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Treadmill exercise in combination with acousto-optic and olfactory stimulation improves cognitive function in APP/PS1 mice through the brain-derived neurotrophic factor-and Cygb-associated signaling pathways

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Neural Regeneration Research 2025年第9期20卷 2706-2726页

作者： Biao Xiao Chaoyang Chu Zhicheng Lin Tianyuan Fang Yuyu Zhou Chuxia Zhang Jianghui Shan Shiyu Chen Liping Li Department of physiology and pharmacology Health Science CenterNingbo UniversityNingboZhejiang ProvinceChina Ningbo Key laboratory of Behavioral Neuroscience Health Science CenterNingbo UniversityNingboZhejiang ProvinceChina Key laboratory of Addiction Research of Zhejiang Province NingboZhejiang ProvinceChina

A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's ***,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and ***,nonpharmacological interventions aimed at inducing adult neurogenesis are currently *** individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully *** this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 *** deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease ***,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus *** findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 ***,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice

关键词： acousto-optic stimulation adult neurogenesis Alzheimer's disease amyloid precursor protein/presenilin 1 mice amyloid-beta deposition brain cell apoptosis cognitive impairment depression-like behavior involuntary treadmill exercise olfactory stimulation serum metabolites

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Akkermansia muciniphila: a promising target for the therapy of metabolic syndrome and related diseases

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Chinese Journal of natural Medicines 2019年第11期17卷 835-841页

作者： ZHOU Ji-Chao ZHANG Xiao-Wei Molecular Immunology and pharmacology Group State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College

The probiotic Akkermansia muciniphila(A. muciniphila) is an intestinal bacterium that was first identified in human feces in 2004. Its specialization in mucin degradation makes it a key microorganism that maintains intestinal mucosal barrier function. As an unique representative strain of the phylum Verrucomicrobia that can be cultured in vitro, A. muciniphila is much easier to detect by metagenomic analysis of intestinal flora. In the past few years, A. muciniphila has been getting increasing attention for the positive correlation between its intestinal colonization and host homeostatic metabolism. In this review, we summarize the relationship between A. muciniphila and host health and diseases, especially focusing on metabolic diseases and related mechanisms, as well as the natural food and drug-derived substrates affecting its colonization in the host, expecting to provide evidence and clues for the development of drugs targeting A. muciniphila.

关键词： Gut microbiota Metabolic syndrome Diabetes Atural medicine

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Ganoderma triterpenes slow cyst growth in polycystic kidney disease

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中国药理学与毒理学杂志 2017年第10期31卷 1006-1007页

作者： Bao-xue YANG Li-min SU Li-ying LIU Hong ZHOU Ruo-yun CHEN State Key laboratory of natural and Biomimetic Drugs Department of PharmacologySchool of Basic Medical SciencesPeking University State Key laboratory of Bioactive substance and Function of natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences & Peking Union Medical College

OBJECTIVE Autosomal dominant polycystic kidney disease(ADPKD)is a common inherited disease with a high morbidity around 1/1000-1/400,characterized by progressive enlargement of fluid-fil ed cysts derived from renal tubular epithelial *** cysts gradually compress renal parenchyma destroying normal renal structures and compromising renal ***,it will cause end-stage renal disease in most of the patients but without effective therapy now,who have to live on hemodialysis or kidney *** on this present situation,it is of great significance to find early intervention to inhibit renal cyst *** projective of this study was to investigate whether Ganoderma triterpenes(GT)can inhibit renal cyst development and study the related *** and RESULTS First,we used MDCK cyst model,cultivated MDCK cells in vitro to form fluid-filled cysts surrounded by monolayer *** inhibited MDCK cyst formation significantly,and inhibited cyst enlargement dose-dependently proving GT cyst inhibition in *** we used an embryonic kidney cyst model,wile-type mice kidneys were taken out on embryonic day 13.5 to form renal cysts stimulated with 8-Br-c *** inhibited embryonic kidney cyst development significantly in a dosedependent and reversible manner proving GT cyst inhibition at organ ***,we used two ADPKD mouse models with severe cystic kidney disease *** dramatically inhibited renal cyst development,decreased ADPKD mouse kidney volume and the cyst index inside proving GT cyst inhibition in *** Western blot,we proved GT down-regulated Ras/MAPK signal pathway without detectable effect on m TOR signal pathway both in MDCK cells and two ADPKD mouse *** GT retard renal cyst development both in vitro and in vivo *** related mechanisms were involved in GT promoting renal tubular epithelial cell differentiation,down-regulating intracellular c AMP level and Ras/MAPK sig

