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Simple and versatile in situ thermo-sensitive hydrogel for rectal administration of SZ-A to alleviate inflammation and repair mucosal barrier in ulcerative colitis

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Chinese Chemical Letters 2024年第6期35卷 462-468页

作者： Yu Yan Jiawei Song Dongdong Liu Zihan Liu Jialing Cheng Zhiyang Chen Yanfang Yang Weizhe Jiang Hongliang Wang Jun Ye Yuling Liu State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China College of Pharmacy Guangxi Medical UniversityNanning 530021China Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

Ulcerative colitis(UC)is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon and disrupted intestinal *** mori(Sangzhi)alkaloids(SZ-A),derived from twigs of mulberry,were approved by the National medical Products Administration in 2020 for treating type 2 diabetes *** evidence has confirmed that SZ-A also alleviates non-alcoholic fatty liver disease and ameliorates inflammation,indicating its potential to address inflammation in ***,the treatment of UC faces challenges due to low drug delivery efficiency and short retention *** overcome these challenges,an injectable and adherent in-situ thermo-sensitive hydrogel containing SZ-A was developed for rectal drug delivery,utilizing the thermo-sensitive polymers Poloxamer 407and *** thermo-sensitive hydrogel system was designed with a moderate gelation temperature of 32±0.5℃,a short gelation time of 64 s,a p H range of 7-10,high moisturizing capability exceeding 90%,and moderate mechanical strength of 4-5 *** a rat model with UC,the in situ thermo-sensitive hydrogel significantly extended the retention time at the colonic site and enabled sustained release after rectal *** of UC were markedly reduced following rectal administration of SZ-A thermosensitive ***,the release of inflammatory factors,such as interleukin-1β(IL-1β),IL-6,IL-18,tumor necrosis factor-α(TNF-α),and transforming growth factor-β1(TGF-β1),significantly decreased in the SZ-A thermo-sensitive hydrogel *** integrity of the colonic mucosal barrier was significantly enhanced following the application of SZ-A thermo-sensitive *** conclusion,rectal administration of SZ-A in situ thermo-sensitive hydrogel effectively alleviated UC symptoms,inhibited the secretion of inflammatory factors,and promoted the repair of the colonic mucosal *** approach holds promise as a potential treatment for UC.

关键词： Ulcerative colitis SZ-A Thermo-sensitive hydrogel Rectal administration Alleviation of inflammation Mucosal barrier repair

Highly oxygenated clerodane furanoditerpenoids from the leaves and twigs of Croton yunnanensis

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Chinese Journal of Natural Medicines 2024年第10期22卷 945-954页

作者： WANG Didi MEI Fang NIE Jinchun LI Zhenwei ZHANG Daidi GUO Dean LI Wei School of Pharmacy Guizhou Medical University Zhongshan institute for Drug Discovery Shanghai Institute of Materia Medica Chinese Academy of Sciences

The phytochemical investigation of the leaves and twigs of Croton yunnanensis resulted in the isolation of eight new clerodane furanoditerpenoids, named croyunfuranoids A-H（1-8）, along with three known analogs（9-11）. The structures of these compounds were elucidated using spectroscopic analyses, and their absolute configurations were determined through a combination of electronic circular dichroism（ECD） calculations and single-crystal X-ray diffraction. Notably, Croyunfuranoid D（4） is identified as a rare 18,19-dinor-clerodane diterpenoid. Additionally, the structure of a previously reported diterpenoid, crotonyunnan B, was *** isolated compounds were evaluated for their inhibitory activities on nitric oxide（NO） production in LPS-induced RAW 264.7 macrophages. Among them, compounds 5 and 6 demonstrated significant inhibitory effects, with IC50values of 20.33 ± 2.31 and 22.80 ±1.31 μmol·L-1, respectively.

