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Self-adjuvant Astragalus polysaccharide-based nanovaccines for enhanced tumor immunotherapy:a novel delivery system candidate for tumor vaccines

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Science China(Life Sciences) 2024年第4期67卷 680-697页

作者： Nan Li Yun Zhang Miaomiao Han Tian Liu Jinjia Wu Yingxia Xiong Yikai Fan Fan Ye Bing Jin Yinghua Zhang Guibo Sun Xiaobo Sun Zhengqi Dong State key laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Chinese Academy of Medical Sciences&Peking Union Medical College(CAMS)Institute of Medicinal Plant Development(IMPLAD)Beijing 100193China key laboratory of Bioactive Substances and Resources Utilization of chinese Herbal medicine from Ministry of Education Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine(Natural Medicine)and Translational MedicineKey Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription from Chinese Academy of Medical SciencesCAMSIMPLADBeijing 100193China Department of Pharmaceutics School of Pharmaceutical SciencesHeilongjiang University of Chinese MedicineHarbin 150036China Jilin Academy of chinese medicine Sciences Changchun 130012China Joint Research Center for chinese Medicinal Herbs IMPLADABRC&ACCLBeijing 100193China

The study of tumor nanovaccines(NVs)has gained interest because they specifically recognize and eliminate tumor ***,the poor recognition and internalization by dendritic cells(DCs)and insufficient immunogenicity restricted the vaccine ***,we extracted two molecular-weight Astragalus polysaccharides(APS,12.19 k D;APSHMw,135.67 k D)from Radix Astragali and made them self-assemble with OVA257–264directly forming OVA/APS integrated nanocomplexes through the microfluidic *** nanocomplexes were wrapped with a sheddable calcium phosphate layer to improve *** in the formed nanocomplexes served as drug carriers and immune adjuvants for potent tumor *** optimal APS-NVs were approximately 160 nm with uniform size distribution and could remain stable in physiological saline *** FITC-OVA in APS-NVs could be effectively taken up by DCs,and APS-NVs could stimulate the maturation of DCs,improving the antigen cross-presentation efficiency in *** possible mechanism was that APS can induce DC activation via multiple receptors such as dectin-1 and Toll-like receptors 2 and *** accumulation of APS-NVs both in draining and distal lymph nodes were observed following *** APS-NVs could easily access the lymph ***,APS-NVs could markedly promote antigen delivery efficiency to DCs and activate cytotoxic T *** addition,APS-NVs achieve a better antitumor effect in established B16-OVA melanoma tumors compared with the OVA+Alum treatment *** antitumor mechanism correlated with the increase in cytotoxic T cells in the tumor ***,the poor tumor inhibitory effect of APS-NVs on the nude mouse model of melanoma also confirmed the participation of antitumor adaptive immune response induced by ***,this study developed a promising APS-based tumor NV that is an efficient tumor immunotherapy without systemic side effects.

关键词： Astragalus polysaccharides nanovaccines OVA immunotherapy self-adjuvant

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A new strategy of enhancing absorptivity and safety for evodiamine: polyamidoamine derivatives modified by polyethylene glycol chain

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Traditional medicine Research 2021年第2期6卷 100-110页

作者： Yao-Chun Gao Yuan-Sheng Lao Meng-Xue Zhang Nan Li Chen-Yang Wu Zheng-Qi Dong Institute of Medicinal Plant Development Chinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100193China key laboratory of Bioactive Substances and Resources Utilization of chinese Herbal medicine Ministry of EducationChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100094China key laboratory of new drug discovery based on classic chinese medicine prescription Beijing 100700China

Background:Traditional chinese medicine involves complex ingredients and mixtures of ingredients that often exhibit low bioavailability,and excipients are often lacking to increase the absorption-enhancing *** study modified the generation 4 polyamidoamine dendrimer with polyethylene glycol of different molecular weights(5000,2000,1000)to form a series of polyamidoamine-co-polyethylene glycol(PAMAM-co-PEG)as a novel class of oral absorption ***,the major alkaloid found in the traditional chinese medicine Wu Zhu Yu(Fructus Evodiae),was used as a model drug to verify the absorption-enhancing effects and the safety of this ***:This study utilized the solubility determination method documented in the Pharmacopoeia of the People’s Republic of China(2015 edition)and the D0 values recommended in the US FDA guidelines to comprehensively evaluate the solubility of *** permeability of evodiamine was assessed using the apparent permeability coefficient in experiments based on in vitro cell *** aspects of the biological safety of PAMAM-co-PEG were explored using the MTT assay,LDH assay,and total protein release of the rat intestinal ***,the absorption-enhancing effects of PAMAM-co-PEG at different molecular weights on evodiamine were verified via the use of in vitro cell models and in vivo intestinal loop circulation experiments with ***:Evodiamine exhibited low solubility and permeability and was classified into class IV compounds using the biopharmaceutical classification ***-co-PEG 2000 demonstrated improvement in the biosafety and absorption-enhancement effect of evodiamine at a specific *** study showed that 0.05%(w/v)of PAMAM-co-PEG 2000 increased the cumulative penetration of evodiamine via cell transport by 1.32 times,and 0.10%(w/v)of PAMAM-co-PEG 2000 increased the area under curve value of evodiamine by 1.31 ***:Evodiamine possesses low solubility and

