Anti-inflammatory Activity of Absinthin and Derivatives in Human Bronchoepithelial Cells.

Bitter taste receptors (hTAS2R) are expressed ectopically in various tissues, raising the possibility of a pharmacological exploitation. This seems of particular relevance in airways, since hTAS2Rs are involved in the protection of the aerial tissues from infections and in bronchodilation. The bis-guaianolide absinthin (1), one of the most bitter compounds known, targets the hTAS2R46 bitter receptor. Absinthin (1), an unstable compound, readily turns into anabsinthin (2) with substantial retention of the bitter properties, and this compound was used as a starting material to explore the chemical space around the bis-guaianolide bitter pharmacophore. Capitalizing on the chemoselective opening of the allylic lactone ring, the esters 3 and 4, and the nor-azide 6 were prepared and assayed on human bronchoepithelial (BEAS-2B) cells expressing hTAS2R46. Anti-inflammatory activity was evaluated by measuring the expression of MUC5AC, iNOS, and cytokines, as well as the production of superoxide anion, qualifying the methyl ester 3 as the best candidate for additional studies.

Plasmodium stage-selective antimalarials from Lophira lanceolata stem bark.

Targeting the transmissible stages of the Plasmodium parasite that develop in the human and mosquito host is a crucial strategy for malaria control and elimination. Medicinal plants offer a prolific source for the discovery of new antimalarial compounds. The recent identification of the gametocytocidal activity of lophirone E, obtained from the African plant Lophira lanceolata (Ochnaceae), inspired the evaluation of the plant also against early sporogonic stages of the parasite development. The bioassay-guided phytochemical study led to the isolation of two known lanceolins and of a new glycosylated bichalcone, named glucolophirone C. Its stereostructure, including absolute configuration of the bichalcone moiety, was elucidated by means of NMR, HRMS, ECD and computational calculations. Lanceolin B proved to be a potent inhibitor of the development of Plasmodium early sporogonic stages indicating that the plant produces two different stage-specific antimalarial agents acting on transmissible stages in the human and mosquito host.

Non volatile constituents of the vermouth ingredient Artemisia vallesiaca.

The Alpine wormwood Artemisia vallesiaca All. was considered the most valuable ingredient of vermouth, a celebrated aromatized wine. A. vallesiaca has a very limited geographical distribution, and the booming market of vermouth decimated its natural population, resulting in the eventual replacement of this rare species with more common and less expensive wormwoods like A. absinthium L.. Over the past years, attempts to revive the original recipe(s) of vermouth have fostered the establishment of cultivations of A. vallesiaca in pre-montane settings. In order to assist these projects, the phytochemical profile of cultivated plants and of several native populations of A. vallesiaca from the Swiss Valais were comparatively evaluated, focusing on sesquiterpene lactones and on lipophilic flavonoids, the hallmark constituents of Artemisia species. Remarkably, no significant difference was detected between the samples, despite the different origins. The lipophilic flavonoids of A. vallesiaca were similar to those of related species used in the production of vermouth, but the presence of C-9 oxygenated 11ß-methyl germacranolides and eudesmanolides (herbolides) made its sesquiterpene lactone profile peculiar. In addition to known compounds, two novel germacranolides were also characterized (herbolides J and K), and the major sesquiterpene lactone from the plant, the bitter germacranolide herbolide D (4), was detected and quantified by 1H NMR in a bitter liqueur aromatized with A. vallesiaca. Taken together, these observations qualify herbolides as marker to identify A. vallesiaca in aromatized alcohol matrixes.

O-Methyl Phytocannabinoids: Semi-synthesis, Analysis in Cannabis Flowerheads, and Biological Activity.

A general protocol for the selective mono-O-methylation of resorcinyl phytocannabinoids was developed. The availability of semisynthetic monomethyl analogues of cannabigerol, cannabidiol, and cannabidivarin (1A: -3A: , respectively) made it possible to quantify these minor phytocannabinoids in about 40 different chemotypes of fiber hemp. No chemotype significantly accumulated mono-O-methyl cannabidiol (2B: ) or its lower homologue (3B: ), while at least three chemotypes containing consistent amounts (≥ 400 mg/kg) of O-methylcannabigerol (1B: ) were identified. O-Methylation of alkyl phytocannabinoids (1B: -3B: ) does not significantly change the activity on peroxisome proliferator-activated receptors in contrast to what was reported for phenethyl analogues.

Effects of Azadirachta indica seed kernel extracts on early erythrocytic schizogony of Plasmodium berghei and pro-inflammatory response in inbred mice.

