Consumption of a high-fat diet (HFD) has increased dramatically over the past few decades (1). Today, the diet of developed countries is rich in saturated fat and refined sugar, and it is well known that people's lifestyle and diet quality play a vital role in their neuronal and brain function (2). Increased fat intake and obesity are associated with mood and mental disorders, such as anxiety and depression (3–6). Prolonged consumption of a HFD impairs brain function through inflammation (7), oxidative stress (8, 9), and induction of insulin resistance (10). Consuming a HFD for 4 months and the resulting obesity increased protein oxidation in the frontal cortex and increased oxidative stress parameters, resulting in anxiety-like behaviors (10). In another study, HFD for 7 weeks reduced the number of new cells produced in the hippocampal gyrus, as well as increased malondialdehyde (MDA) levels and decreased levels of brain-derived neurotrophic factor (BDNF). MDA has a toxic effect on neurons producing stem cells, disrupting neurogenesis in the hippocampus, and increasing lipid peroxidation (LPO) in the brain (8).
Oxidative phosphorylation is the process, by which energy is produced as adenosine triphosphate (ATP), and this process, which is essential for energy metabolism, produces the reactive oxygen species (ROS), such as superoxide and hydrogen peroxide (11). Oxidative stress is caused by an imbalance between the production of free radicals, such as ROS, and the ability of cells to remove them and protect the cell against them (12). The brain is highly prone to oxidative stress damage due to its high oxygen consumption, relatively low antioxidant defenses, and high-fat content (13, 14). Antioxidants are compounds that, in very small amounts relative to the oxidizing substrate, significantly delay or inhibit the oxidation of the substrate. Antioxidants are biologically active compounds that protect the body against the damages caused by ROS and active nitrogen species (RNS) (15). ROS can damage cell lipids, proteins, and DNA, and typically, antioxidants, such as superoxide dismutase (SOD), vitamins E and C, and glutathione (GPX) can reduce ROS-induced cell damage by reducing ROS levels (16). In the presence of oxidative stress, due to the high-fat content of the brain, LPO occurs, which leads to a decrease in membrane fluidity and membrane proteins and inactivation of enzymes, receptors, and ion channels (14, 17). Oxidative stress can affect neurotransmitter transmission, neuronal function, membrane integrity, whole-brain activity, and even neuronal death (18). Recently, there has been evidence that consuming a HFD can increase the production of free radicals and causes oxidative stress (19), and consuming supplements rich in antioxidants can reduce the harmful effects of free radicals on neuronal cells and cognitive function (20–22).
Recent studies have shown an association between oxidative stress and anxiety. The overexpression of glutathione reductase 1 and glyoxalase 1 in the cortex of the cingulate leads to increased anxiety-like behaviors, while inhibition of glyoxalase 1 expression reduces anxiety behavior. Thus, the association between the antioxidant status of the brain and anxiety-related behavior became apparent (23). It has also been shown that there is a close relationship between the level of intracellular ROS in peripheral blood cells (lymphocytes, monocytes, and granulocytes) and anxiety-related behaviors (24). Also, the bamboo extract showed antianxiety effects in laboratory mice fed with a diet containing saturated fatty acids for 2 months by decreasing pro-inflammatory cytokines and increasing glutathione levels (25).
In traditional medicine, the use of various herbs has been suggested to reduce anxiety. For example, Rosa damascene mill L. is a shrub of the family Rosaceae, which has strong antioxidant properties (26). Kalim et al. in 2010 showed that R. damascene due to its high phenolic, flavonoid, and ascorbic acid content has a strong antioxidant power that can scavenge harmful free radicals (27). In a study by Achuthan in 2003, it has been shown that R. damascene hydroalcoholic extract prevented liver damage caused by carbon tetrachloride and oxidative stress in rats and had a protective effect on the liver. These observations are probably due to its antioxidant power and neutralization of free radicals (28). The parts used in this plant include flowers, flower buds, fruits, petals, and flags. Its essential oil is prepared from its petals and was first made in Europe by Rossi in 1574. Chemical compounds in this plant are geraniol, citronellol, essential oil, fat, resin, malic acids, tartaric, christrin, gallic acid, red pigments, such as cyanine, quercetin, kaempferol, phenethyl alcohol, vitamins. C, and carotene. Several studies have also been performed on the analgesic, anti-inflammatory, antibacterial, and anti-viral properties of this plant (29). It also has sedative, anti-flatulence, fever-relieving, thirst-quenching, and invigorating properties. The essential oil of this plant is used in aromatic ointments or disinfectants, cosmetic products, and the perfume industry (30).
Although little is known about the effects of HFD on the nervous system, studies have shown that increased fat intake and obesity play a role in developing mood and psychological disorders, such as anxiety and depression. R. damascene is one of the oldest medicinal plants in traditional medicine with great antioxidant power. Therefore, in this study, we investigated the effect of hydroalcoholic extract of R. damascene on anxiety in rats following the consumption of HFD.