Dihydromyricetin ameliorates vascular endothelial damage by inhibiting NLRP3 inflammasome activity through Sirtuin 3

Minghua LIU; Hui SHEN; Xiaolan WANG; Xi ZHOU; Ting ZHANG

doi:10.16016/j.2097-0927.202211043

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Dihydromyricetin ameliorates vascular endothelial damage by inhibiting NLRP3 inflammasome activity through Sirtuin 3

Basic Medicine | 更新时间：2026-01-09

- Dihydromyricetin ameliorates vascular endothelial damage by inhibiting NLRP3 inflammasome activity through Sirtuin 3
- Journal of Army Medical University Vol. 45, Issue 9, Pages: 964-974(2023)
- 作者机构：
  
  400038 重庆, 陆军军医大学(第三军医大学)军事预防医学系军队营养与食品卫生学教研室, 重庆市营养与食品安全重点实验室, 重庆市医学营养研究中心
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81773409);the Project of Natural Science Foundation of Chongqing(cstc2017jcyjAX0458)
- DOI：10.16016/j.2097-0927.202211043
  CLC： R151.2;R322.12;R329.25
- Received：08 November 2022，
  
  Revised：2023-01-09，
  
  Published：15 May 2023
- 稿件说明：
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Minghua LIU, Hui SHEN, Xiaolan WANG, et al. Dihydromyricetin ameliorates vascular endothelial damage by inhibiting NLRP3 inflammasome activity through Sirtuin 3[J]. Journal of Army Medical University, 2023, 45(9): 964-974.
DOI：

Minghua LIU, Hui SHEN, Xiaolan WANG, et al. Dihydromyricetin ameliorates vascular endothelial damage by inhibiting NLRP3 inflammasome activity through Sirtuin 3[J]. Journal of Army Medical University, 2023, 45(9): 964-974. DOI： 10.16016/j.2097-0927.202211043.

摘要

目的

观察二氢杨梅素(dihydromyricetin

DHM)对通过Sirt3抑制棕榈酸诱导的血管内皮细胞NLRP3炎性小体活化

改善血管内皮细胞损伤的作用机制研究。

方法

棕榈酸(200 μmol/L)处理人脐静脉内皮细胞建立炎症损伤模型

不同浓度DHM (10、20、40 μmol/L)干预后检测内皮细胞活力、LDH释放水平以及内皮细胞黏附因子表达。运用qRT-PCR和蛋白免疫印迹法检测NLRP3炎性小体活化相关细胞因子的mRNA和蛋白表达水平。运用海马能量代谢检测平台和膜电位实验探索DHM对内皮细胞线粒体功能的调节作用。利用Sirt3特异性抑制剂3-TYP (50 μmol/L)和Sirt3过表达质粒干预

探索Sirt3在DHM抑制棕榈酸诱导NLRP3炎性小体活化中的作用。

结果

DHM能显著抑制棕榈酸诱导的内皮细胞活力下降、抑制LDH释放以及ICAM-1和VCAM-1的分泌(

0.05)。并且

DHM可显著改善线粒体呼吸耗氧量下降

ATP产量及剩余呼吸能力以及抑制线粒体膜电位升高(

0.05)。同时

DHM可以抑制棕榈酸诱导的NLRP3、IL-18和ASC等的mRNA和蛋白表达(

0.05)

Sirt3过表达质粒转染可增强DHM这一效应

而Sirt3抑制剂3-TYP处理则显著削弱DHM的作用。

结论

DHM通过激活Sirt3维持内皮细胞线粒体代谢

抑制NLRP3活化

减轻血管内皮细胞炎症损伤。

Abstract

Objective

To investigate the inhibitory effects and mechanism of dihydromyricetin (DHM) on the activation of NLRP3 inflammasome and improvement of palmitic acid induced injury in vascular endothelial cells through Sirtuin 3(Sirt3).

Methods

Human umbilical vein endothelial cells (HUVECs) were treated with palmitic acid (200 μmol/L) to establish an inflammatory injury model

which was subsequently intervened with different concentrations of DHM (10

20 and 40 μmol/L).Cell viability

LDH release level and expression of endothelial cell adhesion factors were detected respectively.qRT-PCR and Western blotting were used to measure the mRNA and protein levels of cytokines related to NLRP3 inflammasome activation.The regulatory effects of DHM on mitochondrial function of endothelial cells were determined by Seahorse Extracellular Flux Platform and mitochondrial membrane potential assay.Moreover

Sirt3-specific inhibitor 3-TYP (50 μmol/L) and Sirt3 overexpression plasmid were adopted to explore the role of Sirt3 in DHM inhibiting the activation of NLRP3 inflammasome induced by palmitic acid.

