Cannabinoid (CB) and opioid systems are both involved in analgesia, food intake, mood and behavior. Due to the co-localization of µ-opioid (MOR) and CB1 receptors in various regions of the central nervous system (CNS) and their ability to form heterodimers, bivalent ligands targeting to both these systems may be good candidates to investigate the existence of possible cross-talking or synergistic effects, also at sub-effective doses. In this work, we selected from a small series of new Rimonabant analogs one CB1R reverse agonist to be conjugated to the opioid fragment Tyr-D-Ala-Gly-Phe-NH2. The bivalent compound (9) has been used for in vitro binding assays, for in vivo antinociception models and in vitro hypothalamic perfusion test, to evaluate the neurotransmitters release.

Irisin, the soluble secreted form of fibronectin type III domain containing 5 (FNDC5)-cleaved product, is a recently identified adipo-myokine that has been indicated as a possible link between physical exercise and energetic homeostasis. The co-localization of irisin with neuropeptide Y in hypothalamic sections of paraventricular nucleus, which receives NPY/AgRP projections from the arcuate nucleus, suggests a possible role of irisin in the central regulation of energy balance. In this context, in the present work we studied the effects of intra-hypothalamic irisin (1μl, 50-200nmol/l) administration on feeding and orexigenic [agouti-related peptide (AgRP), neuropeptide Y (NPY) and orexin-A] and anorexigenic [cocaine and amphetamine-regulated transcript (CART) and proopiomelanocortin (POMC)] peptides in male Sprague-Dawley rats. Furthermore, we evaluated the effects of irisin on hypothalamic dopamine (DA), norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) concentrations and plasma NE levels. Compared to vehicle, irisin injected rats showed decreased food intake, possibly mediated by stimulated CART and POMC and inhibited DA, NE and orexin-A, in the hypothalamus. We also found increased plasma NE levels, supporting a role for sympathetic nervous system stimulation in mediating increased oxygen consumption by irisin.

Members of the genus Lathyrus are used as food and as traditional medicines. In order to find new sources of biologically-active compounds, chemical and biological profiles of two Lathyrus species (L. czeczottianus and L. nissolia) were investigated. Chemical profiles were evaluated by HPLC-ESI-MSn, as well as by their total phenolic and flavonoid contents. In addition, antioxidant, enzyme inhibitory, and cytotoxic effects were also investigated. Antioxidant properties were tested by using different assays (DPPH, ABTS, CUPRAC, FRAP, phosphomolybdenum, and metal chelation). Cholinesterases (AChE and BChE), tyrosinase, α-amylase, and α-glucosidase were used to evaluate enzyme inhibitory effects. Moreover, vitexin (apigenin-8-C-glucoside) and 5-O-caffeoylquinic acid were further subjected to molecular docking experiments to provide insights about their interactions at molecular level with the tested enzymes. In vitro cytotoxic effects were examined against human embryonic kidney cells (HEK293) by using iCELLigence real time cell analysis system. Generally, L. czeczottianus exhibited stronger antioxidant properties than L. nissolia. However, L. nissolia had remarkable enzyme inhibitory effects against cholinesterase, amylase and glucosidase. HPLC-ESI-MSn analysis revealed that flavonoids were major components in these extracts. On the basis of these results, Lathyrus extracts were rich in biologically active components; thus, these species could be utilized to design new phytopharmaceutical and nutraceutical formulations.

