Topclass Journal of Herbal Medicine Vol. 1(1) Pp. 1-7, 26 November, 2012 Available online at http://www.topclassglobaljournals.org ISSN 2315-8840 ©2012 Topclass Global Journals Submitted: 23/06/2012 Accepted: 22/10/2012 Full Length Research Article Dipeptidyl Peptidase IV inhibitory activity of seed extract of Castanospermum australe and molecular docking of their Alkaloids Sudhanshu Kumar Bharti 1 , Neeraj Kumar Sharma 1 , Amit Kumar 2 , Sudhir Kumar Jaiswal 1 , Supriya Krishnan 3 , Ashok Kumar Gupta 1 , Ashis Kumar Ghosh 4 , Om Prakash 2 1 Department of Biochemistry, Patna University, Patna, Bihar, India 2 School of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi, India 3 Department of Humanities, Banaras Hindu University, Varanasi, Uttar Pradesh, India 4 Department of Chemistry, Patna University, Patna, Bihar, India Abstract The glucagon-like peptide 1 (GLP-1) with ‘incretin effect’ is an insulinotropic gut hormone which is metabolized extremely by Dipeptidyl peptidase IV (DPP-IV). Inhibitors of DPP IV enhance the level of GLP-1, which have improved glucose tolerance and increased insulin secretion. The in-vitro DPP-IV inhibitory activity of Castanospermum australe Cunn., seed (CAS) extract was evaluated. The DPP-IV inhibitory potential of CAS extract showed IC 50 value of 13.96 μg/ml while the standard Diprotin A displayed the IC 50 value of 1.543μg/ml. Molecular docking of the three reported alkaloids from the seeds of C. australe showed comparable DPP-IV inhibition with berberine. Our data suggest that CAS extract (150mg/ kg body weight) have strong DPP-IV inhibitory potential. The molecular docking showed that among the three alkaloids (7-Deoxy-6-epi-castanospermine, castanospermine and australine) from the seeds of C. australe, 7-Deoxy-6-epi-castanospermine is a potent DPP-IV inhibitor similar to berberine. The results confirm the inhibitory effect of CAS extract on DPP-IV, and the potential to be a novel, efficient and tolerable approach for diabetes. Key words: Type 2 diabetes, DPP-IV inhibitor, C. australe seed extract, Diprotin A, Molecular docking. INTRODUCTION Type 2 diabetes mellitus (T2DM) is possibly the world's fastest growing metabolic syndrome of multiple aetiologies causing hyperglycemia (Nyenwe et al. 2011; Al-Masri et al. 2009). According to the World Health Organization (WHO), T2DM is the World’s fifth leading cause of death and it is estimated that it will surpass 366 million by the year 2030 (Wild et al. 2004). The progression of T2DM begins with an impairment of glucose tolerance (Zimmet and Thomas 2003) and is often associated with a state of insulin resistance (Robertson and Harmon 2006) A popular theory on meal-induced insulin secretion, the ‘incretin effect’ states that glucose or any other drug is more effective on the pancreatic cells when administered orally than given through intravenous or subcutaneous injections (Vilsboll and Holst 2004). Major glucose regulating incretin hormones are glucagon like peptide-1 (GLP-I) and glucose- dependent insulinotropic polypeptide (GIP) produced from the L-cells and K-cells of the intestinal mucosa, respectively. In T2DM, there is a decrease in the incretin effect and rapid degradation of short lived GLP-I and GIP (Vilsbøll et al. 2001). GLP-I under normal metabolic conditions improve glucose homeostasis by promoting α- and β-cell function, insulin secretion, glycogenesis in muscles and liver (Fehmann and Habener 1992). On the other hand it down regulates the level of gastric emptying and gastric acid secretion to reduce postprandial glucose spikes (Nauck et al. 1997). However, GLP-1 has short plasma half-life of only 1-2 minutes (Mentlein et al. 1993). Corresponding author’s Email: sudhanshu_bharti@rediffmail.com Tel : +91-9852883752