Therapeutic effects of gentiopicroside on adjuvant-induced arthritis by inhibiting inflammation and oxidative stress in rats

Xie, Xiaoqian; He, Lina; Wang, Yale; Wan, Zhijie; Luo, Shasha; Zhao, Zeyue; Liu, Jingjing; Wu, Xiaohan; Li, Xinxin; Li, Xiaotian

doi:10.1016/j.intimp.2019.105840

Cited by 23 publications

(10 citation statements)

References 48 publications

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“…In the present study, we found that Gent was able to relieve primary and secondary swelling as well as arthritis index scores in treated animals, thus suggesting that Gent can reduce arthritis progression in rats. The result was consistent with previous studies (Xie et al, 2019).…”

Section: Discussionsupporting

confidence: 94%

“…Gent has been shown to possess analgesic (Liu et al, 2016), anti-inflammatory (Zhao et al, 2015;Chen et al, 2018), anti-cancer (Li et al, 2019), lipid regulating (Choi et al, 2019), and antidepressant properties (Deng et al, 2018). Gent has been shown to mediate protective efficacy on joints in the adjuvant-induced arthritis (AIA) model (Xie et al, 2019) and reduce the secretion of inflammatory factors in FLS (Zhang et al, 2019). However, the effects of Gent on the abnormal proliferation and migration of FLS have not been reported, and the mechanism in vivo and in vitro has not been studied in depth.…”

Section: Introductionmentioning

confidence: 99%

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Anti-Rheumatic Properties of Gentiopicroside Are Associated With Suppression of ROS-NF-κB-NLRP3 Axis in Fibroblast-Like Synoviocytes and NF-κB Pathway in Adjuvant-Induced Arthritis

Wang

et al. 2020

Front. Pharmacol.

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Rheumatoid arthritis (RA) is among the most prevalent forms of autoimmunity. Gentiopicroside (Gent) is an iridoid glucoside derived from the Gentiana Macrophylla Pall which is used in traditional Chinese medicine to treat RA. The present study was designed to explore the ability of Gent to combat RA and to explore the molecular basis for such anti-RA activity both in vitro using tumor necrosis factor alpha (TNF-a)-stimulated human RA fibroblast-like synoviocytes (RA-FLS) and in vivo using a rat adjuvant-induced arthritis (AIA) model. We found that Gent was able to significantly reduce the swelling of joints and arthritic index scores, with corresponding reductions in synovial inflammatory cell infiltration, synovial hyperplasia, and bone erosion in treated AIA rats. Importantly, Gent 200 mg/kg reduced thymus index in AIA rats, but had no effect on spleen index and body weight, it revealed that Gent was relatively safe at the dose we chose. We further found that Gent was able to suppress the TNF-a-induced proliferation and migration of RA-FLS cells. This suppression was attributed to the ability of Gent to block NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1, thereby disrupting the activation of the NLRP3 inflammasome. Consistent with such suppression, Gent led to a significant decrease in IL-1b secretion by treated cells. Furthermore, this reduction in NLRP3 inflammasome activation was also associated with decreases in the activation of nuclear factor (NF-kB), the production of reactive oxygen species (ROS), and the expression of inflammatory IL-6. Together these findings indicate that Gent can suppress the ROS-NF-kB-NLRP3 axis to alleviate RA symptoms.

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Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Anti-Rheumatic Properties of Gentiopicroside Are Associated With Suppression of ROS-NF-κB-NLRP3 Axis in Fibroblast-Like Synoviocytes and NF-κB Pathway in Adjuvant-Induced Arthritis

Wang

et al. 2020

Front. Pharmacol.

