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Trigonelline mitigates bleomycin-induced idiopathic pulmonary fibrosis in mice

Asian Pacific Journal of Tropical Biomedicine 2024年第9期14卷 391-400,I0008-I0291页

作者： Swapnil Gavhane Chandrakant Gawli Sachin Kumar Biswajit Das Gayatri Marathe Vishal S.Patil Harun M.Patel Basavaraj Bommanahalli Chanakya Nath Kundu Chandragouda R.Patil R.C.Patel institute of pharmaceutical Education and research Karwand NakaShirpurMaharashtra 425405India Department of Pharmacology Delhi Pharmaceutical Sciences and Research UniversityNew Delhi 110017India School of Biotechnology Kalinga Institute of Industrial TechnologyBhubaneshwar 751024India Gadag institute of Medical Sciences GadagKarnataka 582103India

Objective:To evaluate the effect of trigonelline on bleomycin-induced idiopathic pulmonary fibrosis(IPF)and to explore its underlying mechanisms using network ***:IPF was induced in C57BL/6 mice by a single intratracheal instillation of bleomycin(5 mg/kg).Trigonelline was administered at doses of 25,50,and 100 mg/kg/day orally from the 2nd day post-bleomycin induction up to the 14th *** IPF-induced mice,lung coefficient,immune cell infiltration in bronchoalveolar lavage fluid,and oxidative stress were *** alterations in lung tissues were also ***,network pharmacology approach was conducted to reveal molecular interactions of bleomycin and trigonelline with targets of ***:Trigonelline treatment reduced bleomycin-induced oxidative stress and immune cell infiltration,and mitigated physiological changes in the lung tissues of ***,trigonelline alleviated bleomycin-induced histological alterations in lung *** pharmacology analysis showed that bleomycin and trigonelline interacted with IPF targets,such as NFKB1,HDAC2,HIF1A,and ***:The interaction of trigonelline with key IPF targets and its ameliorative effects on lung damage and oxidative stress highlight its potential in treating *** may be considered an antifibrotic agent for further clinical development.

关键词： Trigonelline Idiopathic pulmonary fibrosis Antifibrotic Bleomycin Network pharmacology

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Caffeic acid 3,4-dihydroxyphenethyl ester prevents colorectal cancer through inhibition of multiple cancer-promoting signal pathways in 1,2-Dimethylhydrazine/dextran sodium sulphate mouse model

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Journal of Traditional Chinese Medicine 2024年第1期44卷 70-77页

作者： JIN Tao ZHOU Qian SHEN Jichen ZHANG Zhizhong LIAN Xiaoyuan College of pharmaceutical Sciences Zhejiang UniversityHangzhou 310058China pharmaceutical Informatics institute College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Ocean College Zhoushan Campus of Zhejiang UniversityZhoushan 316021China

OBJECTIVE:To elucidate the potential feature and mechanism of the caffeic acid 3,4-dihydroxyphenethyl ester(CADPE)molecule,which can prevent colorectal cancer(CRC)in the 1,2-Dimethylhydrazine(DMH)/dextran sodium sulphate(DSS)-induced mouse ***:institute of cancer research(ICR)male mice were injected with 20 mg/kg DMH for a *** that,2%DSS was administered in the drinking water for another 7 *** CADPE treatment was given to the DMH/DSS induced male mice at three different periods until their *** examination was used for observing the CRC development at colonic ***(IHC),blood cells smearing and crypt damage scoring methods were used for investigating the anti-inflammation feature of CADPE related to *** reversing targets searching method was applied with artificial intelligence(AI),computeraided drug designing(CADD)and Ingenuity Pathway Analysis(IPA)techniques for predicting the potential targets and mechanism of CADPE highly related to ***:The data indicated that CADPE inhibited CRC tumor development in the colitis-associated DMH/DSS induced mouse model after giving the early *** also impeded the acute inflammation by decreasing the infiltration of neutrophils significantly during the initial stage of CRC ***,our data showed that CADPE prevented CRC by blocking active sites of three pivotal protein targets including epidermal growth factor receptor(EGFR),extracellular signal-regulated kinase(ERK)and mammalian target of rapamycin(m TOR)in two major cancer development ***:CADPE effectively prevented CRC at early stage of tumor germination in the DMH/DSS mouse model highly likely due to its anti-acute inflammation characteristic and the ability of blocking EGFR,ERK and m TOR activities in two highly related CRC developing pathways.