关键词： Clerodane furanoditerpenoid Croton yunnanensis Euphorbiaceae NO inhibitory activity

Reversing artemisinin resistance by leveraging thermo-responsive nanoplatform to downregulating GSH

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Chinese Chemical Letters 2024年第6期35卷 392-397页

作者： Yong-Dan Zhao Yidan Wang Rongrong Wang Lina Chen Hengtong Zuo Xi Wang Jihong Qiang Geng Wang Qingxia Li Canqi Ping Shuqiu Zhang Hao Wang School of Pharmacy Shanxi Medical UniversityTaiyuan 030001China National Center for Nanoscience and Technology Beijing 100190China Artemisinin Research Center Institute of Chinese Materia MedicaBeijing 100700China

Artemisinin(ART)resistance has been an emerging clinical problem,severely compromising antimalarial efficacy and threatening the global malaria elimination *** intensive studies about the molecular mechanism for ART resistance are under way,no effective therapeutic targets for reversing resistance have been ***,we explore glutathione(GSH)as a therapeutic target to develop a thermo-responsive nanoplatform to specifically co-deliver ART and GSH synthesis inhibitor(L-buthionine sulfoximine,BSO)in a sustained manner,effectively reversing ART resistance in *** combining with BSO,ART exerts increased antimalarial activity with reduced half-maximal inhibitory concentration(IC50)by 7.43-fold in ART-resistant *** work reveals that the GSH in ART-resistant parasites can be a promising therapeutic target for reversing ART resistance,paving the way for developing drug candidates and intelligent nanomedicines in malaria therapy.

关键词： Nanomedicines Drug delivery Artemisinins resistance Malaria Glutathione

Integrated gut microbiota,plasma metabolomics and network pharmacology to reveal the anti-ischemic stroke effect of cooked rhubarb

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Traditional Medicine Research 2024年第9期9卷 1-13页

作者： Ting Li Lan-Fang Tan Lin Shen Jie-Hui Kuang Si-Kai Zhan Bang Liu Jia-Le Cai Sheng-Wang Liang Ming-Hua Xian Shu-Mei Wang School of Chinese materia medica Guangdong Pharmaceutical UniversityGuangzhou 510006China Key Laboratory of Digital Quality Evaluation of Chinese materia medica of State Administration of TCM School of Chinese Materia MedicaGuangdong Pharmaceutical UniversityGuangzhou 510006China Engineering&Technology Research Center for Chinese materia medica Quality of the Universities of Guangdong Province School of Chinese Materia MedicaGuangdong Pharmaceutical UniversityGuangzhou 510006China Guangxi Key Laboratory of Functional Phytochemicals Research and Utilization Guangxi Institute of BotanyChinese Academy of SciencesGuilin 541006China Traditional Chinese Medicine Resource Germplasm Bank Management Center Yunfu 527300China

Background:Cooked rhubarb(CR)is obtained by steaming raw rhubarb(Rheum palmatum L.,Rheum officinale Baill.,or Rheum tanguticum *** Balf.)with millet *** is used as a traditional Chinese medicine for treating cerebral stroke,where patients often face severe *** study explored the pharmacological effects and mechanisms of CR against ischemic stroke(IS)in *** used integrated analysis of gut microbiota,metabolomics,and network ***:The compounds in CR were identified using LC-MS/*** impact of CR on rat middle cerebral artery occlusion/reperfusion(MCAO/R)-induced cerebral infarct size and brain tissue pathology was assessed through 2,3,5-triphenyl tetrazolium chloride and HE *** in hemorheology were measured by evaluating blood viscosity,and serum levels of pro-inflammatory cytokine were also *** microbiota composition was analyzed through 16S rRNA gene *** metabolites were examined using untargeted metabolomics and Spearman correlation *** pseudo-germ-free test was used to determine whether tumour necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)improvement in IS are dependent on gut ***:In vivo studies showed CR enhances neurobehavioral function in MCAO/R rats and reduces cerebral infarction *** also ameliorates brain and intestinal barrier damage caused by *** also decreased inflammation and oxidative stress in IS ***,CR promotes the growth of Akkermansia and Verrucomicrobia,aiding in intestinal barrier ***,CR primarily influences the primary bile acid biosynthesis *** pseudo-germ-free experiment and network pharmacology confirmed TNF-αand IL-1βas potential *** relies on gut microbiota for its anti-inflammatory effects to improve ***:Cooked rhubarb offers neuroprotective benefits by enhancing beneficial bacteria abundance and regulating bile acid *** emerges as a potential therapeutic agent for