关键词： Polyamidoamine dendrimers Polyethylene glycol Intestinal absorption enhancer Bioavailability Evodiamine Fructus Evodiae

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Research progress on the pharmacological effects and chemical constituents of Pien Tze Huang and its potential Q-markers

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chinese Journal of Natural medicines 2023年第9期21卷 658-669页

作者： DONG Zhaomin WANG Hong WANG Guangji Jiangsu Provincial key laboratory of drug Metabolism and Pharmacokinetics Research Unit of PK-PD Based Bioactive Components and Pharmacodynamic Target Discovery of Natural Medicine of Chinese Academy of Medical SciencesChina Pharmaceutical UniversityNanjing 210009China

Pien Tze Huang(PTH)was documented as an imperial prescription composed of Notoginseng Radix,Calculus Bovis,Snake Gallbladder,and *** is famous in China and Asian countries due to its excellent effects in heat clearing,detoxifying,swelling reduction,and pain *** pharmacological studies demonstrate that PTH shows excellent effects against various inflammatory diseases,liver diseases,and *** review summaries the pharmacological effects,clinical applications,and mainchemical components of *** importantly,its potential quality markers(Q-markers)were then analyzed based on the“five principles”of Q-markers under the guidance of Traditional chinese medicine theory,including transfer and traceability,specificity,efficacy,compatibility,and *** a result,ginsenosides Rb1,ginsenoside Rg1,ginsenoside Rd,ginsenoside Re,notoginsenoside R1,dencichine,bilirubin,biliverdin,taurocholic acid,and muscone are considered as the Q-markers of *** findings will provide guidance and assistance for the construction of a quality control system for PTH.

关键词： Pien Tze Huang(PTH) Quality marker(Q-marker) Chemical components Pharmacological effects Clinical application Qualitycontrol

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ETCM v2.0:An update with comprehensive resource and rich annotations for traditional chinese medicine

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Acta Pharmaceutica Sinica B 2023年第6期13卷 2559-2571页

作者： Yanqiong Zhang Xin Li Yulong Shi Tong Chen Zhijian Xu Ping Wang Meng Yu Wenjia Chen Bing Li Zhiwei Jing Hong Jiang Lu Fu Wenjing Gao Yanhua Jiang Xia Du Zipeng Gong Weiliang Zhu Hongjun Yang Haiyu Xu Institute of chinese Materia Medica China Academy of Chinese Medical SciencesBeijing 100700China State key laboratory of drug Research Drug Discovery and Design CenterShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China National Resource Center for chinese Materia Medica Chinese Academy of Chinese Medical SciencesBeijing 100700China Institute of Basic Research in Clinical medicine China Academy of Chinese Medical SciencesBeijing 100700China Shaanxi Academy of Traditional chinese medicine Xi'an 710003China State key laboratory of Functions and Applications of Medicinal Plants Guizhou Provincial Key Laboratory of PharmaceuticsGuizhou Medical UniversityGuiyang 550004China China Academy of chinese Medical Sciences Beijing 100700China

Existing traditional chinese medicine(TCM)-related databases are still insufficient in data standardization,integrity and precision,and need to be updated ***,an Encyclopedia of Traditional chinese medicine version 2.0(ETCM v2.0,http://***/ETCM2/front/#/)was constructed as the latest curated database hosting 48,442 TCM formulas recorded by ancient chinese medical books,9872 chinese patent drugs,2079 chinese medicinal materials and 38,298 *** facilitate the mechanistic research and new drug discovery,we improved the target identification method based on a two-dimensional ligand similarity search module,which provides the confirmed and/or potential targets of each ingredient,as well as their binding ***,five TCM formulas/chinese patent drugs/herbs/ingredients with the highest Jaccard similarity scores to the submitted drugs are offered in ETCM v2.0,which may be of significance to identify prescriptions/herbs/ingredients with similar clinical efficacy,to summarize the rules of prescription use,and to find alternative drugs for endangered chinese medicinal ***,ETCM v2.0 provides an enhanced Java Script-based network visualization tool for creating,modifying and exploring multi-scale biological *** v2.0 may be a major data warehouse for the quality marker identification of TCMs,the TCM-derived drug discovery and repurposing,and the pharmacological mechanism investigation of TCMs against various human diseases.

