1.Exploring the Molecular Mechanism of Aconiti Kusnezoffii Radix Ameliorates Diabetes Mellitus Type 2 Based on Systems Pharmacology
Tingting LIU ; Yue WU ; Qi CHEN ; Fuhou CHANG ; Mengdi ZHANG
Chinese Journal of Modern Applied Pharmacy 2024;41(5):606-618
OBJECTIVE
To explore the potential of Aconiti Kusnezoffii Radix in affecting diabetes mellitus type 2(T2DM) and the potential mechanism for T2DM related symptoms based on systematic pharmacology, bioinformatics, molecular docking and in vitro and in vivo experiments.
METHODS
The database was used to search the related chemical components of Aconiti Kusnezoffii Radix, predict the potential targets and intervene related diseases. The differential genes of T2DM relative healthy people were retrieved from GEO database, mapped with the action target of Aconiti Kusnezoffii Radix, and placed in DAVID database for biological function enrichment. The sensitivity of the target gene to T2DM was analyzed by one-way ANOVA, binary logistic regression analysis and ROC curve. The binding position and interaction force between chemical compounds of Aconiti Kusnezoffii Radix and target proteins were analyzed by molecular docking technology. The effect of Aconiti Kusnezoffii Radix and its chemical compounds on the expression of target protein was verified by T2DM model in vivo and in vitro.
RESULTS
Through database retrieval and analysis, 304 kinds of target related diseases(P value<0.05, FDR<0.05) were obtained, and T2DM with the highest degree value(Degree=59) was selected and analyzed. The 43 target genes were obtained from the intersection of differential genes in T2DM relatively healthy people and potential action targets of Aconiti Kusnezoffii Radix. A total of 9 genes with significant differences were obtained by one-way ANOVA, 5 meaningful genes were obtained by binary logistic regression analysis, and 3 genes with area under ROC curve AUC>0.5 were obtained. By molecular docking (+)-Isoboldine binds to proteins APEX1, CASP1 and CBFB, Napelline binds to proteins CBX1 and EHMT2 through different forces such as hydrogen bond interaction, ligand interaction, hydrophobic interaction, ionizability and electrostatic interaction, so as to increase the ability of ligands to target proteins. After 2 weeks of treatment with Aconiti Kusnezoffii Radix aqueous extract, Aconiti Kusnezoffii Radix may alleviated the symptoms of T2DM by improving peripheral neuropathy. Moreover, Aconiti Kusnezoffii Radix could affect the protein expression of APEX1, CASP1, CBFB, CBX1 and EHMT2 in rat liver tissue. The effect of (+)-Isoboldine and Napelline chemical compounds in Aconiti Kusnezoffii Radix on the target protein of the model in vitro was consistent with that in vivo.
CONCLUSION
It is preliminarily revealed that Aconiti Kusnezoffii Radix can be used as a potential therapeutic drug to improve T2DM peripheral neuropathy, which lays a theoretical foundation for the research and development of Chinese Mongolian medicine and the excavation of new target drugs for the treatment of T2DM.
2.Rapid analysis and identification of chemical components of ethanol extract from Mongolian medicine Sanzi san by HPLC-Q-Exactive-MS
Jun LI ; Yuxia HU ; Mengdi ZHANG ; Yuewu WANG ; Qian ZHANG ; Gejihu HU ; Feng GAO ; Fuhou CHANG
China Pharmacy 2022;33(11):1348-1354
OBJECTIVE To systematic ally stu dy the chemic al components of ethanol extract from Sanzi san ,and to provide reference for clarifying the pharmacodynamic material basis of the formulation. METHODS HPLC-Q-Exactive-MS technology was adopted. The determination was performed on Shim-pack GIST-HP C 18 column with mobile phase consisted of acetonitrile- 0.1% formic acid aqueous solution for gradient elution at the flow rate of 1 mL/min. The column temperature was 40 ℃,and sample size was 10 μL. Mass spectrometry conditions included the electrospray spray ion source was used for detection in positive and negative ion detection modes. Full MS/dd-MS 2 detection mode was adopted ,the resolution of Full MS was 70 000 and the resolution of dd-MS2 was 17 500. The scanning range was m/z 110-1 200. The ion peaks were identified by comparing with the information of control substances ,literature references and self-built database. RESULTS A total of 64 components were identified in the ethanol extract of Mongolian medicine Sanzi san , including 9 flavonoids,13 iridoids,14 organic acids ,18 tannins,3 triterpenes,3 amino acids and 4 fatty acids. CONCLUSIONS The ethanol extract of Mongolian medicine Sanzi san mainly include iridoids ,tannins and flavonoids ,which might be the pharmacodynamic material basis of Sanzi san.
