Salvoza Noel, Bedin Chiara, Saccani Andrea, Tiribelli Claudio, Rosso Natalia
Fondazione Italiana Fegato-ONLUS, Area Science Park, Basovizza SS14 km 163.5, 34149 Trieste, Italy.
Philippine Council for Health Research and Development, DOST-Bicutan, Taguig City 1631, Philippines.
Int J Mol Sci. 2022 Mar 24;23(7):3562. doi: 10.3390/ijms23073562.
Triterpenic acid (TA) and acteoside (ACT), the major components of APPLIVER and ACTEOS, respectively, have been reported to exert hepatoprotective effects, but the molecular mechanisms remain elusive, particularly in the NAFLD/NASH context. We assessed their effects in our well-established in vitro model resembling the pathophysiological mechanisms involved in NASH. Human hepatocytes and hepatic stellate cells were exposed to free fatty acids (FFA) alone or in combination with APPLIVER and ACTEOS as a mono- or co-culture. Steatosis, inflammation, generation of reactive oxygen species (ROS), and collagen deposition were determined. ACTEOS reduced both the TNF-α and ROS production, and, most importantly, attenuated collagen deposition elicited by the excess of FFA in the co-culture model. APPLIVER also showed inhibition of both TNF-α production and collagen deposition caused by FFA accumulation. The compounds alone did not induce any cellular effects. The present study showed the efficacy of APPLIVER and ACTEOS on pathophysiological mechanisms related to NASH. These in vitro data suggest that these compounds deserve further investigation for possible use in NASH treatment.
齐墩果酸（TA）和毛蕊花糖苷（ACT）分别是APPLIVER和ACTEOS的主要成分，据报道它们具有肝脏保护作用，但其分子机制仍不清楚，尤其是在非酒精性脂肪性肝病/非酒精性脂肪性肝炎的背景下。我们在我们建立的类似于非酒精性脂肪性肝炎病理生理机制的体外模型中评估了它们的作用。将人肝细胞和肝星状细胞单独或与APPLIVER和ACTEOS一起作为单培养或共培养暴露于游离脂肪酸（FFA）中。测定脂肪变性、炎症、活性氧（ROS）的产生和胶原蛋白沉积。ACTEOS降低了TNF-α和ROS的产生，最重要的是，在共培养模型中减弱了由过量FFA引起的胶原蛋白沉积。APPLIVER也显示出对FFA积累引起的TNF-α产生和胶原蛋白沉积的抑制作用。单独使用这些化合物不会诱导任何细胞效应。本研究显示了APPLIVER和ACTEOS对与非酒精性脂肪性肝炎相关的病理生理机制的疗效。这些体外数据表明，这些化合物值得进一步研究，以探讨其在非酒精性脂肪性肝炎治疗中的可能用途。
