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Single-cell transcriptomics reveals the ameliorative effect of rosmarinic acid on diabetic nephropathy-induced kidney injury by modulating oxidative stress and inflammation

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1661-1676页

作者： Junhui Chen Qian Zhang Jinan Guo Di Gu Jing Liu Piao Luo Yunmeng Bai Jiayun Chen Xinzhou Zhang Sheng Nie Chunbo Chen Yulin Feng Jigang Wang national pharmaceutical engineering center for solid preparation of chinese herbal medicine Jiangxi University of Chinese MedicineNanchang 330006China Department of Pulmonary and Critical Care medicine Shenzhen Institute of Respiratory Diseasesand Shenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalFirst Affiliated Hospital of Southern University of Science and TechnologySecond Clinical Medical College of Jinan UniversityShenzhen 518020China School of Traditional chinese medicine and School of pharmaceutical Sciences Southern Medical UniversityGuangzhou 510515China Department of Urology and Shenzhen Clinical Research Centre for GeriatricsShenzhen People's Hospitalthe First Affiliated HospitalSouthern University of Science and TechnologyShenzhen 518020China Department of Urology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510230China Department of Nephrology Shenzhen Key Laboratory of Kidney Diseasesand Shenzhen Clinical Research Centre for GeriatricsShenzhen People's Hospitalthe First Affiliated HospitalSouthern University of Science and TechnologyShenzhen 518020China Department of Nephrology Nanfang Hospitalthe First Affiliated Hospital of Southern Medical UniversityGuangzhou 510515China Department of Critical Care medicine Shenzhen People's Hospital(the Second Clinical Medical CollegeJinan Universitythe First Affiliated HospitalSouthern University of Science and Technology)Shenzhen 518020China State Key Laboratory for Quality Esurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China Department of Oncology the Affiliated Hospital of Southwest Medical UniversityLuzhou 646000China

Diabetic nephropathy(DN)is a severe complication of diabetes,characterized by changes in kidney structure and function.The natural product rosmarinic acid(RA)has demonstrated therapeutic effects,including anti-inflammation and anti-oxidative-stress,in renal damage or dysfunction.In this study,we characterized the heterogeneity of the cellular response in kidneys to DN-induced injury and RA treatment at single cell levels.Our results demonstrated that RA significantly alleviated renal tubular epithelial injury,particularly in the proximal tubular S1 segment and on glomerular epithelial cells known as podocytes,while attenuating the inflammatory response of macrophages,oxidative stress,and cytotox-icity of natural killer cells.These findings provide a comprehensive understanding of the mechanisms by which RA alleviates kidney damage,oxidative stress,and inflammation,offering valuable guidance for the clinical application of RA in the treatment of DN.

关键词： Rosmarinic acid Diabetic nephropathy scRNA sequencing Injury Oxidative stress Infiammation Proteomics

Integrated data mining and network pharmacology to discover a novel traditional chinese medicine prescription against diabetic retinopathy and reveal its mechanism

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TMR Modern herbal medicine 2024年第2期7卷 41-55页

作者： Kai-Lun Zhang Xu Wang Xiang-Wei Chang Jun-Fei Gu Bo-Yang Zhu Shi-Bing Wei Bo Wu Can Peng Jiu-Sheng Nie De-Ling Wu College of Pharmacy Anhui University of Chinese MedicineHefei 230012China School of Traditional chinese medicine and School of Integrated chinese and Western medicine Nanjing University of Chinese MedicineNanjing 210023China MOE-Anhui Joint Collaborative Innovation center for Quality Improvement of Anhui Genuine chinese Medicinal Materials Anhui University of Chinese MedicineHefei 230012China Institute of Pharmaceutics Anhui Academy of Chinese MedicineHefei 230012China Anhui Province Key Laboratory of pharmaceutical preparation Technology and Application Anhui University of Chinese MedicineHefei 230012China engineering Technology Research center of Modernized Pharmaceutics Anhui Education Department(AUCM)Hefei 230012China The First Clinical Medical College Anhui University of Chinese MedicineHefei 230012China

