Exploring GIP Receptor Targeting Phytochemicals from Camellia sinensis Using Molecular Docking Studies to Develop New Therapies for Obesity

Obesity, characterized by excessive fat accumulation, has become a growing public health concern globally. It significantly increases morbidity and mortality by greatly affecting the prevalence of multiple chronic diseases such as diabetes, high blood pressure, elevated triglycerides, metabolic dysfunction-associated steatotic liver disease, sleep disorders, cancers, and cardiovascular conditions. This in turn places a greater burden on the healthcare system and results in about 30% higher medical expenses for an obese individual compared to a normal person. Further, there is a significant increase in childhood obesity along with adult obesity rates. Only a limited number of FDA approved drugs are available along with lifestyle modifications and surgical options for weight loss. Many of the drugs were withdrawn from the market due to side effects including, abnormal heart rate, pulmonary hypertension, psychiatric, cerebrovascular, cardiovascular and gastrointestinal side effects. Therefore, there is an urgent need to identify and develop effective treatment options for obesity. Recently, the Incretin hormones Gastric Inhibitory Polypeptide (GIP) and Glucagon Like Peptide (GLP) have gained attention in treating diabetes mellitus and obesity. GIP is an incretin hormone that is secreted by the K cells of intestine in response to food intake. GIP based therapies are being explored for managing obesity, as both its agonism and antagonism can show metabolic benefits. Given the traditional use of Camellia sinensis (CS) in obesity, we initiated this study to explore the phytochemicals of CS on GIP agonist, GIP receptor activator and/or GIP-GIPreceptor complex binding enhancers. We identified 24 compounds from CS. The 3D structures of these compounds were acquired from PubChem. We obtained a crystal structure of the extracellular domain of human GIP receptor that is in complex with GIP hormone (2QKH) from RCSB Protein Data Bank. Using this complex structure, we modelled 3D structure of GIP receptor. Molecular docking was performed with GIP receptor and 24 phytochemicals of CS using CB Doc 2 tool. Of all the 24 compounds studied, the compounds CS4, CS14, and CS19 were identified to bind strongly with the GIP receptor based on the VINA score, number of interactions formed, and the cavity of the receptor in which they fit. The strongly bound compounds had higher binding energy, stronger hydrogen bonds with better fit into the receptor cavity. These findings suggest that certain compounds from Camellia sinensis could be potential therapeutic candidates for GIP mediated obesity and diabetes mellitus treatment. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.