Caracterização química e estudos pré-clínicos de segurança e eficácia de Costus spiralis (Jacq.) Roscoe visando sua potencial aplicação. no tratamento da doença renal crônica

Abstract

Costus spiralis (Jacq.) Roscoe (Costaceae) is a medicinal plant popularly known in Brazil as Cana do Brejo and traditionally used for the treatment of kidney diseases. Its ethnopharmacological use and previous studies suggest a possible use of this species in the treatment of severe kidney diseases, such as Chronic Kidney Disease (CKD), currently considered a worldwide public health problem. Thus, we investigated the efficacy and preclinical safety of chemically characterized C. spiralis leaf extracts to assess their potential application in the treatment of CKD. The crude plant material and herbal extracts were submitted to physicochemical characterization assays, and new methods of identification and quantification of markers for the species were developed. The aqueous (AQE) and 80% hydroethanolic (HEE) extracts showed similar composition of total C-glycosylated flavones (average 2.4% ± 0.1%) but differed significantly in relation to total carbohydrate content (41.4% ± 1.4% for AQE and 8.0% ± 0.5% for HEE). Both extracts were subjected to in vitro toxicity assays and showed IC50 values ranging from 74 to 228 µg/mL in cytotoxicity in HepG2 cells and 3T3-A31 fibroblasts. AQE and HEE were found safe at 2,000 mg/kg in acute oral toxicity test in rodents. Experimental model of doxorubicin-induced nephropathy in vivo was employed, and the effect of the extracts on recovery of renal function was evaluated. Treatment with AQE at a dose of 5 mg/kg significantly improved the induced renal impairment, with reduced proteinuria, renal mass/body mass ratio and increased dimercaptosuccinic acid uptake on renal scintigraphy. Plasma metabolomics analysis revealed that the experimental model mainly affected the metabolism of linoleic and linolenic acids, altered levels of omega-3 and omega-6 series fatty acids, and indicated a tendency to reverse this effect after treatment with AQE. It was concluded that the flavonoid and carbohydrate-rich aqueous extract from C. spiralis leaf presents high preclinical safety after acute oral administration and potential for developing a new herbal medicine for chronic kidney disease, corroborating with the traditional use of the species.