Study on the Potential Active Components and Molecular Mechanism of Xiao Huoluo Pills in the Treatment of Cartilage Degeneration of Knee Osteoarthritis Based on Bioinformatics Analysis and Molecular Docking Technology

Abstract

Background: Knee osteoarthritis is a common joint degenerative disease that severely affects the quality of life. Modern pharmacological studies have confirmed that Xiao Huoluo Pills (XHLP) has anti-inflammatory, anti-oxidant, and analgesic effects. At present, it has been used to treat degenerative diseases such as osteoarthritis and hyperosteogeny. However, XHLP's specific effective ingredients and mechanism of action against osteoarthritis have not been explored. Therefore, bioinformatics technology and molecular docking technology are employed in this study to explore the molecular basis and mechanism of XHLP in the treatment of knee osteoarthritis. Methods: Public databases (TCMSP, Batman-TCM, HERB, DrugBank, and UniProt) are used to find the effective active components and corresponding target proteins of XHLP (screening conditions: OB>30%, DL≥0.18). Differentially expressed genes related to cartilage lesions of knee osteoarthritis are obtained based on the GEO database (screening conditions: adjust P Value<0.01, |log2 FC|≥1.0). The Venn package in R language and the BisoGenet plug-in in Cytoscape are adopted to predict the potential molecules of XHLP in the treatment of knee osteoarthritis. The XHLP-active component-target interaction network and the XHLP-knee osteoarthritis-target protein core network are constructed using Cytoscape software. Besides, GO/KEGG enrichment analysis on core genes is performed using the Bioconductor package and clusterProfiler package in the R language to explain the biological functions and signal pathways of the core proteins. Finally, molecular docking is performed through software such as Vina, LeDock, Discovery Studio 2016, PyMOL, AutoDockTools 1.5.6, so as to verify the binding ability between the active components of the drug and the core target protein. Results: XHLP has been screened out of 71 potentially effective active compounds for the treatment of OA, mainly including quercetin, Stigmasterol, beta-sitosterol, Izoteolin, and ellagic acid. Knee osteoarthritis cartilage lesion sequencing data (GSE114007) was screened out of 1672 differentially expressed genes, including 913 up-regulated genes and 759 down-regulated genes, displayed as heat maps and volcano maps. Besides, 33 core target proteins are calculated by Venn data package in R and BisoGenet plug-in in Cytoscape. The enrichment analysis on these target genes revealed that the core target genes are mainly involved in biological processes such as response to oxygen levels, mechanical stimulus, vitamin, drug, and regulation of smooth muscle cell proliferation. These core target genes are involved in signaling pathways related to cartilage degeneration of knee osteoarthritis such as TNF signaling pathway and PI3K-Akt signaling pathway. Finally, the molecular docking verification demonstrates that some active components of the drug have good molecular docking and binding ability with the core target protein, further confirming that XHLP has the effect of inhibiting cartilage degeneration in knee osteoarthritis.Conclusions: In this study, based on the research foundation of bioinformatics and molecular docking technology, the active components and core target molecules of XHLP for the treatment of cartilage degeneration of knee osteoarthritis are screened out, and the potential mechanism of XHLP inhibiting cartilage degeneration of knee osteoarthritis is deeply explored. The results provide theoretical basis and new treatment plan for XHLP in the treatment of knee osteoarthritis.

Clinical Efficacy of Intra‐Articular Injection with P‐PRP Versus that of L‐PRP in Treating Knee Cartilage Lesion: A Randomized Controlled Trial

“…(3) symptoms and imaging findings that were localized in the patellofemoral joint; (4) patients who suffered from malignant neoplasms; (5) patients who had active infection in other parts of the body; (6) female patients who were pregnant, lactating, or preparing for pregnancy; (7) cartilage lesions caused by infectious or gouty arthritis; (8) patients who had autoimmune diseases such as rheumatoid arthritis and ankylosing spondylitis; (9) patients who had diabetes with FBG over 8 mmol/L and had poor control; (10) patients who were generally in poor condition and unable to tolerate surgery; (11) patients who had severe diseases such as cerebral hemorrhage, severe pneumonia, and multiple organ dysfunction; (12) patients with Charcot joint; (13) any conditions that might increase the patient's risk or influence the results of the experiment during the research; (14) other reasons making the patient unsuitable for this study.…”

“…Articular cartilage lesions of the knee are extremely common, with a high morbidity rate of 5% in the general population, and are characterized by the progressive loss of joint function and development of pain 1–6 . Currently, traditional conservative treatments for knee cartilage lesions include nonsteroidal anti‐inflammatory drugs, glucosamine, hyaluronic acid, and glucocorticoids 7–11 . However, as these therapies have limited therapeutic efficacy in the healing of cartilage lesions, their long‐term efficacy is uncertain 12 .…”

“…[1][2][3][4][5][6] Currently, traditional conservative treatments for knee cartilage lesions include nonsteroidal anti-inflammatory drugs, glucosamine, hyaluronic acid, and glucocorticoids. [7][8][9][10][11] However, as these therapies have limited therapeutic efficacy in the healing of cartilage lesions, their long-term efficacy is uncertain. 12 In addition, while these known therapies can be effective for a short period, they can cause several adverse reactions.…”