The Role of Th17/Treg Axis in the Traditional Chinese Medicine Intervention on Immune-Mediated Inflammatory Diseases: A Systematic Review

The Th17/Treg axis plays a crucial role in immune-mediated inflammatory diseases (IMID) and might represent an interesting drug target of treatment strategy for these diseases. Accumulating evidence suggests a role for traditional Chinese medicine (TCM) in the modulation of Th17/Treg axis, but a comprehensive overview which summarizes this field hitherto is lacked. This paper performs a systematic literature review of the regulatory effects of TCM on the imbalance of Th17/Treg axis and its potential mechanisms. In addition, the frequency analysis and network pharmacology for the collected TCM herbs from clinical trial data were performed. The studies reported the changes in the ratio of Th17 and/or Treg cells as well as their transcription factor and related cytokines were included. Frequency analysis of composition of the 39 assessed TCM prescriptions showed that Astragalus membranaceus var.mongholicus (5.20%), Glycyrrhiza uralensis (3.67%), Paeonia obovate (3.06%), Salvia digitaloides (3.06%), and Angelica sinensis (2.75%) were the top five herbal components, which were closely associated to the treatment of IMID. Network pharmacology showed that six target proteins (transforming growth factor (TGF)-beta receptor type-1, TGF-beta receptor type-2, retineic-acid-receptor-related orphan nuclear receptor gamma (ROR-gamma), TGFB2, IL-17 and IL-2, respectively) might be involved in the regulatory effects of TCM on Th17/Treg axis. Moreover, there were nine active ingredients (including Oxymatrine, Baicalin, Triptolide, Paeoniflorin, Sinomenine, Celastrol, Emodin, Diosgenin and Chlorogenic acid) originating from TCM reported to have an immunological regulation effect on the Th17/Treg axis. The highlight of this systematic review is to reveal the pharmacological basis of TCM treating IMID and is helpful for supporting future pharmacologic-driven studies. Further research elucidates the immune-modulating mechanisms on Th17/Treg axis by TCM might provide a broader insight for the treatment of IMID.