Chemical, Nutritional and Biological Evaluation of a Sustainable and Scalable Complex of Phytochemicals from Bergamot By-Products.

The present paper reports a sustainable raw material obtained from the by-products derived from the industrial production of bergamot (Citrus × Bergamia Risso & Poiteau) essential oils. The procedure to obtain the raw material is designed to maintain as much of the bioactive components as possible and to avoid expensive chemical purification. It consists of spray-drying the fruit juice obtained by squeezing the fruits, which is mixed with the aqueous extract of the pulp, i.e., the solid residue remained after fruit pressing. The resulting powder bergamot juice (PBJ) contains multiple bioactive components, in particular, among others, soluble fibers, polyphenols and amino-acid betaines, such as stachydrine and betonicine. LC-MS analysis identified 86 compounds, with hesperetin, naringenin, apigenin and eridictyol glucosides being the main components. In the second part of the paper, dose-dependent anti-inflammatory activity of PBJ and of stachydrine was found, but neither of the compounds were effective in activating Nrf2. PBJ was then found to be effective in an in vivo model of a metabolic syndrome induced by a high-sugar, high-fat (HSF) diet and evidenced by a significant increase of the values related to a set of parameters: blood glucose, triglycerides, insulin resistance, systolic blood pressure, visceral adipose tissue and adiposity index. PBJ, when given to control rats, did not significantly change these values; in contrast, they were found to be greatly affected in rats receiving an HSF diet. The in vivo effect of PBJ can be ascribed not only to bergamot polyphenols with well-known anti-inflammatory, antioxidant and lipid-regulating effects, but also to the dietary fibers and to the non-phenolic constituents, such as stachydrine. Moreover, since PBJ was found to affect energy homeostasis and to regulate food intake, a mechanism on the regulation of energy homeostasis through leptin networking should also be considered and deserves further investigation.

Ferula L. Plant Extracts and Dose-Dependent Activity of Natural Sesquiterpene Ferutinin: From Antioxidant Potential to Cytotoxic Effects.

The employment studies of natural extracts in the prevention and treatment of several diseases highlighted the role of different species of genus Ferula L., belonging to the Apiaceae family, dicotyledonous plants present in many temperate zones of our planet. Ferula communis L. is the main source of sesquiterpene ferutinin, a bioactive compound studied both in vitro and in vivo, because of different effects, such as phytoestrogenic, antioxidant, anti-inflammatory, but also antiproliferative and cytotoxic activity, performed in a dose-dependent and cell-dependent way. The present review will focus on the molecular mechanisms involved in the different activities of Ferutinin, starting from its antioxidant potential at low doses until its ionophoric property and the subsequent mitochondrial dysfunction induced through administration of high doses, which represent the key point of its anticancer action. Furthermore, we will summarize the data acquired from some experimental studies on different cell types and on several diseases. The results obtained showed an important antioxidant and phytoestrogenic regulation with lack of typical side effects related to estrogenic therapy. The preferential cell death induction for tumor cell lines suggests that ferutinin may have anti-neoplastic properties, and may be used as an antiproliferative and cytotoxic agent in an estrogen dependent and independent manner. Nevertheless, more data are needed to clearly understand the effect of ferutinin in animals before using it as a phytoestrogen or anticancer drug.

Metabolic management in overweight subjects with naive impaired fasting glycaemia by means of a highly standardized extract from Cynara scolymus: a double-blind, placebo-controlled, randomized clinical trial.

The aim of this study is to evaluate the efficacy of a dietary supplementation with an extract from Cynara scolymus (Cs) on the glucose pattern in a group of patients with naïve impaired fasting glycaemia (IFG). A randomized, double-blind, placebo-controlled trial has been performed in 55 overweight subjects with IFG (fasting blood glucose [FBG]: 6.11 ± 0.56 mmol/l). These subjects were randomly assigned to supplement their diet with either an extract from Cs (600 mg/d) (26 subjects) or placebo (29 matched subjects) for 8 weeks. The decrease of FBG was the primary endpoint. The assessment of Homeostatic Metabolic Assessment (HOMA), glycosylated haemoglobin, A1c-Derived Average Glucose (ADAG), lipidic pattern and anthropometric parameters were the secondary endpoints. The within groups and percent changes from baseline were analyzed by the signed rank test. The comparison between groups was performed by Wilcoxon's two sample test. The supplemented group had significant decreases of: FBG (-9.6%), HOMA (-11.7%), glycosylated haemoglobin (-2.3%), ADAG (-3.1%) and lipidic pattern. The placebo group did not show any significant difference. Compared with the placebo, the supplemented group showed a significant difference in FBG, HOMA and lipidic pattern. These data demonstrate the efficacy of Cs extract on the reduction of glycometabolic parameters in overweight subjects with IFG.

