Objective: To investigate the effects of syringic acid on HEK 293 and HepG2 cells in the absence and presence of exogenous Cu (II) and Fe (II) ions. Methods: The antiproliferative effects of syringic acid on HEK 293 and HepG2 cells in the absence and presence of exogenous Cu (II) and Fe (II) ions were examined by MTT assay. Additionally, colony-forming, reactive oxidative species (ROS) generation, apoptosis induction, autophagy, mitochondrial membrane potential, and mitochondrial mass were investigated. Results: At 24 and 72 h, no significant differences were observed in the viability of HepG2 cells between the control and syringic acid + Fe (II) groups. However, exposure of HepG2 cells to syringic acid + Cu (II) for 72 h reduced the cell viability significantly. Furthermore, ROS formation, induction of apoptosis, and autophagic vacuoles were significantly increased in HepG2 cells without marked changes in mitochondrial membrane potential and mitochondrial mass. Moreover, syringic acid + Cu (II) reduced the plating efficiency and surviving fraction significantly. Conclusions: The combination of syringic acid with Cu (II) was toxic to cancer cells and showed pro-oxidant activity. In addition, this combination induced autophagy in cancer cells with less cytotoxic effects on normal cells, which is a potential candidate for the development of novel therapeutics towards cancer.

Objective: To determine the effects of syringic acid on hepatic damage in diabetic rats. Methods: Diabetes was induced by streptozotocin. Diabetic rats were given syringic acid at doses of 25, 50 and 100 mg/kg by oral gavage for 6 weeks. Syringic acid effects on the liver were evaluated by examination of plasma biochemical parameters, and pathological study. In addition, biomarkers of lipid peroxidation and antioxidant status of liver tissues were assessed. Real time-PCR was performed to investigate the mRNA expression levels of mitochondrial biogenesis indices in different groups. Results: Syringic acid significantly attenuated the increase in most of plasma biochemical parameters in diabetic rats. Moreover, syringic acid treatment increased the catalase activity while it reduced the superoxide dismutase activity and hepatic malondialdehyde level in diabetic rats. There was no difference between the glutathione content of the treated and untreated groups. These findings were supported by alleviation of histopathological damages in the syringic acid-treated groups compared to the untreated diabetic group. Syringic acid also significantly up-regulated the hepatic mRNA expression of PGC-1a, NRF-1, and NRF-2 and increased the mtDNA/nDNA ratio in diabetic rats. Conclusions: Syringic acid can be considered as a suitable candidate against hepatic complications since it can reduce oxidative damages in diabetic cases. Furthermore, it has the potential of targeting hepatic mitochondria in diabetes.