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

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 CB1 and CB2 . 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 CB1 , CB2 , 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.

Comparative effect of photobiomodulation associated with dexamethasone after sciatic nerve injury model.

To analyze the effect of photobiomodulation and dexamethasone on nerve regeneration after a sciatic nerve crushing model. Twenty-six Swiss mice were divided into the following groups: naive; sham; injured, low-level laser therapy (LLLT) (660 nm, 10 J/cm2, 0.6 J, 16.8 J total energy emitted during the 28 days of radiation, 20 s, for 28 days); dexamethasone (Dex) (local injection of 2 mg/kg for 10 consecutive days); and LLLT group associated with Dex (LLLT/Dex), with the same parameters of the other groups. For nerve injury, a portable adjustable pinch was used. The animals were evaluated using the Sciatic Functional Index (SFI) and Sciatic Static Index (SSI). The results obtained were evaluated with Image J™ and Kinovea™. Data and images were obtained at baseline and after 7, 14, 21, and 28 days after surgery. The evaluation of hyperalgesia, using Hargreaves, and behavior through the open field was also performed. In functional and static analysis, all groups presented significant differences when compared to the injured group. In the analysis of the SSI results, the group treated with both LLLT and dexamethasone was more effective in improving the values of this parameter, and in the SFI, the laser-treated group obtained better results. In the evaluation through the open field and the Hargreaves, there was no difference. The application of LLLT and dexamethasone was effective in nerve regeneration according to the results and was more effective when LLLT was associated with dexamethasone than in LLLT alone for the SSI.