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Investigation and experimental validation of curcumin-related mechanisms against hepatocellular carcinoma based on network pharmacology

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2022年第8期23卷 682-698页

作者： Yang CHEN Qian LI Sisi REN Ting CHEN Bingtao ZHAI Jiangxue CHENG Xiaoyan SHI Liang SONG Yu FAN Dongyan GUO college of Basic Medicine Shaanxi University of Chinese MedicineXianyang 712046China School of pharmacy Shaanxi University of Chinese MedicineXianyang 712046China Medical Experimental Center Shaanxi University of Chinese MedicineXianyang 712046China Shaanxi Provincial Key Laboratory of TCM Constitution and Disease Prevention Shaanxi University of Chinese MedicineXianyang 712046China

Objective:To determine the potential molecular mechanisms underlying the therapeutic effect of curcumin on hepatocellular carcinoma(HCC)by network pharmacology and experimental in vitro ***:The predictive targets of curcumin or HCC were collected from several *** identified overlapping targets were crossed with Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses using the Database for Annotation,Visualization,and Integrated Discovery(DAVID)*** of the candidate pathways were selected to conduct an experimental *** 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium(MTT)assay was used to determine the effect of curcumin on the viability of Hep G2 and LO2 *** apoptosis and autophagy of Hep G2 cells were respectively detected by flow cytometry and transmission electron ***,western blot and real-time polymerase chain reaction(PCR)were employed to verify the p53 apoptotic pathway and adenosine 5’-monophosphate(AMP)-activated protein kinase(AMPK)autophagy *** G2 cells were pretreated with pifithrin-α(PFT-α)and GSK690693 for further ***:The 167 pathways analyzed by KEGG included apoptosis,autophagy,p53,and AMPK *** GO enrichment analysis demonstrated that curcumin was involved in cellular response to drug,regulation of apoptotic pathway,and so *** in vitro experiments also confirmed that curcumin can inhibit the growth of Hep G2 cells by promoting the apoptosis of p53 pathway and autophagy through the AMPK ***,the protein and messenger RNA(m RNA)of the two pathways were downregulated in the inhibitor-pretreated group compared with the experimental *** damage-regulated autophagy modulator(DRAM)in the PFT-α-pretreated group was downregulated,and p62 in the GSK690693-pretreated group was ***:Curcumin can treat HCC through the p53 apoptotic pathway and the AMPK/Unc-51-like kinase 1(ULK1)au

关键词： Curcumin Network pharmacology p53 Adenosine 5’-monophosphate(AMP)-activated protein kinase(AMPK) Apoptosis Autophagy

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Discovery of Eucalyptin C,derived from the fruits of Eucalyptus globulus Labill.,as a novel selective PI3Kγinhibitor for immunosuppressive treatment

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Chinese Journal of Natural Medicines 2021年第11期19卷 844-855页

作者： HU Xiao-Long SHEN Wei WANG Rong LONG Huan WANG Quan FENG Jia-Hao PHAM Thi-Anh XIONG Fei YE Wen-Cai WANG Hao State Key Laboratory of Natural Medicines School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 210009China State Key Laboratory of Bioelectronics Jiangsu Laboratory for Biomaterials and DevicesSoutheast UniversityNanjing 210009China Institute of Traditional Chinese Medicine and Natural Products Jinan UniversityGuangzhou 510632China

The fruits of Eucalyptus globulus *** known to have a plenty of medicinal properties,such as anti-tumor,anti-inflammatory,and immunosuppressive *** previous study found that the phloroglucinol-sesquiterpene adducts in the fruits of *** were immunosuppressive active constituents,especially Eucalyptin C(EuC).Phosphoinositide 3-kinases-γ(PI3Kγ)plays a pivotal role in T cell mediated excessive immune *** this study,EuC was first discovered to be a novel selective PI3Kγinhibitor with an IC50 value of 0.9μmol·L^(−1) and selectivity over 40-fold towards the other PI3K *** docking,molecular dynamics simulation,and cellular thermal shift assay showed that EuC bound to PI3Kγ.Furthermore,EuC suppressed the downstream of PI3Kγto induce the apoptosis and inhibit the activation of primary spleen cells derived from allergic contact dermatitis *** work highlights the role of the fruits of *** as a source of bioactive plant with immunosuppressive activity.