Background:Diabetic retinopathy(DR)is currently the leading cause of blindness in elderly individuals with diabetes.Traditional chinese medicine(TCM)prescriptions have shown remarkable effectiveness for treating DR.This study aimed to screen a novel TCM prescription against DR from patents and elucidate its medication rule and molecular mechanism using data mining,network pharmacology,molecular docking and molecular dynamics(MD)simulation.Method:TCM prescriptions for treating DR was collected from patents and a novel TCM prescription was identified using data mining.Subsequently,the mechanism of the novel TCM prescription against DR was explored by constructing a network of core TCMs-core active ingredients-core targets-core pathways.Finally,molecular docking and MD simulation were employed to validate the findings from network pharmacology.Result:The TCMs of the collected prescriptions primarily possessed bitter and cold properties with heat-clearing and supplementing effects,attributed to the liver,lung and kidney channels.Notably,a novel TCM prescription for treating DR was identified,composed of Lycii Fructus,Chrysanthemi Flos,Astragali Radix and Angelicae Sinensis Radix.Twenty core active ingredients and ten core targets of the novel TCM prescription for treating DR were screened.Moreover,the novel TCM prescription played a crucial role for treating DR by inhibiting inflammatory response,oxidative stress,retinal pigment epithelium cell apoptosis and retinal neovascularization through various pathways,such as the AGE-RAGE signaling pathway in diabetic complications and the MAPK signaling pathway.Finally,molecular docking and MD simulation demonstrated that almost all core active ingredients exhibited satisfactory binding energies to core targets.Conclusions:This study identified a novel TCM prescription and unveiled its multi-component,multi-target and multi-pathway characteristics for treating DR.These findings provide a scientific basis and novel insights into the development of drugs for DR prevention and

关键词： TCM prescriptions diabetic retinopathy medication rule molecular mechanism data mining network pharmacology molecular docking

PEPT1-mediated prodrug strategy for oral delivery of peramivir

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Asian Journal of pharmaceutical Sciences 2018年第6期13卷 555-565页

作者： Yongbing Sun Wei Gan Mingdao Lei Wei Jiang Meng Cheng Junwei He Qi Sun Wan Liu Lvjiang Hu Yi Jin Division of Pharmaceutics National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine Jiangxi University of Traditional Chinese Medicine Department of Pharmacy Jiangxi Maternal and Child Health Hospital Research center of Natural Resources of chinese Medicinal Materials and Ethnic medicine Jiangxi University of Traditional Chinese Medicine Affiliated Hospital of Jiangxi University of Traditional chinese medicine

Peramivir was a novel and highly potent neuraminidase(NA) inhibitor for the treatment of influenza A and B. However, it exhibited a very low oral bioavailability(only 3%) due to the high polarity(log P of-1.4) and the low membrane permeability across the intestine. To utilize the PEPT1-mediated prodrug strategy to improve the oral absorption and develop the oral alternative, seven amino acid ester prodrugs and seven amino acid amide prodrugs have been synthesized. The permeability of these prodrugs across Caco-2 cells were screened. Peramivr-(CH_2)_2-l-Val and Peramivir-l-Ile were of the highest permeability in ester prodrugs and amide prodrugs, respectively, and then they were selected for further studies. Glycylsarcosine(gly-sar) uptake by Caco-2 could be inbihited by Peramivir-(CH_2)_2-l-Val and Peramivir-l-Ile in a concentration-dependent manner, and the IC 50 was 1.34 ± 0.31 m M and 1.78 ± 0.48 m M, respectively. The direct uptake of Peramivir-(CH_2)_2-l-Val and Peramivirl-Ile in MDCK-PEPT1 cells were significantly higher than in MDCK mock cells, and could be markedly inhibited by gly-sar. The uptake of Peramivir-(CH_2)_2-l-Val and Peramivir-l-Ile(0.01 to 50 m M) in MDCK-hPEPT1 cells conformed to Michaelis–Menten Equation. The oral bioavailability of peramivir was 65.3% and 37.3% after the oral administration of Peramivir-(CH_2)_2-l-Val and Peramivir-l-Ile to rats, respectively. The oral absorption and bioactivation of Peramivir-(CH_2)_2-l-Val was rapid and extensive, and no Peramivir-(CH_2)_2-l-Val was found in plasma. Because the amide bond was relatively stable, Peramivir-l-Ile could not be totally converted to the parent drug in vivo. Peramivir-(CH_2)_2-l-Val with good oral profiles and rapid bioactivation might be a promising prodrug for the further clinic development. The present study also corroborated the idea that the PEPT1-mediated prodrug approach has enormous promise for improving the oral absorption of poorly absorbed drug.

关键词： Peramivir Prodrug Peptide transporter 1 Pharmacokinetics Oral bioavailability

A new flavonoid glucoside from Cassia angustifolia

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chinese Chemical Letters 2009年第3期20卷 320-321页

作者： Qiu Ping Wu Zhu Ju Wang Li Ying Tang Mei Hong Fu Yan He Institute of Traditional chinese Materia Medica China Academy of Chinese Medical Sciences Beijing 100700 China The national pharmaceutical engineering center (NPEC) for solid preparation in chinese herbal medicine Nanchang 330006 China

A new flavonoid glucoside with a known one was isolated from the leaves of Cassia angustifolia. Based on the spectral analysis, including MS, ^1H NMR, ^13C NMR, DEPT, ^1H-1HCOSY, HMQC, HMBC and NOSEY, their chemical structures were determined as kaempferol-3-O-[（6＇＇＇-O-trans-sinnapoyt）-β-D-glucopyranosyl （1 → 6）]-β-D-glucopyranoside 1 and apigenin-6,8-di-C-glycoside 2.

