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Is the control of dietary cholesterol intake sufficiently effective to ameliorate nonalcoholic fatty liver disease?

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World Journal of Gastroenterology 2010年第7期16卷 800-803页

作者： Munechika Enjoji Makoto Nakamuta Department of clinical Pharmacology Faculty of Pharmaceutical SciencesFukuoka University8-19-1 NanakumaJonan-kuFukuoka 814-0180Japan Department of Gastroenterology and clinical research Center Kyushu Medical CenterNational Hospital Organization1-8-1 JigyohamaChuo-kuFukuoka 810-8563Japan

In our examination of the distribution of abdominal fat,dietary intake and biochemical data in patients with nonalcoholic fatty liver disease(NAFLD),non-obese NAFLD patients without insulin resistance presented a characteristic pattern of dietary *** cholesterol intake was superabundant in non-obese patients compared with obese patients,although total energy and carbohydrate intake was not ***,excess cholesterol intake appears to be one of the main factors associated with NAFLD development and liver ***,the control of dietary cholesterol intake may lead to an improvement in NAFLD,and the NPC1L1 inhibitor ezetimibe might be a promising treatment for *** review one pathogenic aspect of lipid metabolism dysregulation in NAFLD and survey new strategies for NAFLD treatment based on the modification of cholesterol metabolism.

关键词： Cholesterol Ezetimibe Nonalcoholic fatty liver disease NPC1L1 Polyunsaturated fatty acids

Synergistic anticancer effect of the extracts from Polyalthia evecta caused apoptosis in human hepatoma(HepG2)cells

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Asian Pacific Journal of Tropical Biomedicine 2012年第8期2卷 589-596页

作者： Sasipawan Machana Natthida Weerapreeyakul Sahapat Barusrux Kanjana Thumanu Warapom Tanthanuch Graduate School Faculty of Pharmaceutical SciencesKhon Kaen University Center for research and Development of Herbal Health products Faculty of Pharmaceutical SciencesKhon Kaen University Centre for research and Development of Medical Diagnostic Laboratories Faculty of Associate Medical SciencesKhon Kaen University Synchrotron Light research Institute(Public organization) Nakhon Ratchasima

Objective:To evaluate the anticancer activity of the extract fraction of Polyalthia evecta(P. evecta)(Pierre) Finet & Gagnep and the synergistic anticancer effect of the extracts from *** by using the ATR/FT-IR ***:The 50%ethanol-water crude leaf extract of ***(EW-L) was prepared and was further fractionated to isolate various *** anticancer activity was investigated from cytotoxicity against HepG2 using a neutral red assay and apoptosis induction by evaluation of nuclei morphological changes after DAPI staining. Synergistic anticancer effects of the extracts from *** were performed using the ATR/FTIR ***:The result showed that the EW-L showed higher cytotoxicity and apoptosis induction in HepG2 cells than its fractionated *** hexane extract exhibited higher cytotoxicity and apoptosis induction than the water extracts,but less than the EW-L. The combined water and hexane extracts apparently increased cytotoxicity and apoptosis ***%apoptotic cells induced by the extract mixture were increased about 2-fold compared to the single hexane extract Conclusions:The polar extract fraction is necessary for the anticancer activity of the non-polar extract *** ATR/FT-IR spectra illustrates the physical interaction among the constituents in the extract mixture and reveals the presence of polyphenolic constituents in the EW-L,which might play a role for the synergistic anticancer effect.

关键词： Polyalthia evecta Synergistic Apoptosis induction Cytotoxicity Anticancer activity Hepatoma ATR/FT-IR spectroscopy

A novel vanadium complex VO(p-dmada)inhibits neuroinflammation induced by lipopolysaccharide

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Chinese Chemical Letters 2023年第10期34卷 209-214页

作者： Zhijun He Xiaoqian Li Huajie Zhang Xin Liu Shuangxue Han Anwar Abdurahman Liming Shen Xiubo Du Nan Li Xiaoda Yang Qiong Liu Shenzhen Key Laboratory of Marine Biotechnology and Ecology College of Life Sciences and OceanographyShenzhen UniversityShenzhen 518055China National R&D Center for Se-rich Agricultural products Processing Hubei Engineering Research Center for Deep Processing of Green Se-rich Agricultural ProductsSchool of Modern Industry for Selenium Science and EngineeringWuhan Polytechnic UniversityWuhan 430023China Shenzhen Bay Laboratory Shenzhen 518055China State Key Laboratories of Natural and Biomimetic Drugs Department of Chemical BiologySchool of Pharmaceutical SciencesPeking University Health Science CenterBeijing 100191China Department of Pharmacy Shenzhen People’s Hospital(The Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSouthern University of Science and Technology)Shenzhen 518020China Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental research Institutions Shenzhen 518055China

