Diosgenin From Dioscorea Nipponica Rhizoma Against Graves’ Disease—On Network Pharmacology and Experimental Evaluation

Xin, Jingxin; Cheng, Wei; Yu, Yongbing; Chen, Juan; Zhang, Xinhuan; Shao, Shanshan

doi:10.3389/fphar.2021.806829

Cited by 6 publications

(3 citation statements)

References 83 publications

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“…Then, the putative targets of D7 mapped to the inflammatory osteolysis-related targets to acquire overlapping targets. A Venn diagram was obtained with the Venn diagram website ( http://bioinformatics.psb.ugent.be/webtools/Venn/ ) [ 26 ] to identify the intersection of D7 and inflammatory osteolysis [ 27 ].…”

Section: Methodsmentioning

confidence: 99%

Network Pharmacology Deciphers the Action of Bioactive Polypeptide in Attenuating Inflammatory Osteolysis via the Suppression of Oxidative Stress and Restoration of Bone Remodeling Balance

Cui

Feng

Chen

et al. 2022

Oxidative Medicine and Cellular Longevity

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Oxidative stress involves enormously in the development of chronic inflammatory bone disease, wherein the overproduction of reactive oxygen species (ROS) negatively impacts the bone remodeling via promoting osteoclastogenesis and inhibiting osteogenesis. Lacking effective therapies highlights the importance of finding novel treatments. Our previous study screened a novel bioactive peptide D7 and demonstrated it could enhance the cell behaviors and protect bone marrow mesenchymal stem cells (BMSCs). Since BMSCs are progenitor cells of osteoblast (OB), we therefore ask whether D7 could also protect against the progress of inflammatory osteolysis. To validate our hypothesis and elucidate the underlying mechanisms, we first performed network pharmacology-based analysis according to the molecule structure of D7, and then followed by pharmacological evaluation on D7 by in vitro lipopolysaccharide(LPS)-induced models. The result from network pharmacology identified 20 candidate targets of D7 for inflammatory osteolysis intervention. The further analysis of Gene Ontology (GO)/KEGG pathway enrichment suggested the therapeutic effect of D7 may primarily affect osteoclast (OC) differentiation and function during the inflammatory osteolysis. Through validating the real effects of D7 on OC and OB as postulated, results demonstrated suppressive effects of D7 on LPS-stimulated OC differentiation and resorption, via the inhibition on OC marker genes. Contrarily, by improving the expression of OB marker genes, D7 displayed promotive effects on OB differentiation and alleviated LPS-induced osteogenic damage. Further mechanism study revealed that D7 could reduce LPS-induced ROS formation and strengthen antioxidants expressions in both OC and OB precursors, ameliorating LPS-triggered redox imbalance in bone remodeling. Taken together, our findings unveiled therapeutic effects of D7 against LPS-induced inflammatory osteolysis through the suppression of oxidative stress and the restoration of the bone remodeling process, providing a new therapeutic candidate for chronic inflammatory bone diseases.

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Section: Methodsmentioning

confidence: 99%

Network Pharmacology Deciphers the Action of Bioactive Polypeptide in Attenuating Inflammatory Osteolysis via the Suppression of Oxidative Stress and Restoration of Bone Remodeling Balance

Cui

Feng

Chen

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…In addition, Dio has demonstrated inhibitory effects on the activation and phosphorylation of Rap1-mitogen-activated extracellular signal-regulated kinase (MEK) and PI3K-AKT signaling pathways and promoted cell apoptosis and GD remission. In terms of phosphorylation deactivation in IGF-1R, Dio promoted Nthy-ori three to one cells (normal thyroid cells) apoptosis in vitro and relieved GD in rats ( Xin et al, 2021 ).…”

Section: Tcm and Other Treatmentsmentioning

confidence: 99%

Current and promising therapies based on the pathogenesis of Graves’ ophthalmopathy

Zhang,

Zhao,

2023

Front. Pharmacol.

