Evaluation of anti-obesity activity on the natural Karanjin molecule through the adipogenesis pathway using a high-fat diet-induced rat model

Obesity has reached epidemic proportions globally, with at least 2.8 million people dying each year according to the World Health Organization report (WHO) in June 2021. In Malaysia, the National Health and Morbidity Survey (NHMS) 2019 showed that 50.1% of Malaysian adults were either overweight (30.4%) or obese (19.7%). Pancreatic lipase (PL), a major lipolytic enzyme secreted by the pancreas, has become a common obesity target in recent years. Since the PL works in the duodenum, it has the least involvement pancreas, has become a common obesity target in recent years. Since the PL works in the duodenum, it has the least involvement with the blood or the brain, which means it prevents many drug-related side effects. Even though the fact that PL has been identified as a promising target for obesity treatment, drug discovery, and development in this area is not abundantly explored. Although numerous medications for obesity-associated diseases have been commercialized, most of the drugs are withdrawn due to adverse effects. Plant-based natural products with low toxicity and anti-obesity therapeutics are largely unexplored. Karanjin (KRN), a type of potent bioactive furanoflavonoid biomolecule, was first isolated from Pongamia pinnata (L.). With the potential of KRN bioavailability, it is of great interest to explore its anti-obesity activity in in-vitro and in-vivo studies. With fact that pancreatic lipase (PL) is a molecular target of great importance in the prevention and treatment of obesity by digestion of dietary triglycerides efficiently. Thus, the present study aims to identify the anti-obesity potential of KRN through PL inhibition and prevention of triglyceride accumulation using in vitro and high-fat diet (HFD) obese rat models. In this study, karanjin will be characterized for PL binding using in silico with molecular docking analysis followed by in vitro and in vivo studies. Collectively, exploring the anti-obesity potential of KRN by inhibiting PL activation and preventing triglyceride accumulation could be a novel therapeutic agent for obese patients.