Synergism in Nutraceutical Formulations

Biochemical characterisation and antioxidant activity of mycelium of Ganoderma lucidum from Central Italy

Backgroud In the last few years increasing evidence have reinforced the benefits of low-density lipoprotrein (LDL-C) levels reduction on cardiovascular outcome. Different targets have been suggested based on the cardiovascular risk (CVR). A goal of LDL-C less of 115mg/dL is desiderable for patients at low to moderate CVR according the current european guidelines. However, an high percentage of patients at low to moderate CVR are far from this target. Nutraceuticals are “food supplements” that may help to achieve this goal in this population. The aim of this retrospective analysis was to evaluate the effects of dietary supplementation with a novel nutraceutical formulation on plasma lipid levels in subjects with low to moderate hypercholesterolemia who are not on treatment with conventional drug and/or with other dietary supplements. Methods Adult patients with hypercholesterolemia were retrospectively selected from the database of participant family practitioners. All patients had a baseline evaluation already recorded, including family and medical history, physical examination, and blood test that included total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), C-reactive protein (CRP), and transaminases (AST and ALT) and have started a dietary supplementation with nutraceuticals. After this selection, a total of 504 patients under this novel nutraceutical (given 1 tablet daily at dinner) with blood test at 30-days already performed, were identified. Similarly, 108 subjects with comparable clinical features but not treated with any supplements were also selected. Results At 30-day of follow-up, the use of this novel dietary supplement was associated with significant reduction of LDL-C 124 ± 16 vs. 100 ± 13 mg/dL, p-value <0.001) and TC levels (210 ± 56 vs. 187 ± 60, p-value < 0.0001), in absence of a significant changes of transaminase levels (AST: 30 ± 6 vs. 30 ± 6 U/L, p-value 0.198; ALT: AST: 30 ± 6 vs. 30 ± 6 U/L, p-value 0.325) and in CRP (3.9 ± 1.5 vs. 3.9 ± 1.4 mg/dL, p-value 0.889). No side effects were reported in the database along to the observation period. Conclusion This novel nutraceutical formulation is an effective dietary supplement in obtaining a significant and early reduction of LDL-C in patients with hypercholesterolemia at low to moderate cardiovascular risk.

Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders. IBS is characterized by recurrent chronic abdominal pain and altered bowel habits in the absence of organic damage. Although there are reviews and guidelines for treating IBS, the complexity and diversity of IBS presentation make treatment difficult. Treatment of IBS focuses on relieving symptoms as mild signs and symptoms can often be controlled by managing stress and by making changes in diet and lifestyle. The use of nutraceutical compounds has been advocated as a possible alternative treatment in patients with IBS. COLONIR® (Omega Pharma Srl, Milan, Italy) may be an alternative or adjuvant treatment in patients with gastrointestinal symptoms. This study aimed to evaluate the effect of this new nutraceutical formulation in inducing symptoms remission and improve gastrointestinal habits. An initial cohort of 1004 consecutive patients referred to 25 different Units of Internal Medicine a/o Gastroenterology in Italy to perform colonoscopy for intestinal symptoms was asked to participate. Patients were treated for 2 months with three doses of nutraceuticals/day after meals namely COLONIR®. Patients were assessed at baseline and after 2 months to evaluate the frequency and severity of gastrointestinal symptoms in the past seven days with a questionnaire based on ROMA IV criteria. After 2 months, 899 patients completed the follow-up. COLONIR® achieved a statistically significant reduction of severity of symptoms in the study population without any documented side effects. These promising results, here reported, need to be confirmed, valuating the efficacy of COLONIR® in relieving gastrointestinal symptoms in IBS patients in further studies.

