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Anti-inflammatory and hepatoprotective effects of total flavonoid C-glycosides from Abrus mollis extracts

Chinese Journal of Natural Medicines 2014年第8期12卷 590-598页

作者： CHEN Mi WANG Tao JIANG Zhen-Zhou SHAN Chun WANG Hao WU Mei-Juan ZHANG Shuang ZHANG Yun ZHANG Lu-Yong Jiangsu Center for Drug Screening China Pharmaceutical University Jiangsu Center for pharmacodynamics Research and Evaluation China Pharmaceutical University Department of Natural Medicinal Chemistry China Pharmaceutical University Biology Institute of Shandong Academy of Sciences Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University) Ministry of Education

The aim of this study was to evaluate the anti-inflammatory and hepatoprotective effects of the total flavonoid C-glycosides isolated from Abrus mollis extracts(AME). In the anti-inflammatory tests, xylene-induced ear edema model in mice and carrageenan-induced paw edema model in rats were applied. The hepatoprotective effects of AME were evaluated with various in vivo models of acute and chronic liver injury, including carbon tetrachloride(CCl4)-induced hepatitis in mice, D-galactosamine(D-GalN)-induced hepatitis in rats, as well as CCl4-induced hepatic fibrosis in rats. In the acute inflammation experiment, AME significantly suppressed xylene-induced ear edema and carrageenan-induced paw edema, respectively. In the acute hepatitis tests, AME significantly attenuated the excessive release of ALT and AST induced by CCl4 and D-GalN. In CCl4-induced hepatic fibrosis model, AME alleviated liver injury induced by CCl4 shown by histopathological sections of livers and improved liver function as indicated by decreased liver index, serum ALT, AST, TBIL, and ALP levels and hydroxyproline contents in liver tissues, and increased serum ALB and GLU levels. These results indicated that AME possesses potent anti-inflammatory activity in acute inflammation models and hepatoprotective activity in both acute and chronic liver injury models. In conclusion, AME is a potential anti-inflammatory and hepatoprotective agent and a viable candidate for treating inflammation, hepatitis, and hepatic fibrosis.

关键词： Abrus mollis Flavonoid C-glycosides Inflammation Liver injury

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8-Hydroxyquinolylnitrones as multifunctional ligands for the therapy of neurodegenerative diseases

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Acta Pharmaceutica Sinica B 2023年第5期13卷 2152-2175页

作者： Damijan Knez Daniel Diez-Iriepa Mourad Chioua Andrea Gottinger Milica Denic Fabien Chantegreil Florian Nachon Xavier Brazzolotto Anna Skrzypczak-Wiercioch Ane Meden Anja Pilar Janko Kos Simon akelj Jure Stojan Kinga Saat Julia Serrano Ana Patricia Fernández Aitana Sánchez-García Ricardo Martínez-Murillo Claudia Binda Francisco López-Muoz Stanislav Gobec JoséMarco-Contelles University of Ljubljana Faculty of PharmacyLjubljana 1000Slovenia Laboratory of Medicinal Chemistry(Institute of Organic Chemistry CSIC)Madrid 28006Spain Departamento de Química Orgánicay Química Inorgánica Alcaláde HenaresMadrid 28871Spain Department of Biology and Biotechnology University of PaviaPavia 27100Italy Département de Toxicologie et Risques Chimiques Institut de Recherche Biomédicale des ArméesParis 91220France Department of Animal Anatomy and Preclinical Sciences University Centre of Veterinary Medicine JU-UAUniversity of Agriculture in KrakowKrakow 30-059Poland Institute of Biochemistry Faculty of MedicineUniversity of LjubljanaLjubljana 1000Slovenia Department of pharmacodynamics Chair of PharmacodynamicsFaculty of PharmacyJagiellonian University Medical CollegeKrakow 30-688Poland Department of Translational Neurobiology Neurovascular Research GroupCajal Institute(CSIC)Madrid 28002Spain Biotechnology and Vegetal Biology Department Escuela Técnica Superior de Ingeniería AgronómicaAlimentaria y de BiosistemasUniversidad Politécnica de MadridMadrid 28040Spain Faculty of Health Camilo JoséCela University of Madrid(UCJC)Neuropsychopharmacology Unit“Hospital 12 de Octubre”Research InstituteMadrid 28692Spain

