Greater Efficacy of Black Ginseng (CJ EnerG) over Red Ginseng against Lethal Influenza A Virus Infection.

Black ginseng (BG, CJ EnerG), prepared via nine repeated cycles of steaming and drying of fresh ginseng, contains more accessible acid polysaccharides and smaller and less polar ginsenosides than red ginseng (RG) processed only once. Because RG exhibits the ability to increase host protection against viral respiratory infections, we investigated the antiviral effects of BG. Mice were orally administered either BG or RG extract at 10 mg/kg bw daily for two weeks. Mice were then infected with a A(H1N1) pdm09 (A/California/04/2009) virus and fed extracts for an additional week. Untreated, infected mice were assigned to either the negative control, without treatments, or the positive control, treated with Tamiflu. Infected mice were monitored for 14 days to determine the survival rate. Lung tissues were evaluated for virus titer and by histological analyses. Cytokine levels were measured in bronchoalveolar lavage fluid. Mice treated with BG displayed a 100% survival rate against infection, while mice treated with RG had a 50% survival rate. Further, mice treated with BG had fewer accumulated inflammatory cells in bronchioles following viral infection than did mice treated with RG. BG also enhanced the levels of GM-CSF and IL-10 during the early and late stages of infection, respectively, compared to RG. Thus, BG may be useful as an alternative antiviral adjuvant to modulate immune responses to influenza A virus.

Dried plum alleviates symptoms of inflammatory arthritis in TNF transgenic mice.

Dried plum (DP), a rich source of polyphenols has been shown to have bone-preserving properties in both animal models of osteoporosis and postmenopausal women. We evaluated if DP alleviated the destruction of joints in transgenic mice (TG) that overexpress human tumor necrosis factor (TNF), a genetic model of rheumatoid arthritis (RA). A four-week treatment of 20% DP diet in TG slowed the onset of arthritis and reduced bone erosions in the joints compared to TG on a regular diet. This was associated with fewer tartrate-resistant acid phosphatase (TRAP) positive cells, suggesting decreased osteoclastogenesis. A DP diet also produced significant protection of articular cartilage and reduction of synovitis. Cultures of human synovial fibroblast in the presence of TNF showed a significant increase in inflammatory interleukin (IL)-1ß, chemokines (monocyte chemoattractant protein-1: MCP1 & macrophage inflammatory protein-1 alpha: MIP1α), cartilage matrix metalloproteinases (MMP1&3), and an osteoclastogenic cytokine (receptor activator of nuclear factor-κB ligand: RANKL) compared to controls. Addition of neochlorogenic acid (NC), a major polyphenol in DP to these cultures resulted in down-regulation of these genes. In the cultures of mouse bone marrow macrophage, NC also repressed TNF-induced formation of osteoclasts and mRNA levels of cathepsin K and MMP9 through inhibition of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) expression and nuclear factor kappa B (NF-κB) activation. Our data suggested that dietary supplementation with DP inhibited TNF singling; leading to decreased erosions of bone and articular cartilage as well as synovitis.

Vitamin E suppresses ex vivo osteoclastogenesis in ovariectomized rats.

Postmenopausal osteoporosis may be caused, in part, by oxidative stress and inflammation. Vitamin E is a strong antioxidant which has been shown to have anti-inflammatory and bone-protective effects. The objective of this study was to investigate the effects of various doses of supplemental vitamin E on osteoclastogenesis in ovariectomized rats. Sixty 12-month-old female Sprague-Dawley rats were sham-operated (Sham) or ovariectomized (Ovx; 4 groups) and fed a diet containing basal levels of vitamin E (75 mg D-α tocopherol acetate per kg diet) for 220 days. Rats in three of the Ovx groups were given supplemental doses of vitamin E (300, 525, and 750 mg D-α tocopherol acetate per kg diet) for the last 100 days. Femoral bone marrow cells were isolated, cultured, and osteoclasts were counted and normalized to 1000 total bone marrow cells. Blood monocyte and lymphocyte counts were also determined. Osteoclast number was significantly higher in the Ovx control group and was suppressed by all three doses of vitamin E, although more effectively in the Ovx group that received 300 mg per kg diet vitamin E. Additionally, vitamin E suppressed the Ovx-induced increase in monocyte and lymphocyte production. The results of this study suggest that vitamin E supplementation suppresses osteoclastogenesis, possibly by inhibiting monocyte and lymphocyte production.

Flaxseed but not flaxseed oil prevented the rise in serum cholesterol due to ovariectomy in the Golden Syrian hamsters.