The endocannabinoid system represents an integrated neuronal network involved in the control of several organisms' functions, such as feeding behavior. A series of hybrids of 5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (mimonabant), a well-known inverse agonist of the type-1 cannabinoid receptor (CB1), once used as an antiobesity drug, and the N-(2S)-substitutes of 1-[(4-fluorophenyl)methyl]indazole-3-carboxamide with 1-amino-3-methyl-1-oxobutane (AB-Fubinaca), 1-amino-3,3-dimethyl-1-oxobutane (ADB-Fubinaca), and 3-methylbutanoate (AMB-Fubinaca), endowed with potent agonistic activity towards cannabinoid receptors CB1 and CB2 were in solution as C-terminal amides, acids, methyl esters and N-methyl amides. These compounds have been studied by binding assays to cannabinoid receptors and by functional receptor assays, using rat brain membranes in vitro. The most active among them as an agonist, (S)-1-(2,4-dichlorobenzyl)-N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-1H-indazole-3-carboxamide (LONI11), and an antagonist, (S)-2-(1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxamido)-3-methylbutanoic acid (LONI4), were tested in vivo in mic, to evaluate their ability to stimulate or suppress feeding behavior after intraperitoneal (i.p.) administration. For a LONI11 formalin test and a tail flick test after an administration by the subcutaneous (s.c.) and intracerebroventricular (i.c.v.) routes, respectively, were also carried out in vivo in mice to investigate the antinociceptive property at the central and peripheral levesl. We observed a significant orexant effect for LONI11 and an intense anorexant effect for (S)-methyl 2-(1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate (LONI2) and LONI4. In zymosan-induced edema and hyperalgesia, LONI11 reduced the percent of paw volume increase and paw latency after s.c. administration, also suggesting a possible peripheral anti-inflammatory activity.

Cataract is the leading reason of blindness worldwide and is defined by the presence of any lens opacities or loss of transparency. The most common symptoms of cataract are impaired vision, decreased contrast sensitivity, color disturbance, and glare. Oxidative stress is among the main mechanisms involved in the development of age-related cataract. Surgery through phacoemulsification and intraocular lens implantation is the most effective method for cataract treatment, however, there are chances of serious complications and irreversible loss of vision associated with the surgery. Natural compounds consisting of antioxidant or anti-inflammatory secondary metabolites can serve as potential leads for anticataract agents. In this review, we tried to document medicinal plants and plant-based natural products used for cataract treatment worldwide, which are gathered from available ethnopharmacological/ethnobotanical data. We have extensively explored a number of recognized databases like Scifinder, PubMed, Science Direct, Google Scholar, and Scopus by using keywords and phrases such as "cataract", "blindness", "traditional medicine", "ethnopharmacology", "ethnobotany", "herbs", "medicinal plants", or other relevant terms, and summarized the plants/phytoconstituents that are evaluated in different models of cataract and also tabulated 44 plants that are traditionally used in cataract in various folklore medical practices. Moreover, we also categorized the plants according to scientific studies carried out in different cataract models with their mechanisms of action.

Anogeissus leiocarpus (DC.) Guill. & Perr. (Combretaceae) has a long history of use by folk populations for the management of multiple human ailments. Based on the published literature, there has been no attempt to conduct a comparative assessment of the biological activity and the phytochemical profiles of the leaves and stem bark of A. leiocarpus extracted using methanol, ethyl acetate, and water. By high-performance liquid chromatography with electrospray ionization mass spectrometric detection (HPLC-ESI-MSn) analysis, quinic, shikimic, gallic, and protocatechuic acids were tentatively identified from all the extracts, while chlorogenic, caffeic, ferulic, and dodecanedioic acids were only characterised from the leaves extracts. Additionally, a pharmacological study was carried out to evaluate potential protective effects that are induced by the extracts in rat colon and colon cancer HCT116 cell line. In general, the methanol and water extracts of A. leiocarpus leaves and stem bark showed potent radical scavenging and reducing properties. It was noted that the stem bark extracts were more potent antioxidants as compared to the leaves extracts. The methanol extract of A. leiocarpus leaves showed the highest acetyl (4.68 mg galantamine equivalent/g) and butyryl (4.0 mg galantamine equivalent/g) cholinesterase inhibition. Among ethyl acetate extracts, the pharmacological investigation suggested stem bark ethyl acetate extracts to be the most promising. This extract revealed ability to protect rat colon from lipopolysaccharide-induced oxidative stress, without exerting promoting effects on HCT116 cell line viability and migration. As a conclusion, A. leiocarpus represents a potential source of bioactive compounds in the development of novel therapeutic agents.

