Integrative transcriptomic and metabonomic profiling analyses reveal the molecular mechanism of Chinese traditional medicine huankuile suspension on TNBS-induced ulcerative colitis

摘要

This study aimed to investigate the therapeutic mechanism of Huankuile suspension (HKL), a typical traditional Chinese medicine, on ulcerative colitis (UC) in a rat model. UC model was established by 2,4,6-trinitrobenzene sulfonic acid (TNBS) enema. Then, the rats were randomly divided into three groups: water treated group, HKL treated group and 5- amino salicylic acid (5-ASA) treated group. After 7 days treatment, the histological score in the HKL treated group was comparable with those in the control group. qRT-PCR and western blot demonstrated that HKL could significantly decreased pro-inflammatory cytokines, including TNF-α, IL-1β and IL-6, while having less effect on anti-inflammatory cytokines, including IL-4 and IL-10. Transcriptomic analysis identified 670 differentially expressed genes (DEGs) between HKL treated UC rats and water treated UC rats. These DEGs were mostly related with immune response. Besides, metabonomic profile revealed 136 differential metabolites which were significantly enriched in “pyrimidine metabolism”, “glutathione metabolism”, “purine metabolism” and “citrate cycle”. Finally, integrated analysis revealed that metabonomic pathways including “steroid hormone biosynthesis”, “pyrimidine metabolism”, “purine metabolism”, and “glutathione metabolism” were altered by HKL at both transcriptomic and metabonomic levels. HKL could inhibit inflammation and regulate bile metabolism, pyrimidine metabolism, purine metabolism, glutathione metabolism and citrate cycle.