Molecular hybridization is a widely used strategy in drug discovery and development processes that consists in the combination of two bioactive compounds toward a novel entity. In the current study, two libraries of hybrid derivatives coming from the linkage of sesquiterpene counterparts dihydroartemisinin and artesunic acid with a series of monoterpenes were synthesized and evaluated by cell viability assay on primary and metastatic melanoma cell lines. Almost all the obtained compounds showed micromolar antimelanoma activity and selectivity toward the metastatic form of this cancer. Four hybrid derivatives containing perillyl alcohol, citronellol, and nerol as monoterpene counterpart, emerged as the best compounds of the series, with nerol being active in combination with both sesquiterpenes, dihydroartemisinin and artesunic acid. Preliminary studies on the mechanism of action have shown the dependence of the pharmacological activity of newly synthesized hybrids on the formation of carbon- and oxygen-centered radical species. This study demonstrated the positive modulation of the pharmacodynamic effect of artemisinin semisynthetic derivatives dihydroartemisinin and artesunic acid due to the hybridization with monoterpene counterparts.

An undesirable sensory attribute (“floral taint”) has been recently detected in red wines in some winegrowing jurisdictions in North America (e.g. Ontario, British Columbia, Washington), caused by introduction of frost-killed leaves and petioles [materials-other-than-grapes (MOG)] during mechanical harvest and winemaking. It was hypothesized that terpenes, norisoprenoids, and higher alcohols would be the main responsible compounds. Objectives were to investigate causative volatile compounds for floral taint, and explore threshold concentrations for this problem. Commercial wines displaying varying intensities of floral taints were subjected to GC-MS and sensory analysis. Several odor-active compounds were higher in floral-tainted wines, including terpenes (geraniol, citronellol, cis- and trans-rose oxide), norisoprenoids (β-damascenone, β-ionone), five ethyl esters, and three alcohols. Thereafter, fermentations of Cabernet franc (CF) and Cabernet Sauvignon (CS) (2016, 2017) were conducted. MOG treatments were (wt/wt): 0, 0.5%, 1%, 2% and 5% petioles, and 0, 0.25%, 0.5%, 1%, and 2% leaf blades. Terpenes (linalool, geraniol, nerol, nerolidol, citronellol, citral, cis- and trans-rose oxides, eugenol, myrcene), norisoprenoids (α- and β-ionone), and others (e.g. hexanol, octanol, methyl and ethyl salicylate) increased linearly/quadratically with increasing MOG levels in both cultivars. Principal components analysis separated MOG treatments from the controls with 5% petioles and 2% leaves as extremes. Increasing MOG levels in CF wines increased floral aroma intensity, and were primarily associated with terpenes, higher alcohols, and salicylates. Increased leaf levels in CF were associated with higher vegetal and earthy attributes. Increased petioles in CS were not correlated with floral aromas, but increased leaves increased floral, vegetal and herbaceous attributes. Overall, petioles contributed more to floral taint than leaves through increased terpenes and salicylates (floral notes), while leaves contributed norisoprenoids and C6 alcohols (green notes).

Increasing evidence supports the direct healing effects of forests, partly attributed to the exposure to plant-emitted monoterpenes available in the forest atmosphere. The potential benefits on respiratory functions from inhaling monoterpenes have gained attention, especially due to the global rise in respiratory diseases. This study involved 42 asthmatic adolescents attending a summer rehabilitation camp at an Altitude Pediatric Asthma Center within a densely forested area in the Eastern Italian Alps. Volatile organic compound measurements indicated a pristine atmosphere, enabling modeling of continuous hourly monoterpenes concentration. Monoterpene concentration exposure and total inhaled dose were assessed over a 14-day stay, during which spirometry, lung oscillometry, and fractional exhaled nitric oxide were measured. Statistically significant correlations were observed between modifications in lung function parameters among asthmatic adolescents and monoterpenes exposure. These findings suggest a potential localized airway effect specific to monoterpenes. This pilot cohort study might pave the way for further investigations into the therapeutic effects of forest monoterpenes on lung function tests, asthma, and the broader healing potential of forest environments.

Immersive experiences in green areas and particularly in forests have long been known to produce beneficial effects for human health. However, the exact determinants and mechanisms leading to healthy outcomes remain to be elucidated. The purpose of this study was to investigate whether inhaling plant-emitted biogenic volatile compounds, namely monoterpenes (MTs), can produce specific effects on anxiety. Data from 505 subjects participating in 39 structured forest therapy sessions in different Italian sites, were collected. Monoterpenes air concentration was measured at each site. STAI State questionnaires were administered before and after the sessions as a measure of anxiety. A propensity score matching analysis was then performed, considering an above-average exposure to inhalable air MTs as the treatment: the estimated effect was -1.28 STAI-S points (95% C.I. -2.51 to -0.06, p = 0.04), indicating that the average effect of exposure to high MT air concentrations during forest therapy sessions is to decrease anxiety.

Several plant species produce mixtures of odorous and volatile compounds known as essential oils (EOs). These mixtures play important roles in nature and have been utilized by man for pharmaceutical and agrochemical purposes. There are more than 3000 EOs reported in the literature with approximately 300 having commercial use, including the oils from Eucalyptus species. Such oils are rich in monoterpenes and have found applications as pharmaceuticals, agrochemicals, food flavorants and in the perfume industry. Such applications are related to their diverse biological and organoleptic properties. In view of their importance, we review in this article up to date information concerning chemical composition and biological activities of essential oils from different species of Eucalyptus. Among the 900 species and subspecies of the Eucalyptus genus¸ we examined 68 species. The studies associated with these species were conducted in 27 countries. We have focused on the antimicrobial, acaricide, insecticide and herbicide activities, hoping that such information will contribute in the advances of the research in this field. It is also intended that the information herein described can be useful in the rationalization of the use of Eucalyptus EOs as components for new pharmaceutical and agrochemical applications as well as food preservatives and flavorants.

Heat stress affects the yield of medicinal plants and can reduce biomass and/or metabolite production. In order to evaluate the effect of heat-induced stress on the essential oil production in Mentha x piperita L. var. Mitcham (Mitcham mint) and Mentha x arvensis var. piperascens Malinv. ex L. H. Bailey (Japanese mint), we studied the chemical composition of the oils of the two mint species under different heat shock stress in growth chambers. The antibacterial activity of the essential oils was also evaluated; microscopic observation (fluorescence and electron transmission) was used to assess the effect of the tested samples on bacterial growth. The results obtained shed light on the mint essential oils composition and biological activity in relation to heat stress.

Forest healing effects are increasingly valued for their contribution to human psychological and physiological health, motivating further advances aimed at improving the knowledge of the relevant forest resources. Biogenic volatile organic compounds, emitted by the plants and accumulating in the forest atmosphere, are essential contributors to the forest healing effects, and represent the focus of this study. Using a photoionization detector, we investigated the high frequency variability, in time and space, of the concentration of total volatile organic compounds, on a hilly site, as well as along forest paths and long hiking trails on Italian northern Apennines. The scale of concentration variability was found to be comparable to absolute concentration levels, within time scales of less than one hour, and spatial scales of several hundred meters. During daylight hours, the concentration peaked from noon to early afternoon, followed by early morning, with lowest levels in late afternoon. Based on a conceptual model, these results were related to meteorological variables, including the atmospheric vertical stability profile. Moreover, preliminary evidence pointed to higher concentration of volatile organic compounds in forests dominated by conifer trees, in comparison with pure beech forests.