Developing agents for management of DM that are devoid of adverse effects are still a challenge to the medical care system. Thus, research is increasingly done on medicinal plants with the hope of developing a relatively safe antidiabetic plant-based product alone or in combination with other agents [29
]. In this study, no detectable changes were observed in baseline BGL across groups in both normal (Table ) as well as diabetic animals (Table ), however, significant reductions started to appear when the hydroalcoholic extract and the standard drug were administered, indicating that changes produced were attributed to treatments received. Therefore, the results of this study indicated that hydroalcoholic extract of C. abyssinica
reduces BGL level in normal and diabetic mice as well as in glucose induced hyperglycemic rats.
Among the various doses of the extract, maximum activity was observed with CA200 in all tests. It is interesting to note that CA200 was capable of bringing down streptozocin-induced hyperglycemia close to TW80 and GL-5 values (Table ). The extract also brought the hyperglycemic state in OGTT down within 60
min in the same manner to that of glybenclamide (Table ). Thus, it is plausible to assume that the plant extract and glibenclamide might produce hypoglycemic and antidiabetic effects by a similar mechanism (i.e. by enhancing insulin release or insulin-like effect). Extracts of other plants, including Cassia italic
] and Vinca rosea
] have been reported to have similar mode of action with that of glibenclamide, lending evidence to this assertion.
It was observed that the extract exerted its action in a non-dose dependent manner, particularly the higher dose produced less activity. CA300 did produce a delayed but significant hypoglycemia and antidiabetic action, although it did not improve oral glucose tolerance. The highest dose determined was 400
mg/kg, however, this dose produced an increase in BGL during the preliminary analysis that led to its exclusion from the study. This observation suggests that activity might decrease with dose. BGL reduction, probably, is the net effect of the interplay between various constituents of the extract. It is likely that higher doses may activate non-specifically both BGL lowering and rising mechanisms. Indeed, it has been reported that the presence of interfering substances in plant extracts may diminish hypoglycemic effect [12
]. It is also likely that bigger doses could cause some toxic effect [35
] to specific targets of glucose lowering mechanisms, which could have been the target for hypoglycemic agents.
On the other hand, the lower dose (100
mg/kg) of the extract appeared to be ineffective in reducing BGL in normal (Table ) and glucose loaded animals (Table ). This could be attributed to inability of the dose to overcome counter-regulatory physiological mechanisms [36
], lesser concentration of the active principles to induce hypoglycemia or the small sample size employed that precluded statistical significance. On the other hand, CA100 produced antidiabetic action in streptozocin-induced mice, which might imply that the hypoglycemic nature of the lower dose would be apparent when there is an alteration in normal blood glucose regulatory systems by diabetes.
The results also showed that antidiabetic activity of the extract increased with time, as maximal effect was achieved at the 4th
h (Table ). This could mean that the active principles in the extract need time to reach sufficient concentration at the target site, as a similar pattern was observed with other plants displaying anti-diabetic activity [37
]. The plant extract showed relatively faster antidiabetic onset of action than the standard drug. However, the doses of C. abyssinica
extract exhibited a varied onset of action, which probably resulted from interference of other principles, particularly at higher doses. Constituents such as reducing sugars that have a higher glycemic index could give rise to free glucose after digestion and they may tend to raise BGL following absorption. The appearance of such an effect in the face of the hypoglycemic actions by the active agents could lead to a delay in appearance of the action, especially at higher doses where the extract may result in higher concentrations of such molecules.
Interestingly, in OGTT the hydroalcolic extract showed significant reduction in BGL from 60
min onwards except for the higher dose. This suggests that the extract is endowed with the ability to enhance glucose regulatory mechanisms, reflecting a potential advantage of the extract in minimizing hyperglycemia related complications of diabetes. This is true provided that the extract happens to demonstrate a similar action with repeated administration.
Preliminary phytochemical screening of the hydroalcoholic extract of C. abyssinica
demonstrated the presence of secondary metabolites (Table ), which are known to produce hypoglycemic effects in other plants by various mechanisms [18
]. No previous phytochemical reports could be found in the literature concerning the genus Caylusea. However, other members of the family Resedaceae such as Reseda muricata
and Randonia africana
have been reported to contain flavonoids, phenolic compounds, glycosides and alkaloids [40
], which are in line with the current findings. Thus, the antidiabetic, hypoglycemic and enhanced glucose utilization effect of the hydroalcoholic extract of C. abyssinica
may be associated with the presence of these different secondary metabolites that act individually or synergistically.