Safety and efficacy of a class II medical device based on highly purified and standardized plant extracts in the management of post-menopausal patients with vulvar and vaginal atrophy: a single-center prospective observational study.

BACKGROUND: Despite the gold standard treatment for genitourinary syndrome of menopause (GSM) is based on the use of local or systemic estrogen-containing products, the typical long-term side effects of hormonal treatments and, most importantly, the contraindications in patients with history of breast and endometrial neoplasms do limit in some extent its use. As hyaluronic acid and some highly purified botanicals have clearly demonstrated their anti-inflammatory and mucosa-protecting properties, we have tested, in women with GSM, a class II vaginal medical device containing hyaluronate gel and a mucoadhesive active enriched with purified alkylamides from Zanthoxylum bungeanum, triterpenes from Centella asiatica and high molecular weight polysaccharides from Tamarindus indica. METHODS: Our single-center, open-label, prospective and observational study was conducted on 50 menopausal women enrolled at the Department of Maternal-Fetal Medicine at Umberto I Polyclinic Hospital in Rome, Italy. Gel administration lasted 150 days and was performed daily for the first 12 days and every 48 hours for the remaining 138 days. Clinical evaluations were performed at baseline and after 12, 57 and 150 days. Besides product safety, main outcomes of our study were: 1) vaginal health (by Vaginal Health Index score [VHI]); 2) sexual quality of life (by Female Sexual Distress Scale [FSDS]); and 3) percentage of women declaring regular sexual activity. RESULTS: The product was safe with no specific adverse events reported. It significantly improved VHI (about 5% after 57 days and 8% after 150 days), FSDS (about 7% after 57 days and 10% after 150 days), and sexual activity (about 20% after 150 days). It also reduced dryness, dyspareunia, burning, itching, and dysuria incidence, respectively by about 18%, 14%, 14%, 27% and 11% after 150 days. CONCLUSIONS: In women with GSM, the intravaginal administration of a hyaluronate-based gel enriched with purified botanical actives endowed with anti-inflammatory and mucosal-protecting properties, reduced painful sensation during sexual acts and increased regular sexual activity.

Short-Term Effect of Nutraceutical Fruit Juices on Lipid Metabolism in Patients with Acquired Hypercholesterolemia.

The crucial role of dyslipidaemia, especially hypercholesterolemia, in the development of atherosclerosis-related cardiovascular diseases has been extensively documented in genetic, pathologic, observational and intervention studies. The European guidelines for dyslipidaemia management include the possible use of lipid-lowering nutraceuticals to support a relatively large number of natural compounds. In this context, we have conducted a study to investigate whether dietary supplementation with a functional nutraceutical beverage, containing a standardized polyphenolic fraction from fruit, red yeast rice, phytosterols, and berberine complexed with ß-cyclodextrin, could positively affect serum lipid concentration in 14 subjects with hypercholesterolemia. After 12 weeks of treatment, dietary supplementation with this nutraceutical combination was associated with significant improvements in total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B, compared to baseline. Compliance was excellent and no adverse effects were reported. In conclusion, this study demonstrates that 100 mL of a functional beverage containing lipid-lowering nutraceuticals safely leads to significant improvements in serum lipids in subjects with moderate hypercholesterolemia. Future research is needed to unravel the role that the polyphenols contained in fruit extracts play in the reduction of cholesterolemia and in cardiovascular disease prevention.

A Practical Perspective on the Use of Botanicals During the COVID-19 Pandemic: From Proven to Potential Interactions.

