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Nuciferine alleviates collagen-induced arthritic in rats by inhibiting the proliferation and invasion of human arthritis-derived fibroblast-like synoviocytes and rectifying Th17/Treg imbalance

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chinese Journal of Natural medicines 2024年第4期22卷 341-355页

作者： WANG Hao GENG Xiaolong AI Fangbin YU Zhilun ZHANG Yan ZHANG Beibei LV Cheng GAO Ruiyang YUE Bei DOU Wei The moe key laboratory of Standardization of chinese medicines Shanghai Key Laboratory of Compound Chinese Medicinesand the SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese MedicineInstitute of Chinese Materia MedicaSchool of Traditional Chinese Materia MedicaShanghai University of Traditional Chinese Medicine(SHUTCM)Shanghai 201203China

Rheumatoid arthritis(RA)is a chronic autoimmune disorder marked by persistent synovial inflammation and joint degradation,posing challenges in the development of effective ***,an alkaloid found in lotus leaf,has shown promising anti-inflammatory and anti-tumor effects,yet its efficacy in RA treatment remains *** study investigated the antiproliferative effects of nuciferine on the MH7A cell line,a human RA-derived fibroblast-like synoviocyte,revealing its ability to inhibit cell proliferation,promote apoptosis,induce apoptosis,and cause G1/S phase ***,nuciferine significantly reduced the migration and invasion capabilities of MH7A *** therapeutic potential of nuciferine was further evaluated in a collagen-induced arthritis(CIA)rat model,where it markedly alleviated joint swelling,synovial hyperplasia,cartilage injury,and inflammatory *** also improved collagen-induced bone erosion,decreased pro-inflammatory cytokines and serum immunoglobulins(IgG,IgG1,IgG2a),and restored the balance between T helper(Th)17 and regulatory T cells in the spleen of CIA *** results indicate that nuciferine may offer therapeutic advantages for RA by decreasing the proliferation and invasiveness of FLS cells and correcting the Th17/Treg cell imbalance in CIA rats.

关键词： Rheumatoid arthritis Collagen-induced arthritis Fibroblast-like synoviocyte Immune imbalance Nuciferine

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Notoginsenoside Ft1 inhibits colorectal cancer growth by increasing CD8^(+)T cell proportion in tumor-bearing mice through the USP9X signaling pathway

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chinese Journal of Natural medicines 2024年第4期22卷 329-340页

作者： FENG Yutao LI Yuan MA Fen WU Enjiang CHENG Zewei ZHOU Shiling WANG Zhengtao YANG Li SUN Xun ZHANG Jiwei Shanghai key laboratory of Compound chinese medicines The MOE Key Laboratory for Standardization of Chinese MedicinesInstitute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghai 201203China Gastrointestinal surgery Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China

The management of colorectal cancer(CRC)poses a significant challenge,necessitating the development of innovative and effective *** research has shown that notoginsenoside Ft1(Ng-Ft1),a small molecule,markedly inhibits subcutaneous tumor formation in CRC and enhances the proportion of CD8^(+)T cells in tumor-bearing mice,thus restraining tumor *** into the mechanism revealed that Ng-Ft1 selectively targets the deubiquitination enzyme USP9X,undermining its role in shieldingβ-*** leads to a reduction in the expression of downstream effectors in the Wnt signaling *** findings indicate that Ng-Ft1 could be a promising small-molecule treatment for CRC,working by blocking tumor progression via the Wnt signaling pathway and augmenting CD8^(+)T cell prevalence within the tumor environment.

