Figure 3: Putative therapeutic mechanism for selected major active ingredients in QLY and potential synergistic pairs. The upper network is the ingredient synergy network (including Kurarinone and Matrine in Ku-Shen, Sinomenine in Qing-Feng-Teng, Berberine in Huang-Bai, and Diosgenin in Bi-Xie), and the lower network is RA-specific molecular network which was constructed manually based on the RA-related pathways and the potential targets of the major ingredients. Herbal ingredients and RA-related genes were represented as triangle and circle, respectively. TNF-, IL1B-, and VEGF-induced pathways were highlighted in color line as indicated. NFKB1, NFKB2, RELA, and RELB can form heterogeneous complex as an important transcription factor in the development of RA. The blue line linking two ingredients indicated synergy with the width of the line correlating with the number of synergistic mechanisms: the wider line represented feedback and compensatory mechanisms and the narrow line represented feedback or compensation.