Antimicrobial Activity of Syzygium aromaticum Essential Oil in Human Health Treatment.

The use of natural compounds to prevent and treat infective diseases is increasing its importance, especially in the case of multidrug-resistant (MDR) microorganisms-mediated infections. The drug resistance phenomenon is today a global problem, so it is important to have available substances able to counteract MDR infections. Syzygium aromaticum (L.) Merr. & L.M. Perry (commonly called clove) is a spice characterized by several biological properties. Clove essential oil (EO) consists of numerous active molecules, being eugenol as the principal component; however, other compounds that synergize with each other are responsible for the biological properties of the EO. S. aromaticum is traditionally used for bowel and stomach disorders, cold and flu, oral hygiene, tooth decay, and for its analgesic action. Its EO has shown antioxidant, antimicrobial, anti-inflammatory, neuro-protective, anti-stress, anticancer, and anti-nociceptive activities. This review aims to investigate the role of E. S. aromaticum EO in the counteraction of MDR microorganisms responsible for human disorders, diseases, or infections, such as Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella typhi, Candida albicans, Giardia lamblia, Streptococcus mutans, Porphyromonas gingivalis, and Klebsiella pneumoniae. This study might orient clinical researchers on future therapeutic uses of S. aromaticum EO in the prevention and treatment of infectious diseases.

Suspected adverse reactions to medications and food supplements containing Serenoa repens: A worldwide analysis of pharmacovigilance and phytovigilance spontaneous reports.

The safety of Serenoa repens (SR)-containing products was evaluated conducting a retrospective worldwide analysis of pharmaco- and phytovigilance report forms of suspected adverse reactions (SARs) collected up to 31 January 2022. Multivariate logistic regression was performed to estimate the odds ratios (ORs) of serious SAR. A total of 1810 report forms were analysed; 92% of subjects were males, with a median age of 69 years; 44% of cases were defined as serious. Subjects exposed to dietary supplements had a higher risk of developing serious SARs (OR: 1.60 [95% CI: 1.20-2.15]), as subjects exposed to 2-5 (OR: 1. 83 [95% CI: 1.30-2.58]) or more than 5 (OR: 3.45 [95% CI: 2.36-5.06]) suspect/interacting products. The probability of experiencing serious SAR was higher for subjects exposed to concomitant products (OR: 1.55 [95% CI: 1.15-2.08]), to more than four active compounds (OR: 4.38 [95% CI: 3.21-5.99]) and to SR for more than 14 days (OR: 1.89 [95% CI: 1.10-3, 22]), and lower for subjects exposed to higher doses of SR (OR: of 0.34 [95% CI: 0.20-0.58]). This evidence improves awareness on safety of SR containing products, suggesting the need of a further update of periodic reviews by national and international regulatory agencies.

Safety Profile of Vitamin D in Italy: An Analysis of Spontaneous Reports of Adverse Reactions Related to Drugs and Food Supplements.

Vitamin D (VitD) is largely used in Italy, often inappropriately; thus, an evaluation of its safety is a crucial issue. This study analyses the adverse reactions (ARs) associated with the use of products containing VitD (VitDps) reported to the Italian National Pharmacovigilance and Phytovigilance networks. From March 2002 to August 2022, a total of 643 and 127 reports concerning 903 and 215 ARs were retrieved from Pharmacovigilance and Phytovigilance networks, respectively. Overall, 332 (29.6%) ARs were classified as serious, and the most described ones were hypercalcaemia, renal failure and tachycardia. Serious AR risk was significantly higher for subjects using more than four concomitant products (OR 2.44 [95% CI 1.30-4.60]) and VitD doses higher than 1000 IU/day (OR 2.70 [95% CI 1.30-5.64]). In Italy, there was a modest decrease in AR reporting, despite the slightly increased use of VitD during the COVID-19 pandemic. To the best of our knowledge, this is the first study describing all VitDps-related ARs observed in the Italian general population. Since underreporting is the main limitation of the safety reporting systems, the necessity to continue ARs monitoring, also using real-world data on VitDps prescription, use and outcome patterns is highlighted.

Demographic, Psychosocial, and Lifestyle-Related Characteristics of Forest Therapy Participants in Italy: A Multicenter Cross-Sectional Survey.

