Abstract:
Previously, we reported that a crude polyphenol-enriched fraction of Cyclopia intermedia
(CPEF), a plant consumed as the herbal tea, commonly known as honeybush, reduced lipid content in
3T3-L1 adipocytes and inhibited body weight gain in obese, diabetic female leptin receptor-deficient
(db/db) mice. In the current study, the mechanisms underlying decreased body weight gain in
db/db mice were further elucidated using western blot analysis and in silico approaches. CPEF
induced uncoupling protein 1 (UCP1, 3.4-fold, p < 0.05) and peroxisome proliferator-activated receptor
alpha (PPARα, 2.6-fold, p < 0.05) expression in brown adipose tissue. In the liver, CPEF induced
PPARα expression (2.2-fold, p < 0.05), which was accompanied by a 31.9% decrease in fat droplets in
Hematoxylin and Eosin (H&E)-stained liver sections (p < 0.001). Molecular docking analysis revealed
that the CPEF compounds, hesperidin and neoponcirin, had the highest binding affinities for UCP1
and PPARα, respectively. This was validated with stabilising intermolecular interactions within the
active sites of UCP1 and PPARα when complexed with these compounds. This study suggests that
CPEF may exert its anti-obesity effects by promoting thermogenesis and fatty acid oxidation via
inducing UCP1 and PPARα expression, and that hesperidin and neoponcirin may be responsible for
these effects. Findings from this study could pave the way for designing target-specific anti-obesity
therapeutics from C. intermedia.
