Document Type : Research articles

Authors

• Mohammad Nouri ^{1, 2}
• Fereshteh Farajdokht ¹
• Mohammadali Torbati ³
• Fatemeh Ranjbar ⁴
• Sanaz Hamedyazdan ⁵
• Saeed Sadigh-Eteghad ¹
• Mostafa Araj-Khodaei ^{2, 6}

¹ Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

² Department of Traditional Persian Medicine, School of Traditional Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

³ Department of Food Science and Technology, Faculty of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran

⁴ Research Center of Psychiatry and Behavioral Sciences,Tabriz University of Medical Sciences, Tabriz, Iran

⁵ Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

⁶ Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran

Abstract

Background: Echium amoenum (E. amoenum) is an Iranian medicinal plant with mood-enhancing effects.
Objectives: This study was designed to investigate the effect of standardized E. amoenum hydroalcoholic extract on restraint stress (RS)-evoked anxiety- and- depressive-like behaviors in mice.
Methods: This experimental study was conducted at the Tabriz University of Medical Sciences, Tabriz, Iran, in 2018. Doses of the hy- droalcoholic extract of E. amoenum were optimized for rosmarinic acid (> %2 w/w) concentration of the extract. Other phytochem- ical indices, including total phenolic and flavonoid contents and radical scavenging activity, were also measured. For behavioral studies, 65 mice were randomly assigned into five groups (n = 13) of control, RS, RS + E75, RS + E150, and RS + E300. Animals in the RS group were subjected to the RS (3 h/day for 14 days) and treated with normal saline, while treatment groups received E. amoenum extract (75, 150, and 300 mg/kg, p.o.) concomitantly with RS exposure. Anxiety-like behaviors were assessed by Elevated Plus Maze (EPM) and Open Field Test (OFT). Depression was assessed by the forced swim test (FST) and Tail Suspension Test (TST). Western blot- ting was performed to determine the protein levels of IL-1β, NF-κB, TNF-α, and IL-6 in the prefrontal cortex (PFC) and hippocampus
(HIP). The concentrations of corticosterone, alanine aminotransferase, aspartate aminotransferase, and alanine phosphatase were also measured in serum.
Results: Moderate and high doses of the extract ameliorated RS-induced anxiety- (P < 0.05 in OFT and EPM) and depressive-like (P < 0.05 and P < 0.01 in FST; P < 0.01 and P < 0.001 in TST) behaviors. These results were approved by decreased serum corticosterone levels (P < 0.05 and P < 0.001). Furthermore, E. amoenum reduced the protein expression of neuroinflammatory markers in the HIP and PFC subregions (significant at least at P < 0.05 for IL-1β, NF-κB, and TNF-α). Although RS slightly increased the serum levels of liver enzymes, no histopathological changes were seen in the liver of the RS or E. amoenum-treated groups.
Conclusions: E. amoenum can be an effective and safe complementary strategy for the treatment of stress-associated inflammation and behavioral changes.

Keywords

• Anxiety
• Depression
• Hippocampus
• Inflammation
• Echium amoenum
• Corticosterone
• Prefrontal Cortex
• Rosmarinic Acid
• Stress