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. 2022 May;13(5):11782-11793.
doi: 10.1080/21655979.2022.2072055.

Cynarin suppresses gouty arthritis induced by monosodium urate crystals

Affiliations

Cynarin suppresses gouty arthritis induced by monosodium urate crystals

Changgui Wu et al. Bioengineered. 2022 May.

Abstract

The study is aimed to determine the effects of cynarin (Cyn) on mice with gouty arthritis (GA) induced by monosodium urate (MSU). We measured swelling in the hind paws of mice in vivo using Vernier calipers and ultrasound. The liver, kidney, and hind paws were stained with hematoxylin-eosin, and M1 type macrophages were detected in the hind paws using anti-F4/80 and anti-iNOS antibodies. The mRNA expression of inflammatory factors in bone marrow-derived macrophages (BMDMs) and in the hind paws was detected via quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasomes and the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways were analyzed via western blotting. Cyn was detected in vitro using Cell Counting Kit-8 (CCK-8). Cyn treatment reduced hind paw swelling and M1 macrophage infiltration, suppressed the mRNA expression of inflammatory factors, and inhibited NLRP3 inflammasome activation in vivo, in addition to inhibiting the phosphorylation of IKKa/β, p65, and c-Jun NH 2-terminal kinase (JNK). Furthermore, Cyn exerted anti-inflammatory and anti-swelling effects in mice with GA by regulating the NF-κB and JNK pathways and NLRP3 inflammasomes.

Keywords: Cynarin; JNK; NF-κB; NLRP3 inflammasomes; gouty arthritis.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

None
Graphical abstract
Figure 1.
Figure 1.
The time chart of induction and treatment process in mice with gouty arthritis
Figure 2.
Figure 2.
Cynarin reduced hind paws swelling in mice with gouty arthritis. (a) After 7 days, changes in hind paws of mice with gouty arthritis. (b) The hind paws of mice were measured and recorded daily using vernier calipers. (c) After 7 days, the swelling of the hind paws of mice was measured using an ultrasound, and the results were displayed in B-mode and 3D-mode. (d) Data were collected using ultrasound software. Data were shown as mean ± standard deviation (SD) of ten mice per group. *p<0.05, **p<0.01, ***p<0.001 VS. MSU group. ###p<0.001 VS. PBS group.
Figure 3.
Figure 3.
The effect of Cyn on kidney and liver tissues. (a, b) Hematoxylin-eosin staining of kidney and liver tissues. The scale in the figure is 50μm.
Figure 4.
Figure 4.
Cynarin inhibited the infiltration of inflammatory cells. (a) The hind paws of mice were stained with hematoxylin and eosin (HE). the scale in the figure is 500μm and 200μm. (b) Synovial tissues of mouse hind paw metatarsophalangeal joint. the scale in the figure is 50μm. (c) Statistics and analysis of the proportion of inflammatory area on the hind paws after HE staining. (d) The hind paws of the mice were stained with immunofluorescence. the scale in the figure is 20μm. (e) Statistics and analysis of the percentage of positive area on the hind paws of mice after immunofluorescence staining. Data were shown as mean ± standard deviation (SD) of ten mice per group. ***p<0.001 VS. MSU group, ###p<0.001 VS. PBS group.
Figure 5.
Figure 5.
The effect of Cynarin on BMDMs and inflammatory factors. (a) CCK-8 kit detected the effect of Cyn on BMDMs. (b-e) After BMDMs were processed, the relative expression of inflammatory factors mRNA was detected. (f-i) After RNA extraction on the hind paws of mice, the relative expression of inflammatory factors mRNA was detected. Data were shown as mean ± standard deviation (SD) of three independent experiments. *p<0.05, **p<0.01, ***p<0.001 VS. MSU group or the group handled by LPS and MSU together. ##p<0.01, ###p<0.001 VS. PBS group or the group without LPS, MSU and Cyn.
Figure 6.
Figure 6.
Cynarin inhibits the activation of NF-κB, JNK pathway and NLRP3 inflammasome induced by MSU. (a-j) Western blotting detected the protein levels of p-p38, p-ERK1/2, p-JNK, p-p65, p65, p-IKKa/β, Caspase1, NLRP3 and IL-1β, and analyzed these protein. Data were shown as mean ± standard deviation (SD) of three independent experiments. NS p>0.05, *p<0.05, **p<0.01, ***p<0.001 VS. the group handled by LPS and MSU together.
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References

    1. Li L, Wang D, Wang X, et al. N -Butyrylated hyaluronic acid ameliorates gout and hyperuricemia in animal models. Pharm Biol. 2019;57(1):717–728. - PMC - PubMed
    1. So AK, Martinon F.. Inflammation in gout: mechanisms and therapeutic targets. Nat Rev Rheumatol. 2017;13(11):639–647. - PubMed
    1. Wijnands JM, Viechtbauer W, Thevissen K, et al. Determinants of the prevalence of gout in the general population: a systematic review and meta-regression. Eur J Epidemiol. 2015;30(1):19–33. - PubMed
    1. Fang L, Xu X, Lu Y, et al. Long noncoding RNA SNHG8 accelerates acute gouty arthritis development by upregulating AP3D1 in mice. Bioengineered. 2021;12(2):9803–9815. - PMC - PubMed
    1. Otani N, Ouchi M, Kudo H, et al. Recent approaches to gout drug discovery: an update. Expert Opin Drug Discov. 2020;15(8):943–954. - PubMed

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