"Ciliatoside A, isolated from Peristrophe japonica, inhibits HBsAg expression and cccDNA transcription by inducing autophagy"

作者全名："Fang, Ren; Ming, Tan; Ng, Jerome P. L.; Guo, Wu An; Yu, Yuan Si; Hui, Zhang; Hua, Ren Ji; Tao, Cheng Sheng; Juan, Zhang; Hong, Lo Hang; Wong, Vincent Kam Wai; Law, Betty Yuen Kwan; Juan, Chen"

作者地址："[Fang, Ren; Ming, Tan; Yu, Yuan Si; Hui, Zhang; Hua, Ren Ji; Tao, Cheng Sheng; Juan, Chen] Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Dept Infect Dis,Key Lab Mol Biol Infect Dis Design, Chongqing, Peoples R China; [Ng, Jerome P. L.; Hong, Lo Hang; Wong, Vincent Kam Wai; Law, Betty Yuen Kwan] Macau Univ Sci & Technol, Dr Nehers Biophys Lab Innovat Drug Discovery, State Key Lab Qual Res Chinese Med, Macau, Peoples R China; [Juan, Chen] Chongqing Med Univ, Key Lab Lab Med Diagnost, Chinese Minist Educ, Chongqing, Peoples R China; [Fang, Ren; Juan, Zhang] Chongqing Hosp Tradit Chinese Med, Chongqing Key Lab Sichuan Chongqing Coconstruct Di, Chongqing, Peoples R China; [Guo, Wu An] Southwest Med Univ, Sch Pharm, Sichuan Key Med Lab New Drug Discovery & Drug Abil, Key Lab Med Electrophysiol,Minist Educ, Luzhou, Peoples R China; [Juan, Chen] Room 617,Coll Life Sci Bldg,1 YiXueYuan Rd, Chongqing 400016, Peoples R China; [Wong, Vincent Kam Wai; Law, Betty Yuen Kwan] Macau Univ Sci & Technol, Room 704a-02,Block H,Ave Wai Long, Taipa, Macau, Peoples R China"

通信作者："Juan, C (通讯作者)，Room 617,Coll Life Sci Bldg,1 YiXueYuan Rd, Chongqing 400016, Peoples R China.; Wong, VKW; Law, BYK (通讯作者)，Macau Univ Sci & Technol, Room 704a-02,Block H,Ave Wai Long, Taipa, Macau, Peoples R China."

来源：ANTIVIRAL RESEARCH

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000904290300001

JCR分区：Q1

影响因子：4.5

年份：2023

卷号：209

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Hepatitis B virusB surface antigen; Ciliatoside A; Peristrophe japonica; Autophagy; AMPK

摘要："Hepatitis B surface antigen (HBsAg) loss and seroconversion are considered as an end point of a functional cure. Therefore, it is crucial to find new agents which could efficiently decrease HBsAg. Traditional herbal plants have been considered as an important source of new hepatitis B drugs development for their extensive use in anti-microbial and anti-inflammation. In this study, Peristrophe japonica, which could remarkably reduce HBsAg in the supernatant of HepG2.2.15 cells, was screened out for further extraction. Here, an active ethyl acetate fraction of Peristrophe japonica containing 34 sub-fractions was extracted. Subsequently, the monomeric compound Cil-iatoside A was isolated and identified as a potential antiviral reagent with low cytotoxicity from Fraction 30. Ciliatoside A exhibited strong inhibition on intracellular and circulating HBsAg and HBV RNAs in HBV-infected cells and an HBV recombinant-cccDNA mouse model. The mechanistic study revealed that Ciliatoside A exhibited a potent anti-HBV effect through inducing autophagy-lysosomal pathway to autophagic degradation of HBc by activating AMPK-ULK1 axis and inhibiting mTOR activation. In summary, we have identified a novel antiviral compound Ciliatoside A isolated from Peristrophe japonica. This study may provide important direction and new ideas for the discovery of hepatitis B cure drugs."

基金机构：National Natural Science Foundation of China; Na-tional key research and development program; Creative Research Group of CQ University; Chongqing Natural Science Foundation; Natural Science Foundation Project of Chongqing; China Postdoctoral Science Foun-dation; Macao Science and Technology Devel-opment Fund; FDCT grant from the Macao Science and Technology Development Fund; [81861168035]; [81922011]; [81871656]; [2022YFA1303600]; [CXQT19016]; [CSTB2022NSCQ-MSX1560]; [cstc2019jscx-dxwtBX0020]; [2021MD703920]; [0036/2018/AFJ]; [001/2020/ALC]

基金资助正文："Acknowledgments This work was supported by National Natural Science Foundation of China (Grant No. 81861168035, 81922011 and 81871656 to JC) ; Na-tional key research and development program (2022YFA1303600 to JC) ; Creative Research Group of CQ University (CXQT19016 to JC) ; Chongqing Natural Science Foundation (cstc2018jcyjAX0114 to JC) ; Natural Science Foundation Project of Chongqing (cstc2019jscx-dxwtBX0020 to JC) ; Chongqing Natural Science Foundation (CSTB2022NSCQ-MSX1560 to FR) ; China Postdoctoral Science Foun-dation (2021MD703920 to FR) ; Macao Science and Technology Devel-opment Fund (0036/2018/AFJ to YK L) ; FDCT grant from the Macao Science and Technology Development Fund (001/2020/ALC to KW W) ."