Synergistic antihyperglycaemic effect of combination therapy with gallic acid and andrographolide in streptozotocin-induced diabetic rats

Previous studies had reported on the antidiabetic effect of gallic acid and andrographolide, as monotherapy, in diabetic rats. However, studies on the combination effect of gallic acid and andrographolide in treating diabetes are lacking. Hence, the objective of this study was to investigate the antihyperglycaemic activity of combined gallic acid and andrographolide in streptozotocin-induced diabetic rats compared to single compound treatment. Diabetes was induced with streptozotocin (40 mg/kg, intraperitoneally) in male Sprague Dawley rats. After 7 days, all rats were divided into 8 groups as follows: normal control and diabetic control groups given distilled water, diabetic groups treated with gallic acid (10 or 20 mg/kg), andrographolide (5 or 10 mg/kg), or both in 2:1 combination ratio of gallic acid:andrographolide (10:5 or 20:10 mg/kg). All treatments were given orally, once daily for 15 consecutive days. Non-fasting blood glucose, food and water intake were measured weekly. On day 14, an oral glucose tolerance test was performed. Our results showed that the combination treatment of gallic acid and andrographolide synergistically reduced blood glucose compared to single compound treatment, with higher synergistic effect and favourable dose reduction at higher combination dose. Furthermore, the combination treatment significantly improved glucose tolerance, with significantly reduced area under the curve in diabetic rats. The combination treated diabetic group also demonstrated normalization of their daily food and water intake. In conclusion, our results indicated that the combination therapy at 2:1 combination ratio of gallic acid:andrographolide demonstrated synergistic hypoglycaemic activity with favourable dose reduction in experimental diabetic rats.