A descriptive study of commercial herbal dietary supplements used for dyslipidemia-Sales data and suspected adverse reactions.

Herbal dietary supplements (HDS) used for dyslipidemia represent a category of concern in Italy for suspected adverse reactions (ARs). However, we cannot estimate their safety, as we do not know their commercial profile. Sales data of HDS, and particularly, those used for dyslipidemia, were monitored for 2 years in two pharmacies of Rome. Meanwhile, spontaneous reports of suspected ARs potentially related to dyslipidemia supplements were collected by the Italian Phytovigilance System. The 50% of the total dietary supplements are herbal-derived; the 9% of HDS are recommended for dyslipidemia. From our data, 113 different brands have claims for improving lipids profile and 91% of them are multiingredient preparations. Fifteen spontaneous reports of suspected ARs concerned HDS used, for dyslipidemia. The most frequent ARs were joint, abdominal, and muscles pain; vomiting; erythema and hematological disorders; nausea; and rhabdomyolysis. Our findings point out the limited compliance of commercial dyslipidemia-HDS and scientific research about their intrinsic safety. A wide range of ingredients could not support the risk/benefit profile of the supplement. The variable compositions of HDS do not assure the safety, as they do not support the reproducibility of their pharmacological activities. This study could contribute to optimize consumer guidance about what they purchase and consume.

Anthraquinone laxatives use and colorectal cancer: A systematic review and meta-analysis of observational studies.

This systematic review and meta-analysis were conducted to determine the effects of anthraquinone (AQ) laxatives on colorectal cancer (CRC). We searched PubMed, Embase, Google Scholar, and CENTRAL from inception until March 2021, for randomized controlled trials (RCTs) and observational studies. Through the systematic review, we identified 8 observational studies evaluating AQ laxatives use as a risk factor for CRC development, and 5 studies on CRC risk were included in the meta-analysis using a random-effects model. Through the meta-analysis, we found that a history of AQ laxatives use compared with "other" and "no laxatives" use was associated with CRC development (OR: 1.41; 95% CI: 0.94-2.11), although not at a statistically significant level. The possible association persists even after removal of the outlier studies (OR: 1.51; 95% CI: 0.97-2.34). Selection of cases and controls was judged at low or unclear risk of bias across almost all studies, and the quality of evidence was from moderate to low. In conclusion, it is not possible to associate the use of AQ laxatives with the development of CRC. However, the trend toward an increased risk of CRC provides a strong indication for investigating this issue by performing further high-quality studies.

Characterization of the Phytochemical Composition and Bioactivities of Anacyclus maroccanus Ball. and Anacyclus radiatus Loisel Aerial Parts: Preliminary Evidence for the Possible Development of Moroccan Plants.

In the present study, the phytochemical composition and bioactivities of A. maroccanus (AM) and A. radiatus (AR), two ecotypes collected in the Demnate road and Essaouira regions, respectively, were studied to highlight a pharmacological interest and to enable possible pharmaceutical development. To this end, methanolic and ethyl acetate extracts were prepared for each ecotype by fractionation; next, their phytochemical composition was evaluated by spectrophotometric and chromatographic analysis. Moreover, in line with the available evidence for Anacyclus spp. and their traditional use, a screening of bioactivities, including antioxidant, hypoglycemic, antiglycative, chelating, and antibacterial activities, was performed. The extracts were characterized by high amounts of polyphenols, tannins, and flavonoids, especially in the methanolic extracts; these samples were also enriched in carotenoids despite a lower chlorophyll content. Chlorogenic acid and rutin were the major identified compounds. The extracts also showed interesting hypoglycemic, antiglycative, and antibacterial properties, although with differences in efficacy and potency. Present results provide more scientific basis to the ethnopharmacological uses of Anacyclus spp. and suggest a further interest in AM and AR ecotypes as natural sources of bioactive compounds and/or phytocomplexes for possible pharmaceutical and nutraceutical developments.

Role of Caryophyllane Sesquiterpenes in the Entourage Effect of Felina 32 Hemp Inflorescence Phytocomplex in Triple Negative MDA-MB-468 Breast Cancer Cells.

