Journal of ethnopharmacology · 2025
An antitumoral fraction with casearin-like diterpenes exhibits potent acute anti-inflammatory effectiveness and systemic subchronic toxicity.
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Santos Denise Barbosa, Rodrigues Débora Caroline do Nascimento, Almeida Antonia Amanda Cardoso de, Amorim Viviane Rodrigues, Silva Jurandy do Nascimento, Porto Jhonatas Cley Santos, Timah Acha Boris, Dos Reis Antonielly Campinho, Zalewski Sven, Camargo Júlio Gabriel Sanches de, Carvalho Flávio Alexandre, Oliveira Francisco de Assis, Castro E Sousa João Marcelo de, Santos André Gonzaga Dos, Rizzo Márcia Dos Santos, Ferreira Paulo Michel Pinheiro
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: Casearia sylvestris is a south American species popularly known as "guaçatonga" and commonly used by indigenous tribes and other traditional communities in Brazil (as antiparasitic and to treat syphilis and snake bites), Colombia (for wounds and cuts), Paraguay (for rheumatism, eczema, and scabies), and Peru (for flu and chest colds). Moreover, laboratory investigations have shown different parts of the plant display antitumor, anxiolytic, antimicrobial, anti-ulcerogenic, hypolipidemic, antihypertensive and antinociceptive effects.
AIMS OF THE STUDY: It was evaluated in vivo anti-inflammatory and toxic effects of an ethyl acetate fraction with casearins (FC) from Casearia sylvestris leaves on mice.
MATERIALS AND METHODS: Initially, animals were treated with FC 2.5 and 5 mg/kg/day oral by gavage for 90 days. The follow-up assessments included weight gain, behavior (open field and rota rod), quantification of hematological and key organ markers, and chromosomal damage in blood marrow cells. Next, anti-edematogenic analysis were determined using phlogistic agents to induce paw edema and peritonitis. Pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β)], cell migration of peritoneal cells and paw histological changes were examined. Ifosfamide-induced hemorrhagic bladder cystitis was carried out for investigation of vascular permeability.
RESULTS: Oral doses of FC 25 or 50 mg/kg i. p. And 50 or 100 mg/kg exhibited anti-edematogenic action, decreased IL-1β and TNF-α levels involved in leukocyte chemotaxis, mast cell degranulation and peritonitis, attenuated cellular aspects of dermatitis, and decreased total leukocytes/neutrophil migration and cystitis vascular leakage (p < 0.05). Macroscopic, behavioral or other physiological changes (including gastrointestinal and kidney damage) were not observed, but weight loss and chromosomal alterations were registered in 90-day-treated animals at 5 mg/kg/day (p < 0.05).
CONCLUSIONS: The anti-inflammatory effects indicate the IL-1β - COX-1 - PGE2 axis may be putatively directly or indirectly deactivated by FC. All findings have actually suggested FC is safer if orally introduced and strongly support its effectiveness, whose pharmacological use relies on time of exposure, dose, frequency, and route.
AIMS OF THE STUDY: It was evaluated in vivo anti-inflammatory and toxic effects of an ethyl acetate fraction with casearins (FC) from Casearia sylvestris leaves on mice.
MATERIALS AND METHODS: Initially, animals were treated with FC 2.5 and 5 mg/kg/day oral by gavage for 90 days. The follow-up assessments included weight gain, behavior (open field and rota rod), quantification of hematological and key organ markers, and chromosomal damage in blood marrow cells. Next, anti-edematogenic analysis were determined using phlogistic agents to induce paw edema and peritonitis. Pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β)], cell migration of peritoneal cells and paw histological changes were examined. Ifosfamide-induced hemorrhagic bladder cystitis was carried out for investigation of vascular permeability.
RESULTS: Oral doses of FC 25 or 50 mg/kg i. p. And 50 or 100 mg/kg exhibited anti-edematogenic action, decreased IL-1β and TNF-α levels involved in leukocyte chemotaxis, mast cell degranulation and peritonitis, attenuated cellular aspects of dermatitis, and decreased total leukocytes/neutrophil migration and cystitis vascular leakage (p < 0.05). Macroscopic, behavioral or other physiological changes (including gastrointestinal and kidney damage) were not observed, but weight loss and chromosomal alterations were registered in 90-day-treated animals at 5 mg/kg/day (p < 0.05).
CONCLUSIONS: The anti-inflammatory effects indicate the IL-1β - COX-1 - PGE2 axis may be putatively directly or indirectly deactivated by FC. All findings have actually suggested FC is safer if orally introduced and strongly support its effectiveness, whose pharmacological use relies on time of exposure, dose, frequency, and route.