Kunxian Capsule for Rheumatoid Arthritis: Inhibition of Inflammatory Network and Reducing Adverse Reactions Through Drug Matching

Abstract

Tripterygium wilfordii Hook.f and Tripterygium hypoglaucum (H.Lév.) Hutch is effective herbs to prevent aggravation of Rheumatoid arthritis (RA). However, both of them show severe side effects in the reproductive system and other systems. Kunxian Capsule (KX), a Traditional Chinese Medicine (TCM) patent prescription, comprised of 4 herbs, including H.Lév. Hutch, is reported to be an available prescription in treating RA with fewer side effects as compares to Tripterygium tablets. To reveal the pharmacological mechanism of KX in RA treatment and side effect alleviation, we collected related information of KX from open-access databases and performed various analyses. 1354 targets were identified in KX. These targets were enriched in the calcium signaling pathway, cAMP signaling pathway, cGMP-PKG signaling pathway and PI3K-AKT signaling pathway, forming biological functions, such as cofactor binding, coenzyme binding, etc. These pathways or functions mostly affect cell cycle, differentiation, and maturation of Th17 cells, macrophage, and synovial fibroblast. These targets also act on the IL-17 signaling pathway, Th17 cell differentiation signaling pathway and TNF signaling pathway, which is related to inflammation response inhibition. Next, a disease network was constructed, which indicated IMPDH2, MTHFD1 are the key genes answering for the side effects of H.Lév. Hutch. The side effect-related genes lead to the negative regulation of nucleic acid, which could be restored by the rest 3 herbs through some positive amino acid metabolism. In conclusion, KX is a relatively safe alternative approach in RA intervention.

Tripterygium Ingredients for Pathogenicity Cells in Rheumatoid Arthritis

“…Our previous research using a bioinformatics approach demonstrated that Kunxian Capsule (a Traditional Chinese Medicine (TCM) patent prescription mainly comprises Levl. Hutch) could target at PI3K/AKT/mTOR signaling pathway ( Tang et al., 2020 ). Therefore, we speculate that some proteins in the PI3K-AKT-mTOR signal pathway are the most likely direct targets of tripterygium ingredients.…”

“…Therefore, the AEs of tripterygium ingredients could be due to the inhibition of NF-κB and PI3K pathways. Ameliorating AEs through drug matching may be a feasible strategy ( Tang et al., 2020 ). For example, some Chinese researchers matched the TwHf with Cistanche deserticola Ma or Cuscuta chinensis Lam , to reduce the reproductive toxicity of TwHf ( Dong et al., 2009 ; Jing and He, 2013 ).…”

Network Pharmacology-Based Analysis on the Curative Effect of Kunxian Capsules against Rheumatoid Arthritis

“…The current work investigated the potential mechanisms of the curative effect of KC, a Chinese patent medicine, against RA, by integrating the chemical profiling with network pharmacology analysis, for the first time [ 6 , 41 ]. The establishment of TCM-herb-ingredient-target-pathway network could make a useful reference for further drug development and the treatment of RA.…”

“…Triptolide has been shown to inhibit the phosphorylation of PI3K and AKT in bone marrow mononuclear cells [ 43 ], to decrease the phosphorylation of JAK and STAT in the human leukemic U937 cells and in collagen-induced arthritis rats [ 44 ], and to inhibit the activation of matrix metalloproteinase 9 (MMP-9). Moreover, KC could inhibit the excessive inflammatory response and regulate the immune reaction [ 6 ]. Icariin inhibited STAT3 activation in T cells, resulting in decreased IL-17 production and alleviated RA [ 51 ].…”

Integrated Strategy of Network Pharmacological Prediction and Experimental Validation Elucidate Possible Mechanism of Bu-Yang Herbs in Treating Postmenopausal Osteoporosis via ESR1

“…Hopkins proposed the concept of “network pharmacology” and it’s becoming increasingly popular among researchers in recent years ( Tang et al, 2020 ; Xu J. et al, 2019b ). The characteristic of network pharmacology is following the holistic theory of TCM(S. He et al, 2019b ).…”