关键词： caffeic acids colorectal neoplasms inflammation chemoprevention Sarcandra glabra

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Inhaled multilevel size-tunable,charge-reversible and mucus-traversing composite microspheres as trojan horse:Enhancing lung deposition and tumor penetration

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Chinese Chemical Letters 2024年第9期35卷 273-278页

作者： Lishan Xiong Xinyuan Li Xiaojie Lu Zhendong Zhang Yan Zhang Wen Wu Chenhui Wang Chongqing Key Laboratory of Natural Product Synthesis and Drug research School of Pharmaceutical SciencesChongqing UniversityChongqing 401331China Chongqing Key Laboratory of High Active Traditional Chinese Drug Delivery System Chongqing Engineering Research Center of Pharmaceutical SciencesChongqing Medical and Pharmaceutical CollegeChongqing 404120China

Dry powder inhalation represents a promising approach for the treatment of lung cancer,offering several advantages such as enhanced targeting,improved bioavailability,and reduced ***,traditional dry powder formulations suffer from limitations,notably low pulmonary delivery efficiency and inadequate penetration into tumor tissues,thereby limiting their therapeutic *** response to these challenges,we have developed an innovative trojan horse strategy,harnessing an inhalable nanoparticlein-microsphere system characterized by tunable size,reversible charge,and mucus-penetrating *** inhalable nanoparticle-in-microsphere system exhibit stable structural properties,excellent environmental responsiveness and high *** importantly,the therapeutic effect of MTX@PAMAM@HA@Gel(MPHG)was demonstrated in vitro and in *** system offers improved pulmonary delivery efficiency,enhanced drug retention within tumor tissues,and effective penetration,thus representing a promising strategy in lung cancer treatment.

关键词： Pulmonary delivery Size-tunable nanoparticles Charge-reversible nanoparticles Mucus penetration Lung cancer

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Ganoderma Lucidum Spore Oil enhances the effect of cyclophosphamide via inhibiting programmed death-1 and prolongs the survival of H22 tumor-bearing mice

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Journal of Traditional Chinese Medicine 2024年第4期44卷 652-659页

作者： JIANG Zhaojian CAI Hongfei YUAN Cheng CAO Lin XU Wendong HAN Yaming ZHANG Qin LI Jing WANG Qin LIU Juyan Guangzhou HanFang pharmaceutical Company Limited National Engineering Research Center of Pharmaceutical Processing Technology of Traditional Chinese Medicine and Drug InnovationGuangdong Provincial Key Laboratory of Medicinal LipidsGuangzhou 510240China Zhongshan Medical College Sun Yat-sen UniversityGuangzhou 510080China Guangzhou pharmaceutical Holdings Limited Guangzhou 510130China National Engineering research Center of pharmaceutical Processing Technology of Traditional Chinese Medicine and Drug Innovation Guangzhou 510240China

OBJECTIVE:To investigate the effect of Ganoderma Lucidum Spore Oil(GLSO)on the tumor growth and survival of H22 tumor-bearing mice treated with cyclophosphamide(CTX),and explore the underlying ***:Allograft H22 hepatocellular carcinoma mouse model was applied to investigate the effect of GLSO on the tumor growth and survival of animals,and Kaplan-Meier survival analysis was used to analyze the life *** biochemical examination was used to determine the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),urea(UREA)and creatinine(CRE).Western blot analysis was performed to detect Programmed Death-1(PD-1),Programmed Death Ligand 1(PD-L1),Janus Kinase 2(JAK2),phosphorylated Signal Transducer and Activator of Transcription 3(p-STAT3),and Signal Transducer and Activator of Transcription 3(STAT3)***:GLSO increased the anti-tumor effect of CTX and prolonged the survival of H22 tumor-bearing mice treated with ***,GLSO increased the thymus index and showed no obvious toxicity to liver functions of *** also decreased the level of UREA in H22 tumor-bearing mice treated with ***,GLSO could inhibit the expression of PD-1 in spleen,which was independent of JAK2 expression and STAT3 ***,GLSO did not affect the expression of PD-L1,JAK2,and p-STAT3 in tumor ***:GLSO could strengthen the anti-tumor effect of CTX and prolong the life span of H22 tumorbearing mice,while the underlying mechanism might be relevant to the amelioration effect of thymus function and inhibition of PD-1 expression in ***,these findings implied the promising role of GLSO in combination with CTX to extend the survival of patients in clinical chemotherapy of hepatocellular carcinoma.

