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© 2006 American Society for Nutrition J. Nutr. 136:337-342, February 2006

Biochemical, Molecular, and Genetic Mechanisms

Ginseng Extract Inhibits Lipolysis in Rat Adipocytes In Vitro by Activating Phosphodiesterase 41,2

Hong Wang*, Lisa A. Reaves{dagger} and Neilé K. Edens{dagger},3

* Interdisciplinary Ph.D. Program in Nutrition, The Ohio State University, Columbus, OH 43210 and {dagger} Ross Products Division, Abbott Laboratories, Columbus, OH 43215

3 To whom correspondence and reprint requests should be addressed. E-mail: neile.edens{at}abbott.com.


   ABSTRACT
TOP
 ABSTRACT
METHODS AND MATERIALS
 RESULTS
 DISCUSSION
 LITERATURE CITED
 
Elevated concentrations of plasma free fatty acids (FFA) may cause insulin resistance. Inhibition of lipolysis reduces FFA availability and improves insulin sensitivity. Ginseng extract (Panax spp., GE) was shown to improve glycemia in Type 2 diabetes. In the present study, the antilipolytic effect of GE in rat adipocytes and the signaling pathway for GE antilipolysis were investigated. Adipocytes were isolated from rat fat tissue by collagenase digestion. The ability of GE to inhibit lipolysis was assessed by measuring glycerol and FFA release into the incubation medium. Phosphatidylinositol 3-kinase (PI3-K) inhibitor and various phosphodiesterase (PDE) inhibitors were applied to investigate the signaling pathway for GE antilipolysis. The present study showed that insulin and GE inhibited lipolysis by 42.4 and 49% compared with basal, respectively (P < 0.05). Unlike insulin, the PI3-K inhibitor wortmannin did not reverse GE antilipolysis, and GE did not affect phosphorylation of protein kinase B (PKB). The nonselective PDE inhibitor enprofylline reversed both insulin and GE antilipolysis. The specific phosphodiesterase 3 (PDE3) inhibitor cilostamide reversed insulin antilipolysis completely, but did not significantly affect GE antilipolysis. The specific phosphodiesterase 4 (PDE4) inhibitor rolipram did not significantly affect insulin antilipolysis, but almost completely reversed GE antilipolysis. Moreover, the combination of PDE3 and PDE4 inhibitors completely reversed GE antilipolysis. None of the ginsenosides (Rb1, Re, Rg1, Rc, Rb2, and Rd) were responsible for GE antilipolysis. The results suggest that ginseng exerts its antilipolytic effect through a signaling pathway different from that of insulin. GE antilipolysis is mediated in part by activating PDE4 in rat adipocytes.

KEY WORDS: • Panax • phosphodiesterase • cAMP • glycerol • diabetes

Type 2 diabetes is characterized by insulin resistance and impaired insulin secretion (1). Although it is controversial which is the primary factor in the development of type 2 diabetes, insulin resistance precedes the diagnosis of type 2 diabetes by many years (2). Insulin resistance has been defined as the impaired ability of insulin to appropriately stimulate glucose disposal or suppress endogenous glucose production (3). Although the mechanisms responsible for the development of insulin resistance are still not completely clear, it is likely that free fatty acids (FFA)4 play a key role (4).

Insulin is a potent antilipolytic hormone. When the antilipolytic action of insulin is inhibited, the release of FFA from adipose tissue is increased. Elevated plasma FFA concentrations are common in obese people (5) and people with type 2 diabetes (6), in part as a result of an increased rate of lipolysis and concomitant FFA release from an enlarged fat mass (7,8). The increased plasma FFA may decrease glucose utilization in skeletal muscle by inhibiting glucose uptake and glycogen synthesis, stimulate hepatic glucose production by increasing gluconeogenesis and glycogenolysis, and reduce insulin extraction by the liver (9). Furthermore, the accumulation of intracellular lipids in muscle due to high circulating FFA is correlated with insulin resistance (10). In the pancreas, lipid accumulation in ß cells may impair insulin secretion and lead to apoptosis (11).

Insulin inhibits lipolysis by phosphorylation and activation of phosphodiesterase 3B (PDE3B), which hydrolyzes cAMP to AMP (12,13). The activation of PDE3B decreases intracellular cAMP, which in turn reduces cAMP-dependent protein kinase A (PKA) activity. The reduction of PKA activity decreases the hydrolysis of triglyceride and thus suppresses release of FFA from adipocytes (14). The signaling pathway for insulin to activate PDE3B is not completely clear. Phosphatidylinositol 3-kinase (PI3-K) (15) and protein kinase B (PKB) (16) are likely to be involved in the phosphorylation and activation of PDE3B.

