Atranorin, a Secondary Metabolite of Lichens, Exhibited Anxiolytic/Antidepressant Activity in Wistar Rats

Abstract

Atranorin (ATR) is one of lichens’ many known secondary metabolites. Most current studies have investigated the various effects of ATR in vitro and only sporadically in vivo. The latest data indicate that ATR may have anxiolytic/antidepressive effects. This study aimed to analyze the potential of ATR in a depression-like state in male Wistar rats. Pregnant females were stressed by restricting their mobility in the final week of pregnancy three times a day for 45 min each, for three following days. After birth, progeny aged 60 days was stressed repeatedly. The male progeny was divided into three groups as follows: CTR group as a healthy control (n = 10), DEP group as a progeny of restricted mothers (n = 10), and ATR group as a progeny of restricted mothers, treated daily for one month with ATR (n = 10; 10 mg/kg of body weight, p.o.). Our results show that ATR acts as an antioxidant and markedly changes animal behavior. Concomitantly, hippocampal neurogenesis increases in the hilus and subgranular zone, together with the number of NeuN mature neurons in the hilus and CA1 regions. Our results indicate a potential antidepressant/anxiolytic effect of ATR. However, further studies in this area are needed.

The First In Vivo Study Shows That Gyrophoric Acid Changes Behavior of Healthy Laboratory Rats

“…Because of the lack of available GA amount, we were not able to find lethal and semi-lethal concentrations of this compound, which seems to be a limitation of our study. Due to the absence of prior in vivo studies involving GA, we opted to utilize a similar dosage that has been employed for other secondary metabolites, such as atranorin [ 38 , 39 ], or usnic acid [ 40 ]. Accordingly, GA was administered orally at a concentration of 10 mg/kg body weight on a daily basis for a duration of one month, as outlined in the Materials and Methods section.…”

Antioxidant and antidiabetic activity and phytoconstituents of lichen extracts with temperate and polar distribution

“…According to molecular docking analyses, there is a greater potential for pharmacological effect when evaluating isolated compounds present in the extracts of Psoroma species, which is evident with other Antarctic lichen species, such as H. lugubris where the isolation of compounds such as usnic acid, barbatolic acid, atranol, and 5,7-dihydroxy-6-methylphthalide demonstrates greater antioxidant and enzyme inhibition activity (Areche et al, 2022); likewise, computational studies carried out with compounds present in the extracts of other Antarctic species, such as L. brialmontii, P. pubescens, S. globosus, C. gracilis, and C. chlorophaea (Torres-Benítez et al, 2022;Torres-Benítez et al, 2023a), validate the promising use of compounds of phenolic nature for the treatment of different pathologies of wide prevalence and incidence as well as the understanding of their mechanisms of action at the organismic and cellular level (White et al, 2014). In addition, in the last 2 decades, biologically active metabolites have been isolated, such as atranorin (Melo et al, 2011;Zhou et al, 2017;Urbanska et al, 2022), barbatic acid (Reddy et al, 2019), diffractaic acid (Karagoz et al, 2015;Emsen et al, 2018), evernic acid (Fernandez-Moriano et al, 2017a;Shameera Ahamed et al, 2019;Lee eta al., 2021), fumarprotocetraric acid (Kosanić et al, 2014;Fernández-Moriano et al, 2017b), gyrophoric acid (Candan et al, 2006;Bačkorová et al, 2011), lobaric acid (Hong et al, 2018), physodic acid (Studzińska-Sroka et al, 2021b), protocetraric acid (Nguyen et al, 2023), thamnolan (Omarsdottir et al, 2007), usnic acid (Luzina and Salakhutdinov, 2018), and vulpinic acid (Varol et al, 2016;Kılıç et al, 2018), which are present in the species of the genera Cladonia, Parmotrema, Lepraria, Lethariella, Pseudoevernia, Hypotrachyna, Umbilicaria, Usnea, among others.…”

“…The standard used was orlistat, with which a calibration curve was prepared using concentrations ranging from 80 to 0.5 μg/mL in 70% ethanol (0.5, 1,5,10,20,30,50, and 80 μg/mL). For ethanolic extracts, solutions were prepared at concentrations between 1,000 and 7.8 μg/mL (7.8, 15.6, 31.3, 62.5, 125, 250, 500, and 1,000) from a stock solution of 1 mg/mL in Tris-HCl buffer (1,000 μg/mL).…”

Bioactive Compounds and Their Influence on Postnatal Neurogenesis

“…This was accompanied by an increase in hippocampal neurogenesis in the hilus and SGZ, as well as an increase in the number of mature NeuN neurons in the hilus and CA1 regions of the brain. These effects are believed to be mediated, at least in part, by atranorin's antioxidant properties [127].…”