School of Health and Life Sciences, Pontifical Catholic University of Rio Grande do Sul PUCRS, Porto Alegre, Rio Grande do Sul, Brazil.
School of Health and Life Sciences, Pontifical Catholic University of Rio Grande do Sul PUCRS, Porto Alegre, Rio Grande do Sul, Brazil.
J Ethnopharmacol. 2021 Nov 15;280:114433. doi: 10.1016/j.jep.2021.114433. Epub 2021 Jul 16.
Studies have shown interest in nutraceuticals for the prevention of liver diseases. Methoxyeugenol, is a molecule found in foods, such as nutmeg (Myristica fragrans Houtt.) and Brazilian red propolis. These two sources of methoxyeugenol, propolis and nutmeg, are used in folk medicine for the treatment of hepatic and gastrointestinal disorders, although little is known about their effects on the prevention of liver fibrosis. Natural PPAR (Peroxisome proliferator-activated receptor) agonists would represent unique molecules for therapy, considering the lack of therapeutics to treat liver fibrosis in chronic liver disease. Thus, investigation on new alternatives are necessary, including the search for natural compounds from renewable and sustainable sources. Liver fibrosis is a pathological process characterized by an exacerbated cicatricial response in the hepatic tissue, which compromises liver function. Therefore, inhibition of HSC (hepatic stellate cell) activation and hepatocyte damage are considered major strategies for the development of new anti-fibrotic treatments.
This study aimed to investigate the effects of methoxyeugenol treatment on HSC phenotype modulation in human and murine cells, hepatocyte damage prevention, and protective effects in vivo, in order to evaluate its therapeutic potential for liver fibrosis prevention.
We investigated the effects of methoxyeugenol in (i) in vitro models using human and murine HSC and hepatocytes, and (ii) in vivo models of CCl (carbon tetrachloride) -induced liver fibrosis in mice.
We herein report that methoxyeugenol decreases HSC activation through the activation of PPAR-ɣ, ultimately inducing a quiescent phenotype highlighted by an increase in lipid droplets, loss of contraction ability, and a decrease in the proliferative rate and mRNA expression of fibroblast markers. In addition, methoxyeugenol prevented hepatocytes from oxidative stress damage. Moreover, in mice submitted to chronic liver disease through CCl administration, methoxyeugenol decreased the inflammatory profile, liver fibrosis, mRNA expression of fibrotic genes, and the inflammatory pathway signaled by NF-kB (Nuclear factor kappa B).
We propose methoxyeugenol as a novel and potential therapeutic approach to treat chronic liver disease and fibrosis.
已有研究对用于预防肝脏疾病的营养保健品表现出了兴趣。甲氧基丁香酚是一种存在于食物中的分子，如肉豆蔻（肉豆蔻）和巴西红蜂胶。这两种甲氧基丁香酚的来源，蜂胶和肉豆蔻，在民间医学中用于治疗肝脏和胃肠道疾病，尽管对其预防肝纤维化的作用知之甚少。天然过氧化物酶体增殖物激活受体 (PPAR) 激动剂将代表治疗的独特分子，因为目前缺乏治疗慢性肝病肝纤维化的疗法。因此，有必要对新的替代方法进行研究，包括从可再生和可持续来源寻找天然化合物。肝纤维化是一种病理过程，其特征是肝组织中疤痕反应加剧，从而损害肝功能。因此，抑制 HSC（肝星状细胞）激活和肝细胞损伤被认为是开发新的抗纤维化治疗方法的主要策略。
本研究旨在研究甲氧基丁香酚处理对人源和鼠源 HSC 表型调节、肝细胞损伤预防以及体内保护作用的影响，以评估其预防肝纤维化的治疗潜力。
我们研究了甲氧基丁香酚在（i）人源和鼠源 HSC 和肝细胞的体外模型中的作用，以及（ii）CCl（四氯化碳）诱导的小鼠肝纤维化的体内模型中的作用。
我们在此报告，甲氧基丁香酚通过激活 PPAR-γ 降低 HSC 激活，最终诱导静止表型，表现为脂滴增加、收缩能力丧失、增殖率降低和成纤维细胞标志物的 mRNA 表达降低。此外，甲氧基丁香酚可防止肝细胞氧化应激损伤。此外，在通过 CCl 给药使小鼠患慢性肝病的情况下，甲氧基丁香酚降低了炎症特征、肝纤维化、纤维化基因的 mRNA 表达和 NF-kB（核因子 kappa B）信号传导的炎症途径。
我们提出甲氧基丁香酚是一种治疗慢性肝病和纤维化的新的潜在治疗方法。