关键词： polycystic kidney disease Ganoderma triterpenes mTOR signal pathway

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Antagonism of toll-like receptor 2 attenuates the formation and progression of abdominal aortic aneurysm

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Acta Pharmaceutica Sinica B 2015年第3期5卷 176-187页

作者： Huimin Yan Bing Cui Xiaowei Zhang Xiaoming Fu Jun Yan Xiaoxing Wang Xiaoxi Lv Zhong Chen Zhuowei Hu Molecular Immunology and pharmacology Group State Key Laboratory of Bioactive Substance and Function of Natural MedicinesInstitute of Materia MedicaChinese Academy of Medical Sciences & Peking Union Medical College Beijing Institute of Heart lung and Blood Vessel Diseases An Zhen Hospital of the Capital Medical University

Abdominal aortic aneurysm (AAA) is an inflammatory vascular disorder with high mortality. Accumulating evidence shows that toll-like receptor 2 (TLR2) plays a critical role in the regulation of wound-repairing process after tissue injury. We wondered if TLR2 signaling contributed to the pathogenesis of AAA and that targeting TLR2 would attenuate AAA development and progression. In this study, enhanced expression of TLR2 and its ligands were observed in human AAA tissue. Neutralization of TLR2 protected against AAA development and caused established AAA to regress in mouse models of AAA. In addition, TLR2-deficient mice also failed to develop AAA. The prophylactic and therapeutic effects of blocking TLR2 were accompanied by a significant resolution of inflammation and vascular remodeling, as indicated by the decreased expression or activity of MMP-2/9, alpha-SMA, inflammatory cytokines, and transcription factors NF-kappa B, AP-1 and STAT1/3 in AAA tissue. Mechanistically, blocking TLR2 decreased the expression and interaction of TLR2 and several endogenous ligands, which diminished chronic inflammation and vascular remodeling in the vascular tissue of AAA. Our studies indicate that the interactions between TLR2 and its endogenous ligands contribute to the pathogenesis of AAA and that targeting TLR2 offers great potential toward the development of therapeutic agents against AAA. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

关键词： Abdominal aortss aneury DAMPS Vascular remodeling TLR2 Immune microenvironment

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Design and synthesis of the ring-opened derivative of 3-n-butylphthalide-ferulic acid-glucose trihybrids as potential anti-ischemic agents

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Chinese Chemical Letters 2020年第7期31卷 1881-1886页

作者： Jianbing Wu Wei Yin Yinqiu Zhang Hui Ye Yunman Li Jide Tian Zhangjian Huang Yihua Zhang State Key laboratory of natural Medicines Jiangsu Key Laboratory of Drug Discovery for Metabolic DiseasesCenter of Drug DiscoveryChina Pharmaceutical UniversityNanjing 210009China State Key laboratory of natural Medicines Department of PhysiologyChina Pharmaceutical UniversityNanjing 210009China Department of Molecular and Medical pharmacology University of CaliforniaLos AngelesCA 90095United States

To improve aqueous solubility and anti-ischemic activity of 3-n-butylphthalide(NBP),we designed and synthesized the ring-opened derivative of NBP-ferulic acid-glucose trihybrids(S1-S8).These hybrids inhibited adenosine diphosphate(ADP)-or arachidonic acid(AA)-induced platelet aggregation,among them,S2 was 30-fold more water-soluble,and over 10-fold more potent in inhibition of platelet aggregation,as well as reduced ROS generation and protected primary neuronal cells from OGD/Rinduced damage,in comparison with NB ***,S2 was more active than its three moieties alone or in combination,suggesting that the activity of S2 may be attributed to the synergistic effects of these ***,in vivo studies indicated that S2 not only possessed good pharmacokinetic profile,but also improved NBP distribution in rodent brain,suggesting that the glucose moiety in S2 may be recognized by glucose transporter 1(GLUT1)on blood-brain barrier(BBB),promoting it to penetrate through *** findings suggest that S2 may be a promising candidate for the intervention of ischemic stroke,warranting further study.

