To develop an anti-obesity agent containing dietary components, we focused on the mechanisms that enhance both lipolysis and fatty acid oxidation. Caffeine and arginine (CA), a nonselective adenosine-receptor antagonist and an inducer of lipolytic hormone, respectively, were used to stimulate lipolysis. Soy isoflavones and L-carnitine (SL), stimulators of carnitine palmitoyl transferase 1A and a cofactor for beta-oxidation of fatty acids, respectively, were used to enhance fatty acid oxidation. Effects of a combination of CA and SL (CASL) on lipid metabolism were studied in vitro and in vivo. During 3T3-L1 differentiation, lipid accumulation was significantly lower in cells treated with CASL (50 micromol/L, 1 mmol/L, 1 micromol/L, and 1 mmol/L, respectively) compared with each alone. Lipolysis was also significantly greater in 3T3-L1 adipocytes treated with CASL (50 micromol/L, 1 mmol/L, 10 micromol/L and 0.5 mmol/L, respectively) compared with each alone. In addition, treatment with higher concentrations of CASL (2 mmol/L, 1 mmol/L, 10 micromol/L, and 1 mmol/L, respectively) significantly enhanced beta-oxidation in HepG2 cells. The effects of CASL-containing diets (250 mg, 6 g, 200 mg, and 1.5 g/kg diet, respectively) were studied in vivo. When KK mice were food deprived for 48 h and subsequently refed a fat-free diet for 72 h, hepatic triglyceride (TG) accumulation was significantly lower in mice fed CASL compared with the control mice. In addition, after obese KK mice were fed a low-fat diet for 2 wk, adipose tissue weights were significantly lower in those fed CASL, but not CA or SL alone, compared with the control mice. Plasma and liver TG levels were also lower in mice fed CASL than in the control mice. These results suggest that CASL is effective for controlling obesity.
We have previously reported that heat-killed Lactobacillus plantarum L-137 is a potent inducer of interleukin-12 (IL-12) in vivo as well as in vitro in mice. In order to develop effective usage of L. plantarum L-137 for tumor immunotherapy, we examined its antitumor effect against DBA/2 mice inoculated with syngenic P388D1 tumor cells in different treatment schedules. Daily injection of L. plantarum L-137 from the day of tumor inoculation induced a steep increase in plasma IL-12 only after the first injection but not after subsequent injections, and had no effect on tumor growth and survival time. In contrast, daily injection of L. plantarum L-137 from the 7th day after tumor inoculation exerted a marked antitumor effect but such an effect was not evident in mice treated with L. plantarum L-137 twice a week from the 7th day. IL-12 production was considerably impaired at the first injection but steeply increased after the third injection in the mice injected daily with L. plantarum L-137 from the 7th day. Our results suggest that daily administration of L. plantarum L-137 is required to exert an antitumor effect at the late stages of tumor development when IL-12 production is considerably impaired.
Turmeric (Curcuma longa) is a widely used spice that has various biological effects, and aqueous extracts of turmeric exhibit potent antioxidant activity and anti-inflammatory activity. Bisacurone, a component of turmeric extract, is known to have similar effects. Oxidative stress and inflammatory cytokines play an important role in ethanol-induced liver injury. This study was performed to evaluate the influence of a hot water extract of C. longa (WEC) or bisacurone on acute ethanol-induced liver injury. C57BL/6 mice were orally administered WEC (20 mg/kg body weight; BW) or bisacurone (60 µg/kg BW) at 30 min before a single dose of ethanol was given by oral administration (3·0 g/kg BW). Plasma levels of aspartate aminotransferase and alanine aminotransferase were markedly increased in ethanol-treated mice, while the increase of these enzymes was significantly suppressed by prior administration of WEC. The increase of alanine aminotransferase was also significantly suppressed by pretreatment with bisacurone. Compared with control mice, animals given WEC had higher hepatic tissue levels of superoxide dismutase and glutathione, as well as lower hepatic tissue levels of thiobarbituric acid-reactive substances, TNF-α protein and IL-6 mRNA. These results suggest that oral administration of WEC may have a protective effect against ethanol-induced liver injury by suppressing hepatic oxidation and inflammation, at least partly through the effects of bisacurone.
BackgroundWe have previously shown that a combination of glucosyl hesperidin (G-hesperidin) plus caffeine reduces accumulation of body fat, whereas G-hesperidin or caffeine alone shows little effect on high-fat diet-induced obesity in mice. The aim of this study is to evaluate the anti-obesity effect of G-hesperidin plus caffeine on body fat and serum TG in healthy subjects with moderately high body mass index (BMI) and serum TG. Since we considered that there are individual differences in caffeine sensitivity, we conducted dose-finding study of caffeine combined with G-hesperidin.MethodsSeventy-five healthy subjects with moderately high BMI (24–30 kg/m2) and serum TG (100–250 mg/dl) were divided and assigned to 12-week intervention with daily intakes of 500 mg of G-hesperidin with or without 25, 50, or 75 mg of caffeine, or placebo in a randomized double-blind placebo-controlled design .ResultsAfter intervention, decreases in abdominal fat area (AFA), especially subcutaneous fat area (SFA), were significantly greater in the G-hesperidin with 50-mg caffeine group (AFA:-8.4 ± 21.9 v.s. 16.3 ± 34.1 cm2; p < 0.05, SFA: -9.3 ± 17.1 v.s. 11.2 ± 18.3 cm2; p < 0.01) and in the G-hesperidin with 75-mg caffeine group (AFA:-17.0 ± 31.4 v.s. 16.3 ± 34.1 cm2; p < 0.01, SFA: -12.4 ± 18.7 v.s. 11.2 ± 18.3 cm2; p < 0.01) than in the placebo group. Fat-decreasing effects of G-hesperidin were enhanced dose-dependently by caffeine addition. BMI decreases were significantly greater in the G-hesperidin with 75-mg caffeine group than in the placebo group (-0.56 ± 0.74 v.s. -0.02 ± 0.58 kg/m2; p < 0.05). G-hesperidin with/without caffeine had no effect on serum TG (p > 0.05 v.s. placebo).ConclusionsThese data suggested that a combination of 500-mg G-hesperidin with 50- or 75-mg caffeine may be useful for the prevention or treatment of obesity.Trial registrationUMIN Clinical Trials Registry 000019241.
The immunopotentiating activity ef nigereoligosaccharides (NOS), a mixture of nigerose, nigerosyl glucose and nigerosyl maltose, was studied in vitro and in vivo in mice. Mitogen-induced proliferation of splenocytes from normal mice was augmented in a dose-dependent mallner by nigerose of NOS. NOS enhanced interleukin 12 aL-12) and interferon-7 (IFN-7) production by normal splenocytes in the presence of the potent IL-12 inducer, heat-killed Lac-tobaciUusplantaram L-137, in vitro. Consistent with the in vitro finding, L. plantarum L-137-induced IL-12 production and IL-2-induced IFN-y production were augmented in mice fed with a 14.6% NOS diet for 2 weeks compared with mice fed with a colltrol diet. Notably, mice fed with the NOS diet showed significantly longer suryival time than the control mice after the induction of an endogenous infectien by administering 5-fluorouracil in a Iethal dose. Taken together, these results suggest that NOS may exert immunopotentiating actiyity through the actiyation ef an IL-12-dependent T helper 1-like immune respense.
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