关键词： carcinoma,hepatocellular cyclophosphamide survival programmed cell death 1 receptor Ganoderma Lucidum SporeOil

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Tetramic acid-motif natural products from a marine fungus Tolypocladium cylindrosporum FB06 and their anti-Parkinson activities

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Marine Life Science & Technology 2024年第1期6卷 84-92页

作者： Yuna Jung Chaesun Kwon Taeyeon Kim Jin Woo Lee Min-Kyoo Shin Sang Hee Shim Natural Products research institute College of PharmacySeoul National UniversitySeoul 08826Republic of Korea College of Pharmacy and research institute of pharmaceutical Sciences Seoul National UniversitySeoul 08826Republic of Korea College of Pharmacy Duksung Women’s UniversitySeoul 01369Republic of Korea

Tetramic acid-containing natural products are attracting significantly increasing attention from biologists and chemists due to their intriguing structures and biological *** the present study,two new tetramic acid alkaloids tolypyridone I(1)and tolypyridone J(2),together with five known ones(3–7),were isolated from cultures of a marine fungus Tolypocladium cylindrosporum FB06 isolate obtained from a marine sediment in Beaufort sea of North *** structures were elucidated using 1D,2D NMR,and *** configurations were established on the basis of 1H coupling constants,ROESY correlations and DP4 *** 2 was isolated as mixtures of rotational isomers with C-3 to C-7 axis between 4-hydroxy-2-pyridone and 1-ethyl-3,5-dimethylcyclohexane,hindering *** our unbiased screening to discover neuroprotective compounds in an in vitro Parkinson’s disease(PD)model,SH-SY5Y dopaminergic cells were treated with isolated compounds followed by treatment with 1-methyl-4-phenylpyridinium(MPP^(+)),a parkinsonian *** tested compounds,F-14329(7)significantly protected cells from MPP^(+)-induced ***^(+)-mediated cell death is known to be related to the regulation of Bcl-2 family proteins,specifically the down-regulation of anti-apoptotic Bcl-2 and the up-regulation of pro-apoptotic Bax *** with 2 mmol/L of MPP^(+)for 24 h significantly reduced Bcl-2 levels compared to control treated with ***,treatment with F-14329(7)attenuated such *** study demonstrates that tetramic acid-motif compounds could be potential lead compounds for treating PD.

关键词： Tolypocladium cylindrosporum Tetramic acid Tolypyridone Parkinson’s disease

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A chiral fluorescent probe for molecular recognition of basic amino acids in solutions and cells

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Chinese Chemical Letters 2024年第10期35卷 390-395页

作者： Chuan-Zhi Ni Ruo-Ming Li Fang-Qi Zhang Qu-Ao-Wei Li Yuan-Yuan Zhu Jie Zeng Shuang-Xi Gu School of Chemistry and Environmental Engineering School of Chemical Engineering & Pharmacy Pharmaceutical Research Institute Hubei Key Laboratory of Novel Reactor and Green Chemical Technology Wuhan Institute of Technology Nanjing Pusheng Biomedical Co. Ltd.

A novel and readily available binaphthyl-based fluorescent probe（S）-1 was designed and synthesized.（S）-1 can be used to not only chemoselectively discriminate 3 basic amino acids out of common amino acids, but also enantioselectively recognize histidine. Encouragingly, enantioselective imaging of histidine in cells was achieved for the first time by the probe（S）-1. These performances endowed it potential application in the chiral analysis of basic amino acids in asymmetric synthesis and cell imaging for diagnosis of diseases caused by racemization of histidine. Nuclear magnetic resonance（NMR） and mass spectrometry investigations suggested that different reaction extent of（S）-1 with L/D-histidine and different product structures generated the observed enantioselective fluorescent response. The molecular structures and thermodynamic stability of the complexes, formed from（S）-1 + Zn2+and enantiomers of histidine, were calculated by Gaussian 16 based on density functional theory（DFT） to validate the above action mechanism.