In this review, we examined the top 10 nutraceutical products sold in Italian pharmacies and parapharmacies as well as hypermarkets and supermarkets; in the first, three product categories saw the greatest increase in sales (vitamins and minerals, immunostimulants, and sleep products) for the 12-month period between October 2019 and October 2020 (including first pandemic wave of SARS-CoV-2). We are investigating their respective formulas and isolating the botanicals that are used to make them. Many of these products have undergone preclinical and clinical studies. We performed a systematic literature search in the MEDLINE database using PubMed and Google Scholar from November 15, 2020 to December 15, 2020 (including studies carried out between 1980 and 2020). The search terms that were used included the complete name of the medicinal plant in English or Latin and the terms "cytochrome" or "drug interactions," crossing, respectively, the Latin name and English common names with "cytochrome" and "drug interactions." The search included in vitro and in vivo studies describing the effects of interaction between the plant (extract or botanical medicine) and human cytochromes. Despite their great complexity, there is decidedly limited clinical data on botanical medicine. In fact, of the 28 botanicals that were examined, only 2 (Citrus paradisi and Rhodiola rosea) show in vivo pharmacological interactions in human subjects. On the contrary, for the other botanicals, there is only weak evidence of dubious clinical significance or potential interactions shown in animal models or in vitro without clinical confirmation. This study provides a rational assessment of the most widely used products, including those used in self-medication, to simplify patient management during the COVID-19 health emergency.

Nutraceutical Approach to Preventing Coronavirus Disease 2019 and Related Complications.

Introduction: Several months ago, Chinese authorities identified an atypical pneumonia in Wuhan city, province of Hubei (China) caused by a novel coronavirus (2019-nCoV or SARS-CoV-2). The WHO announced this new disease was to be known as "COVID-19". Evidence Acquisition: Several approaches are currently underway for the treatment of this disease, but a specific cure remains to be established. Evidence Synthesis: This review will describe how the use of selected nutraceuticals could be helpful, in addition to pharmacological therapy, in preventing some COVID-19-related complications in infected patients. Conclusions: Even if a specific and effective cure for COVID-19 still has some way to go, selected nutraceuticals could be helpful, in addition to pharmacological therapy, in preventing some COVID-19-related complications in infected patients.

A role for quercetin in coronavirus disease 2019 (COVID-19).

Several months ago, an outbreak of pneumonia of unknown aetiology was detected in Wuhan City (China) and the aetiological agent of the atypical pneumonia was isolated by the Chinese authorities as novel coronavirus (2019-nCoV or SARS-CoV-2). The WHO announced this new disease was to be known as "COVID-19." When looking for new antiviral compounds, knowledge of the main viral proteins is fundamental. The major druggable targets of SARS-CoV-2 include 3-chymotrypsin-like protease (3CLpro), papain-like protease (PLpro), RNA-dependent RNA polymerase, and spike (S) protein. Quercetin inhibits 3CLpro and PLpro with a docking binding energy corresponding to -6.25 and -4.62 kcal/mol, respectively. Quercetin has a theoretical, but significant, capability to interfere with SARS-CoV-2 replication, with the results showing this to be the fifth best compound out of 18 candidates. On the basis of the clinical COVID-19 manifestations, the multifaceted aspect of quercetin as both antiinflammatory and thrombin-inhibitory actions, should be taken into consideration.

Role of a berberine-based nutritional supplement in reducing diarrhea in subjects with functional gastrointestinal disorders.

BACKGROUND: Berberine, an alkaloid obtained by extraction from Berberis spp., is a botanical that is widely used in the nutraceutical sector to control cholesterol and blood glucose levels. It is also a molecule that is effective in limiting diarrhea due to its multi-factorial properties, including its antimicrobial, gut eubiotic and antisecretive actions, and its ability to slow gut motility. In our routine clinical practice, we have suggested the use of a berberine-based nutraceutical, formulated with melatonin and depolymerized guar gum, to patients affected by functional diarrhea (FD) or by diarrhea-type irritable bowel syndrome (IBS-D). METHODS: We have therefore retrospectively analyzed the clinical effect of such a nutritional supplement in these two sub-groups of patients. RESULTS: Despite the highly pragmatic scheme of our study, our findings strongly confirm the antidiarrheal properties of berberine and recommend its use in some gut functional diseases characterized by frequent evacuation of mushy and/or watery stools. In fact, even after 30 days of treatment, the berberine-based nutritional supplement significantly reduces diarrheal events by 50-70%. After 90 days, this reduction improves to between 70 and 80%, with a reduction of more than 60% in the number of evacuations per week and with more than 50% of treated subjects demonstrating normalized, according to self-reported Bristol Stool Scale categorization, stool consistency. The product is well tolerated and adherence to the proposed therapy is good. Common side effects of the product are flatulence and meteorism, likely due to the "acarbose-like" berberine effects on gut α-glucosidase. CONCLUSIONS: Patients, especially those preferring "natural" therapy, can be successfully treated, when affected by a gut functional disease characterized by diarrhea, by berberine-based products.

