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The antiviral effect of glycyrrhizin (GR), an active component of licorice roots, was investigated in mice infected with influenza virus A2 (H2N2). When mice that had been exposed to 10 50% lethal doses of the virus were treated intraperitoneally with 10 mg of GR per kg of body weight 1 day before infection and 1 and 4 days postinfection, all of the mice survived over the 21-day experimental period. At the end of this period, the mean survival time (in days) for control mice treated with saline was 10.5 days, and there were no survivors. The grade of pulmonary consolidations and the virus titers in the lung tissues of infected mice treated with GR were significantly lower than those in the lung tissues of infected mice treated with saline. GR did not show any effects on the viability or replication of influenza virus A2 in vitro. When splenic T cells from GR-treated mice were adoptively transferred to mice exposed to influenza virus, 100% of the recipients survived, compared to 0% survival for recipient mice inoculated with naive T cells or splenic B cells and macrophages from GR-treated mice. In addition, the antiviral activities of GR on influenza virus infection in mice were not demonstrated when it was administered to infected mice in combination with anti-gamma interferon (anti-IFN-gamma) monoclonal antibody. These results suggest that GR may protect mice exposed to a lethal amount of influenza virus through the stimulation of IFN-gamma production by T cells, because T cells have been shown to be producer cells of IFN-gamma stimulated with the compound.

Dietary supplementation with polyphenolic antioxidants to animals was shown to be associated with inhibition of LDL oxidation and macrophage foam cell formation, and attenuation of atherosclerosis development. We investigated the effects of pomegranate juice (PJ, which contains potent tannins and anthocyanins) consumption by atherosclerotic patients with carotid artery stenosis (CAS) on the progression of carotid lesions and changes in oxidative stress and blood pressure. Ten patients were supplemented with PJ for 1 year and five of them continued for up to 3 years. Blood samples were collected before treatment and during PJ consumption. In the control group that did not consume PJ, common carotid intima-media thickness (IMT) increased by 9% during 1 year, whereas, PJ consumption resulted in a significant IMT reduction, by up to 30%, after 1 year. The patients’ serum paraoxonase 1 (PON 1) activity was increased by 83%, whereas serum LDL basal oxidative state and LDL susceptibility to copper ion-induced oxidation were both significantly reduced, by 90% and 59%, respectively, after 12 months of PJ consumption, compared to values obtained before PJ consumption. Furthermore, serum levels of antibodies against oxidized LDL were decreased by 19%, and in parallel serum total antioxidant status (TAS) was increased by 130% after 1 year of PJ consumption. Systolic blood pressure was reduced after 1 year of PJ consumption by 12% [corrected] and was not further reduced along 3 years of PJ consumption. For all studied parameters, the maximal effects were observed after 1 year of PJ consumption. Further consumption of PJ, for up to 3 years, had no additional beneficial effects on IMT and serum PON1 activity, whereas serum lipid peroxidation was further reduced by up to 16% after 3 years of PJ consumption. The results of the present study thus suggest that PJ consumption by patients with CAS decreases carotid IMT and systolic blood pressure and these effects could be related to the potent antioxidant characteristics of PJ polyphenols.

BACKGROUND AND PURPOSE: Genistein aglycone positively affects bone loss in postmenopausal women, but bone quality data are still lacking. To clarify this, we investigated the effects of genistein compared with alendronate, raloxifene and oestradiol in an animal model of established osteoporosis. EXPERIMENTAL APPROACH: Six months after ovariectomy, 96 ovariectomized (OVX) rats were divided into 8 equal groups, randomized to treatments (genistein aglycone (1 and 10 mg kg(-1) s.c.); alendronate (0.003 and 0.03 mg kg(-1) s.c.); raloxifene hydrochloride (0.05 and 0.5 mg kg(-1) s.c.); 17-alpha-ethinyl oestradiol (0.003 and 0.03 mg kg(-1) s.c.)) for 12 weeks. Untreated OVX (n=12) and sham OVX (n=12) were used as controls. At the beginning and end of treatment, bone mineral density (BMD) and bone mineral content (BMC) were assessed. At the end of the experiment, calcium, phosphorus, bone-alkaline phosphatase (b-ALP), collagen C-telopeptide (CTX), osteoprotegerin (OPG) and soluble receptor activator of nuclear factor-kappaB ligand (sRANKL) were assayed. Femurs were removed and tested for breaking strength and histology. KEY RESULTS: Genistein (10 mg kg(-1)) showed a greater increase in both BMD (P<0.0001 vs OVX) and BMC than all the other treatments. Moreover, genistein significantly increased breaking strength, bone quality, b-ALP (P<0.0001 vs OVX) and OPG, and reduced CTX and sRANKL compared with the other treatments at all dose levels. CONCLUSIONS AND IMPLICATIONS: The results strongly suggest that the genistein aglycone might be a new therapy for the management of postmenopausal osteoporosis in humans.

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.

