Antidepressant‐like effect of rosmarinic acid during LPS‐induced neuroinflammatory model: The potential role of cannabinoid receptors/PPAR‐γ signaling pathway

Abstract

Rosmarinic acid (RA), an ester of caffeic acid and 3, 4-dihydroxyphenyllactic acid, has anti-inflammatory and neuroprotective activities. Herein, this study investigated in silico the drug-likeness and the potential molecular targets to RA. Moreover, it tested the antidepressant-like potential of RA in the lipopolysaccharide (LPS)-induced depression model. RA (MW = 360.31 g/mol) meets the criteria of both Lipinski's rule of five and the Ghose filter. It also attends to relevant pharmacokinetic parameters.Target prediction analysis identified RA's potential targets and biological activities, including the peroxisome proliferator-activated receptor (PPAR) and the cannabinoid receptors CB 1 and CB 2 . In vivo, RA's acute, repetitive, and therapeutic administration showed antidepressant-like effect since it significantly reduced the immobility time in the tail suspension test and increased grooming time in the splash test. Further, the pretreatment with antagonists of CB 1 , CB 2 , and PPAR-γ receptors significantly blocked the antidepressant-like effect of RA. Altogether, our findings suggest that cannabinoid receptors/PPAR-γ signaling pathways are involved with the antidepressant-like effect of RA. Moreover, this molecule meets important physicochemical and pharmacokinetic parameters that favor its bioavailability. RA constitutes a promising, innovative, and safe molecule for the pharmacotherapy of major depressive disorder.

Ursolic acid and rosmarinic acid ameliorate alterations in hippocampal neurogenesis and social memory induced by amyloid beta in mouse model of Alzheimer’s disease

“…Frontiers in Pharmacology frontiersin.org angiogenesis, synaptogenesis, and neurogenesis which are crucial in delaying the progression of AD (Fratiglioni et al, 2004). Notably, RA and UA are previously known to exert anxiolytic and antidepressant effects in various models of neurotoxicity (Colla et al, 2015;Ramos-Hryb et al, 2019;Lataliza et al, 2021). The present study showed that RA and UA treatment post Aβ 1-42 administration exhibited significantly greater sociability levels relative to the diseased group.…”

Rosmarinus officinalis and Methylphenidate Exposure Improves Cognition and Depression and Regulates Anxiety-Like Behavior in AlCl3-Induced Mouse Model of Alzheimer’s Disease

“…Likewise, rosmarinic acid has shown antidepressant effects mediated through its increased antioxidant response (Wang J. et al, 2021) exhibiting neuroprotective effects via activation of GABA A receptors (Wang C. C. et al, 2021). In addition, Lataliza et al suggested the substantial involvement of cannabinoid receptors/PPAR-γ signaling pathways in exerting the antidepressant-like effect of rosmarinic acid (Lataliza et al, 2021).…”

Biomedical features and therapeutic potential of rosmarinic acid

“…Previous reports have affirmed the implication of RA in promoting neurogenesis and alleviation of cognition defects and synaptic regulation (Mirza et al 2021 ). RA has been proven to be a promising, innovative, and effective pharmacotherapy agent for treating depressive disorders (Lataliza et al 2021 ). micro-RNAs play a pivotal role in the pathogenesis of neurodegenerative diseases.…”