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Using Network pharmacology to Explore Therapeutic Effect of Polygonum capitatum on Renal Calculus in Rats

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Medicinal Plant 2024年第3期15卷 45-49页

作者： Bo TU Xu ZHANG Yan LIN Huang YANG Minghui HE Engineering Research Center of Chronic Disease Prevention and Treatment of Authentic Medicinal Materials in Guizhou Higher Education Institutions School of Pharmaceutical SciencesGuizhou Medical UniversityGuiyang 550025China State Key Laboratory of Functions and Applications of Medicinal Plants Guizhou Medical UniversityGuiyang 550004China

[Objectives]To explore the therapeutic effect of Polygonum capitatum on renal calculus in rats based on network pharmacology.[Methods]Through the preliminary construction of ***-urolithiasis disease target network,explore the active components,action pathway and action target of ***-urolithiasis treatment,and use 1%ethylene glycol+2%ammonium chloride to induce SD rat kidney calcium oxalate stone model to verify the efficacy of ***-urolithiasis treatment.[Results]Through the network pharmacological prediction,it is found that the important active components in *** were quercetin,gallic acid,rutin,silybin,catechin,kaempferol and so on;potential active targets include INS,CAT,IL-6,MOCOS,*** results also suggest that forkhead transcription factor signaling pathway(FoxO signaling pathway),tumor necrosis factor signaling pathway(TNF signaling pathway)and hypoxia-inducible factor signaling pathway(HIF-1 signaling pathway)are the core *** results of biochemical indicators in animal experiment showed that the contents of serum urea nitrogen(BUN),creatinine(Cr)and malondialdehyde(MDA)in renal tissue in the treatment group(200,500 mg/kg)were significantly lower than those in the model group,while the content of superoxide dismutase(SOD)was significantly higher than that in the model *** addition,the kidney tissue H&E staining sections showed that *** alcohol extract administration group rats kidney calcium oxalate crystals were significantly reduced compared with the model group,the degree of renal tubular lumen expansion was lighter than the model group,suggesting that *** alcohol extract has the effect of improving renal calculus in rats.[Conclusions]This study provides a theoretical reference for the deep development of *** in the treatment of renal calculus.

关键词： Polygonum capitatum Urolithiasis Network pharmacology

Vascular Basement Membrane-derived Multifunctional Peptide,a Novel Inhibitor of Angiogenesis and Tumor Growth

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Acta Biochimica et Biophysica Sinica 2006年第7期38卷 514-521页

作者： Jian-Guo CAO~(1,2)Shu-Ping PENG~1 Li SUN~2 Hui LI~2 Li WANG~2 Han-Wu DENG~(1*) 1 department of pharmacology,school of pharmaceutical sciences,Central South university,Changsha 410078,China 2 Cancer Research Institute of Nanhua university,Hengyang 421001,China department of pharmacology School of Pharmaceutical Sciences Central South UniversityChangsha 410078 China Cancer Research Institute of Nanhua universityHengyang 421001 China

Vascular basement membrane-derived multifunctional peptide(VBMDMP)gene(fusion geneof the human immunoglobulin G3 upper hinge region and two tumstatin-derived fragments)obtained bychemical synthesis was cloned into vector pUC19,and introduced into the expression vector pGEX-4T-1 toconstruct a prokaryotic expression vector *** VBMDMP produced inEscherichia coli has been shown to have significant activity of antitumor growth and antimetastasis inLewis lung carcinoma transplanted into mouse C57B1/*** the present study,we have studied the ability ofrVBMDMP to inhibit endothelial cell tube formation and proliferation,to induce apoptosis in vitro,and tosuppress tumor growth in *** experimental results showed that rVBMDMP potently inhibited prolif-eration of human endothelial(HUVEC-12)cells and human colon cancer(SW480)cells in vitro,with noinhibition of proliferation in Chinese hamster ovary(CHO-K1)*** also significantly inhibitedhuman endothelial cell tube formation and suppressed tumor growth of SW480 cells in a mouse *** results suggest that rVBMDMP is a powerful therapeutic agent for suppressing angiogenesisand tumor growth.