Uncontrolled microglial activation is decisively involved in the neuroinflammatory pathogenesis of brain diseases. Consequently, suppression of microglial overactivation appears to be a strategy for the prevention of nerve injury. In this paper, a novel vanadium complex, vanadyl N-(p-N,Ndimethylaminophenylcarbamoylmethyl)iminodiacetate(VO(p-dmada)), was synthesized from vanadyl sulfate and N,N-dimethyl-p-phenylenediamine, which was structurally characterized by Fourier transform infrared spectrum and ESI-MS analysis. The effect of VO(p-dmada) on neuroinflammation was investigated by using the models of lipopolysaccharide(LPS)-induced BV2 microglial cells and BALB/c *** data demonstrated that VO(p-dmada) significantly suppressed microglial activation by downregulating inflammatory mediators and associated proteins, and inactivating nuclear factor-κ B(NF-κ B) signaling pathway. VO(p-dmada) also upregulated peroxisome proliferator activated receptor gamma(PPARγ) by reducing transglutaminase 2 and heat shock protein 60 expression. Co-treatment with PPARγ antagonist GW9662 significantly impeded the inhibitory effect of VO(p-dmada) on LPS-induced *** cumulative findings demonstrated that VO(p-dmada) is a potential new drug for the treatment of neuroinflammation-related neurodegenerative diseases.

关键词： Vanadium Vanadyl N-(p-N,Ndimethylaminophenylcarbamoylmethyl)iminodiacetate (VO(p-dmada)) Neuroinflammation Microglia Proteomics Peroxisome proliferator activated receptor gamma(PPARγ)

The role of high mobility group box 1(HMGB1)in the pathogenesis of kidney diseases

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Acta Pharmaceutica Sinica B 2016年第3期6卷 183-188页

作者： Qingjie Chen Xiaofeng Guan Xiaocong Zuo Jianglin Wang Wenjun Yin clinical Pharmacy and Pharmacology research Institute The Third Xiangya Hospital of Central South University School of pharmaceutical Sciences Central South University

High mobility group box 1(HMGB1) is a nuclear protein that can bind to DNA and act as a co-factor for gene transcription. When released into extracellular fluid, it plays a proinflammatory role by acting as a damage-associated molecular pattern molecule(DAMP)(also known as an alarmin) to initiate innate immune responses by activating multiple cell surface receptors such as the receptor for advanced glycation end-products(RAGE) and toll-like receptors(TLRs), TLR2, TLR4 or TLR9. This proinflammatory role is now considered to be important in the pathogenesis of a wide range of kidney diseases whether they result from hemodynamic changes, renal tubular epithelial cell apoptosis, kidney tissue fibrosis or inflammation. This review summarizes our current understanding of the role of HMGB1 in kidney diseases and how the HMGB1-mediated signaling pathway may constitute a new strategy for the treatment of kidney diseases.

关键词： High mobility group box 1 Inflammation Acute kidney injury Chronic kidney disease Diabetic nephropathy Antineutrophil cytoplasmic autoantibody-associated vasculitis Clear cell renal cell carcinoma Nephritis

New opportunities and challenges of natural products research:When target identification meets single-cell multiomics

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Acta Pharmaceutica Sinica B 2022年第11期12卷 4011-4039页

作者： Yuyu Zhu Zijun Ouyang Haojie Du Meijing Wang Jiaojiao Wang Haiyan Sun Lingdong Kong Qiang Xu Hongyue Ma Yang Sun College of Pharmacy Nanjing University of Chinese MedicineNanjing 210023China Institute of Marine Biomedicine School of Food and DrugShenzhen PolytechnicShenzhen 518055China State Key Laboratory of pharmaceutical Biotechnology School of Life ScienceNanjing UniversityNanjing 210023China Jiangsu Key Laboratory of New Drug research and clinical Pharmacy Xuzhou Medical University Xuzhou 221004China