SAMITAL®: a new botanical drug for the treatment of mucositis induced by oncological therapies.

SAMITAL(®) (Indena SpA, Milan, Italy) is a new multicomponent and multiacting botanical formulation rationally designed for the relief of oral mucositis induced by chemotherapy and/or radiotherapy in oncological patients. Each of the individual botanical constituents of SAMITAL-standardized extracts of Vaccinium myrtillus, Macleaya cordata and Echinacea angustifolia have a long history of clinical use that corroborates their safety and activity in SAMITAL. A number of pilot trials in oncological patients demonstrated that SAMITAL has good clinical efficacy and tolerability as evidenced by its significant effects in terms of reduction of mucositis, pain and a general improvement in patient quality of life. Importantly, the use of this botanical formulation had the added benefit that patients were able to complete their chemotherapy/radiotherapy regimen. Phase II trials with SAMITAL as part of an overall clinical development program are currently ongoing in Italy and are planned in the USA.

Effect of SAMITAL® in the treatment of chemotherapy-induced mucositis in adult oncohematological patients.

AIM: We sought to evaluate the efficacy and safety of SAMITAL(®) (Indena SpA, Milan, Italy), a highly standardized botanical formulation, in reducing mucositis in patients undergoing treatment for hematological malignancies. PATIENTS & METHODS: In this observational, uncontrolled study, a total of 25 consecutively enrolled patients (19 males, aged 18-74 years) with chemotherapy-induced mucositis were compassionately treated orally with SAMITAL (three to four times per day) for 4-22 days per cycle. RESULTS: Patients demonstrated clinically relevant reductions in WHO mucositis grade with a reduction in pain, mucosal erosions, bleeding, dysphagia/feeding impairment and improvements in quality of life. SAMITAL was well tolerated and no local or systemic pharmacological, allergic, toxic or synergistic/antagonistic side effects were reported. Of note, SAMITAL also showed efficacy when administered prophylactically. CONCLUSION: These results add weight to previous experiences with SAMITAL. However, randomized, placebo-controlled clinical trials will need to confirm the suitability of SAMITAL for use in the treatment of mucositis.

Biological evaluation of hyperforin and its hydrogenated analogue on bacterial growth and biofilm production.

Bacterial biofilms are organized communities of microorganisms, embedded in a self-produced matrix, growing on a biotic surface and resistant to many antimicrobial agents when associated with a medical device. These biofilms require the development of new strategies for the prevention and treatment of infectious disease, including the potential use of natural products. One interesting natural product example is Hypericum, a plant genus that contains species known to have antimicrobial properties. The major constituent of Hypericum perforatum is an unstable compound named hyperforin (1); for this reason it was not believed to play a significant role in the pharmacological effects. In this investigation a hydrogenated hyperforin analogue (2) was tested on several ATCC and clinical isolate strains, in their planktonic and biofilm form (Staphylococcus aureus, MRSA, and Enterococcus faecalis). Compound 2 was effective against planktonic and biofilm cultures, probably due to higher stability, showing the percentage of cells killed in the range from 45% to 52%. These results are noteworthy from the point of view of future development of these polyprenylated phloroglucinols as potential antibiotics.

Reducing effect of a combination of Phaseolus vulgaris and Cynara scolymus extracts on food intake and glycemia in rats.