3.Qualitative and quantitative analysis of chemical compounds in 3 species of wild Veratrum from Inner Mongolia
Wenjie HAN ; Ping ZHANG ; Fuhou CHANG ; Yuna LIANG ; Hongmei ZHAO ; Baoquan BAO
China Pharmacy 2022;33(8):937-949
OBJECTIVE To conduc t qualitative and quantitative analysis for the chemical compounds in 3 species of wild Veratrum(V. nigrum ,V. maackii ,V. dahuricum )from Inner Mongolia. METHODS HPLC-Q-Exactive-MS/MS technology was used to identify the chemical components of V. nigrum ,V. maackii and V. dahuricum by consulting SciFinder ,ChemSpider database and related literatures and comparing with the reference substance. The contents of polydatin ,oxyresveratrol and resveratrol in 3 species of wild Veratrum were determined by HPLC. RESULTS A total of 31 compounds were identified ,including 13 stilbenes, 11 flavonoids,4 organic acids ,2 glycosides,1 brasilin. Most of the compounds were shared by 2 or 3 species of wild Veratrum, only 2 flavonoids kaempferol and luteolin were owned by V. dahuricum . The total contents of polydatin ,oxyresveratrol and resveratrol in 3 species of wild Veratrum were in the range of 6.618-11.292 mg/g,and the total contents of them in V. nigrum were the highest ,followed by V. maackii and V. dahuricum . The contents of polydatin and resveratrol in V. maackii were the highest ,and the content of oxyresveratrol in V. nigrum was highest. CONCLUSIONS Most of the components of 3 species of wild Veratrum are similar,only kaempferol and luteolin are unique to V. dahuricum . The contents of polydatin ,oxyresveratrol and resveratrol are significantly different among 3 species of wild Veratrum.
4.Screening of Hepatoprotective Activity Fractions from Ixeris chinensis and Study on Its Chemical Compositions
Lijun SUN ; Fuhou CHANG ; Tuya BAI ; Yuhua WANG
China Pharmacy 2021;32(9):1089-1092
OBJECTIVE: To screen the hepatoprotective active fractions from Ixeris chinensis and study its chemical constituents. METHODS:The petroleum ether,ethyl acetate,n-butanol and residual water fractions from 70% ethanol extract of I.chinensis were extracted by systematic solvent method. Human hepatocytes HL-7702 were induced by acetaminophen to induce liver injury model. MTT method was used to detect the protective effect of the above fractions(40 μg/mL,by the dosage of crude drug)on injured cells,and the active fractions were screened. The active fractions were separated and purified by silica gel column and Sephadex column chromatography. The structure of the compounds were identified by physical and chemical properties and spectral data (hydrogen spectrum,carbon spectrum). RESULTS:After treated with different fractions of I. chinensis,the cell survival rate of each administration group was increased significantly,compared with model group(P<0.01),and the n-butanol and water fractions had the strongest activity (the cell survival rates were 49.3% and 52.2% ,respectively). Six compoundswere isolated from n-butanol fraction and identified as sonchifolignan A(Ⅰ),apigenin-7-O-β-D-glucopyranoside methyl ester(Ⅱ),luteolin-7-O-β-D-glucuronopyranoside methyl ester (Ⅲ),luteolin-7-O-β-D-glucopyranoside (Ⅳ),apigenin-7-O-β-Dglucopyranoside(Ⅴ)and luteolin(Ⅵ). CONCLUSIONS:The n-butanol fraction is regarded as an effective position for protecting liver,and flavonoids are the main active omponents.KEYWORDS Ixeris chinensis;Hepatoprotective activi
5.Target organs function damage in elderly patients with H type hypertension and its association with blood pressure variability
Yuhong MA ; Fuhou CHANG ; Tuya BAI ; Weizhong HUANGPU
