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.

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.

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.

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.

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.

Effects of forest bathing (shinrin-yoku) on individual well-being: an umbrella review.

The aim of this review was to outline the most relevant benefits of forest bathing for well-being promotion. This study was designed as an umbrella literature review. Medline (via PubMed), EMBASE, Web of Science, Cochrane Library, Google Scholar, Scopus, PsycINFO, CINAHL and the DOAJ were systematically searched for relevant reviews up to February 2021. After article selection, 16 systematic reviews met inclusion criteria. Overall, the best available evidence supports the use of forest bathing as a complementary practice for the promotion of psychophysical well-being, whereas evidence for its use as a therapeutic practice for the improvement of organic diseases needs to grow before clear and specific clinical indications can be formulated. The positive impact of forest bathing on individual quality of life, along with its favorable cost-effectiveness profile, may justify its possible adoption for public health strategies of well-being promotion. Further investigations on the topic are advised.

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.

The cypsela (achene) of Echinacea purpurea as a diffusion unit of a community of microorganisms.

Echinacea purpurea is a plant cultivated worldwide for its pharmaceutical properties, mainly related to the stimulation of the immune system in the treatment of respiratory infections. The cypselas (fruits) of E. purpurea were examined in order to investigate the presence, localization and potential function(s) of endophytic microorganisms. Electron and confocal microscopy observations showed that three different components of microorganisms were associated to cypselas of E. purpurea: (i) one endocellular bacterial component in the cotyledons, enclosed within the host membrane; (ii) another more generic bacterial component adhering to the external side of the perianth; and (iii) a fungal component inside the porous layer of the perianth, the woody and porous modified residual of the flower, in the form of numerous hyphae able to cross the wall between adjacent cells. Isolated bacteria were affiliated to the genera Paenibacillus, Pantoea, and Sanguibacter. Plate tests showed a general resistance to six different antibiotics and also to an antimicrobial-producing Rheinheimera sp. test strain. Finally, microbiome-deprived E. purpurea seeds showed a reduced ability to germinate, suggesting an active role of the microbiome in the plant vitality. Our results suggest that the endophytic bacterial community of E. purpurea, previously found in roots and stem/leaves, might be already carried at the seed stage, hosted by the cotyledons. A further microbial fungal component is transported together with the seed in the perianth of the cypsela, whose remarkable structure may be considered as an adaptation for fungal transportation, and could influence the capability of the seed to germinate in the soil.Key Points• The fruit of Echinacea purpurea contains fungi not causing any damage to the plant.• The seed cotyledons contain endocellular bacteria.• Seed/fruit deprived of the microbiome showed a reduced ability to germinate.

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.

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.

Therapeutic efficacy of orally administered pollen for nonallergic diseases: An umbrella review.

Pollen has been used for centuries as a tonic and a multipurpose remedy in traditional medicine. The present umbrella review aims to qualitatively assess the therapeutic efficacy of orally administered pollen in the management of nonallergic diseases. MEDLINE via PubMed, Embase, Scopus, Web of Science, CINAHL, Cochrane Library, and Google Scholar were systematically searched for relevant systematic reviews and meta-analyses. Articles were independently screened and selected, then quality of evidence of included studies was evaluated with a dedicated NIH tool. Retrieved evidence was critically appraised and discussed. Two hundred four articles were found and, after selection process, five systematic reviews were included in the present work, including one with a meta-analysis. Evidence from these reviews supports the use of grass pollen extracts for symptomatic benign prostatic hyperplasia (BPH) and chronic prostatitis (CP). Additional preliminary evidence on the topic indicates the potential use of grass pollen extracts for vasomotor symptoms in women. Overall, results of the present review suggest that flower pollen extracts may be useful as a complementary remedy for the management of BPH, CP, and vasomotor symptoms. Evidence regarding bee pollen is too limited to draw any conclusion on its clinical efficacy. Further studies are needed.

The use of complementary and alternative medicines during breastfeeding: results from the Herbal supplements in Breastfeeding InvesTigation (HaBIT) study.

AIMS: The use of complementary and alternative medicines (CAMs) during breastfeeding is increasing, mainly because of their presumed greater safety compared with conventional medications. However, CAMs can cause serious adverse effects, and there is limited high-quality evidence supporting their use during lactation. In Italy, specific investigations on the attitude of lactating women towards CAMs are lacking. The Herbal supplements in Breastfeeding InvesTigation (HaBIT) study aimed to explore attitudes to and knowledge on CAMs among lactating women. METHODS: A web-based survey was conducted over a 6-year period among lactating women resident in Tuscany, Italy. Data on lactating behaviour, CAMs use during pregnancy or breastfeeding, and women's knowledge about the efficacy and safety of CAMs were collected. RESULTS: A total of 388 lactating women answered the questionnaire. The majority of them were primiparae, with a high educational level. Of these, 204 women declared themselves to have used CAMs during breastfeeding. Moreover, 61% and 48% of subjects reported also using CAMs before and during pregnancy, respectively. A significant proportion of subjects were unable to identify correctly the types of CAMs they were using. Seventy-three per cent of women were convinced that CAMs were equally safe or safer than conventional medications; nevertheless, 65% of women admitted to have no scientific information about the potential risks of CAMs, and 14 CAMs users reported that they had experienced side effects. CONCLUSIONS: These results demonstrate the need for healthcare providers to increase the awareness of breastfeeding women about CAMs. Further research is needed to support the evidence base for nonpharmaceutical approaches for symptom control during breastfeeding.

