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Food Science and Human Wellness 2024年

作者： Yushi Zhang Qingyu Cui Lixin Wang Xiaoxue Wang Shupeng Liu Rong Zeng Weidong Li school of chinese materia medica Beijing University of chinese Medicine Qingdao Histep Health Technology Ltd. Department of Cardiology Beijing Anzhen Hospital Capital medical University

chinese dwarf cherry (Cerasus humilis) is a fruit unique to China， which is considered to have osteoprotective effects. However， no systematic experimental characterization was available. In this study， the osteoprotective activity and mechanism of chinese dwarf cherry polyphenol extract (OPE) was studied. In vitro， OPE stimulated the alkaline phosphatase activity in the early differentiation stage， increased the osteocalcin level in the middle differentiation stage， and induced the formation of more bone-mineralized nodules in the late osteogenic stage. In vivo， OPE improved cancellous bone structure and maximum load of the femur in ovariectomized (OVX) rats. The balance between bone formation and resorption was regulated. Oxidative stress levels in the peripheral blood， liver and femur were reduced. OPE alleviated the disturbance in energy metabolism， muscle development， and muscle regulation-related signaling pathways caused by OVX and activated the calcium/adenosine monophosphate-activated protein kinase signaling pathway. Therefore， OPE is a potential dietary supplement for the prevention and treatment of osteoporosis.

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High expression of GPR160 in prostate cancer is unrelated to CARTp-mediated signaling pathways

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1467-1471页

作者： Chenyu Ye Qingtong Zhou Shi Lin Wensheng Yang Xiaoqing Cai Yiting Mai Yanyan Chen Dehua Yang Ming-Wei Wang Department of Pharmacology School of Basic Medical SciencesFudan UniversityShanghai 200032China Research Center for Deepsea Bioresources Sanya 572025China Department of Pharmacy Children’s Hospital of Fudan UniversityNational Children’s Medical CenterShanghai 201102China State Key Laboratory of Chemical Biology Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China The National Center for Drug Screening Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of chinese Academy of Sciences Beijing 100049China Department of Chemistry School of Sciencethe University of TokyoTokyo 113-0033Japan school of Pharmacy Hainan Medical UniversityHaikou 571199China

To the Editor:G protein-coupled receptors(GPCRs)are the largest group of membrane proteins with over 800 members,characteristic of a seven transmembrane domain1.By playing crucial roles in regulation of various physiological processes,GPCRs have been implicated in many diseases including diabetes,obesity,depression and cancer.To initiate different intracellular responses,GPCRs mainly interact with three families of effector proteins upon agonist binding:the heterotrimeric G proteins,G protein-coupled receptor kinases(GRKs)and arrestins1.

关键词： GPR160 CARTp Prostate cancer Signaling pathway

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Structure-based design of pan-coronavirus inhibitors targeting host cathepsin L and calpain-1

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1651-1664页

作者： Xiong Xie Qiaoshuai Lan Jinyi Zhao Sulin Zhang Lu Liu Yumin Zhang Wei Xu Maolin Shao Jingjing Peng Shuai Xia Yan Zhu Keke Zhang Xianglei Zhang Ruxue Zhang jian Li Wenhao Dai Zhen Ge Shulei Hu Changyue Yu Jiang Wang Dakota Ma Mingyue Zheng Haitao Yang Gengfu Xiao Zihe Rao Lu Lu Leike Zhang Fang Bai Yao Zhao Shibo Jiang Hong Liu Drug Discovery and Design Center State Key Laboratory of Drug ResearchCAS Key Laboratory of Receptor ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of chinese Academy of Sciences Beijing 100049China Key Laboratory of medical Molecular Virology(MOE/NHC/CAMS) School of Basic Medical SciencesShanghai Institute of Infectious Disease and BiosecurityFudan UniversityShanghai 200032China Shanghai Institute for Advanced Immunochemical Studies and school of Life Science and Technology ShanghaiTech UniversityShanghai 201210China State Key Laboratory of Virology Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan 430071China school of chinese materia medica Nanjing University of Chinese Medicine138 Xian Lin RoadJiangsu 210023 NanjingChina school of Pharmaceutical Science and Technology Hangzhou Institute for Advanced StudyUCASHangzhou 310024China National Clinical Research Center for Infectious Disease Shenzhen Third People's HospitalShenzhen 518112China

