•  
  •  
 

Corresponding Author(s)

全吉淑(1968—),女,延边大学教授,博士。E-mail: quanjs@ybu.edu.cn金爱花(1984—),女,延边医院检验师,硕士。E-mail:aihua1028@sina.com

Abstract

Objective: This study aimed to investigate the inhibitory effect of Boschniakia rossica polysaccharides (BRPS) on the activation of inflammasome and pyroptosis of J774A.1 macrophages induced by lipopolysaccharide (LPS) and adenosine triphosphate (ATP). Methods: The nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome model was established by stimulating J774A.1 macrophages with LPS and ATP. Cell viability was detected using the cell counting kit-8, the release of lactate dehydrogenase (LDH) was tested with the microplate method, the cellular level of NLRP3 and cell membrane damage were detected using the immunofluorescence staining method, and the secretion of interleukin-1β (IL-1β) was measured by the enzyme-linked immunosorbent assay. The protein expressions of NLRP3, caspase-1, apoptosis associated speck-like protein containing caspase recruitment domains (ASC), IL-1β, gasdermin D (GSDMD), as well as the nuclear factors-κB (NF-κB) and mitogen activated protein kinase (MAPK) was determined with the western blotting method. Results: BRPS could increase the cell viability, reduce the release of LDH in the culture medium, alleviate the membrane damage of macrophages, down-regulate the protein expression of NLRP3, up-regulate the level of caspase-1 precursor, and down-regulate the levels of IL-1β and GSDMD N-terminal active fragment in the model group. In addition, BRPS suppressed the nuclear translocation and phosphorylation of NF-κB, as well as the phosphorylation of extracellular signal-regulated protein kinase, c-Jun amino terminal kinase, and p38 MAPK. Conclusion: BRPS inhibit LPS/ATP-induced activation of macrophage inflammasome and pyroptosis in mouse J774A.1 cells through regulating the NF-κB and MAPK signaling pathways.

