The Effects of Methanol Extracts of Hyssopus officinalis on Model of Induced Glioblastoma Multiforme (GBM) in Rats.

Abstract

Given the complexity of pathophysiological processes of brain tumors, ineffective therapies, and high mortality rate, new therapeutic options with less toxicity are necessary. Hyssopus officinalis (hyssop) is an aromatic plant with important biological activities. The aim of this study is to assess the anti-cancer effect of hyssop extract on damages of glioblastoma multiforme. In this study, total flavonoids, phenolic content, and quantification of phenolic compound of hyssop extracts were analyzed. In vitro antioxidant properties of hyssop extract were also examined. In addition, cell viability, apoptosis, and cell cycle were evaluated in C6 glioma cell culture. In vivo, the rats were divided randomly into four main groups: intact, control, vehicle, and treatment groups. 1 × 106 C6 rat glioma cells were implanted into the right caudate nucleus of the rat's brain. The treatment group received the methanol extract of hyssop (100mg/kg) for 7days. Evolution of locomotor activity, tumor volume, survival rate, activities of antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)), vascular endothelial growth factor (VEGF) expression, TUNEL-positive cells, p53 and p21 mRNA expression, and histological alterations were performed. The results showed that the methanol extract of hyssop increased the apoptosis and reduced the cell division of C6 glioma cells in cell culture. Moreover, methanol extract decreased the tumor volume and prolonged survival. Also, the activity of SOD and CAT enzymes was reduced in tumor tissue and enhanced in surrounding tissue. TUNEL-positive cells were increased in methanol extract of hyssop group. The expression of p53 and p21 mRNA was upregulated in the treatment group. Moreover, the histological analysis indicated a considerable decrease in invasion of tumor cells and inflammation in the hyssop-treated rats. According to the achieved results, it can be stated that hyssop has sufficient potential to inhibit damage of brain tumors, at least in part, by affecting the oxidative stress and cell proliferation pathways.