Results

DHM significantly inhibited the decline in cell viability

release of LDH

and secretion of endothelial cell adhesion factors ICAM-1 and VCAM-1 induced by palmitic acid (

0.05).Moreover

DHM remarkably improved the decrease of oxygen consumption for mitochondrial respiratory activity

enhanced ATP production and residual respiratory capacity

and suppressed the elevation of mitochondrial membrane potential (

0.05).Meanwhile

DHM also suppressed the mRNA and protein levels of NLRP3

IL-18 and ASC induced by palmitic acid (

0.05).Sirt3 overexpression enhanced the above effects of DHM

while the Sirt3 inhibitor 3-TYP obviously attenuated these effects.

Conclusion

DHM maintains mitochondrial metabolism of endothelial cells by activating Sirt3

inhibits the activation of NLRP3 inflammasome

and thus alleviates the inflammatory damage in HUVECs.

关键词

Keywords

references

《中国心血管健康与疾病报告》编写组. 《中国心血管健康与疾病报告2020》概述[J]. 中国心血管病研究, 2021, 19(7): 582-590. DOI: 10.3969/j.issn.1672-5301.2021.07.002.

The Writing Committee of the Reporton Cardiovascular Health and Diseasesin China. Key Points of Reporton Cardiovascular Health and Diseasesin China 2020[J]. Chin J Cardiovasc Res, 2021, 19(7): 582-590. DOI: 10.3969/j.issn.1672-5301.2021.07.002.

陈亚丽, 尹跃霏, 李赟, 等. 二氢杨梅素药理作用研究进展[J]. 中国新药杂志, 2019, 28(2): 173-178.

CHEN Y L, YIN Y F, LI Y, et al . Advances in pharmacological study of dihydromyricetin[J ] . Chin J New Drugs, 2019, 28(2): 173-178.

ZHANG J Y, CHEN Y, LUO H Q, et al . Recent update on the pharmacological effects and mechanisms of dihydromyricetin[J ] . Front Pharmacol, 2018, 9: 1204. DOI: 10.3389/fphar.2018.01204.

CHEN S H, ZHAO X L, WAN J, et al . Dihydromyricetin improves glucose and lipid metabolism and exerts anti-inflammatory effects in nonalcoholic fatty liver disease: a randomized controlled trial[J ] . Pharmacol Res, 2015, 99: 74-81. DOI: 10.1016/j.phrs.2015.05.009.

ZHANG Y W, YANG W L, LI W G, et al . NLRP3 inflammasome: checkpoint connecting innate and adaptive immunity in autoimmune diseases[J ] . Front Immunol, 2021, 12: 732933. DOI: 10.3389/fimmu.2021.732933.

GREBE A, HOSS F, LATZ E. NLRP3 inflammasome and the IL-1 pathway in atherosclerosis[J]. Circ Res, 2018, 122(12): 1722-1740. DOI: 10.1161/CIRCRESAHA.118.311362.

KELLEY N, JELTEMA D, DUAN Y H, et al . The NLRP3 inflammasome: an overview of mechanisms of activation and regulation[J ] . Int J Mol Sci, 2019, 20(13): 3328. DOI: 10.3390/ijms20133328.

SWANSON K V, DENG M, TING J P Y. The NLRP3 inflammasome: molecular activation and regulation to therapeutics[J]. Nat Rev Immunol, 2019, 19(8): 477-489. DOI: 10.1038/s41577-019-0165-0.

GIMBRONE M A Jr, GARCÍA-CARDEÑA G. Endothelial cell dysfunction and the pathobiology of atherosclerosis[J]. Circ Res, 2016, 118(4): 620-636. DOI: 10.1161/CIRCRESAHA.115.306301.

WOLF D, LEY K. Immunity and inflammation in atherosclerosis[J]. Herz, 2019, 44(2): 107-120. DOI: 10.1007/s00059-019-4790-y.

LIU X T, LU B, FU J L, et al . Amorphous silica nanoparticles induce inflammation via activation of NLRP3 inflammasome and HMGB1/TLR4/MYD88/NF-kb signaling pathway in HUVEC cells[J ] . J Hazard Mater, 2021, 404(Pt B): 124050. DOI: 10.1016/j.jhazmat.2020.124050..

HU R, WANG M Q, NI S H, et al . Salidroside ameliorates endothelial inflammation and oxidative stress by regulating the AMPK/NF-κB/NLRP3 signaling pathway in AGEs-induced HUVECs[J ] . Eur J Pharmacol, 2020, 867: 172797. DOI: 10.1016/j.ejphar.2019.172797.

CHEN M L, ZHU X H, RAN L, et al . Trimethylamine-N-oxide induces vascular inflammation by activating the NLRP3 inflammasome through the SIRT3-SOD2-mtROS signaling pathway[J ] . J Am Heart Assoc, 2017, 6(9): e006347. DOI: 10.1161/JAHA.117.006347.

