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Ganoderma lucidum spore oil(GLSO),a novel antioxidant,extends the average life span in Drosophila melanogaster

Food Science and Human Wellness 2021年第1期10卷 38-44页

作者： Yi Zhang Hongfei Cai Zhu Tao Cheng Yuan Zhaojian Jiang Juyan Liu Hiroshi Kurihara Wendong Xu Institute of Integrated Chinese and Western Medicine postdoctoral research station Jinan UniversityGuangzhou 510632China postdoctoral research station of guangzhou pharmaceutical holdings limited Guangdong 510130China Institute of National Engineering research Center for Modernization of Extraction and Separation Process of Traditional Chinese Medicine Hanfang Pharmaceutical Co.LtdGuangdong 510240China guangzhou pharmaceutical holdings Ltd Guangdong 510130China Institute of Traditional Chinese Medicine and Natural Products Jinan University601Huangpu Avenue WestGuangzhou510632China

In ancient China,Ganoderma lucidum was believed to be a medical fungus that could increase lifespan.Recently,pharmacologic studies have found that polysaccharide peptides and triterpenoids extracted from Ganoderma lucidum have various physiological effects as active compounds.However,the effects of spore oil isolated from Ganoderma lucidum remains unknown.In this study,the biological effects of Ganoderma lucidum spore oil(GLSO)were evaluated using a Drosophila melanogaster model.Compared with untreated groups,groups treated with GLSO had significantly longer average and maximum lifespan in both normal conditions and under oxidative stress.The activities of various antioxidant enzymes were measured to determine the antioxidant effect of GLSO.GLSO treatment markedly enhanced total superoxide dismutase(SOD)and catalase(CAT)activity and decreased levels of malondialdehyde(MDA).Further,we found dose-dependent increases in the mRNA expression of Cu,Zn-SOD,Mn-SOD,and CAT in GLSO-treated groups.These results suggest that GLSO may effectively eliminate free radicals and extend lifespan in Drosophila.Future work should investigate the value of GLSO as a functional food for the prevention of aging in larger animal models.

关键词： Ganoderma lucidum spore oil Antioxidant activity Drosophila melanogaster Anti-aging

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Impairment of the autophagy-lysosomal pathway in Alzheimer’s diseases: Pathogenic mechanisms and therapeutic potential

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Acta Pharmaceutica Sinica B 2022年第3期12卷 1019-1040页

作者： Wei Zhang Chengchao Xu Jichao Sun Han-Ming Shen Jigang Wang Chuanbin Yang Department of Geriatrics Shenzhen People’s Hospital(the Second Clinical Medical CollegeJinan Universitythe First Affiliated HospitalSouthern University of Science and Technology)Shenzhen 518020China Integrated Chinese and Western Medicine postdoctoral research station Jinan UniversityGuangzhou 510632China Artemisinin research Center Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China Faculty of Health Sciences University of MacaoTaipaMacao 999078China Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China

Alzheimer’s disease(AD),the most common neurodegenerative disorder,is characterized by memory loss and cognitive dysfunction.The accumulation of misfolded protein aggregates including amyloid beta(Aβ)peptides and microtubule associated protein tau(MAPT/tau)in neuronal cells are hallmarks of AD.So far,the exact underlying mechanisms for the aetiologies of AD have not been fully understood and the effective treatment for AD is limited.Autophagy is an evolutionarily conserved cellular catabolic process by which damaged cellular organelles and protein aggregates are degraded via lysosomes.Recently,there is accumulating evidence linking the impairment of the autophagy-lysosomal pathway with AD pathogenesis.Interestingly,the enhancement of autophagy to remove protein aggregates has been proposed as a promising therapeutic strategy for AD.Here,we first summarize the recent genetic,pathological and experimental studies regarding the impairment of the autophagy-lysosomal pathway in AD.We then describe the interplay between the autophagy-lysosomal pathway and two pathological proteins,Aβand MAPT/tau,in AD.Finally,we discuss potential therapeutic strategies and small molecules that target the autophagy-lysosomal pathway for AD treatment both in animal models and in clinical trials.Overall,this article highlights the pivotal functions of the autophagy-lysosomal pathway in AD pathogenesis and potential druggable targets in the autophagy-lysosomal pathway for AD treatment.

