Solidagenone in vivo leishmanicidal activity acting in tissue repair response, and immunomodulatory capacity in Leishmania amazonensis. (1st July 2022)

• Record Type: Journal Article
• Authors: Bortoleti, Bruna Taciane da Silva; Detoni, Mariana Barbosa; Gonçalves, Manoela Daiele; Tomiotto-Pellissier, Fernanda; Silva, Taylon Felipe; Concato, Virginia Marcia; Rodrigues, Ana Carolina Jacob; Carloto, Amanda Cristina; de Matos, Ricardo Luís Nascimento; Fattori, Victor; Arakawa, Nilton Syogo; Verri Jr, Waldiceu Ap.; Costa, Idessania Nazareth; Conchon-Costa, Ivete; Miranda-Sapla, Milena Menegazzo; Wowk, Pryscilla Fanini; Pavanelli, Wander Rogério
• Is Part Of: Chemico-biological interactions. Volume 361(2022)
• Publication Date: 2022-07-01
• Subjects: Solidagenone (SOL) -- Leishmaniasis -- In vivo -- Immunomodulation -- Collagen; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2022.109969
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Leishmaniasis is a group of chronic parasitic diseases in humans caused by species of the Leishmania genus. Current treatments have high toxicity, cost, duration, limited effectiveness, significantly complex administration, and drug-resistant strains. These factors highlight the importance of research into new therapies that use drugs without toxic effects. Solidagenone (SOL), the main labdane diterpene isolated from the plant Solidago chilensis, has anti-inflammatory, gastroprotective, antioxidant, tissue repair-inducing effects, suggesting a role in novel drug development. This study investigates in vivo mechanism action of SOL treatment in L. amazonensis -infected BALB/c mice. SOL was isolated from the roots of S. chilensis, and L. amazonensis -infected mice were treated daily with SOL (10, 50, 100 mg/kg) by gavage for 30 days. Gastric (NAG, MPO), hepatic (AST, ALT), systemic (body weight, NO) toxicity, leishmanicidal activity (lesion size, parasite burden), cell profile (macrophage, neutrophil infiltration), antioxidant (ABTS, NBT, NO), oxidant parameters (FRAP, ABTS), Th1, Th2, Th17 cytokines (CBA), collagen deposition (picrosirius), arginase, iNOS, NF-kB, and NRF2 (immunofluorescence) were evaluated. In vivo results showed SOL-treatment did not induce gastric, hepatic, or systemic toxicity in L. amazonensis -infected mice. SOL was able to reduce the lesion size and parasite load at the site of infection, increasing macrophage infiltration and neutrophil migration, exerting a balance in antioxidant (increased ABTS, NBT reduction, and NO), oxidative (increased FRAP and ABTS), and anti-inflammatory responses (reduced TNF-α, IFN-γ and increased IL-6, IL-17 production), and inducing arginase, iNOS, NF-kB, NRF2 and collagen deposition (type III), favoring wound healing and accelerating tissue repair at the site injury. Graphical abstract: Image 1 Highlights: SOL does not induce gastric, hepatic, or systemic toxicity in infected mice. SOL leishmanicidal effect reduce lesion size and parasite load in infected mice. SOL is able to increase macrophages and neutrophils in the site of infection. SOL exerts a balance in antioxidant and oxidative response in the site of infection. SOL has anti-inflammatory effect, collagen deposition and wound healing in tissue.