We describe the development of quinolylnitrones(QNs)as multifunctional ligands inhibiting cholinesterases(ChEs:acetylcholinesterase and butyrylcholinesterase—h BChE)and monoamine oxidases(hMAO-A/B)for the therapy of neurodegenerative *** identified QN 19,a simple,low molecular weight nitrone,that is readily synthesized from commercially available *** 19 has no typical pharmacophoric element to suggest ChE or MAO inhibition,yet unexpectedly showed potent inhibition of h BChE(IC50=1.06±0.31 nmol/L)and h MAO-B(IC_(50)=4.46±0.18μmol/L).The crystal structures of 19 with hBChE and hMAO-B provided the structural basis for potent binding,which was further studied by enzyme *** 19 acted as a free radical scavenger and biometal chelator,crossed the blood—brain barrier,was not cytotoxic,and showed neuroprotective properties in a 6-hydroxydopamine cell model of Parkinson's *** addition,in vivo studies showed the anti-amnesic effect of 19 in the scopolamine-induced mouse model of AD without adverse effects on motoric function and ***,chronic treatment of double transgenic APPswe-PS1δE9 mice with 19 reduced amyloid plaque load in the hippocampus and cortex of female mice,underscoring the disease-modifying effect of QN 19.

关键词： Quinolylnitrone Butyrylcholinesterase Monoamine oxidase B Alzheimer's disease Multifunctional ligands 6-Hydroxydopamine model Passive avoidance task Novel object recognition

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Effect of Tetracera potatoria Aqueous Extract on Mellitus Diabetes and Its Complication Preventions in Wistar Rats

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Journal of Biosciences and Medicines 2023年第7期11卷 207-222页

作者： Dhornycia Euroldyne Malaissou Tony Raoul Ampa Abraham Mayoke Roger Pavel Boukongo Hono Mavie Mambeke Berthrand Stéphane Lingomo Wossolo Martin Diatewa Laboratory of pharmacodynamics and Experimental Physiopathology Faculty of Science and Techniques Marien Ngouabi University Brazzaville Republic of the Congo Laboratory of Biochemistry and Pharmacology Faculty of Health Sciences Marien Ngouabi University Brazzaville Republic of the Congo Laboratory of Biochemistry Faculty of Science and Techniques Marien Ngouabi University Brazzaville Republic of the Congo

Background: Diabetes is becoming a serious public health issue with expensive treatment that is less accessible to all patients in least developing countries. The traditional African pharmacopoeia offers accessible and lower cost alternative to diabetics’ treatments. Objective: The objective of this study was to evaluate the effect of the aqueous extract of Tetracera potatoria, on diabetes and the prevention of its complications in Wistar rats. In order to evaluate respectively the hypoglycaemic, anti-hyperglycaemic and antidiabetic activities. Methods: an aqueous extract at doses of 200 and 400 mg/kg was tested on normal rats and orally hyperglycaemic challenged rats by 10% glucose (3 g/kg), to induce diabetes by intraperitoneal injection of Alloxan at 50 mg/kg. The glycaemia monitoring, and the determination of biological parameters were accessed through ASAT, ALAT, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, glycated haemoglobin tests. Results: The aqueous extract at related doses administered to diabetic rats has significantly reduced the mean blood glucose levels in all diabetic rats at 55.56%, 63.34% and 62.38% compared to healthy control batches in the three batches treated. These doses improved the change in body weight compared to the healthy control group. There was an increase of 110.9%, 107.67% and 109.31% respectively after four weeks of treatment compared to the initial weight of the rats. The significant increase (p Conclusions: These results showed hypoglycaemic and antihy-perglycaemic, antidiabetic effects, preventing the installation of some diabetes related complications. The phytochemical parameters of the extract showed chemical compounds which would act the reduction of the putative diabetes and its complications. These indicators show the importance of medicinal plants on diabetes treatment.

