ZNRF3 Regulates Collagen-Induced Arthritis Through NF-kB and Wnt Pathways.

Although the E3 ubiquitin ligase Zinc and ring finger 3 (ZNRF3) negatively regulates the Wnt signaling pathway, its function in rheumatoid arthritis (RA) is elusive. Here, the effects and the mechanism of ZNRF3 on a mouse model of collagen-induced arthritis (CIA) and human fibroblast-like synoviocytes (FLS) obtained from RA patients were determined. Our results showed that ZNRF3 was highly expressed in tissues and FLSs compared to trauma patients. Lentivirus-mediated silencing of ZNRF3 induced apoptosis decreased cell viability and significantly attenuated inflammation in RA-FLSs via tumor necrosis-α (TNF-α). Additionally, silencing of ZNRF3 reduced knee joint damage and also decreased the level of TNF-α, IL-1ß, and IL-6 in the CIA mouse model. These effects were mediated by the crosstalk between Wnt and NF-κB pathways in RA-FLS.

Diallyl Trisulfide can induce fibroblast-like synovial apoptosis and has a therapeutic effect on collagen-induced arthritis in mice via blocking NF-κB and Wnt pathways.

BACKGROUND: Diallyl Trisulfide (DATS) is an organosulfur compound extracted from garlic bulb, and exerts cardioprotective, anti-inflammatory, antioxidant, antimicrobial and anticancer effects. But its role in the pathogenesis of rheumatoid arthritis (RA) is unknown. Here we explored the influence of DATS on human fibroblast-like synoviocytes (FLS) isolated from RA patients and a mouse model of collagen-induced arthritis (CIA) and the underlying mechanism. METHODS: RA-FLS were cultured and treated with different concentrations of DATS. The CCK8 assay was used to assess cell proliferation while cell apoptosis was detected by flow cytometry and western blot. The IL-8, IL-6 and IL-1ß levels were determined using RT-qPCR and ELISA assay. The expression of proteins of the NF-κB and Wnt pathways were measured using western blot. Furthermore, the effect of DATS was also explored in vivo using the collagen-induced arthritis mouse model. The Th17/Treg pattern obtain from cells of spleen of collagen-induced arthritis mouse model was detected by flow cytometry. RESULTS: Our results showed that DATS could decrease cell viability and introduce apoptosis in RA-FLS. Furthermore, DATS significantly attenuated the production of key inflammatory cytokines induced by RA-FLS cells following treatment with tumor necrosis α (TNF-α) at a concentration of 100 µM or higher. This was due to its inhibitory effect on the NF-κB and Wnt pathway signaling in RA-FLS. Additionally, DATS decreased the production of inflammatory cytokines and regulated the immune function by restoring the balance between Th17 and Treg in CIA mouse model. CONCLUSIONS: In conclusion, DATS may serve as a potential curative agent for RA.

Total glucosides of paeony can reduce the hepatotoxicity caused by Methotrexate and Leflunomide combination treatment of active rheumatoid arthritis.

OBJECTIVE: Total glucosides of paeony (TGP) have been confirmed to exert anti-inflammatory and hepatoprotective effects. Methotrexate (MTX) and Leflunomide (LEF) combination has a better efficacy in the treatment of active rheumatoid arthritis (RA), but hepatotoxicity was observed. In this study, we investigated the effect of TGP on hepatic dysfunction caused by MTX and LEF in patients with active RA. METHODS: A total of 268 patients with active RA (disease activity score in 28 joints, DAS28>3.2) were enrolled in this study. All patients were randomly assigned to two groups, the therapeutic group in which patients were treated with TGP (1.8 g/day) combined with MTX and LEF (MTX 10mg/week plus LEF 20mg/day) while in the control group, patients were treated without TGP up to 12 weeks. The efficacy and liver abnormalities were observed. RESULTS: The incidence of abnormal liver function within 12 weeks in TGP group was significantly lower than that in control group (11.38% vs 23.26%, P=0.013). The proportion of patients with ALT/AST >3 times ULN (upper limits of normal) was significantly lower in TGP group than control group (1.63% vs 7.75%, P=0.022). More patients achieved remission, good and moderate response in TGP group than control group at 4, 8 and 12 weeks, but the difference was not significant (P>0.05). The proportions of all adverse events were comparable in the two groups except for diarrhea. CONCLUSIONS: Our study demonstrates that TGP can significantly reduce the incidence and severity of liver damage caused by MTX+LEF in the treatment of active RA patients.