The aim of the present work is to develop nanoemulsions (NEs), nanosized emulsions, manufactured for improving the delivery of active pharmaceutical ingredients. In particular, nanoemulsions composed of Neem seed oil, contain rich bioactive components, and Tween 20 as nonionic surfactant were prepared. A mean droplet size ranging from 10 to 100 nm was obtained by modulating the oil/surfactant ratio. Physicochemical characterisation was carried out evaluating size, ζ-potential, microviscosity, polarity and turbidity of the external shell and morphology, along with stability in simulated cerebrospinal fluid (CSF), activity of Neem oil alone and in NEs, HEp-2 cell interaction and cytotoxicity studies. This study confirms the formation of NEs by Tween 20 and Neem oil at different weight ratios with small and homogenous dimensions. The antioxidant activity of Neem oil alone and in NEs was comparable, whereas its cytotoxicity was strongly reduced when loaded in NEs after interaction with HEp-2 cells.

Caffeic acid (CA) and chlorogenic acid (CGA) are phenolic compounds claimed to be responsible for the metabolic effects of coffee and tea consumption. Along with their structural similarities, they share common mechanisms such as activation of the AMP-activated protein kinase (AMPK) signaling. The present study aimed to investigate the anti-obesity potential of CA and CGA as co-treatment in human adipocytes. The molecular interactions of CA and CGA with key adipogenic transcription factors were simulated through an in silico molecular docking approach. The expression levels of white and brown adipocyte markers, as well as genes related to lipid metabolism, were analyzed by real-time quantitative PCR and Western blot analyses. Mechanistically, the CA/CGA combination induced lipolysis, upregulated AMPK and browning gene expression and downregulated peroxisome proliferator-activated receptor γ (PPARγ) at both transcriptional and protein levels. The gene expression profiles of the CA/CGA-co-treated adipocytes strongly resembled brown-like signatures. Major pathways identified included the AMPK- and PPAR-related signaling pathways. Collectively, these findings indicated that CA/CGA co-stimulation exerted a browning-inducing potential superior to that of either compound used alone which merits implementation in obesity management. Further, the obtained data provide additional insights on how CA and CGA modify adipocyte function, differentiation and lipid metabolism.

The compositions of volatile components in the aerial parts of six Astragalus species, namely A. campylotrichus (Aca), A. chiwensis (Ach), A. lehmannianus (Ale), A. macronyx (Ama), A. mucidus (Amu) and A. sieversianus (Asi), were investigated using gas chromatograph-mass spectrometry (GC-MS) analysis. Ninety-seven metabolites were identified, accounting for 73.28, 87.03, 74.38, 87.93, 85.83, and 91.39% of Aca, Ach, Ale, Ama, Amu and Asi whole oils, respectively. Sylvestrene was the most predominant component in Asi, Amu and Ama, with highest concentration in Asi (64.64%). In addition, (E)-2-hexenal was present in a high percentage in both Ale and Ach (9.97 and 10.1%, respectively). GC-MS based metabolites were subjected to principal component analysis (PCA) and hierarchal cluster analysis (HCA) to explore the correlations between the six species. The PCA score plot displayed clear differentiation of all Astragalus species and a high correlation between the Amu and Ama species. The antioxidant activity was evaluated in vitro using various assays, phosphomolybdenum (PM), 2,2 diphenyl-1-picryl-hydrazyl-hydrate (DPPH), 2,2-azino bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), cupric reducing antioxidant capacity (CUPRAC), ferric reducing power (FRAP) and ferrous ion chelation (FIC) assays. In addition, the potential for the volatile samples to inhibit both acetyl/butyrylcholinesterases (AChE, BChE), α- amylase, α-glucosidase and tyrosinase was assessed. Most of the species showed considerable antioxidant potential in the performed assays. In the DPPH assay, Ama exhibited the maximum activity (24.12 ± 2.24 mg TE/g sample), and the volatiles from Amu exhibited the highest activity (91.54 mgTE/g oil) in the ABTS radical scavenging assay. The effect was more evident in both CUPRAC and FRAP assays, where both Ale and Ama showed the strongest activity in comparison with the other tested species (84.06, 80.28 mgTE/g oil for CUPRAC and 49.47, 49.02 mgTE/g oil for FRAP, respectively). Asi demonstrated the strongest AChE (4.55 mg GALAE/g oil) and BChE (3.61 mg GALAE/g oil) inhibitory effect. Furthermore, the best tyrosinase inhibitory potential was observed for Ale (138.42 mg KAE/g). Accordingly, Astragalus species can be utilized as promising natural sources for many medicinally important components that could be tested as drug candidates for treating illnesses such as Alzheimer's disease, diabetes mellitus and oxidative stress-related diseases.