关键词： Traditional chinese medicine Database Target identification Network visualization new drug research and development Molecular mechanism Quality marker drug repurposing

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Jinbei Oral Liquid ameliorates bleomycin-induced idiopathic pulmonary fibrosis in rats via reversion of Th1/Th2 shift

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chinese Herbal medicines 2020年第3期12卷 273-280页

作者： Xiao-yan Xing Wei-jie Qiang Jia-le Bao Rui-chuang Yang Jun Hou Kai Tao Zhao-qing Meng Jing-hua Zhang Ai-jun Zhang Xiao-bo Sun Institute of Medicinal Plant Development Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100193China Shandong Hongjitang Pharmaceutical Group Co. Ltd.Jinan 250000China key laboratory of new drug discovery based on classic chinese medicine prescription Chinese Academy of Medical SciencesBeijing 100193China Research Center for Clinical and Translational medicine Fifth Medical CenterGeneral Hospital of Chinese PLABeijing 100039China The Affiliated Hospital of Shandong University of TCM Jinan 250011China

Objective:Idiopathic pulmonary fibrosis(IPF)is a progressive and lethal interstitial lung disease with high *** pivotal role of Th1/Th2 immunological balance in the development and progression of IPF has been demonstrated *** study aimed to evaluate the effect of Jinbei Oral Liquid(JBOL)on IPF and its relationship with Th1/Th2 ***:Rats were divided into six groups:control group,model group(bleomycin),pirfenidone group(positive group,54 mg/kg,i.g.)and JBOL(5.4,10.8 and 21.6 mL/kg,i.g.)*** rat model was established by an intratracheal instillation of bleomycin(BLM,5 mg/kg).One day after injection of BLM,pirfenidone or JBOL was given to rats once daily within 28 consecutive days,*** emission tomography/computed tomography(PET/CT)was performed on the treated *** extent of alveolitis and fibrosis was observed by H&E and Masson trichrome *** contents of TGF-β1,TNF-α,IL-4 and IFN-γwere further quantified by ELISA ***:PET/CT and histopathological evidence showed the ability of JBOL to attenuate bleomycininduced alveolitis and fibrosis extent,and the alveolitis lesion score was markedly decreased compared with the model *** increased expression of inflammatory cytokines TGF-β1 and TNF-αinduced by bleomycin was also suppressed by *** Th1 response was limited by the reduced IFN-γafter BLM administration,and the Th2 response predominated significantly marked by the increased *** could increase the level of IFN-γand markedly increased the ratio of IFN-γ/***:These findings suggested that JBOL may attenuate BLM-induced idiopathic pulmonary fibrosis via reducing inflammatory cell infiltration,pro-inflammatory cytokine release and excessive collagen deposition in *** of the mechanisms is the reversion of Th1/Th2 shift caused by BLM.

关键词： bleomycin cytokines idiopathic pulmonary fibrosis Jinbei Oral Liquid Th1/Th2 shift

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Optimization of Jiawei Qing'e Oral Fast Disintegrating Tablets based on Response Surface-Central Composite Design

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chinese Herbal medicines 2013年第2期5卷 138-144页

作者： ZHANG Wei-ling WANG Ya-jing GAO Xiu-mei GAO Xu PENG Shu-juan ZHENG Yin OKEKE Chukwunweike Ikechukwu Tianjin State key laboratory of Modern chinese medicine Engineering Research Center of Modern Chinese Medicine Discovery and Preparation TechniqueMinistry of EducationTianjin University of Traditional Chinese Medicine

Abstract: Objective To apply the response surface-central composite design to developing and optimizing the oral fastdisintegrating tablets (ODT) formulation for Jiawei Qing’e, a kind of prescription of chinese herbal *** The bitterness of Jiawei Qing’e was masked using Eudragit E-100 by solvent evaporation *** surface approach was applied to investigating the interaction of formulation parameters in optimizing theformulation. The independent variables were Eudragit E-100/drug ratio (X1), amount of disintegrants (X2), and theamount of diluents (X3). The disintegration time (Y1), hardness (Y2), and weight variations of the tablets werecharacterized. Results The models predicted levels of X1= 4.63%, X2= 5.25%, and X3= 34.33%, for the optimalformulation having a hardness of 3.0 kg with the disintegration time of 30 s within experimental region. The observedresponse of Y1= 26.5 s and Y2= 3.14 kg reasonably agreed with the predicted response. Conclusion Responsesurface methodology shows the good predictability and reliability in optimizing the formulation. The optimized ODTof Jiawei Qing’e has acceptable taste, rapid disintegrating ability, and good mechanical strength.