Respiratory disease caused by coronavirus infection remains a global health crisis.Although several SARS-CoV-2-specific vaccines and direct-acting antivirals are available,their effcacy on emerging coronaviruses in the future,including SARS-CoV-2 variants,might be compromised.Host-targeting antivirals provide preventive and therapeutic strategies to overcome resistance and manage future outbreak of emerging coronaviruses.Cathepsin L(CTSL)and calpain-1(CAPN1)are host cysteine proteases which play crucial roles in coronaviral entrance into cells and infection-related immune response.Here,two peptidomimetic a-ketoamide compounds,14a and 14b,were identified as potent dual target inhibitors against CTSL and CAPN1.The X-ray crystal structures of human CTSL and CAPN1 in complex with 14a and 14b revealed the covalent binding of a-ketoamide groups of 14a and 14b to C25 of CTSL and C115 of CAPN1.Both showed potent and broad-spectrum anticoronaviral activities in vitro,and it is worth noting that they exhibited low nanomolar potency against SARS-CoV-2 and its variants of concern(VOCs)with ECso values ranging from 0.80 to 161.7 nM in various cells.Preliminary mechanistic exploration indicated that they exhibited anticoronaviral activity through blocking viral entrance.Moreover,14a and 14b exhibited good oral pharmacokinetic properties in mice,rats and dogs,and favorable safety in mice.In addition,both 14a and 14b treatments demonstrated potent antiviral potency against SARS-CoV-2 XBB 1.16 variant infection in a K18-hACE2 transgenic mouse model.And 14b also showed effective antiviral activity against HCoV-OC43 infection in a mouse model with a final survival rate of 60%.Further evaluation showed that 14a and 14b exhibited excellent antiinflammatory effects in Raw 264.7 mouse macrophages and in mice with acute pneumonia.Taken together,these results suggested that 14a and 14b are promising drug candidates,providing novel insight into developing pan-coronavirus inhibitors with antiviral and anti-inflammatory properties.

关键词： calpain overcome entrance

The potential of chinese herbal medicines in treating anxiety disorders

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Integrative Medicine Discovery

Integrative Medicine Discovery 2024年第5期8卷 1-5页

作者： Jia-Qi Xie Jian-Mei Huang Can Wang school of chinese materia medica Beijing University of Chinese MedicineBeijing 100029China

In recent years,there has not been much progress in developing anxiolytic drugs.Amongst the barriers are the lack of clarity on the pathogenesis of anxiety disorders,low product conversion rates for developing drugs targeting the receptors,and species variability.Some scientists have focused on natural medicines,especially herbal medicines in traditional chinese medicine.New drugs with excellent anxiolytic activity are hoped to be found in herbal medicines with anxiolytic effects.This mini-review summarised three chinese herbal medicines with anxiolytic effects and anxiolytic herbal formulas used in the traditional chinese medicine clinic.Several key issues that block the development of new anxiolytic drugs are also discussed.We hope to provide some ideas for researching and developing new anxiolytic drugs and studying anxiolytic components in traditional chinese medicine.

关键词： traditional chinese medicine anxiolytic drugs chinese herbal medicines

Albizzia chinensis(Osbeck)Merr extract YS ameliorates ethanol-induced acute gastric ulcer injury in rats by regulating NRF2 signaling pathway

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Animal Models and Experimental Medicine 2024年第3期7卷 275-282页

作者： Bo Tang Liangning Li Yuanzhi Yu Guibin Wang Shuanggang Ma Shishan Yu Jianjun Zhang Institute of materia medica Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina State Key Laboratory of Digestive Health BeijingChina State Key Laboratory of Bioactive Substance and Function of Natural Medicines BeijingChina