Natural products, and especially the active ingredients found in traditional Chinese medicine(TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such,traditional remedies provide shortcuts for the development of original new drugs in China, and increasing numbers of natural products are showing great therapeutic potential in various diseases. This paper reviews the molecular mechanisms of action of natural products from different sources used in the treatment of inflammatory diseases and cancer, introduces the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients, enumerates the expansive list of TCM used to treat inflammatory diseases and cancer, and summarizes the patterns of action of emerging technologies such as single-cell multiomics, network pharmacology, and artificial intelligence in the pharmacological studies of natural products to provide insights for the development of innovative natural product-based drugs. Our hope is that we can make use of advances in target identification and singlecell multiomics to obtain a deeper understanding of actions of mechanisms of natural products that will allow innovation and revitalization of TCM and its swift industrialization and internationalization.

关键词： Natural products Traditional Chinese medicine Molecular mechanism Inflammatorydiseases Cancer Targetidentification Single-cell multiomics Biosynthesis

Small molecule-based immunomodulators for cancer therapy

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Acta Pharmaceutica Sinica B 2022年第12期12卷 4287-4308页

作者： Yinrong Wu Zichao Yang Kui Cheng Huichang Bi Jianjun Chen Guangdong Provincial Key Laboratory of New Drug Screening NMPA Key Laboratory for Research and Evaluation of Drug MetabolismSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China

Immunotherapy has led to a paradigm shift in the treatment of *** cancer immunotherapies are mostly antibody-based,thus possessing advantages in regard to pharmacodynamics(e.g.,specificity and efficacy).However,they have limitations in terms of pharmacokinetics including long half-lives,poor tissue/tumor penetration,and little/no oral *** addition,therapeutic antibodies are immunogenic,thus may cause unwanted adverse ***,researchers have shifted their efforts towards the development of small molecule-based cancer immunotherapy,as small molecules may overcome the above disadvantages associated with ***,small molecule-based immunomodulators and therapeutic antibodies are complementary modalities for cancer treatment,and may be combined to elicit synergistic *** years have witnessed the rapid development of small molecule-based cancer *** this review,we describe the current progress in small molecule-based immunomodulators(inhibitors/agonists/degraders)for cancer therapy,including those targeting PD-1/PD-L1,chemokine receptors,stimulator of interferon genes(STING),Toll-like receptor(TLR),*** tumorigenesis mechanism of various targets and their respective modulators that have entered clinical trials are also summarized.

关键词： Cancer immunotherapy Small molecules Immunomodulators Inhibitors Agonists

Treatment of Helicobacter pylori infection: Current and future insights

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World Journal of clinical Cases 2016年第1期4卷 5-19页

作者： Maliheh Safavi Reyhaneh Sabourian Alireza Foroumadi Department of Biotechnology Iranian Research Organization for Science and Technology Department of Drug and Food Control Faculty of Pharmacy Tehran University of Medical Sciences pharmaceutical Sciences research Center Tehran University of Medical Sciences

Helicobacter pylori(***) is an important major cause of peptic ulcer disease and gastric malignancies such as mucosa-associated lymphoid tissue lymphoma and gastric adenocarcinoma *** treatment still remains a challenge,since many determinants for successful therapy are involved such as individual primary or secondary antibiotics resistance,mucosal drug concentration,patient compliance,side-effect profile and *** no new drug has been developed,current therapy still relies on different mixture of known antibiotics and anti-secretory agents.A standard triple therapy consisting of two antibiotics and a proton-pump inhibitor proposed as the first-line *** quadruple treatment,sequential treatment or a non-bismuth quadruple treatment(concomitant) are also an alternative *** containing triple treatment are recommended as rescue treatment for infection of *** after defeat of first-line *** rapid acquisition of antibiotic resistance reduces the effectiveness of any regimens involving these ***,adding probiotic to the medications,developing *** photodynamic or phytomedicine therapy,and achieving a successful *** vaccine may have the promising to present synergistic or additive consequence against ***,because each of them exert different effects.

