Gallic acid protects cerebral cortex, hippocampus, and striatum against oxidative damage and cholinergic dysfunction in an experimental model of manic‐like behavior: Comparison with lithium effects

Abstract

Bipolar disorder is characterized by episodes of depression and mania, and oxidative stress has been associated with the observed neurochemical changes in this disease. We evaluated the effects of gallic acid on hyperlocomotion, acetylcholinesterase activity, and oxidative stress in an animal model of ketamine‐induced mania. Rats were pretreated orally with vehicle, gallic acid (50 or 100 mg/kg), or lithium (45 mg/kg twice a day) for 14 days. Between days 8 and 14, the animals also received ketamine (25 mg/kg) or saline daily. On the 15th day, hyperlocomotion was assessed, following which the animals were euthanized, and brains were collected. Results showed that ketamine‐induced hyperlocomotion and caused oxidative damage by increasing reactive oxygen species levels, lipid peroxidation, and nitrite levels, and decreasing the total thiol content and the activities of catalase, superoxide dismutase, and glutathione peroxidase in the brain. Pretreatment with gallic acid and lithium prevented hyperlocomotion and brain oxidative damage. Further, ketamine increased the acetylcholinesterase activity in the hippocampus and striatum, whereas gallic acid and lithium ameliorated this alteration. Thus, gallic acid may provide effective protection against manic‐like behavior by reducing oxidative stress and preventing cholinergic signaling dysfunction in the brain regions involved in emotion regulation.

Pharmacological effects and therapeutic potential of natural compounds in neuropsychiatric disorders: An update

“…Gallic acid (GA) a phenolic acid that is widely spread in the plant kingdom was used in the treatment of ketamine-induced mania in rats and compared to the action of lithium. Similarly to lithium (45 mg/g twice a day) GA (50 and 100 mg/kg) administered for 14 days decreased the hyperlocomotion of the animals, induced the antioxidant properties and prevented the cholinergic disfunctions in the brain (Recart et al, 2021). In the studies of collaborators (2016, 2017) quercetine administered intraperitoneally (10-40 mg/kg b. w.) showed antioxidant properties and inhibition of protein kinase C. In turn the flavonoid regulated sleep deprivation and diminished the…”

“…That is why several experimental studies focus on the development of drug candidates that could restore Frontiers in Pharmacology frontiersin.org oxidation-reduction balance. In the light of this information, natural products that are proved to exhibit antioxidant properties are important to drug candidates in the reduction of manic episodes (Recart et al, 2021). Herbal intervention in bipolar disorder is recommended and prescribed, accompanied by mood stabilizers (Currier and Trenton, 2002;Mohr et al, 2005).…”

Oxidative stress, the blood–brain barrier and neurodegenerative diseases: The critical beneficial role of dietary antioxidants

“… 254 found that it can improve the survival rate of cultured neural stem cells and progenitor cells, upregulate the activity of intracellular antioxidant enzymes and further protect nerve cells. On the other hand, gallic acid can effectively reduce the generation of ROS, significantly increase the activity of antioxidant enzymes in animal models of ketamine-induced mania and reduce the activity of AChE and oxidative stress in the hippocampus and striatum 255 . Teixeira et al.…”

“… 256 demonstrated the ability of gallic acid to prevent mitochondrial lipid peroxidation in a cellular model using thiobarbituric acid reactive substances (TBARS) as the biological endpoint. In addition, ferulic acid can rescue DA neurons in the SNc region and nerve endings in the striatum from rotenone damage, restore antioxidant enzyme (SOD and CAT) activity, prevent glutathione overconsumption, and inhibit lipid peroxidation 257 ( Table 3 ) 252 , 253 , 254 , 255 , 257 . However, further human clinical trials are needed to fully define the beneficial activities and therapeutic effects of phenolic acids on neurons.…”

From Plants to Psycho-Neurology: Unravelling the Therapeutic Benefits of Bioactive Compounds in Brain Disorders

“…It was observed that gallic acid decreased the hyperlocomotion of the animals, induced antioxidant properties, and prevented cholinergic disfunctions in the brain [ 33 ]. Moreover, quercetin, a flavonoid, also showed antioxidant properties and inhibition of protein kinase C [ 34 ]. Table 2 shows the most relevant plant-derived bioactive compounds with neuroprotective effects in BD patients.…”