关键词： Notoginsenoside Ft1 Colorectal cancer CD8^(+)T cell Ubiquitin-specific peptidase 9 X-linked β-Catenin Wnt

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Total flavonoids of Astragalus membranaceus protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice by inhibiting ferroptosis through SLC7A11/GPX-4 signaling pathway

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Food Science and Human Wellness 2024年第1期13卷 414-420页

作者： Zitian Gao Gaorui Wang Yujie Chen Wuke Yuan Jun Cai Aiping Feng Jie Fang Qi Xu Xiaojun Wu School of Public Health Shanghai University of Traditional Chinese MedicineShanghai 201203China Shanghai key laboratory of Compound chinese medicines The Ministry of Education(MOE)Key Laboratory for Standardization of Chinese MedicineInstitute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghai 201203China Longhua Hospital affiliated to Shanghai University of Traditional chinese medicine Shanghai University of Traditional Chinese MedicineShanghai 201203China

Parkinson’s disease(PD)is a common neurodegenerative disorder with no *** membranaceus is used in chinese culture as a food supplement to boost *** present study aimed to explore the neuroprotective effects of total flavonoids extracted from ***(TFA)and their protective *** offered neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)in the mouse model of Parkinsonism,by improving behavior performance in the gait analysis and pole test,and inhibiting the decline of tyrosine hydroxylase(TH)positive neurons and TH protein expression in substantia nigra of *** also prevented 1-methyl-4-phenylpyridinium(MPP+)induced neurotoxicity in SHSY5Y cells,by increasing GSH and GSH/GSSG ratio,and reducing reactive oxygen *** addition,the neuroprotective effects of TFA were associated with its ability to restore MPTP/MPP+induced downregulation of SLC7A11 and glutathione peroxidase 4(GPX-4).In conclusion,we demonstrated that TFA exerted significant neuroprotection against MPTP/MPP+induced neurodegeneration by inhibiting ferroptosis through the regulation of SLC7A11/GPX-4 axis,suggesting the use of TFA as a possible food supplement in the prevention of PD.

关键词： Parkinson’s disease Total fl avonoids of Astragalus membranaceus Ferroptosis SLC7A11

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Allosteric regulation of Keap1 by 8b-hydroxy-acyclocostunolide for the treatment of acute lung injury

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4174-4178页

作者： Juan Zhang Min Zhang Qi-Meng Zhu Xin-Rong Xu Yan-Li Feng Sheng Lin Feng Qiu Cheng-Peng Sun School of chinese Materia Medic1 Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese MedicineTianjin University of Traditional Chinese MedicineTianjin 301617China key laboratory of chinese internal medicine of Ministry of Education and Beijing Dongzhimen HospitalBeijing University of Chinese MedicineBeijing 100700China

To the Editor:Acute lung injury(ALI)is a debilitating lung disease characterized by pulmonary edema,diffuse alveolar damage,and uncontrolled neutrophil *** cases of ALI can potentially lead to the development of acute respiratory distress syndrome(ARDS),which can lead to impaired respiratory function,multiorgan dysfunction,and an extremely high mortality *** may be caused by various factors,including aspiration,severe pneumonia,sepsis,trauma,fatty embolism,pancreatitis,and blood *** clinical approaches to treating ALI/ARDS include mechanical ventilation,extracorporeal membrane oxygenation(ECMO),and other supportive therapies5,***,ALI/ARDS is an urgent problem that needs to be addressed in the field of respiratory critical care and innovative mechanisms and therapies6.

关键词： Macrophage overactivation Keap1 8b-Hydroxy-a-cyclocostunolide Nrf2 Acute lung injury

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A nitric oxide-triggered hydrolysis reaction to construct controlled self-assemblies with complex topologies

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Science China Chemistry 2024年第4期67卷 1289-1299页

作者： Wenzhuo Chen Yuping Tang Shuai Chen Zipei Chen Jia He Hongbin Huo Juan Zhang Jiajia Li Fei Yan Wei Tian laboratory of Shaanxi Administration of Traditional chinese medicine for TCM Compatibility Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs ResearchCollege of PharmacyShaanxi University of Chinese MedicineXianyang 712046China Shaanxi key laboratory of Macromolecular Science and Technology Xi’an Key Laboratory of Hybrid Luminescent Materials and Photonic DeviceMOE Key Laboratory of Material Physics and Chemistry under Extraordinary ConditionsSchool of Chemistry and Chemical EngineeringNorthwestern Polytechnical UniversityXi’an 710072China Department of Polymeric Materials School of Materials Science and EngineeringTongji UniversityShanghai 201804China

