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.

Exercise Reduces Pain and Deleterious Histological Effects in Fibromyalgia-like Model.

Fibromyalgia (FM) is characterized by chronic pain and associated comorbidities such as fatigue, anxiety, depression, and sleep disorders. There is a large amount of evidence regarding the benefits of physical exercise in controlling chronic pain. However, there is no consensus on which exercise modality is most suitable and the real benefits of this intervention to treat FM symptoms. The present study investigated the analgesic and antidepressant effects and morphophysiological responses induced by different physical exercise (aerobic and strength protocols) during the experimental model of FM. Spontaneous pain, mechanical hyperalgesia, thermal allodynia, depression-related behavior, and locomotor activity were evaluated weekly, as well as the morphological evaluation of the spinal cord and dorsal root ganglion. Aerobic and strength training protocols consistently abolished nociceptive behaviors, reducing spontaneous pain scores, cold allodynia, and frequency of response to mechanical hyperalgesia. The strength exercise modulated the depressive-like behavior. Finally, our data demonstrated that physical exercise performed for two weeks increased the number of glial cells in the dorsal root horn. However, it was not sufficient to control the other deleterious effects of the reserpine model on the spinal cord and the dorsal root. Together, these results demonstrated that different physical exercise modalities, when performed regularly in mice, proved to be effective and safe non-pharmacological alternatives for the treatment of FM. However, some gaps have yet to be studied regarding the neuroadaptive effects of physical exercise.

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.