The analgesic and gastroprotective activities of the three fungal extracts and their possible correlation with the inhibition of the P2X7 receptor

• Published in: Biomedicine & pharmacotherapy Vol. 181; p. 117657
• Main Authors: Soares-Bezerra, Rômulo José, da Silva Ferreira, Natiele Carla, de Almeida Alves, Tânia Maria, Zani, Carlos Leomar, Rosa, Luiz Henrique, Calheiros, Andrea Surrage, de Souza, Cristiane Zanon, Miranda, Julliana Alves Azeredo, Lima-Quaresma, Kátia Regina Ferreira, Alves, Luiz Anastacio, da Silva Frutuoso, Válber
• Format: Journal Article
• Language: English
• Published: Elsevier Masson SAS 01.12.2024; Elsevier
• Subjects: Analgesic; Antagonist; Anti-inflammatory; Fungi; P2X7; Ulcer; Fungi; Ulcer; Analgesic; Antagonist; P2X7; Anti-inflammatory
• ISSN: 0753-3322
• DOI: 10.1016/j.biopha.2024.117657

P2X7 is a purinergic receptor physiologically activated by extracellular ATP. Its activation induces proinflammatory responses, including cytokine release, reactive oxygen species formation, and cell death. Previous in vivo experimental models demonstrated that P2X7 blockade has anti-inflammatory effects; however, there are no drugs used in clinical therapy that act on the P2X7 receptor. In the context of inflammatory diseases, nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used as the first-line treatment; however, their major side effects include stomach ulcer formation, which increases patient morbidity and mortality. Here, we analyzed for the first time the analgesic and gastroprotective activities of three fungal extracts that showed antagonistic effects on P2X7 in vitro. The Antarctic fungal extracts obtained from Vishniacozyma victoriae, Metschnikowia australis, and Ascomycota sp. were tested via in vivo models of acute pain and ethanol-induced ulceration. These three extracts reduced paw licking by approximately 50 %, which is related to pain behavior, and reduced the number of stomach ulcers 3–7 times compared with the control (70 % ethanol), making them more efficient than the lansoprazole, an NSAID drug, and Brilliant Blue G (BBG), a known P2X7 antagonist, which only halves the number of ulcers. Furthermore, the extracts also protected the gastric mucosa and significantly reduced the levels of liver and renal enzymes compared with those in the ethanol group. Taken together, the fungal extracts presented both analgesic and possibly anti-inflammatory activities and had a protective effect on the gastric epithelium. •The extracts of Vishniacozyma victoriae, Metschnikowia australis, and Ascomycota sp., significantly alleviated pain in mice.•V. victoriae, M. australis, and Ascomycota sp. extracts significantly reduced ethanol-induced ulceration in mice.•These three fungal extracts also protected the gastric mucosa.