Like other members of the Colchicum genus, C. szovitsii subsp. szovitsii is also of medicinal importance in Turkish traditional medicine. However, its biological properties have not been fully investigated. Herein, we focused on the evaluation of the in vitro antioxidant and enzyme inhibitory effects of flower, root and leaf extracts, obtained using different extraction methods. In addition, a comprehensive (poly)-phenolic and alkaloid profiling of the different extracts was undertaken. In this regard, ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) allowed us to putatively annotate 195 polyphenols and 87 alkaloids. The most abundant polyphenols were flavonoids (83 compounds), whilst colchicine and 2-demethylcolchicine were some of the most widespread alkaloids in each extract analyzed. However, our findings showed that C. szovitsii leaf extracts were a superior source of both total polyphenols and total alkaloids (being, on average 24.00 and 2.50 mg/g, respectively). Overall, methanolic leaf extracts showed the highest (p < 0.05) ferric reducing antioxidant power (FRAP) reducing power (on average 109.52 mgTE/g) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging (on average 90.98 mgTE/g). Interestingly, each C. szovitsii methanolic extract was more active than the water extracts when considering enzymatic inhibition such as against tyrosinase, glucosidase, and acetylcholinesterase (AChE). Strong correlations (p < 0.01) were also observed between polyphenols/alkaloids and the biological activities determined. Multivariate statistics based on supervised orthogonal projections to latent structures discriminant analysis (OPLS-DA) allowed for the detection of those compounds most affected by the different extraction methods. Therefore, this is the first detailed evidence showing that C. szovitsii subsp. szovitsii might provide beneficial effects against oxidative stress and the associated chronic diseases. Nevertheless, the detailed mechanisms of action need to be further investigated.

Industrial hemp (Cannabis sativa) is traditionally cultivated as a valuable source of fibers and nutrients. Multiple studies also demonstrated antimicrobial, anti-proliferative, phytotoxic and insecticide effects of the essential oil from hemp female inflorescences. On the other side, only a few studies explored the potential pharmacological application of polar extracts from inflorescences. In the present study, we investigated the water extract from inflorescences of industrial hemp Futura 75 variety, from phytochemical and pharmacological point of view. The water extract was assayed for phenolic compound content, radical scavenger/reducing, chelating and anti-tyrosinase effects. Through an ex vivo model of toxicity induced by lipopolysaccharide (LPS) on isolated rat colon and liver, we explored the extract effects on serotonin, dopamine and kynurenine pathways and the production of prostaglandin (PG)E2. Anti-proliferative effects were also evaluated against human colon cancer HCT116 cell line. Additionally, antimycotic effects were investigated against Trichophyton rubrum, Trichophyton interdigitale, Microsporum gypseum. Finally, in silico studies, including bioinformatics, network pharmacology and docking approaches were conducted in order to predict the putative targets underlying the observed pharmacological and microbiological effects. Futura 75 water extract was able to blunt LPS-induced reduction of serotonin and increase of dopamine and kynurenine turnover, in rat colon. Additionally, the reduction of PGE2 levels was observed in both colon and liver specimens, as well. The extract inhibited the HCT116 cell viability, the growth of T. rubrum and T. interdigitale and the activity of tyrosinase, in vitro, whereas in silico studies highlighting the inhibitions of cyclooxygenase-1 (induced by carvacrol), carbonic anhydrase IX (induced by chlorogenic acid and gallic acid) and lanosterol 14-α-demethylase (induced by rutin) further support the observed pharmacological and antimycotic effects. The present findings suggest female inflorescences from industrial hemp as high quality by-products, thus representing promising sources of nutraceuticals and cosmeceuticals against inflammatory and infectious diseases.