Extracts from Phaseolus vulgaris and Cynara scolymus may reduce food intake and/or postprandial glycemia. This study investigated the effect of standardized extracts of P. vulgaris and C. scolymus and their combination on food intake and glycemia in rats. P. vulgaris and C. scolymus extracts, and their 1:2 combination, were administered acutely to rats (a) given access to regular food and water, (b) given access to regular food, water, and a chocolate-flavored beverage, or (c) infused with a starch bolus. P. vulgaris extract and the combination produced comparable reductions in intake of regular food and chocolate-flavored beverage; conversely, C. scolymus extract was ineffective on both parameters. P. vulgaris and C. scolymus extracts additively contributed to the reducing effect of the combination on glycemic rise. These results suggest that a mixture of P. vulgaris and C. scolymus extracts is preferable over each single extract, as it combines the anorectic effect of the P. vulgaris extract with the hypoglycemic effect of both extracts. These data support the recent clinical use of the combination of P. vulgaris and C. scolymus extracts in the control of appetite, food intake, and postprandial glycemia and represent a successful example of translational research in the nutraceutical field.

Reducing effect of a combination of Phaseolus vulgaris and Cynara scolymus extracts on operant self-administration of a chocolate-flavoured beverage in rats.

Treatment with a rational combination of standardized extracts of Phaseolus vulgaris and Cynara scolymus reduced food intake and glycemia in rats. The present study was designed to assess the effect of this extract combination and of each single extract in an experimental model of food craving, made up of rats displaying exaggerated seeking and taking behaviors for a chocolate-flavoured beverage. After training to lever-respond for the chocolate-flavoured beverage, rats were treated with vehicle, Phaseolus vulgaris extract alone (200 mg/kg), Cynara scolymus extract alone (400 mg/kg), or combination of Phaseolus vulgaris (200 mg/kg) and Cynara scolymus (400 mg/kg) extracts. The Phaseolus vulgaris extract and the extract combination exerted similar and substantial decrements in the number of lever-responses and amount of self-administered chocolate-flavoured beverage; conversely, the Cynara scolymus extract was totally ineffective. These results suggest that (i) the capacity of the extract combination to reduce the self-administration of the chocolate-flavoured beverage entirely relied on the Phaseolus vulgaris extract, (ii) Phaseolus vulgaris extract may interfere with the mechanisms regulating food-related addictive-like behaviors, and (iii) combinations of Phaseolus vulgaris and Cynara scolymus extracts may possess a broad spectrum of activities, from treatment of metabolic syndrome to overweight, obesity, and possibly food-related addictive disorders.

Beneficial effects of artichoke leaf extract supplementation on increasing HDL-cholesterol in subjects with primary mild hypercholesterolaemia: a double-blind, randomized, placebo-controlled trial.

The aim of this study was to evaluate the effects of artichoke leaf extract (ALE) supplementation (250 mg, 2 b.i.d.) on the lipid pattern. A randomized, double-blind, placebo-controlled clinical trial was performed on 92 overweight subjects with primary mild hypercholesterolaemia for 8 weeks. Forty-six subjects were randomized to supplementation (age: 54.2 ± 6.6 years, body mass index (BMI): 25.8 ± 3.9 kg/m(2), male/female: 20/26) and 46 subjects to placebo (age: 53.8 ± 9.0 years, BMI: 24.8 ± 1.6 kg/m(2), male/female: 21/25). Verum supplementation was associated with a significant increase in mean high-density lipoprotein (HDL)-cholesterol (p < 0.001) and in mean change in HDL-cholesterol (HDL-C) (p = 0.004). A significantly decreased difference was also found for the mean change in total cholesterol (p = 0.033), low-density lipoprotein (LDL)-cholesterol (p < 0.001), total cholesterol/HDL ratio (p < 0.001) and LDL/HDL ratio (p < 0.001), when verum and placebo treatment were compared. These results indicate that ALE could play a relevant role in the management of mild hypercholesterolaemia, favouring in particular the increase in HDL-C, besides decreasing total cholesterol and LDL-cholesterol.

Ferula communis Root Extract: In Vitro Evaluation of the Potential Additive Effect with Chemotherapy Tamoxifen in Breast Cancer (MCF-7) Cells Part II.

