Evaluation of the schistosomicidal activity of the steroidal alkaloids from Solanum lycocarpum fruits

Abstract

Solanum lycocarpum (Solanaceae), a Brazilian medicinal plant known as "wolf fruit," contains about 1.5% of glycoalkaloids in its dried fruits, consisting mainly of solamargine and solasonine. The present work reports the obtainment of the alkaloidic extract of the S. lycocarpum fruit by acid-base extraction and the isolation of the major alkaloid heterosides by chromatographic means, as well as the evaluation of their in vitro schistosomicidal activities. The in vitro schistosomicidal activities of the alkaloidic extract of S. lycocarpum fruits and its isolated steroidal alkaloids were undertaken against adult worms of Schistosoma mansoni. The alkaloidic extract (20, 32, and 50 μg mL(-1)), solasonine (50 μM), solamargine (32 and 50 μM), and equimolar mixture of glycoalkaloids (20, 32, and 50 μM) lead to the separation of all couple worms and extensive disruption on their teguments, such as sloughing, as well as their deaths within 24 h of incubation. In addition, the alkaloidic extract (10 and 15 μg mL(-1)), solasonine (50 μM), solamargine (10, 15, and 20 μM), and equimolar mixtures of glycoalkaloids (10 and 15 μM) reduced the development of eggs produced by the adult worms. Solamargine, containing the sugar chain moiety chacotriose, was more active than the solasonine, which contains solatriose sugar chain moiety. A synergistic effect was also observed for a mixture of solamargine and solasonine. Therefore, the alkaloidic extract of S. lycocarpum, and its major components, solamargine and solasonine, showed promising schistosomicidal activity.

Natural Products with Antischistosomal Activity

“…It is known that the biological activity of glycoalkaloids is largely due to their membrane-disruptive effects [89, and references therein]. In general, against schistosomes, solamargine was more active than solasonine [68]. The mechanism by which the compounds exert their effects remains unclear, but regarding the interruption of the integrity and function of membrane, it has been hypothesized that glycoalkaloids containing the chacotriose sugar chain moiety (rhamnose-glucoserhamnose), such as solamargine, are generally more active than compounds containing the solatriose sugar chain moiety (rhamnose-galactose-glucose), such as solasonine [68].…”

“…Alkaloids are widely distributed in nature and they have been isolated from several plant species [17,18]. Piplartine [62,63], piperamide 1 [61], epiisopiloturine [49,84], sanguinarine [64], solamargine and solasonine [68] are alkaloids with in vitro antischistosomal properties. Mefloquine, an aminoalcohol derived from quinine, has in vitro and in vivo schistosomicidal activity (Figure 2) [57,58].…”

“…(Solanaceae) fruits, a Brazilian plant known as 'wolf fruit' [68]. These compounds (32-50 μM) lead to the separation of all coupled S. mansoni worms and caused mortality of parasites.…”

A validated HPLC analytical method for the analysis of solasonine and solamargine in in vitro skin penetration studies

“…Linearities were observed over the concentration ranges 0.86 to 990.00 µg/mL for SN and 1.74 to 1000.00 µg/mL for SM, showing a highly significant correlation coefficient (r) of 0.9996 for both glycoalkaloids, as described by Tiossi et al. 3 For quantification of SN and SM, the regression equations of the obtained curves were considered, 26 according to Equations 6 and 7: y = 5603.2 x + 9026 for SN (6) y = 6433.3 x + 9204 for SM (7) where y corresponds to the area of the compound and x to the concentration of the compound in µg/mL. To determine the LOD and LOQ of the developed method, the method based on parameters of the calibration curve was adopted, since this is more reliable as it does not depend on analyst interpretation, as does the visual method.…”

“…3 Structurally, SN and SM share a common steroidal aglycone, solasodine, which has been used for the production of steroidal drugs. 4 Previous studies have shown that these glycoalkaloids display antifungical, 5,6 schistosomicidal, 7 antiprotozoal, 8 molluscicidal, 9 antiviral, 10 antimutagenic, 11 and antineoplasic activities against a variety of neoplastic cell lines, [12][13][14] as well as hypoglycemic and gastric emptying inhibitory activities. 15 As stated by Gottlieb and collaborators, 16 Brazilian biodiversity is an important source of wealth, and its benefits do not only depend on the use of biodiversity, but also in its sustainability for proper economic exploitation.…”