Climate Change Dependence in Ex Situ Conservation of Wild Medicinal Plants in Crete, Greece.

Over 80% of the global population addresses their primary healthcare needs using traditional medicine based on medicinal plants. Consequently, there's a rising demand for these plants for both household and industrial use at local, regional, national, and international levels. However, wild harvesting has negatively impacted natural ecosystems. Cultivating medicinal species has been proposed as a conservation strategy to alleviate this pressure. Yet, in this age of global climate change concerns, smallholder farmers' views on the benefits of such cultivation clash with the uncertainties of climate change impacts, amplifying their anxieties. In this context, the climate change dependence of ex situ cultivation of ten wild medicinal taxa with significant ethnopharmacological interest in Crete, Greece, were studied, projecting their potential habitat suitability under various future climate scenarios. The results demonstrated species-specific effects. Based on the potential cultivation area gains and losses, these effects can be categorized into three groups. We also outlined the spatial patterns of these gains and losses, offering valuable insights for regional management strategies benefiting individual practitioners.

From Traditional Ethnopharmacology to Modern Natural Drug Discovery: A Methodology Discussion and Specific Examples.

Ethnopharmacology, through the description of the beneficial effects of plants, has provided an early framework for the therapeutic use of natural compounds. Natural products, either in their native form or after crude extraction of their active ingredients, have long been used by different populations and explored as invaluable sources for drug design. The transition from traditional ethnopharmacology to drug discovery has followed a straightforward path, assisted by the evolution of isolation and characterization methods, the increase in computational power, and the development of specific chemoinformatic methods. The deriving extensive exploitation of the natural product chemical space has led to the discovery of novel compounds with pharmaceutical properties, although this was not followed by an analogous increase in novel drugs. In this work, we discuss the evolution of ideas and methods, from traditional ethnopharmacology to in silico drug discovery, applied to natural products. We point out that, in the past, the starting point was the plant itself, identified by sustained ethnopharmacological research, with the active compound deriving after extensive analysis and testing. In contrast, in recent years, the active substance has been pinpointed by computational methods (in silico docking and molecular dynamics, network pharmacology), followed by the identification of the plant(s) containing the active ingredient, identified by existing or putative ethnopharmacological information. We further stress the potential pitfalls of recent in silico methods and discuss the absolute need for in vitro and in vivo validation as an absolute requirement. Finally, we present our contribution to natural products' drug discovery by discussing specific examples, applying the whole continuum of this rapidly evolving field. In detail, we report the isolation of novel antiviral compounds, based on natural products active against influenza and SARS-CoV-2 and novel substances active on a specific GPCR, OXER1.

Consumers' attitude toward dietary supplements and functional food: a prospective survey in a Greek population sample.

PURPOSE: The main objective of the present study was to investigate the attitudes among a sample of educated Greek consumers toward the use of dietary supplements (DS) and functional foods (FF) given that attitudes and behaviors as regards DS/FF have not been sufficiently evaluated in Southern Europe, where their penetration is lower as compared to northern countries. METHOD: An online questionnaire was completed by 358 individuals (n = 358, 55.6% females, 44.4% males, and 82% of the total with higher education). Questionnaire reliability was assessed by Cronbach's alpha coefficient while independence among qualitative variables was assayed by Pearson's chi-squared test or Fisher's exact test. The different groups of questions were analyzed by factor analysis, with principal component analysis and Varimax rotation, applied after a factor analysis and Kaiser-Meyer-Olkin (KMO) measure of sampling adequacy test. Finally, a hierarchical cluster analysis based on Ward's method, using the squared Euclidean distance as a measure, was performed in order to identify and classify cases. RESULTS: Our results revealed that the majority of responders were aware of the principles of healthy eating, considering DS/FF as valid additives conferring beneficial effects. A surprising finding is that consumers, independently of the use of DS/FF, tend to prepare food at home and to adhere strongly to the Mediterranean diet and its principles. In addition, they express a certain degree of wariness as to product labeling and health claims, following instead the recommendations of health professionals and scientific evidence. Finally, they prefer to purchase DS/FF from pharmacies. CONCLUSION: Our findings provide valuable data concerning active Greek consumers' attitudes toward these relative new products, which could be extended to other Mediterranean and South European populations.