Background:Around the world,there is a high incidence of gastric ulcers.YS,an extract from the chinese herb Albizzia chinensis(Osbeck)Merr,has potential therapeutic applications for gastrointestinal diseases.Here we elucidated the protective effect and underlying mechanism of action of YS on gastric ulcer in rats injured by ethanol.Methods:The ethanol-i nduced gastric ulcer rat model was used to assess the protective effect of YS.A pathological examination of gastric tissue was performed by H&E staining.GES-1 cells damaged by hydrogen peroxide were used to simulate oxidative damage in gastric mucosal epithelial cells.Endogenous NRF2 was knocked down using small interfering RNA.Immunoprecipitation was used to detect ubiquitination of NRF2.Co-i mmunoprecipitation was used to detect the NRF2-Keap1 interaction.Results:YS(10 and 30 mg/kg,i.g.)significantly reduced the ulcer index,decreased MDA level,and increased SOD and GSH levels in gastric tissues damaged by ethanol.YS promoted NRF2 translocation from cytoplasm to nucleus and enhanced the NQO1 and HO-1 expression levels in injured rat gastric tissue.In addition,YS regulated NQO1 and HO-1 via NRF2 in H_(2)O_(2)-i nduced oxidative injured GES-1 cells.Further studies on the underlying mechanism indicated that YS reduced the interaction between NRF2 and Keap1 and decreased ubiquitylation of NRF2,thereby increasing its stability and expression of downstream factors.NRF2 knockdown abolished the effect of YS on MDA and SOD in GES-1 cells treated with H_(2)O_(2).Conclusion:YS reduced the NRF2-Keap1 interaction,promoting NRF2 translocation into the nucleus,which increasing the transcription and translation of NQO1 and HO-1 and improved the antioxidant capacity of rat stomach.

关键词： antioxidative ethanol gastric ulcer NRF2 YS

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Plant resources and diversity analysis of Sejila Mountain in southeast Tibet

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Asian Journal of Traditional Medicines 2024年第3期19卷 152-158页

作者： Lianyu Tang Dongdong Wang Jingming Jia Anhua Wang school of Traditional chinese materia medica Shenyang Pharmaceutical UniversityShenyang 110016China

Sejila Mountain is located in Linzhi City,southeast Tibet.The terrain is high,and the climate is cold and dry.The special ecological environment determines the richness and diversity of plant resources.In this study,the plant resources and diversity of Sejila Mountain were studied through field investigation,literature review and specimen identification.282 plant species belonging to 199 genera and 81 families were collected from July to August in 2021.The dominant families are Asteraceae,Ranunculaceae and Rosaceae.In terms of life form,perennial herbs are the main form,accounting for 58.16%of the total.178 species of medicinal plants were collected,including 33 species of Tibetan medicine.In terms of medicinal parts,the whole grass is mainly used as medicine,followed by roots and rhizomes.In conclusion,our study has updated the plant resources and diversity of Sejila Mountain.Based on the investigation and research,some suggestions were put forward to strengthen the protection and utilization of the plant resources in Sejila Mountain.

关键词： plant resources diversity Tibetan medicine Sejila Mountain

Pharmacognostical s tudies o n Spermacoce p usilla Wallich

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Pharmacology Discovery

Pharmacology Discovery 2024年第1期4卷 12-20页

作者： Ya-Kun Hao Wen-Feng Weng Sheng-Guo Ji school of chinese materia medica Guangdong Pharmaceutical UniversityGuangzhou 510006China.

Background:Spermacoce pusilla Wallich(S.pusilla)is widely used in Guangdong province of China.It has valuable medicinal value in treating trauma,fractures,carbuncle,swelling,and poisonous snake bites.Method:The present study was carried out to provide a scientific basis for the identification and authenticity of S.pusilla with the help of pharmacognostical parameters,which has not been done before.In this study,a series of related identification information such as source,character,microscopic observation,physical and chemical reaction,and molecular markers were employed to establish accurate,comprehensive pharmacognostic identification information of S.pusilla.Results:The study provided some basic data regarding the genuine crude drug.The identification efficiency of ITS sequences obtained in this study is high,the psbA-trnH sequence was obtained from S.pusilla and sequenced for the first time in this study.Conclusion:In this study,traditional pharmacognosy identification and molecular marker identification of S.pusilla in the Guangdong region were carried out,and a systematic and comprehensive pharmacognosy identification information system was established.

