4-Hydroxyderricin,as a PPARγ Agonist,Promotes Adipogenesis,Adiponectin Secretion,and Glucose Uptake in 3T3-L1 Cells

Adipocyte differentiation plays a pivotal role in maintaining the production of small‐size adipocytes with insulin sensitivity, and impaired adipogenesis is implicated in insulin resistance. 4‐Hydroxyderricin (4‐HD), a phytochemical component of Angelica keiskei, possesses diverse biological properties such as anti‐inflammatory, antidiabetic, and antitumor. In the present study, we investigated the effects of 4‐HD on adipocyte differentiation. 4‐HD promoted lipid accumulation in 3T3‐L1 cells, upregulated both peroxisome proliferator‐activated receptor (PPAR)‐γ mRNA and protein expression, and acted as a ligand for PPARγ in the luciferase assay. Moreover, 4‐HD increased the mRNA and protein expression levels of adiponectin. Additionally, it promoted insulin‐dependent glucose uptake into 3T3‐L1 adipocytes and increased Akt phosphorylation and glucose transporter (GLUT) 4 mRNA expression. In summary, these findings suggest that 4‐HD, which promoted adipogenesis and insulin sensitivity in 3T3‐L1 cells, might be a phytochemical with potent insulin‐sensitizing effects.     

Astaxanthin,a Carotenoid,Stimulates Immune Responses by Enhancing IFN-γ and IL-2 Secretion in Primary Cultured Lymphocytes in Vitro and ex Vivo

Astaxanthin, a potent antioxidant carotenoid, plays a major role in modulating the immune response. In this study, we examined the immunomodulatory effects of astaxanthin on cytokine production in primary cultured lymphocytes both in vitro and ex vivo. Direct administration of astaxanthin (70–300 nM) did not produce cytotoxicity in lipopolysaccharide (LPS, 100 µg/ mL)- or concanavalin A (Con A, 10 µg/ mL)-activated lymphocytes, whereas astaxanthin alone at 300 nM induced proliferation of splenic lymphocytes (p < 0.05) in vitro. Although astaxanthin, alone or with Con A, had no apparent effect on interferon (INF-γ) and interleukin (IL-2) production in primary cultured lymphocytes, it enhanced LPS-induced INF-γ production. In an ex vivo experiment, oral administration of astaxanthin (0.28, 1.4 and 7 mg/kg/day) for 14 days did not cause alterations in the body or spleen weights of mice and also was not toxic to lymphocyte cells derived from the mice. Moreover, treatment with astaxanthin significantly increased LPS-induced lymphocyte proliferation ex vivo but not Con A-stimulated lymphocyte proliferation ex vivo. Enzyme linked immunosorbent assay (ELISA) analysis revealed that administration of astaxanthin significantly enhanced INF-γ production in response to both LPS and Con A stimulation, whereas IL-2 production increased only in response to Con A stimulation. Also, astaxanthin treatment alone significantly increased IL-2 production in lymphocytes derived from mice, but did not significantly change production of INF-γ. These findings suggest that astaxanthin modulates lymphocytic immune responses in vitro, and that it partly exerts its ex vivo immunomodulatory effects by increasing INF-γ and IL-2 production without inducing cytotoxicity.     

Flaxseed Oil Supplementation Improve Gene Expression Levels of PPAR-γ, LP(a), IL-1 and TNF-α in Type 2 Diabetic Patients with Coronary Heart Disease

This study was carried out to determine the effects of flaxseed oil administration on gene expression levels related to insulin, lipid and inflammation in overweight diabetic patients with coronary heart disease (CHD). This randomized double‐blind, placebo‐controlled trial was conducted among 60 diabetic patients with CHD. Subjects were randomly allocated into two groups to intake either 1000 mg n‐3 fatty acid from flaxseed oil containing 400 mg α‐Linolenic acid [ALA (18:3n‐3)] (n = 30) or placebo (n = 30) twice a day for 12 weeks. Gene expression related to insulin, lipid and inflammation were quantified in peripheral blood mononuclear cells (PBMC) of diabetic patients with CHD with RT‐PCR method. Results of RT‐PCR demonstrated that after the 12‐week intervention, compared with the placebo, flaxseed oil supplementation could up‐regulate gene expression of peroxisome proliferator‐activated receptor gamma (PPAR‐γ) (P = 0.02) in PBMC of diabetic patients with CHD. In addition, compared with the placebo, taking flaxseed oil supplements down‐regulated gene expression levels of lipoprotein(a) [LP(a)] (P = 0.001), interleukin‐1 (IL‐1) (P = 0.001) and tumor necrosis factor alpha (TNF‐α) (P = 0.02) in PBMC of diabetic patients with CHD. We did not observe any significant effect of flaxseed oil supplementation on gene expression levels of low‐density lipoprotein receptor (LDLR), IL‐8 and transforming growth factor beta (TGF‐β) in PBMC of diabetic patients with CHD. Overall, flaxseed oil supplementation for 12 weeks in diabetic patients with CHD significantly improved gene expression levels of PPAR‐γ, LP(a), IL‐1 and TNF‐α, but did not influence LDLR, IL‐8 and TGF‐β.