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. 2021 Nov 13;9(11):1683.
doi: 10.3390/biomedicines9111683.

Wnt/β-Catenin Pathway in Experimental Model of Fibromyalgia: Role of Hidrox®

Ramona D'Amico  1 , Marika Cordaro  2 , Rosalba Siracusa  1 , Daniela Impellizzeri  1 , Angela Trovato Salinaro  3 , Maria Scuto  3 , Maria Laura Ontario  3 , Roberto Crea  4 , Salvatore Cuzzocrea  1 , Rosanna Di Paola  1 , Roberta Fusco  1 , Vittorio Calabrese  3
Affiliations

Wnt/β-Catenin Pathway in Experimental Model of Fibromyalgia: Role of Hidrox®

Ramona D'Amico et al. Biomedicines. .

Abstract

Fibromyalgia (FM) is a chronic condition characterized by persistent widespread pain that negatively affects the quality of life of patients. The WNT/β-catenin signaling pathway seems to be involved in central sensitization and different pain states. The objective of this study was to investigate the beneficial effects of a new compound called Hidrox® (HD), containing 40-50% hydroxytyrosol, in counteracting the pain associated with FM. An FM-like model was induced in rats by subcutaneous injections of reserpine (1 mg/kg) for three consecutive days. Later, HD (10 mg/kg) was administered orally to the animals for seven days. Reserpine injections induced WNT/β-catenin pathway activation, release of pro-inflammatory mediators as well as a significant increase in oxidative stress. Daily treatment with HD was able to modulate the WNT/β-catenin and Nrf2 pathways and consequently attenuate the behavioral deficits and microglia activation induced by reserpine injection. These results indicate that nutritional consumption of HD can be considered as a new therapeutic approach for human FM.

Keywords: Nrf2 pathway; WNT/β-catenin pathway; fibromyalgia; pain.

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Conflict of interest statement

Roberto Crea is the president of Oliphenol LLC. and owns a patent for the Hidrox compound. The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Effect of HD on WNT/FZ/β-catenin signaling pathway: Western blot analysis of Wnt-3a (A), FZ8 (B), cytosolic β-catenin (C) and nuclear β-catenin (D) expression. *** p < 0.001 vs. sham; ### p < 0.001 vs. vehicle.
Figure 2
Figure 2
Effect of HD on pro-inflammatory cytokines levels: ELISA assay of IL-18 (A) TNF-α (B) and IL-1β (C) *** p < 0.001 vs. sham; ### p < 0.001 vs. vehicle.
Figure 3
Figure 3
Effect of HD on mechanical and thermal hyperalgesia: von Frey hair (A) hot plate (B) and tail-flick warm water (C) tests. * p < 0.05 vs. sham; ** p < 0.01 vs. sham; *** p < 0.001 vs. sham; # p < 0.05 vs. vehicle; ## p < 0.01 vs. vehicle.
Figure 4
Figure 4
Effect of HD on microglia activation and BDNF expression: immunohistochemical evaluation in the spinal cord for Iba1 expression: Sham (A), Vehicle (B), Vehicle + HD (C) and BDNF expression: Sham (D), Vehicle (E), Vehicle + HD (F). Graphical quantification of Iba1 (G) and BDNF expression (H). The black arrows indicated positive cells. A 40× magnification is shown (75-µm scale bar). *** p < 0.001 vs. sham; ### p < 0.001 vs. vehicle.
Figure 5
Figure 5
Effect of HD on oxidative stress: Western blot analysis of Nrf2 (A), HO-1 (B), NQQO-1 (C) expression. * p < 0.05 vs. sham; ** p < 0.01 vs. sham; ### p < 0.001 vs. vehicle.
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