Correlation between cold and hot pattern in traditional Chinese medicine and gene expression profiles in rheumatoid arthritis

Abstract

Clinical manifestations of rheumatoid arthritis (RA) are diversified, and based on the manifestations, the patients with RA could be classified into different patterns under traditional Chinese medicine. These patterns decide the selection of herbal prescription, and thus they can help find a subset of rheumatoid arthritis patients for a type of therapy. In the present study, we combine genome-wide expression analysis with methods of systems biology to identify the functional gene networks for the sets of clinical symptoms that comprise the major information for pattern classification. Clinical manifestations in rheumatoid arthritis were clustered with factor analysis, and two factors (similar to cold and hot patterns in traditional Chinese medicine) were found. Microarray technology was used to reveal gene expression profiles in CD4(+) T cells from 21 rheumatoid arthritis patients. Protein-protein interaction information for these genes from databases and literature data was searched. The highly-connected regions were detected to infer significant complexes or pathways in this protein-protein interaction network. The significant pathways and function were extracted from these subnetworks using the Biological Network Gene Ontology tool. The genes significantly related to hot and cold patterns were identified by correlations analysis. MAPK signalling pathway, Wnt signaling pathway, and insulin signaling pathway were found to be related to hot pattern. Purine metabolism was related to both hot and cold patterns. Alanine, aspartate, and tyrosine metabolism were related to cold pattern, and histindine metabolism and lysine degradation were related to hot pattern. The results suggest that cold and hot patterns in traditional Chinese medicine were related to different pathways, and the network analysis might be used for identifying the pattern classification in other diseases.

Syndrome differentiation in modern research of traditional Chinese medicine

“…In recent years, scientists focused on the molecular network build-up using TCM pattern differentiation for certain diseases (Zhao et al, 2010). For instance, RA can be differentiated into two major TCM patterns: cold and hot patterns, which can be shown in terms of molecular networks (Jiang et al, 2011a). Separate TCM formula used for intervention of RA of cold or hot patterns, with multiple herbal compounds, are targeting on separate biological networks pharmacologically.…”

“…Thus systems biology approaches are expected to open the way to a new convergence of TCM syndrome differentiation information. By analysing microarray, metabolomic data obtained from literature, the TCM syndrome differentiation could be related to biomarkers or biological networks (Cheng et al, in press;Jiang et al, 2011a;. Furthermore, systems biology approaches can assist in identifying the therapeutic mechanism of multiple component herbal drugs, including the build-up of the pharmacological networks of the herbal drugs, which can be merged with the TCM syndrome differentiation network in certain diseases to explore the therapeutic mechanism and the biomarkers for specific indication.…”

Exploring the potential therapeutic mechanism of Da-Fang-Feng-Tang for rheumatoid arthritis

“…About 1% of the world's population has rheumatoid arthritis, women three times more often than men. With several thousand years of clinical practise, some effective herbal formulae have been constructed for its treatments [7]- [9]. According to the textbook of internal medicine of traditional Chinese medicine (TCM) [10], [11], RA is a disease mainly with syndrome Feng-Han-Shi-Bi which is believed to be caused by factors of Feng (wind), Han (cold), and Shi (dampness) [12].…”

Rheumatoid Arthritis with Deficiency Pattern in Traditional Chinese Medicine Shows Correlation with Cold and Hot Patterns in Gene Expression Profiles

“…In TCM, patients with RA are further stratified according to their symptoms, a pattern (also called Zheng or syndrome) diagnosis will be determined for a subgroup of the patients, and then specific therapy will be prescribed based on these pattern classifications [13]. In RA patients, cold, hot, and deficiency patterns were regarded as 3 major pattern classifications in clinical practice [14]; in our previous study, the correlation between cold and hot patterns in TCM and gene expression profiles in RA has been explored [15]. MAPK signaling, Wnt signaling, and insulin signaling pathways were revealed to be related to TCM hot pattern; purine metabolism was related to both TCM hot and cold patterns; alanine, aspartate, and tyrosine metabolisms were related to TCM cold pattern, and histidine metabolism and lysine degradation were related to TCM hot pattern [15].…”