Afrin Mst Rejina, Arumugam Somasundaram, Pitchaimani Vigneshwaran, Karuppagounder Vengadeshprabhu, Thandavarayan Rajarajan Amirthalingam, Harima Meilei, Hossain Chowdhury Faiz, Suzuki Kenji, Sone Hirohito, Matsubayashi Yasuhiro, Watanabe Kenichi
Department of Pharmacy, Faculty of Sciences and Engineering, East West University, Dhaka 1212, Bangladesh.
Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
Heliyon. 2021 Jan 5;7(1):e05888. doi: 10.1016/j.heliyon.2020.e05888. eCollection 2021 Jan.
Le Carbone (LC), a fiber-enriched activated charcoal dietary supplement, claimed to be effective against inflammation associated with colitis, trimethylaminuria, and sclerosis. The study aimed to investigate the underlying mechanisms of LC to protect liver damage and its progression in non-alcoholic steatohepatitis-hepatocellular carcinoma (NASH-HCC) mice. To induce this model, C57BL/6J male baby mice were injected with a low-dose of streptozotocin and fed with a high-fat diet (HFD) 32 during 4 weeks-16 weeks of age. The LC suspension was administered orally at a dose of 5 mg/mouse/day started at the age of 6 weeks and continued until 16 weeks of age along with HFD32 feeding. At the end of the experiment, serum and liver tissues were collected for the biochemical, histological, and molecular analysis. We found that LC suspension improved the histopathological changes, serum aminotransferases in NASH mice. The hepatic expression of metabolic proteins, p-AMPKα and sirtuin 1, and proteins responsible for β-oxidation of fatty acids, peroxisome proliferator-activated receptor (PPAR) γ coactivator-α, PPARα were significantly repressed in NASH mice. LC treatment markedly restored these expressions. LC treatment significantly reduced the hepatic proteins expressions of PPARγ, tissue inhibitor of metalloproteinases 4, p47phox, p-JNK, p-ERK1/2, glypican-3, and prothrombin in NASH mice. Our findings demonstrate that LC prevents the liver damage and progression of NASH, possibly by enhancing the AMPK-SIRT1 signaling pathway.
Le Carbone(LC)是一种富含纤维的活性炭膳食补充剂,据称对与结肠炎、三甲胺尿症和硬化症相关的炎症有效。本研究旨在探讨LC在非酒精性脂肪性肝炎-肝细胞癌(NASH-HCC)小鼠中保护肝脏损伤及其进展的潜在机制。为诱导该模型,在4周龄至16周龄期间,给C57BL/6J雄性幼鼠注射低剂量链脲佐菌素并喂食高脂饮食(HFD)32。从6周龄开始,以5mg/小鼠/天的剂量口服给予LC悬浮液,持续至16周龄,同时喂食HFD32。实验结束时,收集血清和肝脏组织进行生化、组织学和分子分析。我们发现LC悬浮液改善了NASH小鼠的组织病理学变化和血清转氨酶。NASH小鼠中代谢蛋白、p-AMPKα和沉默调节蛋白1以及负责脂肪酸β氧化的蛋白、过氧化物酶体增殖物激活受体(PPAR)γ辅激活因子-α、PPARα的肝脏表达显著受到抑制。LC处理显著恢复了这些表达。LC处理显著降低了NASH小鼠肝脏中PPARγ、金属蛋白酶组织抑制剂4、p47phox、p-JNK、p-ERK1/2、磷脂酰肌醇蛋白聚糖-3和凝血酶原的蛋白表达。我们的研究结果表明,LC可能通过增强AMPK-SIRT1信号通路来预防肝脏损伤和NASH的进展。