Hydrolysis reactions are capable of directing the non-equilibrium assembly of biomolecular scaffolds to realize sophisticated structures and functions in natural ***,utilizing the proper hydrolysis reactions to construct controlled assemblies with complex topologies is still an arduous challenge in artificial systems and needs to be ***,we report a nitric oxide(NO)-triggered slow hydrolysis strategy for the controlled construction of biomimetic supramolecular toroids(STs),thus realizing their visualization of intermediate structures and regulation of geometry *** presented protocol harnesses hydrolysis reactions to control of non-equilibrium self-assembly processes for the construction of self-assemblies with complex topologies successfully,which sheds light on how the hydrolysis reaction rate can modulate the kinetic pathway of assembly,thus realizing the artificial establishment of bio-inspired hierarchical structures.

关键词： supramolecular toroids controlled self-assembly nitic oxide-triggered hydrolysis pathway regulation

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Selective type II TRK inhibitors overcome xDFG mutation mediated acquired resistance to the second-generation inhibitors selitrectinib and repotrectinib

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Acta Pharmaceutica Sinica B 2024年第2期14卷 517-532页

作者： Shuang Xiang Xiaoyun Lu International Cooperative laboratory of Traditional chinese medicine Modernization and Innovative Drug Discovery of chinese Ministry of Education(moe) Guangdong Provincial Key Laboratory of New Drug Design and EvaluationGuangzhou City Key Laboratory of Precision Chemical Drug DevelopmentSchool of PharmacyJinan UniversityGuangzhou 510632China

Neurotrophic receptor kinase(NTRK) fusions are actionable oncogenic drivers of multiple pediatric and adult solid tumors,and tropomyosin receptor kinase(TRK) has been considered as an attractive therapeutic target for "pan-cancer" harboring these ***,two generations TRK inhibitors have been *** representative second-generation inhibitors selitrectinib and repotrectinib were designed to overcome clinic acquired resistance of the first-generation inhibitors larotrectinib or entrectinib resulted from solvent-front and gatekeeper on-target ***,xDFG(TRKAG667C/A/S,homologous TRKCG696C/A/S) and some double mutations still confer resistance to selitrectinib and repotrectinib,and overcoming these resistances represents a major unmet clinical *** this review,we summarize the acquired resistance mechanism of the first-and second-generation TRK inhibitors,and firstly put forward the emerging selective type Ⅱ TRK inhibitors to overcome xDFG mutations mediated ***,we concluded our perspectives on new challenges and future directions in this field.

关键词： NTRK fusions TRK kinase Clinical resistance xDFG mutations Selective type II inhibitors

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Enhancing cancer immunotherapy:Nanotechnology-mediated immunotherapy overcoming immunosuppression

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Acta Pharmaceutica Sinica B 2024年第9期14卷 3834-3854页

作者： Yunna Chen Qianqian Zhou Zongfang Jia Nuo Cheng Sheng Zhang Weidong Chen Lei Wang key laboratory of Molecular Biology(Brain diseases) Anhui University of Chinese MedicineHefei 230012China moe-Anhui Joint Collaborative Innovation Center for Quality Improvement of Anhui Genuine chinese Medicinal Materials Hefei 230012China Anhui Province key laboratory of chinese Medicinal Formul1 Hefei 230012China

Immunotherapy is an important cancer treatment method that offers hope for curing cancer *** immunotherapy has achieved initial success,a major obstacle to its widespread adoption is the inability to benefit the majority of *** success or failure of immunotherapy is closely linked to the tumor’s immune ***,there has been significant attention on strategies to regulate the tumor immune microenvironment in order to stimulate anti-tumor immune responses in cancer *** distinctive physical properties and design flexibility of nanomedicines have been extensively utilized to target immune cells(including tumor-associated macrophages(TAMs),T cells,myeloid-derived suppressor cells(MDSCs),and tumor-associated fibroblasts(TAFs)),offering promising advancements in cancer *** this article,we have reviewed treatment strategies aimed at targeting various immune cells to regulate the tumor immune *** focus is on cancer immunotherapy models that are based on nanomedicines,with the goal of inducing or enhancing anti-tumor immune responses to improve *** is worth noting that combining cancer immunotherapy with other treatments,such as chemotherapy,radiotherapy,and photodynamic therapy,can maximize the therapeutic ***,we have identified the challenges that nanotechnology-mediated immunotherapy needs to overcome in order to design more effective nanosystems.