BACKGROUND: Medicinal plant research may contribute to develop new pharmacological control tools for vector borne diseases, such as malaria. METHODS: The effects of methanol extracts (ME) obtained from seed kernel of ripe and unripe Azadirachta indica fruits were studied on erythrocytic proliferation of the rodent malaria parasite Plasmodium berghei strain ANKA and on mice pro-inflammatory response, as evaluated by measuring the matrix-metalloproteinase-9 (MMP-9) and tumour necrosis factor (TNF) plasma levels, in two mouse strains (C57BL/6 and BALB/c) which are considered as prototypical of Th1 and Th2 immune response, respectively. RESULTS: ME obtained from seed kernel of unripe Azadirachta indica fruits decreased by about 30% the proportion of erythrocytes infected with the malaria parasite in C57BL/6 mice in the 4 days suppressive test. In this treatment group, MMP-9 and TNF levels were notably higher than those measured in the same mouse strain treated with the anti-malarial drug artesunate, Azadirachta indica kernel extracts from ripe fruits or solvent. In BALB/c mice, treatment with kernel extracts did not influence parasitaemia. MMP-9 and TNF levels measured in this mouse strain were notably lower than those recorded in C57BL/6 mice and did not vary among treatment groups. CONCLUSIONS: The effects of the ME on the parasite-host interactions appeared to be mouse strain-dependent, but also related to the ripening stage of the neem fruits, as only the unripe fruit seed kernel extracts displayed appreciable bioactivity.

Detailed Phytochemical Characterization of Bergamot Polyphenolic Fraction (BPF) by UPLC-DAD-MS and LC-NMR.

Bergamot ( Citrus bergamia) is cultivated in Southern Italy almost exclusively to produce the prized essential oil, a top note in several perfumes. The juice of bergamot, until recently poorly studied, is the object of a growing scientific interest due to its claimed activity to treat metabolic syndrome. The aim of this investigation was a detailed characterization of bergamot juice polyphenolic fraction (BPF) based on a UPLC-DAD-MS analysis complemented by preparative chromatographic separations, followed by NMR characterization of the isolated compounds. The combination of these techniques efficiently covered different classes of secondary metabolites, leading to the identification of 39 components, several of which had never been reported from bergamot. One of them, bergamjuicin (35), is a new flavanone glycoside, whose structure has been determined by MS and NMR techniques. The reported results could provide a guide for future routine analyses of BPF, a material of great nutraceutical and industrial interest.

An Artemisia-derived natural product-based fluorescent probe for the bitter taste receptor hTAS2R38.

The discovery of taste receptors hTAS2Rs expression in extra oral tissue, especially in the gastrointestinal tract and in the respiratory system, has endowed bitter receptors of functionalities that exceed the simple perception of taste and flavour. In particular, stimulation of hTAS2Rs by bitter agents in the airway smooth muscle triggers bronchodilation of possible pharmacological relevance. To study the receptor localization in pulmonary smooth muscle cells and to investigate their biological response to hTAS2R38 activation, we have developed a fluorescent probe for hTAS2R38 starting from the sesquiterpene lactone costunolide, available in multigram amounts from Artemisia umbelliformis Lam. The N-methylanthranilate-containing probe demonstrated a very low cytotoxicity compared to the natural product toward human airway smooth muscle cells and epithelial bronchial cells, but fully retained its binding to hTAS2R38, making it possible the fluorescent detection of cells expressing this bitter receptor.

NMR-based identification of the major bioactive molecules from an Italian cultivar of Lycium barbarum.

Lycium barbarum (Solanaceae), long known to the traditional Chinese medicine because of its many health-promoting effects, has of late spread widely across the Western hemisphere, mainly on account of the nutritional richness in vitamins, minerals and antioxidant metabolites of its fruits. Data on bioactive metabolites from fruits and leaves, which are commonly consumed in soups and salads, are scarce and sometimes even contradictory. By means of NMR, the present study identified the specialised products contained in an Italian cultivar of L. barbarum. Kaempeferol, caffeic acid, 3,4,5-trihydroxycinnamic acid and 5-hydroxyferulic acid were found in fresh fruits; rutin and chlorogenic acid were detected in leaves and flowers; also, a previously undescribed N,N-dicaffeoylspermidine derivative was identified in flowers, while N-feruloyltyramine derivatives, for which interesting anti-inflammatory properties have been reported, turned out to be the major bioactive molecules in stems. The plethora of the detected bioactive molecules amplifies the nutraceutical value of berries and leaves and prompts the exploitation of L. barbarum flowers and pruned stems as sources of beneficial compounds.