关键词： Alzheimer’s disease(AD) Amyloid beta(Aβ)peptides MAPT/tau Autophagy-lysosomal pathway Autophagy enhancers Autophagy Mitophagy Neurodegenerative diseases

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Celastrol induces ferroptosis in activated HSCs to ameliorate hepatic fibrosis via targeting peroxiredoxins and HO-1

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Acta Pharmaceutica Sinica B 2022年第5期12卷 2300-2314页

作者： Piao Luo Dandan Liu Qian Zhang Fan Yang Yin-Kwan Wong Fei Xia Junzhe Zhang Jiayun Chen Ya Tian Chuanbin Yang Lingyun Dai Han-Ming Shen Jigang Wang Artemisinin research Center Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China Central People’s Hospital of Zhanjiang Zhanjiang 524037China Department of Urology the Second Clinical Medical CollegeJinan University(Shenzhen People’s Hospital)Shenzhen 518020China Integrated Chinese and Western Medicine postdoctoral research station Jinan UniversityGuangzhou 510632China Faculty of Health Sciences University of MacaoTaipaMacao 999078China Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China

Ferroptosis is a form of regulated cell death, characterized by excessive membrane lipid peroxidation in an iron-and ROS-dependent manner. Celastrol, a natural bioactive triterpenoid extracted from Tripterygium wilfordii, shows effective anti-fibrotic and anti-inflammatory activities in multiple hepatic diseases. However, the exact molecular mechanisms of action and the direct protein targets of celastrol in the treatment of liver fibrosis remain largely elusive. Here, we discover that celastrol exerts anti-fibrotic effects via promoting the production of reactive oxygen species(ROS) and inducing ferroptosis in activated hepatic stellate cells(HSCs). By using activity-based protein profiling(ABPP) in combination with bio-orthogonal click chemistry reaction and cellular thermal shift assay(CETSA), we show that celastrol directly binds to peroxiredoxins(PRDXs), including PRDX1, PRDX2, PRDX4 and PRDX6,through the active cysteine sites, and inhibits their anti-oxidant activities. Celastrol also targets to heme oxygenase 1(HO-1) and upregulates its expression in activated-HSCs. Knockdown of PRDX1, PRDX2,PRDX4, PRDX6 or HO-1 in HSCs, to varying extent, elevated cellular ROS levels and induced ferroptosis. Taken together, our findings reveal the direct protein targets and molecular mechanisms via which celastrol ameliorates hepatic fibrosis, thus supporting the further development of celastrol as a promising therapeutic agent for liver fibrosis.

关键词： Celastrol Ferroptosis Peroxiredoxin HO-1 Hepatic fibrosis ABPP Anti-oxidant Reactive oxygen species

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Single-cell transcriptomic dissection of the cellular and molecular events underlying the triclosan-induced liver fibrosis in mice

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Military Medical research 2023年第5期10卷 599-619页

作者： Yun-Meng Bai Fan Yang Piao Luo Lu-Lin Xie Jun-Hui Chen Yu-Dong Guan Hong-Chao Zhou Teng-Fei Xu Hui-Wen Hao Bing Chen Jia-Hui Zhao Cai-Ling Liang Ling-Yun Dai Qing-Shan Geng Ji-Gang Wang 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 Urology Shenzhen People’s Hospitalthe First Affiliated HospitalSouthern University Science and Technologythe Second Clinical Medical CollegeJinan UniversityShenzhen 518020China Integrated Chinese and Western Medicine postdoctoral research station Jinan UniversityGuangzhou 510632China Artemisinin research Center and Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Center for Reproductive Medicine Dongguan Maternal and Child Health Care HospitalSouthern Medical UniversityDongguan 523125GuangdongChina