Ferula L., belonging to the Apiaceae family, is represented by about 170 species predominantly present in areas with a mild-warm-arid climate, including the Mediterranean region, North Africa and Central Asia. Numerous beneficial activities have been reported for this plant in traditional medicine, including antidiabetic, antimicrobial, antiproliferative, anti-dysentery, stomachache with diarrhea and cramps remedies. FER-E was obtained from the plant F. communis, and precisely from the root, collected in Sardinia, Italy. A total of 25 g of root was mixed with 125 g of acetone (ratio 1:5, room temperature). The solution was filtered, and the liquid fraction was subjected to high pressure liquid chromatographic separation (HPLC). In particular, 10 mg of dry root extract powder, from F. communis, was dissolved in 10.0 mL of methanol, filtered with a 0.2 µm PTFE filter and subjected to HPLC analysis. The net dry powder yield obtained was 2.2 g. In addition, to reduce the toxicity of FER-E, the component ferulenol was removed. High concentrations of FER-E have demonstrated a toxic effect against breast cancer, with a mechanism independent of the oxidative potential, which is absent in this extract. In fact, some in vitro tests were used and showed little or no oxidizing activity by the extract. In addition, we appreciated less damage on the respective healthy cell lines (breast), assuming that this extract could be used for its potential role against uncontrolled cancer growth. The results of this research have also shown that F. communis extract could be used together with tamoxifen, increasing its effectiveness, and reducing side effects. However, further confirmatory experiments should be carried out.

Management of gastrointestinal mucositis due to cancer therapies in pediatric patients: results of a case series with SAMITAL(®).

BACKGROUND: Gastrointestinal mucositis is a common debilitating complication of chemotherapy and one for which there is currently no effective long-term treatment. OBJECTIVES: To report our experience with the use of SAMITAL(®), a new oral suspension formulation based on the combination of three standardized extracts from Vaccinium myrtillus, Macleaya cordata fruits and Echinacea angustifolia roots in the prevention and treatment of chemotherapy-induced gastrointestinal mucositis in pediatric patients. METHODS: 20 pediatric patients undergoing chemotherapy for a range of oncological conditions were followed. Patients initially received oral SAMITAL(®) to treat gastrointestinal mucositis and were then given SAMITAL(®) prophylactically to prevent recurrences with successive cycles of chemotherapy. RESULTS: SAMITAL(®) significantly decreased gastrointestinal mucositis grade after the first episode with a reduction of mean scores from 3.2 ± 0.7 at baseline to 0.4 ± 0.6 at the end of treatment (p < 0.001). SAMITAL(®) reduced pain, mucosal erosions, bleeding and dysphagia/feeding impairment. SAMITAL(®) improved patients' overall condition and quality of life after the first administration and lowered the need for parenteral nutrition. Importantly, it allowed chemotherapy cycles to be continued without complications. CONCLUSION: Results from this case series suggest that SAMITAL(®) may play an important role in the prevention and treatment of chemotherapy-induced gastrointestinal mucositis in children and adolescents and as such warrants investigation in controlled studies.

Pycnogenol®-Centellicum® supplementation improves lung fibrosis and post-COVID-19 lung healing.

BACKGROUND: The aim of this study was to evaluate the combination of Pycnogenol® (150 mg/day) (Horphag Research, London, UK) and Centella asiatica (Centellicum® 3×225 mg/day; Horphag Research) (PY-CE) for 8 months in subjects with sequelae of idiopathic interstitial pneumonia (IIP). Recently, post-COVID-19 lung disease is emerging with large numbers of patients left with chronic lung conditions. Considering the antifibrotic activity of the combination PY-CE, we also tested this supplementary management in post-COVID-19 lung patients. METHODS: Nineteen subjects with idiopathic interstitial pneumonia (IIP) were included in the study. High Resolution CT scans at inclusion confirmed the presence of lung fibrosis: 10 patients were treated with the Pycnogenol® Centellicum® combination and 9 subjects with standard management (SM) served as controls. Oxidative stress that was very high in all subjects at inclusion, decreased significantly in the supplement group (P<0.05). The Karnofsky Performance Scale Index significantly improved in the supplement group in comparison with controls (P<0.05). The symptoms (fatigue, muscular pain, dyspnea) were significantly lower after 8 months in supplemented patients (P<0.05) as compared with controls. RESULTS: At the end of the study, the small cystic lesions (honeycombing) and traction bronchiectasis were stable or in partial regression in 4 subjects in the supplemented group (vs. none in the control group) with a significant improvement in tissue edema in the supplemented subjects. On ultrasound lung scans the white (more echogenic) fibrotic component at inclusion was 18.5±2.2% in the images in controls vs. 19.4±2.7% in the supplement group. At the end of the study, there was no improvement in controls (18.9±2.5%) vs. a significant improvement in supplemented subjects (16.2±2.1%; P<0.05). In addition, 18 subjects with post-COVID-19 lung disease were included in the study; 10 patients were treated with the Pycnogenol® Centellicum® combination and evaluated after 4 weeks; 8 patients served as controls. Preliminary results show that symptoms associated with post-COVID-19 lung disease after 4 weeks were significantly improved with the supplement combination (P<0.05). Oxidative stress and the Karnofsky Performance Scale Index were significantly improved in the supplements group as compared with controls (P<0.05). CONCLUSIONS: According to these observations, Pycnogenol® controls and decreases edema and Centellicum® by modulating the apposition of collagen, slows down the development of irregular cicatrization, the keloidal scarring and fibrosis. More time is needed to evaluate this effect in a larger number of post-COVID-19 patients with lung disease. This disease has affected millions of subjects worldwide, leaving severe consequences. Pycnogenol® and Centellicum® may improve the residual clinical picture in post-COVID-19 lung disease (PCL) patients and may reduce the number of subjects evolving into lung fibrosis. The evolution from edema to fibrosis seems to be slower or attenuated with this supplement combination both in Idiopathic pulmonary fibrosis (IPF) and in PCL patients.

