A polyphenol-enriched fraction of Cyclopia intermedia decreases lipid content in 3T3-L1 adipocytes and reduces body weight gain of obese db/db mice

Extracts of Cyclopia species, indigenous South African fynbos plants used for the production of honeybush tea, have potential as anti-obesity nutraceutical ingredients. Previously, we demonstrated that aqueous extracts of C. maculata and C. subternata exhibited anti-obesity effects in 3T3-L1 adipocytes. In this study, we further explored these anti-obesity effects of C. maculata and C. subternata as well as C. intermedia for the first time. Extracts were prepared using a 40% methanol-water mixture (40% MeOH) in order to enhance the polyphenolic content of the extracts. Moreover, these extracts were separated into aqueous and organic fractions using liquid-liquid partitioning with n-butanol and water to further enrich the polyphenol content of the organic fractions. Extracts of all three Cyclopia species decreased the lipid content in 3T3-L1 adipocytes, although differences in bioactivity of their aqueous and organic fractions were observed. The organic fraction of C. intermedia was further investigated. This fraction dose-dependently decreased the lipid content in 3T3-L1 adipocytes without affecting cell viability, while increasing mRNA expression of HSL (1.57-fold, P < 0.05), SIRT1 (1.5-fold, P = 0.07), UCP3 (1.5-fold, P < 0.05) and PPARγ (1.29-fold, P < 0.05). Daily treatment of obese db/db mice with 351.5 mg/kg bodyweight of the organic C. intermedia fraction for 28 days decreased bodyweight gain by 21% (P < 0.05) without any effect on food or water consumption. The organic fraction was enriched in phenolic content relative to the extract with neoponcirin, a flavanone not previously identified in Cyclopia species, mangiferin, isomangiferin and hesperidin comprising 17.37% of the organic fraction of C. intermedia compared to 4.96% of its “large scale” prepared 40% MeOH extract. Their specific roles as anti-obesity agents in these models needs to be studied to guide product development.