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Protective effects of Dioscin on TNF-α-induced collagen-induced arthritis rat fibroblast-like synoviocytes involves in regulating the LTB4/BLT pathway

ZHIPING WEI1,2, YAJUN LIU1, MEIWEN YANG3, MENGDI LI1, KEXIN LI1, LUXI ZHENG1, HUIQIONG GUO1, FENFANG HONG4,*, SHULONG YANG1,*

1 Department of Physiology, College of Medicine, Nanchang University, Nanchang, 330006, China
2 Henan Vocational College of Nursing, Anyan, 455000, China
3 Nanchang University Hospital, Nanchang, 330031, China
4 Department of Experimental Teaching Center, Nanchang University, Nanchang, 330031, China

* Address correspondence to: Fenfang Hong, email; Shulong Yang, email

BIOCELL 2021, 45(4), 1005-1012. https://doi.org/10.32604/biocell.2021.014581

Abstract

Background and Objective: LTB4 has been shown to be involved in rheumatoid arthritis (RA) pathogenesis. The effect of Dioscin(Dio) on the LTB4 pathway of RA have not been reported yet. This study aimed at further exploring whether Dioscin’s effects on TNF-α induced collagen-induced arthritis (CIA) rat fibroblast-like synoviocytes (FLS) connected with the LTB4 and its receptor pathway. Materials & Methods: In this experiment, control group, TNF-α group, and different concentrations of Dioscin groups were established. Cell viability was evaluated using MTT assay. The levels of LTB4 in the samples of above groups were measured using ELISA. The mRNA expression levels of LTA4H, BLT1, and BLT2 were detected by quantitative real time PCR, while the expression level of LTA4H proteins were detected using western blot. The distribution of LTA4H was assessed by immunofluorescence assay. Results: the LTB4 level of TNF-α group in sample supernatant was higher than both control group and Dioscin groups with decreased LTB4 levels (p< 0.05). Compared with the control group, the expression of LTA4H was significantly increased in TNF-α group (p < 0.05), whereas LTA4H expressions were significantly decreased in all Dioscin groups when compared to TNF-α group (p < 0.05). The mRNA expressions of BLT1 and BLT2 were markedly higher in TNF-α group than those in control group while Dioscin treatment significantly inhibited the increased expressions of BLT1 and BLT2 induced by TNF-α (p < 0.05). Conclusions: These results firstly demonstrate that the protective effect of Dioscin on TNF-α induced FLS may involve in its reducing LTB4 production by down-regulating LTA4H expression, and may inhibit its downstream pathway by decreasing LTB4 receptors levels. This findings suggest that dioscin produces a potential therapeutic effects for RA via its influencing LTA4H/LTB4/BLT pathway.

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WEI, Z., LIU, Y., YANG, M., LI, M., LI, K. et al. (2021). Protective effects of Dioscin on TNF-α-induced collagen-induced arthritis rat fibroblast-like synoviocytes involves in regulating the LTB4/BLT pathway. BIOCELL, 45(4), 1005–1012.



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