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Graves’ ophthalmopathy (GO) is a hyperthyroidism-related and immune-mediated disease that poses a significant threat to human health. The pathogenesis of GO primarily involves T cells, B cells, and fibroblasts, suggesting a pivotal role for the thyrotropin-antibody-immunocyte-fibroblast axis. Traditional treatment approaches for Graves’ disease (GD) or GO encompass antithyroid drugs (ATDs), radioactive iodine, and beta-blockers. However, despite decades of treatment, there has been limited improvement in the global incidence of GO. In recent years, promising therapies, including immunotherapy, have emerged as leading contenders, demonstrating substantial benefits in clinical trials by inhibiting the activation of immune cells like Th1 and B cells. Furthermore, the impact of diet, gut microbiota, and metabolites on GO regulation has been recognized, suggesting the potential of non-pharmaceutical interventions. Moreover, as traditional Chinese medicine (TCM) components have been extensively explored and have shown effective results in treating autoimmune diseases, remarkable progress has been achieved in managing GO with TCM. In this review, we elucidate the pathogenesis of GO, summarize current and prospective therapies for GO, and delve into the mechanisms and prospects of TCM in its treatment.

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“…Studies have reported that TSAb can regulate the proliferation activity of thyroid cells via the PI3K/AKT pathway ( 10 , 11 ). Chinese medicine for hyperthyroidism primarily modulates the proliferation and apoptosis of thyroid cells through regulation of the PI3K/AKT pathway to effectively treat GD ( 12 - 14 ). Furthermore, certain studies suggest that AKT can interact with heat shock protein (HSP) to exert diverse influences on cell signaling mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Puerarin inhibits inflammation and oxidative stress in female BALB/c mouse models of Graves’ disease

Ye,

Wu,

Chen

et al. 2024

Transl Pediatr

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Background Graves’ disease (GD) is an autoimmune thyroid disorder. Our previous study has demonstrated a significant decrease in flavone levels among children with GD compared to the control group. Puerarin, a well-known flavonoid with anti-inflammatory and antioxidant properties. We wanted to investigate its potential impact on GD pathogenesis, aiming to determine whether increasing puerarin intake could prevent or delay the onset of GD. Methods Adenovirus with TSHR-289 subunit was used to establish a GD mice model, and mice were intragastrically administered with puerarin or sterilized water daily. Thyroid function and inflammatory cytokine levels were quantified using ELISA, lymphocyte subsets were analyzed via flow cytometry, oxidative stress (OS) markers were measured with a microplate reader, and the expression of pertinent signaling pathway proteins were assessed by Western blot. Results The results demonstrated that puerarin treatment significantly decreased thyroxin levels and alleviated thyroid pathological changes in GD mice. Furthermore, the immune imbalance of GD mice was improved, as evidenced by reduced inflammatory indexes, elevated antioxidant levels, and decreased malondialdehyde (MDA) levels compared to untreated GD mice. Puerarin-treated GD mice exhibited significantly lower expressions of heat shock protein (HSP): HSP70, HSP90, phosphorylated extracellular regulated kinases (p-ERK) and phosphorylated protein kinase B (p-AKT) than untreated GD mice. Moreover, low dosage puerarin (400 mg/kg) was associated with a better protective effect than high dosage (1,200 mg/kg). Conclusions Puerarin may have the potential to mitigate GD by inhibiting inflammatory and OS, through downregulating the expression of HSP70 and HSP90 and suppressing the activation of the PI3K/AKT/ERK signaling pathway. Furthermore, a lower dose exhibited superior protective effects compared to a higher dose.

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Diosgenin From Dioscorea Nipponica Rhizoma Against Graves’ Disease—On Network Pharmacology and Experimental Evaluation

Cited by 6 publications

References 83 publications

Network Pharmacology Deciphers the Action of Bioactive Polypeptide in Attenuating Inflammatory Osteolysis via the Suppression of Oxidative Stress and Restoration of Bone Remodeling Balance

Network Pharmacology Deciphers the Action of Bioactive Polypeptide in Attenuating Inflammatory Osteolysis via the Suppression of Oxidative Stress and Restoration of Bone Remodeling Balance

Current and promising therapies based on the pathogenesis of Graves’ ophthalmopathy

Puerarin inhibits inflammation and oxidative stress in female BALB/c mouse models of Graves’ disease

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