Exploration on Property-efficacy Association of Sovereign Drug Gypsum Fibrosum in Baihu Guizhitang by Integrating Transcriptomics with Gene Regulatory Network Analysis
10.13422/j.cnki.syfjx.20222245
- VernacularTitle:整合“转录组-基因调控网络”探讨白虎加桂枝汤君药石膏的性-效关联内涵
- Author:
Weijie LI
1
;
Xia MAO
1
;
Yudong LIU
1
;
Kexin WANG
1
;
Yanqiong ZHANG
1
;
Na LIN
1
Author Information
1. Institute of Chinese Materia Medica， China Academy of Chinese Medical Sciences， Beijing 100700，China
- Publication Type:Journal Article
- Keywords:
Baihu Guizhitang;
Gypsum Fibrosum;
heat arthralgia;
association of property and efficacy;
energy metabolism;
immunity-inflammation balance
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2023;29(1):52-60
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo systematically explore the roles and contributions of the sovereign drug Gypsum Fibrosum contained in Baihu Guizhitang （BHGZT） against rheumatoid arthritis （RA） with heat syndrome from property-efficacy association by an approach integrating transcriptomics with gene regulatory network analysis. MethodA total of 20 male Lewis rats were randomly assigned into 4 groups： a control group （n=5）， a group of adjuvant-induced arthritis rat model with heat syndrome （AIA-H， n=5）， an AIA-H + BHGZT group （BHGZT， 21.4 g·kg-1， n=5）， and an AIA-H + BHGZT without Gypsum Fibrosum group （BHGZT-GYP， 10.7 g·kg-1， n=5）. We combined the gene expression profiling based on AIA-H rat model and "disease-gene-drug effective target" network analysis to predict the major function of Gypsum Fibrosum contained in BHGZT against RA with heat syndrome. Furthermore， in vivo experiments with the AIA-H rat model were performed to validate the therapeutic effects on the severity of arthritis based on the representative images of arthritis， limb diameter， infrared thermography， pain thresholds， and joint injury， as well as at the level of immunity-inflammation imbalance. Oil Red O staining was employed for the differentiation of 3T3-L1 pre-adipocytes in the AIA-H rats treated by BHGZT， BHGZT-GYP， and GYP. ResultGene expression profiling and network analysis demonstrated that Gypsum Fibrosum mainly regulated the energy metabolism disorders and the immunity-inflammation imbalance during the development and progression of RA. In vivo experiments showed that both BHGZT and BHGZT-GYP reduced the disease severity of AIA-H rats （P<0.01） by relieving joint redness and distortion， decreasing arthritis score and limb diameter， elevating pain thresholds， alleviating joint erosion， joint inflammation， and bone destruction （P<0.05）. Notably， BHGZT outperformed BHGZT-GYP （P<0.05）. Both BHGZT and BHGZT-GYP inhibited the pathological changes and decreased the indexes of thymus and spleen （P<0.05）， and down-regulated the expression of inflammatory cytokines including Toll-like receptor 4 （TLR4）， tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， IL-12， IL-1β， and IL-18 （P<0.05）. In addition， BHGZT and GYP significantly inhibited the adipogenic differentiation of 3T3-L1 cells， with the performance superior to that of BHGZT-GYP. ConclusionThe sovereign drug Gypsum Fibrosum contained in BHGZT played a crucial role in reversing energy metabolism disorders and immunity-inflammation imbalance， which may be associated with its cold property and function of clearing heat and purging fire.
