Plant-derived phosphocholine facilitates cellular uptake of anti-pulmonary fibrotic HJT-sRNA-m7  

作　　者：Jianchao Du Zhu Liang Jiantao Xu Yan Zhao Xiaoyun Li Yanli Zhang DANDan Zhao Ruxuan Chen Yang Liu Trupti Joshi Jiahui Chang Zhiqing Wang Yanxu Zhang Jindong Zhu Qiang Liu Dong Xu Chengyu Jiang 

机构地区：[1]State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences,Department of Biochemistry, Peking Union Medical College [2]Department of Internal Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College [3]Department of Computer Science, Informatics Institute, and Christopher S.Bond Life Science Center, University of Missouri [4]Department of Health Management and Informatics and Office of Medical Research, School of Medicine, University of Missouri [5]State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University

出　　处：《Science China(Life Sciences)》2019年第3期309-320,共12页中国科学（生命科学英文版）

基　　金：supported by the Ministry of Science and Technology of China (2015CB553406);the National Natural Science Foundation of China (81230002, 81490531);the Ministry of Education (IRT1121, B08007)

摘　　要：Pulmonary fibrosis, a progressive chronic disease with a high mortality rate, has limited treatment options. Currently, lung transplantation remains the only effective treatment. Here we report that a small RNA, HJT-sRNA-m7, from a Chinese herbal medicine Hong Jing Tian(HJT, RHODIOHAE CRENULATAE RADIX ET RHIZOMA, Rhodiola crenulata) can effectively reduce the expressions of fibrotic hallmark genes and proteins both in alveolar in vitro and in mouse lung tissues in vivo. We also discovered over one hundred oil-soluble chemicals from HJT decoctions, most of which are found in lipid extracts from other Chinese herbals decoctions, including Pu Gong Ying(PGY, TARAXACI HERBA, Taraxacum mongolicum), Chuan Xin Lian(CXL, changed to "ANDROGRAPHIS HERBA, Andrographis paniculata"), and Jin Yin Hua(JYH, lonicera japonica or Honeysuckle). We identified the active component in these decoctions as two forms of phosphocholines, PC(18:0/18:2) and PC(16:0/18:2). These PCs potentially could form liposomes with small RNAs to enter human alveolar and gastric cells. Our experimental results suggest an unprecendent lipid complex route through which botanic small RNA can enter human bodies.Our results provide an innovative treatment strategy for oral delivery of siRNAs as therapeutic medication.Pulmonary fibrosis, a progressive chronic disease with a high mortality rate, has limited treatment options. Currently, lung transplantation remains the only effective treatment. Here we report that a small RNA, HJT-sRNA-m7, from a Chinese herbal medicine Hong Jing Tian(HJT, RHODIOHAE CRENULATAE RADIX ET RHIZOMA, Rhodiola crenulata) can effectively reduce the expressions of fibrotic hallmark genes and proteins both in alveolar in vitro and in mouse lung tissues in vivo. We also discovered over one hundred oil-soluble chemicals from HJT decoctions, most of which are found in lipid extracts from other Chinese herbals decoctions, including Pu Gong Ying(PGY, TARAXACI HERBA, Taraxacum mongolicum), Chuan Xin Lian(CXL, changed to "ANDROGRAPHIS HERBA, Andrographis paniculata"), and Jin Yin Hua(JYH, lonicera japonica or Honeysuckle). We identified the active component in these decoctions as two forms of phosphocholines, PC(18:0/18:2) and PC(16:0/18:2). These PCs potentially could form liposomes with small RNAs to enter human alveolar and gastric cells. Our experimental results suggest an unprecendent lipid complex route through which botanic small RNA can enter human bodies.Our results provide an innovative treatment strategy for oral delivery of siRNAs as therapeutic medication.

关 键 词：PC CELLULAR UPTAKE anti-fibrotic HJT SRNA 

分 类 号：Q[生物学]