Toxicity evaluation of an essential oil mixture from the Cretan herbs thyme, Greek sage and Cretan dittany.

The importance of herbal extracts on health, which was initially based on ethnopharmacological and traditional knowledge, becomes increasingly well documented by numerous experimental and intervention studies. The daily use of beverages from different aromatic plants which becomes more popular nowadays, has been a tradition in Crete, and a habit that has been linked to the longevity seen in the island. Additionally, a certain combination of aromatic plants has been used against common cold and influenza. Interestingly, when such a mixture of essential oils from Cretan herbs (Cretan Aromatic Plants essential oil, CAPeo, from thyme, Greek sage, and Cretan dittany) was formulated, significant antiviral properties were observed in vitro and a significant reduction in the duration and severity of symptoms of patients with upper respiratory tract infections was found in a clinical study. However, since many plants extracts can exert toxic effects, toxicity issues should be properly addressed. In the present work we present an acute and sub-chronic toxicity evaluation for this mixture of aromatic plants' essential oils in rats. In fact, it is the only toxicity study for Cretan dittany. We report absence of toxicity, rendering the use of the mixture of essential oils from Cretan dittany, Greek sage and thyme as safe.

Translating vitamin D transcriptomics to clinical evidence: Analysis of data in asthma and chronic obstructive pulmonary disease, followed by clinical data meta-analysis.

Vitamin D (VitD) continues to trigger intense scientific controversy, regarding both its bi ological targets and its supplementation doses and regimens. In an effort to resolve this dispute, we mapped VitD transcriptome-wide events in humans, in order to unveil shared patterns or mechanisms with diverse pathologies/tissue profiles and reveal causal effects between VitD actions and specific human diseases, using a recently developed bioinformatics methodology. Using the similarities in analyzed transcriptome data (c-SKL method), we validated our methodology with osteoporosis as an example and further analyzed two other strong hits, specifically chronic obstructive pulmonary disease (COPD) and asthma. The latter revealed no impact of VitD on known molecular pathways. In accordance to this finding, review and meta-analysis of published data, based on an objective measure (Forced Expiratory Volume at one second, FEV1%) did not further reveal any significant effect of VitD on the objective amelioration of either condition. This study may, therefore, be regarded as the first one to explore, in an objective, unbiased and unsupervised manner, the impact of VitD levels and/or interventions in a number of human pathologies.

From wild harvest towards precision agriculture: Use of Ecological Niche Modelling to direct potential cultivation of wild medicinal plants in Crete.

Understanding the distribution of wild medicinal plants and areas that are suitable for cultivation of these plants is important for both conservation and agriculture. Here, we study ten taxa with known ethnopharmacological uses, which have been used extensively in traditional medicine and as culinary supplements. We aim to (1) predict and map the potential habitat suitability for these taxa across the study area, (2) investigate spatial patterns that could have management implications, such as niche similarities among the taxa and suitability "hotspots" with the use of novel indices, and (3) develop a platform where parts of this information can be accessed and utilized by all interested groups, from the policy-maker level to the individual practitioner level. Ecological Niche Models developed for each study taxon, based on topographic, bioclimatic, soil, and land use variables had high predictive power and were used as the basis for suitability visualization. A series of informative indices were also calculated and mapped, revealing spatial patterns not readily observable from the single-taxon predictions, and providing valuable information to managers. Finally, a web-based, easy-to-use application was also created, where the predicted suitability scores for the study area can be made accessible to anyone interested. The application can provide information both in a visual form (i.e. maps of predicted suitability) and in a numerical form (i.e. estimated suitability scores for all taxa in a given geographical location). This study provides the scientific tools to make a step towards cultivating a group of economically important wild medicinal plants in Crete, as well as the tools to disseminate this information to decision makers and practitioners, and eventually integrate the research findings in local agricultural practices.

Significant metabolic improvement by a water extract of olives: animal and human evidence.

