Plant-derived products, particularly essential oils, represent a promising source of antiviral scaffolds. Although Populus balsamifera L. has been traditionally used to manage respiratory ailments and infections, the antiviral potential of its bud essential oil remains unexplored. In this study, we evaluated the in vitro antiviral cytoprotective activity of P. balsamifera bud essential oil and its major constituents against HCoV-OC43, a human betacoronavirus associated with seasonal respiratory infections, using a cell-based cytoprotection assay. The assay reliably detected the activity of reference antivirals, including chloroquine (EC50 = 0.11 ± 0.01 µg/mL), molnupiravir, and fluvoxamine, supporting its suitability for antiviral screening. Under these conditions, P. balsamifera bud essential oil exhibited strong cytoprotective activity, with an EC50 of 3.3 ± 0.5 µg/mL. Chemical analysis revealed a sesquiterpene-rich composition. Two major constituents, α-bisabolol and nerolidol, also showed marked cytoprotection, with EC50 values of 2.7 ± 0.3 µg/mL and 2.6 ± 0.4 µg/mL, respectively, supporting their contribution to the overall activity of the oil. To our knowledge, this study provides the first experimental evidence of antiviral cytoprotective activity of P. balsamifera bud essential oil against a human coronavirus and identifies α-bisabolol and nerolidol as active compounds in this model.

No induced herbivory effect under defoliation by Eastern spruce budworm (Choristoneura fumiferana Clemens) was detected in young conifer saplings, but a marked difference among species—balsam fir (Abies balsamea (L.) Mill.), white spruce (Picea glauca [Moench] Voss), and black spruce (Picea mariana [Mill.])—in monoterpene compositions. Terpenoids are among the most common defensive compounds in conifers, found in foliage, wood, and bark. Induction of terpenoids by chewing folivorous insects is less understood than stem-feeding xylophagous insects. This study examined whether three conifers —balsam fir (Abies balsamea (L.) Mill.), white spruce (Picea glauca [Moench] Voss), and black spruce (Picea mariana [Mill.])— induce terpenoid variation in response to Eastern spruce budworm (Choristoneura fumiferana Clemens) defoliation. A total of 360 4-years-old saplings from three coniferous species were grown in a greenhouse for a 2-years-long experiment, with half exposed to defoliation and half as controls. Buds and larvae phenology were monitored, and foliage was collected throughout the growing season. Terpenoid compounds from needles were analysed using static headspace gas chromatography (HS-GC). Statistical analyses were performed on the 14 most common compounds that were found. A total of 43 terpenoids were identified, of which 67

A visible-light-mediated chlorotrifluoromethylation catalyzed by a copper-based photo-redox catalyst of internal alkenes is reported. The reaction proceeds with complete regioselectivity under mild reaction conditions using commercially available F3CSO2Cl as both the trifluoromethyl and chlorine source, leading to the synthesis of added-value chemicals with atom-economy. A vast array of internal alkenes were functionalized in decent to good yields, highlighting a great tolerance to various functional groups. A radical process starting from a single electron reduction of F3CSO2Cl with an excited copper catalyst was evidenced, and the synthetic utility of our products was showcased by the synthesis of valuable molecules such as α-trifluoromethylated amides, α-trifluoromethylated-β-aminoamides, and trifluoromethyl alkenes. In addition, the library was evaluated in vitro for its cytotoxicity against lung carcinoma (A549) and colorectal adenocarcinoma (DLD-1) cell lines, and for its antifungal and antibacterial activities against C. albicans, E. coli and S. aureus strains, respectively. Compounds 2a, 2m, 2n, and 2o demonstrated anticancer activities, while compounds 2a, 6g, and 6h exhibited weak antibacterial activities, underscoring the therapeutic potential of this class of molecules and suggesting opportunities for further optimization.