关键词： recombinant vascular basement membrane-derived multifunctional peptide angiogenesis inhibitor therapeutic action

Exposure to Electromagnetic Fields from Mobile Phones and Fructose consumption Coalesce to Perturb Metabolic Regulators AMPK/SIRT1-UCP2/FOXO1 in Growing Rats

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Biomedical and Environmental sciences 2023年第11期36卷 1045-1058页

作者： Ruchi Tripathi Sanjay Kumar Banerjee Jay Prakash Nirala Rajani Mathur department of pharmacology Delhi Institute of Pharmaceutical Sciences & ResearchDelhi Pharmaceutical Sciences and Research University(DPSR-U))New DelhiINDIA Drug Discovery Research Centre Translational Health Science and Technology InstituteFaridabadINDIA department of Biotechnology National Institute of Pharmaceutical Education and ResearchGuwahatiINDIA school of Environmental sciences Jawaharlal Nehru UniversityNew DelhiINDIA

Objective In this study,the combined effect of two stressors,namely,electromagnetic fields(EMFs)from mobile phones and fructose consumption,on hypothalamic and hepatic master metabolic regulators of the AMPK/SIRT1-UCP2/FOXO1 pathway were elucidated to delineate the underlying molecular mechanisms of insulin *** Weaned Wistar rats(28 days old)were divided into 4 groups:Normal,Exposure Only(ExpO),Fructose Only(FruO),and Exposure and Fructose(EF).Each group was provided standard laboratory chow ad libitum for 8 ***,the control groups,namely,the Normal and FruO groups,had unrestricted access to drinking water and fructose solution(15%),***,the respective treatment groups,namely,the ExpO and EF groups,received EMF exposure(1,760 MHz,2 h/day x 8 weeks).In early adulthood,mitochondrial function,insulin receptor signaling,and oxidative stress signals in hypothalamic and hepatic tissues were assessed using western blotting and biochemical *** In the hypothalamic tissue of EF,SIRT1,FOXO 1,p-PI3K,p-AKT,ComplexⅢ,UCP2,MnSOD,and catalase expressions and OXPHOS and GSH activities were significantly decreased(P<0.05)compared to the Normal,ExpO,and FruO *** hepatic tissue of EF,the p-AMPKα,SIRT1,FOXO1,IRS1,p-PI3K,ComplexⅠ,Ⅱ,Ⅲ,Ⅳ,Ⅴ,UCP2,and MnSOD expressions and the activity of OXPHOS,SOD,catalase,and GSH were significantly reduced compared to the Normal group(P<0.05).Conclusion The findings suggest that the combination of EMF exposure and fructose consumption during childhood and adolescence in Wistar rats disrupts the closely interlinked and multi-regulated crosstalk of insulin receptor signals,mitochondrial OXPHOS,and the antioxidant defense system in the hypothalamus and liver.

关键词： EMF-mobile phone Fructose Childhood-adolescence Insulin receptor signal Mitochondrial OxPHOS Antioxidant system Hypothalamic insulin resistance Hepatic insulin resistance

Nanomedicine-based treatment:An emerging therapeutical strategy for pulmonary hypertension

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Nano Research 2023年第5期16卷 7007-7029页

作者： Shuya Wang Qiaohui Chen Tianjiao Zhao Kelong Ai Changping Hu department of pharmacology Xiangya School of Pharmaceutical SciencesCentral South UniversityChangsha 410078China Hunan Provincial Key Laboratory of Cardiovascular Research Changsha 410078China

Pulmonary hypertension(PH)can cause breathing difficulty,a rapid decline of exercise capacity,heart failure,eventually death of the *** latest epidemiological study demonstrates that PH has a much higher incidence than previously *** is still a highly fatal disease due to the many disadvantages of the current drugs,such as short half-life,lack of targeting,potent side *** PH pathological features offer great opportunities for nanomedicines for ***,emerging nanomedicines demonstrated great advantages in the therapeutic effect of PH by enhancing the accumulation of drugs in PH lesion,optimizing drug efficacy,minimizing drug side ***,this promising field of cross-cutting research is far from being widely explored due to the huge professional *** solve this problem,we provide a comprehensive review for the latest progresses of nanomedicines in the treatment of ***,we systematical summarized the PH pathological features and the current clinical drug treatment of *** advantages of nanomedicines are also deeply discussed in the treatment of ***,we focused on the research progresses of nanomedicines in PH through three aspects:advanced nano-drug delivery system for traditional drugs and new target drugs,gene therapy-based nanomedicines,other nanomedicines for the treatment of ***,we also discussed the prospects and challenges for the clinical application of nanomedicines in PH,provided directions for the research and development of nanomedicines for PH treatment in the future.

