Uncovering the mechanism of Ge-Gen-Qin-Lian decoction for treating ulcerative colitis based on network pharmacology and molecular docking verification

Abstract

Background: Ge-Gen-Qin-Lian Decoction (GGQLD), a traditional Chinese medicine (TCM) formula, has been widely used for ulcerative colitis (UC) in China, but the pharmacological mechanisms remain unclear. This research was designed to clarify the underlying pharmacological mechanism of GGQLD against UC. Method: In this research, a GGQLD-compound-target-UC network was constructed based on public databases to clarify the relationship between active compounds in GGQLD and potential targets. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were performed to investigate biological functions associated with potential targets. A protein-protein interaction network was constructed to screen and evaluate hub genes and key active ingredients. Molecular docking was used to verify the activities of binding between hub targets and ingredients. Results: Finally, 83 potential therapeutic targets and 118 corresponding active ingredients were obtained by network pharmacology. Quercetin, kaempferol, wogonin, baicalein, and naringenin were identified as potential candidate ingredients. GO and KEGG enrichment analyses revealed that GGQLD had anti-inflammatory, antioxidative, and immunomodulatory effects. The effect of GGQLD on UC might be achieved by regulating the balance of cytokines (e.g., IL-6, TNF, IL-1β, CXCL8, CCL2) in the immune system and inflammation-related pathways, such as the IL-17 pathway and the Th17 cell differentiation pathway. In addition, molecular docking results demonstrated that the main active ingredient, quercetin, exhibited good affinity to hub targets. Conclusion: This research fully reflects the multicomponent and multitarget characteristics of GGQLD in the treatment of UC. Furthermore, the present study provided new insight into the mechanisms of GGQLD against UC.

Topical Application of Galgeunhwanggeumhwangryeon-Tang Recovers Skin-Lipid Barrier and Ameliorates Inflammation via Filaggrin-Thymic Stromal Lymphopoietin-Interleukin 4 Pathway

“…In addition, previous experimental and clinical studies on GGRT revealed that the herbal formula has a pharmacological effect on diabetes mellitus, dyslipidemia, ulcerative colitis, and acute lung injury [14][15][16][17][63][64][65]. The mechanisms underlying the effect of GGRT on these diseases were estimated and evaluated by several in silico multi-omics and network pharmacological studies [14][15][16][17]64,66,67]. From these previous studies on the ingredients and in silico studies, we estimated that GGRT might have a potent effect on atopic dermatitis and evaluated its effectiveness using the lipid barrier elimination model in mice.…”

Pharmacological Effects of Polyphenol Phytochemicals on the Intestinal Inflammation via Targeting TLR4/NF-κB Signaling Pathway

“…Furthermore, it attenuated intestinal mucosal damage from ischemia-reperfusion injury by inhibiting COX-2 and myeloperoxidase (MPO) expression [112]. Moreover, quercetin was found to be the main active ingredient in a traditional Chinese medicine widely used for UC treatment [113].…”

Scutellaria baicalensis georgi is a promising candidate for the treatment of autoimmune diseases

“…In specific, it dampens LPSinduced tumor necrosis factor α, IL-23 and IRF5 expression while enhancing IL-10, arginase-1 (Arg-1) and IRF4 expression in colon, to reverse macrophage subset redistribution (Zhu et al, 2016). Of notes, a range of ancient prescriptions that contains SBG also demonstrated certain ameliorative effect on IBD in addition to small-molecules from SBG, typical ones include Jiawei Gegen Qinlian decoction , Banxia Xiexin decoction (Wang et al, 2021), Gegen Qinlian decoction (Xu et al, 2021) and Huangqin decoction (Chen et al, 2016), among which BAE, WGI, and BAI are the principal contents accounting for these bioactive effects, and the principal involved molecular pathways include NF-κB, NLRP3 inflammasome, MAPK, JAK/STAT3, IL-17, the Th17 cell differentiation and oxidative stress pathway.…”