This study sought to determine the distribution of free and bound phenolics in some Nigerian citrus peels [orange (Citrus sinensis), grapefruit (Citrus paradisii) and shaddock (Citrus maxima)] and characterize the antioxidant properties. The free phenolics were extracted with 80% acetone, while the bound phenolics were extracted from the alkaline and acid hydrolyzed residue with ethyl acetate. Free phenolic extracts had significantly higher (P < 0.05) DPPH* scavenging ability than the bound phenolic extracts, except in orange peels where the bound phenolic extracts had significantly higher (P < 0.05) DPPH* scavenging ability. Bound phenolics from orange peels had the highest ABTS* scavenging ability (6.09mmol./TEAC g) and ferric reducing antioxidant properties (FRAP) (71.99mg/GAE 100g), while bound phenolics from shaddock peels had the least ABTS* scavenging ability (1.35mmol./TEAC g) and FRAP (2.58mg/GAE 100g) . Bound phenolics from grapefruit peels had the highest OH* scavenging ability (EC50 = 3.8mg/ml), while bound phenolics from shaddock peels had the least (EC50 = 16.1mg/ml). The phenolics chelated Fe(2+) and inhibited malondialdehyde production in rat's pancreas in a dose-dependent manner. The additive and/or synergistic action of the free and bound phenolics could have contributed to the observed medicinal properties of the peels; therefore, the high antioxidant properties of the free and bound phenolic extracts from orange peels could be harness in the formulation of nutraceuticals and food preservatives.

Bioactive peptides (BAPs) are peptides derived from enzymatic hydrolysis of food proteins using exogenous enzymes or during bioprocessing operations such as fermentation. Available scientific information provides strong evidence of several bioactive properties of BAPs. This chapter discusses the methods of production and analysis of BAPs, and their health-promoting bioactivities, including antioxidant, antidiabetic, anti-hyperlipidaemic, antihypertensive, and anti-inflammatory properties. This chapter covers results obtained from a range of in vitro, cellular, and in vivo studies, as well as the opportunities and limitations of the inclusion of BAPs as biofunctional agents in the formulation of nutraceuticals and functional foods.

Polyphenols are natural chemical compounds, common in higher plants as and particularly known and appreciated for their health properties. We focused attention on Citrus bergamia, Citrus sinensis, Mela annurca and Vitis Vinifera. Citrus is one of larges species among plant; it consists of 40 species which are distributed in all continents and its fruits. We have developed a fast HPLC with ion-trap TOF-MS method for the analysis of flavonoids in these juices. With respect to the typical methods for the analysis of these matrices based on conventional HPLC techniques, a tenfold faster separation was attained. The nutraceutical potential of Citrus bergamia and sinensis extract was evaluated in vitro, on J774A.1 murine macrophages induced by LPS and in human hepatoblastoma cells Hepg2. Our results demonstrated that juices act as antioxidant and anti-inflammatory agent in LPS-treated J774A.1 macrophages. Annurca apple, possesses not only a particular taste and flavor, but also several healthy properties. With the aim to thoroughly elucidate the polyphenolic profile of this variety, an extensive qualitative profiling of Annurca apple polyphenolic extract was carried out, by employing a combination of ultra high performance reversed phase (RP-UHPLC) and hydrophilic liquid chromatography (HILIC) coupled to ion trap-time of flight (IT-TOF) mass spectrometry. Thanks to the different selectivity obtained with the HILIC, in combination with accurate mass measurements, an improved separation and detection of procyanidins, was obtained for the first time in this kind. Red grapes are rich in phenolics, flavonoids, anthocyanins and resveratrol, all substances which have been suggested as having nutraceutical and health benefits. The berry skin and wine of grape cultivar Vitis vinifera L. (cv. Aglianico), were examined to determinate the presence of the above mentioned compounds as well as to establish the inorganic cation profile. The wine made with the same grape used for berry skin assays showed a notable presence of quercetin-3-O-glucoside. The processed grape juice processed (lioRGJ) was tested on cardiac-derived H9C2 myocytes to ascertain its effects on reactive oxygen species(ROS) generation and caspase-3 activity. These results would suggest that higher doses of antioxidants occurring in the juice sample may cause apoptotic cell injury via effector caspase-3 activation and subsequent induction of ROS and RNS generation. [edited by author]

Precursor-feeding strategy on the triterpenoid production and anti-inflammatory activity of Antrodia cinnamomea

