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| 1 | Artemisinin, the Magic Drug Discovered from Traditional Chinese Medicine显示文摘Artemisinin and its derivatives represent the most important and influential class of drugs in the fight against malaria. Since the discovery of artemisinin in the early 1970s, the global community has made great strides in characterizing and understanding this remarkable phytochemical and its unique chemical and pharmacological properties. Today, even as artemisinin continues to serve as the foundation for antimalarial therapy, numerous challenges have surfaced in the continued application and development of this family of drugs. These challenges include the emergence of delayed treatment responses to artemisinins in malaria and efforts to apply artemisinins for non-malarial indications. Here, we provide an overview of the story of artemisinin in terms of its past, present, and future. In particular, we comment on the current understanding of the mechanism of action (MOA) of artemisinins, and emphasize the importance of relating mechanistic studies to therapeutic outcomes, both in malarial and non-malarial contexts. | Jigang Wang Chengchao Xu Yin Kwan Wong Yujie Li Fulong Liao Tingliang Jiang Youyou Tu | 2019 | Engineering2019，5，1： | 16 |
| 2 | 18beta-glycyrrhetinic acid induces ROS-mediated apoptosis to ameliorate hepatic fibrosis by targeting PRDX1/2 in activated HSCs显示文摘Hepatic stellate cells(HSCs)are essential drivers of fibrogenesis.Inducing activated-HSC apoptosis is a promising strategy for treating hepatic fibrosis.18beta-glycyrrhetinic acid(18b-GA)is a natural compound that exists widely in herbal medicines,such as Glycyrrhiza uralensis Fisch,which is used for treating multiple liver diseases,especially in Asia.In the present study,we demonstrated that 18b-GA decreased hepatic fibrosis by inducing the apoptosis in activated HSCs.18b-GA inhibited the expression of a-smooth muscle actin and collagen type Ⅰ alpha-1.Using a chemoproteomic approach derived from activity-based protein profiling,together with cellular thermal shift assay and surface plasmon resonance,we found that 18b-GA covalently targeted peroxiredoxin 1(PRDX1)and peroxiredoxin 2(PRDX2)proteins via binding to active cysteine residues and thereby inhibited their enzymatic activities.18b-GA induced the elevation of reactive oxygen species(ROS),resulting in the apoptosis of activated HSCs.PRDX1 knockdown also led to ROS-mediated apoptosis in activated HSCs.Collectively,our findings revealed the target proteins and molecular mechanisms of 18b-GA in ameliorating hepatic fibrosis,highlighting the future development of 18b-GA as a novel therapeutic drug for hepatic fibrosis. | Qian Zhang Piao Luo Liuhai Zheng Jiayun Chen Junzhe Zhang Huan Tang Dandan Liu Xueling He Qiaoli Shi Liwei Gu Jiahao Li Qiuyan Guo Chuanbin Yang Yin Kwan Wong Fei Xia Jigang Wang | 2022 | Journal of Pharmaceutical Analysis2022，12，4： | 3 |
| 3 | Antifungal and antiviral products of marine organisms显示文摘 | Randy Chi Fai Cheung Jack Ho Wong Wen Liang Pan Yau Sang Chan Cui Ming Yin Xiu Li Dan He Xiang Wang Evandro Fei Fang Sze Kwan Lam Patrick Hung Kui Ngai Li Xin Xia Fang Liu Xiu Yun Ye Guo Qing Zhang Qing Hong Liu Ou Sha Peng Lin Chan Ki Adnan A Bekhit Alaa | 2014 | Applied Microbiology and Biotechnology2014，，8： | 2 |
| 4 | Target identification of natural medicine with chemical proteomics approach:probe synthesis,target fishing and protein identification显示文摘Natural products are an important source of new drugs for the treatment of various diseases.However,developing natural productbased new medicines through random moiety modification is a lengthy and costly process,due in part to the difficulties associated with comprehensively understanding the mechanism of action and the side effects.Identifying the protein targets of natural products is an effective strategy,but most medicines interact with multiple protein targets,which complicate this process.In recent years,an increasing number of researchers have begun to screen the target proteins of natural products with chemical proteomics approaches,which can provide a more comprehensive array of the protein targets of active small molecules in an unbiased manner.Typically,chemical proteomics experiments for target identification consist of two key steps:(1)chemical probe design and synthesis and(2)target fishing and identification.In recent decades,five different types of chemical proteomic probes and their respective target fishing methods have been developed to screen targets of molecules with different structures,and a variety of protein identification approaches have been invented.Presently,we will classify these chemical proteomics approaches,the application scopes and characteristics of the different types of chemical probes,the different protein identification methods,and the advantages and disadvantages of these strategies. | Xiao Chen Yutong Wang Nan Ma Jing Tian Yurou Shao Bo Zhu Yin Kwan Wong Zhen Liang Chang Zou Jigang Wang | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 2 |