关键词： cooked rhubarb ischemic stroke gut microbiota metabolomics

Molecular quantification of herbs(Herb-Q):a pyrosequencingbased approach and its application in Pinellia ternata

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Chinese Journal of Natural Medicines 2024年第7期22卷 663-672页

作者： PEI Yifei LIU Ziyi YU Dade ZHANG Xiangyu SUN Wei CHEN Xiaofang FENG Xue LI Xiwen institute of Chinese materia medica China Academy of Chinese Medical SciencesBeijing 100700China Bijie institute of Traditional Chinese Medicine Bijie 551700China The Key Laboratory for Health Industry of Bijie Bijie Medical CollegeBijie 551700China

Variations in herb dosage due to species adulteration and dosing inaccuracies can substantially affect clinical safety and *** species quantification remains challenging,as current methods often yield inconsistent *** study introduces a novel pyrosequencing-based technique,termed herb molecular quantification(Herb-Q),designed to precisely quantify herbal *** evaluated its effectiveness using Pinellia ternata and five of its ***,we assessed commonly used DNA barcodes with sequences from a public database,identifying two candidate regions,Maturase K(matK)and internal transcribed spacer 2(ITS2),for screening specific single nucleotide polymorphism(SNP)loci,allowing for species-specific *** loci were validated by amplifying and sequencing genomic material from collected *** validation studies showed that Herb-Q demonstrated excellent linearity,accuracy,repeatability,and detection *** established quantitative standard curves with high R^(2)values(>0.99)to enable precise species quantification,which were combined with external standards to provide clear and accurate visual quantification *** average bias in quantifying the tuber of *** was 2.38%,confirming that Herb-Q can accurately identify and quantify herbal product ***,the entire quantification process took less than 4 *** study presents a novel,rapid method for accurately quantifying species in herbal products and advances the application of DNA barcoding from species identification to quantitative detection.

关键词： Quantification Adulterant DNA barcodes Single nucleotide polymorphism

Neg-Entropy Mechanism as a Target for Natural Medicines

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Engineering 2024年第7期38卷 11-12页

作者： Tian-Le Gao Hui-Hui Guo Jian-Dong Jiang institute of materia medica Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China institute of Medicinal Biotechnology Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

Current strategies for drug discovery research mainly focus on molecular targets,in which structure biology plays a central role,such as the detailed mechanism of a drug-target *** principle of this approach is the presumed molecular mechanism or genetic background of the disease being *** this approach has brought progress in understanding the mode of action for some drugs,most prevalent illnesses-especially chronic diseases-are multifactorial and present with a group of symptoms,as is often the case in cardiovascular diseases,metabolic disorders,cancers,and so *** newly emerging term“multi-morbidity”(i.e.,multiple co-occurring diseases)describes a grand challenge for this strategy,and successful drug intervention for multimorbidity should be multifaceted[1].So,our research team has shifted its attention to a new direction that views the disease as a whole instead of a single-molecule abnormality,and focusing on drugs with multiple targets.

关键词： drugs diseases cardiovascular

Review on dietary supplements as an effective improvement of Alzheimer's disease:focus on structures and mechanisms

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Food Science and Human Wellness 2024年第4期13卷 1787-1805页

作者： Sheng Li Yinling Wei Zhenzhen Liang Lingli Guo Xiaojiang Hao Yu Zhang State Key Laboratory of Phytochemistry and Plant Resources in West China Kunming Institute of BotanyChinese Academy of SciencesKunming 650201China College of Traditional Chinese materia medica Shenyang Pharmaceutical UniversityShenyang 110016China