Cannabis sativa L. crops have been traditionally exploited as sources of fibers, nutrients, and bioactive phytochemicals of medical interest. In the present study, two terpene-rich organic extracts, namely FOJ and FOS, obtained from Felina 32 hemp inflorescences collected in June and September, respectively, have been studied for their in vitro anticancer properties. Particularly, their cytotoxicity was evaluated in different cancer cell lines, and the possible entourage effect between nonintoxicating phytocannabinoids (cannabidiol and cannabichromene) and caryophyllane sesquiterpenes (ß-caryophyllene, ß-caryophyllene oxide and α-humulene), as identified at GC/MS analysis, was characterized. Modulation of cannabinoid CB1 and CB2 receptors was studied as a mechanistic hypothesis. Results highlighted marked cytotoxic effects of FOJ, FOS, and pure compounds in triple negative breast cancer MDA-MB-468 cells, likely mediated by a CB2 receptor activation. Cannabidiol was the main cytotoxic constituent, although low levels of caryophyllane sesquiterpenes and cannabichromene induced potentiating effects; the presence in the extracts of unknown antagonistic compounds has been highlighted too. These results suggest an interest in Felina 32 hemp inflorescences as a source of bioactive phytocomplexes with anticancer properties and strengthen the importance of considering the possible involvement of minor terpenes, such as caryophyllane sesquiterpenes, in the entourage effect of hemp-based extracts.

Suspected adverse reactions associated with herbal products used for weight loss: spontaneous reports from the Italian Phytovigilance System.

PURPOSE: Overweight and obesity represent worldwide a rising health problem. In this context, dietary supplements and herbal preparations are often used as self-medication for weight loss. The aim of this study was to describe the safety profile of dietary supplements for weight control by analyzing spontaneous reports of suspected adverse reactions (ARs) received by the Italian Phytovigilance System, from July 2010 to October 2017. METHODS: The suspected ARs were collected using an ad hoc reporting form, registered in a database at the National Institute of Health and evaluated by a multidisciplinary group of experts. The causality assessment was performed using the WHO-UMC system or the CIOMS/RUCAM score. In case of serious adverse reactions, a feedback is provided to the reporter by e-mail. RESULTS: Sixty-six spontaneous reports were collected. ARs involved cardiovascular system (26%), liver (14%), central nervous system (12%), skin (9%), gastrointestinal system (17%), thyroid (8%), kidney (4%), and other organs/systems (10%). In 64% of cases, the reaction was serious. Dechallenge was positive in 46 cases; three cases of positive rechallenge were reported. After the causality assessment, the association between the product intake and the adverse reaction was judged as possible in the majority of the cases (n = 43; 65%). CONCLUSIONS: The data collected confirmed the existence of safety concerns on herbal dietary supplements used for body weight control, mainly related to quality of products and their use as self-medication. In this scenario, spontaneous reports represent the only tools available to monitor safety of these products.

Epilobium spp: Pharmacology and Phytochemistry.

The Epilobium species and their extracts are very popular in folk medicine, for a wide range of applications. The purpose of this review is the analysis of the pharmacological properties of Epilobium spp, considering whether their effects (e.g., anti-inflammatory, antioxidant, antitumor, antimicrobial, analgesic, and antiandrogenic) could rationally justify the use of Epilobium as a treatment of numerous diseases. Even if numerous preclinical studies have been reported, randomized controlled clinical trials (for the evaluation of safety and efficacy), and eventually cost-effectiveness studies (to estimate the long-term cumulative costs), are still needed to confirm the usefulness of these medicinal plants in human diseases.

A Polyphenol Rich Extract from Solanum melongena L. DR2 Peel Exhibits Antioxidant Properties and Anti-Herpes Simplex Virus Type 1 Activity In Vitro.