The search for safer and more effective vaccine adjuvants has intensified in recent years, with triterpenoid saponins like QS-21 and its analogues emerging as promising candidates. We report the synthesis of a novel QS-21 analogue featuring betulinic acid as aglycone, a lupane-type triterpenoid with low toxicity derived from white birch bark. Two convergent synthetic routes, involving different protecting groups and glycosyl donors (bromide and trichloroacetimidate), were optimized to construct the QS-21-based linear trisaccharide motif critical for adjuvant activity. This strategy also enabled efficient preparation of the structurally similar echinocystic acid analogue reported by Gin. The immunological and toxicological profiles of these chimeric saponins, along with Lewis-X-containing and rhamnose-modified derivatives, were evaluated in C57BL/6 wild-type and hDC-SIGN transgenic mice. While the synthetic saponins exhibited low toxicity in vitro and in vivo, replacing echinocystic acid with betulinic acid reduced immunogenicity when tested with ovalbumin as a model antigen compared to alhydrogel and QS-21. These findings provide a foundation for developing saponin-based adjuvants and demonstrate the utility of advanced glycosylation strategies for synthesizing complex unnatural triterpenoid saponins.

Greenhouse gas (GHG) emissions from wild lowbush blueberry (WLB) production after fertilization with conventional mineral (MIN) and organic (ORG) or industrial pulp and paper mill sludge (PPMS) and synthetic anhydrite (SA; calcic amendment; CaSO4) remain unknown. We assessed nitrous oxide (N2O) and methane (CH4) emissions following application of combined PPMS and SA under WLB production compared to MIN and ORG fertilizers during a two-year cropping cycle. A 50 kg nitrogen (N) ha-1 recommended input was broadcasted before stem emergence during the pruning phase with MIN, ORG, and PPMS treatments alongside an unfertilized control (0 N; CTL). The PPMS treatment was also combined with SA as 6 Mg ha-1 (1SA) and 12 Mg ha-1 (2SA) inputs, which were also applied alone for a total of eight treatments. The GHG emissions were monitored using non-flow-through, non-steady-state chambers during two growing seasons. The N2O and CH4 emissions were unaffected by fertilizer applications. The N2O emissions were significantly higher during the pruning phase (0.06 f 0.009 kg N2O-N ha-1 yr-1) than during the harvesting phase (0.03 f 0.005 kg N2O-N ha-1 yr-1). The fertilizer-induced emission factor (FIEF) values (-0.01 f 0.02 %) were much lower than the default 1 % used for GHG inventories. A CH4 uptake was observed during both growing seasons, with higher uptake during the pruning phase (-2.1 f 0.1 kg CH4-C ha-1 yr-1) than in the harvesting phase (-1.6 f 0.1 kg CH4-C ha-1 yr-1). High aeration of sandy soils combined with low soil NO3 contents (0.9 mu g NO3-N cm-2 yr-1 during the pruning phase) might constrain N2O emissions. Proposed WLB-specific FIEF should be used in future GHG inventories to prevent emission overestimates. Further research is needed on the agronomic benefits and yield effects of combining PPMS and SA for WLB productivity.

Plaque psoriasis is a chronic inflammatory skin disorder characterized by excessive T lymphocyte infiltration and keratinocyte hyperproliferation, resulting in epidermal thickening. Current treatments often require lifelong administration and carry risks of systemic toxicity, limiting patient adherence. Microneedle patches represent a promising alternative, offering localized, minimally invasive, and controlled drug delivery. This study evaluates the therapeutic potential of a sustained-release microneedle patch delivering phloretin or methotrexate using a tissue-engineered human psoriatic skin model. The model was developed using keratinocytes and fibroblasts isolated from lesional skin of patients with psoriasis, preserving the disease's genetic profile. Human T lymphocytes were incorporated to replicate the inflammatory microenvironment. This study demonstrates a significant reduction in epidermal thickness while no changes were observed in healthy skin substitutes, confirming specificity for hyperproliferative tissue. The therapeutic effect was comparable to systemic methotrexate. To assess molecular diffusion, Cy5-COOH was used as a fluorescent tracer, revealing sustained dermal and longitudinal diffusion for up to 2 weeks. These results suggest that a single application could provide extended therapeutic benefit for at least 2 weeks. This is the first study to demonstrate the efficacy of microneedle patch treatment in a human psoriatic skin model, supporting their potential as a targeted, long-acting therapy for psoriasis.

