STUDY OF THE MECHANISM OF ACTION OF ALPHA MANGOSTIN AND XANTHONE COMPUNDS AS ANTIDIABETIC

• Main Author: RATWITA - NIM: 30712302, WELLY
• Format: Dissertations
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/31568
• Institution: Institut Teknologi Bandung

<p align="justify">Objective: This research elaborated the role of ?-mangostin and xanthone on glucose and insulin tolerance, fasting blood glucose, plasma insulin and islet of Langerhans regeneration in alloxan induced diabetic mice, Glucose Transporter (GLUT)-4 by measuring GLUT-4 expression in cardiac muscle cell and adipocyte culture and peroxisome proliferator–activated receptor (PPAR)-? expression on adipocyte culture. We also elaborated the effect of ?-mangostin and xanthone as inhibitor for ?-glucosidase and glication, in order to find ?-mangostin and xanthone mechanism of action as antidiabetic agent. <br /> <br /> Methods: Glucose tolerance test were conducted using male wistar rat divided into 9 groups, which were normal, control (D-Glucose induced only), glibenclamide at 0.45 m/kgbw, ? mangostin and xanthone (at different dose ofdoses 5, 10, 20 mg/kgbw). All groups were induced with D-glucose 2 g/kgbw orally. Thirty minutes later, blood glucose level changes were observed at 60th to 150th minute. The insulin tolerance test used 45 male Wistar rats, which were divided randomly into the normal group, control group received only high fatty emulsion diet, treatment group which received high fat emulsion diet and ?-mangostin or xanthone at 5, 10 or 20 mg/kgbw, or metformin at dose of 45 mg/kgbw. Normal group received only regular drinking water, while control and treatment groups received a high fat emulsion for 10 days. Blood sugar level were measured six times after insulin administration (0.05 IU/kgbw) intraperitoneally, every 30 minutes for 150 minutes. Fasting blood glucose, insulin and islet of Langerhans examination were conducted using male Swiss webster mice, divided into 10 groups randomly, which were normal, control (alloxan induced only), glibenclamide at 0.65 mg/kgbw, various doses of ?-mangostin and xanthone (at 5, 10, or 20 mg/kgbw) for 21 days, then they were sacrificed by cervical decapitation on day 21st. Fasting blood glucose and insulin plasma were then measured. Pancreatic tissues were isolated from sacrificed animals, and then fixed in neutral buffered formalin. Histologic observations of the Islet of Langerhans were performed after staining using Gomori staining method. The heart was also isolated and kept in formaline buffered to be subsequently stained using immunohistochemistry to observed GLUT-4 expression. Adypocite was cultured to observed GLUT-4 and PPAR-? expression. In vitro study was carried out to measure inhibition of ?-glucosidase and glycation using spectrophotometer 530 nm. <br /> <br /> Results: Normal group (non diabetic) responded slightly to the administration of glucose in glucose tolerance test. Blood glucose level in every group in the 90th to 150th minute decreased significantly when compared to the control group (p <0.05). This showed that glucose tolerance increased in all treated groups althought they were treated with high glucose consentration. Coefficient of insulin tolerance test in ?-mangostin groups were significantly different (p<0.05) when compared to the control group, except in group treated with xanthone at dose 5 mg/kgbw. This suggests that ?-mangostin 5, 10 and 20 mg/kgbw, xanthone 10 and 20 mg/kgbw, as well as metformin at 45 mg/kgbw, increased insulin tolerance in Wistar rats given fatty emulsion for ten days. The effects of ?-mangostin and xanthone on fasting blood glucose were not significantly different from glibenclamide and metformin. Plasma insulin analysis showed that there were no significant difference between 20 mg/kgbw ?-mangostin compared with control. Alpha mangostin, xanthone had magnificant effect on the islet of Langerhans compared to control group and glibenclamid and metformin groups. GLUT-4 expressions in mice cardiac muscle cells treated with ?-mangostin, xanthone, glibenclamide, and metformin significantly increased when compared to the control group, except in group treated with xanthone at dose 5 mg/kgbw. These increasing were not significantly different from glibenclamide and metformin. GLUT-4 expressions also increased in adipocytes treated with 3.13 mM; 6.25 mM and 25 mM ?-mangostin. All treatment group results were significantly different when compared with control. The effect of ?-mangostin on GLUT-4 expression was better than that of xanthone. Almost similar as pioglitazone, ?-mangostin and xanthone increased PPAR-? expression in adipocyte, but the effect of xanthone was not as good as that of ?-mangostin or pioglitazone effect. IC50 of ?-mangostin for ?-glucosidase was better than acarbose and xanthone, while IC50 of pyridoxamine for glycation was better than ?-mangostin and xanthone. <br /> <br /> Conclusion: Alpha mangostin and xanthone are two substances that may improve glucose and insulin tolerance. In addition they showed antidiabetic effect by improving fasting blood glucose level, insulin plasma and the regeneration of islet of Langerhans, GLUT-4 expression in cardiac muscle and adipocyte, PPAR-? expression in adipocyte, and also ?-glucosidase and glycation inhibiting activities.<p align="justify"> <br /> <br />