DR2B and DR2C extracts, obtained by ethanolic maceration of peel from commercially and physiologically ripe aubergine berries, were studied for the antioxidative cytoprotective properties and anti-HSV-1 activity, in line with the evidence that several antioxidants can impair viral replication by maintaining reducing conditions in host cells. The antioxidative cytoprotective effects against tBOOH-induced damage were assessed in Caco2 cells, while antiviral activity was studied in Vero cells; polyphenolic fingerprints were characterized by integrated phytochemical methods. Results highlighted different compositions of the extracts, with chlorogenic acid and delphinidin-3-rutinoside as the major constituents; other peculiar phytochemicals were also identified. Both samples reduced reactive oxygen species (ROS) production and exhibited scavenging and chelating properties. DR2C partly counteracted the tBOOH-induced cytotoxicity, with a remarkable lowering of lactate metabolism under both normoxia and hypoxia; interestingly, it increased intracellular GSH levels. Furthermore, DR2C inhibited the HSV-1 replication when added for 24 h after viral adsorption, as also confirmed by the reduction of many viral proteins' expression. Since DR2C was able to reduce NOX4 expression during HSV-1 infection, its antiviral activity may be correlated to its antioxidant properties. Although further studies are needed to better characterize DR2C activity, the results suggest this extract as a promising new anti-HSV-1 agent.

Role of the area postrema in the hypophagic effects of oleoylethanolamide.

The satiety-promoting action of oleoylethanolamide (OEA) has been associated to the indirect activation of selected brain areas, such as the nucleus of the solitary tract (NST) in the brainstem and the tuberomammillary (TMN) and paraventricular (PVN) nuclei in the hypothalamus, where noradrenergic, histaminergic and oxytocinergic neurons play a necessary role. Visceral ascending fibers were hypothesized to mediate such effects. However, our previous findings demonstrated that the hypophagic action of peripherally administered OEA does not require intact vagal afferents and is associated to a strong activation of the area postrema (AP). Therefore, we hypothesized that OEA may exert its central effects through the direct activation of this circumventricular organ. To test this hypothesis, we subjected rats to the surgical ablation of the AP (APX rats) and evaluated the effects of OEA (10mgkg-1 i.p.) on food intake, Fos expression, hypothalamic oxytocin (OXY) immunoreactivity and on the expression of dopamine beta hydroxylase (DBH) in the brainstem and hypothalamus. We found that the AP lesion completely prevented OEA's behavioral and neurochemical effects in the brainstem and the hypothalamus. Moreover OEA increased DBH expression in AP and NST neurons of SHAM rats while the effect in the NST was absent in APX rats, thus suggesting the possible involvement of noradrenergic AP neurons. These results support the hypothesis of a necessary role of the AP in mediating OEA's central effects that sustain its pro-satiety action.

Green Tea and Bone Marrow Transplantation: From Antioxidant Activity to Enzymatic and Multidrug-resistance Modulation.

Epigallocatechin-3-gallate (EGCG), the main flavonoid of green tea (GT), could play an active role in the prevention of oxidative-stress-related diseases, such as hematologic malignancies. Some effects of EGCG are not imputable to antioxidant activity, but involve modulation of antioxidant enzymes and uric acid (UA) levels. The latter is the major factor responsible of the plasma non-enzymatic antioxidant capacity (NEAC). However, hyperuricemia is a frequent clinical feature caused by tumor lysis syndrome or cyclosporine side effects, both before and after bone marrow transplantation (BMT). Besides this, food-drug interactions could be associated with GT consumption and could have clinical implications. The molecular mechanisms involved in the redox and drug metabolizing/transporting pathways were discussed, with particular reference to the potential role of GT and EGCG in BMT. Moreover, on reviewing data on NEAC, isoprostanes, uric acid, and various enzymes from human studies on GT, its extract, or EGCG, an increase in NEAC, without effect on isoprostanes, and contrasting results on UA and enzymes were observed. Currently, few and contrasting available evidences suggest caution for GT consumption in BMT patients and more studies are needed to better understand the potential impact of EGCG on oxidative stress and metabolizing/transporting systems.

Hepatotoxicity of green tea: an update.