关键词： Mellitus Diabetes Tetracera potatoria Aqueous Extract Alloxan

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Surprising Separation of Cannabinoid Physical Dependence and Withdrawal in an Invertebrate Model

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Pharmacology & Pharmacy 2018年第12期9卷 489-502页

作者： Wanhui Sheng Robert B. Raffa Department of Pharmaceutical Sciences Temple University School of Pharmacy Philadelphia Pennsylvania USA Department of pharmacodynamics College of Pharmacy University of Florida Gainesville FL USA Department of Pharmacology and Toxicology University of Arizona College of Pharmacy Tucson AZ USA Neumentum Inc. Palo Alto CA USA

Planarians have mammalian-like neurotransmitter systems and have been established as a novel in vivo model for neuropharmacology. In previous research, planarians that have been exposed to the cannabinoid receptor (CB-R) agonist WIN 55,212-2 for 1 h displayed abstinence-induced withdrawal when tested in drug-free, but not in drug-containing, water. The goals of the present study were to extend previous work and to further establish a cannabinoid behavioral model with planarians. The results showed 1) four different CB-R antagonists (AM251, AM281, SLV319 and SR144528) dose-relatedly blocked development of physical dependence induced by two different CB-R agonists (WIN 55,212-2 and JWH251);2) none of the same four antagonists (AM251, AM281, SLV319 or SR144528) precipitated withdrawal;3) short wavelength (254 nm), but not long wavelength (366 nm), ultraviolet (UV) light attenuated abstinence-induced withdrawal from WIN 55,212-2, while short wavelength UV light induced moderate withdrawal behavior. The results confirm the use of a planarian model as a simple yet robust way to study development of physical dependence to cannabinoid agonists. The effect of UV irradiation adds to the evidence that the results are receptor-related. The results also give rise to the surprising suggestion, within the limitations of the methodology, that development of cannabinoid physical dependence and antagonist-induced precipitated withdrawal might be separable phenomena in planarians.

关键词： Cannabinoid Physical Dependence Withdrawal Planarians UV Light

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Solid phase microextraction chemical biopsy tool for monitoring of doxorubicin residue during in vivo lung chemo-perfusion

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Journal of Pharmaceutical Analysis 2021年第1期11卷 37-47页

作者： Barbara Bojko Nikita Looby Mariola Olkowicz Anna Roszkowska Bogumiła Kupcewicz Pedro Reck dos Santos Khaled Ramadan Shaf Keshavjee Thomas K.Waddell German Goomez-Rios Marcos Tascon Krzysztof Gorynski Marcelo Cypel Janusz Pawliszyn Department of Chemistry University of WaterlooWaterlooON M1B 6G3Canada Department of pharmacodynamics and Molecular Pharmacology Faculty of PharmacyCollegium Medicum in BydgoszczNicolaus Copernicus University in Torun85-089BydgoszczPoland Jagiellonian Centre for Experimental Therapeutics(JCET) Jagiellonian University30-348 KrakowPoland Department of Pharmaceutical Chemistry Medical University of Gdansk80-416GdanskPoland Department of Inorganic and Analytical Chemistry Faculty of PharmacyCollegium Medicum in BydgoszczNicolaus Copernicus University in Torun85-089BydgoszczPoland University Health Network-TGH TorontoON M5G 2C4Canada

Development of a novel in vivo lung perfusion(IVLP)procedure allows localized delivery of high-dose doxorubicin(DOX)for targeting residual micrometastatic disease in the ***,DOX delivery via IVLP requires careful monitoring of drug level to ensure tissue concentrations of this agent remain in the therapeutic window.A small dimension nitinol wire coated with a sorbent of biocompatible morphology(Bio-SPME)has been clinically evaluated for in vivo lung tissue extraction and determination of DOX and its key *** in vivo Bio-SPME-IVLP experiments were performed on pig model over various(150 and 225 mg/m^(2))drug doses,and during human clinical *** patients with metastatic osteosarcoma were treated with a single 5 and 7 μg/mL(respectively)dose of DOX during a 3-h *** both pig and human cases,DOX tissue levels presented similar trends during *** lung tissue concentrations of drug ranged between 15 and 293 μg/g over the course of the IVLP *** addition to DOX levels,Bio-SPME followed by liquid chromatography-mass spectrometry analysis generated 64 metabolic features during endogenous metabolite screening,providing information about lung status during drug ***-time monitoring of DOX levels in the lungs can be performed effectively throughout the IVLP procedure by in vivo Bio-SPME chemical biopsy ***-SPME also extracted various endogenous molecules,thus providing a real-time snapshot of the physiology of the cells,which might assist in the tailoring of personalized treatment strategy.

