Multi Targeted Strategies Towards Identification of Potential Drug Candidates from Natural Products in the Management of Obesity

Obesity, a chronic metabolic disorder, is caused by an imbalance between energy intake and expenditure, and has been associated with insulin resistance, Type 2 Diabetes Mellitus (T2DM), hypertension, myocardial infarction, fatty liver disease, stroke, osteoarthritis and certain cancers. Currently, drugs used for the management of obesity like orlistat (lipase inhibitor) and Phentermine (norepinephrine and dopamine releasing agent) have been reported to exhibit adverse side effects.

Recent advancements in the understanding of biological systems have opened up new possibilities towards a multi targeted approach, designed to target more than one biological mechanism that might ultimately be more effective in producing sustained weight loss along with improvement in comorbidities. Multi-targeted drugs have emerged as a new paradigm in the last decade owing to their advantages in the treatment of complex multifactorial diseases such as obesity and T2DM. Most recently, glucagon-like peptide-1 (GLP-1) mimetics and insulin secretagogues have been reported for their anti-obesity activity, due to their property of delaying the rate of gastric emptying and appetite suppression in CNS, thus promoting satiety and weight loss.

Medicinal plants have been established as rich resources for the identification of potential drug candidates. Most of these isolated natural products exhibit multi-targeted action owing to their diverse and complex structure. Numerous natural bioactive molecules including polyphenols, alkaloids, sterols, glycosides, terpenes and saponins have been identified as potential drug candidates for the management of obesity. Cellular and molecular studies have shown that these natural products suppress appetite and reduce food intake, reduce intestinal absorption of fats, attenuate lipid synthesis and accumulation, stimulate lipolysis, promote oxidation of fatty acids and reduce inflammation.

This chapter will focus on the molecular targets and mechanisms involved in weight regulation, provide an insight into the isolation of bioactive compounds from medicinal plants, and the multi targeted strategies for the control of obesity.

Keywords: Adiponectin, Adipogenesis, Allosteric PTP1B inhibitor, Antiobesity drugs, Appetite suppressors, AMPK, β-oxidation, C/EBP, Cholecystokinin agonists, DPP4, GLP1, HSL, Leptin, Lipolysis, Multi targeted drugs, Natural products, Neuropeptide Y antagonist, Obesity, Pancreatic lipase, Partial PPARγ agonist, PPARα, Sirtuins, SREBP, Thermogenesis, UCPs.