 A activity. Further investigation revealed the increasing of CYP2 E1 and CYP3 A protein was significantly inhibited in pretreatment group,while no obvious effect on gene expression was found. Therefore, this study clearly demonstrates that RB exhibited significant protective action against APAP-induced acute live injury via pretreatment, and which is partly through inhibiting the increase of activity and translation of cytochrome P450 enzymes, rather than gene transcription.

关键词： Hepatoprotection Radix Bupleuri Acetaminophen Acute liver injury Cytochrome P450 enzymes

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Effect of type 2 diabetes mellitus on flavonoid pharmacokinetics and tissue distribution after oral administration of Radix Scutellaria extract in rats

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Chinese Journal of Natural Medicines 2018年第6期16卷 418-427页

作者： ZHANG Xue-Ju LIU Shu XING Jun-Peng LIU Zhi-Qiang SONG Feng-Rui National Center of Mass Spectrometry in Changchun Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass SpectrometryChangchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China University of Chinese Academy of Sciences Beijing 100039China

Radix Scutellaria is widely applied to the treatment of diabetes mellitus in China. Its main bioactive constituents contain baicalin, wogonoside, oroxyloside, and their aglycones. To investigate the effect of type 2 diabetes mellitus on both pharmacokinetics and tissue distribution of these flavonoid compounds, the six flavonoids in plasma and tissues from the normal and type 2 diabetic rats after oral administration of Radix Scutellaria extract were simultaneously measured by ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method. The results showed that baicalin, wogonoside, and oroxyloside had higher Cmax and AUC values(P Radix Scutellaria extract between diabetic and normal rats were found for the first time. The results from the present study provided a crucial basis for a better understanding of in vivo anti-diabetic mechanism of action of the six flavonoids from Radix Scutellaria.

关键词： Radix Scutellaria Diabetes mellitus Flavonoid Pharmacokinetics Tissue distribution

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Effects of Radix curcumae-derived diterpenoid C on Helicobacter pylori-induced inflammation and nuclear factor kappa B signal pathways

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World Journal of Gastroenterology 2013年第31期19卷 5085-5093页

作者： Xuan Huang Bin Lv Shuo Zhang Qun Dai Bing-Bing Chen Li-Na Meng Department of Gastroenterology the First Affiliated Hospital Zhejiang Chinese Medical University

AIM:To study effect of diterpenoid C extracted from Radix curcumae on Helicobacter pylori(H.pylori)-infected inflammation,intestinal metaplasia,and nuclear factor kappa B(NF-κB)signaling pathway in vitro.METHODS:We used I-type H.pylori to infect human gastric epithelial gastric epithelium cell line(GES-1)cell lines,and then H.pylori-infected GES-1 cells were treated with Radix curcumae(RC)-derived diterpenoid C of different concentrations(5,10,20μg/mL)and amoxicillin.The expression of p65,IκB kinase(IKK)αand IKKγproteins was detected with Western blotting,and the expression of interleukin(IL)-8,IL-6 and IL-4 was determined with enzyme-linked immunosorbent assay method.Data were analyzed using SPSS software ver18.0.For comparisons between groups of more than two unpaired values,one-way analysis of variance(ANOVA)was used.If an ANOVA F value was significant,post hoc comparisons were performed between groups.If results were not normally distributed,the Mann-Whitney U test was used to compare two groups of unpaired values,whereas for comparisons between groups of more than two unpaired values,the Kruskal-Wallis H test was used.Statistical significance was established at P<0.05.RESULTS:The MTT assay results revealed the inhibited rate of GES-1,and indicated that the IC5 of RCderived diterpenoid C and amoxicillin all were 5μg/mL for gastric GES-1 cells.The expression of IL-8 was significantly increased,especially at 12 h time point;and the expression of IL-4 was decreased in H.pyloriinfected GES-1 cells.After H.pylori-infected GES-1 cells were treated with RC-derived diterpenoid C of different concentrations and amoxicillin,the expression of IL-8was decreased at 12,24,48,72 h points(P<0.01),especially in high-concentration diterpenoid C(20μg/mL)group;and the expression of IL-4 was increased,especially in moderate and high-concentration diterpenoid C(10 and 20μg/mL)groups.RC-derived diterpenoid C had the inhibitory effects on H.pylori-induced p65 translocation from cytoplasm into cell nucleus,H.pylori-stimulant IkBαdegr

关键词： Radix curcumae-derived diterpenoid C Helicobacter pylori Nuclear factor-κB Inflammatory cytokine

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Effect of Aconiti Lateralis Radix Praeparata combined with Cinnamomi Cortex on intestinal motility and expression of SCF and c-Kit in slow transit constipation rats with Yang deficiency syndrome

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China Medical Abstracts(Internal Medicine) 2024年第1期41卷 12-13页

作者：张远哲 Basic Med Coll Guizhou TCM UnivGuiyang 550025

Objective To investigate the effects of the Aconiti lateralis Radix Praeparata-Cinnamomi Cortex (ALRP-CC)compound on the expression of intestinal neurotransmitters and stem cell factor (SCF),c-kitprotooncogeneprotein (c-Kit) in slow transit constipation (STC) rats with Yang deficiency syndrome,and to explore its mechanism of action for improving intestinal motility.

关键词： Radix motility rats

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