Alzheimer’s disease(AD),the major form of neurodegenerative diseases that can severely impede normal cognitive function,makes it one of the most common fatal *** are currently over 50 million AD patients *** neuropathology of AD is perplexing and there is a scarcity of disease-modifying ***,early diagnosis of AD has been made possible with the discovery of biological markers associated with pathology,providing strong support for the improvement of the disease *** search for inhibitors of AD markers from dietary supplements(DSs)has become a major hot *** with the widespread use of DSs,DSs containing polyphenols,alkaloids,terpenes,polysaccharides and other bioactive components can prevent AD by reducing Aβdeposition,inhibiting tau protein hyperphosphorylation,reconstructing synaptic dysfunction,weakening cholinesterase activity,regulating mitochondrial oxidative stress,neuronal inflammation and *** review summarizes the anti-AD effects of the main DSs and their bioactive constituents,as well as the potential molecular mechanisms covers from 2017 to ***,we discussed the opportunities and challenges faced by DSs in the process of AD prevention and treatment,aiming to further provide new perspectives for functional food development.

关键词： Dietary supplements Bioactive ingredients Alzheimer’s disease Mechanism of action

Antidepressant effects of Peiyuan Jieyu formula in a mouse model of chronic stress in conjunction with lipopolysaccharide-induced depression

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Journal of Traditional Chinese medical Sciences 2024年第1期11卷 111-119页

作者： Qin Tang Yu Li Tao Yang Xiaoxu Fan Lina Li Hongsheng Chang School of Chinese materia medica Beijing University of Chinese MedicineBeijing 102488China institute of Chinese materia medica China Academy of Chinese Medical SciencesBeijing 100700China Chinese Medicine Department Tianjin Institute of Pharmaceutical InspectionTianjin 300070China School of Chinese Medicine Beijing University of Chinese MedicineBeijing 102488China

Objective:To explore the mechanism of the Peiyuan Jieyu formula in treating depression by assessing its impact on a lipopolysaccharide-induced(LPS-induced)depression mouse ***:We created a mouse model of depression by exposing mice that had previously received chronic stress to intraperitoneal LPS *** mice were divided into the following groups:control,model,fluoxetine,Tiansi Yin,Sini powder,and low-,medium-,and high-dose Peiyuan Jieyu formula *** swim and tail suspension tests were used to assess the efficacy of the depression(despair)model,and weight gain rates were also ***,serum levels of various depression and inflammation-associated molecules,including tumor necrosis factor-a(TNF-a),interferon-γ(IFN-γ),tryptophan,5-hydroxytryptamine,kynurenine(KYN),and kynurenic acid(KA)were ***,the expression levels of ionic calcium-binding adaptor molecule-1(IBA-1)and indoleamine 2,3-dioxygenase(IDO)mRNA in hippocampal microglia were ***:The model group displayed greater despair-associated immobility,which was shortened in response to various doses of Peiyuan Jieyu ***,formula administration significantly reduced serum TNF-a levels and hippocampal IDO mRNA *** high formula dose also reduced IFN-γand IBA-1 levels,the latter was also decreased in response to the medium formula ***,the low formula dose reduced serum KYN level and KYN/tryptophan(TRP)and KYN/KA ***:The Peiyuan Jieyu formula holds immense potential in treating depression in a mouse model,potentially inhibiting inflammation and improving TRP-KYN metabolic disorders.

关键词： Peiyuan Jieyu formula Depression Chronic stress Lipopolysaccharide Inflammation Tryptophan pathway

Study Decodes Dimerization and Antidepressant Recognition at Noradrenaline Transporter

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Bulletin of the Chinese Academy of Sciences 2024年第2期38卷 117-118页

作者： JIANG Qingling Shanghai institute of materia medica Chinese Academy of Sciences

Noradrenaline transporter,also known as the norepinephrine transporter(NET),is a member of the monoamine transporters(MATs)family,which also includes serotonin transporter(SERT)and dopamine transporter(DAT).These transporters collectively regulate neurotransmitter concentrations at synapses and maintain neurotransmitter balance in the body.

关键词： dopamine collective maintain