关键词： Immunotherapy Nanomedicine Tumor immunosuppressive microenvironment Cancer T cells Immunogenic cell death Immune checkpoint inhibitors Extracellular matrix

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Mechanism of Qili Qiangxin Capsule for Heart Failure Based on miR133a-Endoplasmic Reticulum Stress

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chinese Journal of Integrative medicine 2024年第5期30卷 398-407页

作者： JI Xiao-di YANG Ding CUI Xi-yuan LOU Li-xia NIE Bo ZHAO Jiu-li ZHAO Ming-jing WU Ai-ming Dongzhimen Hospital Affiliated to Beijing University of chinese medicine Key Laboratory of Chinese Internal Medicine of Ministry of Education and BeijingBeijing 100700China Department of Traditional chinese medicine Fuwai HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100037China

Objective:To investigate the pharmacological mechanism of Qili Qiangxin Capsule(QLQX)improvement of heart failure(HF)based on miR133a-endoplasmic reticulum stress(ERS)***:A left coronary artery ligation-induced HF after myocardial infarction model was used in this *** were randomly assigned to the sham group,the model group,the QLQX group[0.32 g/(kg·d)],and the captopril group[2.25 mg/(kg·d)],15 rats per group,followed by 4 weeks of *** function such as left ventricular ejection fraction(EF),fractional shortening(FS),left ventricular systolic pressure(LVSP),left ventricular end diastolic pressure(LVEDP),the maximal rate of increase of left ventricular pressure(+dp/dt max),and the maximal rate of decrease of left ventricular pressure(–dp/dt max)were monitored by echocardiography and *** and eosin(HE)and Masson stainings were used to visualize pathological changes in myocardial *** m RNA expression of mi R133a,glucose-regulated protein78(GRP78),inositol-requiring enzyme 1(IRE1),activating transcription factor 6(ATF6),X-box binding protein1(XBP1),C/EBP homologous protein(CHOP)and Caspase 12 were detected by *** protein expression of GRP78,p-IRE1/IRE1ratio,cleaved-ATF6,XBP1-s(the spliced form of XBP1),CHOP and Caspase 12 were detected by Western *** T-mediated d UTP nick-end labeling(TUNEL)staining was used to detect the rate of ***:QLQX significantly improved cardiac function as evidenced by increased EF,FS,LVSP,+dp/dt max,-dp/dt max,and decreased LVEDP(P<0.05,P<0.01).HE staining showed that QLQX ameliorated cardiac pathologic damage to some *** staining indicated that QLQX significantly reduced collagen volume fraction in myocardial tissue(P<0.01).Results from RT-PCR and Western blot showed that QLQX significantly increased the expression of mi R133a and inhibited the m RNA expressions of GRP78,IRE1,ATF6 and XBP1,as well as decreased the protein expressions of GRP78,cleave

关键词： heart failure Qili Qiangxin Capsule miR133a endoplasmic reticulum stress apoptosis

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Chiral resolution of furofuran lignans and their derivatives from the stems of Dendrobium 'Sonia'

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chinese Journal of Natural medicines 2024年第10期22卷 937-944页

作者： QIU Kaimei QIU Hao XIE Yanqiao ZHANG Siyu ZHANG Qian WANG Zhengtao HAN Zhuzhen YANG Li The moe key laboratory of Standardization of chinese medicines The SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines The Shanghai Key Laboratory for Compound Chinese Medicines Institute of Chinese Materia Medica Shanghai University of Traditional Chinese Medicine