关键词： In vivo solid phase microextraction Metabolite profiling Spatial resolution Therapeutic drug monitoring Tissue analysis

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PUMA facilitates EMI 1-promoted cytoplasmic Rad51 ubiquitination and inhibits DNA repair in stem and progenitor cells

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Signal Transduction and Targeted Therapy 2021年第4期6卷 1377-1387页

作者： Jin Wook Kang Zhiyan Zhan Guangzhen Ji Youzhou Sang Daohong Zhou Yanxin Li Haizhong Feng Tao Cheng State Key Laboratory of Experimental Hematology Institute of Hematology&Blood Diseases HospitalCenter for Stem Cell MedicineChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjinChina Key Laboratory of Pediatric Hematology and Oncology Ministry of Health Department of Hematology&OncologyShanghai Children's Medical CenterShanghai Jiao Tong University School of medicineShanghaiChina Renji-Med X Clinical Stem Cell Research Center Ren Ji HospitalShanghai Cancer InstituteSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of pharmacodynamics College of PharmacyUniversity of Florida at GainesvilleGainesvilleFLUSA

Maintenance of genetic stability via proper DNA repair in stem and progenitor cells is essential for the tissue repair and regeneration,while preventing cell transformation after *** of PUMA dramatically increases the survival of mice after exposure to a lethal dose of ionizing radiation(IR),while without promoting tumorigenesis in the long-term *** finding suggests that PUMA(p53 upregulated modulator of apoptosis)may have a function other than regulates ***,we identify a novel role of PUMA in regulation of DNA repair in embryonic or induced pluripotent stem cells(PSCs)and immortalized hematopoietic progenitor cells(HPCs)after *** found that PUMA-deficient PSCs and HPCs exhibited a significant higher doublestrand break(DSB)DNA repair activity via Rad51-mediated homologous recombination(HR).This is because PUMA can be associated with early mitotic Inhibitor 1(EMI1)and Rad51 in the cytoplasm to facilitate EMI1-mediated cytoplasmic Rad51 ubiquitination and degradation,thereby inhibiting Rad51 nuclear translocation and HR DNA *** data demonstrate that PUMA acts as a repressor for DSB DNA repair and thus offers a new rationale for therapeutic targeting of PUMA in regenerative cells in the context of DNA damage.

关键词： progenitor PUMA repair

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DT-13, a saponin of dwarf lilyturf tuber, exhibits anti-cancer activity by down-regulating C-C chemokine receptor type 5 and vascular endothelial growth factor in MDA-MB-435 cells

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Chinese Journal of Natural Medicines 2014年第1期12卷 24-29页

作者： ZHAO Ren-Ping LIN Sen-Sen YUAN Sheng-Tao YU Bo-Yang BAI Xian-Shu SUN Li ZHANG Lu-Yong Jiangsu Center for Drug Screening China Pharmaceutical University Jiangsu Center for pharmacodynamics Research and Evaluation China Pharmaceutical University Department of Complex Prescription of Traditional Chinese Medicine School of Chinese Material Medicine China Pharmaceutical University Department of Molecular Physiology University of Saarland Key Laboratory of Drug Quality Control and Pharmacovigilance China Pharmaceutical University Ministry of Education