Effectiveness of a nutraceutical supplement containing highly standardized perilla and ginger extracts in patients with functional dyspepsia.

BACKGROUND: In Western countries functional dyspepsia (FD) has a prevalence of 10-20% among adults and although many drugs are currently available for use within clinical practice, FD remains an important challenge for physicians. Recently, food supplements that are ginger-based, along with other botanicals, have been proposed to be a possible natural alternative to pharmaceutical drugs to empirically counteract the symptoms of FD. METHODS: We have therefore retrospectively analyzed the efficacy and safety profiles of a nutraceutical containing, in addition to a highly standardized ginger root extract, a multi-fractionated botanical obtained from Perilla frutescens leaf containing an innovative bouquet of compounds, including hydrophilic polyphenols and the lipophilic terpenoid perilla ketone. RESULTS: The results of our single-group study, obtained from patients with a diagnosis of FD who were treated with the perilla/ginger nutraceutical, demonstrated a good efficacy profile, with a significant reduction observed in nearly all evaluated symptoms (epigastric pain, heartburn, gastric reflux, nausea, borborygmi, early satiety, diarrhea/constipation) starting from the first week of treatment that was further improved after 2 weeks. The treatment was well tolerated with very mild side effects (flatulence, meteorism, gastric burning, difficulty in falling asleep) lasting 3-4 days, which disappeared without stopping the treatment. CONCLUSIONS: Despite all the limitations of our pragmatic study, we believe that the perilla and ginger supplement we have used can be considered a valid tool for an empirical approach to treating patients with FD, especially when a non-conventional drug treatment is preferable to the patient and considered suitable by the physician.

Possible therapeutic role of a highly standardized mixture of active compounds derived from cultured Lentinula edodes mycelia (AHCC) in patients infected with 2019 novel coronavirus.

The outbreak of SARS-CoV-2 disease (COVID-19) is currently, March 2020, affecting more than 100,000 people worldwide and, according to the WHO (World Health Organization), a pandemic is shortly expected. The virus infects the lower respiratory tract and causes severe pneumonia and mortality in approximately 10% and 3-5%, respectively, of cases, mainly among the elderly and/or people affected by other diseases. AHCC is an α-glucan-based standardized mushroom extract that has been extensively investigated as an immunostimulant both in animals and/or in humans affected by West Nile virus, influenza virus, avian influenza virus, hepatitis C virus, papillomavirus, herpes virus, hepatitis B virus and HIV by promoting a regulated and protective immune response. Although the efficacy of AHCC has not yet been specifically evaluated with respect to SARS-CoV-2 disease, its action in promoting a protective response to a wide range of viral infections, and the current absence of effective vaccines, could support its use in the prevention of diseases provoked by human pathogenic coronavirus, including COVID-19.

Efficacy of Nutraceutical Combination of Monacolin K, Berberine, and Silymarin on Lipid Profile and PCSK9 Plasma Level in a Cohort of Hypercholesterolemic Patients.