This research aims to provide a comprehensive overview of the key demographic, psychosocial, and lifestyle-related characteristics of forest therapy participants in Italy. A survey was conducted among 1070 adults who had engaged in standardized forest therapy experiences between June 2021 and October 2022. The findings indicate that most forest therapy participants in Italy share certain distinctive traits. They are primarily female, aged between 45 and 54 years, employed, and unmarried. Moreover, they possess a high level of education, predominantly reside in urban areas, demonstrate a strong environmental awareness, maintain a nature-oriented attitude, and typically exhibit moderate levels of trait anxiety. Additionally, they tend to be nonsmokers, possess a healthy BMI within the normal range, and consume an adequate quantity of fruits and vegetables on a daily basis. However, it should be noted that their male counterparts tend to be overweight and exhibit poorer dietary habits. Irrespective of gender, approximately 40% of forest therapy participants in Italy live with a chronic disease that requires daily medicinal treatment. Subsequent research should investigate whether these characteristics hold true in different countries. Furthermore, exploring the potential effectiveness of health-promoting interventions integrated with forest therapy sessions could prove beneficial in addressing these specific issues among forest therapy participants. By doing so, such interventions have the potential to contribute significantly to public health promotion and overall community well-being.

Echinacea purpurea against neuropathic pain: Alkamides versus polyphenols efficacy.

Chemotherapy-induced neuropathy represents the main dose-limiting toxicity of several anticancer drugs, such as oxaliplatin, leading to chronic pain and an impairment of the quality of life. Echinacea purpurea n-hexane extract (EP4 -RE ; rich in alkamides) and butanolic extract (EP4 -RBU ; rich in polyphenols) have been characterized and tested in an in vivo model of oxaliplatin-induced neuropathic pain, addressing the endocannabinoid system with alkamides and counteracting the redox imbalance with polyphenols. Thermal hypersensitivity was evaluated by the Cold Plate test. EP4 -RE showed a dose-dependent anti-hyperalgesic profile. The extract was more effective than its main constituent, dodeca-2 E,4 E,8Z,10 E/Z-tetraenoic acid isobutylamide (18 mg kg-1 , twofold to equimolar EP4 -RE 30 mg kg-1 ), suggesting a synergy with other extract constituents. Administration of cannabinoid type 2 (CB2) receptor-selective antagonist completely blocked the anti-allodynic effect of EP4 -RE , differently from the antagonism of CB1 receptors. EP4 -RBU (30 mg kg-1 ) exhibited anti-neuropathic properties too. The effect was mainly exerted by chicoric acid, which administered alone (123 µg kg-1 , equimolar to EP4 -RBU 30 mg kg-1 ) completely reverted oxaliplatin-induced allodynia. A synergy between different polyphenols in the extract had not been highlighted. Echinacea extracts have therapeutic potential in the treatment of neuropathic pain, through both alkamides CB2-selective activity and polyphenols protective properties.

The Different Phytochemical Profiles of Salvia officinalis Dietary Supplements Labelled for Menopause Symptoms.

Phytochemical screening of four commercial products containing Salvia officinalis was carried out. Total phenolic content was estimated spectrophotometrically through the use of the Folin-Ciocalteau method, flavonoid content was measured through the use of aluminum chloride and 2,4-dinitrophenylhydrazine colorimetric assays, and isoflavones and α/ß-thujones were analyzed through the use of high-performance liquid chromatograph (HPLC) and the gas chromatographic method. The analyses revealed the absence of thujones and isoflavones (i.e., genistin, genistein, and daidzein) in all four different extracts. The content of polyphenolic compounds varied among the samples, with the extract T being richer in both polyphenols and flavonoids than the other products by 1.8-3.2 and 1.4-4.0 times, respectively (p-value < 0.05). These results highlight the importance of quality control in salvia-based products since a thujone-free extract rich in polyphenols and flavonoids could be a good candidate for further preclinical and clinical studies to identify an effective herbal approach suitable for the long-term therapy of menopausal symptoms.

Acmella oleracea (L.) R.K. Jansen: Alkylamides and phenolic compounds in aerial parts and roots of in vitro seedlings.