关键词： pulmonary hypertension nanomedicines enhanced penetration and retention effects polymer liposome

Anticancer effect of Psidium guajava(Guava) leaf extracts against colorectal cancer through inhibition of angiogenesis

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Asian Pacific Journal of Tropical Biomedicine 2020年第7期10卷 293-307页

作者： Bronwyn Lok Doblin Sandai Hussein M.Baharetha Mansoureh Nazari V Muhammad Asif Chu Shan Tan AMS Abdul Majid EMAN Laboratory Discipline of PharmacologySchool of Pharmaceutical SciencesUniversiti Sains MalaysiaPenangMalaysia Infectomics Cluster Advance Medical and Dental InstituteUniversiti Sains MalaysiaPenangMalaysia department of Pharmacy College of Medicine and Health SciencesHadhramout UniversityHadhramoutYemen department of pharmacology Faculty of Pharmaceutical SciencesGovernment College University FaisalabadFaisalabadPakistan Discipline of pharmacology School of Pharmaceutical SciencesUniversiti Sains MalaysiaPenangMalaysia ACRF department of Cancer Biology and Therapeutics John Curtin School of Medical ResearchAustralian National UniversityCanberraAustralia

Objective:To evaluate the anti-angiogenic and anticancer activities of Psidium guajava leaf extracts against angiogenesis-dependent colorectal ***:Three extracts were produced using distilled water,ethanol,and n-hexane as *** extracts were physically characterised through gas chromatography–mass spectrometry,ultraviolet–visible spectroscopy,and Fourier transform infrared *** antioxidant activity was evaluated using the 2,2-diphenyl-1-picrylhydrazyl,total phenolic content,and total flavonoid content *** assess their anti-angiogenic activity,cell viability and rat aortic ring assays were conducted,while cell migration,tube formation,colony formation,and VEGF ELISA assays were conducted to elucidate their effects on different aspects of *** docking was used to assess the antiangiogenic potential of some possible compounds in the *** spheroid assay was used to assess the extracts’potential as a treatment for colorectal ***:The ethanol extract showed the best antioxidant *** distilled water and ethanol extracts exhibited more inhibitory activity against ***926 cell viability and aortic ring microvessel *** addition,the ethanol extract performed significantly better than the distilled water extract against cell migration and colony formation,and VEGF expression of the cells was suppressed by the ethanol *** the distilled water and ethanol extracts showed significant inhibitory effect on ***926 tube formation and tumour spheroids consisting of ***926 and HCT116 *** ethanol extract containedβ-caryophyllene andβ-elemene by phytochemical analysis and subsequent docking studies,which may contribute to its anti-angiogenic ***:The ethanol extract of Psidium guajava has potential in the treatment of colorectal cancer through the inhibition of angiogenesis.

关键词： Angiogenesis Antioxidant Colorectal cancer Psidium guajava VEGF

Cardioprotective activity of alcoholic extract of Tinospora cordifolia (Willd.) Miers in calcium chloride-induced cardiac arrhythmia in rats

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The Journal of Biomedical Research 2011年第4期25卷 280-286页

作者： Ashish Kumar Sharma Kunal Kishore Divya Sharma B.P Srinivasan Shyam Sunder Agarwal Ashok Sharma Santosh Kumar Singh Samir Gaur Vijay Singh Jatav department of pharmacology Gyan Vihar School of PharmacySuresh Gyan Vihar UniversityJagatpuraJaipur (Rajasthan)302025India Delhi Institute of pharmaceutical sciences & Research Department of PharmacologyPushpviharSector Ⅲ.New Delhi 110017India

