Hepatoprotective mechanisms of chemically characterized Aloe striata gel with and without loading on nanoparticles, involving ERK-JNK signaling pathway

Aloe striata Haw. (AS) is one of the beneficial Aloe species that is still underutilized. In this sense, phytochemical characterization, and biological investigation of AS gel protective efficacy against paracetamol (APAP) induced hepatic injury were evaluated in a mice model, with and without loading on chitosan nanoparticles (AS gel and CS-AS NPs, respectively). Spectrophotometric determination of AS gel showed high total soluble carbohydrate content representing 3.41±0.07 μg glucose equivalent (G eq)/mg and its protein content was 0.176±0.03 g/100 g. Twenty-two metabolites [sugars (90.23 %) and organic acids (5.80 %)] were determined by GC–MS, while 7 sugars were identified and quantified by HPLC where mannose (5679.73±4.28 μg) was the predominant. Chitosan gel nanoparticles were prepared and analyzed by dynamic light scattering, high resolution transmission electron microscopy, and X-ray diffraction methods. The CS-AS NPs were the most potent antioxidant of all tested samples with respect to quercetin in several in vitro antioxidant assays. Oxidative status, architectural or immuno-histochemical and histological signs in the context of the presence of caspase-3, c-Jun-N-terminal kinase (JNK), and extracellular signal-regulated kinase 1 (ERK-1) genes were evaluated in liver AS gel could significantly restore liver biochemical, antioxidant, and anti-inflammatory activities and liver architecture. Moreover, caspase-3 contents, and ERK-1 and JNK genes expression were significantly downregulated compared to the APAP group. CS-AS NPs showed superior hepatoprotective activity than AS. CS-AS NPs hepatoprotective mechanisms could be attributed to its activation of antioxidant enzymes, and downregulation of malondialdehyde pro-inflammatory markers along with apoptosis and anti-inflammatory related genes (BAX, JNK, and ERK-1 genes). To the best of our knowledge, it is the first study reporting the hepatoprotective efficiency of AS gel and its CS-AS NPs.