Editorial
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Sep 10, 2015; 6(11): 1179-1185
Published online Sep 10, 2015. doi: 10.4239/wjd.v6.i11.1179
Computational pharmacokinetics and in vitro-in vivo correlation of anti-diabetic synergistic phyto-composite blend
Baishakhi De, Koushik Bhandari, Nishant Chakravorty, Ranjan Mukherjee, Rohit Gundamaraju, Rajeev K Singla, Prakash Katakam, Shanta K Adiki, Biswajoy Ghosh, Analava Mitra
Baishakhi De, Koushik Bhandari, Nishant Chakravorty, Ranjan Mukherjee, Biswajoy Ghosh, Analava Mitra, School of Medical Science and Technology, IIT Kharagpur 721302, India
Rohit Gundamaraju, Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia
Rajeev K Singla, Division of Biotechnology, Netaji Subhas Institute of Technology, Sector-3, Dwarka, New Delhi 110078, India
Prakash Katakam, Faculty of Pharmacy, University of Zawia, Az-Zawiya 13, Libya
Shanta K Adiki, Nirmala College of Pharmacy, Guntur 522503, Andhra Pradesh, India
Author contributions: De B developed the central theme of the manuscript under the guidance of Chakravorty N, Katakam P and Mitra A; Bhandari K, Mukherjee R, Gundamaraju R and Singla RK contributed in literature review, and provided their valuable suggestions; De B developed the manuscript under the guidances of Chakravorty N, Shanta KA and Mitra A; Ghosh B prepared the pictorial presentations of receptor pathways and gave his suggestions.
Conflict-of-interest statement: All authors declare that the conflict of interest is nil.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Analava Mitra, MBBS, PhD, School of Medical Science and Technology, B-145, IIT Campus, IIT Kharagpur 721302, India. analavamitra@gmail.com
Telephone: +91-94-75258298 Fax: +91-32-22279970
Received: June 12, 2015
Peer-review started: June 16, 2015
First decision: August 4, 2015
Revised: August 11, 2015
Accepted: September 1, 2015
Article in press: September 2, 2015
Published online: September 10, 2015
Processing time: 94 Days and 17.6 Hours
Abstract

Despite tremendous strides in modern medicine stringent control over insulin resistance or restoration of normoglycemia has not yet been achieved. With the growth of molecular biology, omics technologies, docking studies, and in silico pharmacology, modulators of enzymes and receptors affecting the molecular pathogenesis of the disease are being considered as the latest targets for anti-diabetic therapy. Therapeutic molecular targets are now being developed basing on the up or down regulation of different signaling pathways affecting the disease. Phytosynergistic anti-diabetic therapy is in vogue both with classical and non-classical medicinal systems. However its chemo-profiling, structural and pharmacokinetic validation awaits providing recognition to such formulations for international acceptance. Translational health research with its focus on benchside product development and its sequential transition to patient bedside puts the pharma RDs to a challenge to develop bio-waiver protocols. Pharmacokinetic simulation models and establishment of in vitro-in vivo correlation can help to replace in vivo bioavailability studies and provide means of quality control for scale up and post approval modification. This review attempts to bring different shades highlighting phyto-synergy, molecular targeting of antidiabetic agents via different signaling pathways and bio-waiver studies under a single umbrella.

Keywords: In silico pharmacology; Phytosynergistic; Anti-diabetic; Simulation models; Translational health research; Bio-waiver; Signaling pathways

Core tip: The current research scenario on anti-diabetic drug development pipeline focuses on pharmacological targets influencing the molecular pathogenesis of the disease. It encompasses receptors and enzymes that will increase insulin sensitivity, intracellular insulin signaling, enhance peripheral glucose utilizations, suppress hepatic glucose production and reduce circulating triglycerides levels. Combination therapy has gained significance either with herbal or synthetic drugs, though “phytosynergy” awaits proper validation to give rise to new generations of “phytopharmaceuticals”. Pharmacokinetic simulation models and established in vitro-in vivo correlation that may be extrapolated to humans can serve the purpose of bio-waiver in product transition from lab bench to patient bedside.