Exploring the Pharmacological Mechanism of Duhuo Jisheng Decoction in Treating Osteoporosis Based on Network Pharmacology

Abstract

Objective. The purpose of this work is to study the mechanism of action of Duhuo Jisheng Decoction (DHJSD) in the treatment of osteoporosis based on the methods of bioinformatics and network pharmacology. Methods. In this study, the active compounds of each medicinal ingredient of DHJSD and their corresponding targets were obtained from TCMSP database. Osteoporosis was treated as search query in GeneCards, MalaCards, DisGeNET, Therapeutic Target Database (TTD), Comparative Toxicogenomics Database (CTD), and OMIM databases to obtain disease-related genes. The overlapping targets of DHJSD and osteoporosis were identified, and then GO and KEGG enrichment analysis were performed. Cytoscape was employed to construct DHJSD-compounds-target genes-osteoporosis network and protein-protein interaction (PPI) network. CytoHubba was utilized to select the hub genes. The activities of binding of hub genes and key components were confirmed by molecular docking. Results. 174 active compounds and their 205 related potential targets were identified in DHJSD for the treatment of osteoporosis, including 10 hub genes (AKT1, ALB, IL6, MAPK3, VEGFA, JUN, CASP3, EGFR, MYC, and EGF). Pathway enrichment analysis of target proteins indicated that osteoclast differentiation, AGE-RAGE signaling pathway in diabetic complications, Wnt signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, JAK-STAT signaling pathway, calcium signaling pathway, and TNF signaling pathway were the specifically major pathways regulated by DHJSD against osteoporosis. Further verification based on molecular docking results showed that the small molecule compounds (Quercetin, Kaempferol, Beta-sitosterol, Beta-carotene, and Formononetin) contained in DHJSD generally have excellent binding affinity to the macromolecular target proteins encoded by the top 10 genes. Conclusion. This study reveals the characteristics of multi-component, multi-target, and multi-pathway of DHJSD against osteoporosis and provides novel insights for verifying the mechanism of DHJSD in the treatment of osteoporosis.

Network Pharmacology and Molecular Docking Elucidate the Pharmacological Mechanism of the OSTEOWONDER Capsule for Treating Osteoporosis

“…Here, we found that quercetin has been used as an agent for OP by reducing EGFR, HIF1A, and IL6 expression. EGFR, HIF1A, and IL6 have also been demonstrated as the therapeutic targets of OP ( Fayed et al, 2019 ; Luo et al, 2021 ; Xiong et al, 2021 ). Nobiletin, a polymethoxylated flavone, exhibits anti-oxidative, anti-inflammatory, and anti-cancer properties ( Murakami et al, 2000 ; Hagenlocher et al, 2019 ; Feng et al, 2020 ).…”

Evaluation of the Efficacy of Stem Cell Therapy in Ovariectomized Osteoporotic Rats Based on Micro-CT and Dual-Energy X-Ray Absorptiometry: A Systematic Review and Meta-Analysis

“…Exclusion criteria included the following: (1) the study lacked a control group that met the inclusion criteria; (2) the animal model was a mouse, rabbit, or other experimental animals; (3) the osteoporosis model was not established by ovariectomy; (4) the data related to outcome measurements could not be extracted; (5) the study type was a review, conference abstract, commentary, case report, or letter; and (6) all studies that did not meet the inclusion criteria.…”

“…Because osteoporosis is usually an imbalance of bone resorption and bone formation caused by estrogen deficiency or aging, certain pharmacological agents, such as those that promote bone formation (parathyroid hormone) and those that inhibit osteoclast resorption (bisphosphonates), are widely used in the treatment of osteoporosis [4]. However, with the widespread clinical use of these drugs, adverse side effects have also been observed, such as drug-related osteonecrosis of the jaw [5]. Therefore, the search for new osteoporosis treatment strategies is of great clinical importance.…”

The Mechanism of Ginseng and Astragalus Decoction in the Treatment of Malignant Pleural Effusion Based on Network Pharmacology and Molecular Docking Technology

“…The Ginseng and Astragalus decoction (GAD) are composed of Astragalus and Ginseng to strengthen qi and help yang [ 8 ]. Astragalus and Ginseng are the top medicines described in the Shennong Materia Medica; they taste sweet and have the effect of tonifying qi [ 9 ]. In the “Elbow Reserve Urgent Prescription” written by Gehong in the Eastern Jin Dynasty, records of Ginseng and Astragalus were shared and then they subsequently appeared in the classic prescriptions for treating abnormal water metabolism, such as Baoyuan Decoction, Buzhong Yiqi Decoction, and Guipi Decoction.…”