关键词： 3-n-Butylphthalide Ferulic acid Glucose Hybrids Ischemic Brain-blood barrier

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Eubacterium coprostanoligenes alleviates chemotherapy-induced intestinal mucositis by enhancing intestinal mucus barrier

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1677-1692页

作者： Dongsheng Bai Jiawei Zhao Runde Wang Jiaying Du Chen Zhou Chunyang Gu Yuxiang Wang Lulu Zhang Yue Zhao Na Lu State Key laboratory of natural Medicines Jiangsu Key Laboratory of Carcinogenesis and InterventionDepartment of PhysiologySchool of Basic Medicine and Clinical PharmacyChina Pharmaceutical UniversityNanjing 210009China Department of Clinical pharmacology School of PharmacyNanjing Medical UniversityNanjing 211166China

Chemotherapy-induced mucositis represents a severe adverse outcome of cancer treatment,significantly curtailing the efficacy of these treatments and,in some cases,resulting in fatal *** identifying intestinal epithelial cell damage as a key factor in chemotherapy-induced mucositis,the paucity of effective treatments for such damage is *** our study,we discovered that Eubacterium coprostanoligenes promotes mucin secretion by goblet cells,thereby fortifying the integrity of the intestinal mucus *** enhanced barrier function serves to resist microbial invasion and sub-sequently reduces the inflammatory ***,this effect remains unobtrusive to the anti-tumor efficacy of chemotherapy ***,*** up-regulates the expression of AUF1,leading to the stabilization of Muc2 mRNA and an increase in mucin synthesis in goblet *** espe-cially significant finding is that *** activates the AhR pathway,thereby promoting the expression of *** summary,our results strongly indicate that *** enhances the intestinal mucus barrier,effec-tively alleviating chemotherapy-induced intestinal mucositis by activating the AhR/AUFl pathway,consequently enhancing Muc2 mRNA stability.

关键词： Chemotherapy Mucositis Eubacterium coprostanoligenes MUC2 AUF1

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Identification of the dietary supplement capsaicin as an inhibitor of Lassa virus entry

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Acta Pharmaceutica Sinica B 2020年第5期10卷 789-798页

作者： Ke Tang Xiaoyu Zhang Ying Guo State Key laboratory of Bioactive substance and Function of natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Department of pharmacology Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

The limited treatment options for the increasing occurrence of Lassa hemorrhagic fever in West Africa poses an urgent need for the discovery and development of novel *** supplements,especially natural products that are edible and safe for human use,are a good source of drug discovery with potential for uncovering novel applications,In this study,we tested 40 natural products of dietary supplements and identified capsaicin,a common dietary supplement abundant in chili peppers,as an inhibitor of Lassa virus(LASV)entry with EC5,of 6.9-10.0μmol/L using an HIV based pseudo virus *** inhibits the entry of five LASV strains but not against the Old World arenavirus lymphocytic choriomeningitis virus(LCMV),showing a preferential activity against *** inhibits LASV entry by blocking the pH dependent viral fusion through affecting the stable signal peptide(SSP)-GP2 transmembrane(GP2TM)region of the LASV surface *** study revealed the key residues Ala25,Val431,Phe434 and Val435 in SsP-CP2TM region in capsaicin’s antiviral *** study for the first time reveals a direct acting antiviral effect of capsaicin against the hemorrhagic fever causing LASV,providing detailed interaction hot spots in the unique SSP-GP2TMinterface of LASV glycoprotein that is crucial in fusion inhibition,and offering a new strategy in discovering and developing antivirals from natural products that are safe for human use.

关键词： Lassa virus Fusion inhibitor Capsaicin Dietary supplement natural product antivirals Viral entry Hemorrhagic fever SSP-GP2TM region

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Network pharmacology-based analysis of Chinese herbal Naodesheng formula for application to Alzheimer＇s disease

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Chinese Journal of natural Medicines 2018年第1期16卷 53-62页

作者： PANG Xiao-Cong KANG De FANG Jian-Song ZHAO Ying XU Lv-Jie LIAN Wen-Wen LIU Ai-Lin DU Guan-Hua Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050 China Beijing Key laboratory of Drug Target and Screening Research Beijing 100050 China State Key laboratory of Bioactive substance and Function of natural Medicines Beijing 100050 China Institute of Clinical pharmacology Guangzhou University of Chinese Medicine Guangzhou 510006 China