PURPOSE: Dyslipidemia and impaired glucose metabolism are the main health issues of growing prevalence and significant high healthcare cost, requiring novel prevention and/or therapeutic approaches. Epidemiological and animal studies revealed that olive oil is an important dietary constituent, inducing normolipidemia. However, no studies have specifically investigated the polyphenol-rich water extract of olives (OLWPE), generated during olive oil production. METHODS: In the present work, we initially examined the effect of OLPWE on animals' metabolic parameters. Rats fed with a high-fat diet were treated with three different doses of OLPWE for 4 months. Additionally, bioavailability was explored. Afterwards, OLWPE's metabolic effect was explored in humans. Healthy volunteers consumed microencapsulated OLWPE for 4 weeks, in a food matrix [one portion (30 g) of a meat product]. RESULTS: High-fat-fed rats developed a metabolic dysfunction, with increased LDL and insulin levels and decreased HDL; this syndrome was significantly impaired when treated with OLWPE. Treated rats had increased total plasma antioxidant capacity, while several phenolic compounds were detected in their blood. These findings were also verified in humans that consumed OLWPE, daily, for 4 weeks. Interestingly, in individuals with elements of cardio-metabolic risk, OLWPE consumption resulted in reduced glucose, insulin, total cholesterol, LDL and oxLDL levels. CONCLUSIONS: Our data clearly show that OLWPE can improve glucose and lipid profile, indicating its possible use in the design of functional food and/or therapeutic interventions.

Post-market outcome of an extract of traditional Cretan herbs on upper respiratory tract infections: a pragmatic, prospective observational study.

BACKGROUND: The beneficial effects of traditional herbs of Crete, Greece for the treatment of upper respiratory tract infections have been reported in observational and laboratory studies. Following a published, double blind, randomized, placebo controlled trial, this study aimed to assess the effectiveness of an extract of three Cretan herbs on the treatment of upper respiratory tract infections, upon its market release. METHODS: An observational study was conducted in Heraklion, Crete, Greece. Participants were patients presenting at selected pharmacies with symptoms of upper respiratory tract infection, choosing to receive the extract for their treatment. Patients' symptoms (local, general, total) where recorded at three time points within 1 week, using a questionnaire developed based on the Wisconsin Upper Respiratory System Survey. For each patient, symptoms were scored on a 0-7 Likert scale and three indexes were calculated: the score of local symptoms, the score of general symptoms and the total score of symptoms. Effectiveness was assessed by examining the reduction in these indexes over the 1-week observation period. RESULTS: Mean score of general symptoms was 19.1 (SE: 0.9) in day 1, dropping to 8.6 (SE: 0.6) and 3.1 (SE: 0.4) in days 4 and 7 respectively. Mean score of local symptoms declined from 7.9 (SE: 0.5) in day 1 to 2.3 (SE: 0.3) in day 4 and to 0.5 (SE: 0.1) in day 7. Total score of symptoms reached 27.0 (SE: 1.2) in day 1, decreasing to 10.9 (SE: 0.8) in day 4 and to 3.5 (SE: 0.5) in day 7. The percentage of participants reporting fever was 82.1% at baseline, 8.0% in day 4 and 2.0% in day 7 (p < 0.0001 for paired differences). Multiple regression models indicated that supplementary medication intake did not seem to affect symptoms' severity or the day patients reported that their symptoms ceased completely. CONCLUSIONS: This pragmatic study added evidence about the potential therapeutic effects of an extract of Cretan herbs on the amelioration of upper respiratory tract infection symptoms.

Impact of religiosity/spirituality on biological and preclinical markers related to cardiovascular disease. Results from the SPILI III study.

