In Vitro Evidence for the Use of Astragali Radix Extracts as Adjuvant against Oxaliplatin-Induced Neurotoxicity.

Abstract

The repeated exposure to the anticancer drug oxaliplatin induces a disabling, painful neuropathy. The current pharmacological treatments are unsatisfactory and unable to modify the complex nervous damage induced by the platin derivative. Recently, we described a system of cellular measures of oxidative stress as a method for studying features of oxaliplatin neurotoxicity and screening new compounds able to reduce oxaliplatin-induced neuropathy. Based on this experimental design, the protective properties of Astragali radix were studied comparing aqueous and two hydroalcoholic root extracts. Aqueous and the 20 % hydroalcoholic (20 % water) extract were prepared from plant material, while the 50 % hydroalcoholic (50 % water) extract was a commercial one. All of the extracts were characterized in terms of drug extract ratio and content of typical isoflavonoids, Astragaloside IV, and related saponins. Furthermore, the molecular weight of the polysaccharide fraction was evaluated by light scattering analysis. Oxaliplatin increased the superoxide anion production both in the neuronal-derived cell line SH-SY5Y and in primary cultures of rat cortical astrocytes. Aqueous and the 50 % hydroalcoholic extract (50 µg/mL) showed significant antioxidant effects. In astrocytes, aqueous and the 50 % hydroalcoholic extract showed protective effects against oxaliplatin-induced lipid peroxidation (malonyl dialdehyde levels), protein (carbonylated proteins), and DNA oxidation (8-OH-2-dG levels). The 50 % hydroalcoholic extract was the most active in preventing the activation of the apoptotic enzyme caspase-3 and it was the only able to stimulate astrocyte viability. None of the tested extracts interfered with the toxicity elicited by oxaliplatin in the human colon adenocarcinoma cell line HT-29. The pharmacological profile of Astragali radix extracts, in particular, the aqueous and 50 % hydroalcoholic extracts, makes these natural products candidates as therapeutic adjuvant agents against oxaliplatin neurotoxicity.