This study was designed to investigate whether flaxseed oil (FO) exerts hypocholesterolemic effects similar to ground whole flaxseed (WF) and to gain insight into its hypocholesterolemic mechanism. Forty-eight 6-month-old female Golden Syrian hamsters were either sham-operated (Sham) or ovariectomized (Ovx) and randomly assigned to one of four treatment groups (n = 12/group) for 90 days: Sham, Ovx, Ovx+WF, or Ovx+FO. Hamsters in the Sham and Ovx groups were fed a semipurified diet (control), whereas Ovx+WF and Ovx+FO received the same basic diet supplemented with either WF (15% wt/wt) or FO (amount equivalent to the oil contribution of WF). Ovariectomy significantly (P < .05) increased serum total concentrations by approximately 15%. WF, but not FO, prevented (P < .05) the ovariectomy-induced increase in serum total cholesterol concentration (12% and 4% reduction by WF and FO, respectively). Hamsters fed FO or WF had high-density lipoprotein (HDL)-cholesterol concentrations similar to those of the Ovx hamsters receiving the control diet. Non-HDL-cholesterol concentrations were lowest in the WF group, albeit not statistically different from the other treatment groups. There were no significant differences among groups in serum triglyceride concentration and liver lipids. Both WF and FO more than doubled the hepatic protein levels of 7α-hydroxylase in comparison to the Ovx hamsters receiving the control diet (P < .05). Our findings suggest that increased bile acid synthesis is one of the major cholesterol-lowering mechanisms of flaxseed and that other flaxseed components, aside from its oil, contribute to its hypocholesterolemic property. The cholesterol-lowering effects of other components of flaxseed and their mechanisms of action need to be further explored.

Ipriflavone modulates IGF-I but is unable to restore bone in rats.

Previously it has been reported that ipriflavone can prevent bone loss in ovarian hormone deficient rats. The present study evaluated whether ipriflavone was able to restore bone mass in osteopenic ovariectomized rats. Seventy-two, 90 day-old Sprague-Dawley rats were divided into six groups (sham two groups; ovariectomized four groups). Thirty-five days from the date of surgery, one sham and one ovx group were killed to verify the occurrence of bone loss. The remaining four groups were sham, ovx, ovx + ipriflavone (100 mg[sol ]kg body weight per day), or ovx + 17beta-estradiol (10 microg[sol ]kg body weight daily) for a period of 65 days. Ipriflavone was ineffective in restoring bone density and unlike estrogen did not prevent bone resorption as evidenced by increased (p < 0.05) urinary excretion of hydroxyproline and serum tartrate-resistant acid phosphatase activity. Ipriflavone increased (p < 0.05) the expression of IGF-I in the femur. These observations suggest that higher doses of ipriflavone or longer-term studies may be necessary to restore bone mass.

Soy isoflavones prevent ovariectomy-induced atherosclerotic lesions in Golden Syrian hamster model of postmenopausal hyperlipidemia.

OBJECTIVE: Soy isoflavones, as dietary supplements, may reduce the formation of atherosclerotic lesions that increase in women after menopause. The objectives of this study were to determine whether (1) ovariectomized (ovx) hamsters will develop atherosclerotic lesions and (2) soy isoflavones can dose-dependently prevent the ovariectomy-induced rise in plasma cholesterol and atherosclerotic lesions in hamsters. DESIGN: Seventy-two 6-month-old female Golden Syrian hamsters were randomly assigned to six groups: sham-operated; ovx control; ovx + 17beta-estradiol (E(2); 10 microg E(2) per kilogram of body weight); and ovx + 9.5 (low-dose), 19 (medium-dose), or 38 (high-dose) mg isoflavones per kilogram diet. Treatments were initiated immediately after surgery and continued for 120 days. Blood was drawn via abdominal aorta for assessment of circulating lipids, and tissues were collected, including the aortic arch for assessment of atherosclerotic lesions. RESULTS: All three doses of isoflavones prevented the rise in plasma total cholesterol from ovx; and, as the isoflavone dose increases, the cholesterol-lowering effects of isoflavones become more pronounced (7.8%, 11.8%, and 19.6% reductions in total cholesterol for low-dose, medium-dose, and high-dose, respectively). Ovx hamsters developed atherosclerotic lesions without being on an atherogenic diet. Ninety-two percent of hamsters in the ovx control group had atherosclerotic lesions compared with only 8% in sham, 62% in the E(2) group, 29% in the low-dose group, 38% in the medium-dose group, and 58% in the high-dose group. The aortic fatty streak area was approximately 20 times higher in ovx hamsters compared with the sham animals. All doses of isoflavones were able to significantly reduce fatty streak area to that of the sham group. CONCLUSIONS: Soy isoflavones, independent of the protein source, prevent hypercholesterolemia and the formation of atherosclerotic lesions induced by ovarian hormone deficiency in hamsters. The antiatherogenic mechanisms of isoflavones need further investigation.