Five new furofuran lignans and their derivatives,（-）-glaberide I 4-O-β-D-glucopyranoside（1a）,（+）-glaberide I 4-O-β-D-glucopyranoside（1b）,（+）-glaberide I 7'-ethoxy-4-O-β-D-glucopyranoside（2a）,（-）-glaberide I 7'-ethoxy-4-O-β-D-glucopyranoside（2b）, and（-）-isoeucommin A（3b）, along with fifteen known analogs were isolated from the stems of Dendrobium 'Sonia'. These compounds were classified into ten pairs of enantiomers or diastereoisomers via chiral resolution, and their structures were determined based on extensive spectroscopic data. Their absolute configurations were determined by hydrolysis, comparison of experimental and calculated electronic circular dichroism（ECD） data, and single-crystal X-ray diffraction analysis. The isolates were evaluated for their ability to inhibit nitric oxide（NO） production in RAW264.7 cells. Among them, syringaresinol（5） exhibited prominent inhibition activity, with an IC50 value of 28.4 ± 3.0 μmol·L-1, and there was a slight difference between 5a, 5b and the racemic mixture 5.

关键词： Anti-inflammatory Chiral resolution Dendrobium 'Sonia' Diastereoisomers Enantiomers Furofuran lignans

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Banxia Xiexin Decoction Alleviated Cerebral Glucose Metabolism Disorder by Regulating Intestinal Microbiota in APP/PS1 Mice

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chinese Journal of Integrative medicine 2024年第8期30卷 701-712页

作者： GAO Chen-yan QIN Gao-feng ZHENG Ming-cui TIAN Mei-jing HE Yan-nan WANG Peng-wen key laboratory of chinese internal medicine of Ministry of Education and Beijing Dongzhimen HospitalBeijing University of Chinese MedicineBeijing100700China Neurology Department Binzhou Medical University HospitalBinzhouShandong Province256603China

Objective To identify whether Banxia Xiexin Decoction(BXD)alleviates cerebral glucose metabolism disorder by intestinal microbiota regulation in APP/PS1 *** Forty-five 3-month-old male APP/PS1 mice were divided into 3 groups using a random number table(n=15 per group),including a model group(MG),a liraglutide group(LG)and a BXD group(BG).Fifteen 3-month-old male C57BL/6J wild-type mice were used as the control group(CG).Mice in the BG were administered BXD granules by gavage at a dose of 6 g/(kg·d)for 3 months,while mice in the LG were injected intraperitoneally once daily with Liraglutide Injection(25 nmol/kg)for 3 ***,liquid chromatography with tandem-mass spectrometry was used to analyze the active components of BXD granules and the medicated serum of ***,the cognitive deficits,Aβpathological change and synaptic plasticity markers,including synaptophysin(SYP)and postsynaptic density protein 95(PSD95),were measured in APP/PS1 *** glucose uptake was detected by micropositron emission *** microbial constituents were detected by 16S rRNA *** levels of intestinal glucagon-like peptide 1(GLP-1)and cerebral GLP-1 receptor(GLP-1R),as well as the phosphoinositide-3-kinase/protein kinase B/glycogen synthase kinase-3β(PI3K/Akt/GSK3β)insulin signaling pathway were determined by immunohistochemical(IHC)staining and Western blot analysis,*** BXD ameliorated cognitive deficits and Aβpathological features(P<0.01).The expressions of SYP and PSD95 in the BG were higher than those in the MG(P<0.01).Brain glucose uptake in the BG was higher than that in the MG(P<0.01).The intestinal microbial composition in the BG was partially *** levels of intestinal GLP-1 in the BG were higher than those in the MG(P<0.01).Compared with the MG,the expression levels of hippocampal GLP-1R,Akt,PI3K and p-PI3K in the BG were significantly increased(P<0.01),while the levels of GSK3βwere reduced(P<0.01).Conclusion BXD

关键词： Banxia Xiexin Decoction Alzheimer's disease intestinal microbiota glucagon-like peptide 1 cerebral insulin resistance phosphoinositide-3-kinase/proteinkinase B/glycogen synthase kinase-3β chinese medicine

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