关键词： chinese herbal medicine oral fast disintegrating tablets response surface-central composite design solvent evaporation technique taste masking

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Differential metabolite analysis of the pharmacodynamic differences between different ratios of Dahuang(Radix Et Rhizoma Rhei Palmati)-Taoren(Semen Persicae) herb pair

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Journal of Traditional chinese medicine 2024年第3期44卷 515-523页

作者： WANG Xiang HUANG Jianping WANG Yupeng WANG Qilong JING Yajiang ZHANG Gang PENG Liang GAO Jing WANG Hongyan YAN Yonggang Department of key laboratory of"Qin Pharmaceutical"Research and Development Shaanxi University of Traditional Chinese MedicineXianyang 712046China Department of Yupeng Shaanxi Haitian Pharmaceutical Co. Ltd.Xianyang 712046China Department of Acupuncture and Tuina Shaanxi University of Traditional Chinese MedicineXianyang 712000China

OBJECTIVE: To explore the material basis of the difference of efficacy of Dahuang(Radix Et Rhizoma Rhei Palmati)-Taoren(Semen Persicae)(DT) drugs with different proportions. METHODS: Samples of different ratios of Dahuang(Radix et Rhizoma Rhei Palnati, DH) to Taoren(Semen Persicae, TR)(Group A 1∶1, B 2∶3, C 3∶2) were analyzed based on gas chromatography time-of-flight mass spectrometry untargeted metabolomics technique. RESULTS: A total of 240 primary metabolites were detected. Forty-one differential metabolites involved nine differential metabolic pathways, of which four were closely related to the efficacy of DT in the treatment of heat and blood stasis syndrome. These pathways included the biosynthesis of amino acid(phenylalanine tyrosine and tryptophan), flavonoids, unsaturated fatty acids, and the glycolysis/glycogenesis pathway. CONCLUSION: There are significant differences in the efficacy of different ratios of DT drugs, and their optimal ratio for the treatment of heat and blood stasis syndrome should be 1∶1.

关键词： metabolomics metabolic networks and pathways differential metabolites Dahuang(Radix Et Rhizoma Rhei Palmati) Taoren(Semen Persicae) kernel drug pairs

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Biomolecular network-based synergistic drug combination discovery:a combination of paeoniflorin and liquiritin alleviates neuropathic pain by inhibiting neuroinflammation via suppressing the chemokine signaling pathway

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1804-1806页

作者： Qiuyan Guo Weijie Li Chao Wang Xia Mao Xiaoyue Wang Wenjia Chen Haiyu Xu Qian Wang Yanqiong Zhang Na Lin Institute of chinese Materia Medica China Academy of Chinese Medical Sciences100700 BeijingChina State key laboratory of Natural and Biomimetic drugs School of Pharmaceutical SciencesPeking University100191 BeijingChina

Dear Editor,Neuropathic pain(NP)resulting from injuries or diseases affecting the somatosensory nervous system is highly prevalent in various pathological conditions.1 Since NP is debilitating and impacts health and the quality of life,there is an urgent need for effective non-addictive new *** chinese medicine(TCM)has been increasingly used for its benefits in relieving pain in ***-Tou Decoction(WTD),which was first described by the famous TCM classic“Jin Gui Yao Lue”,is one of the most effective TCM herbal prescriptions for pain management.A growing body of clinical evidence shows that WTD markedly alleviates different types of NP,such as trigeminal neuralgia,inflammatory pain,and cancer-induced pain,with a total effectiveness of~80%.2 Our previous data demonstrated the analgesic effects of WTD via suppression of glial cell activation and neuroinflammation and further revealed that WTD attenuated NP partially by inhibiting spinal astrocytic IL-1R1/TRAF6/JNK signaling and regulating the glutamatergic system in CA3 in spinal nerve ligation(SNL)-induced NP in vivo.3,4 However,the bioactive compounds(BACs)of WTD that have an effect on NP and the underlying mechanisms remain unclear.