Ginseng (Panax spp.) is regarded as a tonic in traditional Chinese medicine; it has been used to treat a number of diseases for thousands of years in Asian countries. Korean ginseng (Panax ginseng) and American ginseng (Panax quinquefolius) are common species of ginseng. Previous studies showed that extracts from ginseng roots decreased blood glucose level in alloxan diabetic mice (17) and in streptozotocin diabetic rats (18). A recent animal study showed that i.p. injection of Korean ginseng berry extract (extracted in 75% ethanol) decreased blood glucose in obese diabetic mice (19). Clinically, American ginseng (3 g) taken orally decreased postprandial glycemia acutely in healthy subjects and subjects with type 2 diabetes (20). A long-term study showed that American ginseng extract (3 g/d for 4 wk) decreased fasting blood glucose and glycated hemoglobin in patients with type 2 diabetes (21). Korean red ginseng (6 g/d for 6 wk) also improved postprandial glycemia and insulin sensitivity in type 2 diabetes (22). Another long-term clinical study showed that ginseng (200 mg/d for 8 wk) reduced fasting blood glucose and improved glycated hemoglobin in patients newly diagnosed with type 2 diabetes (23). The proposed mechanisms for the hypoglycemic effect of ginseng involve stimulation of cellular glucose uptake (24), stimulation of insulin biosynthesis (25), inhibition of glucose absorption from the small intestine (26), and inhibition of lipolysis (27).

The purpose of the present study was to determine the effect of ginseng extract (GE) on lipolysis in rat adipocytes in vitro, to compare the intracellular signaling pathways for GE and insulin antilipolysis, and to determine the role of PDE in GE antilipolysis. The hypothesis tested was that if GE inhibits lipolysis in rat adipocytes, GE will activate intracellular signaling pathways similar to those activated by the antilipolytic hormone insulin.


   METHODS AND MATERIALS
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 ABSTRACT
 METHODS AND MATERIALS
RESULTS
 DISCUSSION
 LITERATURE CITED
 
    Chemicals. Collagenase (Type I) was purchased from Worthington Biochemical. Recombinant human insulin (Humulin-R) was purchased from Eli Lilly. Bovine serum albumin (BSA, Type V) and adenosine deaminase were purchased from Roche Biochemical. Ginsenosides were purchased from Indofine Chemical. Enzyme inhibitors (wortmannin, cilostamide, and rolipram) and other chemicals were purchased from Sigma-Aldrich. Protein was measured with the bicinchoninic acid kit using BSA as a standard (Pierce).

    Ginseng preparation. American ginseng extract (Panax quinquefolius; extracted in 80% ethanol) was obtained from Chai-Na-Ta. Korean ginseng extract (Panax ginseng; extracted in 50% ethanol) was obtained from Flachsmann. Preliminary experiments showed that Korean ginseng extract (100 g/L for stock solutions) required propylene glycol (100%) for best solubility, whereas American ginseng extract dissolved well in plain water. Stock solutions were stored at –20°C until use. The final concentration of propylene glycol never exceeded 0.1% (w:v) in adipocyte incubations and did not affect glycerol release when added to basal incubations. The effects of American and Korean ginseng extracts on lipolysis were compared in preliminary experiments and did not differ (data not shown). Both American and Korean ginseng extracts were used in this study.

    Animals and adipocyte isolation. Young male Sprague-Dawley rats weighing 150 ± 10 g were purchased from Harlan and housed in a temperature- and humidity-controlled environment with free access to tap water and a nonpurified commercial diet (Teklad Rodent Diet 8640; 22% protein, 5% fat, and 4.5% crude fiber; Harlan). Lights were on at 0600 and off at 1800. Rats were acclimated to the laboratory for at least 6 d before being killed (in the fed state, between 1000 and 1100) by decapitation. The epididymal and retroperitoneal fat pads of 4 rats were removed and pooled for each adipocyte preparation. All animal protocols were reviewed and approved by The Ohio State University Institutional Laboratory Animal Care and Use Committee. The adipocytes were isolated by a modification (28) of method described by Rodbell (29). Adipocytes were washed and suspended at a 20% concentration (v:v) in Krebs-Ringer's-HEPES (KRH) medium containing 25 g/L BSA (KRH-BSA), 200 nmol/L adenosine, and 5 mmol/L glucose.

