Objective To explore the rules of using compatibility herbs and the possible molecular mechanism in treating osteoarthritis（ OA）. Methods Clinical researches of Chinese medicine treating OA were searched in Chinese Biological Medical Literature Database. The names of included compound prescriptions

the names of herbs and herbs’ nature were inputted in an Access 2003 database. Herbs’ incidence relation was calculated

and based on the results compatibility herbs complex network was built. Top 5 herbs which got high network relative centrality were chosen to composite the core compound prescription for OA

and they were divided into different core herb-pairs. Human active target proteins and OA related genes of herbs main effective components in the compound prescriptions were searched. Confluence analysis of target proteins and biological pathway of OA were made with Ingenuity Pathway Analysis（ IPA） platform. Results Totally 208 compound prescriptions were included. Top 5 herbs which got high complex compatibility network relative centrality were Niuxi（ Radix Achyranthis Bidentatae

牛膝）（ 0. 83）

Danggui（ Radix Angelicae Sinensis

当归）（ 0. 79）

Gancao（ Radix Glycyrrhizae

甘草）（ 0. 73）

Duzhong（ Cortex Eucommiae

杜仲）（ 0. 71） and Baishao（ Radix Paeoniae Alba

白芍）（ 0. 71）

which could be divided into 3 herb-pairs

Danggui-Baishao

Baishao-Gancao and Duzhong-Niuxi. There were 32 of main effective components target proteins in Duzhong

16 in Niuxi

30 in Danggui

36 in Baishao

and 16 in Gancao. There were 365 genes related to OA in total. There were 8 networks with many import genes and high correlation score in core compound prescriptions

as well as 6 these kind of networks in Danggui-Baishao

5 in Baishao-gancao

4 in Duzhong-Niuxi and 25 in OA. Molecular network confluence analysis showed that all herb-pairs and OA had common direct effect molecules. Among them

CA1

NF-κB1 and VDR were the common key targets of Danggui-Baishao

Baishao-Gancao and OA. Confluence analysis between top 10 pathways with high OA genes association degree and all herb-pairs pathways showed that Danggui-Baishao had the greatest impact among 10 pathways

followed by Baishao-Gancao and then Duzhong-Niuxi.Danggui-Baishao got the highest occurrence rate of herb-pairs in the key target of each pathway. Baishao-Gancao got the second higher

and Duzhong-Niuxi was the lowest. Conclusion The herb compatibility principle of nourishing blood and softening liver

and harmonizing liver and spleen seems have strong intervention on OA. The core herbpairs

such as Danggui-Baishao

Baishao-Gancao

and Duzhong-Niuxi

might treat OA through different molecules or pathways

from many aspects of cell multiplication

apoptosis

organism immunity

metabolism

etc.