The guidelines for the treatment of dyslipidemias include the use of nutraceuticals (NUTs) in association with lifestyle modifications to achieve therapeutic goals. In NUT pill, different substances may be associated; in this study we investigated a combined NUT containing monacolin K (MonK)+KA (1:1), berberine (BBR), and silymarin. The aim of the study was to evaluate low-density lipoprotein cholesterol (LDL-C) reduction in 53 patients suffering from polygenic hypercholesterolemia, characterized by a low/intermediate cardiovascular risk calculated with SCORE algorithm. The effects on lipid profile of 2-month treatment with NUT containing MonK+KA (1:1), BBR, and sylimarin, were compared with Atorvastatin (ATO) 10 mg administrated in a matched control group. Serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and the cholesterol loading capacity (CLC) were determined at baseline and at the end of the study in NUT-treated group; variations were assessed. NUT was effective as lipid-lowering agent with a wide interindividual response variability (mean LDL-C from 170.8 ± 19.9 to 123.8 ± 20.0 with a change of -47.0 ± 21.5 mg/dL; P < .001) and the effect was similar to that induced by ATO. The use of NUT significantly modified PCSK9 levels (P < .01) and CLC (P < .001), ultimately suppressing the serum-mediated foam cell generation directly measured on human macrophages. NUT reduces LDL-C levels with an effect similar to what is induced by 10 mg of ATO and ex vivo improves the functional profile of lipoproteins with antiatherogenic action.

A novel lecithin-based delivery form of Boswellic acids as complementary treatment of radiochemotherapy-induced cerebral edema in patients with glioblastoma multiforme: a longitudinal pilot experience.

BACKGROUND: Glioblastoma multiforme (GBM) is an extremely challenging neurological disease for which the development of more effective therapeutic options and of adjuvant/complementary treatment is needed. We investigated the effects of an innovative phytosome-based delivery form of boswellic acids extract (Monoselect AKBA™) on radiochemotherapy-induced cerebral edema in patients with primary GBM. METHODS: Patients with de novo GBM treated with surgery, radiotherapy and chemotherapy with temozolomide were enrolled in this longitudinal study and received boswellia-based product 4500 mg/die for a maximum of 34 weeks. Cerebral edema was assessed at 4, 12, 22 and 34 weeks post-surgery, together with steroids consumption and patients' psychological status. RESULTS: A total of 20 patients were included in the study. The percentage of patients with reduced edema was constant during the study, while the percentage of those with reduced or stable edema tended to increase over time. Of note, two patients achieved a considerable reduction in brain edema, which led to a more favorable and beneficial surgical resection. In addition, a good percentage of patients assumed a stable/reduced steroids dose or were dexamethasone free during the study. Lastly, patients' QoL and psychological state were maintained throughout the study. CONCLUSIONS: Complementary treatment with Monoselect AKBA™ might exert a beneficial effect in reducing radiochemotherapy-induced cerebral edema, thanks to the anti-inflammatory properties of the boswellia serrata extract. The reduction in brain edema might diminish dexamethasone assumption, thus minimizing steroids-induced side effects, and in few cases may allow a complete surgical excision of the tumor mass.

Role in depression of a multi-fractionated versus a conventional Hypericum perforatum extract.

BACKGROUND: Hypericum perforatum is used as medicinal plant for mild to moderately severe depression. Several trials have found hypericum to be more effective than placebo or some antidepressant drugs, but the exact mechanism and most relevant compounds are still unclear. A possible hypothesis is that the antidepressant activity might be due to its multiplicity of bioactive compounds. Aim is to test if greater chemical complexity could result in a greater hypericum antidepressant action. METHODS: A retrospective, 12-month, open-label, observational, controlled trial was conducted to compare the antidepressant clinical activity of a conventional Hypericum perforatum (C-Hp) versus a multi-fractionated (M-Hp) one (IperiPlex®). RESULTS: Treatment with C-Hp demonstrated no efficacy after 6 months and partial (P<0.05) efficacy after 12 months. Treatment with MF-Hp demonstrated highly (P<0.01) significant results at both 6 and 12 months. Analysis of the monthly reduction coefficient demonstrated that treatment with MF-Hp was twice as effective as treatment with C-Hp (0.96 versus 0.48). No side effects were reported. CONCLUSIONS: A multi-fractionated hypericum extract has better clinical outcomes in subjects with depression without determining an increased risk of toxicity or reduced tolerability.

Retrospective analysis of the effects of a highly standardized mixture of Berberis aristata, Silybum marianum, and monacolins K and KA in diabetic patients with dyslipidemia.