Pomegranate is receiving renewed commercial and scientific interest, therefore a deeper knowledge of the chemical composition of the fruits of less studied varieties is required. In this work, juices from arils and decoctions from mesocarp plus exocarp were prepared from fifteen varieties. Samples were submitted to High Performance Liquid Chromatography-Diode Array Detector-Mass Spectrometry, spectrophotometric and colorimetric CIEL*a*b* analyses. Antioxidant, antiradical and metal chelating properties, inhibitory activity against tyrosinase and α-amylase enzymes were also evaluated. All varieties presented the same main phenols; anthocyanins and ellagitannins were widely variable among varieties, with the richest anthocyanin content in the juices from the Wonderful and Soft Seed Maule varieties (approx. 660 mg/L) and the highest ellagitannin content in the peel of the Black variety (approx. 133 mg/g dry matter). A good correlation was shown between the colour hue and the delphinidin/cyanidin ratio in juices (R2 = 0.885). Total polysaccharide yield ranged from 3% to 12% of the peels' dry weight, with the highest content in the Black variety. Decoctions (24.44-118.50 mg KAE/g) showed better in vitro antioxidant properties and higher inhibitory capacity against tyrosinase than juices (not active-16.56 mg KAE/g); the inhibitory capacity against α-amylase was similar and quite potent for juices and decoctions. Knowledge about the chemical composition of different pomegranate varieties will allow for a more aware use of the different parts of the fruit.

In the present study, we investigated the water extract of Harpagophytum procumbens DC. ex Meisn. in an experimental model of inflammatory bowel diseases (IBDs). Additionally, a microbiological investigation was carried out to discriminate the efficacy against bacterial and fungal strains involved in IBDs. Finally, an untargeted proteomic analysis was conducted on more than one hundred colon proteins involved in tissue morphology and metabolism. The extract was effective in blunting the production of oxidative stress and inflammation, including serotonin, prostaglandins, cytokines, and transcription factors. Additionally, the extract inhibited the growth of Candida albicans and C. tropicalis. The extract was also able to exert a pro-homeostatic effect on the levels of a wide plethora of colon proteins, thus corroborating a protective effect. Conversely, the supraphysiological downregulation of cytoskeletal-related proteins involved in tissue morphology and antimicrobial barrier function suggests a warning in the use of food supplements containing H. procumbens extracts.

The genus Hypericum is one of the most popular genera in both traditional medicine and scientific platform. This study is designed to provide conceptual insights on the biological potential and chemical characterization of H. salsugineum, which is endemic to Turkey. The qualitative and quantitative phenolic content of the extracts was characterized by HPLC-ESI-MSn. Biological efficiency was investigated by enzyme inhibitory assays (cholinesterases, tyrosinase, amylase, and glucosidase) and anti-cancer efficacy tests (anti-proliferative activities with the iCELLigence technology, colony formation and wound healing scratch assays). Phenolic acids (3-O-caffeoylquinic, 5-O-caffeoylquinic, and 4-O-caffeoylquinic acids) were the predominant group in the studied extracts, although several flavonoids were also detected and quantified. The extracts exhibited good inhibitory effects on tyrosinase and glucosidase, while they had weak ability against cholinesterases and amylase. Computational studies were also performed to explain the interactions between the major phenolics and these enzymes. The extracts displayed significant anti-cancer effects on breast carcinoma cell lines. Our findings suggest that Hypericum salsugineum could be valued as a potential source of biologically-active compounds for designing novel products.

Even though Salvia genus is one of the most known and studied taxa of Lamiaceae family, the knowledge regarding the chemical composition and health-related benefits of some locally used Salvia species (mostly endemic) is still scarce. In this regard, the present work aims to evaluate the chemical profile and potential bioactivities of 70% (v/v) ethanolic extracts obtained from the less-studied S. transsylvanica and S. glutinosa in comparison with S. officinalis. HPLC-PDA analysis revealed the presence of rutin and catechin as the main compounds in the extracts of the three studied species (using the employed HPLC method), whereas the presence of naringenin was highlighted only in S. glutinosa extract. Chlorogenic acid, rutin and quercetin were identified and quantified for the first time in S. transsylvanica extracts. The in vitro antioxidant capacity of each extract was tested through complementary methods (phosphomolybdenum assay, DPPH, ABTS, CUPRAC and FRAP assays), and correlated with the presence of phenolics (especially flavonoids) in high amounts. The neuroprotective and antidiabetic abilities of S. officinalis (the most active as AChE, BChE and α-glucosidase inhibitor), S. glutinosa (the most active as α-amylase inhibitor) and S. transsylvanica were also studied. For each extract it was determined the antimicrobial, antifungal and cytotoxic effects using in vitro assays. The obtained results confirm the potential of S. transsylvanica and S. glutinosa as promising sources of bioactive compounds and as a starting point for further analyses.

