Mohsen Araghi-Niknam

Antioxidant activity of dioscorea and dehydroepiandrosterone (DHEA) in older humans.

Dioscorea is a yam steroid extract used in commercial steroid synthesis and consumed by people. DHEA is a steroid which declines with age, but without known activity. This study was designed to determine whether dioscorea supplementation could increase serum dehydroepiandrosterone sulfate (DHEAS) in humans and modulate lipid levels in older people. The subjects were selected volunteers aged 65-82 years. The serum DHEAS level, lipid peroxidation and lipid profile were assessed. Three weeks of dioscorea supplementation had no affect on serum DHEAS level. However DHEA intake of 85 mg/day increased serum DHEA levels 100.3%. DHEA and dioscorea significantly reduced serum lipid peroxidation, lowered serum triglycerides, phospholipid and increased HDL levels. Both DHEA and the steroid yam extract, dioscorea, have significant activities as antioxidant to modify serum lipid levels.

Inhibition of Smoking-Induced Platelet Aggregation by Aspirin and Pycnogenol

The effects of a bioflavonoid mixture, Pycnogenol, were assessed on platelet function in humans. Cigarette smoking increased heart rate and blood pressure. These increases were not influenced by oral consumption of Pycnogenol or Aspirin just before smoking. However, increased platelet reactivity yielding aggregation 2 hours after smoking was prevented by 500 mg Aspirin or 100 mg Pycnogenol in 22 German heavy smokers. In a group of 16 American smokers, blood pressure increased after smoking. It was unchanged after intake of 500 mg Aspirin or 125 mg Pycnogenol. In another group of 19 American smokers, increased platelet aggregation was more significantly reduced by 200 than either 150 mg or 100 mg Pycnogenol supplementation. This study showed that a single, high dose, 200 mg Pycnogenol, remained effective for over 6 days against smoking-induced platelet aggregation. Smoking increased platelet aggregation that was prevented after administration of 500 mg Aspirin and 125 mg Pycnogenol. Thus, smoking-induced enhanced platelet aggregation was inhibited by 500 mg Aspirin as well as by a lower range of 100-125 mg Pycnogenol. Aspirin significantly (p<0.001) increased bleeding time from 167 to 236 seconds while Pycnogenol did not. These observations suggest an advantageous risk-benefit ratio for Pycnogenol.

Prevention of immune dysfunction and vitamin E loss by dehydroepiandrosterone and melatonin supplementation during murine retrovirus infection

Female C57BL/6 mice infected with the LP‐BM5 leukaemia retrovirus developed murine acquired immune‐deficiency syndrome (AIDS). Dehydroepiandrosterone (DHEA) and melatonin (MLT) modify immune dysfunction and prevent lipid peroxidation. We investigated whether DHEA and MLT could prevent immune dysfunction, excessive lipid peroxidation, and tissue vitamin E loss induced by retrovirus infection. Retrovirus infection inhibited the release of T helper 1 (Th1) cytokines, stimulated secretion of Th2 cytokines, increased hepatic lipid peroxidation, and induced vitamin E deficiency. Treatment with DHEA or MLT alone, as well as together, largely prevented the reduction of B‐ and T‐cell proliferation as well as of Th1 cytokine secretion caused by retrovirus infection. Supplementation also suppressed the elevated production of Th2 cytokines stimulated by retrovirus infection. DHEA and MLT simultaneously reduced hepatic lipid peroxidation and prevented vitamin E loss. The use of DHEA plus MLT was more effective in preventing retrovirus‐induced immune dysfunction than either DHEA or MLT alone. These results suggest that supplementation with DHEA and MLT may prevent cytokine dysregulation, lipid oxidation and tissue vitamin E loss induced by retrovirus infection. Similarly, hormone supplementation also modified immune function and increased tissue vitamin E levels in uninfected mice.

MODULATION OF IMMUNE DYSFUNCTION DURING MURINE LEUKAEMIA RETROVIRUS INFECTION OF OLD MICE BY DEHYROEPIANDROSTERONE SULPHATE (DHEAS)

Ageing, leukaemia and acquired immune deficiency syndrome (AIDS) are conditions with dysregulated cytokine production. As dehydroepiandrosterone sulphate (DHEAS) restored normal cytokine production in old mice its effects on retrovirally infected old mice were investigated. Retrovirus infection and ageing‐induced immune dysfunction. Murine retrovirus‐infected old C57BL/6 female mice consumed 0·22 or 0·44 μg of DHEAS/mouse/day beginning 2 weeks postinfection for 10 weeks. DHEAS largely prevented the retrovirus‐induced reduction in T‐cell and B‐cell mitogenesis. DHEAS supplement prevented loss of cytokines [interleukin‐2 (IL‐2) and interferon‐γ] secretion by mitogen‐stimulated splenocytes representing T helper 1 (Th1) cell phenotypes. It also suppressed the retrovirus‐induced, excessive production of cytokines (IL‐6 and IL‐10) by Th2 cells. The highest dose of DHEAS reduced IL‐6 production by splenocytes from uninfected old mice by 75% while increasing their IL‐2 secretion by nearly 50%. Thus immune dysfunction induced by ageing, even when exacerbated by murine retrovirus infection, was largely prevented by DHEAS.

