# Antihyperglycemic Potential of Mace Water Extract from _Myristica_ fragments [PERSON]
## 3 Results and Discussion
### Correlation Between Clinical Parameters
This is proven by the FBG level of hyperglycemic rats, which reached > 400 mg/dL on the 7 th day after administration of streptozotocin. This hyperglycemic status is categorized as severe diabetes. Apart from the limited dosage and duration of ME intervention, the severe diabetic condition in hyperglycemic rats at the beginning of the experimental period is also thought to be the reason why the mace extract intervention in this study was unable to improve the glycemic status of hyperglycemic rats to the same or close to the glycemic status of normal rats. Nevertheless, ME still had a positive effect on several parameters observed in hyperglycemic rats when compared with negative controls (Table 4). This study used male Sprague Dawley rats as experimental animals. The selection of male rats helped to avoid the confounding effects of the hormonal cycle that could interfere with the effects of the studied intervention in the case of females. However, the inclusion of female animals in future studies should be considered to allow for investigating the effectiveness of the ME, taking into account sex-specific metabolic differences [59]. The effect of ME on glycemic parameters was evaluated based on the results of oral starch and glucose tolerance tests, as well as measurements of fasting blood glucose and HbA1c after 28 days of treatment. Compared with the negative control, ME intervention (dose B) was able to reduce the AUC value in the oral starch tolerance test by up to 12.56%. These results may suggest the ability of ME to inhibit the hydrolysis of starch into simpler molecules to glucose, which will then be absorbed into the circulatory system. The suggested inhibition of starch hydrolysis is in line with findings of previous in vitro studies, where ME showed an inhibitory effect on the \(\alpha\)-amylase enzyme with an IC\({}_{50}\) value of 360.18 \(\pm\) 6.83 mg phenolics / L [28]. The phenolic compounds contained in ME are suggested to play a role in inhibiting the \(\alpha\)-amylase enzyme. The complex that occurs between starch and polyphenols causes the side or part of starch that is normally hydrolyzed by digestive enzymes to become unrecognizable. The more starch bonds with polyphenols, the more sites cannot be recognized by digestive enzymes, so the ability of starch hydrolysis decreases. As a result, starch digestibility becomes low, which can suppress blood glucose spikes [16]. [PERSON] [21] also reported that inhibition of the \(\alpha\)-amylase enzyme by phenolic compounds was 4.5 times more effective in reducing IG than inhibition of the \(\alpha\)-glucosidase enzyme, through an uncompetitive type of inhibition. In addition, an oral glucose tolerance test was also conducted to see the effect of ME on the glycemic status of rats. Compared with the negative control, ME intervention was able to reduce the AUC value in the oral glucose tolerance test by 8.50%. These results suggest the possibility of inhibiting glucose absorption in the intestine as another mechanism of ME in inhibiting blood glucose spikes. In this case, ME is suggested to act as an inhibitor of glucose transporters in the intestine. Various glucose transfer pathways across the small intestinal epithelium and their contribution to glucose absorption were studied in recent years. Most researchers agree that glucose in the intestinal lumen is transferred across the apical membrane of enterocytes via active transport mediated by the SGLT1 transporter, whereas its exit into the bloodstream is carried out via facilitated diffusion mediated by the GLUT2 transporter localized on the basolateral membrane [60; 61; 62; 63]. Another hypothesis has been proposed that at high carbohydrate loads, the GLUT2 transporter may be rapidly inserted into the brush border membrane of enterocytes and participate in facilitated glucose diffusion across this membrane [60; 63].