The Antioxidant, Anti-Inflammatory, Pathological, and Behavioural Effects of Medicago sativa L. (Alfalfa) Extract on Brain Injury Caused by Nicotine in Male Rats

Nicotine is one of the most important compounds in cigarette which can cause changes in the concentration of neurotransmitters and damage to the nervous system. The aim of this study was to investigate the effect of the hydroalcoholic extract of Medicago Sativa L. (alfalfa) on controlling nicotine-induced brain damage and anxiety behaviour in rats. Forty-two male Wistar rats were randomly divided into six equal groups and treated daily as follows: a control group, T1 and T2 groups where animals were subcutaneously injected 250 and 500 mg/kg alfalfa extract, respectively, T3 and T4 groups where animals were injected subcutaneously 0.2 mg/kg nicotine and 250 and 500 mg/kg alfalfa extract, and T5 group in which only nicotine at the dose of 0.2 mg/kg was injected. At the end of the period after weighing, the elevated plus-maze test was taken from the animals. Serum assay was conducted to measure TCA, IL-1, and TNFα, and half of the brain tissue was used to measure oxidative stress parameters (GPx, SOD, TAC, and MDA) and the other parts were used for histopathological studies. Body weight in the T5 group was significantly different from that of the other groups. The time and number of open arms reduced in the T5 group. The duration and number of times in the open arm significantly decreased in the treated groups in a dose-depended manner. Malondialdehyde concentration was the highest in the nicotine group and the lowest in T2. The concentration of GPx and SOD was significantly increased in the presence of alfalfa extract in nicotine groups. TNFα and IL-1 in the T5 group showed a significant increase compared to the other groups. Moreover, the number of neurons and the level of necrotic neurons and gliosis significantly decreased and increased in the nicotine group, respectively, while these histopathological damages improved by treatment with alfalfa extract in T3 and T4 groups. Alfalfa extract can have a significant dose-dependent therapeutic effect on inducing oxidative damage and inflammatory responses of nicotine in the brain and reducing anxiety behaviours.