    Lipolysis assay. Adipocytes, at a final concentration of 2% (v:v), were incubated in 2 mL KRH medium containing 25 g/L BSA, 800 U/L adenosine deaminase, 10 mmol/L glucose, and other additions as noted in Results. Incubations were carried out at 37°C for 1 h with shaking (80 cpm). The concentrations of insulin and GE that inhibited lipolysis by ~50% were determined in preliminary studies before each set of experiments. Because 50% inhibition was obtained with slightly different concentrations in different sets of experiments, 150 pmol/L insulin and 63 mg/L GE were used in the experiments with American ginseng extract, whereas 90 pmol/L insulin and 100 mg/L GE were used in the experiments with Korean ginseng extract. In addition, 100 nmol/L wortmannin and 1 mmol/L enprofylline were used because they are well-established concentrations of inhibitors used in previous studies, e.g., Van Harmelen et al. (30).

The concentration of cilostamide, a phosphodiesterase 3 (PDE3) inhibitor, used in lipolysis experiments was chosen on the basis of preliminary experiments. Because PDE3B activation mediates insulin antilipolysis, it was desirable to use a concentration of cilostamide that completely reversed the antilipolytic effect of insulin with minimal nonspecific effects. To determine this concentration, freshly isolated rat adipocytes (n = 3) were incubated with insulin, GE, and a range of concentrations of cilostamide. Cilostamide (1 µmol/L) did not completely reverse the antilipolytic effect of insulin, whereas both higher concentrations of cilostamide (5 and 23 µmol/L) were completely effective (Table 1). No concentration of cilostamide completely reversed GE antilipolysis. The lowest concentration of cilostamide (5 µmol/L) that completely reversed the antilipolytic effect of insulin was used in the remaining experiments. A similar analysis could not be performed for the specific phosphodiesterase 4 (PDE4) inhibitor, rolipram, because rolipram does not affect insulin antilipolysis. Consequently, the concentration of rolipram used (10 µmol/L) was based on the previous literature (31).


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  		TABLE 1 Glycerol release by rat adipocytes incubated with a range of concentrations of the specific PDE3 inhibitor cilostamide12

 
Phosphodiesterase (PDE) inhibitors and wortmannin were dissolved in dimethyl sulfoxide (DMSO). The final concentration of DMSO in adipocyte incubation medium never exceeded 0.1%, which we determined did not affect glycerol release in preliminary experiments (unpublished observations). Glycerol release into the incubation medium was assessed with the Trinder kit (Sigma-Aldrich); FFA release was measured with the NEFA-C kit (Wako Chemical) using palmitic acid standards prepared in KRH-BSA. Preliminary experiments showed that the lipolysis rate of rat adipocytes was linear up to 2 h (data not shown).

    Ginsenoside analysis. GE was analyzed to determine the level of 6 major ginsenosides (Rb1, Re, Rg1, Rc, Rb2, and Rd) using a HPLC method (32). Levels of ginsenosides in GE were quantitated by comparison to ginsenoside standards purchased from Indofine Chemical.

    Western blot analysis. Isolated adipocytes were suspended [2 mL of 20% cell suspension (v:v)] in KRH-BSA and incubated at 37°C with insulin (900 pmol/L) and GE (125, 250, 500, and 1000 mg/L) for 10 min. The incubations were stopped by adding 5 mL of room temperature homogenization buffer containing HEPES (40 mmol/L, pH 7.4), NaF (10 mmol/L), phenylmethylsulfonyl fluoride (1 mmol/L), sodium orthovanadate (0.25 mmol/L), antipain (10 mg/L), leupeptin (10 mg/L), and pepstatin A (1 mg/L). Adipocytes were centrifuged at 125 x g for 2 min at room temperature, resuspended in 0.8 mL of homogenization buffer, homogenized at room temperature with 10 strokes in a 2-mL ground glass homogenizer (Wheaton), and then placed on ice immediately. For cell lysates, homogenates were centrifuged at 1000 x g for 10 min at 4°C and then the fat layer was removed. For the particulate fraction, homogenates were centrifuged at 16,100 x g for 60 min at 4°C. The fat layer was removed, the infranatant (referred to as the cytosol fraction) was withdrawn, and the pellet (referred to as the particulate fraction) was resuspended in 120 µL of homogenization buffer. Protein (10 µg) was separated by 7.5% SDS-PAGE and transferred to nitrocellulose. Western blot was performed using phospho-PKB (Ser 473) and PKB polyclonal antibodies (Cell Signaling), visualized using Supersignal chemiluminescence (Pierce), and quantified using a Kodak 1D software (Version 3.6.2; Scientific Imaging Systems) on Kodak Image Station 2000RT.