Ninety men and women with recurrent genital HSV type 2 participated in a randomized, single-blind, masked investigator, controlled multi-centre study comparing the efficacy of ointment of Canadian propolis containing natural flavonoids with ointments of acyclovir and placebo (vehicle) on healing ability and capacity to remedy symptoms. Thirty individuals were randomized to each group. Treatment was intended to start in the blister phase. All participants had HSV type 2 isolated, confirmed by serum immunoglobulin levels. The participants were examined on the 3rd, 7th and 10th days of treatment by gynaecologists, dermatovenerologists or urologists at seven different medical centres. Apart from clinical symptoms the number and size of the herpetic lesions were noted. At each examination the lesions were classified into four stages: vesicular, ulcerated, crusted and healed. The study ointments were applied to affected areas four times daily. In women with vaginal or cervical lesions a tampon with the appropriate ointment was inserted four times daily for 10 days. Endpoint variables were healing time and time until loss of symptoms. RESULTS: On Day 10, 24 out of 30 individuals in the propolis group had healed. In the acyclovir group 14 out of 30 and in the placebo group 12 out of 30 had healed. (p = 0.0015). The healing process appeared to be faster in the propolis group. In the propolis group 15 individuals had crusted lesions on Day 3 compared to 8 individuals in the acyclovir group and none in the placebo group (p = 0.0006). On Day 7, 10 participants in the propolis group, 4 in the acyclovir group and 3 in the placebo group had healed. At the initial examination all patients had local symptoms and 28% general symptoms. At Day 3, 3 patients in the propolis group had local symptoms compared to 8 and 9 in the acyclovir and placebo groups respectively. Of the women, 66% had vaginal superinfections of microbial pathogens at the initial examination. In the acyclovir and placebo groups no change in the vaginal flora was found following treatment whereas in the propolis group the incidence of superinfection was reduced by 55%. (p = 0.10 n.s.). CONCLUSION: An ointment containing flavonoids appeared to be more effective than both acyclovir and placebo ointments in healing genital herpetic lesions, and in reducing local symptoms.

BACKGROUND: Red yeast rice is an herbal supplement that decreases low-density lipoprotein (LDL) cholesterol level. OBJECTIVE: To evaluate the effectiveness and tolerability of red yeast rice and therapeutic lifestyle change to treat dyslipidemia in patients who cannot tolerate statin therapy. DESIGN: Randomized, controlled trial. SETTING: Community-based cardiology practice. PATIENTS: 62 patients with dyslipidemia and history of discontinuation of statin therapy due to myalgias. INTERVENTION: Patients were assigned by random allocation software to receive red yeast rice, 1800 mg (31 patients), or placebo (31 patients) twice daily for 24 weeks. All patients were concomitantly enrolled in a 12-week therapeutic lifestyle change program. MEASUREMENTS: Primary outcome was LDL cholesterol level, measured at baseline, week 12, and week 24. Secondary outcomes included total cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, liver enzyme, and creatinine phosphokinase (CPK) levels; weight; and Brief Pain Inventory score. RESULTS: In the red yeast rice group, LDL cholesterol decreased by 1.11 mmol/L (43 mg/dL) from baseline at week 12 and by 0.90 mmol/L (35 mg/dL) at week 24. In the placebo group, LDL cholesterol decreased by 0.28 mmol/L (11 mg/dL) at week 12 and by 0.39 mmol/L (15 mg/dL) at week 24. Low-density lipoprotein cholesterol level was significantly lower in the red yeast rice group than in the placebo group at both weeks 12 (P < 0.001) and 24 (P = 0.011). Significant treatment effects were also observed for total cholesterol level at weeks 12 (P < 0.001) and 24 (P = 0.016). Levels of HDL cholesterol, triglyceride, liver enzyme, or CPK; weight loss; and pain severity scores did not significantly differ between groups at either week 12 or week 24. LIMITATION: The study was small, was single-site, was of short duration, and focused on laboratory measures. CONCLUSION: Red yeast rice and therapeutic lifestyle change decrease LDL cholesterol level without increasing CPK or pain levels and may be a treatment option for dyslipidemic patients who cannot tolerate statin therapy.

Depression is one of the most common neuropsychiatric conditions, with a lifetime prevalence approaching 17%. Although a variety of pharmaceutical agents is available for the treatment of depression, psychiatrists find that many patients cannot tolerate the side effects, do not respond adequately, or finally lose their response. On the other hand, many herbs with psychotropic effects have far fewer side effects. They can provide an alternative treatment or be used to enhance the effect of conventional antidepressants. A number of recent preclinical and clinical studies indicate that stigma and petal of Crocus sativus have antidepressant effect. Our objective was to compare the efficacy of petal of C. sativus with fluoxetine in the treatment of depressed outpatients in an 8-week pilot double-blind randomized trial. Forty adult outpatients who met the DSM- IV criteria for major depression based on the structured clinical interview for DSM- IV participated in the trial. Patients have a baseline Hamilton Rating Scale for Depression score of at least 18. In this double-blind and randomized trial, patients were randomly assigned to receive capsule of petal of C. sativus 15 mg bid (morning and evening) (Group 1) and fluoxetine 10 mg bid (morning and evening) (Group 2) for a 8-week study. At the end of trial, petal of C. sativus was found to be effective similar to fluoxetine in the treatment of mild to moderate depression (F=0.03, d.f.=1, P=0.84). In addition, in the both treatments, the remission rate was 25%. There were no significant differences in the two groups in terms of observed side effects. The present study is supportive of other studies which show antidepressant effect of C. sativus.