Involvement of 5‐HT‐BDNF signaling axis in mediating synergistic antidepressant‐like effects after combined administration of two oligosaccharide esters

Abstract

Potential mechanisms of depression involving herbal medicines and their specific compounds include elevated 5‐HT level and downstream BDNF pathway. To identify potentially new combined therapeutic strategies, 3,6'‐disinapoylsucrose (DISS) and tenuifoliside A (TFSA) have been observed to show antidepressant‐like effects and its related 5‐HT‐BDNF pathway. We have tried to investigate whether combined administration of DISS and TFSA exerted more effective in the treatment of depression, as assessed through tail suspension test (TST) and forced swimming test (FST). In addition, we also analyzed the expression of three important proteins, cyclic adenosine monophosphate (cAMP) response element binding (CREB), brain‐derived neurotrophic factor (BDNF), and cAMP‐regulated transcriptional coactivators (CRTC1), which have been shown to be involved in the regulation of the neurotrophic factors in the hippocampus. The DISS and TFSA separately, both at a dose of 5 mg/kg each, displayed small effect in the immobility time. However, combined treatment of these two in multiple doses exhibited better effect. Moreover, combined treatment of DISS and TFSA also demonstrated enhanced levels of 5‐hydroxytryptamine (5‐HT), and stronger increase in the phosphorylation levels of CREB, BDNF, and CRTC1 proteins in the hippocampus. Overall, our results indicated that coadministration of these two oligosaccharide esters at low dose may induce more pronounced antidepressant activity, in comparison with individual treatment even at high dosage. Thus, the antidepressant properties of both these compounds can be attributed to their ability to influence 5‐HT and BDNF pathway, and thereby suggesting that this combination strategy can definitely act as alternative therapy for depression disorder with very limited side effects.

Exploring the Role and Potential of Probiotics in the Field of Mental Health: Major Depressive Disorder

“…5-HT stimulates BDNF expression while BDNF promotes the neurogenesis and neuronal survival of 5-HT. Impairment in the 5-HT-BDNF signaling mechanism has been implicated in the pathophysiology of depression [120,121]. The administration of Lactobacillus helveticus and citalopram, an antidepressant of the SSRI class, in rodent models demonstrated similar outcomes of increased levels of 5-HT with anti-depressive effects.…”

Hesperidin reduces depressive symptoms in post‐coronary artery bypass graft patients with mild depression

“…Brain‐derived neurotrophic factor (BDNF) is a member of the family of neurotrophic growth factors. It has been demonstrated that serum or plasma BDNF levels are decreased in depressed patients, as compared to the healthy controls, and attenuated BDNF levels are boosted by antidepressants (Gonul et al, 2005 ; Jones & Reichardt, 1990 ; Yang et al, 2021 ). On the other hand, previous research suggests that hesperidin exhibits antidepressant‐like properties due to induced BDNF in the hippocampus (Donato et al, 2014 ; El‐Marasy et al, 2014 ; Kosari‐Nasab et al, 2018 ; Li et al, 2016 ).…”