A behavioral and molecular study; ameliorated anxiety-like behavior and cognitive dysfunction in a rat model of chronic unpredictable stress treated with oregano extract.

OBJECTIVE: Chronic stress is considered a severe risk factor leading to various disorders, including anxiety and cognitive decline. The present study aimed to investigate the effects of Origanum vulgare (oregano) extract on improving anxiety-like behavior and learning and memory defection caused by chronic unpredictable stress (CUS). METHOD: A 10-day CUS protocol was executed on male rats, and on day 10, their anxiety, learning, and memory status were evaluated. After that, in addition to the CUS, the rats were treated with the oregano extract for 2 weeks. Then, the expression of BDNF, TrkB, and TLR2/4 genes in the hippocampus and prefrontal cortex of the rats was evaluated. Also, the liver- and kidney-related serum parameters, including triglycerides, total cholesterol, HDL, LDL, creatinine, urea, serum glucose, alanine aminotransferase, and aspartate aminotransferase were assessed. Further, the extract's lethal effect and its impact on animals' body weight were investigated. RESULTS: Behavioral tests confirmed the anxiety-like behavior and learning-memory function impairment caused by CUS. In contrast, the administration of the extract could significantly alleviate the mental deficiencies and diminished anxiety-like behaviors. Molecular assessments showed that CUS could markedly decrease the BDNF and TrkB genes' expression levels while increasing that of TLR2 and TLR4. In contrast, in extract-treated animals, mRNA levels of BDNF and TrkB considerably increased, yet TLR2 and TLR4 mRNA levels reduced. Additionally, consumption of the extract caused weight gain, while having no lethality and detrimental effect on the liver and kidneys functions. CONCLUSIONS: These findings indicate the anxiolytic properties of the extract and its improving effect on cognitive dysfunction.

Effects of oregano essential oil on brain TLR4 and TLR2 gene expression and depressive-like behavior in a rat model.

The aim of the present study was to evaluate the effects of oregano essential oil (OEO) on the hippocampus and prefrontal cortex TLR 2/4 gene expression and depressive like behavior induced by chronic unpredictable stress (CUS). Sucrose preference and forced swim tests were adopted to examine the antidepressant effect. Control (CON), OEO, CUS, and CUS + OEO groups were used. The OEO and CUS + OEO groups received OEO (0.2 mL/kg, i.p.), CON and CUS received saline (0.2 mL/kg, i.p.), and the positive drug groups of CUS rats received fluoxetine (10 mg/kg) and diazepam (3 mg/kg) once daily for 14 days. The expression of TLR 2/4 was determined using real time quantitative polymerase chain reaction with the SYBR green reporter dye. The compositions of the OEO were determined by gas chromatography-mass spectroscopy. The main constituents were thymol (20.72%), gamma-terpinene (8.83%), borneol (8.72%), cymene (6.83%), carvacrol (6.274%), alfa-terpinene (5.26%), and sabinene (4.92%). Administration of OEO significantly alleviated the depressive symptoms of CUS. A higher level of TLR2/4 mRNA was seen in the brain of CUS group (P < 0.05). The CUS-induced increases in the TLR2/4 levels were not reversed by OEO. According to the present study OEO may have the antidepressant-like activity but have no effect on the stress-induced TLR-2/4 upregulation.