Polyphenols from Thinned Young Apples: HPLC-HRMS Profile and Evaluation of Their Anti-Oxidant and Anti-Inflammatory Activities by Proteomic Studies.

The qualitative profile of thinned apple polyphenols (TAP) fraction (≈24% of polyphenols) obtained by purification through absorbent resin was fully investigated by LC-HRMS in positive and negative ion mode and using ESI source. A total of 68 polyphenols were identified belonging to six different classes: flavanols, flavonols, dihydrochalchones, flavanones, flavones and organic and phenolic acids. The antioxidant and anti-inflammatory activities were then investigated in cell models with gene reporter for NRF2 and NF-κB and by quantitative proteomic (label-free and SILAC) approaches. TAP dose-dependently activated NRF2 and in the same concentration range (10-250 µg/mL) inhibited NF-κB nuclear translocation induced by TNF-α and IL-1α as pro-inflammatory promoters. Proteomic studies elucidated the molecular pathways evoked by TAP treatment: activation of the NRF2 signaling pathway, which in turn up-regulates protective oxidoreductases and their nucleophilic substrates such as GSH and NADPH, the latter resulting from the up-regulation of the pentose phosphate pathway. The increase in the enzymatic antioxidant cellular activity together with the up-regulation of the heme-oxygenase would explain the anti-inflammatory effect of TAP. The results suggest that thinned apples can be considered as a valuable source of apple polyphenols to be used in health care products to prevent/treat oxidative and inflammatory chronic conditions.

Ferula communis L. (Apiaceae) Root Acetone-Water Extract: Phytochemical Analysis, Cytotoxicity and In Vitro Evaluation of Estrogenic Properties.

Ferula communis L. (F. communis) belongs to the Apiaceae family and is a herbaceous plant with various pharmaceutical properties, due to the different contents of bioactive compounds extracted mainly from its roots, as well as its leaves and rhizome. To date, this plant extract has demonstrated estrogenic, anti-inflammatory, antiproliferative, cytotoxic, antimicrobial and anti-neoplastic properties. Its estrogenic activity is justified by the presence of ferutinin, an ester of a sesquiterpenic alcohol that acts as an agonist for estrogen receptors, with a chemical formula equal to C22H3O4. The component present in F. communis responsible for the toxicity of the plant is ferulenol, a prenylated coumarin with the chemical formula C24H30O3. This compound is capable of inducing mortality via its strong anti-coagulant properties, leading to a lethal hemorrhagic syndrome, ferulosis, in animals that feed on a chemotype of F. communis containing a high amount of ferulenol. The removal of the component ferulenol makes extracts of Ferula non-toxic. In fact, the remaining prenylated coumarins are not present in concentrations sufficient to induce toxicity. The intake of high concentrations of the extract of this plant leads a double dose-dependent effect that is typical of sesquiterpenes such as ferutinin. Here, we assessed the cytotoxicity and the estrogenic properties of the F. communis phytocomplex obtained through extraction using a mixture of acetone and water. Among the active constituents of F. communis, the identification of ferutinin and ferulenol was performed using HPLC. The effects of the extract were evaluated, following the removal of ferulenol, on three cell lines: human breast cancer MCF-7, human cervical cancer HeLa and human osteoblastic sarcoma Saos-2. The choice of these cell lines was justified by the need to mimic certain processes which may occur in vivo and which are estrogen-dependent. The obtained results demonstrated that F. communis extract, in addition to possessing an estrogenic-like property, showed a dose-dependent effect. Low concentrations (0.1-0.8 µM) demonstrated a hyperproliferative effect, whereas higher concentrations (1.6-50 µM) were toxic. Therefore, this extract could be an excellent candidate to make up for a reduction or lack of estrogen.