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“…GPS has been reported to have an obvious inhibition on swelling in arthritis induced by adjuvant [ 28 ]. Research [ 29 ] also demonstrated that GPS has an analgesic effect on mechanical, thermal, cold hyperalgesia in CCI model.…”

Section: Discussionmentioning

confidence: 99%

Effects of Gentiopicroside on activation of NLRP3 inflammasome in acute gouty arthritis mice induced by MSU

Chen

et al. 2021

J Nat Med

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Acute gouty arthritis is a self-limiting inflammatory disease resulting from the deposition of monosodium urate (MSU) crystals. It has been shown that Gentiopicroside (GPS) possesses anti-inflammatory and analgesic functions. The aim of this study was to parse out whether GPS has an effect on acute gouty arthritis. We established an acute gouty arthritis model by the injection of MSU into the paw, and found that GPS relieves MSU-induced mechanical, thermal hyperalgesia, and paw swelling. Furthermore, GPS down-regulated the release of pro-inflammatory cytokines in paw tissues, including IL-1β, IL-6, IL-18, and TNF-α. The results of H&E staining and MPO activity measurement showed that GPS inhibits neutrophil infiltration. And the over-expressions of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and Caspase-1 induced by MSU were inhibited by treatment with GPS. These results revealed that GPS can treat acute gouty arthritis based on anti-inflammatory and analgesic properties in vivo, which might be ascribed to the inhibition on NLRP3 inflammasome. Furthermore, we performed in vitro study to confirm the results of in vivo study. Consistently, the results proved that GPS could inhibit the activation of NLRP3 inflammasome in RAW264.7 macrophages stimulated by LPS-MSU. In conclusion, this study provides an experimental basis for the application of GPS and expands the potential value of GPS in the therapy of acute gouty arthritis.

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“…However, each cross-reactive compound is biologically active. [29][30][31][32][33][34] Thus, each of these compounds impact the efficacy of S. japonica. The amounts of SM in the S. japonica samples usually exceeded the amounts of gentiopicroside and sweroside.…”

Section: Binding Selectivity Of Mab D2mentioning

confidence: 99%

A monoclonal antibody‐based indirect competitive enzyme‐linked immunosorbent assay to quantify swertiamarin and related compounds in Swertia japonica Makino

Nuntawong

Horikawa

Ochi

et al. 2020

Phytochemical Analysis

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Introduction: Swertia japonica Makino (S. japonica) has a long history of use as a folk medicine, and it is one of the three essential Japanese folk medicines. S.japonica has been reported to have various biological activities. The biologically active secoiridoid glycoside swertiamarin (SM) has been isolated from S. japonica. The efficacy of this plant is attributed to SM and related secoiridoid glycosides. To control the quality of S. japonica for medicinal use, a method for the determination of SM and other secoiridoid glycosides in the plant is needed.Objective: To produce an anti-SM monoclonal antibody (MAb) and develop an indirect competitive enzyme-linked immunosorbent assay (icELISA) for S. japonica standardisation and quality control.Methodology: SM was conjugated to cationised bovine serum albumin (cBSA), and the SM-cBSA conjugate was used to immunise BALB/c mice. Splenocytes from the immunised mice were then fused with SP2/0 myeloma cells to produce hybridoma cells that expressed anti-SM MAb.Results: The developed icELISA was sufficiently sensitive and had a quantitative range of 0.78 to 12.5 μg/mL. Coefficients of variation below 10% indicated good repeatability. Recoveries in a spike and recovery assay ranged from 91.84% to 115.50%, which confirmed that the icELISA was accurate. The SM content measured using the icELISA was in agreement with the results of a high-performance liquid chromatography-ultraviolet (HPLC-UV) assay. Conclusion:The icELISA is suitable for the high-throughput analysis of SM and other secoiridoid glycosides in S. japonica. The method is fast, economical, and reliable for S. japonica quality control.

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Therapeutic effects of gentiopicroside on adjuvant-induced arthritis by inhibiting inflammation and oxidative stress in rats

Cited by 23 publications

References 48 publications

Anti-Rheumatic Properties of Gentiopicroside Are Associated With Suppression of ROS-NF-κB-NLRP3 Axis in Fibroblast-Like Synoviocytes and NF-κB Pathway in Adjuvant-Induced Arthritis

Anti-Rheumatic Properties of Gentiopicroside Are Associated With Suppression of ROS-NF-κB-NLRP3 Axis in Fibroblast-Like Synoviocytes and NF-κB Pathway in Adjuvant-Induced Arthritis

Effects of Gentiopicroside on activation of NLRP3 inflammasome in acute gouty arthritis mice induced by MSU

A monoclonal antibody‐based indirect competitive enzyme‐linked immunosorbent assay to quantify swertiamarin and related compounds in Swertia japonica Makino

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