Green tea (GT), obtained from the leaves of Camellia sinensis (L.) Kuntze (Fam. Theaceae), is largely used for its potential health benefits such as reduction in risk of cardiovascular diseases and weight loss. Nevertheless, it is suspected to induce liver damage. Present work reviews the hepatic adverse reactions associated with GT-based herbal supplements, published by the end of 2008 to March 2015. A systematic research was carried out on PubMed, MedlinePlus, Scopus and Google Scholar databases, without any language restriction. Moreover, some accessible databases on pharmacovigilance or phytovigilance were consulted. The causality assessment was performed using the CIOMS/RUCAM score. Nineteen cases of hepatotoxicity related to the consumption of herbal products containing GT were identified. The hepatic reactions involved mostly women (16/19); the kind of liver damage was generally classified as hepatocellular (16/19). The causality assessment between consumption of herbal preparation and hepatic reaction resulted as probable in eight cases and as possible in eleven cases. In seven cases, patients used preparations containing only GT, while twelve reactions involved patients who took multicomponent preparations (MC). The reactions induced by GT had a generally long latency (179.1 ± 58.95 days), and the outcome was always resolution, with recovery time of 64.6 ± 17.78 days. On the contrary, liver injury associated with MC had a shorter latency (44.7 ± 13.85 days) and was more serious in four cases that required liver transplantation and, when resolution occurred, the recovery time was longer (118.9 ± 38.79). MC preparations contained numerous other components, many of which are suspected to induce liver damage, so it is difficult to ascribe the toxicity to one specific component, e.g., GT. Present data confirm a certain safety concern with GT, even if the number of hepatic reactions reported is low considering the great extent of use of this supplement. The mechanism of GT hepatotoxicity remains unclear, but factors related to the patient are becoming predominant. A major safety concern exists when GT is associated with other ingredients that can interact between them and with GT, enhancing the risk of liver damage. Patients should be discouraged from using herbal or dietary supplements containing complex mixtures and should be encouraged to use herbal and dietary supplement possibly under supervision of healthcare professionals.

Antimutagenic and antioxidant activity of a protein fraction from aerial parts of Urtica dioica.

CONTEXT: Urtica dioica L. (Urticaceae), stinging nettle, has been employed as a folklore remedy for a wide spectrum of ailments, including urinary disorders, prostatic hyperplasia, and liver diseases. It has been also used traditionally for cancer treatment. OBJECT: To evaluate the potential chemopreventive properties of a protein fraction from the aerial part of Urtica dioica (namely UDHL30). MATERIALS AND METHODS: UDHL30 has been tested for the antimutagenic activity in bacteria (50-800 µg/plate; Ames test by the preincubation method) and for the cytotoxicity on human hepatoma HepG2 cells (0.06-2 mg/mL; 24 and 48 h incubation). Moreover, the antioxidant activity of UDHL30 (0.1-1200 µg/mL; ABTS and superoxide-radical scavenger assays) was evaluated as potential protective mechanisms. RESULTS: UDHL30 was not cytotoxic on HepG2 cells up to 2 mg/mL; conversely, it exhibited a strong antimutagenic activity against the mutagen 2-aminoanthracene (2AA) in all strains tested (maximum inhibition of 56, 78, and 61% in TA98, TA100, and WP2uvrA strains, respectively, at 800 µg/plate). In addition, a remarkable scavenging activity against ABTS radical and superoxide anion (IC50 values of 19.9 ± 1.0 µg/mL and 75.3 ± 0.9 µg/mL, respectively) was produced. DISCUSSION AND CONCLUSIONS: UDHL30 possesses antimutagenic and radical scavenging properties. Being 2AA a pro-carcinogenic agent, we hypothesize that the antimutagenicity of UDHL30 can be due to the inhibition of CYP450-isoenzymes, involved in the mutagen bioactivation. The radical scavenger ability could contribute to 2AA-antimutagenicity. These data encourage further studies in order to better define the potential usefulness of UDHL30 in chemoprevention.

1H NMR-based urinary metabolic profiling reveals changes in nicotinamide pathway intermediates due to postnatal stress model in rat.