PurposeLiterature has shown that phenolic acids and flavonoids are bearing with hypoglycemic and anti-adipogenic properties. Therefore, this study aims to evaluate the possibility of phenolic-rich soya bean husk powder extract (SHPE) in combating diabetes and obesity using in vitro models.Design/methodology/approachThe hypoglycemic properties were evaluated by determining the ability of SHPE (25-100 µg/mL) in inhibiting a-amylase and a-glucosidase enzymes and in triggering insulin secretion in BRIN-BD11 cells. Murine 3T3-L1 adipocytes were used for evaluating the anti-adipogenic properties of SHPE through the determination of relative lipid accumulation, triglyceride content and glycerol-3-phosphate dehydrogenase (GPDH) activity.FindingsThe hypoglycemic properties of SHPE was in the dose-dependent manner, where 100 µg SHPE/mL exhibited a significant higher (p < 0.05) a-amylase inhibitory activity (56.8 ± 0.11 per cent) and insulin secretion activity (0.73 ± 0.02 µg/l) against other concentrations. In contrast to the aforementioned findings, a significant lower a-glucosidase inhibitory activity (52.0 ± 0.44 per cent) was also observed in 100 µg SHPE/mL. Nevertheless, findings revealed that all the SHPE were able to inhibit the activity of a-amylase and a-glucosidase and stimulated the insulin secretion in BRIN-BD11 cells. On the other hand, the anti-adipogenic properties of SHPE were in the reverse dose-dependent manner, where 100 µg SHPE/mL demonstrated a significant lower (p < 0.05) relative lipid accumulation (48.5 ± 0.03 per cent), intracellular triglyceride content (5.7 ± 0.07 mg/dL) and GPDH activity (1.0 ± 0.01 mU/mL). These findings reflected that 100 µg SHPE/mL was a potent anti-adipogenic agent when compared with other concentrations. In conclusion, soya husk could emerge as a potential hypoglycemic and anti-adipogenic agents in in vitro models.Originality/valueThis was the first study to explore the effectiveness of phytochemicals derived from soya bean husk in ameliorating hyperglycemia and adipogenesis. Promising findings that derived from the present study could enable the scientists to re-evaluate the potential use of agricultural wastes, especially in the formulation of nutraceuticals.

Isolation of valuable substances from berry seeds and pomace by the green high-pressure methods, their evaluation and application in cosmetic creams

Traditional nutraceuticals and cosmeceuticals hold pragmatic nature with respect to their definitions, claims, purposes and marketing strategies. Their definitions are not well established worldwide. They also have different regulatory definitions and registration regulatory processes in different parts of the world. Global prevalence of nutraceuticals and cosmeceuticals is noticeably high with large market share with minimal regulation compared to traditional drugs. The global market is flooded with nutraceuticals and cosmeceuticals claiming to be of natural origin and sold with a therapeutic claim by major online retail stores such as Amazon and eBay. Apart from the traditional formulations, many manufacturers and researchers use novel formulation technologies in nutraceutical and cosmeceutical formulations for different reasons and objectives. Manufacturers tend to differentiate their products with novel formulations to increase market appeal and sales. On the other hand, researchers use novel strategies to enhance nutraceuticals and cosmeceuticals activity and safety.The objective of this review is to assess the current patents and research adopting novel formulation strategies in nutraceuticals and cosmeceuticals. Patents and research papers investigating nutraceutical and cosmeceutical novel formulations were surveyed for the past 15 years. Various nanosystems and advanced biotechnology systems have been introduced to improve the therapeutic efficacy, safety and market appeal of nutraceuticals and cosmeceuticals, including liposomes, polymeric micelles, quantum dots, nanoparticles, and dendrimers. This review provides an overview of nutraceuticals and cosmeceuticals current technologies, highlighting their pros, cons, misconceptions, regulatory definitions and market. This review also aims in separating the science from fiction in the nutraceuticals and cosmeceuticals development, research and marketing.

Agro-industrial wastes contain a large number of important active compounds which can justify their use as innovative ingredients in nutraceutical products. This study aimed to provide a complete analysis of active molecules, namely (poly)phenols in pea pods water-based extracts, through a UHPLC-Q-Orbitrap HRMS methodology. Data showed that 5-caffeoylquinic acid, epicatechin, and hesperidin were the most relevant (poly)phenols found in the assayed extracts, with a mean value of 59.87, 29.46, and 19.94 mg/100 g, respectively. Furthermore, changes in antioxidant capacity and bioaccessibility of total phenolic compounds (TPC) after the simulated gastrointestinal (GI) process were performed using spectrophotometric assays (FRAP, DPPH, ABTS, and TPC by Folin-Ciocalteu). The acid-resistant capsules (ARC) and the non-acid resistant capsules (NARC) containing the pea pod extract underwent simulated GI digestion. The results suggested that the ARC formulations were able to preserve the active compounds along the simulated GI process, highlighting a higher TPC value and antioxidant capacity than the NARC formulations and the not-encapsulated extracts. Hence, the pea pods water-based extracts could be utilized as a potential alternative source of active compounds, and the use of ARC could represent a suitable nutraceutical formulation to vehiculate the active compounds, protecting the chemical and bioactive properties of (poly)phenols.

