Sonographic Investigation Of The Effect Of Gongronema Latifolium On Gastric Emptying Of Semi - Solid Meals In Healthy, Diabetic And Gastroparetic Dogs

ABSTRACT

Gongronema latifolium is an edible tropical rainforest plant traditionally used as a spice,

staple vegetable and in the treatment and management of diabetes. Extensive studies have

established its hypoglycaemic effect. However, scanty information is available on the

mechanism by which it exerts its hypoglycaemic effect. Studies have noted the presence of

saponin in G. latifolium, a component noted to affect gastric emptying (GE). Presently, the

possible effect of G. latifolium on GE has not been investigated. Chronic diabetes may

precipitate gastroparesis. How such condition may respond to treatment with G. latifolium is

yet to be investigated. Therefore, this study investigated sonographically the possible effect

of G. latifolium on GE in healthy and diabetic dogs. It also investigated if the effect of G.

latifolium on GE in healthy and/or diabetic dogs is dose-dependent. The study further

ascertained the relationship between its hypoglycaemic effect and GE. Finally, it investigated

the possible effect of G. latifolium on GE in gastroparetic dogs. In a randomized placebocontrolled

experimental design, sixty mongrel dogs whose mean age of 6.07 ± 0.80 months

and mean weight of 5.20 ± 1.23kg did not vary significantly (p > 0.05) were randomly

allotted to healthy, diabetic and gastroparetic groups. Twenty dogs in each group were

randomly allotted into five subgroups. The subgroups were the placebo that served as control,

low dose (100mg/kg), moderate dose (250mg/kg) and high dose (500mg/kg) of G. latifolium.

A prokinetic dose of 0.5mg/kg of metoclopramide also served as a positive control.

Intravenous injection of 100mg/kg of alloxan monohydrate was used to induce diabetes and

0.03mg/kg of clonidine injected subcutaneously in the back of the neck immediately after

ingestion of a test meal, was used to induce gastroparesis. G. latifolium was extracted with

80% methanol. The coarse powdered extracts were pulverised, sieved, weighed out in doses

of 100mg, 250mg and 500mg and subsequently encapsulated. After a 12 - hour fast, each dog

was dosed once orally with the appropriate extract or drug depending on the group, 30

minutes before the administration of the test meal. The test meal used consisted of 100g

Nestle cerelac and 150ml of water. GE was estimated by ultrasound measurements of gastric

antral area. Antral images were acquired 30 minutes before ingestion of test meal and at

regular intervals for the next six hours. Initial baseline measurements of the antral area were

taken, from which subsequent measurements after the ingestion of the test meal were

subtracted. All measurements were expressed as percentage of the maximal antral area

measured during each test and plotted against time. Gastric antral area was measured

concurrently with blood glucose concentrations using glucometer. The percentage maximal

antral area and incremental blood glucose concentrations were computed and plotted against

time respectively. The time in minutes at which the antral area decreased to 50 percent of its

maximal area (T50) was used to describe the rate of GE. The blood glucose area under the

curve (AUC) in mmol/L x minutes was calculated from the incremental postprandial blood

glucose curve. All values were expressed as mean ± standard deviation. ANOVA with

Dunnett’s post test were used to compare the means of the groups with control. Paired t test

was used to compare pre and post intervention values while Pearson correlation was used to

assess the linear association between the values of two variables. These analyses were

performed using SPSS version 15.0 and GraphPad prism version 5.03. Probability (p) values

less than 0.05 were considered significant. The GE in minutes in healthy dogs were 135.5 ±

3.5, 155.5 ± 3.9 ,198 ± 5.3 and 59 ± 2.5 for low, moderate, high doses of G. latifolium and

prokinetic dose respectively whereas for the diabetic dogs the values were 169.8 ± 3.8, 227.8

± 9.9, 261.3 ± 19.3 and 107.3 ± 13.2 respectively. The values for the control that received the

placebo were 126.6 ± 8.2 for the healthy and 143 ± 17.8 for the diabetics.

In both the healthy and diabetic dogs treated with G. latifolium the GE values were

significantly longer (p < 0.0001) compared with the placebo groups for only moderate and

high doses. There was no significant (p > 0.05) difference between the low dose and the

control in health and diabetes. The prokinetic groups GE were significantly shorter in healthy

(p < 0.0001) and diabetics (p < 0.001) compared with their placebo controls. Significant

positive correlations between dose and GE were noted in healthy (r = 0.94; p < 0.0001) and

diabetics (r = 0.98; p < 0.0001) treated with G. latifolium. The dose trends of G. latifolium on

GE were also significant (p < 0.0001) in healthy and diabetics. The blood glucose AUC in

healthy dogs were 938.1 ± 40, 559.1 ± 101.8 , 223.5 ± 52.2 and 1426 ± 108.2 for low,

moderate, high doses of G. latifolium and the prokinetic dose respectively whereas for the

diabetic dogs the values were 3357 ± 539.1, 1905 ± 434 , 385.3 ± 298.1 and 6485 ± 322.4

respectively. The values for the controls were 1028.6 ± 204.2 for the healthy and 3453 ±

217.6 for the diabetics. A strong inverse relationship between the hypoglycaemic effect of G.

latifolium and GE was noted in healthy (r = -0.95; p < 0.0001) and diabetics (r = -0.90; p 0.05) difference between the GE of low, moderate and high doses of

G. latifolium and the control whereas the prokinetic group GE values were significantly

shorter (p< 0.001) compared with gastroparetic control.