Maria Rosaria Perri

Background/Objectives: Essential Oils (EO), complex mixtures of organic compounds, exhibit a wide range of properties useful in the pharmaceutical, cosmetic, perfumery and agri-food fields. In particular, well-recognized EO anti-inflammatory properties push towards the investigation of the mechanisms underlying them. One of the signaling pathways targeted by EOs is the Janus Kinase Signal of Transducer and Activator of Transcription (JAK/STAT), whose hyperactivation is associated with inflammation, immune diseases and tumor progression. Methods: A comprehensive search on the major bibliographic databases was conducted; current findings and recent insights about the role of EOs in modulating the JAK/STAT Signaling Pathway were collected. Results: EOs derived from different plant species showed efficacy in attenuating the release of pro-inflammatory cytokines and mediators and in inhibiting phosphorylation of both JAK and STAT proteins. These results could be due to the EO’s multi-component nature and to the synergistic interaction occurring within these complex mixtures, both reflecting multi-target effects and modulations. Limitations concerning formulations, lack of standardization, efficacy and safety profiles, sustainable and eco-friendly approaches, and the gap between the literature and translation to the clinic were addressed. Conclusions: EOs represent emergent, promising and high-value candidates able to modulate the JAK/STAT Signaling Pathway.

Background/Objectives: Among the Inflammatory Skin Diseases (ISDs), psoriasis represents a recalcitrant and disabling dermatological disorder associated with perpetuated inflammatory conditions. Recent findings showed that psoriasis pathogenesis is sustained by the interplay of different inflammatory Signaling Pathways, among which the JAK/STAT stands out. Methods: This review aims to investigate the state of the art and the most recent insights concerning the efficacy of plant extracts in psoriasis management via modulation of the JAK/STAT Signaling Pathway. Results: In vitro and in vivo studies revealed that several different plant species showed promising results in modulating the dysregulation of the JAK/STAT Signaling Pathway associated with psoriasis. Raw and enriched extracts and herbal remedy formulations were discussed. Then, present insights, future directions, and gaps of literature were addressed. Conclusions: Promising studies suggested that plant-based products, able to downregulate the JAK/STAT Signaling Pathway, could represent an effective tool for psoriasis management.

Urtica dioica L. and Parietaria judaica L. subsp. judaica are two members of the Urticaceae family well-known for their sensitization and allergenic potential. Nevertheless, both species were used in traditional medicine, and various pharmacological properties have been described so far. Here, the dried aerial parts from Southern Italy were extracted through maceration, and a preliminary comparative study focused on the in vitro antioxidant and anti-denaturation properties, as well as on the pancreatic lipase inhibitory effects, was carried out. The most apolar constituents were extracted by means of liquid–liquid extraction, and the phytochemical profile of the two species was verified with gas chromatography–mass spectrometry (GC–MS) analyses and compared using principal component analysis (PCA). The correlation between detected phytochemicals and observed biological properties was also verified. A positive correlation was observed between lipase inhibition and the compounds mainly abundant in the U. dioica dichloromethane fraction, which showed the best activity (IC₅₀ = 1.67 ± 0.01 mg/mL). The two P. judaica fractions instead showed the best anti-denaturation effects (IC₅₀ = 321.6 ± 3.3 and 424.4 ± 1.8 μg/mL). Further studies are needed to optimize the solvent partitioning method and to deeply study the interesting biological properties of investigated species.

Glycyrrhiza glabra L. (Fabaceae) is a plant species with already demonstrated countless biological properties and many more still to be discovered. Here, root sample extracts from different geographical areas were compared based on their phytochemical profiles and biological activities. Both raw and hydrolysate extracts, as well as 18β-glycyrrhetinic acid, glycyrrhizin, and isoliquiritigenin, considered as the main licorice secondary metabolites, were screened for antiproliferative and anti-migration properties in MCF-7, MDA-MB-231, A2780, HeLa, SiHa, and C33A breast and gynecological cancer cell lines. Hydrolysate extracts showed higher cytotoxicity than the raw extracts at the same final concentrations, 30 and 60 µg/mL, respectively. Among the standards, isoliquiritigenin showed the most pronounced cytotoxic activity, with inhibitory percentages exceeding 70% in each of the investigated cell lines at the lowest tested dose of 30 µg/mL. Then, the most effective extracts in the MTT assay, LIT2-H and LMO-H, were screened in a wound-healing test, demonstrating efficacy against ovarian (A2780) and cervical (C33A) cancer cell lines after 24 and 48 h of exposure.

Stilbenoids, a group of phytoalexin polyphenols produced by plants as a defence mechanism in response to stress conditions, are known for their anti-inflammatory potential. Pinosylvin, a naturally occurring molecule traditionally found in pinus trees, was here identified in Pinus nigra subsp. laricio var. calabrica from Southern Italy through HPLC analysis. Both this molecule and its well-known analogue resveratrol, the most famous wine polyphenol, were compared for their in vitro potential anti-inflammatory activity. Pinosylvin significantly inhibited the release of pro-inflammatory cytokines (TNF-α and IL-6) and NO mediator in LPS-stimulated RAW 264.7 cells. Moreover, its ability to inhibit the JAK/STAT signaling pathway was assessed: Western blot analyses showed a downregulation of both phosphorylated JAK2 and STAT3 proteins. Finally, in order to verify whether this biological activity could be attributed to a direct interaction of pinosylvin with JAK2, a molecular docking study was performed, confirming the capability of pinosylvin to bind the active site of the protein.