关键词： pain inflammation inhibiting

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discovery of CECR2 Bromodomain Inhibitors with High Selectivities over BPTF Bromodomain

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chinese Journal of Chemistry 2022年第17期40卷 2072-2080页

作者： Haibo Lu Shijia Zu Zhe Duan Yueyao Feng Jie Wang Jingyi Ma Qi Li Dongying Chen Bo Li Kaixian Chen Cheng Luo Jin Lin Tian Lu Hua Lin Biomedical Research Center of South China College of Life SciencesFujian Normal UniversityFuzhouFujian350117 China School of Pharmacy Fudan University826 Zhangheng RoadShanghai201203 China State key laboratory of drug Research Shanghai Institute of Materia MedicaChinese Academy of Sciences555 Zuchongzhi RoadShanghai201203 China University of chinese Academy of Sciences 19 Yuquan RoadBeijing100049 China School of Pharmacy Nanchang UniversityNanchangJiangxi330006 China laboratory of Pharmaceutical Analysis Shanghai Institute of Materia MedicaChinese Academy of Sciences555 Zuchongzhi RoadZhangjiang Hi-Tech ParkShanghai201203 China School of Pharmacy Fujian Medical UniversityFuzhouFujian350122 China Guizhou University of Traditional chinese medicine GuiyangGuizhou550025 China

Cat's eye syndrome chromosome candidate 2 bromodomain(CECR2 BRD)and Bromodomain PHD transcription factor bromodomain(BPTF BRD)are the same subfamily proteins,both of which are highly conserved in sequence and binding *** remain in the development of small molecules to inhibit one of the two bromodomains(BRDs),in view of each subtype may possess unique physiological and pathological *** is still a lack of effective selective inhibitors of CECR2 BRD,which makes it difficult to fully understand the pathogenesis of CECR2-BRD in diseases,especially ***,we report our efforts to discover a series of highly selective CECR2 BRD inhibitors over BPTF BRD based on ***-based molecular optimization led to the discovery of DC-CEi-26,whose IC_(50) for CECR2 BRD was 96.7±14.9 nmol/L and selectivity was up to 590×over BPTF ***-CEi-26 showed weak potencies for other classic BRDs in different subfamily,which may serve as a chemical probe for CECR2 BRD biological research.

关键词： CECR2 bromodomain BPTF bromodomain Inhibitors Structure-activity relationships chemical probe

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Study on the Mechanism of Qingre Huoxue prescription in the Intervention and Treatment of Acute Myocardial Infarction based on Network Pharmacology

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World Journal of Traditional chinese medicine 2019年第4期5卷 220-227页

作者： Cai-Xia Jia Jin-Ping Wang Fei-Long Zhang Xiao-Han Pang Wei-Lu Wang Paulin-Xue Xu Kuo Gao Jian-Xin Chen Pharmacology Major of Integrated Traditional chinese and Western medicine School of Preclinical MedicineBeijing University of Chinese Medicine Harvard Medical School 25 Shattuck Street BostonMA 02115USA Scientific Research and Experiment Center Dongfang HospitalBeijing University of Chinese MedicineBeijingChina

Objective:The objective is to study the mechanism of Qingre Huoxue prescription in the intervention and treatment of acute myocardial infarction(AMI)based on the method of network *** and Methods:Five databases were used to screen the chemical compounds and targets of Ligusticum wallichii(chuanxiong),Radix Paeoniae Rubra(chishao),Lignum acronychiae(jiangxiang),Safflower(honghua),Salvia miltiorrhiza(danshen),Scutellaria baicalensis(huangqin),and Ilex pubescens(mao dong qing)in Qingre Huoxue ***,Cytoscape-V3.2.1 software was used to construct the drug-component-target *** protein association networks'database and the Database for Annotation,Visualization,and Integrated discovery(DAVID)were used to visualize the protein interaction,pathway enrichment,and ***:A total of 44 active ingredients were screened out in Qingre Huoxue *** them,178 targets and 41 compounds related to Qingre Huoxue prescription's function in treating AMI were *** the analysis of the drug-component-action target network on Qingre Huoxue prescription,14 key compounds and nine key targets with three scores above average were *** addition,pathway enrichment and biological processes were conducted with the aid of the DAVID;and 8 related pathways and 10 biological processes were associated with AMI and related diseases;the PI3 K-AKT signaling pathway,MAPK signaling pathway,and HIF-1 signaling pathway are the main pathways of Qingre Huoxue prescription for the treatment of AMI and related ***:Qingre Huoxue prescription could treat AMI by multiple components,targets,and *** study provides ideas and theoretical basis for further clinical studies on Qingre Huoxue prescription in treating AMI.

关键词： Acute myocardial infarction mechanism network pharmacology Qingre Huoxue prescription

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