AIM： To investigate the anticancer activity of DT-13 under normoxia and determine the underlying mechanisms of action. METHODS： MDA-MB-435 cell proliferation, migration, and adhesion were performed to assess the anticancer activity of DT-13, a saponin from Ophiopogonjaponicus, in vitro. In addition, the effects of DT-13 on tumor growth and metastasis in vivo were evaluated by orthotopic implantation of MDA-MB-435 cells into nude mice; mRNA levels of vascular endothelial growth factor （VEGF）, C-C chemokine receptor type 5 （CCR5） and hypoxia-inducible factor 1a （HIF-1a） were evaluated by real-time quantitative PCR; and CCR5 protein levels were detected by Western blot assay. RESULTS： At 0.01 to 1 umol·L -1, DT-13 inhibited MDA-MB-435 cell proliferation, migration, and adhesion significantly in vitro. DT-13 reduced VEGF and CCR5 mRNAs, and decreased CCR5 protein expression by down-regulating HIF-1 a. In addition, DT-13 inhibited MDA-MB-435 cell lung metastasis, and restricted tumor growth slightly in vivo. CONCLUSION： DT-13 inhibited MDA-MB-435 cell proliferation, adhesion, and migration in vitro, and lung metastasis in vivo by reducing VEGF, CCR5, and HIF-la expression.

关键词： DT- 13 Saponin Ophiopogonjaponicus Anticancer activity CCR5 VEGF HIF- 1 a

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Changes in Chemical Composition of Soluble Organic Chemical Compounds during Litters Decomposition into Tropical Forest of Milletia laurentii De Wild

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Open Journal of Forestry 2019年第1期9卷 70-87页

作者： Gouolaly Tsiba Mavoungou Naiving Flovique Rosère Edzonga Josianne Milandou Matoko Jodhry Préféré Malonga Urielle Marini Madingou Parfait Noé Binsangou Stoffenne Ifo Suspense Averti National Institute for Research in Health Science Department of Pharmacopeia and Folk Medicine ChemistryOrganic Biomolecules and Pharmacodynamics LaboratoryBrazzavilleRepublic of Congo Sciences and Technologies Faculty Marien Ngouabi UniversityBrazzavilleRepublic of Congo LGETA ENSMarien Ngouabi UniversityBrazzavilleRepublic of Congo ENSAF Marien Ngouabi UniversityBrazzavilleRepublic of Congo

Recent publication attested that in the urban forest of Brazzaville, litter decomposition is faster with almost 45% of initial weight loss than in the dry season, where an average loss of 26% in initial litter weight is noted (Ifo et al., 2018). This study was carried out in the urban forest of Brazzaville to follow the decomposition of some organic compounds/secondary metabolites (reducing Sugars, total Flavonoid and Polyphenols) of the leaves litters of two tropical species Antiaris toxicaria Lesch and Millettia laurentii De Wild. Thin-layer chromatography and spectrophotometric assay of these metabolites were used on the samples of litters collected in the field on various dates of follow-up of the decomposition (0 d, 14 d, 28 d, 42 d, 56 d, 72 d and 84 d). The chromatographic profile of initial litters shows a series of spots on yellow florescence materializing presence of flavonoids, green fluorescence revealing the presence of the acids phenols derived from the cinnamic acid. But the chromatographic profile of the two litters in decomposition after two weeks remains without structural information, being able to characterize the decomposition of the chemical families highlighted in the initial litters. Also, the analysis of quantitative total reducing sugar in the initial litters, gives average concentrations of 64.4, 58.6, 57.5 g EG/kg Ms respectively for the litters of Millettia laurentii De Wild, Antiaris toxicaria Lesch and the mixed litters (Millettia laurentii and Antiaris toxicaria). Comparatively with the other types of litters, the initial average concentrations in phenolic compounds (polyphenols and flavonoids totals) were the highest for the litters of Antiaris toxicaria Lesch (27.3 g EAG/kg Ms and 13.07 g EC/kg Ms) (P = 0.001). The losses of organic chemical compounds are more significant during the first two weeks of experiment than after this period. Antiaris toxicaria Lesch loses on average 43.8 g EG/kg Ms of reducing Sugars, 12.21 g EC/kg Ms of

关键词： Tropical Urban Forest Litter Decomposition Organic Chemical Compounds

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Chemical Constituents from Leaves of Camellia nitidissima and Their Potential Cytotoxicity on SGC7901 Cells

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Chinese Herbal Medicines 2016年第1期8卷 80-84页

