Volume 1 • Issue 4• 1000116 Nat Prod Chem Res ISSN: 2329-6836 NPCR, an open access journal Samala and Veeresham, Nat Prod Chem Res 2013, 1:4 DOI: 10.4172/2329-6836.1000116 Research Article Open Access Enhanced Bioavailability of Glimepiride in the Presence of Boswellic Acids in Streptozotocin-Induced Diabetic Rat Model Sujatha Samala* and Ciddi Veeresham University College of Pharmaceutical Sciences, Kakatiya University, Warangal, AP-506009, India Abstract The effect of Boswellia serrata standardized extract (BSE) and Boswellic acids (BA) on the pharmacokinetics and pharmacodynamics of glimepiride in normal as well as diabetic rats was studied. In normal and streptozotocin induced diabetic rats the combination of glimepiride with BSE and BA increased all the pharmacokinetic parameters, such as Cmax, AUC0-n, AUCtotal, t½, MRT and decreased the clearance, Vd markedly as compared with the control group. In pharmacodynamic studies, the combination of glimepiride with BSE and BA provided signifcant protection against the diabetes induced alterations in the biochemical parameters. In addition, the combination of glimepiride with BSE and BA also improved the total antioxidant status and reduced the lipid peroxide levels signifcantly in diabetic rats compared with BSE, BA and glimepiride alone treated groups. The results revealed that a combination of glimepiride with BSE and BA led to the enhancement of the bioavailability of glimepiride by inhibiting the CYP2C9 enzyme, which suggested that boswellia might be benefcial as an adjuvant to glimepiride in a proper dose, in diabetic patients. *Corresponding author: Sujatha Samala, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, AP-506009, India, E-mail: sujathasamala@gmail.com Received September 11, 2013; Accepted September 23, 2013; Published September 30, 2013 Citation: Samala S, Veeresham C (2013) Enhanced Bioavailability of Glimepiride in the Presence of Boswellic Acids in Streptozotocin-Induced Diabetic Rat Model. Nat Prod Chem Res 1: 116 doi:10.4172/ 2329-6836.1000116 Copyright: © 2013 Samala S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Keywords: CYP2C9; Boswellia serrata standardized extract; Boswellic acids; Glimepiride; Pharmacokinetics; Pharmacodynamics Introduction Te use of herbal medicine as alternative and/or complementary therapy in the western world is on the rise and gaining increasing popularity. As people ofen take diferent herbs in combination with prescribed modern medication, there is a potential for both pharmacokinetic and pharmacodynamic interaction [1]. However, it has been reported that herbal products containing a number of natural compounds can cause pharmacokinetic and pharmacodynamic interaction with modern drugs when they were administrated simultaneously [2,3]. Glimepiride, a sulphonylurea used as an oral hypoglycemic agent, is widely used for the treatment of type 2 diabetes mellitus. Te hypoglycemic efect of glimepiride was changed during co-administration with Carica papaya extract [4], thus there is a need to study the interaction between glimepiride and other drugs to avoid adverse efects. In addition, people with diabetes are likely to select alternative therapy, including herbal medicine, to treat diabetes. For these reasons, BSE or BA might be used together with antidiabetic drugs. Boswellia serrata, known as sallaki or salai guggal or frankincense, is widely used in India to treat various types of blood disorders, infammatory health ailments, pain and cardiac debility [5]. Te 6 major active components in B. serrata are α-Boswellic acid, β-Boswellic acid, 3-Acetyl- α-Boswellic acid, 3-Acetyl- β-Boswellic acid, 11-keto- β-Boswellic acid and 3-Acetyl-11-keto- β-Boswellic acid. Many studies have shown that B. serrata and its major component, BA have various pharmacological activities, such as anti-infammatory [6], anticancer [7], anti-arthritic [8], immunomodulatory [9], antidiabetic [10] and analgesic [11]. Tere are several in vitro reports of BSE or BA on inhibition of microsomal enzyme system (CYP1A2, 2C8, 2C9, 2D6 and 3A4) and may lead to change in the bioavailability of concomitant drugs [12]. Hence, there is the possibility of BSE or BA for the metabolic inhibition of glimepiride, which is also completely metabolized by CYP2C9 microsomal liver enzymes [13]. In view of the efect of BSE or BA on CYP enzymes especially on CYP2C9 and also antidiabetic property, its presence in herbal antidiabetic preparations may infuence the bioavailability of glimepiride, particularly because the later is metabolized by CYP2C9. Terefore, the aim of the present investigation was to study the efect of BSE or BA on bioavailability and pharmacodynamics of glimepiride. Experimental Drugs and chemicals Glimepiride and gliclazide were obtained as gif samples from Dr. Reddy’s laboratories (Hyderabad, India). Methanol (HPLC-grade), potassium dihydrogen orthophosphate and orthophosphoric acid of AR grade (99.5%) were procured from Merck Specialties Pvt. Ltd., Mumbai. Boswellic acid (BA) was purchased from Yucca Enterprises, Mumbai. Boswellia serrata standardized extract (BSE) was obtained as gif sample from Amsar Pvt. Ltd., Indore. Ascorbic acid, α, α-diphenyl- β-picrylhydrazyl (DPPH), 1,1,3,3-tetraethoxy propane (TEP), thiobarbituric acid and streptozotocin (STZ) were purchased from Hi Media Laboratories Pvt. Ltd, Mumbai. Merck analytical kits were used to estimate the serum biochemical parameters. Water for analytical purpose is double distilled, fltered by using direct-Quv millipore and sonicated for removing air bubbles. All other chemicals used were of analytical grade. Maintenance of animals Male Albino rats of Wistar strain weighing 180-250 g were purchased from Mahaveera enterprises, Hyderabad, India and used for the studies afer obtaining the permission from institutional animal ethical committee (CPCSEA Reg. No.146/1999). Te animals were housed in standard polypropylene cages and maintained under standard laboratory conditions (12:12 h light and dark cycle; at an ambient temperature of 25 ± 5°C; 35-60% of relative humidity). Te animals were fed with standard rat pellet diet and water ad libitum. N a t u r a l P r o d u c t s C h e m i s t r y & R e s e a r c h ISSN: 2329-6836 Natural Products Chemistry & Research