Phytochemical profile, toxicological evaluation, and therapeutic potential of the ethanolic extract of Combretum leprosum Mart. stem bark in an ovalbumin-induced asthma model in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants are widely used in traditional medicine to treat various diseases, especially in communities with limited access to conventional healthcare. Among these, Combretum leprosum Mart. (Combretaceae), popularly known as "mofumbo," holds a prominent place in Brazilian folk medicine, where it is traditionally used to treat respiratory conditions such as asthma and cough. Besides its ethnomedical relevance, several studies have reported diverse pharmacological activities for this species, supporting its potential as a therapeutic resource.

AIM OF THE STUDY: This study aimed to investigate the spasmolytic, anti-inflammatory, and antioxidant effects of the ethanolic extract from the stem bark of Combretum leprosum (Cl-EtOH) in a rat-model of ovalbumin-induced asthma, as well as its potential to prevent bronchial smooth muscle hypertrophy in asthmatic rats. Additionally, the extract was subjected to phytochemical characterization and toxicity assessment.

MATERIALS AND METHODS: The stem bark of C. leprosum Mart. was collected in Palmeirais - PI. The plant material was dried, ground, and macerated with absolute ethanol (99.9 %) for seven days, followed by filtration and evaporation under reduced pressure to obtain the ethanolic extract Cl-EtOH. A fraction of the extract was subjected to phytochemical profiling through UPLC-ESI-QToF-MS/MS analysis. Acute toxicity of Cl-EtOH was assessed in Zophobas morio. The study was conducted following approval by the local Ethics Committee for Animal Experimentation of Federal University of Piaui (Protocol No. 783/2023). Ovalbumin-induced asthma was induced in male Wistar rats (200-250 g). Spasmolytic effect of Cl-EtOH was evaluated in isolated tracheal preparations from both non-asthmatic and asthmatic rats. In asthmatic animals treated with Cl-EtOH (50, 100, and 150 mg/kg), tracheal reactivity was evaluated. Bronchoalveolar lavage (BAL) was performed to assess total and differential leukocyte counts. Lung samples were processed for histological analysis and quantification of oxidative stress markers. Data were analyzed using analysis of variance (ANOVA) followed by Tukey's post hoc test, or to the Kruskal - Wallis test followed by Dunn's post hoc test. Differences were considered statistically significant at p < 0.05.

RESULTS: Phytochemical analysis demonstrated that Cl-EtOH contains high levels of flavonoids, phenolic compounds, and terpenoids. Acute toxicity testing confirmed its safety. In tracheal preparations, Cl-EtOH induced concentration-dependent relaxation, although with reduced potency in asthmatic rats. In vivo, treatment with the extract significantly attenuated tracheal hyperreactivity, reduced inflammatory cell infiltration in BAL fluid, improved oxidative stress parameters, and prevented thickening of the bronchial smooth muscle layer.

CONCLUSION: Cl-EtOH exhibited significant spasmolytic, anti-inflammatory, and antioxidant effects in an OVA-induced asthma model, supporting its traditional use. The flavonoid-rich extract showed a favorable safety profile, thereby highlighting its potential as an adjuvant therapy for asthma. Further studies are needed to elucidate its molecular mechanisms.