Banana inflorescence as a new source of bioactive and pharmacological ingredients for food industry

There is a large demand for nutraceuticals in the market and studies related to their action are needed. In this paper, the antimicrobial activity and the immunomodulatory effect of a nutraceutical formulation containing 14.39% of ascorbic acid, 7.17% of coenzyme Q10, 1.33% of Echinacea polyphenols, 0.99% of pine flavan-3-ols, 0.69% of resveratrol and 0.023% of Echinacea alkylamides were studied using in vitro assays and cell-based metabolomics. Chromatographic analysis allowed us to study the nutraceutical composition. The antibacterial activity was evaluated on S. aureus, K. pneumoniae, P. aeruginosa, E. coli, H. influenzae, S. pyogenes, S. pneumoniae and M. catarrhalis. The immunomodulatory activity was assessed on human macrophages and dendritic cells. The production of IL-1β, IL-12p70, IL-10 and IL-8 was evaluated on culture medium by ELISA and the activation/maturation of dendritic cells with cytofluorimetric analysis. Treated and untreated macrophages and dendritic cell lysates were analysed by liquid chromatography coupled with high-resolution mass spectrometry, and results were compared using multivariate data analysis to identify biological markers related to the treatment with the food supplement. The food supplement decreased K. pneumoniae, P. aeruginosa, E. coli, Methicillin-resistant Staphylococcus aureus (MRSA) and M. catharralis growth, reduced the inflammatory response in macrophages exposed to lipopolysaccharide (LPS) and modulated the activation and maturation of the dendritic cells. Oxidized phospholipids were identified as the main biological markers of treated cell lysates, compared with controls.

Olea europaea L. leaves extract (Oe) and Hybiscus sabdariffa L. flowers extract (Hs) have calcium antagonistic properties. Aim of this work was to study the cardiovascular effects of Pres Phytum(®), a nutraceutical formulation containing a mixture of the two extracts and the excipients, and investigate its possible off-target effects, using in vitro biological assays on guinea pig isolated organs. Cardiovascular effects were assessed using guinea pig atria and aorta. The effects of Pres Phytum on spontaneous gastrointestinal, urinary, and respiratory tracts smooth muscle contractility were evaluated. Pres Phytum exerted a vasorelaxant effect (IC50 = 2.38 mg/mL) and a negative chronotropic effect (IC50 = 1.04 mg/mL) at concentrations lower than those producing smooth muscle spontaneous contractility alterations in the other organs. Compared to Pres Phytum, the mixture did not exert negative inotropic activity, while it maintained a negative chronotropic efficacy (IC50 = 1.04 mg/mL). These experimental data suggest a possible nutraceutical use of this food supplement for the management of preclinical hypertension.

This comprehensive study investigates the pharmacological properties of Daucus carota (carrot), with particular emphasis on its potent antioxidant activity and hepatoprotective effects. Daucus carota represents a valuable medicinal plant species that has garnered significant attention in contemporary phytopharmacological research due to its rich phytochemical composition and therapeutic potential. The present investigation focuses on elucidating the mechanisms through which carrot extracts exert their biological activities, particularly in combating oxidative stress and protecting hepatic tissue from chemical-induced damage. The phytochemical analysis revealed that Daucus carota contains an impressive array of bioactive compounds that contribute to its therapeutic efficacy. Key constituents identified include phenolic compounds such as chlorogenic acid and trans-ferulic acid, which serve as primary antioxidant agents Both in vitro and in vivo experimental evidence substantiates the robust antioxidant mechanisms of Daucus carota. Cell-based assays demonstrated significant free radical scavenging capacity, while animal model studies revealed protective effects against oxidative stress-induced hepatotoxicity. Given the rising incidence of liver diseases globally and the limitations of conventional synthetic drugs, natural hepatoprotective agents like Daucus carota offer promising therapeutic alternatives. The findings suggest potential applications in developing functional foods, nutraceutical formulations, and complementary therapeutic interventions for managing oxidative stress-related hepatic disorders. This study contributes valuable insights into the pharmacological validation of traditional medicinal uses of carrot and establishes a scientific foundation for its integration into evidence-based complementary medicine practices.