关键词： Cassia angustifolia Flavonol glucoside Kaempferol-3-O-[ （6＇＇＇-O-trans-sinnapoyl）-β-D-glucopyranosyl-（1→6）]-β-D-glucopyranoside

A new sulfated triterpenoid from the bark of Zygophyllum fabago L.

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chinese Chemical Letters 2010年第9期21卷 1100-1102页

作者： Yu Lin Feng Bin Xie He Ran Li Qiong Ming Xu Xiao Juan Zhang Yue Sheng Wang Shi Lin Yang national pharmaceutical engineering Centre for solid preparation in chinese herbal medicine Nanchang 330006 China Jiangxi University of Traditional chinese medicine Nanchang 330006 China College of Pharmacy. Soochow University. Suzhou 215123. China

A new sulfated triterpenoid,3β,24-dihydroxyurs-20-ene-24-O-sulphonyl-28-oic acid（fabagoin.1） was isolated from the barks of Zygophyllum fabago L.Its structure was elucidated on the basis of spectroscopic data.

关键词： Zygophyllum fabago L. Sulfated triterpenoid Fabagoin

Heterologous biosynthesis of medicarpin using engineered Saccharomyces cerevisiae

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Synthetic and Systems Biotechnology 2023年第4期8卷 749-756页

作者： Chujie Lu Rui Du Hao Fu Jizhao Zhang Ming Zhao Yongjun Wei Wei Lin Jiangsu Collaborative Innovation center of chinese Medicinal Resources Industrialization NanjingChina School of Pharmacy Nanjing University of Chinese MedicineNanjingChina Key Laboratory of Advanced Drug preparation Technologies Ministry of EducationSchool of Pharmaceutical SciencesZhengzhou UniversityZhengzhouChina Department of Pathogen Biology School of Medicine&Holistic Integrative MedicineNanjing University of Chinese MedicineNanjingChina Xinjiang Institute of Traditional chinese medicine and Ethnic medicine UrumqiChina

Medicarpin is an important bioactive compound with multiple medicinal activities,including anti-tumor,anti-osteoporosis,and anti-bacterial effects.Medicarpin is associated with pterocarpans derived from medicinal plants,such as Sophora japonica,Glycyrrhiza uralensis Fisch.,and Glycyrrhiza glabra L.However,these medicinal plants contain only low amounts of medicarpin.Moreover,the planting area for medicarpin-producing plants is limited;consequently,the current medicarpin supply cannot meet the high demands of medicinal markets.In this study,eight key genes involved in medicarpin biosynthesis were identified using comparative transcriptome and bioinformatic analyses.In vitro and in vivo enzymatic reaction confirmed the catalytic functions of candidate enzymes responsible for the biosynthesis of medicarpin and medicarpin intermediates.Further engineering of these genes in Saccharomyces cerevisiae achieved the heterologous biosynthesis of medicarpin using liquiritigenin as a substrate,with a final medicarpin yield of 0.82±0.18 mg/L.By increasing the gene copy numbers of vestitone reductase(VR)and pterocarpan synthase(PTS),the final medicarpin yield was increased to 2.05±0.72 mg/L.This study provides a solid foundation for the economic and sustainable production of medicarpin through a synthetic biology strategy.

关键词： Medicarpin Glycyrrhiza glabra L. Saccharomyces cerevisiae Medicarpin biosynthesis pathway Transcriptome sequencing Pterocarpan

Limitation standard of toxic aconitines in Aconitum proprietary chinese medicines using on-line extraction electrospray ionization mass spectrometry

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Acta Pharmaceutica Sinica B 2020年第8期10卷 1511-1520页

作者： Zi-Dong Qiu Xu-Ya Wei Rui-Qi Sun Jin-Long Chen Ting Tan Jia-Quan Xu Guang-Hong Cui Tong Chen Juan Guo Chang-Jiang-Sheng Lai Lu-Qi Huang State Key Laboratory Breeding Base of Dao-di Herbs National Resource Center for Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China The national pharmaceutical engineering center for solid preparation in chinese herbal medicine Jiangxi University of Traditional Chinese MedicineNanchang 330006China State Key Laboratory of Natural medicines China Pharmaceutical UniversityNanjing 210009China Jiangxi Key Laboratory for Mass Spectrometry and Instrumentation College of ChemistryBiology and Material SciencesEast China Institute of TechnologyNanchang 330013China