关键词： Helicobacter pylori Therapeutic regimens Probiotics Photodynamic Phytomedicine

Visualization of supramolecular assembly by aggregation-induced emission

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聚集体(英文)

聚集体(英文) 2023年第2期4卷 102-122页

作者： Wu-Jie Guo Tuokai Peng Wenping Zhu Shixiang Ma Guang Wang Ying Li Bin Liu Hui-Qing Peng Beijing Advanced Innovation Center for Soft Matter Science and Engineering State Key Laboratory of Chemical Resource EngineeringBeijing University of Chemical TechnologyBeijingChina Innovation research Center for AIE pharmaceutical Biology Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target and Clinical PharmacologyThe NMPA and State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences and The Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhouChina Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates South China University of TechnologyGuangzhouChina

Supramolecular architectures are constructed by the self-assembly of small building blocks via the use of metal-ligand coordination,π–πstacking interactions,hydrogen bonding,host-guest interactions,and other noncovalent driving forces,which confer unique dynamic reversibility and stimulus responsiveness to the supramolecular materials and also lead to the demand of expensive and complex equipment for the characterization of supramolecular assembly ***,the self-assembly processes bring the monomeric chromophores together,offering possibilities to establish ties between the supramolecular assembly and aggregation-induced emission(AIE)*** to conventional luminescent molecules,AIE luminogens(AIEgens)exhibit significant fluorescence enhancement upon the restriction of molecular motions,thus displaying the advantages of signal amplification and low background *** the above,the real-time,sensitive,and in situ visualization of the formation of self-assemblies and their stimuli responsiveness based on AIE becomes ***,we review recent works that encompass the visualization of supramolecular assembly-related behaviors by means of AIE characteristics of *** organization of this review will be by different types of supramolecular architectures,including metallacycles/cages,micelles/vesicles,supramolecular polymers,and supramolecular *** overview of future opportunities and challenges for the real-time monitoring of supramolecular assembly by AIE is also provided.

关键词： aggregation-induced emission metallacycles/cages micelles/vesicles supramolecular gels supramolecular polymers visualization

Study of the safety of oral Triphala aqueous extract on healthy volunteers

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Journal of Integrative Medicine 2020年第1期18卷 35-40页

作者： Pratya Phetkate Tanawan Kummalue Prasob-orn Rinthong Somboon Kietinun Kusuma Sriyakul Graduate Program in Integrative Medicine Chulabhorn International College of MedicineThammasat UniversityPathum Thani 12120Thailand Department of clinical Pathology Faculty of Medicine Siriraj HospitalMahidol UniversityBangkok 10700Thailand pharmaceutical Chemistry and Natural products research Unit Faculty of PharmacyMahasarakham UniversityMaha Sarakham 44150Thailand

Background:Triphala extract is a well known medicinal herbal formula which is usually prescribed by Thai traditional doctors to adjust the physiological functions of the *** studies have reported that Triphala has antioxidant,anti-inflammatory,antihypercholesterolemia and anticancer *** this herbal recipe is commonly used in Thailand,its human safety,especially in the oral form,has not been *** therefore conducted a clinical trial(Phase I).Objective:This study evaluated the safety of administering the aqueous extract of Triphala to healthy volunteers at 2500 mg/***,setting,participants and interventions:An open-label,single-arm trial was conducted at Chulabhorn International College of Medicine,Thammasat University,Pathum Thani,Thailand,between July 2017 and July *** study enrolled 10 male and 10 female healthy volunteers;all were given Triphala(water extract;five capsules of 500 mg each)orally,once a day,at bedtime,for four consecutive *** outcome measures:Signs and symptoms,physical examinations,hematology and blood chemistry were assessed at the beginning of the trial and every week thereafter,for four consecutive *** finishing the trial,on day 28,all volunteers were invited to a follow-up session on day 35 to evaluate the safety of the herbal recipe using the same ***:At the oral dose of 2500 mg/d,Triphala had no serious adverse effects in healthy ***,it was found to have significantly improved the volunteers’high-density lipoprotein cholesterol(HDL-C)levels on day 35 and also reduced their blood sugar levels on days 14 and ***:We conclude that aqueous extract of Triphala is safe for healthy volunteers and that it elevates HDL-C levels and lowers blood *** clinical study should investigate its effects on HDL-C and blood sugar levels among the dyslipidemic and prediabetic *** registration:This trial was registered in the Thai clinical Trial Regis

关键词： Triphala clinical trial Safety Healthy volunteers