Andrographolide Pretreatment Enhances the Bioavailability and Hypoglycemic Action of Glimepiride and Metformin

Sujatha Samala, Ciddi Veeresham


Herbal antidiabetic preparations are often used as an add-on therapy in diabetes. Hence, in the present investigation the effect of andrographolide (AD) on the pharmacokinetics and pharmacodynamics of glimepiride and metformin in normal as well as in STZ - induced diabetic rats was studied. In normal and diabetic rats the combination of glimepiride and metformin with AD increased significantly (p < 0.01) all the pharmacokinetic parameters, such as Cmax, AUC0 to n, AUCtotal, t½, MRT and decreased the clearance, Vd markedly as compared with the control group. In pharmacodynamic studies, the combination of glimepiride and metformin with AD provided significant protection against the diabetes induced alterations in the biochemical parameters. In addition, the combination of glimepiride and metformin with AD also improved the total antioxidant status and decreased lipid peroxide levels significantly in diabetic rats compared with AD, glimepiride and metformin alone treated groups. The results revealed that combination of glimepiride and metformin with AD led to the enhancement of the bioavailability of glimepiride and metformin by inhibiting the CYP450 enzymes. In conclusion, add-on preparations containing AD may increase the bioavailability of glimepiride and metformin, which suggested that AD might be beneficial as an adjuvant to glimepiride and metformin in a proper dose, in diabetic patients and hence the doses should be monitored.


Glimepiride; Metformin; Andrographolide; Pharmacokinetics; Pharmacodynamics

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. Kelly JP, Kaufman DW, Kelley K, Rosenberg L, Anderson TE, Mitchell AA. Recent trends in use of herbal and other natural products. Arch Intern Med. 2005; 165: 281-286.

. Fakeye TO, Oladipupo T, Showande O, Ogunremi Y. Effects of co administration of extract of Carica papaya Linn (Cariaceae) on activity of two oral hypoglycemic agents. Trop J Pharm Res. 2007; 6: 671-678.

. Veeresham C, Sujatha S, Sandya rani T. Effect of piperine on the pharmacokinetics and pharmacodynamics of glimepiride in normal and streptozotocin induced diabetic rats. Natural Product Communications. 2012; 7: 1283-1286.

. Sandya rani T, Sujatha S, Veeresham C. Pharmacokinetic and pharmacodynamic interaction of curcumin with glimepiride in normal and diabetic rats. Pharmacognosy Communications. 2012; 2: 14-21.

. Anil Kumar, Jyotsna D, Anup Singh, Tripathi R. A review on king of bitter (Kalmegh). Int J Res Pharm Chem. 2012; 2: 116-124.

. Shen YC, Chen CF, Chiou WF. Andrographolide prevents oxygen radical production by human neutrophils: possible mechanism(s) involved in its anti-inflammatory effect. Br J Pharmacol. 2002; 135: 399-406.

. Kumar RA, Sridevi K, Kumar NV, Nanduri S, Rajagopal S. Anticancer and immunostimulatory compounds from Andrographis paniculata. J Ethnopharmacol. 2004; 92: 291-295.

. Thisoda P, Rangkadilok N, Pholphana N, Worasuttayangkurn L, Ruchirawat S, Satayavivad J. Inhibitory effect of Andrographis paniculata extract and its active diterpenoids on platelet aggregation. Eur J Pharmacol. 2006; 553: 39-45.

. Calabrese C, Berman SH, Babish JG, Ma X, Shinto L, Dorr M, Wells K, Wenner CA, Standish LJ. A phase I trial of andrographolide in HIV positive patients and normal volunteers. Phytother Res. 2000; 14: 333-338.

. Yu BC, Hung CR, Chen WC, Cheng JT. Antihyperglycemic effect of andrographolide in streptozotocin induced diabetic rats. Planta Med. 2003; 69: 1075-1079.

. Singha PK, Roy S, Dey S. Protective activity of andrographolide and arabinogalactan proteins from Andrographis paniculata Nees. against ethanol-induced toxicity in mice. J Ethnopharmacol. 2007; 111: 13-21.

. Qiu F, Hou XL, Takahashi K, Chen LX, Azuma J, Kang N. Andrographolide inhibits the expression and metabolic activity of cytochrome P450 3A4 in the modified Caco-2 cells. J Ethnopharmacol. 2012; 141: 709-713.

