Stigmasterol protects rats from collagen induced arthritis by inhibiting proinflammatory cytokines

Anti-inflammatory potential of orally administrated bioflavonoid-robinin, active sub-stance of original drug Flaroninum™ (FL), was investigated in the combination with methotrexate (MTX) and in monotherapy in rats suffering from adjuvant-induced arthritis (AA). Robinin (kaempferol-3-O-robinoside-7-O-rhamnoside) was isolated from the aerial parts of Astragalus falcatus Lam. The monotherapy with robinin was not efficient in alleviating symptoms of AA. The combination of MTX with robinin was similarly active as MTX alone in reducing the hind paw volume and change of body weight during the whole experiment. The combination, however, reduced plasma levels of Interleukin-17Aand activity of gamma-glutamyl transferase in joint more efficiently then MTX alone. Our results demonstrate that the novel combination of robinin and MTX mildly improved the reduction of inflammation in experimental arthritis.

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“…This also applies for AA [62][63][64]. RB alone has no effect on the IL-17A levels in plasma (Figure 5).…”

Section: Discussionmentioning

confidence: 68%

Bioflavonoid Robinin from Astragalus falcatus Lam. Mildly Improves the Effect of Metothrexate in Rats with Adjuvant Arthritis

et al. 2021

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“…Collagen-induced arthritis (CIA) is a widely-used experimental model to explore RA pathogenesis and screening new drugs for treatment of RA. [15][16][17] We revealed that the synovial AQP1 overexpression aggravated rat CIA, and β-catenin signaling might be implicated in the pathogenesis of AQP1 in CIA. In vitro, we observed the inhibitory effects of AQP1 siRNA on cell proliferation, migration, invasion and β-catenin signaling pathway in CIA FLS.…”

Section: Introductionmentioning

confidence: 84%

“…Rat CIA model shares many pathological changes of RA, such as joint damage, extremities swelling and synovial inflammation, highlighting the value of this animal model for studying RA pathology and therapeutic drugs. [15][16][17] In this study, rat CIA model was successfully set up, evidenced by increased secondary hind paw swelling and the pathological changes of ankle joints. We revealed that there existed the overexpression of AQP1 in synovial tissues from CIA rats, consistent with previous findings that synovial AQP1 expression was up-regulated in RA joints compared to normal and OA joints.…”

Section: Discussionmentioning

confidence: 99%

<p>Overexpression of Aquaporin 1 in Synovium Aggravates Rat Collagen-Induced Arthritis Through Regulating β-Catenin Signaling: An in vivo and in vitro Study</p>

Zhou

Cai

et al. 2020

JIR

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Introduction: Previous studies have confirmed that aquaporin 1 (AQP1) is up-regulated in synovium of rheumatoid arthritis (RA), but its exact pathogenic mechanisms in RA are unclear. This study revealed the pathogenic role of AQP1 in rat collagen-induced arthritis (CIA) and the underlying mechanisms related to β-catenin signaling. Materials and Methods: Secondary paw swelling and pathological changes of ankle joints were used to evaluate the severity of rat CIA. Synovial AQP1 and β-catenin expression were measured by immunohistochemistry (IHC) and Western blot assay. AQP1 siRNA was applied to knockdown AQP1 in cultured CIA fibroblast-like synoviocyte (FLS). Assays of MTT, PCNA immunofluorescence and transwell were performed to detect cell proliferation, migration and invasion. The protein levels of β-catenin pathway members and ratio of TOP/ FOP luciferase activity were also measured. Results: In vivo, we revealed that synovial AQP1 and β-catenin expressions in CIA rats were higher than normal rats, and synovial AQP1 expression of CIA rats increased in parallel with secondary paw swelling and total pathological score on joint damage. Correlation analysis of IHC results indicated that synovial AQP1 expression positively correlated with β-catenin expression in CIA rat. In vitro, AQP1 siRNA apparently reduced the proliferation, migration and invasion of CIA FLS by inhibiting β-catenin signaling pathway. As an activator of β-catenin signaling, lithium chloride (an inhibitor of GSK-3β) reversed the inhibitory effects of AQP1 siRNA on the cultured CIA FLS. Conclusion: We concluded that the overexpression of synovial AQP1 aggravated rat CIA by promoting the activation of FLS through β-catenin signaling pathway.

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“…Stigmasterol, as a natural, plant-derived product with an anti-inflammatory effect, is found in Radix Angelicae Sinensis , Radix Ginseng , Radix Achyranthis Bidentatae , Rhizoma Ligustici , Cortex Moutan , Radix Paeoniae Alba , and Radix Glycyrrhizae . It has been reported that rats treated with stigmasterol have significantly suppressed the expression of proinflammatory mediators and increased the expression of anti-inflammatory cytokines [ 39 ]. Moreover, the molecular docking results showed that these five main compounds of WJD had a high binding affinity to the top four target proteins from the PPI network ( Figure 6 ).…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology-Based Prediction of Bioactive Compounds and Potential Targets of Wenjing Decoction for Treatment of Endometriosis

Liu

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Endometriosis is a chronic estrogen-dependent inflammatory disorder that negatively affects the quality of life in women. The Wenjing decoction (WJD) is a traditional Chinese medicine that has been shown to have a therapeutic effect on endometriosis. Our study systematically explored the mechanism of WJD against endometriosis using a network pharmacology approach. Potentially bioactive compounds of WJD and their possible targets were retrieved from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. The protein-protein interaction network and herbs-compounds-genes multinetwork were constructed using Cytoscape for visualization. Subsequently, the signaling pathways of common targets were retrieved from the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, and molecular docking was performed using PyRx software. In total, 48 common targets were screened, such as IL6 and ESR1, which were related to inflammation and the endocrine system. The top five bioactive compounds were quercetin, kaempferol, wogonin, beta-sitosterol, and stigmasterol. KEGG enrichment analysis revealed 65 pathways containing inflammatory- and endocrine-related signaling pathways, such as the “TNF signaling pathway” and the “estrogen signaling pathway.” Taken together, the results of our network pharmacology analysis predicted that certain active ingredients of WJD might treat endometriosis by regulating inflammation and/or endocrine, which provided references for further understanding and exploration of WJD on endometriosis.

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Stigmasterol protects rats from collagen induced arthritis by inhibiting proinflammatory cytokines

Cited by 82 publications

References 35 publications

Bioflavonoid Robinin from Astragalus falcatus Lam. Mildly Improves the Effect of Metothrexate in Rats with Adjuvant Arthritis

Bioflavonoid Robinin from Astragalus falcatus Lam. Mildly Improves the Effect of Metothrexate in Rats with Adjuvant Arthritis

<p>Overexpression of Aquaporin 1 in Synovium Aggravates Rat Collagen-Induced Arthritis Through Regulating β-Catenin Signaling: An in vivo and in vitro Study</p>

Network Pharmacology-Based Prediction of Bioactive Compounds and Potential Targets of Wenjing Decoction for Treatment of Endometriosis

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