Hakami Zaki H, Abdo Walied, Nazeam Jilan A, Osman Samir M, Goda Wael, Fadl Sabreen E, Alsulimani Ahmad, Al-Noshokaty Tohada M, Haridy Mohie, Alnasser Sulaiman Mohammed, Abdeen Ahmed
Department of Medical Laboratory Technology, College of Nursing and Health Sciences, Jazan University, Jazan, Saudi Arabia.
Department of Pathology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh, Egypt.
Phytother Res. 2025 Feb;39(2):1090-1106. doi: 10.1002/ptr.8412. Epub 2024 Dec 28.
(1) Background and aim: Aloe arborescens Mill. ( A. arborescens ) is one of the most widely distributed species in the genus Aloe and has garnered widespread recognition for its anticancer properties. However, the molecular mechanisms underlying these activities have not yet been fully elucidated. This study aimed to explore the effects of the plant polar glycosidic fraction (AAG) on hepatocellular carcinoma (HCC) in an in vivo model induced by diethylnitrosamine (DEN). (2) Experimental procedure: The fraction was standardized using HPLC-PDA-MS/MS fingerprinting, and two distinct intragastric AAG dose regimens were examined (10 and 20 mg/kg) in combination with DEN 200 mg/kg. Serum alpha-fetoprotein (AFP), gamma-glutamyl transferase (γ-GGT), glutathione S-transferase placental (GST-P), mRNA expression of metabolic cytochrome enzymes (CYP1A3 and CYP2B2), inflammatory genes (nuclear factor kappa-B p65 subunit; NF-κB p65), metalloproteases 9 (MMP9), tissue inhibitors of metalloproteases (TIMP1), transforming growth factor beta 1 (TGFβ1), and histological features were assessed. (3) Key results and conclusions and implications: AAG was characterized by five major secondary metabolites: saponins, chromones, anthraquinone, and triterpenes. The fraction reduced hepatic malignancy characteristics by diminishing the size and number of altered foci and lowering hepatic cancer biomarkers, such as γ-GGT, AFP, and GST-positive foci. It also reduced the mRNA levels of CYP1A3 and CYP2B2, NF-κB p65, and MMP9, hepatic Ki-67, and TGFβ1 while upregulating TIMP1 levels. This study revealed that AAG exhibited a marked suppressive effect on HCC cell proliferation, displaying a range of mechanistic actions, including decreasing the metabolic activation of cytochrome enzymes, which consequently reduced the production of reactive oxygen species and other genes implicated in cancer development. AAG could be a significant therapeutic candidate for patients diagnosed with hepatocarcinoma.
(1) 背景与目的：木立芦荟（Aloe arborescens Mill.，A. arborescens）是芦荟属中分布最广的物种之一，其抗癌特性已获得广泛认可。然而，这些活性背后的分子机制尚未完全阐明。本研究旨在探讨植物极性糖苷组分（AAG）对二乙基亚硝胺（DEN）诱导的体内肝癌模型的影响。(2) 实验步骤：采用高效液相色谱 - 光电二极管阵列 - 串联质谱（HPLC - PDA - MS/MS）指纹图谱对该组分进行标准化，并研究了两种不同的胃内给予AAG剂量方案（10和20 mg/kg）与200 mg/kg DEN联合使用的情况。检测血清甲胎蛋白（AFP）、γ - 谷氨酰转移酶（γ - GGT）、胎盘型谷胱甘肽S - 转移酶（GST - P）、代谢细胞色素酶（CYP1A3和CYP2B2）的mRNA表达、炎症基因（核因子κB p65亚基；NF - κB p65）、金属蛋白酶9（MMP9）、金属蛋白酶组织抑制剂（TIMP1）、转化生长因子β1（TGFβ1）以及组织学特征。(3) 关键结果、结论及意义：AAG的特征在于含有五种主要次生代谢产物：皂苷、色酮、蒽醌和三萜。该组分通过减小病变灶的大小和数量以及降低肝癌生物标志物（如γ - GGT、AFP和GST阳性灶）来减轻肝脏恶性特征。它还降低了CYP1A3和CYP2B2、NF - κB p65和MMP9、肝脏Ki - 67以及TGFβ1的mRNA水平，同时上调TIMP1水平。本研究表明，AAG对肝癌细胞增殖具有显著的抑制作用，表现出一系列作用机制，包括降低细胞色素酶的代谢活化，从而减少活性氧的产生以及其他与癌症发展相关的基因。AAG可能是肝癌患者的一种重要治疗候选药物。