The maternal separation protocol in rodents is a widely recognized model of early life stress allowing acute and chronic physiological consequences to be studied. An (1)H NMR-based metabolomic approach was applied to urines to evaluate the systemic metabolic consequences of maternal separation stress in female rats after the beginning of weaning and 4 weeks later when the rats were reaching adulthood. Furthermore, because maternal separation is considered as a model mimicking the inflammatory bowel syndrome, the lactulose/mannitol test was used to evaluate the influence of postnatal maternal separation on gut permeability and mucosal barrier function by (1)H NMR spectroscopy analysis of urine. The results showed no statistical differences in gut permeability due to maternal separation. The application of ANOVA simultaneous component analysis allowed the contributions of physiological adaptations to the animal's development to be separated from the metabolic consequences due to postnatal stress. Systemic metabolic differences in the maternally separated pups were mainly due to the tryptophan/NAD pathway intermediate levels and to the methyladenosine level. Urinary NMR-based metabolic profiling allowed us to disentangle the metabolic adaptive response of the rats to postnatal stress during the animal's growth, highlighting the metabolic changes induced by weaning, gut closure, and maturity.

Characterization of the Chemopreventive Properties of Cannabis sativa L. Inflorescences from Monoecious Cultivars Grown in Central Italy.

Hemp bioproducts hold great promise as valuable materials for nutraceutical and pharmaceutical applications due to their diverse bioactive compounds and potential health benefits. In line with this interest and in an attempt to valorize the Lazio Region crops, this present study investigated chemically characterized hydroalcoholic and organic extracts, obtained from the inflorescences of locally cultivated Felina 32, USO 31, Ferimon and Fedora 17 hemp varieties. In order to highlight the possible chemopreventive power of the tested samples, a bioactivity screening was performed, which included studying the antimutagenic activity, radical scavenging power, cytotoxicity in human hepatoma HepG2 cells, leakage of lactate dehydrogenase (LDH) and modulation of the oxidative stress parameters and glucose-6-phosphate dehydrogenase (G6PDH) involved in the regulation of the cell transformation and cancer proliferation. Tolerability studies in noncancerous H69 cholangiocytes were performed, too. The organic extracts showed moderate to strong antimutagenic activities and a marked cytotoxicity in the HepG2 cells, associated with an increased oxidative stress and LDH release, and to a G6PDH modulation. The hydroalcoholic extracts mainly exhibited radical scavenging properties with weak or null activities in the other assays. The extracts were usually well-tolerated in H69 cells, except for the highest concentrations which impaired cell viability, likely due to an increased oxidative stress. The obtained results suggest a possibility in the inflorescences from the Felina 32, USO 31, Ferimon and Fedora 17 hemp varieties as source of bioactive compounds endowed with genoprotective and chemopreventive properties that could be harnessed as preventive or adjuvant healing strategies.

Analysis of Safety Concerns on Herbal Products with Assumed Phytoestrogenic Activity.

Phytoestrogens (PEs) are plant-based compounds that can interact with estrogen receptors and are mainly used to treat menopausal complaints. However, the safety of products with assumed phytoestrogenic activity is not fully understood. This study aimed to identify plant species with assumed phytoestrogenic activity, review existing literature on their use and safety, and critically evaluate adverse reaction (AR) reports of single-herb, multi-herb, and mixed-multiple products, as submitted to the Netherlands Pharmacovigilance Centre Lareb and to VigiBase of the World Health Organization (WHO). In the Lareb database, the most commonly reported plant species to cause ARs (total of 67 reports) were Actaea racemosa L. (black cohosh) (47.8%), Humulus lupulus L. (hops) (32.8%), and Glycine max (L.) Merr. (soybean) (22.4%). In the VigiBase database (total of 21,944 reports), the top three consisted of Glycine max (L.) Merr. (71.4%), Actaea racemosa L. (11.6%), and Vitex agnus-castus L. (chaste tree) (6.4%). In the scoping review (total of 73 articles), Actaea racemosa L. (30.1%), Glycine max (L.) Merr. (28.8%), and Trifolium pratense L. (13.7%) were the most frequently mentioned plant species. ARs were most frequently reported in the system organ classes "gastrointestinal disorders", "skin and subcutaneous tissue disorders", "reproductive system and breast disorders", and "general disorders and administration site conditions". Furthermore, from the scoping review, it appeared that the use of products with assumed phytoestrogenic activity was associated with postmenopausal bleeding. It was concluded that, while the potential benefits of products with assumed phytoestrogenic activity have been extensively pursued, the potential occurrence of ARs after using these products is less well understood. This study highlights the need for further investigation and careful monitoring of these products to better understand their effects and ensure the safety and well-being of individuals using them.