[Studies on flavonoid constituents from herbs of Artemisia ordosica II].

OBJECTIVE: To study the chemical constituents of herbs of Artemisia ordosica. METHOD: The chemical constituents were isolated and repeatedly purified on silica gel column and the structures were elucidated by the NMR spectra and physicochemical properties. RESULT: Eight flavones were obtained and they were identified as isosakuranetin, 7, 4'-dimethylaro madendrin, acacetin, cirsimaritin, rhamnetin, eupatolin, 5, 7, 2', 4'-tetrahydroxy-6, 5'-dimethoxyflavone, hyperoside. CONCLUSION: All the compounds were obtained from herbs of A. ordosica for the first time.

[Studies on chemical constituents of Acroptilon repens].

OBJECTIVE: To investigate the chemical constituents of Acroptilon repens. METHOD: The ethanol extract of A. repens was isolated and purified by means of chromatography. These compounds were identified by their spectral data. RESULT: 11 compounds were isolated and identified as 2alpha, 9beta-dihydroxy-dehydrocostus lactone (1) , cynaropicrin (2) , apigenin (3) , stigmasterol (4) , 4' -hydroxywogonin (5) , ethyl caffeate (6) , p-methoxy-cinnamic acid (7) , luteolin (8) , daucosterol (9) , apigenin-7-O-beta-D-glucoside (10) , syringin (11). CONCLUSION: Compounds 5-11 were isolated from A. repens for the first time. Compound 1 is new compounds.

[Studies on flavonoids from herb of Artemisia ordosica].

OBJECTIVE: To study the chemical constituents of Artemisia ordosica. METHOD: The chemical constituents were isolated and repeatedly purified on silica gel column and the structures were elucidated by the NMR spectra and physico-chemical properties. RESULT: Eight flavonoids were obtained and identified as 5-hydroxy-7, 4'-dimethoxyflavanone, 5-hydroxy-7, 4'-dimethoxyflavone, 5, 4'-dihydroxy-7-methoxyflavone, 5, 7-dihydroxy-6, 4'-dimethoxyflavone, 5, 4'-dihydroxy-7-methoxyflavanone, 5, 3', 4'-trihydroxy-7-methoxyflavanone, 5, 7-dihydroxy-3', 4'-dimethoxyflavone and 5, 3', 4'-trihydroxy-7-methoxyflavone. CONCLUSION: All the compounds were obtained from A. ordosica for the first time.

[Studies on chemical constituents in herb of Chondrilla piptocoma].

OBJECTIVE: To study the chemical constituents of Chondrilla piptocoma. METHOD: The chemical constituents were isolated and repeatedly purified on silica gel column and the structures were elucidated by the NMR spectra and physico-chemical properties. RESULT: Seven compounds were obtained and they are identified as luteolin, 5,7,4'-trihydroxy-3'-methoxy flavone, luteolin-7-O-beta-D-glucoside, apigenin, beta-sitosterol, stigmasterol, ursolic acid. CONCLUSION: All the compounds were obtained from C. piptocoma for the first time.

[Studies on the alkaloids from herb of Corydalis adunca].

OBJECTIVE: To study the alkaloid constituents of Corydalis adunca. METHOD: The constituents were isolated on silica gel column and their structures were elucidated by IR, NMR, MS data. RESULT: Four alkaloid compounds were isolated from alcohol extract of the herb of C. adunca, and identified as tetrahydropalmatine, 1, 2, 3, 4-tetrahydro-6-methoxy-1-(4'-methoxyphenyl) methyl-7-isoquinolinol, coptisine and palmatine. CONCLUSION: Four compounds were isolated from C. adunca for the first time.