The present study investigated the antiarrhythmic activity of alcoholic extract of Tinospora cordifolia （T. cordifolia） in CaCl2 induced arrhythmia. CaCl2 （25 mg/kg） was administered by intravenous infusion （iv） to produce arrhythmia in rats. The animals were then treated with T. cordifolia extract （150, 250, and 450 mg/kg） and verapamil （5 mg/kg,iv）. Lead II electrocardiogram was monitored. Plasma calcium, sodium and potassium levels were measured. In CaCl2 induced arrhythmia, heart rate was decreased by 41.10%, T. cordifolia at 150, 300, and 450 mg/kg decreased the heart rate by 26.30%, 29.16%, and 38.29%, respectively, and verapamil reduced the heart rate by 9.70% compared to the normal group. The PQRST waves were normalized and atrial and ventricular fibrillation was controlled in rats treated with verapamil and T. cordifolia. CaCl2 increased calcium and sodium levels and decreased potassium levels in blood. T. cordifolia dose-dependently decreased calcium and sodium levels and increased potassium levels. Hence, T. cordifolia can be used in antiarrhythmic clinical settings and beneficial in atrial and ventricular fibrillation and flutter and may be indicated in ventricular tachyarrhythmia.

关键词： Tinospora cordifolia arrhythmia cardioprotection.

SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade

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Acta Pharmaceutica Sinica B 2019年第2期9卷 304-315页

作者： Mingxia Zhao Wenjie Guo Yuanyuan Wu Chenxi Yang Liang Zhong Guoliang Deng Yuyu Zhu Wen Liu Yanhong Gu Yin Lu Lingdong Kong Xiangbao Meng Qiang Xu Yang Sun State Key Laboratory of pharmaceutical Biotechnology Deparment of Biotechnology and Pharmaceutical Sciences School of Life Sciences Nanjing University Jiangsu Key Laboratory for pharmacology and Safety Evaluation of Chinese Materia Medica School of Pharmacy Nanjing University of Chinese Medicine State Key Laboratory of Natural and Biomimetic Drugs Department of Chemical Biology School of Pharmaceutical Sciences Peking University department of Oncology the First Affiliated Hospital with Nanjing Medical University

Tyrosine phosphatase SHP2 is a promising drug target in cancer immunotherapy due to its bidirectional role in both tumor growth promotion and T-cell inactivation. Its allosteric inhibitor SHP099 is known to inhibit cancer cell growth both in vitro and in vivo. However, whether SHP099-mediated SHP2 inhibition retards tumor growth in vivo via anti-tumor immunity remains elusive. To address this, a CT-26 colon cancer xenograft model was established in mice since this cell line is insensitive to ***, SHP099 minimally affected CT-26 tumor growth in immuno-deficient nude mice, but significantly decreased the tumor burden in CT-26 tumor-bearing mice with intact immune ***099 augmented anti-tumor immunity, as shown by the elevated proportion of CD8tIFN-γtT cells and the upregulation of cytotoxic T-cell related genes including Granzyme B andPerforin, which decreased the tumor load. In addition, tumor growth in mice with SHP2-deficient T-cells was markedly slowed down because of enhanced anti-tumor responses. Finally, the combination of SHP099 and antiPD-1 antibody showed a higher therapeutic efficacy than either monotherapy in controlling tumor growthin two colon cancer xenograft models, indicating that these agents complement each other. Our study suggests that SHP2 inhibitor SHP099 is a promising candidate drug for cancer immunotherapy.

关键词： Cancer immunotherapy SHP2 SHP099 PD-1 Colon cancer

Regulation of drug metabolism and toxicity by multiple factors of genetics,epigenetics,lncRNAs,gut microbiota,and diseases:a meeting report of the 21st International Symposium on Microsomes and Drug Oxidations(MDO)

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Acta Pharmaceutica Sinica B 2017年第2期7卷 241-248页

