Efeitos anti-inflamatório e osteoprotetor do extrato de Agaricus blazei: uma revisão de escopo e um estudo experimental em ratos submetidos a periodontite induzida por ligadura

Abstract

Periodontitis is a chronic infectious-inflammatory disease resulting from microbial dysbiosis in the supporting tissues of the teeth, associated with an immune response in susceptible individuals. Its treatment is based on scaling and root planing; however, considering the role of the host response in the etiology of periodontitis, adjuvant interventions are sometimes necessary to modulate inflammation and contribute to treatment success. In this context, the mushroom Agaricus blazei (Ag) stands out as a natural pharmacological agent with antioxidant, angiogenic, and anti-inflammatory properties. However, its effects are poorly explored in periodontitis. Thus, the objectives of this study were: 1) to conduct a scoping review on the effects of Ag on inflammation and bone metabolism and 2) to investigate the anti-inflammatory and osteoprotective effects of Ag extract on inflammatory bone loss in Wistar rats with experimental periodontitis (EP) by ligature. For the first objective, two reviewers mapped 37 studies in six databases. The findings indicate that Ag plays a significant anti-inflammatory role in pathological conditions, which has resulted in an anabolic effect on bone. However, research with more standardized compounds is needed. For the second objective, the study sought to evaluate the anti-inflammatory and osteoprotective effects of the Ag extract administered systemically and locally in periodontitis. To this end, 30 animals were divided into 5 groups (n=6/group): Naive (N), Experimental Periodontitis (PE), Ag-PROF at doses of 25 mg/kg p.o. (Ag 25) or 50 mg/kg p.o. (Ag 50) prophylactically 30 minutes before the induction of PE, as well as an Ag-TERAP group that received 50 mg/kg from the 5th day after PE induction (Ag50T) until euthanasia. For local administration, 24 animals were divided into 4 groups: Naive (N), PE, and Ag, receiving 1% Ag-PROF gel twice daily prophylactically, 30 minutes before PE induction, or therapeutic Ag-TER, from day 5 twice daily after PE induction until euthanasia. PE was induced in all animals, except in group N, by inserting a 3.0 nylon suture around the left upper second molar for 11 days, at which point they were euthanized and their maxillae removed for microtomographic, histological, histometric, biochemical, oxidative stress, and gene expression analyses by RT-pPCR. The extract at doses of 25 and 50 attenuated macroscopic and microscopic alveolar bone loss compared to the PE group. It stimulated bone remodeling, as well as improved organization and thickness of collagen fibers in the periodontal ligament. The antigen reversed the GSH levels found in PE, highlighting its antioxidant role. The antigen gel, prophylactically and therapeutically, attenuated alveolar bone loss by improving bone mineral density and increasing the number and function of osteoblasts; explained by the increased expression of beta-catenin and reduction of GSK3b and RANKL (p<0.05). Thus, we can infer that the antigen, systemically and locally, attenuated inflammatory alveolar bone loss and reduced oxidative stress, potentially representing a relevant, natural, and sustainable pharmacological strategy for the therapeutic management of periodontitis.