ReferenceID 5308
Anti-Inflammatory Effect of Geniposide on Regulating the Functions of Rheumatoid Arthritis Synovial Fibroblasts via Inhibiting Sphingosine-1-Phosphate Receptors1/3 Coupling Gαi/Gαs Conversion
Front Pharmacol
The activated Galpha protein subunit (Galphas) and the inhibitory Galpha protein subunit (Galphai) are involved in the signal transduction of G protein coupled receptors (GPCRs). Moreover, the conversion of Galphai/Galph
Relationship Network
Interactive first-hop connections across herbs, ingredients, formulas, targets, diseases, symptoms, syndromes, evidence, and monographs.
Click a node to open it in a new tab
Ingredient: 1Reference: 1Links: 1
Arranging relationship network...
Record Fields
Scalar fields from the final reference record.
- Reference Id
- 5308
- Evidence Id
- 21898
- Core Evidence Id
- 21898
- Source Reference Id
- 3868
- Herb2 Reference Id
- HBREF004665
- Subject Paper Key
- HBIN027450_33363467
- Pubmed Id
- 33363467
- Doi
- 10.3389/fphar.2020.584176
- Paper Title
- Anti-Inflammatory Effect of Geniposide on Regulating the Functions of Rheumatoid Arthritis Synovial Fibroblasts via Inhibiting Sphingosine-1-Phosphate Receptors1/3 Coupling Gαi/Gαs Conversion
- Paper Abstract
- The activated Galpha protein subunit (Galphas) and the inhibitory Galpha protein subunit (Galphai) are involved in the signal transduction of G protein coupled receptors (GPCRs). Moreover, the conversion of Galphai/Galphas can couple with sphingosine-1-phosphate receptors (S1PRs) and have a critical role in rheumatoid arthritis (RA). Through binding to S1PRs, sphingosine-1-phosphate (S1P) leads to activation of the pro-inflammatory signaling in rheumatoid arthritis synovial fibroblasts (RASFs). Geniposide (GE) can alleviate RASFs dysfunctions to against RA. However, its underlying mechanism of action in RA has not been elucidated so far. This study aimed to investigate whether GE could regulate the biological functions of MH7A cells by inhibiting S1PR1/3 coupling Galphai/Galphas conversion. We use RASFs cell line, namely MH7A cells, which were obtained from the patient with RA and considered to be the main effector cells in RA. The cells were stimulated with S1P (5 mumol/L) and then were treated with or without different inhibitors: Galphai inhibitor pertussis toxin (0.1 mug/mL), S1PR1/3 inhibitor VPC 23019 (5 mumol/L), Galphas activator cholera toxin (1 mug/mL) and GE (25, 50, and 100 mumol/L) for 24 h. The results showed that GE may inhibit the abnormal proliferation, migration and invasion by inhibiting the S1P-S1PR1/3 signaling pathway and activating Galphas or inhibiting Galphai protein in MH7A cells. Additionally, GE could inhibit the release of inflammatory factors and suppress the expression of cAMP, which is the key factor of the conversion of Galphai and Galphas. GE could also restore the dynamic balance of Galphai and Galphas by suppressing S1PR1/3 and inhibiting Galphai/Galphas conversion, in a manner, we demonstrated that GE inhibited the activation of Galpha downstream ERK protein as well. Taken together, our results indicated that down-regulation of S1PR1/3-Galphai/Galphas conversion may play a critical role in the effects of GE on RA and GE could be an effective therapeutic agent for RA.
- Journal
- Front Pharmacol
- Publish Year
- 2020
- Experiment Subject
- patient; mh7a cells; rasfs cell line
- Experiment Type
- Cell Experiment
- Phenotype Related
- Rasfs Dysfunctions; Rheumatoid Arthritis
- Paper Title Cn
- Paper Title En
- Anti-Inflammatory Effect of Geniposide on Regulating the Functions of Rheumatoid Arthritis Synovial Fibroblasts via Inhibiting Sphingosine-1-Phosphate Receptors1/3 Coupling Gαi/Gαs Conversion
- Bilingual Status
- semi_complete