Multiple cycles of repeated treatments with a Phaseolus vulgaris dry extract reduce food intake and body weight in obese rats.

Previous lines of experimental evidence have suggested that Phaseolus vulgaris extracts reduce food intake, body weight, lipid accumulation, hedonic properties of food, carbohydrate absorption and metabolism, and glycaemia in rats. The present study was designed to assess the effect of multiple cycles of repeated treatments with a standardised P. vulgaris dry extract on daily food intake and body weight in genetically obese Zucker fa/fa rats (Expt 1). Additionally, the study tested the effect of acute treatment with P. vulgaris dry extract on postprandial glycaemia in Zucker fa/fa rats (Expt 2). In Expt 1, P. vulgaris dry extract was administered daily, at doses of 50 and 500 mg/kg, in three 5 d treatment periods followed by three 20 d off-treatment periods. Administration of P. vulgaris dry extract resulted in dose-dependent decreases in daily food intake and body weight in each treatment phase. Reductions in food intake were of comparable magnitude in each treatment phase. In Expt 2, food-deprived rats were acutely treated with 50 and 500 mg P. vulgaris dry extract per kg immediately before access to a fixed amount of a starch-enriched chow. Treatment with P. vulgaris dry extract resulted in a dose-dependent suppression of glycaemia. These results extend previous data on the anorectic and hypoglycaemic effects of the P. vulgaris dry extract to a validated animal model of obesity. Together with data published previously in the literature, these results strengthen the hypothesis that potentially effective, novel pharmacotherapies for obesity and related disorders may originate from extracts and derivatives of P. vulgaris.

Evidence of glycemia-lowering effect by a Cynara scolymus L. extract in normal and obese rats.

Several recent preliminary clinical studies have suggested that artichoke (Cynara scolymus L., Asteraceae family) preparations may be capable of lowering post-prandial glycemia. The present study was designed to test this hypothesis in laboratory rats. To this aim, non-selected Wistar and genetically obese Zucker rats were treated acutely with a purified extract of Cynara scolymus flowering heads (500-1500 mg/kg by gavage) immediately prior to 1 h access to a fixed amount of food. Glycemia was recorded 60, 120 and 360 min after food presentation. Treatment with Cynara scolymus flowering head extract resulted in a significant decrease of post-prandial glycemia in both rat strains. The lack of any fiber content in this Cynara scolymus flowering head extract excludes the involvement of dietary fibers in glycemia reduction. The results obtained constitute the first evidence of a hypoglycemic effect of an artichoke preparation in laboratory rodents and confirm previous observations made in humans.

Effects of quercetin and artemetin prenylation on bioavailability and bioactivity.

Flavonoids are a huge class of polyphenolic compounds ubiquitous in higher plants, in most food and beverages of natural origin. They could be considered as dietary phenols, which exert many health-promoting effects on human and animal physiology with a wide range of biomedical and nutritional functions such as activation or inhibition of enzymes like lipoxygenase and cyclooxygenase, the detoxification of carcinogens and chemoprevention. From a chemical point of view, these aromatic compounds can be divided in six subgroups depending on the position of aromatic B ring on C ring, the degree of unsaturation and oxidation, the position of hydroxyl groups and their functionalization. Between flavonoids, the prenylated ones represent a unique class occurring in nature where the C-prenylation is the most common, whereas O-prenylation is rarely present. The presence of this lipophilic functional group in different positions on the scaffold of flavonoids can sometimes lead to relevant changes in their biological activity due to an increased bioavailability. Capitalizing on the restricted incidence in nature of prenylated flavonoids, we have assessed the synthesis of C- and O-prenylated derivatives starting from two flavonoids, quercetin and artemetin, aimed at the exploration of structure-activity relationships. Results showed that prenylation significantly increased the cytotoxic effect of flavonoids in cancer HeLa cells, also improving their capacity to affect cell phospholipid and fatty acid composition. A marked cell bioavailability increase was demonstrated for the artemetin C-prenylated derivative.