关键词： Phosphoinositide 3-kinase-γ(PI3Kγ) Eucalyptin C Immunosuppressive effects Activated spleen cells Phloroglucinol-sesquiterpene adducts

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Chinese Herbal Medicines 2023年第1期15卷 33-36页

作者： Hongjing Pan Miamoiao Le Chunnian He Chung S.Yang Tiejun Ling State Key Laboratory of Tea Plant Biology and Utilization Anhui Agricultural UniversityHefei 230036China Institute of Medicinal Plant Development Chinese Academy of Medicinal SciencesPeking Union Medicinal CollegeBeijing 100193China Ernest Maria School of pharmacy Rutgers UniversityPiscatawayNJ 08854-8020USA International Joint Laboratory on Tea Chemistry and Health Effects of Ministry of Education Anhui Agricultural UniversityHefei 230036China

Tea is a famous beverage that is produced from leaves of Camellia *** the six major tea categories in China,dark tea is the only one that involves microbial fermentation in the manufacturing process,which contributes unique flavors and functions for the *** the recent decade,the reports about the biofunctions of dark teas have increased *** it may be the proper time to consider dark tea as one potential homology of medicine and *** this viewpoint,our current understanding of the chemical constituents,biological activities and possible health beneficial effects of dark teas were *** future directions and challenges to the development perspectives of dark teas were also discussed.

关键词： biological activities dark tea metabolites medicinal development perspectives

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Liensinine attenuates inflammation and oxidative stress in spleen tissue in an LPS-induced mouse sepsis model

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第2期24卷 185-190页

作者： HANYU WANG YUANHAO YANG XIAO ZHANG YAN WANG HUI FAN JINFENG SHI XUELIAN TAN BAOSHI XU JINGCHAO QIANG ENZHUANG PAN MINGYI CHU ZIBO DONG JINGQUAN DONG Jiangsu Key Laboratory of Marine Bioresources and Environment Co-Innovation Center of Jiangsu Marine Bio-industry TechnologyJiangsu Key Laboratory of Marine Pharmaceutical Compound ScreeningCollege of PharmacyJiangsu Ocean UniversityLianyungang 222005China Department of Rheumatology and Immunology the Second People's Hospital of Lianyungang CityLianyungang 222000China

Sepsis is a complex syndrome caused by multiple pathogens and involves multiple organ failure,particularly spleen *** 2017,the worldwide incidence was 48.9 million sepsis cases and 1l million sepsis-related deaths were reported(Rudd et al.,2020).Inflammation,oxidative stress,and apoptosis are the most common pathologies seen in ***(LIE)is a bisbenzylisoquinoline-type alkaloid extracted from the seed embryo of Nelumbo *** seed hearts have high content of LIE which mainly has antihypertensive and antiarrhythmic pharmacological *** can exert anti-carcinogenicactivityby regulating cell.

关键词： oxidative alkaloid benzyl

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On the necessity of an integrative approach to understand protein structural dynamics

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2019年第6期20卷 496-502页

作者： Qing-fen YANG Chun TANG Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation School of PharmacyTongji Medical CollegeHuazhong University of Science and Technology CAS Key Laboratory of Magnetic Resonance in Biological Systems State Key Laboratory of Magnetic Resonance and Atomic Molecular PhysicsNational Center for Magnetic Resonance at WuhanWuhan Institute of Physics and Mathematics of the Chinese Academy of Sciences

