The significant antidyslipidemic, hypoglycemic, antihyperglycemic, and antiobesity activities of the aqueous extracts of Agave Sisalana juice are partly mediated via modulation of calcium signaling pathways.

Plant species in the genus Agave, including , have found extensive application in African and Asian traditional medicine. Inspired by the use of the edible sweet sap known as Aguamiel (obtained from specific mature agave species such as ) in Mexico by diabetic patients to improve their diabetic condition, this study investigated the effects of extracts prepared by lyophilization, fermentation, and saponin extraction from sisal juice in a rodent model of metabolic syndrome. The metabolic syndrome was induced by administering a high fat and high fructose diet to freshly weaned Sprague-Dawley rats for eight weeks. The extracts possessed significant hypoglycemic effects [3.883 ± 0.371 mmol/L (normal group) vs. 8.183 ± 0.5845 mmol/L (negative control) vs. 3.767 ± 0.2716 mmol/L (positive control) vs. 4.167 ± 0.4602 mmol/L (FSP) vs. 4.533 ± 0.3169 mmol/L (FerSP) vs. 3.5 ± 0.2309 mmol/L (FS LD) vs. 3.867 ± 0.3353 mmol/L (FS HD) vs. 4.617 ± 0.2725 mmol/L (FerS LD) vs. 4.383 ± 0.3114 mmol/L (FerS HD): p < 0.0001]. The extracts also possessed significant antihyperlipidemic effects with significant differences in total serum cholesterol between the groups [1.398 ± 0.1232 mmol/L (normal group) vs. 4.225 ± 0.4135 mmol/L (negative control) vs. 1.582 ± 0.154 mmol/L (positive control) vs. 1.245 ± 0.0911 mmol/L (FSP) vs. 1.393 ± 0.1423 mmol/L (FerSP) vs. 1.387 ± 0.0924 mmol/L (FS LD) vs. 1.761 ± 0.1495 mmol/L (FS HD) vs. 1.698 ± 0.1294 mmol/L (FerS LD) vs. 1.6975 ± 0.0982 mmol/L (FerS HD): p < 0.0001]. Further, significant antiobesity effects of the extracts were observed with significant differences in weight among the groups [196.3 ± 6.49 g (normal group) vs. 298.9 ± 6.67 g (negative control) vs. 215.3 ± 6.06 g (positive control) vs. 195.4 ± 3.92 g (FSP) vs. 213.1 ± 5.21 g (FerSP) vs. 190.8 ± 6.49 g (FS LD) vs. 198.9 ± 4.31 g (FS HD) vs. 204.7 ± 4.78 g (FerS LD) vs. 208.7 ± 6.21 g (FerS HD): p < 0.0001]. Network pharmacology studies indicated that the chemical components found in sisal juice primarily exert their effects by modulating the voltage-gated calcium channels CACNA1S, CACNA1D, and CACNA1C, in the beta cells of the islets of Langerhans.