Naodesheng(NDS) formula, which consists of Rhizoma Chuanxiong, Lobed Kudzuvine, Carthamus tinctorius, Radix Notoginseng, and Crataegus pinnatifida, is widely applied for the treatment of cardio/cerebrovascular ischemic diseases, ischemic stroke, and sequelae of cerebral hemorrhage, etc. At present, the studies on NDS formula for Alzheimer's disease(AD) only focus on single component of this prescription, and there is no report about the synergistic mechanism of the constituents in NDS formula for the potential treatment of dementia. Therefore, the present study aimed to predict the potential targets and uncover the mechanisms of NDS formula for the treatment of AD. Firstly, we collected the constituents in NDS formula and key targets toward AD. Then, drug-likeness, oral bioavailability, and blood-brain barrier permeability were evaluated to find drug-like and lead-like constituents for treatment of central nervous system diseases. By combining the advantages of machine learning, molecular docking, and pharmacophore mapping, we attempted to predict the targets of constituents and find potential multi-target compounds from NDS formula. Finally, we built constituent-target network, constituent-target-target network and target-biological pathway network to study the network pharmacology of the constituents in NDS formula. To the best of our knowledge, this represented the first to study the mechanism of NDS formula for potential efficacy for AD treatment by means of the virtual screening and network pharmacology methods.

关键词： Alzheimer’s disease Network pharmacology Docking Pharmacophore Machine learning

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Discovery of the anti-influenza A virus activity of SB216763 and cyclosporine A by mining infected cells and compound cellular signatures

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Chinese Chemical Letters 2022年第5期33卷 2541-2544页

作者： Ke Tang You Wu Shubing Chen Yijing Xin Ying Guo State Key laboratory of Bioactive substance and Function of natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Department of pharmacology Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

In this study,SB216763 and cyclosporine A were identified as anti-influenza A virus(IAV)agents by tran-scriptome signature reversion(TSR)analysis through deep mining of the cellular transcriptome of hu-man airway and lung cell lines infected with 3 strains of IAV and the chemical perturbations library.A synergistic effect of SB216763 and cyclosporine A against influenza A was disclosed by quantification of the network-based relationship,which was validated in *** with burgeoning omics approaches,transcriptome-based drug development is flourishing,which provides a novel insight into antivirals dis-covery with comprehensive cellular transcriptional information of disease and chemical perturbations in multicomponent *** strategy can be applied as a new approach in discovering multitar-get antiviral agents from approved drugs,clinical compounds,natural products or other known bioactive compounds.

关键词： Chemical perturbagen signature Host factor Transcriptome signature reversion Influenza A virus SB216763 Cyclosporine A Drug combination

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Anti-asthma effects of synthetic salidroside through regulation of Th1/Th2 balance

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Chinese Journal of natural Medicines 2014年第7期12卷 500-504页

作者： WANG Jing JIN Rong-Guang XIAO Lu WANG Qiu-Juan YAN Tian-Hua Department of physiology and pharmacology China Pharmaceutical University

AIM: The aim of the study was to investigate the effect and mechanism of action of synthetic salidroside in an ovalbumin(OVA)-induced asthma model in mice. METHOD: BALB/c mice were sensitized with an intraperitoneal injection of ovalbumin(OVA) to induce a mouse model of asthma in paracmasis. The mice were treated with dexamethasone as the positive control. At the end of the study, respiratory reactivity was detected, the numbers of various kinds of white blood cells in the bronchoalveolar lavage fluid(BALF) were counted, and the levels of IL-4 and INF-γ in BALF were determined. Quantitative PCR was used to detect the mRNA contents of IL-4 and INF-γ in lung tissue. Histologic examination was performed to observe inflammatory cellular infiltration. RESULTS: Salidroside treatment virtually eliminated airway hyper-reactivity, markedly reduced the eosinophil percent, obviously reduced the levels of IL-4 and raised INF-γ in the bronchoalveolar lavage fluid(BALF) compared with the sham-treated group. Quantitative PCR on the mRNA content of IL-4 and INF-γ provided confirmation. Lung histologic observations showed that salidroside reduced inflammation and edema. These effects were equivalent to the effects of dexamethasone. CONCLUSION: Synthetic salidroside exhibits an anti-asthma effect which is related to the regulation of Th1/Th2 balance. This provides a new possibility for treatment of allergic asthma.

关键词： Synthetic salidroside Asthma Th1/Th2

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