Proteins are dynamic,fluctuating between multiple conformational *** dynamics,spanning orders of magnitude in time and space,allow proteins to perform specific ***,under certain conditions,proteins can morph into a different set of ***,a complete understanding of protein structural dynamics can provide mechanistic insights into protein ***,we review the latest developments in methods used to determine protein ensemble structures and to characterize protein *** including X-ray crystallography,cryogenic electron microscopy,and small angle scattering can provide structural information on specific conformational states or on the averaged shape of the protein,whereas techniques including nuclear magnetic resonance,fluorescence resonance energy transfer(FRET),and chemical cross-linking coupled with mass spectrometry provide information on the fluctuation of the distances between protein domains,residues,and atoms for the multiple conformational states of the *** particular,FRET measurements at the single-molecule level allow rapid resolution of protein conformational states,where information is otherwise obscured in bulk *** together,the different techniques complement each other and their integrated use can offer a clear picture of protein structure and dynamics.

关键词： Conformational dynamics Integrative structural biology Distance restraint Ensemble averaging Nuclear magnetic resonance(NMR)

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Nutraceutical with Anti-Inflammatory Activity for the Management of Airway Remodeling in Bronchial Asthma: <i>Kalanchoe integra</i>Var. Crenata (Andr.) Cuf Leaf Extract

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Pharmacology & pharmacy 2014年第3期5卷 250-261页

作者： Asiedu-Gyekye Isaac Julius Awortwe Charles Nyamekye Effah Samuel Antwi Daniel Ansong Seidu Mahmood Adjei Samuel Banga N’guessan Benoit Kwame Amoateng Patrick Nkansah Edwin Department of Animal Experimentation Noguchi Memorial Institute for Medical Research College of Health Sciences Legon Ghana Department of Chemical Pathology School of Allied Health Sciences College of Health Sciences Korle-Bu Ghana Department of Pharmacology and Toxicology University of Ghana School of Pharmacy College of Health Sciences Legon Ghana Department of Physiology University of Ghana Medical School Col-lege of Health Sciences Korle-Bu Ghana Division of Pharmacology Faculty of Health Sciences University of Stellenbosch Cape Town South Africa

Background: Kalanchoe integra is widely used in folklore medicine as an antiasthmatic agent. Previous studies have shown the ameliorating effect of Kalanchoe integra leaf extract [KILE] on bronchial hyperesponsiveness and inflammation. Further, the stabilizing effect of Kalanchoe sp on mast cell degranulation, suggests that Kalanchoe species are suitable candidates for allergic asthma therapy. This study is designed to investigate the anti-asthmatic potential of KILE and monitor the accompanying histopathological and immunobiochemical changes that occur in an animal model of bronchial asthma using ovalbumin sensitized guinea pigs. Method: Thirty male guinea pigs were divided into five groups of six animals each. Bronchial asthma was simulated in guinea pigs using ovalbumin. Both low dose (300 mg/kg) and high dose extract (900 mg/kg) were administered daily for 42 days. Prednisolone (2.5 mg/kg) was the standard drug used. Results: Guinea pigs in all KILE treated groups maintained the integrity of their airway structures: bronchial folds and walls, alveoli, alveolar ducts and sacs. KILE and prednisolone caused a reduction in immune parameters (p 0.001), extent of bronchoconstriction, bronchial wall thickness and goblet cell accumulation in the sensitized guinea pigs. Conclusion: This study demonstrates the anti-asthmatic potential of KILE during prolonged administration by the oral route.

关键词： Kalanchoe Integra Asthma Bronchoconstriction Goblet Cells Perivascular Oedema

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Plant distribution and pharmacological activity of flavonoids

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Traditional Medicine Research 2019年第5期4卷 269-287页

作者： Shao-Hui Wang Yan-Lan Hu Tong-Xiang Liu Medical college Qingdao Binhai University Qingdao 266555 China Affiliated Hospital of Qingdao Binhai University Qingdao 266555 China Key Laboratory of Ethnomedicine (Minzu University of China) Ministry of Education Beijing 100081 China School of pharmacy Minzu University of China Beijing 100081 China

