Evaluation of the hypoglycemic, hypolipidemic and anti alpha amylase effects of extracts of the twigs and fruits of ficus ovata vahl (moraceae)

LIST OF FIGURES

Figure 1: The role of the pancreas in glucose homeostasis 3

Figure 2: Type 1 Diabetes mellitus 7

Figure 3: Type 2 Diabetes mellitus 8

Figure 4: Metabolic syndrome 11

Figure 5: Lipoprotein metabolism 12

Figure 6: Hyperglycemia induced endothelial dysfunction 13

Figure 7: Action site of western medicine in diabetes treatment 15

Figure 8: Hepatic fructose metabolism: highly lipogenic pathway 21

Figure 9: Protocol for the extraction by maceration in ethanol and hydroethanol (1:1) 26

Figure 10: Mechanism of pancreatic alpha-amylase activity 30

Figure 11: Antiradical activity of extracts using DPPH method 42

Figure 12: Effect of extracts on the inhibition of pancreatic á-amylase activity 43

Figure 13: Effect of extracts on variation of body weight during toxicity 44

Figure 14: Effect of extracts on fasting blood glucose after experimentation 46

Figure 15: Effect of extracts on nitric oxide level in the plasma and heart 48

LIST OF TABLES

Table I: Diabetes classification: etiologic types and stages 3

Table II: Polarity and chemical profiles of most of the common extraction solvents 19

Table III: Uses of some Ficus in traditional pharmacopoeia to treat diabetes 23

Table IV: Previous work on the biological activities of some Ficus 24

Table V: Preparation of the working solution of our extracts 28

Table VI: Methodology of á-amylase inhibition 31

Table VII: Repartition of animals for acute toxicity study of extracts 32

Table VIII: Repartition of animals for the hypoglycemic test 33

Table IX: Repartition of animals for the antihyperglycemic test 33

Table X: Slightly modify food composition as proposed by Dhandapani (2007) 34

Table XI: Repartition of animals for the preventive treatment with extracts 34

Table XII: Yield of extraction 41

Table XIII: The phytochemical screening results. 41

Table XIV: Polyphenols content results 42

Table XV: Behaviour of rats during acute toxicity study (48hours) 43

Table XVI: Effect of extracts on markers of toxicity (ASAT, ALAT and Creatinine) 44

Table XVII: Hypoglycemic effects of extracts on hyperglycemic rats 45

Table XVIII: Antihyperglycemic effect of extracts on normal rats 45

Table XIX: Effect of extracts on the variation of body weight 46

Table XX: Effect of extracts on the markers of lipid profile after experimentation 47

Table XXI: Effect of extracts on the activity of transaminases (ASAT, ALAT), creatinine and total protein levels 48

ABSTRACT

The phytochemical components of many medicinal plants have most often been linked to the modulation of biomarkers associated to diabetes type 2. This study was aimed at evaluating the anti á-amylase, antihyperglycemic, hypoglycemic and antihyperlipidemic activities of twigs and fruits extracts of Ficus ovata.

Hydroethanolic and ethanolic extracts of twigs and fruits of F. ovata were prepared and used for the phytochemical analysis and antioxidant potential screening in vitro. The most active extracts were selected for the evaluation of in vitro antiamylase activity, acute toxicity study as well as their effects on fasting (hypoglycemic test) and postprandial (antihyperglycemic test) blood glucose levels. In addition, the preventive effects of the extracts against some biomarkers of diabetes (body weight, fasting blood glucose, lipid profile, endothelia dysfunction, hepatic and renal toxicities) were evaluated at dose of 300mg/kg of body weight in rats fed on high fructose-high cholesterol diet for 14 days.

Phytochemical screening revealed the presence of alkaloids, tannins, saponins, glycosides, phenols and flavanoids in all extracts except phlobatannin that was absent in the fruit extracts. Fruits extracts had the highest polyphenol content (EF= 718.142 #177; 12.910 mg CatEq vs HF= 486.876 #177; 8.606 mg CatEq; P< 0.05) and the best DPPH antiradical scavenging effect (IC₅₀; EF= 2.7mg/ml, HF=0.70mg/ml) compared to twigs (P< 0.05). Hydroethanolic twigs and fruits (FOHT and FOHF) extracts selected were the most active for each plant part. FOHF had significantly high (p=0.05) antiamylase effects as compared to FOHT and both FOHT and FOHF were weakly toxic since no dead was recorded at LD50>5000mg/Kg of BW. In addition, both extracts had hypoglycemic and antihyperglycemic effects (percentage decrease 8.908% vs 5.747% and 21.566% vs 8.208% respectively) with FOHT being more active than FOHF(p=0.05). Finally, the preventive study results show that, co-administration of extracts especially FOHF was observed to significantly reduce fasting blood glucose (p<0.05), Triglyceride (p<0.05), Total & LDL-Cholesterol (p<0.05), creatinine and total protein levels, and significantly increase HDL-Cholesterol (p<0.05) and Nitric oxide (plasma; P< 0.05) levels. Thus the extracts enable us to maintain or ameliorate these changes to nearly normal levels and reveal its preventive effects.

These results suggest that FOHF and FOHT could be of interest in the prevention of hyperlipidemia and hyperglycemia associated with type 2 diabetes.

Key words: antihyperglycemia, antihyperlipidemia, diabetes, Ficus ovata, hypoglycemia.