作者： Jing Qi Ruo-fu Shi Jian-ming Yu Yi Li Sheng-tao Yuan Ji-zhu Yang Jiang-miao Hu Ai-qun Jia School of Environmental and Biological Engineering Nanjing University of Science and Technology Jiangsu Center for pharmacodynamics Research and Evaluation China Pharmaceutical University Guangxi Gui-Ren-Tang Co. Ltd. State Key Laboratory of Phytochemistry and Plant Resources in West China Kunming Institute of Botany Chinese Academy of Sciences

Objective To isolate and identify the bioactive phytochemicals from the leaves of Camellia nitidissima. Methods The chemical constituents were isolated and purified by repeated silica gel, Sephadex LH-20, MCI gel columns, recrystallization, and semi-preparative HPLC techniques. The chemicl structures of these compounds were identified on the basis of spectral data including NMR and MS. Then quorum sensing inhibition （QSI） activities of these compounds were tested using Chromobacterium violaceum CV026 as the bioindicator strain. The antitumor activities of these compounds were measured using SGC7901 as cell proliferation and cytotoxicity. Results cx-Spinasteryl-I^-D-glucopyranoside （1）, stigmasta-7,22-diene-3-O-[c^-L-arabinopyranosyl （1 -2）]-β-D-galactopyranoside （2）, kaempferol 3-O-[2-O-（trans-p-coumaroyl）-3-O-α -D-glucopyranosyl]-α-D-glucopyranoside （3）, aromadendrin （4）, catechin （5）, phlorizin 4＇-O-β-D-glucopyranoside （6）, （3R,6R,7Lg-3-hydroxy-4,7-megastigmadien- 9-one （7）, dodecanoic acid （8）, 3α-acetoxy-20-1upanol （9）, and 3β,6α- trihydroxyolean- 7-one （1 0） were successively isolated from the leaves of C. nitidissima. Unfortunately, these compounds had no QSI activity. Based on Cell Counting Kit-8 （CCK-8） assay, compound 10 showed the best anti-tumor activity or all compounds （ICs0 = 91.7 μg/mL）. Conclusion Apart from compounds 4 and 5, other eight compounds are reported in this plant for the first time. All compounds show no QSI activity, compound 10 shows potential cytotoxic activity on SGC7901 cells in vitro.

关键词： antitumor Camellia nitidissima C-27 steroidal saponins flavonoids quorum sensinginhibitors SGC7901 triterpenes

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Triptolide reduces prostate size and androgen level on testosterone-induced benign prostatic hyperplasia in Sprague Dawley rats

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Chinese Journal of Natural Medicines 2017年第5期15卷 341-346页

作者： WANG Yu-Rong XU Yuan JIANG Zhen-Zhou ZHANG Lu-Yong WANG Tao State Key Laboratory of Natural Medicines China Pharmaceutical University Nanjing 210009 China Center for Molecular Metabolism School of Environmental and Biological Engineering Nanjing University of Science andTechnology Nanjing 210014 China Jiangsu Key Laboratory of Drug Screening and Jiangsu Center for pharmacodynamics Research and Evaluation China Pharmaceutical University Nanjing 210009 China Jiangsu Key Laboratory of TCM Evaluation and Translational Research China Pharmaceutical University Nanjing 210009China

Benign prostatic hyperplasia(BPH) is an age-related disease of unknown etiology, characterized by prostatic enlargement coincident with distinct alterations in tissue histology. In the present study, we investigated whether triptolide can prevent testosterone-induced prostatic hyperplasia in rats. Castration was performed via the scrotal route after urethane aesthesia. BPH was induced in experimental groups by daily subcutaneous injections of testosterone propionate(TP) for two weeks. Triptolide was administered daily by oral gavage at a dose of 100 and 50 μg×kg^(-1) for 2 weeks, along with the TP injections. On day 14, the animals were humanely killed by cervical dislocation after aesthesia. Prostates were excised, weighed, and used for histological studies. Testosterone and dihydrotestosterone(DHT) levels in serum and prostate were measured. The results showed that triptolide significantly reduced the prostate weight, and the testosterone and DHT levels in both the serum and prostate. Histopathological examination also showed that triptolide treatment suppressed TP-induced prostatic hyperplasia. In conclusion, triptolide effectively inhibits the development of BPH induced by testosterone in a rat model.

关键词： Triptolide Benign prostatic hyperplasia Androgen

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