Interesting photobiological properties have been demonstrated for some Cachrys species, including C. libanotis L., C. sicula L., and C. pungens Jan. The present study was designed to assess the photocytotoxic activity of Prangos ferulacea Lindl. (synonym of C. ferulacea (L.) Calest.). This plant was previously considered a Cachrys species but, at present, it is part of the Prangos genus. P. ferulacea is an orophilous plant present in the eastern Mediterranean and in western Asia. Three different extraction techniques were utilized. Obtained extracts were compared both for their phytochemical content and for their photobiological properties on human melanoma cells irradiated with UVA light. The apoptotic responses, together with the antioxidant activity, were also assessed. P. ferulacea extracts were able to affect cell viability in a concentration-dependent manner, with the sample obtained through supercritical CO₂ extraction showing the highest activity (IC₅₀ = 4.91 μg/mL). This research points out the interesting content in the photoactive compounds of this species, namely furanocoumarins, and could provide a starting point for further studies aimed at finding new photosensitizing agents useful in cancer photochemotherapy.

The Cachrys L. genus belongs to the Apiaceae family and it is widely distributed in the Mediterranean basin, with plant species being endemic to southern Europe, Asia, and northern Africa. Different studies, focused on the phytochemical composition of Cachrys spp. and the biological properties of their phytocomplexes, have been reported. These works mostly focused on the essential oils obtained from these plants, and pointed out that Cachrys species are a rich source of coumarins, mainly furanocoumarins. Other phytochemicals, such as terpenes, fatty acids, phytosterols, and flavonoids have been also identified. Moreover, a number of biological properties such as antioxidant, antimicrobial, anti-inflammatory, cytotoxic, and photocytotoxic effects have been assessed. Nevertheless, a review of the chemical and pharmacological properties of this genus is not available in the literature. The aim of this paper is to provide an overview of the reports concerning the identified phytochemicals and the biological effects reported for Cachrys spp., and to offer a comprehensive understanding of the potential of this genus as a source of bioactive compounds. The current taxonomy, the traditional uses, and the toxicological aspects of plants belonging to this genus are also reported, and the future research directions are discussed.

Ornamental plants often gain relevance not only for their decorative use, but also as a source of phytochemicals with interesting healing properties. Herein, spontaneous Centranthus ruber (L.) DC. and Tropaeolum majus L., mainly used as ornamental species but also traditionally consumed and used in popular medicine, were investigated. The aerial parts were extracted with methanol trough maceration, and resultant crude extracts were partitioned using solvents with increasing polarity. As previous studies mostly dealt with the phenolic content of these species, the phytochemical investigation mainly focused on nonpolar constituents, detected with GC-MS. The total phenolic and flavonoid content was also verified, and HPTLC analyses were performed. In order to explore the potential antiarthritic and anti-obesity properties, extracts and their fractions were evaluated for their anti-denaturation effects, with the use of the BSA assay, and for their ability to inhibit pancreatic lipase. The antioxidant properties and the inhibitory activity on the NO production were verified, as well. Almost all the extracts and fractions demonstrated good inhibitory effects on NO production. The n-hexane and dichloromethane fractions from T. majus, as well as the n-hexane fraction from C. ruber, were effective in protecting the protein from heat-induced denaturation (IC₅₀ = 154.0 ± 1.9, 270.8 ± 2.3 and 450.1 ± 15.5 μg/mL, respectively). The dichloromethane fractions from both raw extracts were also effective in inhibiting pancreatic lipase, with IC₅₀ values equal to 2.23 ± 0.02 mg/mL (for C. ruber sample), and 2.05 ± 0.02 mg/mL (T. majus). Obtained results support the traditional use of these species for their beneficial health properties and suggest that investigated plant species could be potential sources of novel antiarthritic and anti-obesity agents.

Different phytochemical compounds have been demonstrated to modulate the JAK/STAT signaling pathway. Here, three Cachrys species from Southern Italy were investigated for both the phytochemical profile and the potential anti-inflammatory properties. The aerial parts were extracted with methanol through Naviglio Extractor^®, an innovative solid-liquid extraction technique that allows to obtain high quality extracts by working with gradient pressure. Extracts were analyzed with GC-MS and standardized in furanocoumarin content, resulting rich in xanthotoxin, bergapten and isopimpinellin. Given the known ability of bergapten to inhibit the JAK/STAT signaling pathway by decreasing the levels of pro-inflammatory cytokines (TNF-α, IL-6) and inflammatory mediators (NO) in RAW 264.7 cells activated by LPS, Cachrys extracts were investigated for their biological properties. The results obtained in this study showed that Cachrys pungens extract, presenting the highest content in furanocoumarins (7.48 ± 0.48 and 2.94 ± 0.16 mg/50 mg of extract for xanthotoxin and bergapten, respectively), significantly decreased STAT3 protein levels, pro-inflammatory cytokines (TNF-α, IL-6) and increased IL-10 anti-inflammatory cytokine. Cachrys ferulacea significantly decreased JAK2 phosphorylation, being even more effective than bergapten. In conclusion, investigated extracts could be potential candidates for the search of novel anti-inflammatory agents acting via inhibiting the JAK/STAT signaling pathway.