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. 2022 Jul 1:361:109969.
doi: 10.1016/j.cbi.2022.109969. Epub 2022 May 5.

Solidagenone in vivo leishmanicidal activity acting in tissue repair response, and immunomodulatory capacity in Leishmania amazonensis

Bruna Taciane da Silva Bortoleti  1 , Mariana Barbosa Detoni  2 , Manoela Daiele Gonçalves  3 , Fernanda Tomiotto-Pellissier  1 , Taylon Felipe Silva  2 , Virginia Marcia Concato  2 , Ana Carolina Jacob Rodrigues  2 , Amanda Cristina Carloto  2 , Ricardo Luís Nascimento de Matos  3 , Victor Fattori  4 , Nilton Syogo Arakawa  3 , Waldiceu Ap Verri Jr  4 , Idessania Nazareth Costa  2 , Ivete Conchon-Costa  2 , Milena Menegazzo Miranda-Sapla  2 , Pryscilla Fanini Wowk  5 , Wander Rogério Pavanelli  6
Affiliations

Solidagenone in vivo leishmanicidal activity acting in tissue repair response, and immunomodulatory capacity in Leishmania amazonensis

Bruna Taciane da Silva Bortoleti et al. Chem Biol Interact. .

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.

Keywords: Collagen; Immunomodulation; In vivo; Leishmaniasis; Solidagenone (SOL).

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