Chongqing Medicine 2018;47(6):740-743,747
Objective To investigate the target organs function damage in elderly patients with H type hypertension and its association with blood pressure variability.Methods Ninety-two patients with H type hypertension in the Affiliated Hospital of Inner Mongolia Medical University from January 2014 to January 2016 were collected as the observation group and contemporaneous 135 elderly patients with non-H type hypertension were collected as the control group.The main observation indicators included 24 h systolic/diastolic blood pressure variability,24 h average systolic/diastolic blood pressure,glomerular filtration rate(GFR),serum creatinine,24 h urinary microalbumin,carotid intima-media thickness and left ventricular mass index.Results Compared with the control group,24 h systolic blood pressure variability,24 h diastolic blood pressure variability,creatinine,24 h urinary microalbumin,carotid intima-media thickness and left ventricular mass index in the observation group were significantly increased(P<0.05);GFR was significantly decreased (P<0.05).The multiple linear regression analysis showed that 24 h systolic blood pressure variability was the factors affecting GFR (P<0.05);24 h systolic blood pressure variability was the factor affecting~the creatinine level (P<0.05);24 h systolic blood pressure,24 h systolic blood pressure variability and 24 h diastolic blood pressure variability were the influence factors of carotid intima-media thickness (P<0.05);24 h systolic blood pressure variability was the influence factor of left ventricular mass index (P<0.05).Conclusion The target organs function damage in the patients with H type hypertension is serious,and the blood pressurevariability enlargement is the influencing factor of target organs function damage.
6.3Q verification of automatic blood coagulation analyzer under good laboratory practice system
Qian ZHANG ; Wei ZHANG ; Xiaoli LV ; Xiaodong CAO ; Fuhou CHANG ;
International Journal of Laboratory Medicine 2016;37(23):3241-3242,3245
Objective To explore the procedures of 3Q validation for blood coagulation analyzer under the good laboratory prac‐tice(GLP) system based on the Sysmex CA7000 automatic blood coagulation analyzer .Methods Four test indicators of PT ,APTT , TT and FIB were chosen to conduct the performance verification in the within‐run precision ,between‐day precision ,accuracy ,linear‐ity ,carry‐over contamination rate of the automatic blood coagulation analyzer .They were prothrombin time(PT) ,activated partial thromboplastin time(APTT) ,thrombin time(TT) ,and fibrinogen(FIB) .Results The within‐run precision CV values of PT , APTT ,TT and FIB were 1 .33% ,1 .57% ,1 .47% and 1 .90% ,respectively ;the inter‐day precision CV values of PT ,APTT ,TT and FIB were 1 .73% ,1 .52% ,1 .55% and 2 .14% respectively ;in terms of accuracy ,the normal quality control CV values were 7 .45% ,3 .88% ,-4 .98% and 4 .36% respectively ;the abnormal quality control CV values of PT and APTT were 8 .11% and 8 .77% respectively ;the r value of FIB linear correlation coefficient was 0 .999 3 ,the a value was 1 .02 ;the highest CV value of car‐ry‐over contamination rate was 2 .15% ;the detected results all conformed to the general industry standards and requirements of in‐strument manufacturer .Conclusion The 3Q validation under the GLP system proves that the Sysmex CA7000 automatic blood co‐agulation analyzer is good in performance and is appropriate for the laboratory work of clinical laboratory department .