作者： Ai-Ming Yu Magnus Ingelman-Sundberg Nathan J.Cherrington Lauren M.Aleksunes Ulrich M.Zanger Wen Xie Hyunyoung Jeong Edward M.Morgan Peter J.Turnbaugh Curtis D.Klaassen Aadra P.Bhatt Matthew R.Redinbo Pengying Hao David J.Waxman Li Wang Xiao-bo Zhong department of Biochemistry and Molecular Medicine School of MedicineUniversity of California at Davis department of Physiology and pharmacology Karolinska Institutet department of pharmaceutical sciences College of PharmacyUniversity of Arizona department of pharmacology and Toxicology School of PharmacyRutgers University Dr. Margarete Fischer-Bosch-Institute of Clinical pharmacology Eberhard Karls university Center of Pharmacogenomics and department of pharmaceutical sciences School of PharmacyUniversity of Pittsburgh department of Pharmacy Practice School of PharmacyUniversity of Illinois at Chicago department of pharmacology School of MedicineEmory University department of Microbiology and Immunology and the George William Hooper Research Foundation University of California at San Francisco department of Environmental and Occupational Health sciences University of Washington department of Chemistry University of North Carolina at Chapel Hill department of Biology and Bioinformatics Program Boston University department of Physiology and Neurobiology University of Connecticut department of pharmaceutical sciences School of PharmacyUniversity of Connecticut

Variations in drug metabolism may alter drug efficacy and cause toxicity;better understanding of the mechanisms and risks shall help to practice precision *** the 21 st International Symposium on Microsomes and Drug Oxidations held in Davis,California,USA,in October 2-6,2016,a number of speakers reported some new findings and ongoing studies on the regulation mechanisms behind variable drug metabolism and toxicity,and discussed potential implications to personalized medications.A considerably insightful overview was provided on genetic and epigenetic regulation of gene expression involved in drug absorption,distribution,metabolism,and excretion(ADME) and drug *** drug metabolism and disposition as well as molecular mechanisms among diseased and special populations were *** addition,the roles of gut microbiota in drug metabolism and toxicology as well as long non-coding RNAs in liver functions and diseases were *** findings may offer new insights into improved understanding of ADME regulatory mechanisms and advance drug metabolism research.

关键词： Drug metabolism and toxicity Genetics Epigenetics Gut microbiota Long non-coding RNAs Disease Personalized medication

Role of farnesoid X receptor in establishment of ontogeny of phase-I drug metabolizing enzyme genes in mouse liver

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Acta Pharmaceutica Sinica B 2016年第5期6卷 453-459页

作者： Lai Peng Stephanie Piekos Grace L.Guo Xiao-bo Zhong department of pharmaceutical sciences School of PharmacyUniversity of Connecticut Key Laboratory of System Biomedicine Center for Comparative BiomedicineInstitute of Systems BiomedicineShanghai Jiao Tong University department of pharmacology and Toxicology School of PharmacyRutgers University

The expression of phase-I drug metabolizing enzymes in liver changes dramatically during postnatal liver *** X receptor(FXR) is critical for bile acid and lipid homeostasis in ***,the role of FXR in regulating ontogeny of phase-I drug metabolizing genes is not ***,we applied RNA-sequencing to quantify the developmental expression of phase-I genes in both Fxr-null and control(C57BL/6) mouse livers during *** samples of male C57BL/6 and Fxr-null mice at6 different ages from prenatal to adult were *** Fxr-null showed an overall effect to diminish the "day-1 surge" of phase-I gene expression,including cytochrome P450 s at neonatal *** the 185 phase-I genes from 12 different families,136 were expressed,and differential expression during development occurred in genes from all 12 phase-I families,including hydrolysis: carboxylesterase(Ces),paraoxonase(Pon),and epoxide hydrolase(Ephx); reduction: aldoketo reductase(Akr),quinone oxidoreductase(Nqo),and dihydropyrimidine dehydrogenase(Dpyd); and oxidation: alcohol dehydrogenase(Adh),aldehyde dehydrogenase(Aldh),flavin monooxygenases(Fmo),molybdenum hydroxylase(Aox and Xdh),cytochrome P450(P450),and cytochrome P450 oxidoreductase(Por).The data also suggested new phase-I genes potentially targeted by *** results revealed an important role of FXR in regulation of ontogeny of phase-I genes.

关键词： Drug metabolizing enzymes Farnesoid X receptor Liver Ontogeny Fxr-null mouse Gene expression