Anoectochilus roxburghii polysaccharide reduces D-GalN/LPS-induced acute liver injury by regulating the activation of multiple inflammasomes.

Autor:	Yan Y; Ningde Hospital of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fujian, 352100, China., Ye X; Ningde Hospital of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fujian, 352100, China., Huang C; Ningde Hospital of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fujian, 352100, China., Wu J; Ningde Hospital of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fujian, 352100, China., Liu Y; Pingnan County Hospital of Traditional Chinese Medicine, Ningde City, Fujian Province, 352300, China., Zheng P; Shouning County Hospital of Traditional Chinese Medicine, Ningde City, Fujian Province, 355500, China., Shen C; Shanxi University of Traditional Chinese Medicine, 030619,China., Bai Z; China Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China., Tingming S; Ningde Hospital of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fujian, 352100, China.
Jazyk:	angličtina
Zdroj:	The Journal of pharmacy and pharmacology [J Pharm Pharmacol] 2024 Sep 03; Vol. 76 (9), pp. 1212-1224.
DOI:	10.1093/jpp/rgae077
Abstrakt:	Background: Acute liver injury (ALI) is a serious syndrome with a high mortality rate due to viral infection, toxic exposure, and autoimmunity, and its severity can range from mildly elevated liver enzymes to severe liver failure. Activation of the nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is closely associated with the development of ALI, and the search for an inhibitor targeting this pathway may be a novel therapeutic option. Anoectochilus roxburghii polysaccharide (ARP) is a biologically active ingredient extracted from Anoectochilus roxburghii with immunomodulatory, antioxidant, and anti-inflammatory bioactivities and pharmacological effects. In this study, we focused on D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver injury by ARP through inhibition of NLRP3 inflammasome. Methods: An inflammasome activation model was established in bone marrow-derived macrophages (BMDMs) to investigate the effects of ARP on caspase-1 cleavage, IL-1β secretion, and ASC oligomerization in inflammasomes under different agonists. We used the D-GalN/LPS-induced acute liver injury model in mice, intraperitoneally injected ARP or MCC950, and collected liver tissues, serum, and intraperitoneal lavage fluid for pathological and biochemical indexes. Results: ARP effectively inhibited the activation of the NLRP3 inflammasome and had an inhibitory effect on non-classical NLRP3, AIM2, and NLRC4 inflammasomes. It also effectively inhibited the oligomerization of apoptosis-associated speck-like protein (ASC) from a variety of inflammatory vesicles. Meanwhile, ARP has good therapeutic effects on acute liver injury induced by D-GaIN/LPS. Conclusion: The inhibitory effect of ARP on a wide range of inflammasomes, as well as its excellent protection against acute liver injury, suggests that ARP may be a candidate for acute liver injury. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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