Elucidation of the Underlying Mechanism of Gujian Oral Liquid Acting on Osteoarthritis through Network Pharmacology, Molecular Docking, and Experiment

Abstract

Gujian oral liquid (GJ), a traditional herbal formula in China, has been widely used to treat patients with osteoarthritis (OA). Nevertheless, the active component and potential mechanism of GJ are not fully elucidated. Thus, we investigate the effect of GJ and explore its underlying mechanism on OA through network pharmacology and experimental validation. First, a total of 175 bioactive compounds were identified, and 134 overlapping targets were acquired after comparing the targets of the GJ with those of OA. 8 hub targets, including IL6 and AKT1, were obtained in PPI network analysis. Then, we built up GJ-target-OA network and protein-protein interaction (PPI) network, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The results underlined inflammatory tumor necrosis factor (TNF) as a promising signaling pathway of GJ for OA treatment. Moreover, molecular docking also verified the top two active compounds had direct bindings with the top three target genes. Finally, we verified the effect of GJ on OA in vivo and in vitro. In vivo experiments validated that GJ not only significantly attenuated OA phenotypes including articular cartilage degeneration and subchondral bone sclerosis but also reduced the expressions of tumor necrosis factor-α (TNF-α) and p-p65 in articular chondrocytes. Besides, GJ serum also had a protective effect on chondrocytes against inflammation caused by TNF-α in vitro. Hence, our study predicted and verified that GJ could exert anti-inflammation and anticatabolism effects partially via regulating TNF-α/NF-kappa B (NF-κB) signaling.

Integrated bioinformatics and wet-lab analysis revealed prominent inflammatory genes of Extracellular Matrix as prognostic biomarkers in patients with advance IBD requiring early surgery

“…Recent discoveries have shown the essential role of ECM in regulating inflammatory responses, including cell extravasation and uptake, immune cell differentiation, polarization, activation, and retention in tissues(14, 15).…”

“…During this process, quantitative and qualitative changes of its components occur in order to control homeostasis and tissue architecture (10,11).The ECM is composed of various glycoproteins such as collagens, laminins, and fibronectins, and there are dozens of cellular receptors that directly interact with ECM components, for example, integrins or cadherins (10,12).The interaction between ECM and receptors on the cell surface regulates cell behavior and plays an important role in cell-to-cell communication, cell proliferation, adhesion, and migration(13). Recent discoveries have shown the essential role of ECM in regulating inflammatory responses, including cell extravasation and uptake, immune cell differentiation, polarization, activation, and retention in tissues (14,15). Notably, cellular matrix proteins are highly expressed in developing tissues and show lower expression levels in healthy mature tissues (16).…”