| 5 | Single-cell transcriptome analysis reveals the regulatory effects of artesunate on splenic immune cells in polymicrobial sepsis显示文摘Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ dysfunction.Studies on the therapeutic effect and mechanism of immunomodulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various immune cells remain limited.This study aimed to investigate the protective effects and underlying mechanism of artesunate(ART)on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing(scRNA-seq)and experimental validations.The scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during sepsis.ART could restore neutrophils’chemotaxis and immune function in the septic spleen.It inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during sepsis.ART also promoted the differentiation and activity of splenic B cells in mice with sepsis.These results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the host.Overall,this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis,thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis. | Jiayun Chen Xueling He Yunmeng Bai Jing Liu Yin Kwan Wong Lulin Xie Qian Zhang Piao Luo Peng Gao Liwei Gu Qiuyan Guo Guangqing Cheng Chen Wang Jigang Wang | 2023 | Journal of Pharmaceutical Analysis2023，13，7： | 1 |
| 6 | Chemical proteomic profling with photoaffinity labeling strategy identifies antimalarial targets of artemisinin显示文摘Present research on the antimalarial mechanisms of artemisinin(ART)is mainly focused on covalent drug binding targets alkylated by free radicals,while non-covalent binding targets have rarely been reported.Here,we developed a novel photoaffinity probe of ART to globally capture and identify the antimalarial target proteins of ART through chemical proteomics.The results demonstrated that ART can bind to par-asite proteins by both covalent and non-covalent modification,and these may jointly contribute to the antimalarial effects.Our work enriches the research on the antimalarial targets of ART,and provides a new perspective for further exploring the antimalarial mechanism of ART. | Peng Gao Jiayun Chen Peng Sun Jianyou Wang Huan Tang Fei Xia Liwei Gu Huimin Zhang Chen Wang Yin Kwan Wong Yinhua Zhu Chengchao Xu Jigang Wang | 2023 | Chinese Chemical Letters2023，34，12： | 1 |
| 7 | Single-cell RNA sequencing deciphers the mechanism of sepsis-induced liver injury and the therapeutic effects of artesunate显示文摘Liver,as an immune and detoxification organ,represents an important line of defense against bacteria and infection and a vulnerable organ that is easily injured during sepsis.Artesunate(ART)is an anti-malaria agent,that also exhibits broad pharmacological activities including anti-inflammatory,immune-regulation and liver protection.In this study,we investigated the cellular responses in liver to sepsis infection and ART hepatic-protective mechanisms against sepsis.Cecal ligation and puncture(CLP)-induced sepsis model was established in mice.The mice were administered ART(10 mg/kg,i.p.)at 4 h,and sacrificed at 12 h after the surgery.Liver samples were collected for preparing single-cell RNA transcriptome sequencing(scRNA-seq).The scRNA-seq analysis revealed that sepsis-induced a dramatic reduction of hepatic endothelial cells,especially the subtypes characterized with proliferation and differentiation.Macrophages were recruited during sepsis and released inflammatory cytokines(Tnf,Il1b,Il6),chemokines(Ccl6,Cd14),and transcription factor(Nfkb1),resulting in liver inflammatory responses.Massive apoptosis of lymphocytes and abnormal recruitment of neutrophils caused immune dysfunction.ART treatment significantly improved the survival of CLP mice within 96 h,and partially relieved or reversed the above-mentioned pathological features,mitigating the impact of sepsis on liver injury,inflammation,and dysfunction.This study provides comprehensive fundamental proof for the liver protective efficacy of ART against sepsis infection,which would potentially contribute to its clinical translation for sepsis therapy. | Xue-ling He Jia-yun Chen Yu-lin Feng Ping Song Yin Kwan Wong Lu-lin Xie Chen Wang Qian Zhang Yun-meng Bai Peng Gao Piao Luo Qiang Liu Fu-long Liao Zhi-jie Li Yong Jiang Ji-gang Wang | 2023 | Acta Pharmacologica Sinica2023，44，9： | 1 |
| 8 | 通过鉴定关键靶标蛋白探究青蒿素抗疟机制显示文摘The widespread use of artemisinin(ART)and its derivatives has significantly reduced the global burden of malaria;however,malaria still poses a serious threat to global health.Although significant progress has been achieved in elucidating the antimalarial mechanisms of ART,the most crucial target proteins and pathways of ART remain unknown.Knowledge on the exact antimalarial mechanisms of ART is urgently needed,as signs of emerging ART resistance have been observed in some regions of the world.Here,we used a combined strategy involving mass spectrometry-coupled cellular thermal shift assay(MS-CETSA)and transcriptomics profiling to identify a group of putative antimalarial targets of ART.We then conducted a series of validation experiments on five prospective protein targets,demonstrating that ART may function against malaria parasites by interfering with redox homeostasis,lipid metabolism,and protein synthesis processes.Taken together,this study provides fresh perspectives on the antimalarial mechanisms of ART and identifies several crucial proteins involved in parasite survival that can be targeted to combat malaria. | Peng Gao Jianyou Wang Jiayun Chen Liwei Gu Chen Wang Liting Xu Yin Kwan Wong Huimin Zhang Chengchao Xu Lingyun Dai Jigang Wang | 2023 | Engineering2023，31，12： | 0 |
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