TY - JOUR
T1 - Imperatorin and β-sitosterol have synergistic activities in alleviating collagen-induced arthritis
AU - Guo, Qingqing
AU - Li, Li
AU - Zheng, Kang
AU - Zheng, Guang
AU - Shu, Haiyang
AU - Shi, Yingjie
AU - Lu, Cheng
AU - Shu, Jun
AU - Guan, Daogang
AU - Lu, Aiping
AU - He, Xiaojuan
N1 - Funding Information:
This study was supported by the National Key R&D Program of China (2018YFC1705205), Hong Kong Baptist University Strategic Development Fund (SDF13-1209-P01, SDF15-0324-P02(b) and SDF19-0402-P02), Hong Kong Baptist University Interdisciplinary Research Matching Scheme (RC/IRCs/17-18/04) and Startup fund from Southern Medical University (G619280010).
Publisher copyright:
© 2019 The Authors. Journal of Leukocyte Biology published by Wiley Periodicals, Inc. on behalf of Society for Leukocyte Biology
PY - 2020/8
Y1 - 2020/8
N2 - Rheumatoid arthritis (RA) is a chronic disease with complex molecular network of pathophysiology, single drug is usually not full satisfactory because it is almost impossible to target the whole molecular network of the disease. Drug combinations that act synergistically with each another is an effective strategy in RA therapy. In this study, we aimed to establish a new strategy to search effective synergized compounds from Chinese herbal medicine (CHM) used in RA. Based on multi-information integrative approaches, imperatorin (IMP) and β-sitosterol (STO) were predicted as the most effective pair for RA therapy. Further animal experiments demonstrated that IMP+STO treatment ameliorated arthritis severity of collagen-induced arthritis (CIA) rats in a synergistic manner, whereas IMP or STO administration separately had no such effect. RNA sequencing and IPA analysis revealed that the synergistic mechanism of IMP+STO treatment was related to its regulatory effect on 5 canonical signaling pathways, which were not found when IMP or STO used alone. Moreover, LTA, CD83, and SREBF1 were 3 important targets for synergistic mechanism of IMP+STO treatment. The levels of these 3 genes were significantly up-regulated in IMP+STO group compared to model group, whereas IMP or STO administration separately had no effect on them. In conclusion, this study found that IMP and STO were 2 synergistic compounds from the CHM in RA therapy, whose synergistic mechanism was closely related to regulate the levels of LTA, CD83, and SREBF1.
AB - Rheumatoid arthritis (RA) is a chronic disease with complex molecular network of pathophysiology, single drug is usually not full satisfactory because it is almost impossible to target the whole molecular network of the disease. Drug combinations that act synergistically with each another is an effective strategy in RA therapy. In this study, we aimed to establish a new strategy to search effective synergized compounds from Chinese herbal medicine (CHM) used in RA. Based on multi-information integrative approaches, imperatorin (IMP) and β-sitosterol (STO) were predicted as the most effective pair for RA therapy. Further animal experiments demonstrated that IMP+STO treatment ameliorated arthritis severity of collagen-induced arthritis (CIA) rats in a synergistic manner, whereas IMP or STO administration separately had no such effect. RNA sequencing and IPA analysis revealed that the synergistic mechanism of IMP+STO treatment was related to its regulatory effect on 5 canonical signaling pathways, which were not found when IMP or STO used alone. Moreover, LTA, CD83, and SREBF1 were 3 important targets for synergistic mechanism of IMP+STO treatment. The levels of these 3 genes were significantly up-regulated in IMP+STO group compared to model group, whereas IMP or STO administration separately had no effect on them. In conclusion, this study found that IMP and STO were 2 synergistic compounds from the CHM in RA therapy, whose synergistic mechanism was closely related to regulate the levels of LTA, CD83, and SREBF1.
KW - compounds combination
KW - mechanism
KW - prediction
KW - rheumatoid arthritis
KW - synergism
UR - http://www.scopus.com/inward/record.url?scp=85084498685&partnerID=8YFLogxK
U2 - 10.1002/JLB.3MA0320-440RR
DO - 10.1002/JLB.3MA0320-440RR
M3 - Journal article
C2 - 32392637
AN - SCOPUS:85084498685
SN - 0741-5400
VL - 108
SP - 509
EP - 517
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 2
ER -