Cytokine dysregulation and increased oxidation is prevented by dehydroepiandrosterone in mice infected with murine leukemia retrovirus.

Abstract The effects of murine leukemia retrovirus infection on production of cytokines was investigated in mice fed different doses of dehydroepiandrosterone (DHEA). Young C57BL/6 female mice were injected with LP-BM5 murine retrovirus or were kept as uninfected controls. Two weeks later, each group was divided into subgroups: fed unsupplemented AIN 93 diet as the control, or diets supplemented with 0.02% DHEA (0.9 mg/mouse/day) or 0.06% DHEA (2.7 mg/mouse/day). The uninfected mice supplemented with 0.06% DHEA showed a significant (P < 0.05) increase in interleukin-2 (IL-2) and γ-interferon (IFN-γ) production, and hepatic vitamin E levels. Retroviral infection induced severe oxidative stress that was reduced by DHEAS supplementation in retrovirally infected mice. DHEA supplementation prevented the retrovirus-induced loss of cytokines (IL-2 and IFN-γ) secretion by mitogen stimulated spleen cells. DHEA also suppressed the production of cytokines interleukin-6 (IL-6) and tumor necrosis factor-β (TNF-β) by T helper 2 (Th2) cells which were otherwise stimulated by retrovirus infection. Thus, immune dysfunction and increased oxidation induced by murine retrovirus infection were largely prevented by DHEA.

Modulation of Cytokine Production by Dehydroepiandrosterone (DHEA) Plus Melatonin (MLT) Supplementation of Old Mice

Abstract Tissue levels of the antioxidants melatonin (MLT) and dehydroepiandrosterone (DHEA) decline with age, and this decline is correlated with immune dysfunction. The aim of the current study is to determine whether hormone supplementation with MLT and DHEA together would synergize to reverse immune senescence. Old (16.5 months) female C57BL/6 mice were treated with DHEA, MLT, or DHEA + MLT. As expected, splenocytes were significantly (P < 0.05) higher in old mice as compared to young mice. DHEA, MLT, and DHEA + MLT significantly (P < 0.005) increased B cell proliferation in young mice. However, only MLT and DHEA + MLT significantly (P < 0.05) increased B cell proliferation in old mice. DHEA, MLT, and DHEA + MLT help to regulate immune function in aged female C57BL/6 mice by significantly (P < 0.05) increasing Th1 cytokines, IL-2, and IFN-γ or significantly (P < 0.05) decreasing Th2 cytokines, IL-6, and IL-10, thus regulating cytokine production. DHEA and MLT effectively modulate suppressed Th1 cytokine and elevated Th2 cytokine production; however, their combined use produced only a limited additive effect.

Pine bark extract reduces platelet aggregation

The effects of long-term consumption of the bioflavonoid mixture, French maritime pine bark extract (Pycnogenol(R)), were assessed on aggregation of platelets from cigarette smokers and nonsmokers. Previously we showed that a single dose of Pycnogenol(R) reduced platelet aggregation in cigarette smokers in a dose-response fashion. Cigarette smoking increased platelet reactivity aggregation when measured 2 h after smoking the first cigarette of the day. Blood was collected immediately before and 5 min after smoking three cigarettes each. Smoking increased platelet aggregation (1.17 +/- 0.04). However 200 mg Pycnogenol(R)/day, taken 3 h prior to first cigarette for the day for 2 months, significantly (p <.0023) reduced smoke-induced platelet aggregation (0.98 +/- 0.05) to the level of nonsmokers. In a group of 19 nonsmokers, platelet aggregation was measured during in vitro stimulation by platelet aggregation factor (PAF) after 4 or 8 weeks of 200 mg/day of Pycnogenol(R) consumption. Platelet aggregation was significant when induced in vitro by PAF. However, Pycnogenol(R) consumption did not change platelet aggregation, suggesting that Pycnogenol(R)s regulation of aggregation is by another mechanism. Thromboxane A2 (TxA2) is increased in smokers by release from platelets and rapidly becomes thromboxane B2 (TxB2). Smoking increased TxB2, which was prevented by Pycnogenol(R), lowering TxB2 levels to those of nonsmokers. However, Pycnogenol(R) had no effect on the lower levels of TxB2 in nonsmokers. These observations suggest that Pycnogenol(R) supplementation reduces a risk factor for cardiovascular diseases, that is, platelet aggregation in smokers. The bioflavonoids in Pycnogenol(R) reduced platelet aggregation stimulated by tobacco smoke.