关键词： Basic amino acids Cell imaging Chemoselectivity Chiral recognition Enantioselectivity Fluorescent probe

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High-throughput discovery of highly selective reversible hMAO-B inhibitors based on at-line nanofractionation

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1772-1786页

作者： Yu Fan Jincai Wang Jingyi Jian Yalei Wen Jiahao Li Hao Tian Jacques Crommen Wei Bi Tingting Zhang Zhengjin Jiang institute of pharmaceutical Analysis/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs research/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education(MOE)of China/College of Pharmacy Jinan UniversityGuangzhou 510632China KU Leuven-University of Leuven Pharmaceutical AnalysisDepartment of Pharmaceutical and Pharmacological SciencesLeuven 3000Belgium Laboratory of Analytical pharmaceutical Chemistry Department of Pharmaceutical SciencesCIRMUniversity of LiegeLiege B-4000Belgium Department of Neurology the First Affiliated Hospital of Jinan University/Clinical Neuroscience Institutethe First Affiliated Hospital of Jinan UniversityGuangzhou 510630China

Human monoamine oxidase B(hMAO-B)has emerged as a pivotal therapeutic target for Parkinson's *** to adverse effects and shortage of commercial drugs,there is a need for novel,highly selective,and reversible hMAO-B inhibitors with good blood-brain barrier *** this study,a high-throughput at-line nanofractionation screening platform was established with extracts from Chuanxiong Rhizoma,which resulted in the discovery of 75 active compounds,including phenolic acids,volatile oils,and phthalides,two of which were highly selective novel natural phthalide hMAO-B inhibitors that were potent,selective,reversible and had good blood‒brain *** docking and molecular dynamics simulations elucidated the inhibition ***(IC_(50)=103 nmol/L;SI=645)and neocnidilide(IC_(50)=131 nmol/L;SI=207)demonstrated their excellent potential as hMAO-B *** offset the limitations of deactivating enzymes associated with irreversible hMAO-B inhibitors such as *** SH-SY5Y cell assays,sedanolide(EC_(50)=0.962μmol/L)and neocnidilide(EC_(50)=1.161μmol/L)exhibited significant neuroprotective effects,comparable to the positive drugs rasagiline(EC_(50)=0.896μmol/L)and safinamide(EC_(50)=1.079μmol/L).These findings underscore the potential of sedanolide as a novel natural hMAO-B inhibitor that warrants further development as a promising drug candidate.

关键词： Human monoamine oxidase B inhibitors High-throughput screening At-linenanofractionation Parkinson's disease Cellular neuroprotection Traditional Chinese medicines(TCMs)

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Reversibly size-switchable polyion complex micelles for antiangiogenic cancer therapy

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Chinese Chemical Letters 2024年第7期35卷 377-382页

作者： Mengjuan Sun Muye Zhou Yifang Xiao Hailei Tang Jinhua Chen Ruitao Zhang Chunjiayu Li Qi Ya Qian Chen Jiasheng Tu Qiyue Wang Chunmeng Sun NMPA Key Laboratory for research and Evaluation of pharmaceutical Preparations and Excipients China Pharmaceutical UniversityNanjing 210009China State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 211198China Department of Pharmaceutics School of PharmacyChina Pharmaceutical UniversityNanjing 211198China Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics China Pharmaceutical UniversityNanjing 210009China School of pharmaceutical Science Nanjing Tech UniversityNanjing 211816China

Size is one of the most important characteristics of nanoparticles to influence their biodistribution and antitumoral *** with large sizes have difficulty in deep tumor penetration,while small particles are easily removed from tumor tissues due to the high tumor interstitial fluid *** address these issues,an intelligent core-crosslinked polyion complex micelle(cPCM)with a reversibly sizeswitchable feature was engineered in this *** micelles are consisting of methoxy poly(ethylene glycol)-poly(D,L-lactide)copolymer(mPEG-PLA),mPEG-PLA-(HE)6CC,and mPEG-PLA-(RG)6CC at an optimal mass ratio of 6:1:1 with an antiangiogenic compound,dabigatran etexilate(DE),*** net charge inside the micelles is switchable when exposed to different pH conditions,thereby leading to revisable size-change of ***-loaded micelles(DE@cPCM)can swell and release drugs at the tumor sites with a mildly acidic pH,while they shrink and protect the cargo from leaking into the blood circulation with a neutral *** indicated that DE@cPCM can inhibit tumor angiogenesis in vitro and in vivo,thereby efficiently restraining tumor growth in a 4T1-bearing mouse ***,the sizeswitchable cPCM is a promising nanoplatform for targeting delivery of anticarcinogens into the matrix of tumor tissues.

