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DOI: 10.1055/a-1373-6074
Optimization of Coumarins Extraction from Pterocaulon balansae by Box-Behnken Design and Anti-Trichomonas vaginalis Activity
Supported by: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Finance code 001Supported by: Conselho Nacional de Desenvolvimento Científico e Tecnológico 459619/2014-4
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Abstract
Trichomonas vaginalis causes trichomoniasis, a nonviral sexually transmitted infection with a high prevalence worldwide. Oral metronidazole is the drug of choice for the treatment of this disease, although high levels of T. vaginalis resistance to this agent are well documented in the literature. This study describes the anti-T. vaginalis activity of an optimized coumarin-rich extract from Pterocaulon balansae. Optimization was performed to maximize extraction of total coumarins by means of a 3-level Box-Behnken design, evaluating the effect of three factors: extraction time, plant : solvent ratio, and ethanol concentration. Optimum conditions were found to be 5 h extraction time and a plant : solvent ratio of 1% (w/v) and 60% (v/v) ethanol, which resulted in approximately 30 mg of total coumarins/g of dry plant. The coumarin-enriched extract exhibited a minimum inhibitory concentration of 30 µg/mL and an IC50 of 3.2 µg/mL against T. vaginalis, a low cytotoxicity, and a high selectivity index (18 for vaginal epithelial cells and 16 for erythrocytes). The coumarins permeation/retention profile through porcine vaginal mucosa was evaluated in Franz-type diffusion cells. After 8 h of kinetics, coumarins were detected in the tissue (4.93 µg/g) without detecting them in the receptor compartment. A significant increase of coumarins in the mucosa layers (8.18 µg/g) and receptor compartment (0.26 µg/g) was detected when a T. vaginalis suspension (2 × 105 trophozoites/mL) was previously added onto the mucosa. No alterations were visualized in the stratified squamous non-keratinized epithelium of the porcine vaginal mucosa after contact with the extract. Overall, these results suggest that the P. balansae coumarin-rich extract may have potential as a treatment for trichomoniasis.
Key words
Pterocaulon balansae - Asteraceae - coumarins - Box-Behnken design - Trichomonas vaginalis - vaginal mucosaSupporting Information
- Supporting Information
The chromatographic profile of HEE of P. balansae (Fig. 1S), BBD arrangement and experimental values (Table 1S), linearity, precision, and accuracy (Table 2S), and recovery of P. balansae coumarins from porcine vaginal mucosa (Table 3S) are available as Supporting Information.
Publication History
Received: 25 May 2020
Accepted after revision: 19 January 2021
Article published online:
12 February 2021
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