Metabolomic approach and Molecular docking for identification of a-Glucosidase Inhibitors from Caatinga plants

Raimundo Rigoberto Barbosa Xavier FIlho1,2,3, Elisabeth Mariano Batista4, Yasmim Aquino Milhome5, Paulo Riceli Vasconcelos Ribeiro2, Natalia Florencio Martins2, Marisa Jadna SIlva Frederico3,4, Luciana de Siqueira Oliveira4, Kirley Marques Canuto1,2

1. UECE, UNIVERSIDADE ESTADUAL DO CEARÁ; Av. Dr. Silas Munguba, 1700 - Itaperi, Fortaleza - CE, 60714-903
2. EMBRAPA, EMBRAPA AGROINDÚSTRIA TROPICAL; R. Pernambuco, 2270 - Pici, Fortaleza - CE, 60511-110
3. NPDM, NÚCLEO DE PESQUISA E DESENVOLVIMENTO DE MEDICAMENTOS; R. Coronel Nunes de Melo, 1000 - Rodolfo Teófilo, Fortaleza - CE, 60430-275
4. UFC, UNIVERSIDADE FEDERAL DO CEARÁ; R. 5, 100 - Pres. Kennedy, Fortaleza - CE, 60355-636
5. UNYLEA, FACULDADE UNYLEYA ; R. Antônio Gadelha, 623 - Messejana, Fortaleza - CE, 60871-055

Introduction: The Caatinga is a unique semi-arid biome found exclusively in northeastern Brazil, characterized by thorny vegetation and seasonal droughts. Despite its harsh climate, it harbors rich biodiversity, including numerous endemic plant species. Among them, Amburana cearensis (Fabaceae) and Justicia pectoralis (Acanthaceae)—popularly known as ‘cumaru’ and ‘chambá,’ respectively—are traditionally used in folk medicine. Both species are widely employed to treat respiratory disorders, with their therapeutic effects attributed to the bronchodilator and anti-inflammatory activities of coumarins, flavonoids, and phenolic acid derivatives. In addition, these secondary metabolites are associated with other pharmacological effects, such as hypoglycemic activity, which can be evaluated by measuring inhibition of the enzyme a-glucosidase, a key therapeutic target for managing postprandial hyperglycemia in patients with type 2 diabetes mellitus (T2DM). Objective: This study aimed to identify a-glucosidase inhibitors in A. cearensis and J. pectoralis extracts using a combination of metabolomic analysis and in vitro and in silico assays. Materials and Methods: Extracts were prepared by decocting dried leaves in boiling water, followed by filtration and lyophilization. Their chemical composition was determined using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS). The a-glucosidase inhibition assay was performed in microplates by measuring absorbance at 415 nm using a spectrophotometer. Acarbose was used as a positive control and inhibition percentages were calculated. Results: A total of 28 and 15 compounds were tentatively identified in A. cearensis and J. pectoralis extracts, respectively, primarily consisting of phenolic acids, flavonoid glycosides, and hydrolyzable tannins. Both extracts (5 mg/mL) inhibited more than 50% of the enzyme activity. Molecular docking revealed two phenolic compounds with high binding affinity to a-glucosidase, suggesting they may be responsible for the observed hypoglycemic effects. Conclusion: The plant extracts demonstrated promising hypoglycemic potential and represent valuable sources of bioactive compounds for use as adjuvants in the treatment of T2DM. Funding: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico (FUNCAP).

Agradecimentos: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico (FUNCAP).