OBJECTIVE: This study aimed at exploring to what extent psychosocial factors, such as religiosity/spirituality and sense of coherence, mediate the negative effects of stress on a variety of cardiometabolic indicators, i.e., hypertension, diabetes, cardiovascular and cerebrovascular disease, and atherosclerotic bio-clinical markers. DESIGN: A total of 220 subjects (66.2±16.0 years) of the SPILI III cohort (1988-2012) attending a primary care setting in Spili, a rural town in Crete, represented the target group for the present study. Of these, 195 (88.6%) participated in the re-examination (67.2±15.2 years). All participants underwent a standardized procedure including evaluation of anthropometric measurements, biochemical indicators of atherosclerosis, stress hormones, in parallel with ultrasound measurements of carotid intima media thickness (IMT). Religiosity, spirituality and sense of coherence were evaluated with the use of international questionnaires translated into the Greek language and linguistically validated. RESULTS: Participants with higher levels of religious and spiritual beliefs presented lower levels of carotid IMT (1.01±0.101 vs 1.53±0.502 mm, p<0.001). Patterns of inverse relationships were also observed between religiosity/spirituality and prevalence of diabetes (35.1% vs. 2%, p<0.001) with an estimated diabetes risk, fully adjusted odds ratio, 95% CI: 0.91 (0.87-0.94). Highly religious participants presented lower serum cortisol levels (12.3±5.8 vs. 18.2±5.1 µg/dl, p<0.001). Sense of coherence was positively associated with religiosity/spirituality [mean SOC (SD): 123±20 vs. 158±15) p<0.001]. CONCLUSIONS: These findings may be associated with a possible favourable effect of religiosity/spirituality on several cardio-metabolic determinants, therefore deserving further attention by healthcare practitioners and researchers.

Novel oligomeric proanthocyanidin derivatives interact with membrane androgen sites and induce regression of hormone-independent prostate cancer.

Prostate cancer is the most common malignancy among men in Western societies, and current therapeutic approaches are evolving to manage growth, recurrence, and mortality neoplasia. Membrane androgen receptors (mARs) have been characterized in human prostate cancer, being preferentially expressed in tumor rather than benign gland areas. Furthermore, mAR agonists (protein-conjugated testosterone) decrease in vitro prostate cancer cell growth and induce apoptosis, whereas in vivo they regress growth of tumor xenografts alone or in combination with taxane drugs. In this respect, targeting mARs might be a novel therapeutic approach in prostate cancer. In our search for new small-molecule ligands of mAR, we report that flavanol dimers B1-B4 (oligomeric procyanidins) decrease in vitro growth of the androgen-sensitive (LnCaP) and androgen-resistant (DU145) human prostate cancer cell lines in the following order: B3 = B4 > B2 ≫ B1 (LnCaP) and B2 ≫ B3 = B4 ≫ B1 (DU145). Some of these analogs were previously shown to trigger signaling cascades similar to testosterone-bovine serum albumin (BSA) conjugate. Galloylation does not confer an additional advantage; however, oleylation increases the dimers' antiproliferative potency by a factor of 100. In addition, we report that B2, oleylated or not, displaces testosterone from mARs with an IC(50) value at the nanomolar range and induces DU145 tumor xenograft regression by 50% (testosterone-BSA 40%). In this respect, oleylated B2 is a potent small-molecule agonist of mAR and could be a novel therapeutic agent for advanced prostate cancer, especially when taking into account the absence of androgenic actions and (liver) toxicity.

ArF-193 excimer laser and Emdogain in the treatment of experimental periodontitis: an experimental study in rabbits.

OBJECTIVE: We aimed to investigate how the progress made on laser technology during the last ten years could overcome this obstacle and allow the use of lasers in periodontology, together with the application of a number of products permitting the regeneration of periodontal tissues. BACKGROUND DATA: The use of lasers in dentistry remains controversial, in spite of their increasing application in medical practice. The main reason for this discrepancy is the frequent report of damage to surrounding tissues and the dental pulp, due to the energy transfer, from the site of laser impact. METHODS: Experimental periodontitis was initiated in fifteen rabbits. Animals were divided into five equal groups. In the control group, no therapy was applied. The remaining four groups were treated with curettage or ArF 193 excimer laser, under conditions of strict control of frequency, fluency, and application, without or with the application of a periodontal healing product (Emdogain). Laser was applied by the use of a new, articulated arm for beam delivery. Pocket depth and microscopic analysis were performed three weeks after treatment. RESULTS: Our results show that all treatment groups decreased pocket depth significantly. ArF193 excimer laser does not produce any histological damage to the dental pulp, and facilitates periodontal regeneration. This result is highly facilitated by the application of Emdogain). CONCLUSIONS: The use of UV lasers, under a tight control of its energy, may be a valuable tool for the treatment of periodontal diseases, especially combined with the use of healing products. Further study is need to confirm these results.