    Statistical analysis. Data are presented as means ± SEM; n = number of independent adipocyte preparations. When a single comparison was performed, the significance of the differences between means was analyzed by paired t test. When multiple comparisons were performed, the significance was analyzed by 1- or 2-way ANOVA, depending on the number of factors considered (SPSS 12.0). When a significant effect was found, differences between means were determined by Fisher's Least Significant Difference post hoc test. The {alpha} level was set at 0.05.


   RESULTS
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 ABSTRACT
 METHODS AND MATERIALS
 RESULTS
DISCUSSION
 LITERATURE CITED
 
GE inhibited lipolysis in a dose-responsive fashion, with a 50% effective dose of 63 mg/L (Fig. 1). The 6 major ginsenosides comprised 8.06% of the weight of American GE, with Rb1 3.79%, Re 2.41%, Rg1 0.31%, Rc 0.55%, Rb2 0.11%, and Rd 0.89%, respectively. None of the individual ginsenosides (8 mg/L) alone inhibited lipolysis (n = 3; data not shown).


Figure 1
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  		FIGURE 1  Lipolysis measured by glycerol release in rat adipocytes incubated with a range of concentrations of American GE. Data are presented as means ± SEM, n = 4 except for n = 1 at 1 mg/L. Means without a common letter differ, P < 0.05. Data at 1 mg/L were not analyzed because n = 1.

 
Increasing the insulin concentration decreased both glycerol and FFA release into the incubation medium, leading to a decline in the FFA:glycerol ratio from 3.1 to 0.4 (Fig. 2A). Increasing the GE concentration also decreased both glycerol and FFA release into the incubation medium; however, it did not affect the FFA:glycerol ratio, which varied only from 2.3 to 2.1 (Fig. 2B).


Figure 2
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  		FIGURE 2  Glycerol and FFA release in rat adipocytes incubated with a range of concentrations of insulin (A, n = 3) or American GE (B, n = 5). Data are presented as means ± SEM. Means without a common letter differ, P < 0.05.

 
To determine whether GE affected adipocyte viability, adipocytes were incubated with a range of concentrations of insulin and ginseng in the absence and presence of isoproterenol [ISO; 3 µmol/L used to obtain a robust stimulation of lipolysis (33)]. Insulin inhibited lipolysis in the absence of ISO (Control) with the maximal effect at 600 pmol/L, but did not inhibit lipolysis in the presence of ISO (Fig. 3A). Similarly, GE potently inhibited lipolysis in the absence of ISO, but did not inhibit lipolysis in the presence of ISO (Fig. 3B).


Figure 3
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  		FIGURE 3  Responsiveness of rat adipocytes to the ß-adrenergic agonist ISO (3 µmol/L) in the presence of a range of concentrations of insulin (A, n = 3) or American GE (B, n = 6). Control indicates that no ISO is present. Data are presented as means ± SEM. Means without a common letter at each concentration of insulin or GE differ, P < 0.05. (A) Two-way ANOVA: effect of insulin, P < 0.001; effect of ISO, P < 0.001; interaction between insulin and ISO, P < 0.001. (B) Two-way ANOVA: effect of GE, P < 0.005; effect of ISO, P < 0.001; interaction between GE and ISO, P < 0.003.

 
The PI3-K inhibitor wortmannin (100 nmol/L) partially reversed the antilipolytic effect of insulin (150 pmol/L, Fig. 4), but did not affect the antilipolytic effect of GE (63 mg/L). Similarly, GE did not affect phosphorylation of PKB, the downstream target of PI3-K, whereas insulin increased phosphorylation of PKB in defatted cell lysates (Fig. 5A). Increased PKB phosphorylation was detected in cell lysates, the cytosolic fraction, and the particulate fraction of adipocytes treated with insulin (Fig. 5B and C).


Figure 4
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  		FIGURE 4  Lipolysis in rat adipocytes incubated with the PI3-K inhibitor wortmannin (100 nmol/L) in the absence and presence of insulin (150 pmol/L) and American GE (63 mg/L). Basal indicates that no treatment is present; control indicates that no wortmannin is present. Data are presented as means ± SEM, n = 4. Means without a common letter differ, P < 0.05. Two-way ANOVA: effect of treatment, P < 0.001; effect of inhibitor, P < 0.009; interaction between treatment and inhibitor, P < 0.03.

