Network Pharmacology Prediction and Molecular Docking-Based Strategy to Discover the Potential Pharmacological Mechanism of Huai Hua San Against Ulcerative Colitis

Abstract

Background: Huai Hua San (HHS), a famous Traditional Chinese Medicine (TCM) formula, has been widely applied in treating ulcerative colitis (UC). However, the interaction of bioactives from HHS with the targets involved in UC has not been elucidated yet. Aim: A network pharmacology-based approach combined with molecular docking and in vitro validation was performed to determine the bioactives, key targets, and potential pharmacological mechanism of HHS against UC. Materials and Methods: Bioactives and potential targets of HHS, as well as UC-related targets, were retrieved from public databases. Crucial bioactive ingredients, potential targets, and signaling pathways were acquired through bioinformatics analysis, including protein-protein interaction (PPI), as well as the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Subsequently, molecular docking was carried out to predict the combination of active compounds with core targets. Lastly, in vitro experiments were conducted to further verify the findings. Results: A total of 28 bioactive ingredients of HHS and 421 HHS-UC-related targets were screened. Bioinformatics analysis revealed that quercetin, luteolin, and nobiletin may be potential candidate agents. JUN, TP53, and ESR1 could become potential therapeutic targets. PI3K-AKT signaling pathway might play an important role in HHS against UC. Moreover, molecular docking suggested that quercetin, luteolin, and nobiletin combined well with JUN, TP53, and ESR1, respectively. Cell experiments showed that the most important ingredient of HHS, quercetin, could inhibit the levels of inflammatory factors and phosphorylated c-Jun, as well as PI3K-Akt signaling pathway in LPS-induced RAW264.7 cells, which further confirmed the prediction by network pharmacology strategy and molecular docking. Conclusion:Our results comprehensively illustrated the bioactives, potential targets, and molecular mechanism of HHS against UC. It also provided a promising strategy to uncover the scientific basis and therapeutic mechanism of TCM formulae in treating diseases.

Network Pharmacology and Molecular Docking Analysis on Molecular Mechanism of Qingzi Zhitong Decoction in the Treatment of Ulcerative Colitis

“…Furthermore, QZZTD inhibited PI3K-AKt pathway activation, reduced inflammation, and alleviated UC. The aforementioned study also yielded the same results, revealing that TCM treatment of UC may mainly produce efficacy by regulating the PI3K-Akt signaling pathway ( Liu J. et al, 2021 ; Liu X. et al, 2021 ; Song et al, 2021 ; Yu et al, 2021 ).…”

“…Similarly, some studies have used network pharmacology combined with molecular docking to predict the efficacy and mechanism of drug action in UC, suggesting that potential mechanisms of drug action on the disease can be explored in this way. In a study composed of Huai Hua San formula, the investigators used this approach and validated it in vitro , discovering the binding properties of three key compounds (quercetin, luteolin, and nobiletin) to three key proteins (JUN, tumor protein P53, and estrogen receptor 1) and revealing the mechanism of quercetin affecting the protein expression of c-jun and the PI3K/Akt pathway to improve UC ( Liu J. et al, 2021 ). Another study also used this approach and combined it with animal studies to screen for key components (puerarin, baicalein, berberine, and glabridin) and key pathways (hypoxia inducible factor 1, PI3K-AKT, and TNF).…”

Screening and identification of a novel antidiabetic peptide from collagen hydrolysates of Chinese giant salamander skin: network pharmacology, inhibition kinetics and protection of IR-HepG2 cells

“…11 JUN, including JNK, JUNB and JUNC, belonged to the AP-1 transcription factor family and played an important role in the inflammatory response. 33 Y. Pan et al reported that the inhibition of JNK kinase activity could reduce the inflammatory response and apoptosis induced by high glucose, and protect the heart from the effects of diabetes. 34 These studies suggested that GPPGPA might regulate glucose consumption, cell activity and oxidative stress response of cells by acting on core targets such as AKT1, MAPK8, MAPK10 and JUN to improve insulin resistance and treat T2DM.…”

Network Pharmacology and Experimental Validation to Reveal the Pharmacological Mechanisms of Liuwei Dihuang Decoction Against Intervertebral Disc Degeneration

“…[14][15][16] By network pharmacological analysis, Liu et al found 28 compounds and 421 targets in Huaihua-San formed the main pathways linked to ulcerative colitis, which revealed the mechanism of Huaihua-San against ulcerative colitis. 17 Similarly, with the help of network pharmacology, we predicted and verified the potential pharmacological mechanism of Bu-Yang herbs for postmenopausal osteoporosis via regulating the Wnt/β-catenin signaling pathway. 18 Therefore, all this evidence indicated that network pharmacology analysis may be a good tool for exploring the chemical compositions of LWDHD and its relationships with IVDD.…”