Industrial hemp is a multiuse crop that has been widely cultivated to produce fibers and nutrients. The capability of the essential oil (EO) from inflorescences as antimicrobial agent has been reported. However, literature data are still lacking about the hemp EO antiprotozoal efficacy in vivo. The present study aims to unravel this concern through the evaluation of the efficacy of hemp EOs (2.5 mL/kg, intraperitoneally) of three different cultivars, namely Futura 75, Carmagnola selezionata and Eletta campana, in mice intraperitoneally infected with Leishmania tropica. A detailed description of EO composition and targets-components analysis is reported. Myrcene, α-pinene and E-caryophyllene were the main components of the EOs, as indicated by the gas-chromatographic analysis. However, a prominent position in the scenario of the theoretical interactions underlying the bio-pharmacological activity was also occupied by selina-3,7(11)-diene, which displayed affinities in the micromolar range (5.4-28.9) towards proliferator-activated receptor α, cannabinoid CB2 receptor and acetylcholinesterase. The content of this compound was higher in Futura 75 and Eletta campana, in accordance with their higher scavenging/reducing properties and efficacy against the tissue wound, induced by L. tropica. Overall, the present study recommends hemp female inflorescences, as sources of biomolecules with potential pharmacological applications, especially towards infective diseases.

Dorycnium pentaphyllum subsp. haussknechtii is an important medicinal plant in several countries, including Turkey. This study aimed to evaluate the cytotoxicity of a crude extract of D. pentaphyllum subsp. haussknechtii against different breast cell lines to determine invasion, adhesion, and lipid peroxidation. The cytotoxic effects on MCF-7 breast cancer and MCF-12A as the immortalized cell line were examined by the XTT assay. Invasion and adhesion studies were performed according to the manufacturer's kit procedure to IC50 values for 48 h. Lipid peroxidation was measured in the MCF-7 cell. A bioinformatics analysis was conducted to unravel the mechanism of action underlying antiproliferative effects, as well. According to XTT results, the tested extract showed a time- and a concentration-dependent cytotoxic effect. The most effective concentration was 100.5 µg/mL (48 h), which was selected for biological activities, such as apoptotic activity, invasion, adhesion, and lipid peroxidation assays. The extract caused tumoral cell death, and it did not have a cytotoxic effect on healthy human breast cells. Duplication times and measurement of CI analyses of cells were performed using the real-time cell analysis system xCELLigence. Finally, the bioinformatics analysis indicated the prominent role of quercetin as an extract component exerting a key role in the observed antiproliferative effects. This was supported by the micromolar/submicromolar affinity of quercetin towards proto-oncogene serine/threonine-protein kinase (PIM-1) and hematopoietic cell kinase (HCK), both involved in breast cancer. Altogether, our findings proposed that the extraction of the plant can be an effective strategy to isolate biomolecules with promising cytotoxic effects against breast cancer cells.

Industrial hemp is characterized by a huge amount of by-products, such as inflorescences, that may represent high-quality sources of biomolecules with pharmaceutical interest. In the present study, we have evaluated the phytochemical profile, including terpene and terpenophenolic compounds, of the essential oils (EOs) of Futura 75, Carmagnola selezionata and Eletta campana hemp varieties. The EOs were also tested for antifungal properties toward Trichophyton mentagrophytes, Trichophyton rubrum, Arthroderma crocatum, Arthroderma quadrifidum, Arthroderma gypseum, Arthroderma curreyi, and Arthroderma insingulare. In parallel, we investigated the inhibitory effects of the EOs against tyrosinase, and the production of prostaglandin E2 in isolated mouse skin exposed to hydrogen peroxide. In human H1299 lung adenocarcinoma cells, we also evaluated the influence of the EOs on the gene expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2), which are involved in SARS-CoV-2 entry in human host. E-caryophyllene and α-pinene were the prominent terpenes in the EOs, whereas the cannabidiolic acid was the terpenophenol present at higher concentration. The EOs inhibited the growth of all tested dermatophytes species. In isolated skin specimens, EOs prevented the hydrogen-peroxide-induced synthesis of prostaglandin E2, consistent with the intrinsic antityrosinase activity. Finally, in H1299 cells, all tested EOs reduced the gene expression of ACE-2 and TMPRSS2, as well. Therefore, the present findings highlight the rationale for the use of the present EOs against infectious diseases.