Background: Triclosan [5-chloro-2-(2,4-dichlorophenoxy) phenol, TCS], a common antimicrobial additive in many personal care and health care products, is frequently detected in human blood and urine. Therefore, it has been considered an emerging and potentially toxic pollutant in recent years. Long-term exposure to TCS has been suggested to exert endocrine disruption effects, and promote liver fibrogenesis and tumorigenesis. This study was aimed at clarifying the underlying cellular and molecular mechanisms of hepatotoxicity effect of TCS at the initiation stage.Methods: C57BL/6 mice were exposed to different dosages of TCS for 2 weeks and the organ toxicity was evaluated by various measurements including complete blood count, histological analysis and TCS quantification. Single cell RNA sequencing(scRNA-seq) was then carried out on TCS-or mock-treated mice livers to delineate the TCS-induced hepatotoxicity. The acquired single-cell transcriptomic data were analyzed from different aspects including differential gene expression, transcription factor(TF) regulatory network, pseudotime trajectory, and cellular communication, to systematically dissect the cellular and molecular events after TCS exposure. To verify the TCS-induced liver fibrosis,the expression levels of key fibrogenic proteins were examined by Western blotting, immunofluorescence, Masson’s trichrome and Sirius red stainings. In addition, normal hepatocyte cell MIHA and hepatic stellate cell LX-2 were used as in vitro cell models to experimentally validate the effects of TCS by immunological, proteomic and metabolomic technologies.Results: We established a relatively short term TCS exposure murine model and found the TCS mainly accumulated in the liver. The scRNA-seq performed on the livers of the TCS-treated and control groups profiled the gene expressions of > 76,000 cells belonging to 13 major cell types. Among these types, hepatocytes and hepatic stellate cells(HSCs)were significantly increased in TCS-treated group. We found that TCS promoted fibros

关键词： Triclosan Single cell RNA sequencing Liver fibrogenesis Hepatic stellate cell

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Biotransformation ofα-asarone by Alternaria longipes CGMCC 3.2875

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Chinese Journal of Natural Medicines 2021年第9期19卷 700-705页

作者： ZOU Jian ZHANG Shuai ZHAO Huan WANG Yong-Heng ZHOU Zheng-Qun CHEN Guo-Dong HU Dan LI Ning YAO Xin-Sheng GAO Hao Institute of Traditional Chinese Medicine&Natural Products College of Pharmacy/Guangdong Province Key Laboratory of Pharmacodynamic Constituents ofTCM and New Drugs ResearchJinan UniversityGuangzhou 510632China College of Traditional Chinese Materia Medica Shenyang Pharmaceutical UniversityShenyang 110016China College of Traditional Chinese Medicine Jinan UniversityGuangzhou 510632China Integrated Chinese and Western Medicine postdoctoral research station Jinan UniversityGuangzhou 510632China

Biotransformation ofα-asarone by Alternaria longipes CGMCC 3.2875 yielded two pairs of new neolignans,(+)(7 S,8 S,7’S,8’R)iso-magnosalicin(1 a)/(-)(7 R,8 R,7’R,8’S)iso-magnosalicin(1 b)and(+)(7 R,8 R,7’S,8’R)magnosalicin(2 a)/(-)(7 S,8 S,7’R,8’S)magnosalicin(2 b),and four known metabolites,(±)acoraminol A(3),(±)acoraminol B(4),asaraldehyde(5),and 2,4,5-trimethoxybenzoic acid(6).Their structures,including absolute configurations,were determined by extensive analysis of NMR spectra,X-ray crystallography,and quantum chemical ECD calculations.The cytotoxic activity and Aβ_(42)aggregation inhibitory activity of all the compounds were evaluated.Compound 2 displayed significant anti-Aβ_(42)aggregation activity with an inhibitory rate of 60.81%(the positive control EGCG:69.17%).In addition the biotransformation pathway ofα-asarone by Alternaria longipes CGMCC 3.2875 was proposed.

