RESUMEN
Background: Marmesine, a major active ingredient isolated from Radix Angelicae biseratae (Duhuo), has been reported to have multiple pharmacological activities. However, its therapeutic effects against knee osteoarthritis (OA) remain poorly investigated. The present study is aimed at uncovering the core targets and signaling pathways of marmesine against osteoarthritis using a combined method of bioinformatics and network pharmacology. Methods: We utilized SwissTargetPrediction and PharmMapper to collect the potential targets of marmesine. OA-related differentially expressed genes (DEGs) were identified from GSE98918 dataset. Then, the intersection genes between DEGs and candidate genes of marmesine were subjected to protein-protein interaction (PPI) network construction and functional enrichment analysis. The core targets were verified using the molecular docking technology. Results: A total of 320 marmesine-related genes and 5649 DEGs and 60 ingredient-disease targets between them were identified. The results of functional enrichment analyses revealed that response to oxygen levels, neuroinflammatory response, PI3K-Akt signaling pathway, MAPK signaling pathway, FoxO signaling pathway, and osteoclast differentiation was identified as the potential mechanisms of marmesine against OA. EGFR, CASP3, MMP9, PPARG, and MAPK1 served as hub genes regulated by marmesine in the treatment of OA, and the molecular docking further verified the results. Conclusion: Marmesine exerts the therapeutic effects against OA through multitarget and multipathways, in which EGFR, CASP3, MMP9, PPARG, and MAPK1 might be hub genes. Our research indicated that the combination of bioinformatics and network pharmacology could serve as an effective approach for investigating the potential mechanisms of natural product.
Asunto(s)
Medicamentos Herbarios Chinos , Osteoartritis de la Rodilla , Humanos , Osteoartritis de la Rodilla/tratamiento farmacológico , Osteoartritis de la Rodilla/genética , Simulación del Acoplamiento Molecular , Caspasa 3 , Metaloproteinasa 9 de la Matriz , PPAR gamma , Fosfatidilinositol 3-Quinasas , Receptores ErbB , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
BACKGROUND: This study aimed to systematically evaluate the therapeutic effects of acupotomy combined with acupuncture and moxibustion on knee osteoarthritis (KOA), which was expected to provide a reference for clinical treatment of KOA using traditional Chinese medicine (TCM). METHODS: The databases PubMed, Embase, Medline, Ovid, and Springer were searched to retrieve randomized controlled trials (RCTs) on KOA treatment by acupotomy combined with acupuncture and moxibustion. The search time was set as from the date the database was established to 31 December 2020. The Cochrane Handbook for Systematic Reviews of Intervention 5.0.2 was used to conduct bias risk assessment on the included literature, and Review Manager 5.3 software was used for meta-analysis. RESULTS: A total of 10 RCTs were included in this study, including 1,073 participants. Meta-analysis results showed that compared with the control group, the clinical treatment efficiency of the experimental group was higher [mean difference (MD) =5.72; 95% confidence interval (CI): 3.39 to 9.64; Z=6.54; P<0.00001], and the postoperative visual analogue scale (VAS) scores were reduced (MD =-1.72; 95% CI: -2.41 to -1.03; Z=4.86; P<0.00001). DISCUSSION: Acupotomy combined with acupuncture and moxibustion treatment for KOA can increase clinical treatment efficiency, and relieve postoperative pain, suggesting that the combination of acupotomy, acupuncture, and moxibustion has better therapeutic effects on KOA and can be promoted clinically.
Asunto(s)
Terapia por Acupuntura , Moxibustión , Osteoartritis de la Rodilla , Humanos , Osteoartritis de la Rodilla/terapia , Punciones , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
A capsule of Qili Jiegu, a traditional Chinese medicine with numerous biological activities, may exert a protective eï¬ ;ect against postmenopausal bone loss. However, it remains unclear whether Qili Jiegu-containing serum regulates the osteogenic diï¬ ;erentiation of bone marrow stromal cells (BMSCs) in vitro. In this study, BMSCs were treated with medium and Qili Jiegu-containing serum over a 14-day period. We found that Qili Jiegu-containing serum promoted the BMSC proliferation and alkaline phosphatase (ALP) activities, as well as stimulated the expression of osteogenic markers and Wnt/ß-catenin pathway-related genes, i.e., runt-related transcription factor 2 (Runx2), osteocalcin (OCN), ß-catenin and Wnt4a, in BMSCs. Finally, we found that Qili Jiegu-containing serum activated the Wnt/ß-catenin pathway. An addition of Dickkopf-related protein-1 (an inhibitor of the Wnt/ß-catenin signaling pathway) to the Qili Jiegu-containing serum could decrease the stimulatory osteogenic effect of Qili Jiegu-containing serum on BMSCs. Therefore, Qili Jiegu-containing serum could promote the osteogenic diï¬ ;erentiation of BMSCs, and the potential mechanism may involve regulation of Wnt/ß-catenin signaling.