Anti-Obesity Potential of Ponciri Fructus: Effects of Extracts, Fractions and Compounds on Adipogenesis in 3T3-L1 Preadipocytes.

Gopal Lamichhane,Hari Prasad Devkota,Hyun-Ju Jung,Prakash Raj Pandeya,Su-Jin Rhee,Ramakanta Lamichhane

doi:10.3390/molecules27030676

Gopal Lamichhane, Hari Prasad Devkota + Show 4 more

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https://doi.org/10.3390/molecules27030676

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Abstract

Background: Ponciri Fructus, a crude drug consisting of the dried immature fruits of Poncirus trifoliata (L.) Raf., is a popular folk medicine used for the treatment of allergy and gastrointestinal disorders in Korea and China. In this study, the anti-adipogenic activity of extracts and isolated compounds were evaluated using 3T3-L1 preadipocytes. Methods: Dried immature fruits were extracted and fractionated into n-hexane, ethyl acetate (EtOAc), n-butanol and water-soluble fractions. The ethanol extract and fractions were tested for anti-adipogenic activity in the 3T3-L1 cell line. The active fractions (n-hexane and EtOAc fractions) were further subjected to chromatographic techniques to isolate and identify active compounds. Furthermore, the isolated compounds were evaluated for their anti-adipogenic activity. Results: Altogether, seven compounds, including two flavonoids, one phytosteroid and four coumarin derivatives, were isolated. Ethanol extract, n-hexane fraction, EtOAc fraction and three isolated compounds (phellopterin, oxypeucedanin and poncirin) showed significant anti-adipogenic activity as observed by reduced lipid deposition in differentiated 3T3-L1 cells. Further, oxypeucedanin downregulated the key adipogenic markers, such as peroxisome proliferator-activated receptors proteins γ (PPAR-γ), sterol response element binding proteins-1 (SREBP-1), CCAAT/enhancer binding proteins-α (C/EBP-α), adipocyte-specific lipid binding proteins (FABP-4), adipocyte fatty acid binding proteins (aP2), lipoprotein lipase (LPL) and leptin. Conclusion: This study indicated that the ethanol extract, hexane fraction and ethyl acetate fraction of P. trifoliata fruits possess strong anti-adipogenic activity, containing the active compounds such as phellopterin, oxypeucedanin and poncirin. Further research is recommended to explore their efficacy and safety in animal and clinical models.

Highlights

Obesity is a clinical condition resulting from the disruption of homeostasis between food intake and energy expenditure causing a deposition of excess fat in adipocytes of the body [1]
This feedback loop of CCAAT/enhancer binding proteins-α (C/EBP-α) and peroxisome proliferator–activated receptors (PPAR)-γ induces the transcriptional activation of adipogenic genes, such as sterol response element binding proteins (SREBPs), fatty acid synthase (FAS), lipoprotein lipase (LPL), adipocyte-specific lipid binding proteins (FABP) and adipokines, which collectively results in the deposition of fatty acids and triglycerides in adipocytes [4,5,6,7]
Compounds 1 and 2 were identified as poncirin and naringin, respectively. The conformation of these flavonoids was made based on exactly the same retention time and similar UV spectra as that of standard compounds (Merck, Darmstadt, Germany), as shown in Supplementary Figures S1 and S2 based on the ultra-performance liquid chromatography (UPLC) evaluation

Summary

Introduction

Obesity is a clinical condition resulting from the disruption of homeostasis between food intake and energy expenditure causing a deposition of excess fat in adipocytes of the body [1]. An increase in the cyclic adenosine monophosphate (cAMPs) load in the cell triggers the release of cAMPs responsive elements binding proteins (CREB), which, in turn, activates adipogenesis signaling molecule CCAAT/enhancer binding proteins (C/EBP)β, which further activate C/EBP-α and the peroxisome proliferator–activated receptors (PPAR)-γ cascade, forcing the cell to the terminal differentiation stage This feedback loop of C/EBP-α and PPAR-γ induces the transcriptional activation of adipogenic genes, such as sterol response element binding proteins (SREBPs), fatty acid synthase (FAS), lipoprotein lipase (LPL), adipocyte-specific lipid binding proteins (FABP) and adipokines, which collectively results in the deposition of fatty acids and triglycerides in adipocytes [4,5,6,7]. N-hexane fraction, EtOAc fraction and three isolated compounds (phellopterin, oxypeucedanin and poncirin) showed significant anti-adipogenic activity as observed by reduced lipid deposition in differentiated 3T3-L1 cells. Further research is recommended to explore their efficacy and safety in animal and clinical models

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