Publication Date

7-22-2024

First Page

137

Last Page

145

DOI

10.13652/j.spjx.1003.5788.2023.80829

References

[1] 李彩峰, 王晓琴, 刘勇, 等. 草苁蓉化学成分及药理活性研究进展[J]. 中草药, 2014, 45(7): 1 016-1 023. LI C F, WANG X Q, LIU Y, et al. Advances in studies on chemical constituents of Boschniakia rossica and their pharmacological activities[J]. Chinese Traditional and Herbal Drugs, 2014, 45(7): 1 016-1 023.
[2] ZHANG L, ZHAO Y, WANG Z A, et al. The genus Boschniakia in China: An ethnopharmacological and phytochemical review[J]. Journal of Ethnopharmacology, 2016, 194: 987-1 004.
[3] 张航, 王辉, 杨树东. 草苁蓉的本草考证及药理研究[J]. 长春中医药大学学报, 2016, 32(1): 40-42. ZHANG H, WANG H, YANG S D.Herbalogical study and pharmacological effect of Boschniakia rossica[J]. Journal of Changchun University of Chinese Medicine, 2016, 32(1): 40-42.
[4] LIN L C, LEE L C, HUANG C, et al. Effects of boschnaloside from Boschniakia rossica on dysglycemia and islet dysfunction in severely diabetic mice through modulating the action of glucagon-like peptide-1[J]. Phytomedicine, 2019, 62: 152946.
[5] YAO C, CAO X, FU Z, et al. Boschniakia rossica polysaccharide triggers laryngeal carcinoma cell apoptosis by regulating expression of Bcl-2, caspase-3, and p53[J]. Medical Science Monitor, 2017, 23: 2 059-2 064.
[6] 陈虹, 黄明伟, 程振东, 等. 草苁蓉多糖下调miR-302a-3p表达对缺氧/复氧诱导的心肌细胞损伤的影响[J]. 中国药理学通报, 2023, 39(7): 1 241-1 247. CHEN H, HUANG M W, CHENG Z D, et al. Effect of Boschniakia rossica polysaccharides on hypoxia/reoxygenation-induced cardiomyocyte damage by down-regulating miR-302a-3p expression[J]. Chinese Pharmacological Bulletin, 2023, 39(7): 1 241-1 247.
[7] 宋全胜. 草苁蓉根茎粗多糖的分离纯化及其部分性质的研究[D]. 延吉: 延边大学, 2005: 17-18. SONG Q S. Purification and character of the crude polysaccharide from the root and stem of the Boschnikiarossica Fedtsch. et Flerov[D]. Yanji: University of Yanbian, 2005: 17-18.
[8] 刘莉园, 张钊, 葛乃嘉, 等. 草苁蓉多糖对脂多糖诱导的RAW264.7巨噬细胞炎症反应的影响[J]. 中国药学杂志, 2021, 56(18): 1 479-1 485. LIU L Y, ZHANG Z, GE N J, et al. Effect of Boschniakia rossica polysaccharides on LPS-induced inflammation of RAW264.7 macrophages[J]. Chinese Pharmaceutical Journal, 2021, 56(18): 1 479-1 485.
[9] 张天, 王园园, 张钊, 等. 草苁蓉多糖对脂多糖诱导的小鼠J774A.1巨噬细胞炎症反应的抑制作用[J]. 食品与发酵工业, 2021, 47(12): 117-122. ZHANG T, WANG Y Y, ZHANG Z, et al. Inhibitory effect of Boschniakia rossica polysaccharides on lipopolysaccharide-induced inflammatory response in mouse J774A.1 macrophages[J]. Food and Fermentation Industries, 2021, 47(12): 117-122.
[10] QIAN L, LI J Z, SUN X, et al. Safinamide prevents lipopolysaccharide (LPS)-induced inflammation in macrophages by suppressing TLR4/NF-κB signaling[J]. Int Immunopharmacol, 2021, 96: 107712.
[11] RATHINAM V A, FITZGERALD K A. Inflammasome complexes: Emerging mechanisms and effector functions[J]. Cell, 2016, 165(4): 792-800.
[12] BRAHADEESWARAN S, DASGUPTA T, MANICKAM V, et al. NLRP3: A new therapeutic target in alcoholic liver disease[J]. Frontiers in Immunology, 2023, 14: 1215333.
[13] ZHANG Y, DONG Z, SONG W. NLRP3 inflammasome as a novel therapeutic target for Alzheimer's disease[J]. Signal Transduction and Targeted Therapy, 2020, 5(1): 37.
[14] PAGLIARO P, PENNA C. Inhibitors of NLRP3 inflammasome in ischemic heart disease: Focus on functional and redox aspects[J]. Antioxidants (Basel), 2023, 12(7): 1 396.
[15] HUANG Y, XU W, ZHOU R. NLRP3 inflammasome activation and cell death[J]. Cellular & Molecular Immunology, 2021, 18(9): 2 114-2 127.
[16] CHAN A H, SCHRODER K. Inflammasome signaling and regulation of interleukin-1 family cytokines[J]. Journal of Experimental Medicine, 2020, 217(1): e20190314.
[17] YU P, ZHANG X, LIU N, et al. Pyroptosis: Mechanisms and diseases[J]. Signal Transduction and Targeted Therapy, 2021, 6(1): 128.
[18] 张钊. 没食子酸对脂多糖诱导的小鼠J774.1巨噬细胞炎症反应的抑制作用[D]. 延吉: 延边大学, 2022: 11-13. ZHAN Z. Inhibitory effect of gallic acid on LPS-induced inflammatory response in mouse J774A.1 macrophages[D]. Yanji: Yanbian University, 2022: 11-13.
[19] 杜宝双, 陈尚卫, 李玥, 等. 二氢杨梅素及其酰化衍生物对肝细胞氧化损伤的保护作用[J]. 食品与机械, 2022, 38(6): 30-33, 150. DU B S, CHEN S W, LI Y, et al. The protection effect of dihydromyricetin and its acylated derivatives on oxidative damage of hepatocytes[J]. Food & Machinery, 2022, 38(6): 30-33, 150.
[20] JORGENSEN I, MIAO E A. Pyroptotic cell death defends against intracellular pathogens[J]. Immunological Reviews, 2015, 265(1): 130-142.
[21] 陈卓, 方兴刚, 郭兴荣, 等. 基于网络药理学及实验研究探讨紫檀芪调控凋亡及GSDME介导的细胞焦亡途径抗脑胶质瘤的作用机制[J]. 中国中药杂志, 2023, 48(13): 3 589-3 601. CHEN Z, FANG X G, GUO X R, et al. Anti-glioma mechanism of pterostilbene by regulating apoptosis and GSDME-mediated pyroptosis pathways: A study based on network pharmacology and experimental research[J]. China Journal of Chinese Materia Medica, 2023, 48(13): 3 589-3 601.
[22] ZHAO N, LI C C, DI B, et al. Recent advances in the NEK7-licensed NLRP3 inflammasome activation: Mechanisms, role in diseases and related inhibitors[J]. Journal of Autoimmunity, 2020, 113: 102515.
[23] MIAO E A, RAJAN J V, ADEREM A. Caspase-1-induced pyroptotic cell death[J]. Immunol Rev, 2011, 243(1): 206-214.
[24] BERGSBAKEN T, FINK S L, COOKSON B T. Pyroptosis: Host cell death and inflammation[J]. Nature Reviews Microbiology, 2009, 7(2): 99-109.
[25] HAN Y, LI X, ZHANG X,et al. Isodeoxyelephantopin, a sesquiterpene lactone from Elephantopus scaber linn, inhibits pro-inflammatory mediators' production through both NF-κB and AP-1 pathways in LPS-activated macrophages[J]. International Immunopharmacology, 2020, 84: 106528.
[26] CUI L, ZHENG Y, WANG H, et al. Cortisol inhibits the Escherichia coli-induced endometrial inflammatory response through NF-κB and MAPK pathways in postpartum goats[J]. Animal Reproduction Science, 2020, 215: 106333.
[27] LANG Y, CHU F, LIU L, et al. Potential role of BAY11-7082, a NF-κB blocker inhibiting experimental autoimmune encephalomyelitis in C57BL/6J mice via declining NLRP3 inflammasomes[J]. Clinical and Experimental Immunology, 2022, 207(3): 378-386.
[28] WANG Y H, GAO X, TANG Y R, et al. Resolvin D1 alleviates mechanical allodynia via ALX/FPR2 receptor targeted Nod-like receptor protein 3/extracellular signal-related kinase signaling in a neuropathic pain model[J]. Neuroscience, 2022, 494: 12-24.
[29] DUMONT A, DE ROSNY C, KIEU T L, et al. Docosahexaenoic acid inhibits both NLRP3 inflammasome assembly and JNK-mediated mature IL-1β secretion in 5-fluorouracil-treated MDSC: Implication in cancer treatment[J]. Cell Death & Disease, 2019, 10(7): 485.
[30] CHEN X, LUO D, JIA G, et al. L-theanine attenuates porcine intestinal tight junction damage induced by LPS via p38 MAPK/NLRP3 signaling in IPEC-J2 cells[J]. Food and Chemical Toxicology, 2023, 178: 113870.

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.