ABSTRACT
Tylosema fassoglense (TFG) is used as an antidiarrheal traditional medicine in Western Kenya. This study aimed to investigate the antidiarrheal activity of its aqueous extracts in-vivo and the putative mechanism (s) of action ex-vivo using Sprague-Dawley rats and New Zealand white rabbits respectively. The in-vivo antidiarrheal effects of the extract were evaluated in castor oil-induced diarrhea, the castor oil-induced enteropooling, and phenol red gastric motility tests. On the other hand, isolated rabbit's jejunal segments were used to evaluate the spasmolytic effect of TFG on spontaneous contraction, in acetylcholine-induced contraction, in presence of 80mMK+, calcium chloride-induced contraction as well as in presence of the following antagonists: naloxone, methylene blue, L-NAME, prazosin, and propranolol in the ex-vivo studies. The data were express as Mean ± S.E.M and analyzed by one-way ANOVA and Tukey's post hoc test in cases of significance which was set at p < 0.05. The extract was phytochemically characterized using Liquid chromatography Mass spectroscopy (LC-MS).The extract possessed significant inhibitory effect in the in-vivo experiments. The extract exhibited significant spasmolytic effect on both spontaneous contraction and in jejunal segment pre-contracted acetylcholine as well as in presence of 80mMK+ solution. It also attenuated the spasmogenic effect of various concentration of calcium chloride. The extract's spasmolytic effect was, however, significantly attenuated in presence of several antagonists (methylene blue and L-NAME) but the adrenergic blockers (prazosin and propranolol) had no significant effect in the ex-vivo studies. LC-MS identified thirty compounds where Proathocyanidin (11.54%), Syringic acid (7.30%), and 4-Hydroxybenzoic acid (6.19%) had the highest percentage abundance. In conclusion, the results obtained in this study partially validate the traditional uses of the tubers of this plant species as an antidiarrheal. These antidiarrheal effects are probably mediated via modulation of nitrous oxide pathway, voltage gated calcium channels, and muscarinic receptors.
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.