Flavonoids are natural organic compounds that are widely found in nature, their structural types are complex, and they mainly include flavonoids, flavonols, dihydroflavonols, isoflavones, dihydroisoflavones, chalcones, orange ketones, flavanoids, anthocyanidins, and biflavonoids. This review covers the plant distribution and pharmacological activities of flavonoids. Flavonoids are mainly distributed in angiosperms and gymnosperms, and they are abundant in plants such as Rutaceae, Labiatae, Zingiberaceae, Scrophulariaceae, and Leguminosae. Because of their wide distribution and variety, researchers have found that flavonoids have diverse biological activities, mainly focusing on anti-inflammatory, antibacterial and antitumor activities. Mechanistically, the anti-inflammatory effects are mainly related to the NF-κB and MAPK (mitogen-activated protein kinase) signaling pathway and then the inhibition of the production of inflammatory cytokines and mediators. The antibacterial activity is mainly manifested as inhibitory effects on many strains, including Escherichia coli, Cryptococcus neoformans, and Pseudomonas aeruginosa, via destroying the stability of the microbial membrane, inhibiting the invasion of virulent bacteria into host cells, promoting the apoptosis of bacteria, inhibiting bacterial fatty acid synthesis, etc. The antitumor activity of flavonoids is related to their inhibition of cell proliferation and induction of apoptosis via the mitochondria-mediated, endoplasmic reticulum-mediated, and death factor and its receptor-mediated signal transduction pathways. Understanding the plant distribution and pharmacological activity of flavonoids not only reveals the importance of identifying such valuable flavonoids in another genus or family but also provides a basis for fully exploiting the therapeutic potential of flavonoids.

关键词： Flavonoids Plant distribution Pharmacological activity Antitumor Anti-inflammatory Antibacterial

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Anti-aging effects of chlorpropamide depend on mitochondrial complex-Ⅱ and the production of mitochondrial reactive oxygen species

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Acta Pharmaceutica Sinica B 2022年第2期12卷 665-677页

作者： Zhifan Mao Wenwen Liu Yunyuan Huang Tianyue Sun Keting Bao Jiali Feng Alexey Moskalev Zelan Hu Jian Li State Key Laboratory of Bioreactor Engineering Frontiers Science Center for Materiobiology and Dynamic ChemistryShanghai Key Laboratory of New Drug DesignEast China University of Science and TechnologyShanghai 200237China Laboratory of Geroprotective and Radioprotective Technologies Institute of BiologyKomi Science CentreUral BranchRussian Academy of SciencesSyktyvkar 167982Russia Yunnan Key Laboratory of Screening and Research on Anti-pathogenic Plant Resources from West Yunnan College of PharmacyDali UniversityDali 671000China Clinical Medicine Scientific and Technical Innovation Center Shanghai Tenth People’s HospitalTongji University School of MedicineShanghai 200092China

Sulfonylureas are widely used oral anti-diabetic ***,its long-term usage effects on patients’lifespan remain controversial,with no reports of influence on animal ***,the anti-aging effects of chlorpropamide along with glimepiride,glibenclamide,and tolbutamide were studied with special emphasis on the interaction of chlorpropamide with mitochondrial ATP-sensitive K+(mito K-ATP)channels and mitochondrial complex *** delayed aging in Caenorhabditis elegans,human lung fibroblast MRC-5 cells and reduced doxorubicin-induced senescence in both MRC-5 cells and *** addition,the mitochondrial membrane potential and ATP levels were significantly increased in chlorpropamide-treated worms,which is consistent with the function of its reported targets,mito K-ATP *** levels of mitochondrial reactive oxygen species(mt ROS)were observed in chlorpropamide-treated ***,the lifespan extension by chlorpropamide required complex II and increased mt ROS levels,indicating that chlorpropamide acts on complex II directly or indirectly via mito K-ATP to increase the production of mt ROS as a pro-longevity *** study provides mechanistic insight into the anti-aging effects of sulfonylureas in ***.

