Systems pharmacology approach reveals protective mechanisms of Jian-Pi Qing-Chang decoction on ulcerative colitis

Abstract

BACKGROUND Given the complex pathogenesis of ulcerative colitis (UC), the conventional therapeutic methods are not fully curative. As a sort of systematic complementary and alternative medicine, traditional Chinese medicine (TCM) provides new options for the standard therapy. Nevertheless, there are still numerous problems with the promotion of TCM attributed to its complexity, and consequently, new research approaches are urgently needed. Thus, we explored the protective effects of Jian-Pi Qing-Chang (JPQC) decoction on UC based on systems pharmacology approach, which might fill the current innovation gap in drug discovery and clinical practice pertaining to TCM. AIM To investigate the protective mechanisms of JPQC decoction on UC based on systems pharmacology approach. METHODS We performed systems pharmacology to predict the active ingredients, the matched targets, and the potential pharmacological mechanism of JPQC on UC. In vivo , we explored the effects of JPQC in a colitis model induced by dextran sulfate sodium. In vitro , we adopted the bone marrow-derived macrophages (BMDMs) as well as BMDMs co-cultured with Caco2 cells to verify the underlying mechanisms and effects of JPQC on UC under TNF-α stimulation. RESULTS Systems pharmacology revealed 170 targets for the 107 active ingredients of JPQC and 112 candidate targets of UC. Protein-protein interaction networks were established to identify the underlying therapeutic targets of JPQC on UC. Based on enrichment analyses, we proposed our hypothesis that JPQC might have a protective effect on UC via the NF-κB/HIF-1α signalling pathway. Subsequent experimental validation revealed that treatment with TNFα activated the NF-κB/HIF-1α signalling pathway in BMDMs, thereby damaging the epithelial barrier permeability in co-cultured Caco2 cells, while JPQC rescued this situation. The findings were also confirmed in a dextran sulfate sodium-induced colitis model. CONCLUSION JPQC could improve the mucosal inflammatory response and intestinal epithelial barrier function via the NF-κB/HIF-1α signalling pathway, which provides new perspectives on the pharmaceutical development and clinical practice of TCM.

Targeting NF-κB pathway for treating ulcerative colitis: comprehensive regulatory characteristics of Chinese medicines

“…It is reported that JPQCD (17.1 g/kg) treatment reduces the mRNA levels of IL-1β, IL-8, TNF-α and NF-κB in DSSinduced UC mice, suppresses activation of NF-κB and increases phosphorylation of IκB [140]. Using systems pharmacology to predict the active ingredients, it shows that 170 targets for the 107 active ingredients of JPQC and 112 candidate targets of UC, and JPQC treatment can improve the mucosal inflammatory response and intestinal epithelial barrier function via the NF-κB/ HIF-1α signaling pathway [141].…”

The Landscape of Interactions between Hypoxia‐Inducible Factors and Reactive Oxygen Species in the Gastrointestinal Tract

“…However, there were also studies that suggest that HIF-1 α contributes to pathological progress in gastrointestinal diseases. As has been reported, Jian-Pi Qing-Chang treatment attenuated the intestinal epithelial permeability and inflammation by inhibiting NF- κ B/HIF-1 α pathways in colitis mice [ 37 ]. Further, the interferon-gamma (IFN- γ ) induced intestinal epithelial permeability and disruption of the intestinal tight junction by activating HIF-1 α [ 38 ].…”

Mechanism of Jianpi Qingchang Huashi Recipe in treating ulcerative colitis: A study based on network pharmacology and molecular docking

“…, MPO, interleukin (IL)-1β, IL-8, and tumor necrosis factor alpha (TNF-α)], and improve the barrier function of the intestinal epithelium. In addition, JPQCR can regulate DSS-induced abnormal intestinal motility in UC mice by inhibiting the cascade of intestinal inflammation and reducing autophagy in interstitial cells of Cajal[ 10 , 11 ]. Based on JPQCR, the Jianpi Qingchang Huashi Recipe (JPQCHSR) has newly added TCM drugs including Poria, Tangerine Peel, Coix Seed, Alisma, and Radix Scutellariae .…”