关键词： Biotransformation α-Asarone Alternaria longipes CGMCC 3.2875 Anti-Aβ_(42)aggregation activity

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Crosstalk between nano/micro particulate technologies and Chinese medicine: a bibliometric analysis

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Traditional Medicine research 2023年第6期8卷 9-23页

作者： Zheng-Wei Huang Meng-Qin Guo Wen-Hao Wang Jian-Bo He Chuan-Bin Wu Xin Pan Xue-Juan Zhang Ying Huang Ping Hu College of Pharmacy Jinan UniversityGuangzhou 511436China School of pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006China Guangdong Engineering research Center of Chinese Medicine&Disease Susceptibility Integrated Chinese and Western Medicine Postdoctoral Research StationJinan UniversityGuangzhou 510632China

Background:Chinese medicine is widely applied in Asian and Western countries for its outstanding therapeutic effect,but there are still unsolved problems such as unclear active ingredients and pharmacological effects.The application of nano/microparticle technology in Chinese medicine may become a promising strategy to solve this problem in the near future(provided that more efforts are made to in-depth exploration).In this work,a comprehensive analysis of the field was carried out from a bibliometrics perspective,and further the publishing trends and research hotspots were figured out.Methods:The articles or reviews from 2000 to 2020 were retrieved in the database of Web of Science Core Collection.The documents were processed by Clarivate Analytic,Visualization of Similarities viewer,Statistical Analysis Toolkit for Informetrics and bibliometric online platform,and the data were visualized.Finally,a bibliometric summary,citation analysis results and research trends were described.Results:A bibliometric analysis of 773 articles of interest showed that research in this field had continued to grow in recent years,with a high degree of interdisciplinary integration.Secondly,this field attached great importance to the quantitative analysis of Chinese medicine combined with nano/micro particle technology.Chinese medicine,nanoparticles and liposomes were the most accessed keywords.China was the main contributing country,and the top-10 contributing organizations were all located in China.Co-authorship was a common phenomenon in this field.Conclusion:The published literature on the application of nano/micro particle technology in Chinese medicine was summarized.The results suggested that bibliometric analysis could predict possible directions for future research in this field.

关键词： Chinese medicine nanotechnology bibliometric analysis Web of Science

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Alleviating effects and mechanisms of action of large-leaf yellow tea drinking on diabetes and diabetic nephropathy in mice

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Food Science and Human Wellness 2023年第5期12卷 1660-1673页

作者： Guangshan Zhao Jianyuan Teng Ruixia Dong Qiuyan Ban Lian Yang Kang Du Yifei Wang Hanlin Pu Chung S.Yang Zhe Ren Innovation Team of Food Nutrition and Safety Control College of Food Science&TechnologyHenan Agricultural UniversityZhengzhou 450002China Biology postdoctoral research station Department of Cell BiologyCollege of Life Science and TechnologyJinan UniversityGuangzhou 510632China College of Horticulture Jinling Institute of TechnologyNanjing 211169China Department of Forestry and Technology Lishui Vocational and Technical CollegeLishui 323000China Department of Tea Science College of HorticultureHenan Agricultural UniversityZhengzhou 450002China Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System School of PharmacyGuangdong Pharmaceutical UniversityGuangzhou 510006China Department of Chemical Biology Ernest Mario School of PharmacyRutgersThe State University of New JerseyPiscataway 08901USA International Joint research Laboratory of Tea Chemistry and Health Effects Anhui Agricultural UniversityHefei 230036China

