JOURNAL OF THE HELLENIC VETERINARY MEDICAL SOCIETY, cilt.74, sa.2, ss.5753-5764, 2023 (SCI-Expanded)
The etiology of anxiety and depression is linked to inflammation and oxidative stress. Isorhamnetin
and Kaempferol are strong antioxidants with anti-inflammatory neuroprotective properties. This study, it was aimed to
investigate the effect of Kaempferol and Isorhamnetin in Lipopolysaccharide (LPS)-induced anxiety and depression
model in mice. Thirty Balb/C mice were divided into six groups of five mice each weighing 25-35 g. Kaempferol (50
mg/kg and 100 mg/kg) and Isorhamnetin (30 mg/kg and 60 mg/kg) were given orally to the treatment group, and the
vehicle was given to the control and LPS groups for fourteen days, followed by intraperitoneal (0.83 mg/kg) LPS injection (control group excluding) on the fifteenth day. At 3 hours after the administration of LPS, each group was applied
with the Elevated Plus-Maze (EPM) test, the Light/Dark test, and the Open Field test (OFT). At 24 hours after LPS
administration, the Forced Swimming Test (FST) was applied and at 28 hours, the Tail Suspension Test (TST). After
the behavioral test, the prefrontal cortex and hippocampus tissues of rats were harvested by cervical dislocation under
high-dose anesthesia. From these tissues, malondialdehyde (MDA) levels, total oxidant status (TOS) and total antioxidant status (TAS) levels, tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β), and interleukin-6 (IL-6) levels, and brain-derived neurotrophic factor (BDNF) levels were measured. Kaempferol and Isorhamnetin ameliorated
LPS-induced anxiety evaluated by OFT, Light/Dark test, and EPM, and LPS-induced depression evaluated by FST and
TST. Kaempferol and Isorhamnetin alleviated LPS-induced increased oxidative stress in the prefrontal cortex and hippocampus by decreasing MDA and TOS levels and increasing TAS levels. In addition, it was observed that Kaempferol
and Isorhamnetin regulated the increase in prefrontal and hippocampal inflammation caused by LPS by decreasing
TNF-α, IL-1β, and IL-6 levels. Most importantly, LPS reduced prefrontal and hippocampal BDNF levels, but the treatment groups reversed it. These results show the possible therapeutic potential of Kaempferol and Isorhamnetin, along
with the importance of oxidative stress, inflammation, and BDNF in the etiopathogenesis of anxiety and depression