Therapeutic Effect of Rhizoma Dioscoreae Nipponicae on Gouty Arthritis Based on the SDF‐1/CXCR 4 and p38 MAPK Pathway: An <i>In Vivo</i> and <i>In Vitro</i> Study

Liu, Feng; Liu, Lei; Yu, Donghua; Li, Xu‐zhao; Zhou, Qi; Liu, Shumin

doi:10.1002/ptr.4997

Cited by 34 publications

(25 citation statements)

References 24 publications

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“…However, TDN significantly decreased the expression of p-ERK1/2, p-JNK, p-P-38, p-IKKα, and p-c-Jun. This result is different from our previous study in which TDN decreased the expression of p-38 in a rat model of GA. 19 This difference may be due to both different time periods of treatment and drug concentrations. At the same time, it may also be because one is an in vivo study and the other is an in vitro study.…”

Section: Discussionmentioning

confidence: 99%

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

Zhou

Zhang

et al. 2020

Natural Product Communications

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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.

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Section: Discussionmentioning

confidence: 99%

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

Zhou

Zhang

et al. 2020

Natural Product Communications

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“…Steroidal saponins are widely spread throughout the plant kingdom, an example being Dioscorea nipponica Makino, which is a famous traditional Chinese medicinal plant that has diversified pharmacological efficacies (Lu et al, 2010). It has been widely used in China for relieving cough and asthma, eliminating rheumatic aches, alleviating pain, improving blood circulation, and having antilipemic and anticancer properties (Kim et al, 2011;Chien et al, 2012;Kwon et al, 2003;Lu et al, 2014). Recently, the total saponins from Dioscorea nipponica Makino (TSDN) was reported to exert a hepatoprotective effect against CCl 4 -induced liver damage in mice through the suppression of inflammation and apoptosis .…”

Section: Introductionmentioning

confidence: 99%

Effects of the Total Saponins fromDioscorea nipponicaon Immunoregulation in Aplastic Anemia Mice

Wang

Yan

et al. 2015

Am. J. Chin. Med.

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Dioscorea nipponica Makino, a popular folk medicine, exerts anti-inflammation properties. The present study investigated the therapeutic effect of the total saponins from Dioscorea nipponica Makino (TSDN) on aplastic anemia (AA) and possible immune regulation mechanisms. Using a mouse model of AA, three different doses of TSDN were orally administrated for 14 consecutive days. We first demonstrated that TSDN was found to be effective in alleviating pancytopenia with a hypocellular bone marrow as compared with AA model group. Moreover, gastrogavage administration of a medium dose of TSDN was found to dramatically increase the percentage of CD4(+) cells in bone marrow nucleated cells (BMNC) and restore the CD4(+)/CD8(+) ratio. The pro-inflammatory cytokine concentrations of IL-2 and IFN-γ were significantly decreased, and anti-inflammatory cytokine IL-4 was significantly increased in culture supernatant of BMNC. Further investigations showed that TSDN obviously inhibited Fas-FasL-induced BMNC apoptosis as well as effectively suppressed intracellular apoptosis protein of caspase-3 and -8 expressions. Taken together, these findings suggested that TSDN could alleviate AA by elevating the CD4(+)/CD8(+) T-cell ratio, inhibiting inflammatory Th1-cytokines, and exerting anti-apoptosis effects.

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“…Total saponins from RDN could reduce uric acid levels of hyperuricemic mice by inhibiting the production of uric acid. There were some therapeutic effects on GA [16][17][18][19]. Little is known about the mechanism by which the concentration of uric acid is reduced.…”

Section: Feuamentioning

confidence: 99%

Total Saponins from Discorea nipponica Ameliorate Urate Excretion in Hyperuricemic Mice

Zhou

Zhang

et al. 2014

Planta Med

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Rhizoma Dioscoreae Nipponicae, from Discorea nipponica, is a widely used traditional Chinese herb. It is used to treat arthroncus, arthrodynia, and arthritis. Hyperuricemia is an important foundation of gouty arthritis. The current study was aimed at investigating whether the effects of total saponins from Rhizoma Dioscoreae Nipponicae on hyperuricemia were due to renal organic ion transporters in potassium oxonate-induced hyperuricemia mice. Hyperplasia of synovial cells prepared from Wistar rats was induced by IL-1β (1 × 10(4) µg/mL). MTT was used and to screen active components in the inhibition of hyperplasia by total saponins from Rhizoma Dioscoreae Nipponica, individual pure compounds, and different combinations of these compounds. Sixty Kun Ming mice were randomly divided into six groups: normal, model, allopurinol (40 mg/kg), and three total saponins groups receiving dose (600 mg/kg), middle (300 mg/kg), and low doses (60 mg/kg). Hyperuricemic mice were induced with potassium oxonate (300 mg/kg) intragastrically. The total saponins were given six days and the positive drug allopurinol was given one day before inducing hyperuricemia. The serum and urine levels of uric acid and creatinine and the fractional excretion of uric acid were measured in normal and hyperuricemic mice treated with Rhizoma Dioscoreae Nipponicae and allopurinol. The mRNA and protein levels of the mouse urate transporter 1, glucose transporter 9, organic anion transporter 1, and organic anion transporter 3 were analyzed by real-time-PCR and Western blotting methods, respectively. Total saponins from Rhizoma Dioscoreae Nipponicae could effectively reverse potassium oxonate-induced alterations in renal mouse urate transporter 1, glucose transporter 9, organic anion transporter 1, and organic anion transporter 3 mRNA and protein levels, resulting in enhancement of renal urate excretion in mice. These findings suggested that the total saponins from Rhizoma Dioscoreae Nipponicae had a uricosuric effect on the regulation of renal organic ion transporters in hyperuricemic animals.

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Therapeutic Effect of Rhizoma Dioscoreae Nipponicae on Gouty Arthritis Based on the SDF‐1/CXCR 4 and p38 MAPK Pathway: An In Vivo and In Vitro Study

Cited by 34 publications

References 24 publications

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

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

Effects of the Total Saponins fromDioscorea nipponicaon Immunoregulation in Aplastic Anemia Mice

Total Saponins from Discorea nipponica Ameliorate Urate Excretion in Hyperuricemic Mice

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