Acmella oleracea L. is an edible and medicinal plant commonly known for its local anaesthetic effect induced by the alkylamide spilanthol. It is also rich of secondary metabolites of biological interest, mainly phenolic acids and glycosylated flavonoids. This study evaluated for the first time alkylamides and phenolic compounds in aerial parts and roots of seedlings grown in vitro and produced from single seed and from regenerating lines. The extracts obtained showed similar chemical profiles and the caffeic acid derivatives were the most abundant phenolic compounds. Spilanthol was prevalent in the aerial parts, especially in samples of seedlings obtained from regenerating lines, in which reached maximum value of 1.72 mg/g dried matter (DM). The roots contained a lower content of alkylamides, while showing twice as much total phenols (11.19 mg/g DM) as the aerial parts. A hexane fractionation step allowed to recover spilanthol and its derivatives in a concentrated extract, which reached a value of 63.4 mg/g dried extract in the aerial parts from seedlings from regenerating lines. Hydroalcoholic dried extracts showed high yields (30-45 % on dried matter) and those obtained from aerial parts contained up to 5.69 mg/g of spilanthol.

An Optimized Terpene Profile for a New Medical Cannabis Oil.

The purpose of this analytical study was to develop an advanced formulation of medical Cannabis oil (MCO) comparing the chemical profile of different extracts obtained with two existing methods (SIFAP and CALVI) and one original upgraded (CERFIT) method. Preparation methods were applied with varying solvent, temperature, and duration of the decarboxylation and extraction steps. HPLC-MS/MS TSQ and GC/FID-HS analyses were performed to investigate cannabinoid and terpene contents in the three oil extracts. Cannabinoids profile remained comparable between the formulations. CERFIT extracts exhibited a superior quantity of total terpene hydrocarbon forms (e.g., limonene and α-pinene) with no degradation occurrence (i.e., oxidized terpenes not quantifiable). Thus, this new method optimized the phytochemical profile of the MCO presenting a value opportunity to obtain a standardized high-level therapeutic product.

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.

Acute liver injury following turmeric use in Tuscany: An analysis of the Italian Phytovigilance database and systematic review of case reports.

AIMS: Several cases of acute non-infectious cholestatic hepatitis recently appeared in Italy following consumption of Curcuma longa-containing dietary supplements. The aim of this research was to describe the Tuscan (Italy) cases of acute hepatitis and to compare them with similar cases of hepatotoxicity published in the literature by performing a systematic review. METHODS: Records of Tuscan cases of acute hepatitis were obtained from the Italian Phytovigilance system. Each spontaneous report was analysed in order to collect all relevant clinical information of patients and information concerning the Curcuma longa-containing dietary supplement. Moreover, both the RUCAM and WHO-UMC systems were used to evaluate the causal relationship between the use of dietary supplement and acute hepatitis. A systematic literature review was performed in MEDLINE and Embase and all case-reports and case-series published in English were included. RESULTS: Seven cases of acute hepatitis occurring in Tuscany up to September 2019 are described. In all cases, hepatotoxicity was associated with Curcuma longa formulations with high bioavailability and high dosage of curcumin/curcuminoids. The causal relationship was also supported by the positive dechallenge observed in most cases. In the 23 cases identified through the systematic review, the majority of patients were concomitantly exposed to at least one other medication and 16 of them experienced a positive dechallenge. CONCLUSIONS: Within the frame of poorly controlled and regulated products, such as dietary supplements, the evaluation of Italian cases of Curcuma longa-induced acute hepatitis and the systematic review of literature confirmed the association between Curcuma longa and liver injury.

Association between anthraquinone laxatives and colorectal cancer: protocol for a systematic review and meta-analysis.

INTRODUCTION: Products containing anthraquinones (AQ) are mainly used as laxatives and have several biological effects. Long-term use of AQ laxatives is associated with an increased risk of serious adverse events (AEs), such as colorectal cancer (CRC). We will systematically synthesize the evidence on the potential association between the use of AQ laxatives and the risk of CRC. METHODS AND ANALYSIS: We will search MEDLINE, Embase, Scopus, the Cochrane Library, Google Scholar, and Clinicaltrials.gov. To avoid missing any relevant studies, we will search the bibliographies of retrieved papers and recent reviews in the field. Interventions will include products containing oral AQ laxatives, in particular, those derived from rhubarb, senna, cascara, buckhorn, and aloe. Two review authors will independently screen title, abstract, and full texts and will independently extract data from included studies. The primary outcome is the number of participants diagnosed with CRC, while the secondary outcome will be cases of melanosis coli. We will also consider all other AEs reported in the included studies, in particular, intestinal bleeding, alterations of gastrointestinal motility, and potential for dependence. When possible and appropriate, for each outcome, a meta-analysis will be performed. DISCUSSION: This protocol is prepared in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. The protocol gives an insight into the scope and parameters for the systematic review to be carried out. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019125414.

