Therapeutic Effects of Total Saponins From Dioscorea nipponica Makino on Gouty Arthritis Based on the MAPK-PPARγ Signaling Pathway: An In Vitro Study

Abstract

Gouty arthritis (GA) is an inflammatory disease caused by the deposition of monosodium urate in the synovial membrane and cartilage due to a high concentration of uric acid in the blood. Dioscorea nipponica Makino is widely used in the clinic to treat GA. Total saponins are its main components and showed an anti-inflammatory effect on GA in a previous study. The mitogen-activated protein kinase (MAPK)-peroxisome proliferator-activated receptor γ (PPARγ) signaling pathway plays a key role during the onset of GA; however, little is known about its potential mechanism. Based on in vitro experiments, this study aims to determine the mechanism of total saponins from Dioscorea nipponica Makino (TDN) in treating GA by regulating the MAPK-PPARγ signaling pathway. Fibroblast-like synoviocytes were divided into 3 groups: the model group, which was given 10 µg/L IL-1β to induce proliferation; TDN group (10 µg/L IL-1β + 100 µg/L TDN); and indomethacin group (10 µg/L IL-1β + 100 µg/L indomethacin). Seventy-two hours after treatment, the real-time PCR method was used to detect the mRNA expression levels of extracellular signal regulated kinase 1/2 (ERK1/2), p-38, c-Jun N-terminal kinase (JNK), IKKα, c-Jun, MAPK phosphatase (MKP), vascular cell adhesion molecule 1 (VCAM1), intercellular adhesion molecule 1 (ICAM1), C-X-C motif chemokine ligand 1 (CXCL1), PPARγ, and Adipor2. The Western blot method was used to detect the protein expression of ERK1/2, p-ERK1/2, p-38, p-P38, JNK, p-JNK, IKKα, p-IKKα, c-Jun, p-c-Jun, MKP, p-MKP, VCAM1, ICAM1, CXCL1, PPARγ, and Adipor2. Compared with the model group, the TDN group displayed significantly increased mRNA expression of c-Jun, MKP, CXCL1, PPARγ, and Adipor2 and significantly decreased mRNA expression of ICAM1. Compared with the model group, the TDN group exhibited significantly increased protein expression of MKP and significantly decreased protein expression of p-ERK1/2, p-38, p-JNK, p-IKKα, p-c-Jun, VCAM1, ICAM1, and PPARγ. Our results indicated that TDN could treat GA by influencing the MAPK-PPARγ signaling pathway.

Anti-inflammation effects of the total saponin fraction from Dioscorea nipponica Makino on rats with gouty arthritis by influencing MAPK signalling pathway

“…AdipoR2 mRNA levels; however, AdipoR2 protein levels did not differ compared with the control group. The result is quite consistent with our in vitro study [20]. This finding may be explained by the self-recovery features of GA.…”

“…To protect the animals, ethical approval for the experiments was obtained based on the Legislation on the Protection of Animals Used for Experiment Purposes (Directive 86/609/EEC). The Institutional Animal Care Committee approved the experiment (approval number was 20,190,921).…”

“…Our previous study showed that RDN could treat GA by interfering with the NALP3 inflammasome and the TLR2/4-IL-1R signal pathway, in this way, it influenced the expression and activities of inflammatory factors [18,19]. Given that the MAPK-PPARγ is another branch down-stream signal pathway of TLR2/4-IL-1R that could influence the activities of transcriptional factors and thus regulates the expression of inflammatory factors, adhesion factors and chemokines, we assumed that it may also influence this signal pathway and had approved this by an in vitro study [20]. This study aims to further investigate the effect of RDN on interfering with the MAPK-PPARγ signalling pathway to treat GA by using animal models.…”

Dioscorea spp.: Bioactive Compounds and Potential for the Treatment of Inflammatory and Metabolic Diseases

“…The underlying molecular mechanism may be that dioscin reduces inflammation by reducing the production of pro-inflammatory cytokines and inhibiting the activation of inflammasome NLRP3 and Toll-like receptor 4 (TLR 4)/NF-κB signaling pathway [ 80 ]. In addition, in vivo studies in mice with GA found that total yam saponins, the main components of which are dioscin, protodioscin, and pseudo protodioscin, exert anti-inflammatory effects for GA by regulating the expression of some key genes in the neutrophilic alkaline phosphatase-3 (NALP3), caspase-1, apoptosis-associated speck-like (ASC), and mitogen-activated protein kinase (MAPK)-peroxisome proliferator-activated receptor γ (PPARγ) signaling pathways [ 81 , 82 ]. Diosgenin from Dioscorea nipponica Makino had a therapeutic effect on collagen-induced arthritis in mice.…”