 

Figure 5
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  		FIGURE 5  Effects of insulin and GE on PKB phosphorylation. (A) Effects of insulin (Ins, 900 pmol/L) and a range of concentrations of Korean GE (125–1000 mg/L) on PKB phosphorylation in cell lysates. (B) Effects of insulin (900 pmol/L) and Korean GE (500 mg/L) on PKB phosphorylation in cell lysates, cytosolic fraction, and particulate fraction. Control (Con) indicates that no treatment is present. Results shown are representative of 3 independent experiments. (C) Densitometric analysis of phospho-PKB (P-PKB) and total PKB (T-PKB) in cell lysates, cytosolic fraction, and particulate fraction. AU, arbitrary units. Data are presented as means ± SEM, n = 3. Means in each fraction without a common letter differ, P < 0.05.

 
The nonselective PDE inhibitor enprofylline completely reversed the antilipolytic effects of both insulin (150 pmol/L) and GE (63 mg/L, Fig. 6A). However, although the specific PDE3 inhibitor cilostamide (5 µmol/L) completely reversed insulin antilipolysis compared with basal with cilostamide, it did not affect GE antilipolysis (P > 0.2, Fig. 6B). In contrast, the specific PDE4 inhibitor rolipram (10 µmol/L) did not affect insulin antilipolysis (P > 0.3), but reversed the effect of GE such that GE inhibited lipolysis by only 23.4% compared with basal with rolipram (P > 0.1). The combination of cilostamide and rolipram completely reversed GE antilipolysis compared to basal with cilostamide and rolipram.


Figure 6
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  		FIGURE 6  Effects of various PDE inhibitors on insulin and GE antilipolysis. (A) Lipolysis in rat adipocytes incubated with the nonselective PDE inhibitor enprofylline (1 mmol/L) in the absence and presence of insulin (150 pmol/L) and American GE (63 mg/L). Data are presented as means ± SEM, n = 4. Means without a common letter differ, P < 0.05. Two-way ANOVA: effect of treatment, P < 0.009; effect of inhibitor, P < 0.001; interaction between treatment and inhibitor, P < 0.02. (B) Lipolysis in rat adipocytes incubated with the specific PDE3 inhibitor cilostamide (CIL, 5 µmol/L), the specific PDE4 inhibitor rolipram (ROL, 10 µmol/L), and the combination of cilostamide (5 µmol/L) and rolipram (10 µmol/L) in the absence and presence of insulin (90 pmol/L) and Korean GE (100 mg/L). Basal indicates that no treatment is present; control (Con) indicates that no PDE inhibitor is present. Data are presented as means ± SEM, n = 8. Means without a common letter differ, P < 0.05. Two-way ANOVA: effect of treatment, P < 0.003; effect of inhibitor, P < 0.001; interaction between treatment and inhibitor, P < 0.05.

 

   DISCUSSION
TOP
 ABSTRACT
 METHODS AND MATERIALS
 RESULTS
 DISCUSSION
LITERATURE CITED
 
This study aimed to investigate the antilipolytic effect of GE in rat adipocytes and the intracellular signaling pathway for GE antilipolysis. PDE3B is the key enzyme mediating the antilipolytic action of insulin in adipocytes. Our present study showed that, like insulin, GE inhibits lipolysis but the signaling pathway for GE antilipolysis is different from that activated by insulin. Unlike insulin antilipolysis, the activation of PI3-K and PKB is not involved in GE antilipolysis. Moreover, PDE3B is not the only downstream target for GE antilipolysis; PDE4 also mediates GE antilipolysis.

GE and insulin inhibited both glycerol and FFA release from rat adipocytes. However, the FFA:glycerol ratio for insulin ranged from 3.1 to 0.4, whereas the FFA:glycerol ratio for GE varied only from 2.3 to 2.1. Increasing the concentration of insulin should both reduce lipolysis and increase FFA reesterification (30,34), thus decreasing the FFA:glycerol ratio in a concentration-dependent manner. In contrast, the FFA:glycerol ratio for GE was independent of concentration, suggesting that GE reduced lipolysis but did not increase FFA reesterification. This is consistent with the observation that GE stimulates glucose transport only minimally (27,35). Moreover, inhibition of lipolysis by GE could not be ascribed to nonspecific cell damage because adipocytes continued to respond to isoproterenol in the presence of GE.