Piper spices represent an inexhaustible reservoir of bioactive compounds that may act as drug leads in natural product research. The aim of this study was to investigate a series of methanolic fruit extracts obtained from P. nigrum (black, green, white and red), P. longum and P. retrofractum in comparative phytochemical and multi-directional biological (antimicrobial, antioxidant, anti-enzymatic and anti-melanogenic) assays. The metabolite profiling revealed the presence of 17 piperamides, with a total content of 247.75-591.42 mg piperine equivalents/g. Among the 22 tested microorganism strains, Piper spices were significantly active (MIC < 0.1 mg/mL) against the anaerobes Actinomyces israelii and Fusobacterium nucleatum. The antioxidant and anti-enzymatic activities were evidenced in DPPH (10.64-82.44 mg TE/g) and ABTS (14.20-77.60 mg TE/g) radical scavenging, CUPRAC (39.94-140.52 mg TE/g), FRAP (16.05-77.00 mg TE/g), chelating (0-34.80 mg EDTAE/g), anti-acetylcholinesterase (0-2.27 mg GALAE/g), anti-butyrylcholinesterase (0.60-3.11 mg GALAE/g), anti-amylase (0.62-1.11 mmol ACAE/g) and anti-glucosidase (0-1.22 mmol ACAE/g) assays. Several Piper extracts (10 μg/mL) inhibited both melanin synthesis (to 32.05-60.65% of αMSH+ cells) and release (38.06-45.78% of αMSH+ cells) in αMSH-stimulated B16F10 cells, partly explained by their tyrosinase inhibitory properties. Our study uncovers differences between Piper spices and sheds light on their potential use as nutraceuticals or cosmeceuticals for the management of different diseases linked to bacterial infections, Alzheimer's dementia, type 2 diabetes mellitus or hyperpigmentation.

The genus Pleurotus (Fr.) P. Kumm (Pleurotaceae, Basidiomycota) comprises a cosmopolitan group of mushrooms highly appreciated for their nutritional value and health-promoting benefits. Despite there being many studies about the phytochemical composition of Pleurotus spp., there are very few reports dealing with the phytochemistry, antioxidant and antimicrobial activities of P. columbinus Quél. In this study, a mass spectrometry ultra-performance liquid chromatography mass spectrometry (UHPLC)-QTOF method, coupled with principal component analysis (PCA), was applied to the P. columbinus metabolome in order to investigate the influence of different agri-food residues as growth substrates for P. columbinus cultivation, on the bioactive chemical profile of fruiting bodies and evaluated their potential as antioxidants and antimicrobials. Additionally, a quantitative HPLC-DAD-MS analysis was conducted on phenolic and flavonoid compounds, that could explain, albeit partially, the observed biological effects of P. columbinus extracts. The qualitative metabolic profile identified 97 metabolites, whereas the quantitative HPLC-DAD-MS analysis confirmed the presence of phenolic and flavonoids, in the mushroom extracts, which also showed intrinsic scavenging/reducing and antimicrobial effects. The antibacterial effects were particularly evident against Escherichia coli, whereas Tricophyton and Aspergillus were the dermatophytes more sensitive to the mushroom extracts. The present study supports more in-depth investigations, aimed at evaluating the influence of growth substrate on P. columbinus antimicrobial and antioxidant properties. The extracts from P. columbinus revealed valuable sources of primary and secondary metabolites, thus suggesting potential applications in the formulation of food supplements with biological properties, above all in terms of antioxidant and antimicrobial properties.