Herbal pair Huangqin-Baishao: mechanisms underlying inflammatory bowel disease by combined system pharmacology and cell experiment approach

Abstract

Background Inflammatory bowel disease (IBD) is a severe digestive system condition, characterized by chronic and relapsing inflammation of the gastrointestinal tract. Scutellaria baicalensis Georgi (Huangqin, HQ) and Paeonia lactiflora Pall (Baishao, BS) from a typical herbal synergic pair in traditional Chinese medicine (TCM) for IBD treatments. However, the mechanisms of action for the synergy are still unclear. Therefore, this paper aimed to predict the anti-IBD targets and the main active ingredients of the HQ-BS herbal pair. Methods A systems pharmacology approach was used to identify the bioactive compounds and to delineate the molecular targets and potential pathways of HQ-BS herbal pair. Then, the characteristics of the candidates were analyzed according to their oral bioavailability and drug-likeness indices. Finally, gene enrichment analysis with DAVID Bioinformatics Resources was performed to identify the potential pathways associated with the candidate targets. Results The results showed that, a total of 38 active compounds were obtained from HQ-BS herbal pair, and 54 targets associated with IBD were identified. Gene Ontology and pathway enrichment analysis yielded the top 20 significant results with 54 targets. Furthermore, the integrated IBD pathway revealed that the HQ-BS herbal pair probably acted in patients with IBD through multiple mechanisms of regulation of the nitric oxide biosynthetic process and anti-inflammatory effects. In addition, cell experiments were carried out to verify that the HQ-BS herbal pair and their Q-markers could attenuate the levels of nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated THP-1-derived macrophage inflammation. In particular, the crude materials exerted a much better anti-inflammatory effect than their Q-markers, which might be due to their synergistic effect. Conclusion This study provides novel insight into the molecular pathways involved in the mechanisms of the HQ-BS herbal pair acting on IBD.

Bioinformatics‐based and molecular docking study on the mechanism of action of Galla chinensis in the treatment of diabetic foot ulcers

“…Potential targets of GC active ingredients were calculated by taking intersections with DFU targets and database topology parameters of protein interactions predicted by the STRING database (Table 2), deleting targets without interactions. The target information was imported into Cytoscape 3.7.0 software for visual analysis and processing, 48 and its topological parameters were calculated and constructed. In the interactions network graph between the proteins acting on GC active compounds, the larger the network degree (degree) in the network, the darker the color (Combined score) indicating the greater the possibility of a connection between the targets acting on GC active compounds.…”

Latent Interacting Variable-Effects Modeling of Gut Microbiome Multi-Omics in Inflammatory Bowel Disease

“…In total, forty-four metabolites that were downregulated in Crohn's Disease were predicted by our model at one of the highest levels of restriction (VIP > 5). Among the most important metabolite features are flavonoids, steroidal glucuronide conjugates, fatty acids and conjugates, dipeptides, terpene glycosides, tetrapyrroles and derivates, benzenesulfonic acids and derivatives, triterpenoids, benzopyrans and alpha-acyloxy carbonyl compounds [9,[21][22][23].…”

Clinical Efficacy and Safety of Chinese Herbal Medicine in the Treatment of Uremic Pruritus: A Meta-Analysis of Randomized Controlled Trials

“…Rhubarb (Dahuang), used as a laxative, is used for alleviating constipation [ 72 ] and showing nephroprotective effects in CKD [ 73 ]. Baishao has been shown to reduce inflammation by significantly inhibiting cAMP-phosphodiesterase (PDE) activity [ 74 ] and by displaying synergistic anti-inflammatory effects with Huangqin (another herb in the formula) in a cell model [ 75 ]. Huangqi, Dahuang, Fuling, and Danshen are important ingredients in UCG [ 42 ].…”