6‐Paradol Acts as a Potential Anti‐obesity Vanilloid from Grains of Paradise

Grains of Paradise (GOP), the seeds of Aframomum melegueta, has anti-obesity effects. However, the mechanisms underlying the effects remain unclear.This study sets up to study the anti-obesity impact and homeostatic effects of 6-paradol, a major vanilloid found in GOP, and investigates the physiological outputs and the lipometabolism-related gene in fat and liver in high-fat-induced obese mice with a comparison with structurally similar vanilloids (6-gingerol and 6-shogaol). The vanilloids are synthesized in adequate quantities for performing animal experiments and orally administered to 6-week-old male mice over 2 weeks. This study found that 6-paradol decreased body weight gain and visceral and subcutaneous fats in 2 weeks, whereas 6-gingerol and 6-shogaol have no effect. Additionally, 6-paradol suppresses the hepatic cholesterol and triglyceride and significantly decreases the gene expression related to fatty acid synthesis, lipid transportation, and adipocyte differentiation in both liver and adipose tissue. Moreover, phosphorylation of AMP-activated protein kinase (AMPK) that greatly contributes to lipometabolism is promoted by 6-gingerol but not 6-paradol.These results suggest that 6-paradol regulates several obesity-related genes in an AMPK-independent manner. Therefore, it could be the principal active vanilloid in GOP giving it anti-obesity properties with a different mechanism.