. Ooi JP, Kuroyanagi M, Sulaiman SF, Sifzizul T, Muhammad T, Tan ML. Andrographolide and 14-Deoxy-11,12-Didehydroandrographolide inhibit cytochrome P450s in HepG2 hepatoma cells. Life Sci. 2011; 88: 447-454.

. Pekthong D, Martin H, Abadie C, Bonet A, Heyd B, Mantion G, Richert L. Differential inhibition of rat and human hepatic cytochrome P450 by Andrographis paniculata extract and andrographolide. J Ethnopharmacol. 2008; 115: 432-440.

. Chien CF, Wu YT, Lee WC, Lin LC, Tsai TH. Herb-drug interaction of Andrographis paniculata extract and andrographolide on the pharmacokinetics of theophylline in rats. Chem Biol Int. 2010; 184: 458-465.

. Pekthong D, Blanchard N, Abadie C, Bonet A et al. Effects of Andrographis paniculata extract and Andrographolide on hepatic cytochrome P450 mRNA expression and monooxygenase activities after in vivo administration to rats and in vitro in rat and human hepatocyte cultures. Chem Biol Int. 2009; 179: 247-255.

. Robkamp R, Wernicke-Panten K, Draeger E. Clinical profile of the novel sulphonylurea glimepiride. Diabetes Res Clin Pr. 1996; 31: S33-S42.

. Choi YH, Lee U, Lee BK and Lee MG. Pharmacokinetic interaction between itraconazole and metformin in rats: competitive inhibition of metabolism of each drug by each other via hepatic and intestinal CYP3A1/2. Br J Pharmacol. 2010; 161: 815-829.

. Riley V. Adaptation of orbital bleeding technique to rapid serial blood studies. Experi Biol Med. 1960; 104: 751-754.

. Tuitoek PJ, Ziari S, Tsin ATC, Rajotte RV, Miyoung S, Tapan KB. Streptozotocin-induced diabetes in rats is associated with impaired metabolic availability of vitamin A (retinol). Br J Nutr. 1996; 75: 615-622.

. Sujatha S, Sandhya Rani T, Veeresham C. Determination of glimepiride in rat serum by RP-HPLC method. Ame J Anal Chem. 2011; 2: 160-165.

. Wanjari MM, There AW, Tajne MR, Chopde CT and Umathe SN. Rapid and simple RP-HPLC method for the estimation of metformin in rat plasma. Indian J Pharm Sci. 2008; 70: 198-202.

. Trinder P. Determination of blood glucose using 4-amino phenazone as oxygen acceptor. J Clin Pathol. 1969; 22: 246.

. Sachin LB, Subhash LB. Interaction of aqueous extract of Pleurotus pulmonarius (Fr.) Quel.-Champ with acarbose in alloxan induced diabetic mice. J Appl Biomed. 2007; 5: 157-166.

. Syed mansoor A, Vrushabendra swamy BM, Dhanapal PGR, Chandrashekara VM. Antidiabetic activity of Terminalia catappa Linn. leaf extracts in alloxan-induced diabetic rats. Iranian J Pharmacol Ther. 2005; 4: 36-39.

. Reddy YN, Murthy SV, Krishna DR, Prabhakar MC. Role of free radicals and antioxidants in tuberculosis patients. Indian J Tuberc. 2004; 51: 213-218.

. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by Thiobarbituric acid reaction. Anal Biochem. 1979; 95: 351-358.

. Chakrabarti S, Tuhin KB, Tapan S, Begum R, Liaquat A, Azad Khan AK, Nilufer N, Mosihuzzaman M, Biswapati M. Antidiabetic activity of Caesalpinia bonducella F in chronic type 2 diabetic model in Long-Evans rats and evaluation of insulin secretagogue property of its fractions on isolated islets. J Ethnopharmacol. 2005; 97: 117-122.

. Felig P, Marliss E, Ohman J, Cahill JF. Plasma amino acid levels in diabetic ketoacidosis. Diabetes. 1970; 19: 727-730.

. Chakrabarti R, Rajagopalan R. Diabetes and insulin resistance associated disorders: disease and the therapy. Curr Sci. 2002; 83: 1533-1538.

. Abdel-Zaher AO, Salim SY, Assaf MH, Abdel-Hady RH. Antidiabetic activity and toxicity of Zizyphus spinachristi leaves. J Ethnopharmacol. 2005; 101: 129-138.


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