Ginsenosides, the best-studied active constituents of ginseng, have effects on the central nervous system, cardiovascular system, and immune function (36). Adipocytes were incubated with individual ginsenosides at 8 mg/L to match the concentration of total ginsenosides in GE, but even at this high concentration, individual ginsenosides did not inhibit lipolysis. It is not known whether a combination of 2 or more ginsenosides can generate an antilipolytic effect. Adenosine and pyroglutamic acid contained in Korean red ginseng powder inhibited lipolysis in rat adipocytes (27). The effect of adenosine was eliminated in the present study by inclusion of adenosine deaminase in the incubation. Currently, it is not known whether the antilipolytic effect of GE in the present study is attributable to pyroglutamic acid or to other, as yet uncharacterized components of GE.

The insulin signaling pathway includes a cascade of phosphorylation from the insulin receptor through PDE3B, including insulin receptor substrates, PI3-K and PKB (37). The present study showed that GE antilipolysis was independent of PI3-K, and also that GE did not affect PKB phosphorylation. Therefore, PI3-K and PKB are not involved in the signaling pathway for GE antilipolysis. However, the present study showed that the nonselective PDE inhibitor enprofylline reversed both GE and insulin antilipolysis, suggesting that the downstream target of GE is PDE. In agreement with a recent study (38), our data showed that the specific PDE3 inhibitor cilostamide and the specific PDE4 inhibitor rolipram both increased basal lipolysis by ~30%, indicating an antilipolytic role for both PDE3 and PDE4 in basal lipolysis in rat adipocytes. The novel finding in the present study is that the PDE4 inhibitor alone reversed GE antilipolysis nearly completely and the combination of PDE3 and PDE4 inhibitors completely reversed GE antilipolysis. It is reasonable to conclude that GE inhibits lipolysis by activating both PDE3 and PDE4 through a signaling pathway that differs from that of insulin.

The antilipolytic effect of GE in vitro is consistent with its hypolipidemic effects in humans. Administration of GE (Panax ginseng, extracted in 50% ethanol) for 8 wk (6 g/d) decreased serum total cholesterol, triglyceride, LDL, and increased HDL in humans (39). It would be expected that inhibition of lipolysis reduces plasma FFA concentration and availability for hepatic triglyceride synthesis. Whether the same constituent of GE is responsible for its antilipolytic effects in vitro and its hypolipidemic effects in humans is not known and should be a subject for future investigation.

In summary, GE inhibits lipolysis in rat adipocytes and its antilipolytic action is mediated in part by PDE4. Furthermore, activation of PDE3 and PDE4 in rat adipocytes by GE is through a signaling pathway that is different from that activated by insulin. Therefore, GE has the potential to serve as a useful tool for the investigation of alternative signaling pathways for activating PDE in rat adipocytes.


   ACKNOWLEDGMENTS
 
The authors thank Yung-Shen Huang for helpful discussions and Paul Johns for ginsenoside analysis.


   FOOTNOTES
 
1 Presented in part at the 2001 annual meeting of the North American Association for the Study of Obesity, October 7-10, 2001, Québec City, QC, Canada [Reaves LA, Edens NK. Extract of American ginseng (Panax quinquefolius) inhibits lipolysis in vitro (abstract). Obes. Res. 2001;9(Suppl. 3):143S] and in part at the 2003 annual meeting of the North American Association for the Study of Obesity, October 11-15, 2003, Ft. Lauderdale, FL [Wang H, Reaves LA, Edens NK. Korean ginseng antilipolysis may be mediated in part by phosphodiesterase 4 in rat adipocytes in vitro (abstract). Obes. Res. 2003;11(Suppl.):A46]. Back

2 Funded by Ross Products Division, Abbott Laboratories, Columbus, OH. Back

4 Abbreviations used: BSA, bovine serum albumin; DMSO, dimethyl sulfoxide; FFA, free fatty acids; GE, ginseng extract; ISO, isoproterenol; KRH, Krebs-Ringer's-HEPES; PDE, phosphodiesterase; PDE3, phosphodiesterase 3; PDE4, phosphodiesterase 4; PI3-K, phosphatidylinositol 3-kinase; PKB, protein kinase B. Back

Manuscript received 15 April 2005. Initial review completed 18 May 2005. Revision accepted 6 November 2005.


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 ABSTRACT
 METHODS AND MATERIALS
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 DISCUSSION
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