关键词： Sulfonylureas Chlorpropamide Anti-aging Mitochondrial complexⅡ Mitochondrial reactive oxygen species ATP sensitive potassium channels Senescence Succinate dehydrogenase

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mRNA delivery in cancer immunotherapy

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Acta Pharmaceutica Sinica B 2023年第4期13卷 1348-1357页

作者： Yichen Zhong Shi Du Yizhou Dong Division of Pharmaceutics&Pharmacology College of PharmacyThe Ohio State UniversityColumbusOH 43210USA Department of Radiation Oncology Department of Biomedical EngineeringCenter for Clinical and Translational ScienceComprehensive Cancer CenterDorothy M.Davis Heart&Lung Research InstituteCenter for Cancer EngineeringCenter for Cancer MetabolismPelotonia Institute for Immune-OncologyThe Ohio State UniversityColumbusOH 43210USA Icahn Genomics Institute Precision Immunology InstituteDepartment of Oncological SciencesTisch Cancer InstituteFriedman Brain InstituteIcahn School of Medicine at Mount SinaiNew YorkNY 10029USA

Messenger RNA(mRNA)has drawn much attention in the medical *** various treatment approaches including protein replacement therapies,gene editing,and cell engineering,mRNA is becoming a potential therapeutic strategy for ***,delivery of mRNA into targeted organs and cells can be challenging due to the unstable nature of its naked form and the low cellular ***,in addition to mRNA modification,efforts have been devoted to developing nanoparticles for mRNA *** this review,we introduce four categories of nanoparticle platform systems:lipid,polymer,lipid-polymer hybrid,and protein/peptide-mediated nanoparticles,together with their roles in facilitating mRNA-based cancer *** also highlight promising treatment regimens and their clinical translation.

关键词： Cancer immunotherapy Lipid nanoparticles Lipid—polymer hybrid nanoparticles Messenger RNA mRNA delivery Polymeric nanoparticles Protein/peptide-mediated nanoparticles

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Microcolin H, a novel autophagy inducer, exerts potent antitumour activity by targeting PITPα/β

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Signal Transduction and Targeted Therapy 2023年第12期8卷 5931-5943页

作者： Hange Yang Xiaowei Zhang Cong Wang Hailong Zhang Juan Yi Kun Wang Yanzhe Hou Peihong Ji Xiaojie Jin Chenghao Li Min Zhang Shan Huang Haoyuan Jia Kuan Hu Lingyun Mou Rui Wang Key Laboratory of Preclinical Study for New Drugs of Gansu Province School of Basic Medical Sciences&Research Unit of Peptide ScienceChinese Academy of Medical Sciences2019RU066Lanzhou UniversityLanzhouGansuP.R.China Institute of Materia Medica Chinese Academy of Medical SciencesBeijingP.R.China Gansu University Key Laboratory for Molecular Medicine&Chinese Medicine Prevention and Treatment of Major Diseases College of PharmacyGansu University of Chinese MedicineLanzhouChina School of Life Science Lanzhou University730000 LanzhouP.R.China

The identification of effective drug targets and the development of bioactive molecules are areas of high need in cancer *** phosphatidylinositol transfer protein alpha/beta isoform(PITPα/β)has been reported to play an essential role in integrating phosphoinositide trafficking and lipid metabolism in diverse cellular processes but remains unexplored as a potential target for cancer ***,data analysis of clinical cancer samples revealed that PITPα/βexpression is closely correlated with the poor *** identification by chemical proteomic methods revealed that microcolin H,a naturally occurring marine lipopeptide,directly binds PITPα/βand displays antiproliferative activity on different types of tumour cell ***,we identified that microcolin H treatment increased the conversion of LC3I to LC3II,accompanied by a reduction of the level of p62 in cancer cells,leading to autophagic cell ***,microcolin H showed preeminent antitumour efficacy in nude mouse subcutaneous tumour models with low *** discoveries revealed that by targeting PITPα/β,microcolin H induced autophagic cell death in tumours with efficient anti-proliferating activity,which sheds light on PITPα/βas a promising therapeutic target for cancer treatment.

关键词： tumour metabolism nude

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