Surveillance of suspected adverse reactions to herbal products used as laxatives.

AIM: To describe and evaluate spontaneous reports of suspected adverse reactions (ARs) associated with herbal laxatives received by the Italian Medicines Agency and the Italian National Institute of Health between April 2002 and January 2011. METHODS: Spontaneous reports of suspected ARs were individually analyzed by a multidisciplinary group of experts, and a causality assessment was performed. RESULTS: Twenty-six reactions were reported during the study period. Of these, eight were associated with herbal medicinal products and 18 were related to herbal food supplements. Almost 80% of the reports on ARs involved women. The ARs, classified by System Organ Class, were associated with gastrointestinal, skin and subcutaneous tissue, and hepatobiliary disorders. Fifty percent of the reactions were serious, with the patients requiring hospitalization; of these, one was life-threatening. Most of the herbal remedies associated with the reported ARs contained liquorice, dandelion, and/or plants containing anthraquinones. Possible causes of the ARs were long-term use, idiosyncratic reactions or hypersensitivity, and interaction with other treatments. All of these factors and the presence of a large number of components in the same product increased the unpredictability of the final effect. CONCLUSIONS: The total number of 26 ARs recorded in 8 years is limited; however, the an under-reporting effect cannot be excluded. Moreover, taking into account the seriousness of the reported ARs, the low number of reports does not represent a guarantee of safety. To reduce the risk of an adverse outcome, herbal laxatives should be used only over the short term.

Antimutagenic thio compounds from Sisymbrium officinale.

Glucoputranjivin (1) and isopropyl isothiocyanate (2) were isolated from an aqueous dry extract of Sisymbrium officinale and were identified by spectroscopic analysis. The antimutagenic activity of these compounds was evaluated in a bacterial reverse mutation assay using E. coli WP2, WP2uvrA, and WP2uvrA/pKM101 strains, in comparison with the extract. In the absence of the exogenous metabolic activation system S9, the thio compounds exerted antimutagenic activity against the direct-acting mutagen methyl methanesulfonate, in all strains. In the presence of S9, both thio compounds were active against the indirect mutagens 2-aminoanthracene, in WP2uvrA, and 2-aminofluorene, in WP2. The antimutagenicity seems to be due to specific mechanisms, such as the induction of the adaptive response or the excision repair system. Conversely, the inhibition of the CYP450-mediated activation of mutagens was not supported by the present results. An antimutagenic effect was also observed for the S. officinale aqueous extract against the arylamines 2AA and 2AF, but not against MMS. These results suggest that both thio compounds are involved in the antimutagenicity of S. officinale. The antimutagenicity of glucosinolate 1 is reported for the first time.

Efficacy and Safety of Oral Green Tea Preparations in Skin Ailments: A Systematic Review of Clinical Studies.

Green-tea-based products and their polyphenols, especially epigallocatechin-3-gallate, have attracted great attention over the years as possible nutraceuticals, due to their promising bioactivities, especially antioxidant and anti-inflammatory, which could be exploited in several diseases, including skin ailments. In this context, the present study aimed at reviewing clinical evidence about the benefits of the oral administration of green tea preparations and its polyphenols to relieve skin disorders, to point out the current knowledge, and to suggest possible novel strategies to effectively exploit the properties of green tea, also managing safety risks. To this end, a systematic review of the existing literature was carried out, using the PRISMA method. Few studies, including five focused on UV-induced erythema and skin alterations, three on photoaging, two on antioxidant skin defenses, and one on acne and genodermatosis, were retrieved. Despite several benefits, clinical evidence only supports the use of oral green tea preparations to protect skin from damage induced by ultraviolet radiation; in other cases, conflicting results and methodological limits of clinical trials do not allow one to clarify their efficacy. Therefore, their application as adjuvant or alternative sunscreen-protective interventions could be encouraged, in compliance with the safety recommendations.

