Cenostigma pluviosum var. peltophoroides, known as “sibipiruna,” is a plant rich in polyphenols used in traditional medicine for gastrointestinal disorders. The study aimed to investigate the chemical composition of the crude ethanolic extract of the stem bark (CEECP), evaluating its in vivo toxicity, genotoxicity, mutagenicity and anti-inflammatory activity. The plant material was macerated in 95% ethanol for 72 h, and the solvent was removed by rotary evaporation to obtain CEECP. Chemical characterization was performed by HPLC-ESI-MS/MS in negative mode. In vivo approaches were performed using male/female Swiss albino mice. Acute toxicity was assessed at a single high dose of 2000 mg/kg. Mutagenicity was investigated by the micronucleus test and genotoxicity by the comet assay, both at a dose of 2000 mg/kg. Anti-inflammatory activity was evaluated in carrageenan-induced paw edema and peritonitis models, at doses of 50, 100, and 200 mg/kg. HPLC-ESI-MS/MS analysis showed the presence of hydrolyzable tannins, phenolic acid heterosides, and biflavonoids. The safety profile of the CEECP was demonstrated for the first time, with no evidence of acute toxicity, mortality, mutagenicity, or genotoxicity at the tested doses. The extract significantly reduced paw edema in a dose-dependent manner at doses of 100 and 200 mg/kg, with inhibition rates of 65.78% and 73.12%, respectively, and also decreased leukocyte migration in the peritonitis model by 61.81% and 72.79% at the same doses. These findings indicate the CEECP as a source of pharmacologically relevant phytocompounds and, most notably, demonstrate its pronounced anti-inflammatory activity. Furthermore, the extract exhibited a favorable safety profile in the toxicological evaluations, highlighting the extract as a promising anti-inflammatory agent.

A busca por agentes anti-inflamatórios mais eficazes é imprescindível devido aos elevados efeitos colaterais associados aos fármacos atualmente utilizados para a inflamção. Nesse contexto, os produtos naturais surgem como fontes terapêuticas promissoras. Estudos in silico, como a ancoragem molecular, têm contribuído para a descoberta de novos compostos bioativos, a exemplo da sakuranetina, isolada pela primeira vez da espécie Varronia globosa Jacq. (Maria-preta), conhecida por suas propriedades espasmolíticas, anticancerígenas e anti-inflamatórias. O estudo objetivou avaliar o composto isolado através de métodos cromatográficos e espectroscópicos, assim como analisar seu perfil farmacodinâmico para doenças inflamatórias relevantes, os parâmetros farmacocinéticos e as propriedades de drug-likeness. O extrato etanólico bruto do caule foi particionado nas fases hexânica, clorofórmica, acetato de etila e metanol. A partir da fase acetato de etila foi possível isolar o KGV8, identificado por técnicas espectroscópicas. Os estudos farmacodinâmicos foram realizados in silico, utilizando o ancoramento molecular e os perfis farmacocinéticos por ferramentas computacionais. Desse modo, o KGV8, identificado como a flavanona 4’,5-dihidroxi-7-metoxiflavanona (Sakuranetina), apresentou maior afinidade pelos alvos inflamatórios mPGES-1, PDE4-β e DHODH, pois o complexo KGV8-alvo inflamatório formado foi mais estável e demonstrou uma menor energia de ligação, o que não foi visualizado com as estruturas enzimáticas de PGHS-2 e iNOS. Ademais, o composto isolado exibiu perfil farmacocinético adequado para canditados a fármacos. Portanto, a Sakuranetina se apresenta como uma potencial molécula para o desenvolvimento de novos medicamentos anti-inflamatórios, com alta afinidade para inibição de alvos de doenças inflamatórias e relevantes paramêtros farmacocinéticos e de drug-likeness. No entanto, modelos experimentais de dinâmica molecular, in vitro e in vivo são necessários para consolidação dos resultados.

Calotropis procera, known as “Silk cotton”, stands out for the presence of various classes of bioactive compounds responsible for its ethnopharmacological properties. The study aimed to conduct a phytochemical investigation, evaluating the in vitro and in vivo toxicity together with the antinociceptive potential of an n-butanolic fraction (FB) from the leaves. The crude ethanolic extract (CEE) was obtained by maceration in ethanol for 72 h. It was then partitioned using a gradual solvent sequence. The FB was analyzed by HPLC-ESI-MS/MS in negative mode and ¹H and ¹³C NMR. Toxicity was assessed by the erythrocyte hemolytic assay and acute oral toxicity test at a single dose of 300 mg·kg⁻¹. The antinociceptive effect was assessed by the acetic acid-induced abdominal writhing test and the formalin test in mice at doses of 3.75, 7.5 and 15 mg·kg⁻¹ per os. HPLC-ESI-MS/MS analysis identified flavonoids, phenolic acids, and the megastigmane roseoside, isolated for the first time in C. procera. The FB did not cause hemolytic effects or behavioral or physiological changes in mice. It showed an antinociceptive effect at all doses, reducing abdominal writhing by up to 91.46% and the licking time in phases 1 and 2 of the formalin test by up to 63.83% and 91.73%, respectively. In this study, it was possible to determine that an FB of a crude extract of C. procera leaves has antinociceptive activity, possibly associated with the phenolic compounds and roseoside found, with a lack of toxicity in vitro and in vivo, validating its ethnopharmacological use.