Our previous study found that large-leaf yellow tea(LYT)had interesting hypoglycemic activity in high-fat diet-induced obese mice and highly safety in healthy mice. To study the anti-diabetic potential of LYT, the present study further investigated the preventive effects and mechanisms of action of LYT administration on diabetes and diabetic nephropathy in high-fat diet plus streptozotocin-induced diabetic mice. Results showed that LYT infusions(1/100 and 1/50, m/V)as drinking fluid for 4 weeks reduced diabetic polydipsia and polyuria, enhanced glucose tolerance and insulin sensitivity, and lowered fasting blood glucose level. The underlying mechanisms involve downregulation of gluconeogenesis(lower protein levels of TXNIP and FBP and enzyme activity of FBP), upregulation of lipid catabolism(higher protein levels of CPT-1α and PPARα), downregulation of lipogenesis(lower protein level of SREBP-1), and modification of the structure and abundance of gut microbiota to modulate metabolic homeostasis. Moreover, LYT administration prevented diabetic nephropathy, possibly due to reduced glucose-caused osmotic diuresis and lowered levels of renal PKC-β2, NLRP3 as well as membrane PKC-α, AQP2 and glycosylated AQP2 proteins. Taken together, LYT exhibits the activities in alleviating diabetic symptoms, ameliorating glucose and lipid dysmetabolism and fatty liver, and preventing diabetic nephropathy in diabetic mice. These activities may be explored for the prevention and treatment of diabetes in humans.

关键词： Diabetes Glucose and lipid metabolism Gut microbiota Diabetic nephropathy Large-leaf yellow tea

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New ent-kaurane diterpenes with chiral epoxyangelate moieties from Wedelia prostrata

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Chinese Chemical Letters 2019年第2期30卷 451-453页

作者： Zhongnan Wu Yubo Zhang Wen Li Nenghua Chen Qianwen Niu Yingying Li Qingguo Li Dan Yang Yaolan Li Guocai Wang Institute of Traditional Chinese Medicine ξ Natural Products College of Pharmacy and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs ResearchJinan University Integrated Chinese and Western Medicine postdoctoral research station Jinan University School of pharmaceutical Sciences Guangzhou University of Chinese Medicine Department of Specific Diagnosis The 324th Military Hospital

Four new ent-kaurane diterpenes with chiral epoxyangelate moieties, (2′R,3′R)-3 a- (2′,3′-epoxyangeloyloxy)-kaur-16-en-19-oic acid (1), (2′S,3′S)-3 a- (2′,3′-epoxyangeloyloxy)-kaur-16-en-19-oic acid (2), (2′S,3′R)-3 a- (2',3'-epoxyangeloyloxy)-kaur-16-en-19-oic acid (3) and (2′R,3′S)-3α- (2′,3'-epoxyangeloyloxy)-kaur-16-en-19-oic acid (4), along with eight known diterpenes (5-12), were isolated from Wedelia prostrata. The absolute configurations of the new structures were determined by X-ray crystallography,ECD calculations and chemical methods. All compounds were evaluated for their cytotoxicity activities on human HepG-2 cells,with IC_(50) values of 11.72 ±0.22 μmol/L to 54.75±1.12 μmol/L.

关键词： Wedelia prostrata Chiral epoxyangelate moieties Ent-kaurane diterpenes Absolute configuration Cytotoxicity activities

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Electrochemical detection of methyl-paraoxon based on bifunctional cerium oxide nanozyme with catalytic activity and signal amplification effect

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Journal of pharmaceutical Analysis 2021年第5期11卷 653-660页

作者： Yuzhou Sun Jinchao Wei Jian Zou Zehua Cheng Zhongming Huang Liqiang Gu Zhangfeng Zhong Shengliang Li Yitao Wang Peng Li State Key Laboratory of Quality research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao999078China Institute of Traditional Chinese Medicine&Natural Products College of PharmacyJinan UniversityGuangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs ResearchGuangzhou510632China Integrated Chinese and Western Medicine postdoctoral research station Jinan UniversityGuangzhou510632China Center of Super-Diamond and Advanced Films(COSDAF)and Department of Chemistry City University of Hong KongHong Kong999077China