BACKGROUND: Berberine, an alkaloid with both glucose- and cholesterol-lowering action, is also characterized by an anti-diarrheal effect. Consequently, berberine-based therapies are recommended for diabetic patients with irritable bowel syndrome (IBS) or gut discomfort caused by metformin. AIM: As the anti-glycemic and cholesterol-lowering action of berberine is improved by co-administration with P-glycoprotein inhibitors and naturally derived statins, we have analyzed the effect of the food supplement Berberol®K (hereafter referred to as BSM) containing, berberine, silymarin, and a highly standardized red yeast rice containing monacolins K and KA in the ratio 1:1 but no secondary monacolins, dehydromonacolins, or citrinin (Monakopure™-K20). METHODS: We retrospectively evaluated the effects of BSM in 59 diabetic patients with dyslipidemia and compared the results to those obtained in patients without treatment. Enrolled subjects had a diagnosis of IBS (and diarrhea), had diarrhea caused by metformin, or were statin intolerant. RESULTS: After 6 months of BSM treatment, significant reductions of approximately 5%, 23%, 31%, and 20% were observed in glycated hemoglobin (HbA1c), total cholesterol (TC), low density lipoprotein-cholesterol (LDL), and triglyceride (TG) levels, respectively, and only five of the 31 treated subjects reported diarrhea compared with 22 of the 28 untreated patients. Regarding safety, treatment with BSM did not significant modify creatine phosphokinase (CPK), creatine, aspartate aminotransferase (AST) or alanine aminotransferase (ALT). CONCLUSION: BSM is a safe and effective food supplement likely useful as add-on therapy in diabetic subjects with dyslipidemia, especially if they are statin intolerant or with diarrhea caused by IBS or metformin.

Role for a water-soluble form of CoQ10 in female subjects affected by fibromyalgia. A preliminary study.

Decreased antioxidant capacity and increased oxidative stress have been observed in fibromyalgia patients. Some trials have also shown that CoQ10 levels are reduced in these patients but that supplementation can restore levels and reduce fibromyalgia symptoms, including pain and fatigue. We evaluated the effect of administration of a finished form of CoQ10 (DDM Chinone®) at a dose of 200 mg×2/day in 22 female subjects with a diagnosis of fibromyalgia in a randomized, open-label, cross-over study. Our results show that, compared to a control group, administration of CoQ10 significantly improved most pain-related outcomes by 24-37%, including fatigue (by ~22%) and sleep disturbance (by ~33%). These results confirm the considerable role played by CoQ10 in reducing pain, fatigue, and sleep disturbance in subjects affected by fibromyalgia.

Effects of Greenselect Phytosome® on weight maintenance after weight loss in obese women: a randomized placebo-controlled study.

BACKGROUND: Most subjects regain weight after weight loss due to compensatory adaptations finalized to maintain stable body energy stores. Green tea (GT) preparations, which help maintain energy expenditure while dieting could be a useful strategy to facilitate weight maintenance. The usefulness of GT preparations in weight maintenance has been poorly studied so far with conflicting results. This study evaluated if a supplement of GSP and piperine helps obese women to maintain the weight loss obtained with a 3-month lifestyle intervention. METHODS: In a randomized placebo-controlled study, we examined whether a highly bioavailable GT extract may counteract weight regain after weight loss. Forty obese women (age 50.1 ± 10.1 years, Body Mass Index (BMI) 36.3 ± 2.7 kg/m(2)) underwent a 3-month lifestyle intervention. At the end of the intervention, the women were randomized in two groups for the weight-maintenance phase: 20 of them were prescribed twice a day, for 3 months, with a formula containing 150 mg/dose of Greenselect Phytosome® and 15 mg/dose of pure piperine (GSP group), and 20 were given placebo (P group). Anthropometric measures and body composition were measured before (V-3) and after lifestyle intervention (V0), 1 (V1), 2 (V2), and 3 (V3) months after prescribing supplements and 3 months following the discontinuation of supplements (V6). RESULTS: Lifestyle intervention induced a significant weight reduction in both groups with similar weight change (-6.2 ± 2.6 in GSP group vs. -4.8 ± 3.1 % in P group). In the GSP group, V1 in comparison to V0, had further reduction in weight and fat mass, which remained stable at V2 and V3 and increased at V6. In the P group, weight and fat mass increased from V2 onwards. Weight changes in GSP group and P group from V0 to V3 were -1.0 kg (95 % CI -2.5 to +0.5) and + 0.3 kg (95 % CI -0.9 to +1.6), respectively. The proportion of women with weight loss ≥ 5 % was greater in the GSP group than in the P group (75 % vs. 45 % at V1, and 60 % vs. 30 % at V6, p < 0.05 for both groups). CONCLUSIONS: Greenselect Phytosome® devoid of caffeine may have a clinical potential for the maintenance of weight after intentional weight loss. TRIAL REGISTRATION: Clinicaltrials.gov NCT02542449 (September 2015).