Analytical Profile and Antioxidant and Anti-Inflammatory Activities of the Enriched Polyphenol Fractions Isolated from Bergamot Fruit and Leave.

The aim of the study is to compare the qualitative and semi-quantitative profile of the polyphenol fraction purified from the leaf (BLPF) and fruit (BFPF) of bergamot (Citrus bergamia), and to evaluate their antioxidant and anti-inflammatory activity. The analytical qualitative profile was carried out by LC-ESI/MS using three different approaches: targeted (searching analytes already reported in bergamot extract), semi-targeted (a selective search of 3-hydroxy-3-methylglutarate [HMG] derivatives involved in the cholesterol reducing activity of BPF) and untargeted. A total number of 108 compounds were identified by using the three approaches, 100 of which are present in both the extracts thus demonstrating a good qualitative overlapping of polyphenols between the two extracts. The antioxidant activity was higher for BLPF in respect to BFPF but when normalized in respect to the polyphenol content they were almost overlapping. Both the extracts were found to dose dependently inhibit cell inflammation stimulated with IL-1α. In conclusion, the comparison of the qualitative and quantitative profile of polyphenols as well as of the antioxidant and anti-inflammatory activity of bergamot leaf and fruit well indicates that leaf is a valid source of bergamot polyphenol extraction and an even richer source of polyphenol in respect to the fruit.

Reducing effect of a Phaseolus vulgaris dry extract on operant self-administration of a chocolate-flavoured beverage in rats.

Extracts from or derivatives of Phaseolus vulgaris beans reduce body weight and food intake, including highly palatable foods and fluids, in multiple rodent models of overeating and obesity. The present study was designed to assess whether a standardised P. vulgaris dry extract was effective in reducing also the operant self-administration of a chocolate-flavoured beverage. To this end, rats were initially trained to lever-press for a chocolate-flavoured beverage under a fixed ratio 10 schedule of reinforcement in daily 60 min sessions. Once lever-responding reached stable levels, the effect of a P. vulgaris dry extract on the number of lever-responses for the chocolate-flavoured beverage was determined. Pretreatment with 50, 200 and 500 mg (intragastric) P. vulgaris dry extract per kg produced an approximate 15, 35 and 40 % reduction, respectively, in lever-responding for the chocolate-flavoured beverage. These results indicate the capacity of a P. vulgaris preparation to reduce the reinforcing properties of a highly palatable fluid in rats.

Randomized Clinical Trial: Bergamot Citrus and Wild Cardoon Reduce Liver Steatosis and Body Weight in Non-diabetic Individuals Aged Over 50 Years.

Background: Non-alcoholic fatty liver disease is the most common cause of liver-related morbidity and mortality in the world. However, no effective pharmacological treatment for this condition has been found. Purpose: This study evaluated the effect of a nutraceutical containing bioactive components from Bergamot citrus and wild cardoon as a treatment for individuals with fatty liver disease. The primary outcome measure was the change in liver fat content. Methods: A total of 102 patients with liver steatosis were enrolled in a double-blind placebo controlled clinical trial. The intervention group received a nutraceutical containing a Bergamot polyphenol fraction and Cynara Cardunculus extract, 300 mg/day for 12 weeks. The control group received a placebo daily. Liver fat content, by transient elastography, serum transaminases, lipids and glucose were measured at the baseline and the end of the study. Results: We found a greater liver fat content reduction in the participants taking the nutraceutical rather than placebo (-48.2 ± 39 vs. -26.9 ± 43 dB/m, p = 0.02); The percentage CAP score reduction was statistically significant in those with android obesity, overweight/obesity as well as in women. However, after adjustment for weight change, the percentage CAP score reduction was statistically significant only in those over 50 years (44 vs. 78% in placebo and nutraceutical, respectively, p = 0.007). Conclusions: This specific nutraceutical containing bioactive components from Bergamot and wild cardoon reduced the liver fat content during 12 weeks in individuals with liver steatosis over 50 years. If confirmed, this nutraceutical could become the cornerstone treatment of patients affected by liver steatosis. Clinical Trial Registration: www.isrctn.com, identifier ISRCTN12833814.