Development of rapid analytical methods and establishment of toxic component limitation standards are of great importance in quality control of traditional chinese medicine. Herein, an online extraction electrospray ionization mass spectrometry(oEESI-MS) coupled with a novel whole process integral quantification strategy was developed and applied to direct determination of nine key aconitine-type alkaloids in 20 Aconitum proprietary chinese medicines(APCMs). Multi-type dosage forms(e.g., tablets, capsules, pills, granules, and liquid preparation) of APCM could be determined directly with excellent versatility. The strategy has the characteristics of high throughput, good tolerance of matrix interference, small amount of sample(~0.5 mg) and reagent(~240 μL) consumption, and short analysis time for single sample(chinese Pharmacopoeia severally, and turned out that HWT-based toxicity evaluation results were closer to the real clinical applications. Hence,a more accurate and reliable APCM toxicity limitation was established and expected to play an important guiding role in clinics. The current study extended the power of ambient MS as a method for the direct quantification of molecules in complex samples, which is commonly required in pharmaceutical analysis,food safety control, public security, and many other disciplines.

关键词： Aconitum dosage tablets

Using the Box-Behnken Response Surface Method to Optimize the preparation and Characterization of Lavender and Fennel Volatile oilβ-cyclodextrin Form Inclusion Complex

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World Journal of Traditional chinese medicine 2018年第2期4卷 54-61页

作者： Yuan-Yuan Liu Guo-Song Zhang Guang-Wei Zhu Ai-Ni-Wa-Er Aikemu Jia-Jia Ai Dong-Xun Li The national pharmaceutical engineering center for solid preparation in chinese herbal medicine Jiangxi University of Traditional Chinese Medicine chinese medicine Research Institute Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Basic Medical College Xinjiang Medical University

Objective:The objective of this study is to study the best inclusion technology of Lavender-and fennel-mixed volatile oil by beta?cyclodextrin(β-CD) and characterize the final product thereafter.Methods:Using the saturated water solution method,the volatile β-CD inclusion complex was produced.The effect of volatile oil weight ratio,inclusion temperature and inclusion time on the inclusive quality was studied by measuring the yield of inclusion and inclusion rate of volatile oil as evaluation indexes.The preparation method of inclusion complex was then optimized by the Box-Behnken response surface method.The inclusion complex was characterized by ultraviolet spectrophotometry,thin-layer chromatography,thermogravimetry and differential thermal analysis,and the microscopic imaging method.Results:The optimized conditions were the weight ratio of β-CD to volatile oil was 8.13:1(g/ml).The inclusion temperature was 44°C.The inclusion time was 1 h.Conclusion:We were able to produce an inclusion complex with high inclusion rate of volatile oil and high yield of inclusion using the preparation method mentioned above.Furthermore,the method can also improve the stability of volatile oil in abnormal savda munziq.This study can provide a good reference for the development of new preparations.

关键词： Fennel inclusion complex lavender response surface method volatile oil β-cyclodextrin

Enhanced treatment for cerebral ischemia-reperfusion injury of puerarin loading liposomes through neutrophils-mediated targeted delivery

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Nano Research 2021年第12期14卷 4634-4643页

作者： Wei Liu Haowei Lu Xiaoyong Rao Xiang Li Hongdan Lu Feifei Li Yan He Riyue Yu Rongsheng Zhong Yao Zhang Xiaojian Luo Hongliang Xin national pharmaceutical engineering center for solid preparation in chinese herbal medicine Jiangxi University of Traditional Chinese MedicineNanchang330006China The Affiliated Hospital of Jiangxi University of Traditional chinese medicine Nanchang330006China Department of Pharmaceutics and Key Laboratory of Cardiovascular&Cerebrovascular medicine School of PharmacyNanjing Medical UniversityNanjing211166China Department of Pharmacy Kangda College of Nanjing Medical UniversityLianyungang222000China

The recovery of blood circulation following cerebral infarction-associated thrombolysis brings new damage to the brain,which is cerebral ischemia-reperfusion injury(CIRI).Inflammation is the main pathological mechanism of CIRI.The inflammatory response triggered by cerebral ischemia-reperfusion provides neutrophils with a special opportunity to facilitate drug delivery to the site of ischemic penumbra through the chemotaxis of inflammatory factors by neutrophils.Puerarin is an isoflavone derivative with a significant neuroprotective effect in vitro.But the blood-brain barrier(BBB)impedes its therapeutic efficacy on CIRI within the brain.Inspired by the pathological process,we have used neutrophils as carriers to enhance the BBB penetration of liposomes loaded with puerarin and improve the concentration of puerarin in the brain parenchyma in this study.These results showed that puerarin-containing liposomes were released in response to inflammatory conditions associated with brain injury to enhance the neuroprotection effect at the ischemic penumbra.

关键词： cerebral ischemia-reperfusion injury neuroprotection neutrophils puerarin liposomes