Betulin Targets Lipin1/2-Meidated P2X7 Receptor as a Therapeutic Approach to Attenuate Lipid Accumulation and Metaflammation

Autor:	Zhao-Xu Li, Yu-Chen Jiang, Yue Liu, Ji-Xing Nan, Zhong-He Hu, Ming-Hui Yuan, Yan-Ling Wu, Li-Hua Lian, Kun-Chen Yao, Xiao-Xue Bao, Jia-Yi Dou, Mei-Jie Zhou
Rok vydání:	2022
Předmět:	Pharmacology chemistry.chemical_classification Betulin Lipopolysaccharide Peroxisome proliferator-activated receptor Inflammation Biochemistry chemistry.chemical_compound chemistry In vivo Drug Discovery medicine Molecular Medicine Oil Red O medicine.symptom Signal transduction Receptor
Zdroj:	Biomolecules & Therapeutics. 30:246-256
ISSN:	2005-4483 1976-9148
DOI:	10.4062/biomolther.2021.136
Popis:	The present study focused on the potential mechanism of betulin (BT), a pentacyclic triterpenoid isolated from the bark of white birch (Betula pubescens), against chronic alcohol-induced lipid accumulation and metaflammation. AML-12 and RAW 264.7 cells were administered ethanol (EtOH), lipopolysaccharide (LPS) or BT. Male C57BL/6 mice were fed Lieber-DeCarli liquid diets containing 5% EtOH for 4 weeks, followed by single EtOH gavage on the last day and simultaneous treatment with BT (20 or 50 mg/kg) by oral gavage once per day. In vitro, MTT showed that 0-25 mM EtOH and 0-25 μM BT had no toxic effect on AML-12 cells. BT could regulate sterolregulatory-element-binding protein 1 (SREBP1), lipin1/2, P2X7 receptor (P2X7r) and NOD-like receptor family, pyrin domains-containing protein 3 (NLRP3) expressions again EtOH-stimulation. Oil Red O staining also indicated that BT significantly reduced lipid accumulation in EtOH-stimulated AML-12 cells. Lipin1/2 deficiency indicated that BT might mediate lipin1/2 to regulate SREBP1 and P2X7r expression and further alleviate lipid accumulation and inflammation. In vivo, BT significantly alleviated histopathological changes, reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and triglyceride (TG) levels, and regulated lipin1/2, SREBP1, peroxisome proliferator activated receptor α/γ (PPARα/γ) and PGC-1α expression compared with the EtOH group. BT reduced the secretion of inflammatory factors and blocked the P2X7r-NLRP3 signaling pathway. Collectively, BT attenuated lipid accumulation and metaflammation by regulating the lipin1/2-mediated P2X7r signaling pathway.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::179556e7e6c4e567867f81ebcd626663 https://doi.org/10.4062/biomolther.2021.136 Zobrazit plný text záznamu