Microhemodynamic indices to evaluate the effectiveness of herbal medicine in diabetes: A comparison between alpha-mangostin and curcumin in the retina of type 2 diabetic rats.

OBJECTIVE: This study was aimed to develop microhemodynamic indices to evaluate the effectiveness of herbal medicine in diabetic tissues. METHODS: Male Sprague-Dawley rats were divided into four groups: normal control rats (Control), type 2 diabetic rats without (DM2) and with supplementation of alpha mangostin (DM2-MG) or curcumin (DM2-CUR). Alpha-mangostin or curcumin (200 mg/kg BW) were fed followed by i.p. injection of streptozotocin (STZ). Mean arterial pressure (MAP) and retinal blood flow (RBF) were measured and retinal flow resistance (RFR) was calculated. Three indices were developed to evaluate the effectiveness of herbal medicines in RFR-MAP diagram based on experimental data of MAP and RFR in type 2 diabetic rats. These indices are α, ß, and γ where α is a ratio of reduction in MAP, ß is a ratio of reduction in RFR increasing with MAP increase, and γ indicates a ratio of reduction in RFR. RESULTS: The elevated MAP and RFR and decreased RBF were observed in DM2 rats.Interestingly, alpha-mangostin or curcumin supplementation significantly increased RBF while decreased MAP and RFR. Using α, ß and γ indices, it was found that alpha-mangostin is more effective than curcumin in type 2 diabetic retina. CONCLUSIONS: These microhemodynamic indices may be useful to compare various herbal medicines in different tissues.

Alpha-mangostin attenuation of hyperglycemia-induced ocular hypoperfusion and blood retinal barrier leakage in the early stage of type 2 diabetes rats.

The present study examined effects of alpha-mangostin (α-MG) supplementation on the retinal microvasculature, including ocular blood flow (OBF) and blood-retinal barrier (BRB) permeability in a type 2 diabetic animal model. Male Sprague-Dawley rats were divided into four groups: normal control and diabetes with or without α-MG supplementation. Alpha-mangostin (200 mg/Kg/day) was administered by gavage feeding for 8 weeks. The effects of α-MG on biochemical and physiological parameters including mean arterial pressure (MAP), OBF, and BRB leakage were investigated. Additionally, levels of retinal malondialdehyde (MDA), advance glycation end products (AGEs), receptor of advance glycation end products (RAGE), tumour necrosis factor alpha (TNF-α), and vascular endothelial growth factor (VEGF) were evaluated. The elevated blood glucose, HbA1c, cholesterol, triglyceride, serum insulin, and HOMA-IR were observed in DM2 rats. Moreover, DM2 rats had significantly decreased OBF but statistically increased MAP and leakage of the BRB. The α-MG-treated DM2 rats showed significantly lower levels of retinal MDA, AGEs, RAGE, TNF-α, and VEGF than the untreated group. Interestingly, α-MG supplementation significantly increased OBF while it decreased MAP and leakage of BRB. In conclusion, α-MG supplementation could restore OBF and improve the BRB integrity, indicating its properties closely associated with antihyperglycemic, antioxidant, anti-inflammatory, and antiglycation activities.

Effects of Long-Term Alpha-mangostin Supplementation on Hyperglycemia and Insulin Resistance in Type 2 Diabetic Rats Induced by High Fat Diet and Low Dose Streptozotocin.

OBJECTIVE: The present study investigated the effects of long-term supplementation of alpha-mangostin (MG; a xanthone isolated from mangosteen fruit) on hyperglycemia, and insulin resistance in type 2 diabetic rats. MATERIAL AND METHOD: Type 2 diabetes (DM2) was induced in male Sprague-Dawley rats by feeding high fat diet for three weeks followed by an IP injection of low dose streptozotocin. The rats were divided into four groups: control and diabetes without or with alpha-MG supplementation (CON, DM2, CON-MG and DM2-MG group, respectively). Alpha-MG was administered by gavage feeding in the amount of 200 mg/kg BW/day for 8 or 40 weeks. Fasting blood glucose, plasma HbA1c, cholesterol, and triglyceride were determined in all groups of rats. Serum insulin, calculated HOMA-IR and Oral glucose tolerance test were also carried out. RESULTS: The results showed that both 8 and 40 weeks DM2 groups had a significant increase in fasting blood glucose, HbA1c, plasma cholesterol and triglyceride compared with their aged-match control groups. Furthermore, the serum insulin and HOMA-IR were significantly elevated in 8 weeks DM2 whereas these two parameters were significantly decreased in 40 weeks DM2 group compared with their aged-match CON groups (p < 0.001). The OGTT showed impaired glucose tolerance in DM2 groups. Interestingly, alpha-MG supplemented DM2-MG group had significantly decreased levels of fasting blood glucose, HbA1c, plasma cholesterol, triglyceride when compared with the untreated DM2 groups. Supplementation of alpha-MG for 40 weeks in DM2-MG group showed significantly increase serum insulin levels compared with that of DM2 group (p < 0.001). Moreover alpha-MG supplemented DM-MG group demonstrated a better glucose tolerance pattern which was different from that of DM2 group at both 8 weeks and 40 weeks experimental periods. CONCLUSION: Long-term alpha-mangostin supplementation has anti-hyperglycemic, anti-hyperlipidemic effects and increase insulin sensitivity by improving beta-cell functions in type 2 diabetes mellitus.