7.A network pharmacology study of the association between cigarette toxic components and lung cancer genetic susceptibility
Chinese Journal of Biochemical Pharmaceutics 2016;36(9):158-161
Objective To investigate the effects of the main harmful components in cigarette smoke on the expression of lung cancer susceptibility genes by use of the method of network pharmacology, and to explore the correlations of multiple targets and multiple components and diseases.Methods Literatures about the 11 main tobacco toxic ingredients of cigarette smoke were collected from PubMed and the multicomponent-genes-disease network was structured, and then, shared genes which affect the expression of lung cancer susceptibility were screened out.Then use Cytoscape software to construct the multicomponent-shared genes-disease network.Results Network analysis showed that 11 main harmful components in cigarette smoke influnce 106 lung cancer susceptibility genes, 57 lung cancer susceptibility genes of which were affected by at least 2 of the 11 components.Conclusion From the genetic point of view, the relationship of cigarette smoking and lung cancer was elucidated, and the effect of 11 components on the susceptibility genes of other diseases was also explored.This study may provide some statistical references for further detailed research targeting the relationship of cigarette toxic components and lung cancer genetic susceptibility.
8.Role of polycyclic aromatic hydrocarbons and aryl hydrocarbon receptor in the development of tumor
Yuxia HU ; Fuhou CHANG ; Tuya BAI ; Xiaoli LV ; Wanjia YU
Chinese Journal of Biochemical Pharmaceutics 2015;(6):185-188
Polycyclic aromatic hydrocarbons ( PAHs) are ubiquitous environmental pollutants, whose carcinogenicity is determinated.The mechanism of their carcinogenicity: PAHs are able to combine with aryl hydrocarbon hydrocarbon receptor ( AhR ) , resulting in some toxicity and carcinogenicity.AhR is a ligand-dependent activation transcription factor, which is activated by a large variety of ligands, regulating the expression of a series of gene involved in metabolism, and participating in important biological processes, such as singal transduction, cell proliferation,differentiation and apoptosis,and so on.Besides, it's closely related with the tumor development.Thus, it will provide a new approach for cancer prevention and treatment to study the role of PAHs and AhR in the development of tumor.
9.Protective effect of GuanXinShiWeiWan on isolated rat hearts with ischemia reperfusion injury
Lijuan LIU ; Lei FAN ; Fuhou CHANG ; Tuya BAI ; Xiaoli LV ; Lin LI
Chinese Journal of Biochemical Pharmaceutics 2015;(3):21-24
Objective To investigate the protective effect of GuanXinShiWeiWan on ischemia reperfusion(I-R) injury rat.Methods 50 Wistar rats were randomly divided into normal group, model group, GuanXinShiWeiWan low ( 0.3 mg/kg ) and high ( 0.9 mg/kg ) dose group and positive group, each had 10 rats.Adopting the model of ischemia reperfusion injury of isolated rat hearts, the contents of SOD,MDA,LDH,CK and Ca2 +-ATP, Ca2 +-Mg2 +-ATP, Na +-K +-ATP in cardiac muscle tissue were tested and compared.Results Compared with model group, GuanXinShiWeiWan significantly improved the activities of SOD、Ca2 +-ATP,Ca2 +-Mg2 +-ATP and Na +-K +-ATP (P<0.05 or P<0.01) in cardiac muscle tissue which injured by ischemia reperfusion, while reducing markedly the contents of MDA,LDH,CK(P<0.05 or P<0.01).Conclusion GuanXinShiWeiWan can profect the cardiac muscle of ischemia reperfusion.
10.Research on the relationship between lung cancer with CYP1A1,CYP1B1,VEGF,CAIX genes
Feng GAO ; Lixia CHEN ; Fuhou CHANG ; Tuya BAI ; Jianxin ZHANG ; Xiaomin SHENG
Chinese Journal of Biochemical Pharmaceutics 2014;(2):151-152,156
Cytochrome P 4501 A 1, Cytochrome P 4501 B 1,Vascular endothelial growth factorand carbonic anhydrase Ⅸ belong to the downstream genes of aryl hydrocarbon receptor (AhR)and hypoxia inducible factor 1(HIF-1)signaling pathways. The abnormal expression of those genes were regarded to associated with the occurrence,development and angiogenesis of lung cancer. In this paper, the relationship between CYP1 A 1,CYP1 B 1,VEGF,CAⅨgenes and lung cancer was summarized, which aims to provide new ideas for lung cancer research.


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