关键词： Spermacoce pusilla Wallich identification phytochemical screening phytochemical analysis DNA barcoding

Analysis of vascular plant resources and diversity in Fanjing Mountain,Guizhou Province

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Asian Journal of Traditional Medicines 2024年第3期19卷 137-151页

作者： Hu Chen Guoqing Long Anhua Wang Jingming Jia school of Traditional chinese materia medica Shenyang Pharmaceutical UniversityShenyang 110016China

Fanjing Mountain Nature Reserve is located at the junction of Jiangkou,Yinjiang and Songtao counties in the Tongren region of Guizhou Province.Because of the topography and humid climate of the central subtropical monsoonal mountains,the plant species in this area are rich and diverse.The vascular plant resources and diversity of Fanjing Mountain Nature Reserve in Guizhou Province were studied through field survey,literature review and specimen identification.The results show that there are 284 species of vascular plants in the region,belonging to 205 genera in 93 families,mainly angiosperms.Liliaceae,Asteraceae,Polygonaceae,Leguminosae,Ranunculaceae and Polygonum have the most species,followed by Sedum,Dioscorea,Actinidia Lindl and Thalictrum.In terms of life types,perennial herbs are the most dominant,accounting for 68.47%of the total number of species,and annual(or biennial)herbs,shrubs and vine types also present.There are 222 species identified as medicinal vascular plants,accounting for 78.2%of the total number of species.The medicinal parts are primarily found in the whole herb category,followed by the root and rhizome category.

关键词： plant resources diversity medicinal use conservation and utilization Fanjing Mountain Nature Reserve

Targeting NRP1 axis as a strategy for treating energy metabolism impairment induced by SARS-CoV-2 spike

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Science China Life Sciences 2024年

作者： Lihui Zhang Wanting Hu Jingxuan Li Yuehan Li Feng Liu Wenyi Xiao Ning Jiang Zhiyong Xiao Lu Han Wenxia Zhou Beijing Institute of Pharmacology & Toxicology State Key Laboratory of Toxicology and medical Countermeasures Beijing Institute of Pharmacology & Toxicology school of chinese materia medica Tianjin University of Traditional Chinese Medicine

Dear Editor,Free spike protein of SARS-CoV-2 alone can cause abnormal energy metabolism(Table S1 in Supporting Information), and limited research suggested a potential correlation between spike-induced mitochondrial damage and the ACE2 receptor(Lei et al., 2021; Yang et al., 2023). In order to further explore the mechanisms involved, we observed that the wild-type S1 protein of SARS-CoV-2 exerts a more potent inhibitory effect on host cell ATP compared to the wild-type S protein, S2protein, the Omicron variant S1 protein and HCoV-NL63 S1protein in HLMVEC and 293T cell lines(Figure 1A and B),indicating the importance of exploring the mechanism by which the S1 protein causes ATP decrease. Meanwhile, the S1protein did not lead to significant changes in cellular lactate levels, indicating that its primary mechanism involves impairing oxidative phosphorylation and mitochondrial damage(Figure 1C and D).

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A novel strategy for treating oncogene-mutated tumors by targeting tumor microenvironment and synergistically enhancing anti-PD-1 immunotherapy

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Cancer Communications 2024年第3期44卷 438-442页

作者： Yingqiang Liu Linjiang Tong Mengge Zhang Qi Zhang Qiupei Liu Fang Feng Yan Li Mengzhen Lai Haotian Tang Yi Chen Meiyu Geng Wenhu Duan Jian Ding Hua Xie Division of Antitumor Pharmacology&State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiP.R.China University of chinese Academy of Sciences BeijingP.R.China Department of Chemical and Environmental Engineering University of Nottingham Ningbo ChinaNingboZhejiangP.R.China Zhongshan Institute for Drug Discovery Shanghai Institute of Materia MedicaChinese Academy of SciencesZhongshanGuangdongP.R.China Shandong Laboratory of Yantai Drug Discovery Bohai Rim Advanced Research Institute for Drug DiscoveryYantaiShandongP.R.China Small-Molecule Drug Research Center Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiP.R.China

Oncogenes are critical factors in tumorigenesis of diverse cancer types and play essential roles in tumor immune escape.Mutations in Kirsten rat sarcoma viral oncogene homolog(KRAS)and epidermal growth factor receptor(EGFR)are among the most frequent gain-of-function alterations[1].After many years of in-depth research,inhibitors targeting EGFR or KRAS mutations have been successfully developed,however,their clinical benefit is relatively limited,and they will inevitably encounter the challenge of drug resistance.The emergence of resistance is attributed to secondary mutations in driver genes and other complicated factors.

关键词： alterations KRAS sarcoma