Volatile profile of Echinacea purpurea plants after in vitro endophyte infection.

The differences in volatile profile of Echinacea purpurea plants not-inoculated (EpC) and inoculated with their endophytes from roots (EpR) and stem/leaves (EpS/L) were analysed and compared by GC-FID/GC-MS in an in vitro model. Non-terpenes and sesquiterpene hydrocarbons were the most abundant classes with an opposite behaviour of EpS/L showing a decreased emission of sesquiterpenes and an increase of non-terpene derivatives. The main compounds obtained from EpS/L were (Z)-8-dodecen-1-ol and 1-pentadecene, while germacrene D and ß-caryophyllene were the key compounds in EpC and EpR. For the first time, this work indicates that bacterial endophytes modify the aroma profiles of infected and non-infected in vitro plants of the important medicinal plant E. purpurea. Therefore, our model of infection could permit to select endophytic strains to use as biotechnological tool in the production of medicinal plants enriched in volatile bioactive compounds.

Adverse events following cannabis for medical use in Tuscany: An analysis of the Italian Phytovigilance database.

AIMS: Despite a significant increase in using cannabis for medical purposes, current evidence on its safety in real-world clinical practice is still poorly characterised. By a case-by-case analysis of spontaneous reports of suspected adverse events (AEs) collected in Tuscany within the Italian Phytovigilance database, the aim of the present study was to describe AEs occurred in patients exposed to medical cannabis. METHODS: We evaluated all reports of cannabis-related suspected AEs collected within the Phytovigilance database up to December 2018. Information regarding cannabis therapy, patient's demographic and clinical characteristics, concomitant medications, AE description according to the Medical Dictionary for Regulatory Activities (MedDRA) classification, AE seriousness and AE outcome, were collected. The causality assessment was performed following World Health Organisation-Uppsala Monitoring Centre criteria. RESULTS: Fifty-three cannabis-related AE reports were analysed. The majority of patients were females (77.3%), with a mean age of 61.9 years. Thirty-nine (73.6%) cases were defined as nonserious and the majority of them (86.9%) showed a complete resolution or improvement. Forty-six (86.8%) cases were judged as probably related to cannabis consumption. The most frequently reported system organ class was psychiatric and nervous system disorders, and a potential drug-drug interaction was present in 16 cases. CONCLUSION: Cannabis was generally well tolerated and the majority of AEs were mild and transient. Our analysis highlighted important safety issues for clinical practice, in particular the need for an accurate prescription monitoring during the titration phase, particularly in the presence of concomitant medications.

The influence of Echinacea purpurea leaf microbiota on chicoric acid level.

The controversial anti-proliferative effects of Echinacea purpurea (L.) Moench (Asteraceae) might be related to different plant metabolites contained in plant samples, extracts and products. The influence of bacterial endophytes on the synthesis of bioactive compounds in the medicinal plants has been previously demonstrated but there are only few studies addressing anticancer effects and mechanisms of E. purpurea extracts following endophytic colonization. The present study aimed to test and compare the lactate dehydrogenase (LDH) inhibition potential of n-hexane and methanol extracts from in vitro endophyte non-inoculated and inoculated E. purpurea plants. An in vitro model was previously set up to perform the infection of axenic E. purpurea plants with bacterial endophytic strains isolated from E. purpurea aerial part. Only methanol extracts showed LDH5 inhibition, in particular the richest in chicoric acid and most strongly inhibiting extract was obtained from inoculated stem and leaves of E. purpurea (IC50 = 0.9 mg/ml). Chicoric acid showed an IC50 value (66.7 µM) in enzymatic assays better than that of the reference compound galloflavin. Modeling studies were carried out to suggest the putative interaction mode of chicoric acid in the enzyme active site. This in vitro model on plant-bacterial interaction may lead to obtain extracts from plants enriched in bioactive compounds and it is a new approach for the discovery of novel anticancer compounds.

Tissue specificity and differential effects on in vitro plant growth of single bacterial endophytes isolated from the roots, leaves and rhizospheric soil of Echinacea purpurea.