关键词： Polyion complex micelle Size-switchable Revisable size-change pH response Antiangiogenic cancer

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A novel marine-derived anti-acute kidney injury agent targeting peroxiredoxin 1 and its nanodelivery strategy based on ADME optimization

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3232-3250页

作者： Ping Yu Tanwei Gu Yueyang Rao Weimin Liang Xi Zhang Huanguo Jiang Jindi Lu Jianglian She Jianmin Guo Wei Yang Yonghong Liu Yingfeng Tu Lan Tang Xuefeng Zhou Guangdong Provincial Key Laboratory of New Drug Screening Guangdong-Hong Kong-Macao Joint Laboratory for New Drug ScreeningSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology Guangdong Key Laboratory of Marine Materia MedicaSouth China Sea Institute of OceanologyChinese Academy of SciencesGuangzhou 510301China NMPA Key Laboratory for research and Evaluation of Drug Metabolism School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Guangdong Lewwin pharmaceutical research institute Co. Ltd.Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and ResearchGuangdong Engineering Research Center for Innovative Drug Evaluation and ResearchGuangzhou 510990China

Insufficient therapeutic strategies for acute kidney injury(AKI)necessitate precision therapy targeting its *** study reveals the new mechanism of the marine-derived anti-AKI agent,piericidin glycoside S14,targeting peroxiredoxin 1(PRDX1).By binding to Cys83 of PRDX1 and augmenting its peroxidase activity,S14 alleviates kidney injury efficiently in Prdx1-overexpression(Prdx1-OE)***,S14 also increases PRDX1 nuclear translocation and directly activates the Nrf2/HO-1/NQO1 pathway to inhibit ROS *** to the limited druggability of S14 with low bioavailability(2.6%)and poor renal distribution,a pH-sensitive kidney-targeting dodecanaminechitosan nanoparticle system is constructed to load S14 for precise treatment of AKI.L-Serine conjugation to chitosan imparts specificity to kidney injury molecule-1(Kim-1)-overexpressed *** developed S14-nanodrug exhibits higher therapeutic efficiency by improving the in vivo behavior of S14 *** encapsulation with micelles,the AUC_(0-t),half-life time,and renal distribution of S14 increase 2.5-,1.8-,and 3.1-fold,*** main factors contributing to the improved druggability of S14 nanodrugs include the lower metabolic elimination rate and UDPglycosyltransferase(UGT)-mediated *** summary,this study identifies a new therapeutic target for the marine-derived anti-AKI agent while enhancing its ADME properties and druggability through nanotechnology,thereby driving advancements in marine drug development for AKI.

关键词： Acute kidney injury Piericidin glycoside Peroxiredoxin 1 Nanodrug Kim-1 targeted ADME Marine drug Druggability

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Synthetic host-guest pairs as novel bioorthogonal tools for pre-targeting

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Chinese Chemical Letters 2024年第2期35卷 44-56页

作者： Yan-Long Ma Shi Yan Xiong-Jie Xu Hua Cao Ruibing Wang School of Chemistry and Chemical Engineering and Guangdong Cosmetics Engineering & Technology research Center Guangdong Pharmaceutical UniversityZhongshan 528458China State Key Laboratory of Quality research in Chinese Medicine and the Institute of Chinese Medical ScienceUniversity of MacaoMacao 999078China

Due to its simplicity, high efficiency, and chemo-selectivity, bioorthogonal chemistry has shown a great application potential in ***, four bioorthogonal pairs as targeting tools, including (strept)avidin/biotin, antibody/antigen, oligonucleotide hybridization and IEDDA tools, have been developed and applied in targeted ***, all of these tools still suffer from some limitations, such as difficult modification, biochemical fragility and larger molecular weight for biological association tools, as well as chemical instability for IEDDA *** host-guest pairs with relatively small molecular sizes not only possess strong chemical stability, but also have the features of fast conjugation rate, tunable binding affinity , easy modification, and high ***, they can be used as a novel non-covalent bioorthogonal tool for *** order to further promote the development of host-guest pairs as novel bioorthogonal tools for pre-targeted delivery, we firstly calculate their conversion rate to make researcher aware of their unique advantages;next, we summarize the recent research progress in this *** future perspectives and limitations of these unique tools will be *** review will provide a systemic overview of the development of synthetic host-guest pairs as novel bioorthogonal tools for pre-targeting, and may serve as a “go for” resort for researchers who are interested in searching for new synthetic tools to improve pre-targeting.

关键词： Bioorthogonal chemistry Synthetic host-guest pairs Pre-targeting Molecular recognition Biomedical applications

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