| Autor: |
Jack BU; Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town 7505, South Africa., Ramharack P; Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town 7505, South Africa.; Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4001, South Africa., Malherbe C; Plant Bioactives Group, Post-Harvest and Agro-Processing Technologies, Agricultural Research Council (ARC), Infruitec-Nietvoorbij, Stellenbosch 7599, South Africa., Gabuza K; Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town 7505, South Africa., Joubert E; Plant Bioactives Group, Post-Harvest and Agro-Processing Technologies, Agricultural Research Council (ARC), Infruitec-Nietvoorbij, Stellenbosch 7599, South Africa.; Department of Food Science, University of Stellenbosch, Stellenbosch 7602, South Africa., Pheiffer C; Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town 7505, South Africa.; Centre for Cardio-Metabolic Research in Africa (CARMA), Division of Medical Physiology, Faculty of Medicine and Health Sciences, University of Stellenbosch, Cape Town 7505, South Africa.; Department of Obstetrics and Gynaecology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa. |
| Abstrakt: |
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 . |
