ABSTRACT
Plant species in the genus Agave, including Agave sisalana, 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 Agave salmiana) in Mexico by diabetic patients to improve their diabetic condition, this study investigated the effects of Agave sisalana 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 A. sisalana 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 A.sisalana 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.
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Rotheca myricoides (Hochst.) Steane & Mabb is a plant species used in traditional medicine for the management of diabetes in the lower eastern part of Kenya (Kitui, Machakos and Makueni Counties, Kenya) that is mainly inhabited by the Kamba community. AIM: This study investigated the antihyperglycaemic, antidyslipidemic and antihyperinsulinemic activity of the freeze-dried extracts of Rotheca myricoides (Hochst.) Steane & Mabb (RME) in an animal model of type 2 diabetes mellitus. METHODS: Type 2 diabetes was induced by dietary manipulation for 56 days via (high fat- high fructose diet) and intraperitoneal administration of streptozocin (30â¯mg/kg). Forty freshly-weaned Sprague Dawley rats were randomly assigned into the negative control (high fat/high fructose diet), low dose test (50mg/kg RME, high dose test (100mg/kg RME and positive control (Pioglitazone, 20mg/kg) groups. Fasting blood glucose and body weight were measured at weekly intervals. Oral glucose tolerance tests were performed on days 28 and 56. Lipid profile, hepatic triglycerides, fasting serum insulin levels and serum uric acid were determined on day 56. RESULTS: The RME possessed significant antihyperglycemic [FBG: 6.5⯱â¯0.11â¯mmol/l (negative control) vs. 4.62⯱â¯0.13â¯mmol/l (low dose test) vs. 5.25⯱â¯0.15â¯mmol/l in (high dose test) vs. 4.33⯱â¯0.09â¯mmol/l (positive control): pâ¯<â¯0.0001] and antihyperinsulinemic effects [1.84⯱â¯0.19 (negative control) vs. (0.69⯱â¯0.13 (low dose test) vs. (0.83⯱â¯0.17 (high dose test) vs. (0.69⯱â¯0.10 (positive control): F (3, 36)â¯=â¯0.6421: pâ¯<â¯0.0001. The extracts also possessed significant antidyslipidemic effects [LDL levels: 3.52⯱â¯0.19â¯mmol/l (negative control) vs. 0.33⯱â¯0.14â¯mmol/l (low dose test) vs. 0.34⯱â¯0.20â¯mmol/l (high dose test) vs. 0.33⯱â¯0.01â¯mmol/l (positive control): pâ¯<â¯0.0001].RME significantly lowered plasma uric acid levels, as well as hepatic triglycerides and hepatic weights. Network pharmacology analysis indicated that the observed pharmacological effects are mediated via the modulation of Peroxisome proliferator-activated gamma receptor. CONCLUSIONS: The freeze dried extracts of Rotheca myricoides possessed significant antihyperglycemic and antidyslidemic effects. In addition it lowered serum uric levels, as well as hepatic triglycerides and hepatic weight. These results appear to validate the traditional use of this plant species in the management of diabetes mellitus.
