Pathway of PPAR-gamma coactivators in thermogenesis: a pivotal traditional Chinese medicine-associated target for individualized treatment of rheumatoid arthritis
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Yanqiong Zhang1,*, Xia Mao1,*, Qiuyan Guo1,*, Ming Bai2, Bo Zhang2,3, Chunfang Liu1, Yanqun Sun1, Shao Li2, Na Lin1
1Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
2MOE Key Laboratory of Bioinformatics and Bioinformatics Division, TNLIST, Department of Automation, Tsinghua University, Beijing 100084, China
3Tianjin International Joint Academy of Biotechnology & Medicine, Tianjin 300457, China
*These authors contributed equally to this work
Na Lin, e-mail: firstname.lastname@example.org
Shao Li, e-mail: email@example.com
Keywords: rheumatoid arthritis, traditional Chinese medicine syndrome, network pharmacology, PPAR-gamma, individualized treatment
Received: January 11, 2016 Accepted: February 06, 2016 Published: February 16, 2016
Traditional Chinese medicine (TCM) syndromes have been regarded as the crucial clinical manifestations for individualized diagnosis and treatment of complex diseases, including rheumatoid arthritis (RA) and cancer. Especially, RA patients are classified into cold and hot syndromes with different clinical manifestations, interventions and molecular mechanisms. Better effectiveness of a classic cold syndrome-specific herbal formula Wu-tou decoction (WTD) has been achieved. To explore molecular mechanisms of syndrome-specific formulae is of great clinical significance to improve the effectiveness and pertinence of treatment for the complex diseases with personalized conditions. However, the scientific basis of WTD treatment on RA with the cold syndrome remains unclear. Here, we predicted the putative targets for composite compounds contained in WTD using drugCIPHER-CS and constructed a WTD herbs-putative targets-RA related genes network. Next, a list of major WTD targets was identified based on their topological features, including the degree, node betweenness, closeness and k-coreness in the above pharmacological network. Importantly, pathway enrichment analysis revealed that these major WTD targets were significantly associated with the pathway of peroxisome proliferator-activated receptor (PPAR)-gamma (PPAR-γ) coactivators in thermogenesis. These computational findings were subsequently verified by experiments on a rat model of collagen-induced arthritis (CIA) with cold or hot syndromes, and on human fibroblast-like synoviocytes-rheumatoid arthritis (HFLS-RA) cell line. In conclusion, the pathway of PPAR-γ coactivators in thermogenesis might be one of the potential pharmacological targets of WTD to alleviate RA with the TCM cold syndrome. These findings may open new avenues for designing individualized treatment regimens for RA patients.
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