HE M, CHIANG H H, LUO H Z, et al . An acetylation switch of the NLRP3 inflammasome regulates aging-associated chronic inflammation and insulin resistance[J ] . Cell Metab, 2020, 31(3): 580-591. e5. DOI: 10.1016/j.cmet.2020.01.009.

BAI R R, LANG Y, SHAO J, et al . The role of NLRP3 inflammasome in cerebrovascular diseases pathology and possible therapeutic targets[J ] . ASN Neuro, 2021, 13: 17590914211018100. DOI: 10.1177/17590914211018100.

ROVIRA-LLOPIS S, APOSTOLOVA N, BAÑULS C, et al . Mitochondria, the NLRP3 inflammasome, and sirtuins in type 2 diabetes: new therapeutic targets[J ] . Antioxid Redox Signal, 2018, 29(8): 749-791. DOI: 10.1089/ars.2017.7313.

CUI Z F, ZHAO X T, AMEVOR F K, et al . Therapeutic application of quercetin in aging-related diseases: SIRT1 as a potential mechanism[J ] . Front Immunol, 2022, 13: 943321. DOI: 10.3389/fimmu.2022.943321.

JIN X, FU W, ZHOU J X, et al . Oxymatrine attenuates oxidized low-density lipoprotein-induced HUVEC injury by inhibiting NLRP3 inflammasome-mediated pyroptosis via the activation of the SIRT1/Nrf2 signaling pathway[J ] . Int J Mol Med, 2021, 48(4): 187. DOI: 10.3892/ijmm.2021.5020..

DING Y, GONG W W, ZHANG S P, et al . Protective role of sirtuin3 against oxidative stress and NLRP3 inflammasome in cholesterol accumulation and foam cell formation of macrophages with ox-LDL-stimulation[J ] . Biochem Pharmacol, 2021, 192: 114665. DOI: 10.1016/j.bcp.2021.114665.

YU H L, LIU Q, CHEN G D, et al . SIRT3-AMPK signaling pathway as a protective target in endothelial dysfunction of early sepsis[J ] . Int Immunopharmacol, 2022, 106: 108600. DOI: 10.1016/j.intimp.2022.108600.

TRABA J, KWARTENG-SIAW M, OKOLI T C, et al . Fasting and refeeding differentially regulate NLRP3 inflammasome activation in human subjects[J ] . J Clin Invest, 2015, 125(12): 4592-4600. DOI: 10.1172/JCI83260.

ZENG X L, YANG J N, HU O, et al . Dihydromyricetin ameliorates nonalcoholic fatty liver disease by improving mitochondrial respiratory capacity and redox homeostasis through modulation of SIRT3 signaling[J ] . Antioxid Redox Signal, 2019, 30(2): 163-183. DOI: 10.1089/ars.2017.7172.

SHI L Y, ZHANG T, ZHOU Y, et al . Dihydromyricetin improves skeletal muscle insulin sensitivity by inducing autophagy via the AMPK-PGC-1α-Sirt3 signaling pathway[J ] . Endocrine, 2015, 50(2): 378-389. DOI: 10.1007/s12020-015-0599-5..

LIU P, ZOU D, CHEN K, et al . Dihydromyricetin improves hypobaric hypoxia-induced memory impairment via modulation of SIRT3 signaling[J ] . Mol Neurobiol, 2016, 53(10): 7200-7212. DOI: 10.1007/s12035-015-9627-y..

ZHOU J, HOU P F, YAO Y, et al . Dihydromyricetin improves high-fat diet-induced hyperglycemia through ILC3 activation via a SIRT3-dependent mechanism[J ] . Mol Nutr Food Res, 2022, 66(16): e2101093. DOI: 10.1002/mnfr.202101093..

HU Q, ZHANG T, YI L, et al . Dihydromyricetin inhibits NLRP3 inflammasome-dependent pyroptosis by activating the Nrf2 signaling pathway in vascular endothelial cells[J ] . Biofactors, 2018, 44(2): 123-136. DOI: 10.1002/biof.1395.

HUA Y Y, ZHANG Y, GONG W W, et al . Dihydromyricetin improves endothelial dysfunction in diabetic mice via oxidative stress inhibition in a SIRT3-dependent manner[J ] . Int J Mol Sci, 2020, 21(18): 6699. DOI: 10.3390/ijms21186699..

SUN W, LIU C X, CHEN Q H, et al . SIRT3: a new regulator of cardiovascular diseases[J ] . Oxid Med Cell Longev, 2018, 2018: 7293861. DOI: 10.1155/2018/7293861.

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