A new electrochemical sensor for organophosphate pesticide(methyl-paraoxon)detection based on bifunctional cerium oxide(CeO_(2))nanozyme is here reported for the first time.Methyl-paraoxon was degraded into p-nitrophenol by using CeO_(2) with phosphatase mimicking activity.The CeO_(2) nanozymemodified electrode was then synthesized to detect p-nitrophenol.Cyclic voltammetry was applied to investigate the electrochemical behavior of the modified electrode,which indicates that the signal enhancement effect may attribute to the coating of CeO_(2) nanozyme.The current research also studied and discussed the main parameters affecting the analytical signal,including accumulation potential,accumulation time,and pH.Under the optimum conditions,the present method provided a wider linear range from 0.1 to 100 mmol/L for methyl-paraoxon with a detection limit of 0.06 mmol/L.To validate the proof of concept,the electrochemical sensor was then successfully applied for the determination of methyl-paraoxon in three herb samples,i.e.,Coix lacryma-jobi,Adenophora stricta and Semen nelumbinis.Our findings may provide new insights into the application of bifunctional nanozyme in electrochemical detection of organophosphorus pesticide.

关键词： Chinese medicine Nanozyme Organophosphorus Pesticide Methyl-paraoxon Electroanalysis

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Efficient induction of neural progenitor cells from human ESC/iPSCs on Type I Collagen

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Science China(Life Sciences) 2021年第12期64卷 2100-2113页

作者： Pengfei Liu Shubin Chen Yaofeng Wang Xiaoming Chen Yiping Guo Chunhua Liu Haitao Wang Yifan Zhao Di Wu Yongli Shan Jian Zhang Chuman Wu Dongwei Li Yanmei Zhang Tiancheng Zhou Yaoyu Chen Xiaobo Liu Chenxu Li Lihui Wang Bei Jia Jie Liu Bo Feng Jinglei Cai Duanqing Pei CAS Key Laboratory of Regenerative Biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China Ambulatory Surgical Center The 2nd Clinical medical College(Shenzhen People’s Hospital)of Jinan UniversityThe 1st Affiliated Hospitals of Southern University of Science and TechnologyShenzhen 518020China Integrated Chinese and Western Medicine postdoctoral research station Jinan UniversityGuangzhou 510632China Bioland Laboratory Guangzhou Regenerative Medicine and Health Guangdong LaboratoryGuangzhou 510005China School of Biomedical Sciences The Chinese University of Hong KongHong Kong SARChina Centre for Regenerative Medicine and Health Hong Kong Institute of Science&InnovationChinese Academy of SciencesHong Kong SARChina Department of Regenerative Medicine School of Pharmaceutical ScienceJilin UniversityChangchun 130012China Department of Pathology Medical CollegeJinan UniversityGuangzhou 510632China The Center for Prenatal and Hereditary Disease Diagnosis Department of Obstetrics and GynecologyNanfang HospitalSouthern Medical UniversityGuangzhou 510515China Department of Obstetrics and Gynecology Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China

A stable,rapid and effective neural differentiation method is essential for the clinical applications of human embryonic stem cells(ESCs)or induced pluripotent stem cells(iPSCs)in treating neurological disorders and diseases.Herein,we established a novel and robust monolayer differentiation method to produce functional neural progenitor cells(NPCs)from human ESC/iPSCs on Type I Collagen.The derived cells not only displayed the requisite markers,but also behaved similarly to classic NPCs both in vitro and in vivo.Upon transplantation into traumatic brain injury model,the derived NPCs facilitated recovery from injury.We also found that SMAD signaling stayed down throughout the differentiation process on Type I Collagen,and the pluripotent signals were rapidly downregulated along with raising up of neural early markers on the third day.Meanwhile,ATAC-seq data showed the related mediation of distinct transcriptome and global chromatin dynamics during NPC induction.Totally,our results thus provide a convenient way to generate NPCs from human ESC/iPSCs for neural diseases’treatment.

关键词： ESCs iPSCs NPCs neural differentiation Type I Collagen

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