Immunomodulation by pycnogenol® in retrovirus-infected or ethanol-fed mice

Pycnogenol is a commercial mixture of bioflavonoids that exhibits antioxidative activity. The effects of dietary pycnogenol on immune dysfunction in normal mice as well as those fed ethanol or infected with the LP-BM5 murine retrovirus were determined. The ethanol consumption and retrovirus infection caused abnormalities in the function and/or structure of a broad array of cells involved in humoral and cellular immunity. Pycnogenol enhanced in vitro IL-2 production by mitogen-stimulated splenocytes if its production was suppressed in ethanol-fed or retrovirus-infected mice. Mitogenesis of splenocytes did not show a significant change in mice treated with pycnogenol. It reduced the elevated levels of interleukin-6 produced in vitro by cells from retrovirus infected mice and IL-10 secreted by spleen cells from mice consuming ethanol. Natural killer cell cytotoxicity was increased with pycnogenol treatment.

Dehydroepiandrosterone (DHEA) sulfate prevents reduction in tissue vitamin E and increased lipid peroxidation due to murine retrovirus infection of aged mice

Abstract Dietary effects of dehydroepiandrosterone sulfate (DHEAS) supplementation on tissue antioxidants and lipids were investigated in retrovirus infected mice. DHEA is a powerful antioxidant and immunomodulator whose production declines with age. For this study, twenty-four female, 15-month-old C57BL/6 mice were left uninfected while twenty-four were infected with LP-BM5 murine leukemia virus, causing murine AIDS. The retroviral infection caused immune dysfunction and loss of hepatic and cardiac vitamins E and A, resulting in increased lipid peroxides. Treatment with DHEAS at 0.01 or 0.005% in drinking water for 10 weeks post-infection significantly (P < 0.05) lowered lipid peroxidation in both heart and liver tissues. Treatment with DHEAS also largely prevented loss of the antioxidants, such as vitamin E and A, and prevented loss of phospholipid in the hearts and livers of the old uninfected as well as infected mice. This study suggests that DHEAS supplementation reduces damage associated with elevated oxidation due to aging and retrovirus infection.

Prevention of Retrovirus-Induced Aberrant Cytokine Secretion, Excessive Lipid Peroxidation, and Tissue Vitamin E Deficiency by T Cell Receptor Peptide Treatments in C57BL/6 Mice

Abstract To test whether T cell receptor (TCR) peptide treatment can prevent immune dysfunction, excessive lipid peroxidation, and malnutrition caused by retrovirus infection, female C57BL/6 mice were infected with LP-BM5 retrovirus. Infection with retrovirus inhibited lymphocyte proliferation, cytokine release T helper 1 cells, stimulated cytokine secretion by T helper 2 cells, induced abnormal hepatic and cardiac lipid profiles, and produced excessive tissue lipid peroxidation with hepatic and cardiac vitamin E deficiency. Two weeks after infection, TCR peptides Vβ5.2, Vβ8.1, Vβ8.1 + Vβ5.2, Vβ8.1(N), and Vβ8.1© were injected to the mice at dose of 200 μg/mouse. Vβ8.1 and Vβ5.2 treatments largely maintained lymphocyte proliferation and IL-2 and IFN-γ release, and prevented excessive IL-6, IL-10, and TNF-α secretion. Concomitantly, these treatments normalized hepatic and cardiac lipid profiles, reduced tissue lipid peroxidation, and thereby significantly maintained vitamin E in the liver and heart. Vβ8.1 segments treatment did not prevent the immune dysfunction, abnormal lipid profile and lipid peroxidation, and vitamin E deficiency caused by the retrovirus infection. In conclusion, injection of intact TCR peptides during murine retrovirus infection largely prevented immune dysfunction by blocking the excessive stimulation of a T cell subset caused by retroviral superantigens. It also ameliorated malnutrition status by normalizing lipid profile, lipid peroxidation, and vitamin E deficiency. T cell immune dysfunction and its prevention by TCR peptide treatment is important in the therapy of vitamin E deficiency induced by retrovirus infection.