Roles of chemical complexity and evolutionary theory in some hepatic and intestinal enzymatic systems in chemical reproducibility and clinical efficiency of herbal derivatives.

Despite the great marketing success, most physicians attribute poor efficacy to herbals. This perception is due to two situations that are an integral part of the herbal topic. The first is the poor phytochemical reproducibility obtained during the production process of herbal extracts, as herbal extracts are not always standardized in the whole manufacturing process, but only in their titer. The second problem is linked to the evolution of important enzymatic systems: cytochromes and ABC proteins. They are both enzyme classes with detoxifying properties and seem to have evolved from the molecular mould provided by active plant substances. During the evolution, as still happens today, polyphenols, saponins, terpenes, and alkaloids were ingested together with food. They do not possess any nutritional value but seem to be provided with a potential pharmacological activity. Cytochromes and ABC proteins, which evolved over time to detoxify food from vegetable chemical "actives," now seem to limit the action of herbal derivatives. The comprehension of these 2 events may explain the origin of the widespread scepticism of physicians about herbal medicine and suggests that, after correct herbal standardization, use of antagonists of cytochromes and ABC systems will make it possible to recover their pharmacological potential.

Safety and efficacy of an add-on therapy with curcumin phytosome and piperine and/or lipoic acid in subjects with a diagnosis of peripheral neuropathy treated with dexibuprofen.

We conducted an 8-week, open, randomized controlled clinical trial on 141 subjects affected by neuropathic pain to investigate the role of an adjunctive therapy added to the administration of dexibuprofen (400 mg twice a day) and based on a multi-ingredient formula (Lipicur), consisting of lipoic acid plus curcumin phytosome and piperine, in patients with a diagnosis of lumbar sciatica, lumbar disk herniation, and/or lumbar canal stenosis (96 subjects), or with carpal tunnel syndrome (45 subjects). A total of 135 participants completed the study. Treatment with the multi-ingredient formula (Lipicur) reduced neuropathic pain by more than 66% in both conditions (subjects with lumbar sciatica and with carpal tunnel syndrome), and these reductions were statistically significant. Moreover, the treatment reduced dexibuprofen use by about 40%. An add-on therapy with only lipoic acid has not shown any significant results. On the basis of its safety and efficacy, Lipicur could be considered an effective complementary therapy to be added to conventional treatments to achieve better efficacy in reducing neuropathic pain.

An amino acids mixture improves the hepatotoxicity induced by acetaminophen in mice.

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, but at high dose it leads to undesirable side effects, such as hepatotoxicity and nephrotoxicity. The aim of this study was to evaluate the protective role of DDM-GSH, a mixture of L-cysteine, L-methionine, and L-serine in a weight ratio of 2 : 1 : 1, in comparison to N-acetylcysteine (NAC), against acetaminophen- (APAP-) induced hepatotoxicity in mice. Toxicity was induced in mice by the intraperitoneal (ip) administration of low dose (2 mmol/kg) or high dose (8 mmol/kg) of APAP. DDM-GSH (0.4 to 1.6 mmol/kg) was given ip to mice 1 h before the APAP administration. The same was done with NAC (0.9 to 3.6 mmol/kg), the standard antidote of APAP toxicity. Mice were sacrificed 8 h after the APAP injection to determine liver weight, serum alanine aminotransferase (ALT), and total glutathione (GSH) depletion and malondialdehyde (MDA) accumulation in liver tissues. DDM-GSH improved mouse survival rates better than NAC against a high dose of APAP. Moreover, DDM-GSH significantly reduced in a dose-dependent manner not only APAP-induced increases of ALT but also APAP-induced hepatic GSH depletion and MDA accumulation. Our results suggest that DDM-GSH may be more potent than NAC in protecting the liver from APAP-induced liver injury.

