The effects of lemon flavonoids, as crude flavonoids prepared from lemon juice, were investigated in diabetic rats. The oxidative stress of eriocitrin (eriodictyol 7-O-beta-rutinoside) and hesperidin (hesperetin 7-O-beta-rutinoside) on streptozotocin-induced diabetic rats was investigated. Diabetic rats were given a diet which contained 0.2% crude flavonoids, 0.2% eriocitrin, and 0.2% hesperidin. After the 28-d feeding period, the concentration of the thiobarbituric acid-reactive substance in the serum, liver, and kidney of diabetic rats administered crude flavonoids, eriocitrin, and hesperidin significantly decreased as compared with that of the diabetic group. The levels of 8-hydroxydeoxyguanosine, which is exchanged from deoxyguanosine owing to oxidative stress, in the urine of diabetic rats administered eriocitrin and hesperidin significantly decreased as compared with that of the diabetic rat group. Crude flavonoids, eriocitrin, and hesperidin suppressed the oxidative stress in the diabetic rats. These results demonstrated that dietary lemon flavonoids of eriocitrin and hesperidin play a role as antioxidant in vivo.

Although the sesame lignans, sesaminol and sesamolinol, have been shown to possess antioxidative activity, less is known about the metabolism and antioxidative properties of sesamolin, a major constituent of sesame oil. To determine the ability of sesamolin to act as an antioxidant in vivo, we fed rats a diet containing 1% sesamolin for 2 wk and studied its metabolism and its effects on oxidative stress. About 75% of the ingested sesamolin was excreted unmetabolized in feces, but it was not detected in urine. Sesamolin and its metabolites, sesamol and sesamolinol, were excreted primarily as sulfates and glucuronides. The amount of sesamolin and its metabolites was lower in the plasma than in the liver or kidneys. When we compared rats fed a diet containing 1% sesamolin for 14 d with those fed a control diet, we found that liver weight was significantly greater in the former group. Lipid peroxidation activity, measured as 2-thiobarbituric acid reactive substances, was significantly lower in the kidneys and liver of the sesamolin-fed rats than in the controls. In addition, the amount of 8-hydroxy-2'-deoxyguanosine excreted in the urine was significantly lower in the sesamolin-fed rats. These results suggest that sesamolin and its metabolites may contribute to the antioxidative properties of sesame seeds and oil and support our hypothesis that sesame lignans reduce susceptibility to oxidative stress.

Diosgenin (Dio) is a steroid sapogenin found in plants such as Dioscorea species, and is recognized as a phytochemical against various disorders as well as a natural precursor of steroidal drugs. The present study used rats fed high-cholesterol (Chol) diets supplemented with or without 0.5% Dio for 6 wk to investigate the effects of dietary Dio on lipid metabolism. Dio supplementation significantly increased serum high-density lipoprotein Chol concentrations and fecal Chol content, and significantly decreased fecal bile acid content compared rats fed a high-Chol diet alone, showing that dietary Dio may facilitate excretion of Chol rather than bile acids. A reduction in the liver triglyceride content and intra-abdominal visceral fat was observed in Dio-supplemented rats. Interestingly, dietary Dio also significantly increased the skeletal muscle-fiber diameter and area in the thigh muscles of the rats. Mouse myoblast-derived C2C12 cells were used to examine whether Dio directly affected skeletal muscle. Dio promoted fusion of myoblasts into multinucleated cells or myotubes. Furthermore, in myotube C2C12 cells, protein levels of phosphorylated AMPactivated protein kinase (AMPK) increased with Dio treatment in a dose-dependent manner. These results indicate that Dio may not only induce myoblast fusion and enhance skeletal muscle as an energy expenditure organ, but may also activate the catabolic pathway via AMPK in skeletal muscle cells. Thus, these effects of Dio on skeletal muscles may contribute to inhibition of visceral fat accumulation. Key Words dietary supplements, lipid metabolism, cholesterol, visceral fat, skeletal muscle, skeletal muscle cells, myoblast fusion, AMPK Diosgenin (Dio; Pubchem ID 99474) is a steroid sapogenin found in plants such as Dioscorea, Trigonella, Costus, and Smilax species, and is a constituent of the saponin, dioscin, which is found in the rootstock of yam (Dioscorea) (1, 2). Dio is a natural precursor of steroidal drugs, including sex hormones and corticosteroids, indicating its importance in the pharmaceutical industry. Additionally, Dio itself has pharmacological potential and behaves as a biologically active phytochemical that is used in the treatment of various disorders, including inflammation, hypercholesterolemia, cancer, and several types of infections. Tohda et al. identified 1,25D3-membrane-associated, rapid response steroidbinding protein (1,25D3-MARRS) as a target protein of Dio and demonstrated that Dio induces axonal growth and regrowth of neurons as an exogenous stimulator of 1,25D3-MARRS, and may act on critical signaling path

SummaryWe investigated the effects of dietary Japanese yam (Dioscorea japonica Thunb.) on lipid metabolism. Male Wistar rats (6 wk old) were fed a high-cholesterol diet for 6 wk and then supplemented with 26% of Japanese yam or 0.5% of its constituent diosgenin for a further 4 wk of high-cholesterol feeding (C6-J4 and C6-D4 groups, respectively). In the C6-J4 group, body weight gains significantly decreased, but skeletal muscle fiber sizes in quadriceps significantly increased compared with the other groups. Furthermore, Japanese yam supplementation resulted in the reduction of triglyceride contents in their liver, quadriceps, and intra-abdominal visceral fat. Diosgenin supplementation resulted in an increase in the numbers of skeletal muscle fibers and decrease in the fat accumulations in liver and of the lipid contents in quadriceps. Although quadriceps cholesterol contents decreased concomitantly with increased serum HDL-cholesterol in both the groups, fecal bile acid, fecal cholesterol contents, and fecal weight were higher in the C6-J4 group than in the C6-D4 group. Meanwhile, we demonstrated that Japanese yam inhibited micellar cholesterol solubility in vitro in a concentration-dependent manner. These results suggest that Japanese yam is more effective than diosgenin in reducing fat accumulation and improving cholesterol metabolism during chronic consumption of a high-cholesterol diet.

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