Effect of xanthone from Kielmeyera coriacea stems on serotonergic neurons of the median raphe nucleus

Abstract

Kielmeyera coriacea Mart. (Clusiaceae), known as "Pau Santo", is used to treat several tropical diseases. The hydroethanolic extract (HE) of Kielmeyera coriacea stems and its semi-pure dichloromethane constituent (DCM) produced an anti-immobility effect in rats submitted to the forced swimming test (FST), suggesting a antidepressant-like profile. This study evaluated the effect of intra-median raphe nucleus (MRN) microinjection of 1,3,7-trihydroxy-2-(3-methylbut-2-enyl)-xanthone, present in large quantity in the HE from Kielmeyera coriacea stems, on immobility behaviour in the FST in rats. The effects of xanthone were compared with intra-MRN microinjections of Way100635 (5-HT1A antagonist) or (+) 8-OH-DPAT (5-HT1A agonist). Locomotor activity in the open-field test (OFT) was evaluated as a complementary measure. Xanthone (0.3ng) or Way100635 (2.5microg) reduced, whereas (+) 8-OH-DPAT (5.0microg) increased immobility time in the FST. Way100635 (2.5 or 5.0microg) completely reversed the effects of (+) 8-OHDPAT (5.0microg), and potentiated the anti-immobility effect of the ineffective dose of xanthone (0.2ng) in the FST. The association of effective doses of (+) 8-OH-DPAT (5.0microg) and xanthone (0.3ng) annulled the effect of each compound on immobility time. These results suggest that xanthone acts as an antagonist at 5-HT1A autoreceptors in MRN and increases serotonin (5-HT) availability in projection regions, proving to be a prototype drug that may be useful in mood isorders such as depression, or indeed be a beneficial adjunctive treatment improving the efficacy and/or accelerating the effects of antidepressant drugs in patients with major depression.

Antidepressant-like activity of a new piperazine derivative of xanthone in the forced swim test in mice: The involvement of serotonergic system

“…Similarly, some xanthone derivatives show antidepressant-like activity in various animal tests and models [5][6][7]. Taking into consideration the fact that HBK-6 is a xanthone derivative with a piperazine moiety in its structure, the results of our findings are in agreement with above findings.…”

Effect of Xanthone Derivatives on Animal Models of Depression

“…A component of HPL, xanthone has been shown to be effective in mood disorders, such as depression 7 . According to literature procedures, we consequently separated, purified, and modified the HPL to obtain 10 derivatives of xanthone.…”

The antidepressant-like activity of 6-methoxy-2-[4-(2-methoxyphenyl)piperazin-1-yl]-9H-xanthen-9-one involves serotonergic 5-HT1A and 5-HT2A/C receptors activation

“…It has been proven that xanthone derivatives possess various biological properties, including antiarrhythmic, hypotensive, anticonvulsant and antidepressant-like (Jastrzebska-Wiesek et al, 2003;Pytka et al, 2015;Rapacz et al, 2014;Szkaradek et al, 2013;Zhao et al, 2014). Xanthones form Kielmeyera coriacea and Gentiana kochiana have been shown to produce antidepressant-like effects in the rat forced swim test (Sela et al, 2010;Tomić et al, 2005). Furthermore, diethylether extract of aerial parts of G. kochiana, which mostly consist of two tetraoxygenated xanthones: gentiacaulein (1,7-dihidroxy-3,8-dimethoxyxanthone; 76.1%) and gentiakochianin (1,7,8-trihidroxy-3-methoxyxanthone; 14.2%) inhibited monoaminoxydase A (MAO A) in a competitive manner and this mechanism may be responsible for its antidepressant-like activity (Tomić et al, 2005).…”