Ginseng (Panax quinquefolius) Reduces Cell Growth, Lipid Acquisition and Increases Adiponectin Expression in 3T3-L1 Cells

Evidence-Based Complementary and Alternative Medicine, Feb 2011

An American ginseng (Panax quinquefolius) extract (GE) that contained a quantifiable amount of ginsenosides was investigated for the potential to inhibit proliferation, affect the cell cycle, influence lipid acquisition and adiponectin expression in 3T3-L1 cells. Six fingerprint ginsenosides were quantified by high performance liquid chromatography and the respective molecular weights were confirmed by LC-ESI-MS analysis. The extract contained Rg1 (347.3 ± 99.7 μg g−1, dry weight), Re (8280.4 ± 792.3 μg g−1), Rb1 (1585.8 ± 86.8 μg g−1), Rc (32.9 ± 8 μg g−1), Rb2 (62.6 ± 10.6 μg g−1) and Rd (90.4 ± 3.2 μg g−1). The GE had a dose-dependent effect on 3T3-L1 cell growth, the LC50 value was determined to be 40.3 ± 5 μg ml−1. Cell cycle analysis showed modest changes in the cell cycle. No significant changes observed in both G1 and G2/M phases, however there was a significant decrease in the S phase after 24 and 48 h treatment. Apoptotic cells were modest but significantly increased after 48 h (3.2 ± 1.0%) compared to untreated control cells (1.5 ± 0.1%). Lipid acquisition was significantly reduced by 13 and 22% when treated at concentrations of 20.2 and 40.3 μg ml−1 compared to untreated control cells. In relation to adiponectin activation, western blot analysis showed that the protein expression was significantly increased at concentrations tested. A quantified GE reduced the growth of 3T3-L1 cells, down-regulated the accumulation of lipid and up-regulated the expression of adiponectin in the 3T3-L1 adipocyte cell model.

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Ginseng (Panax quinquefolius) Reduces Cell Growth, Lipid Acquisition and Increases Adiponectin Expression in 3T3-L1 Cells

Ginseng (Panax quinquefolius) Reduces Cell Growth, Lipid Acquisition and Increases Adiponectin Expression in 3T3-L1 Cells Chia-Rou Yeo, Sea-Ming Lee, and David G. Popovich Department of Chemistry, National University of Singapore, Science Drive 4, Singapore 117543 Received 26 November 2009; Accepted 12 April 2010 Copyright © 2011 Chia-Rou Yeo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract An American ginseng (Panax quinquefolius) extract (GE) that contained a quantifiable amount of ginsenosides was investigated for the potential to inhibit proliferation, affect the cell cycle, influence lipid acquisition and adiponectin expression in 3T3-L1 cells. Six fingerprint ginsenosides were quantified by high performance liquid chromatography and the respective molecular weights were confirmed by LC-ESI-MS analysis. The extract contained Rg1 (347.3 ± 99.7 μg g−1, dry weight), Re (8280.4 ± 792.3 μg g−1), Rb1 (1585.8 ± 86.8 μg g−1), Rc (32.9 ± 8 μg g−1), Rb2 (62.6 ± 10.6 μg g−1) and Rd (90.4 ± 3.2 μg g−1). The GE had a dose-dependent effect on 3T3-L1 cell growth, the LC50 value was determined to be 40.3 ± 5 μg ml−1. Cell cycle analysis showed modest changes in the cell cycle. No significant changes observed in both G1 and G2/M phases, however there was a significant decrease in the S phase after 24 and 48 h treatment. Apoptotic cells were modest but significantly increased after 48 h (3.2 ± 1.0%) compared to untreated control cells (1.5 ± 0.1%). Lipid acquisition was significantly reduced by 13 and 22% when treated at concentrations of 20.2 and 40.3 μg ml−1 compared to untreated control cells. In relation to adiponectin activation, western blot analysis showed that the protein expression was significantly increased at concentrations tested. A quantified GE reduced the growth of 3T3-L1 cells, down-regulated the accumulation of lipid and up-regulated the expression of adiponectin in the 3T3-L1 adipocyte cell model. 1. Introduction There are many natural plant compounds that have been shown to possess bioactive properties. Many of these compounds are plant secondary metabolites that function as deterrents to herbivores [1]. Groups of natural compounds isolated from plants such as polyphenol epigallocatechin-3-gallate (EGCG) from tea (Camellia sinensis) [2], vanilloids such as capsaicin from chili peppers (Capsaicum annuum) [3] and water extracts from cinnamon (Cinnamomum zeylanicum) [4] have all been shown to influence the regulation of cultured adipocytes (3T3-L1 cells). In vivo, the molecular regulation of adipocyte is thought to be a contributing factor to the development of the metabolic syndrome and diabetes [5]. These disorders share a common risk factor of obesity. Adipocytes are a metabolically active organ that release a complex set of cytokines that contribute to the maintenance of health or to the development of disease. The increase in adipocyte lipid content can influence adipocyte function such as reducing adiponectin secretion which has been related to insulin resistance and increase risk of diabetes [5, 6]. Reports have shown that ginseng (Panax quinquefolius) may improve blood glucose control in normal and diabetic subjects [7]. Animal studies also indicate that ginsenosides, dammarane triterpenoids (Figure 1), such as Re may improve glucose control [8]. It is unclear if an individual ginsenoside or a group of compounds classified into either protopanaxatriol or protopanaxadiol ginsenoside groups [9] such as those contained in an extract or decoction are responsible for these reported effects. The literature on the effect of specific ginsenosides on the promotion or inhibition of adipogenesis is currently unclear. In four reported studies using specific ginsenosides to test the effect on adipogenesis in cultured adipocytes (3T3-L1 cells), two studies reported an inhibition of PPARγ, the master regulator of adipocyte differentiation, using ginsenosides Rh2 and Rg3 [10, 11] and two studies reported increased expression PPARγ and adipogenesis [12, 13]. The objective of this study was to study the effect of a ginseng extract (GE) on adipocyte cell growth, differentiation and lipid acquisition of 3T3-L1 cells and the influence on adiponectin expression. These effects were investigated in terms of its cytotoxic effects on preadipocyte viability, the changes in cell cycle distribution, lipid accumulation after differentiation as well as the expression of adiponectin in the 3T3-L1 cell line, a model system often used to study adipocyte metabolism. Figure 1: Chemical structure of dammarane-type ginsenoside triterpenoids detected in the GE (P. quinquefolius). Regions R1–R3 consist of different attachments of sugar moieties and refer to the following abbreviations: Af: arabinofuranose, Ap: arabinopyranose, G: g (...truncated)


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Chia-Rou Yeo, Sea-Ming Lee, David G. Popovich. Ginseng (Panax quinquefolius) Reduces Cell Growth, Lipid Acquisition and Increases Adiponectin Expression in 3T3-L1 Cells, Evidence-Based Complementary and Alternative Medicine, 2011, 2011, DOI: 10.1093/ecam/neq051