Morin Improves Experimental Autoimmune Thyroiditis in Rats via NLRP3/Caspase-1 Pathway

SUN Ya-jun, ZHANG Yan-fang, XU Hui-min, MA Yong-tao, LI Chun, NIE Chun-hong, ZHAO Min

Abstract

To investigate the effects of morin-regulated NLRP3/Caspase-1 pathway on experimental autoimmune thyroiditis in rats.   Methods   The rats were randomly assigned to 6 groups: control group, experimental autoimmune thyroiditis group (EAT), low-, medium- and high-dose morin groups (post-modeling gavage of 50, 100 and 200 mg/kg morin hydrate per day for 6 weeks) and tripterygium wilfordii polyglycosides group (LGT group, post-modeling gavage of 6.25 mg/kg tripterygium wilfordii polyglycosidesper day for 6 weeks). Except for the control group, the rat model of experimental autoimmune thyroiditis was established by subcutaneous injection of 0.1 mL incomplete Freund’s adjuvant containing porcine thyroglobulin. The levels of serum thyroglobulin (TgAb), thyroid peroxidase antibody (TPOAb), triiodothyronine (T3) and tetraiodothyronine (T4) in serum were detected by radioimmunoassay. The mRNA levels of interleukin-17 (IL-17), interleukin-4 (IL-4) and interferon γ (INF-γ) were detected by reverse transcription-polymerase chain reaction. The levels of serum protein carbonyl content, 8-hydroxydeoxyguanosine (8-OHdG), and malondialdehyde (MDA) activity were checked with test kits. Expressions of NLRP3, apoptosis-related speck-like protein (ASC), and Caspase-1 were detected by Western blot.   Results   Compared with the EAT group, serum levels of TPOAb, TgAb, T3, and T4 in low-, medium- and high-dose Morin groups and LGT group were reduced (P<0.01) and the mRNA levels of IL-17, INF-γ and IL-4 were increased (P<0.01), the protein hydroxyl content, MDA activity, and 8-OHdG levels were reduced (P<0.01). The levels of NLRP3, ASC and Caspase-1 were reduced (P<0.01), the levels of 8-OHdG were significantly reduced (P<0.01), and the levels of NLRP3, ASC and Caspase-1 were significantly reduced (P<0.01). There were statistically significant differences between the data from the low-dose and the medium-dose Morin groups and the data of the LGT group (P<0.05), while data from the high-dose Morin group showed no significant difference compared with the data of the LGT group. Data from low-, medium- and high-dose Morin groups showed no statistically significant differences (P<0.05).   Conclusion   The findings suggest that Morin improved experimental autoimmune thyroiditis in rats through regulating NLRP3/Caspase-1 pathway.

 

Keywords: Morin hydrate, Experimental autoimmune thyroiditis, Inflammation, NLRP3/Caspase-1

 

Full Text:

PDF


References


JIN X， GUAN Y F， SHEN H M， et al. Copy number variation of immune-related genes and their association with iodine in adults with autoimmune thyroid diseases. Int J Endocrinol，2018，2018: 1705478[2020-08-25]. https://doi.org/10.1155/2018/1705478.

KRYSIAK R， OKOPIEN B. The effect of levothyroxine and selenomethionine on lymphocyte and monocyte cytokine release in women with Hashimoto's thyroiditis. J Clin Endocrinol Metab，2011，96(7): 2206–2215.

HOFLING D B， CHAVANTES M C， JULIANO A G， et al. Low-level laser therapy in chronic autoimmune thyroiditis: a pilot study. Lasers Surg Med，2010，42(6): 589–596.

SANG L， WANG X M， XU D Y， et al. Morin enhances hepatic NRF2 expression in a liver fibrosis rat model. World J Gastroenterol，2017， 23(47): 8334–8344.

LI J F. Neuroprotective effect of (-)-epigallocatechin-3-gallate on autoimmune thyroiditis in a rat model by an anti-inflammation effect, anti-apoptosis and inhibition of trail signaling pathway. Exp Ther Med， 2018，15(1): 1087–1092.

DUAN Y， KELLEY N， HE Y. Role of the NLRP3 inflammasome in neurodegenerative diseases and therapeutic implications. Neural Regen Res，2020，15(7): 1249–1250.

GUO Q， WU Y， HOU Y， et al. Cytokine secretion and pyroptosis of thyroid follicular cells mediated by enhanced NLRP3， NLRP1， NLRC4， and AIM2 inflammasomes are associated with autoimmune thyroiditis. Front Immunol， 2018， 9:1197[2019-10-10]. https://doi.org/10.3389/fimmu.2018.01197.

CHISTIAKOV D A. Immunogenetics of Hashimoto’s thyroiditis. J Autoimmune Dis，2005，2(1): 1[2020-08-25]. https://doi.org/10. 1186/1740-2557-2-1.

LICHIARDOPOL C， MOTA M. The thyroid and autoimmunity. Rom J Intern Med，2009，47(3): 207–215.

KRISTENSEN B， HEGEDÜS L， MADSEN H O， et al. Altered balance between self-reactive t helper (Th)17 cells and Th10 cells and between full-length forkhead box protein 3 (Foxp3) and Foxp3 splice variants in Hashimoto's thyroiditis. Clin Exp Immunol，2015，180(1): 58–69.

GU M， ZHANG Y， LIU C， et al. Morin, a novel liver X receptor α/β dual antagonist, has potent therapeutic efficacy for nonalcoholic fatty liver diseases. Br J Pharmacol，2017，174(18): 3032–3044.

OLONODE E T， ADERIBIGBE A O， ADEOLUWA O A， et al. Protective effects of morin hydrate on acute stress-induced behavioral and biochemical alterations in mice. Basic Clin Neurosci，2018，9(3): 195–208. experimental autoimmune thyroiditis in mice. Exp Ther Med，2016， 12(6): 4049–4054.

SIEMINSKA L， WOJCIECHOWSKA C， KOS-KUDLA B， et al. Serum concentrations of leptin, adiponectin, and Interleukin-6 in postmenopausal women with Hashimoto’s thyroiditis. Endokrynol Pol， 2010，61(1): 112–116.

LI H， MIN J， MAO X， et al. Edaravone ameliorates experimental autoimmune thyroiditis in rats through HO-1-dependent STAT3/PI3K/AKT pathway. Am J Transl Res，2018，10(7): 2037–2046.

MA S， CHEN X， WANG L， et al. Repairing effects of ICAM-1-expressing mesenchymal stem cells in mice with autoimmune thyroiditis. Exp Ther Med，2017，13(4): 1295–1302.

ROSTAMI R， AGHASI M R， MOHAMMADI A， et al. Enhanced oxidative stress in Hashimoto’s thyroiditis: inter-relationships to biomarkers of thyroid function. Clin Biochem，2013，46(4/5): 308–312.

ZHANG R， KANG K A， PIAO M J， et al. Cellular protection of morin against the oxidative stress induced by hydrogen peroxide. Chem Biol Interact，2009，177(1): 21–27.

GUO Q， WU Y， HOU Y， et al. Cytokine secretion and pyroptosis of thyroid follicular cells mediated by enhanced NLRP3, NLRP1, NLRC4, and AIM2 inflammasomes are associated with autoimmune thyroiditis. Front Immunol，2018，9: 1197[2020-08-25]. https://doi.org/10.3389/fimmu.2018.01197.

JIANG W， LV H， WANG H， et al. Activation of the NLRP3/caspase-1 inflammasome in human dental pulp tissue and human dental pulp fibroblasts. Cell Tissue Res，2015，361(2): 541–555.


Refbacks

  • There are currently no refbacks.