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.