Use of a standardized extract from Echinacea angustifolia (Polinacea) for the prevention of respiratory tract infections.

Echinacea preparations are extensively used for the prevention and the management of the common cold. Despite this popularity, the clinical studies on Echinacea have produced mixed results, possibly in part because of the poor characterization of the extracts investigated and the use of different species and/or plant parts for the preparations investigated in the various trials. To address this issue, Polinacea, a highly standardized extract from a well-defined botanical source (roots of Echinacea angustifolia) with a specific phytochemical profile (presence of the complex polysaccharide IDN5405, the phenylethanoid echinacoside, and substantial lack of alkamides) was developed. We have studied whether Polinacea could enhance the immune response subsequent to the influenza vaccination, and whether the use of this preparation could translate into a decreased morbidity from influenza. The preliminary results were encouraging, and suggest that Polinacea could be used for improving the immune response to influenza vaccine.

Interaction between ticlopidine or warfarin or cardioaspirin with a highly standardized deterpened Ginkgo biloba extract (VR456) in rat and human.

Ginkgo biloba is available in Europe as an over-the-counter drug and it is reported to cause hemorrhage when co-administered with other anti-platelet agents. We set out to study the interactions of ticlopidine with Ginkgo biloba extract or VR456, a new highly standardized deterpened extract from Ginkgo biloba leaves. Male Wistar rats were used to study the effects of ticlopidine (50-100 mg/kg/day), given alone and in combination for 5 days with Ginkgo biloba extract (50 mg/kg/day) or VR456 (50 mg/kg/day), on bleeding time and ex vivo ADP-induced platelet aggregation measurements. In addition, human studies were performed with the compounds under investigation. Combined treatment of ticlopidine and undeterpened Ginkgo biloba extract increased anti-platelet effect and prolonged the bleeding time in the rat. On the contrary, the combination treatment of ticlopidine and VR456 increased anti-platelet effect but did not prolong bleeding time. Moreover, daily administration of 360 mg of VR456 for 14 days to ticlopidine-treated humans did not highlight any unwanted effect and did not alter PT/INR and PTT parameters. Same results have been also obtained in warfarin or in cardioaspirin-treated patients. These data point out the clear role played by the terpenoid, PAF-antagonist fraction of Ginkgo biloba extract in affecting bleeding risk in anticoagulant-treated subjects and suggest VR456 as a possible option treatment in geriatric people subjected to anticoagulant treatment where the use of standard Ginkgo biloba extracts are discouraged.

Clinical efficacy, safety and tolerability of BIO-C (micronized Silymarin) as a galactagogue.

BACKGROUND AND AIM OF THE WORK: The authors have previously reported the use of Silymarin (a Silybum marianum standardized extract) as a promoter of milk production in cows. Due to the important psychological impact of hypogalactia in women after delivery, we evaluated the role of Silymarin as a safe and effective galactogogue for human species. METHODS: 50 healthy women during lactation were enrolled in order to verify the galactogogue role played by an oral treatment with micronized Silymarin (420 mg/day) in comparison with an undistinguishable placebo product. RESULTS: Women orally treated for 63 days with Silymarin showed a clear galactagogue role for the product with an increase of 85.94% of the daily milk production (placebo: +32.09%). No drop out, nor unwanted effects were reported in both groups. Compliance and tolerability were also very good. CONCLUSIONS: Silymarin may be considered as a safe and effective herbal product that can be orally administered in order to improve the daily milk production in healthy women after delivery, without affecting milk quality.