Phytochemical Composition and Cytoprotective Properties of the Endemic Sideritis sipylea Boiss Greek Species: A Valorization Study.

Sideritis sipylea Boiss. (Fam. Lamiaceae) is an endemic plant of the North Aegean Islands (Greece), commonly known as ironwort. Traditionally, its aerial parts have been used to relieve several ailments, especially gastrointestinal disorders, however, with scant knowledge about the pharmacological basis. In the present study, an endemic S. sipylea Greek species from Lesvos Island has been characterized for phytochemical composition and biological activities, in order to give a possible scientific basis to its traditional use and to highlight a further nutraceutical interest as a source of bioactive phytochemicals and extracts. Three different fractions obtained from a methanolic extract of S. sipylea aerial parts by using ethyl acetate with 10 (S10), 20 (S20), and 50% (S50) methanol as fractionation solvents were phytochemically characterized. Moreover, their antioxidant power and cytoprotective activity in different human cell lines were evaluated. The phytochemical analysis highlighted the presence of flavonoids, iridoids, and phenolic acids in all the tested samples. Particularly, the S10 fraction mainly contained iridoids, while S20 and S50 lavandulifolioside and chlorogenic acid, respectively. The fractions also showed antioxidant properties, S10 and S20 being the most potent. When assessed in human cholangiocytes, they counteracted the cytotoxicity of the tBOOH pro-oxidant agent, by reducing ROS levels and affecting GSH antioxidant system. The present findings highlight a possible interest in S10 and S20 fractions from S. sipylea as sources of bioactive molecules and stimulate further studies in order to characterize their possible application for nutraceutical and pharmaceutical purposes.

Recent Advances in the Neuroprotective Properties of Ferulic Acid in Alzheimer's Disease: A Narrative Review.

Alzheimer's disease (AD) is a progressive degenerative disorder of the central nervous system, characterized by neuroinflammation, neurotransmitter deficits, and neurodegeneration, which finally leads to neuronal death. Emerging evidence highlighted that hyperglycemia and brain insulin resistance represent risk factors for AD development, thus suggesting the existence of an additional AD form, associated with glucose metabolism impairment, named type 3 diabetes. Owing to the limited pharmacological options, novel strategies, especially dietary approaches based on the consumption of polyphenols, have been addressed to prevent or, at least, slow down AD progression. Among polyphenols, ferulic acid is a hydroxycinnamic acid derivative, widely distributed in nature, especially in cereal bran and fruits, and known to be endowed with many bioactivities, especially antioxidant, anti-inflammatory and antidiabetic, thus suggesting it could be exploited as a possible novel neuroprotective strategy. Considering the importance of ferulic acid as a bioactive molecule and its widespread distribution in foods and medicinal plants, the aim of the present narrative review is to provide an overview on the existing preclinical and clinical evidence about the neuroprotective properties and mechanisms of action of ferulic acid, also focusing on its ability to modulate glucose homeostasis, in order to support a further therapeutic interest for AD and type 3 diabetes.

Adverse events related to herbal dietary supplements and over-the-counter medications containing laxatives: a 10-year update from the Italian Phytovigilance and Pharmacovigilance systems.

INTRODUCTION: Products containing anthraquinones (AQ) are associated with an increased risk of serious adverse events (AEs). We performed an update of the available evidence retrieved by the spontaneous reports of AE associated with herbal dietary supplement (DS) and over-the-counter medications (OTC-M) used as laxatives. METHODS: Analysis and evaluation of AE reports retrieved from the Italian Phytovigilance and Pharmacovigilance systems was performed from February 2011 to December 2020. RESULTS: Totally 110 AE reports, 24 related to herbal DS and 86 to OTC-M, were analyzed. Most subjects were females. Herbal products analyzed mostly contained AQ derivatives. Most AEs were gastrointestinal (41.6%), central nervous system (18.2%), and dermatological disorders (12.6%). CONCLUSIONS: The number of AE reports recorded in the last 10 years is still relatively low. However, given the seriousness of some AEs, that does not represent a guarantee of safety. This study may contribute to enhance public awareness on the risks associated with misuse or abuse of laxatives.