BACKGROUND: Echinacea-endophyte interaction might affect plant secondary metabolites content and influence bacterial colonization specificity and plant growth, but the underlying mechanisms need deepening. An in vitro model, in which E. purpurea axenic plants as host species and E. angustifolia and Nicotiana tabacum as non-host species inoculated with single endophytes isolated from stem/leaf, root and rhizospheric soil, were used to investigate bacterial colonization. RESULTS: Colonization analysis showed that bacteria tended to reach tissues from which they were originally isolated (tissue-specificity) in host plants but not in non-host ones (species-specificity). Primary root elongation inhibition as well as the promotion of the growth of E. purpurea and E. angustifolia plants were observed and related to endophyte-produced indole-3-Acetic Acid. Bacteria-secreted substances affected plant physiology probably interacting with plant regulators. Plant metabolites played an important role in controlling the endophyte growth. CONCLUSIONS: The proposed in vitro infection model could be, generally used to identify novel bioactive compounds and/or to select specific endophytes contributing to the host metabolism properties.

Safety of complementary and alternative medicine in children: A 16-years retrospective analysis of the Italian Phytovigilance system database.

BACKGROUND: Dietary supplements and homeopathic medicines are largely used in children as complementary and alternative medicine (CAM) to treat different health conditions. Safety of CAM is unknown when they are marketed. This study analysed suspected CAM-related adverse reaction (AR) in pediatric population. METHODS: The Italian Phytovigilance system was searched for reports of suspected AR related to CAM use in children (0-18 years) from 2002 to 2018. AR reports were evaluated and information about patient's demographic characteristics, suspected CAM, conventional medications, and ARs were collected. In particular, we evaluated whether patient's and CAM characteristics, and concomitant drugs could be potential predictors of ARs seriousness. RESULTS: We evaluated 206 pediatric CAM-related AR reports, of which 69 were serious. Patients were mostly treated with only one CAM (n = 193), and 39% of AR reports were related to products containing 2-5 components. Most reported ARs were related to dietary supplements (57.18%), and skin and subcutaneous tissue disorders (40.29%) were the most involved System Organ Class. CAM-related AR reported as serious were higher in subjects exposed to homeopathic medicines (ROR 3.13 [1.88-5.22]), to CAM in presence of concomitant medications (ROR 1.77 [1.01-3.10]), to CAM containing 2-4 components (ROR 2.18 [1.13-4.22]), and to more than three concomitant CAM (ROR 7.81 [1.97-32.69]). CONCLUSION: We provide new insights on factors that might increase the risk of serious AR associated with CAM use in children: products containing more than two components and simultaneously administered with conventional medications can represent a potential risk in children.

The Impact of Previous Pregnancy Loss on Lactating Behaviors and Use of Herbal Medicines during Breastfeeding: A Post Hoc Analysis of the Herbal Supplements in Breastfeeding InvesTigation (HaBIT).

INTRODUCTION: Complementary and alternative medicines (CAMs) are commonly used among lactating women, despite the poor knowledge of these products and of their safety. Perception of pregnancy- and breastfeeding-related difficulties and consequent use of CAMs may differ in bereaved women, by force of the distress related to previous loss, although no literature evidence is available. This Herbal supplements in Breastfeeding InvesTigation (HaBIT) post hoc analysis explored the impact of previous pregnancy loss on lactating behaviors and on use of CAMs during breastfeeding. METHODS: A web-based survey was conducted among lactating women with no previous alive child, resident in Tuscany (Italy). Data on lactating behavior and on CAMs use were collected and evaluated among women with previous pregnancy loss as compared to control women. RESULTS: Out of 476 women answering the questionnaire, 233 lactating women with one child were considered. Of them, 80 had history of pregnancy loss. Cesarean birth was significantly more frequent among women with history of pregnancy loss as compared to controls (41% versus 22%; p=0.004). Proportion, length of exclusive breastfeeding, and occurrence of breastfeeding-related complications were comparable among the two cohorts. More than half of women used CAMs during breastfeeding. Use of CAMs was more frequent among women with previous pregnancy loss (54% versus 68%; p=0.050), specifically considering herbal preparations (16% versus 30%; p=0.018). Major advisors for CAMs use were midwives. 18% and 23% of women without and with history of pregnancy loss declared no clear perception on CAMs efficacy and safety. CONCLUSION: Overcoming the social taboo of pregnancy loss and training healthcare professionals for an adequate management of the perinatal period are essential for an effective and safe care. Despite the common use and advice on CAMs use during breastfeeding, it is important to acknowledge that limited evidence supports their safety and efficacy during such critical period.