Antagonistic interactions between endophytic cultivable bacterial communities isolated from the medicinal plant Echinacea purpurea.

In this work we have studied the antagonistic interactions existing among cultivable bacteria isolated from three ecological niches (rhizospheric soil, roots and stem/leaves) of the traditional natural medicinal plant Echinacea purpurea. The three compartments harboured different taxonomic assemblages of strains, which were previously reported to display different antibiotic resistance patterns, suggesting the presence of differential selective pressure due to antagonistic molecules in the three compartments. Antagonistic interactions were assayed by the cross-streak method and interpreted using a network-based analysis. In particular 'within-niche inhibition' and 'cross-niche inhibition' were evaluated among isolates associated with each compartment as well as between isolates retrieved from the three different compartments respectively. Data obtained indicated that bacteria isolated from the stem/leaves compartment were much more sensitive to the antagonistic activity than bacteria from roots and rhizospheric soil. Moreover, both the taxonomical position and the ecological niche might influence the antagonistic ability/sensitivity of different strains. Antagonism could play a significant role in contributing to the differentiation and structuring of plant-associated bacterial communities.

Pharmacovigilance of herb-drug interactions among preoperative patients.

The Pharmacovigilance Center of the University of Florence conducted a survey across 3 hospitals in Tuscany (Empoli, Florence, and Prato) on a sample population consisting of 478 patients admitted to the hospital for a preoperative assessment before surgical intervention. The aim of the study was to assess the concomitant use of herbal remedies (HRs) and prescribed medications and to evaluate the most important potential interactions. Almost 50% of the patients surveyed-238 of 478 (49.8 %)-used at least 1 HR. Among them, 55 (23.1%) were actually exposed to at least 1 potential interaction. In particular, 42 participants had an HR-drug interaction and 17 participants had a dietary supplement drug interaction. A large percentage of patients undergoing surgery take HRs that could potentially interact with drugs administered perioperatively. Antihypertensive, antiplatelet, anticoagulant, and central nervous system (CNS) agents were the main products involved. The use of HRs is not devoid of risks and adverse effects due to potential interactions that may be serious or even lifethreatening. HR-drug interactions should be deeply investigated, especially in high-risk patient populations. Health care professionals should pay close attention and always investigate the consumption of HRs among their patients.

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.

Novel Sources of Biodiversity and Biomolecules from Bacteria Isolated from a High Middle Ages Soil Sample in Palermo (Sicily, Italy).

The urban plan of Palermo (Sicily, Italy) has evolved throughout Punic, Roman, Byzantine, Arab, and Norman ages until it stabilized within the borders that correspond to the current historic center. During the 2012 to 2013 excavation campaign, new remains of the Arab settlement, directly implanted above the structures of the Roman age, were found. The materials investigated in this study derived from the so-called Survey No 3, which consists of a rock cavity of subcylindrical shape covered with calcarenite blocks: it was probably used to dispose of garbage during the Arabic age and its content, derived from daily activities, included grape seeds, scales and bones of fish, small animal bones, and charcoals. Radiocarbon dating confirmed the medieval origin of this site. The composition of the bacterial community was characterized through a culture-dependent and a culture-independent approach. Culturable bacteria were isolated under aerobic and anaerobic conditions and the total bacterial community was characterized through metagenomic sequencing. Bacterial isolates were tested for the production of compounds with antibiotic activity: a Streptomyces strain, whose genome was sequenced, was of particular interest because of its inhibitory activity, which was due to the Type I polyketide aureothin. Moreover, all strains were tested for the production of secreted proteases, with those belonging to the genus Nocardioides having the most active enzymes. Finally, protocols commonly used for ancient DNA studies were applied to evaluate the antiquity of isolated bacterial strains. Altogether these results show how paleomicrobiology might represent an innovative and unexplored source of novel biodiversity and new biotechnological tools. IMPORTANCE One of the goals of paleomicrobiology is the characterization of the microbial community present in archaeological sites. These analyses can usually provide valuable information about past events, such as occurrence of human and animal infectious diseases, ancient human activities, and environmental changes. However, in this work, investigations about the composition of the bacterial community of an ancient soil sample (harvested in Palermo, Italy) were carried out aiming to screen ancient culturable strains with biotechnological potential, such as the ability to produce bioactive molecules and secreted hydrolytic enzymes. Besides showing the biotechnological relevance of paleomicrobiology, this work reports a case of germination of putatively ancient bacterial spores recovered from soil rather than extreme environments. Moreover, in the case of spore-forming species, these results raise questions about the accuracy of techniques usually applied to estimate antiquity of DNA, as they could lead to its underestimation.