Several species belonging to the Pinaceae family have historically been employed in traditional folk remedies for managing various health conditions such as colds, stomach discomfort, digestive issues, and ailments affecting the vascular, respiratory, and reproductive systems. These plants are recognized for exhibiting a wide range of biological activities, including insect juvenile hormone-like effects, along with antitumor, antibacterial, antifungal, anti-ulcer, anti-inflammatory, antihypertensive, antitussive, and central nervous system-related properties. This study aimed to evaluate the chemical composition and biological activities of Abies nordmanniana (Stev.) Spach needles collected from Georgia's Kartli floristic region in 2024. Gas chromatography-mass spectrometry (GC-MS) analysis revealed the presence of over 100 compounds in the essential oil (EO) extracted from the needles, with pinenes identified as the major constituents. The EO demonstrated potent anti-inflammatory activity (IC50 = 0.113 +/- 0.008 v/v; NO inhibition: 100%) and marked antioxidant capacity, as indicated by both the ORAC assay (7 +/- 2 mu mol TE/mL) and in vitro testing on WS-1 cells (>0.125 v/v), while exhibiting minimal cytotoxicity toward both normal and cancerous cells. Antibacterial efficacy was relatively weak, with IC90 values of 169 +/- 4 mu g/mL for Escherichia coli and 163 +/- 36 mu g/mL for Staphylococcus aureus. No antifungal effect was observed against Candida albicans, with IC90 exceeding 200 mu g/mL.

We present the isolation and structural characterization of a novel nonionic dirhamnolipid methyl ester produced by the bacterium Burkholderia lata. The structure and the absolute configuration of the isolated dirhamnolipid bearing a symmetrical C14-C14 methyl ester chain were thoroughly investigated through chemical degradation and spectroscopic methods including 1D and 2D NMR analysis, HR-ESI-TOF-MS, chiral GC-MS, and polarimetry. Our work represents the first mention in the literature of a rhamnolipid methyl ester from Burkholderia species.

Plaque psoriasis is a chronic inflammatory skin disease causing red inflamed lesions covered by scales. Leukocytes, including dendritic cells and T cells, participate in the inflammation of the skin by producing multiple cytokines, thus contributing to the hyperproliferation of keratinocytes. Lack of effectiveness and toxic side effects are the main concerns with conventional treatments, and research involving new antipsoriatic molecules is essential. In this study, the anti-inflammatory and antiproliferative effects of two natural polyphenols, phloretin and balsacone C, were investigated using the coculture of T cells and psoriatic keratinocytes. Phloretin exerted antiproliferative activity by regulating the expression of antigen Ki67 and proliferating cell nuclear antigen (PCNA). These effects were comparable to those of methotrexate, a reference treatment for moderate to severe psoriasis. With balsacone C, the expression of Ki67 was also reduced. Additionally, phloretin decreased the levels of multiple pro-inflammatory cytokines: monocyte chemoattractant protein-1 (MCP-1/CCL2), macrophage inflammatory protein-1α (MIP-1α), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 alpha (IL-1α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-17A (IL-17A), and tumor necrosis factor alpha (TNF-α). The increased interleukin-2 (IL-2) levels with phloretin and methotrexate also represented anti-inflammatory activity. Balsacone C and methotrexate decreased the levels of IL-1α and IL-1β, but methotrexate exerted a higher reduction. In summary, the anti-inflammatory effects of phloretin were more pronounced than those of methotrexate and balsacone C. In addition, the expression of lymphocyte common antigen (CD45) was more similar to that of the healthy condition after using phloretin or methotrexate. Finally, phloretin stood out from the other compounds and appears promising for psoriasis treatment.

Ursolic acid and uvaol are naturally occurring triterpenoids that exhibit a broad spectrum of pharmacological activities, including cytotoxicity. However, a primary challenge in the development of ursane-type pentacyclic triterpenoids for pharmacological use is their poor aqueous solubility, which can impede their effectiveness as therapeutics agents. In this study, we present the facile synthesis of ursolic acid monodesmosides and uvaol bidesmosides, incorporating naturally occurring and water-soluble pentoses and deoxyhexose sugar moieties of opposite d- and l-configurations at the C3 or C3/C28 positions of the ursane core. The twenty synthetic saponins were evaluated in vitro for their cytotoxicity against lung carcinoma (A549) and colorectal adenocarcinoma (DLD-1) cell lines. Notably, all the bidesmosidic uvaol saponins were shown to be cytotoxic as compared to their non-cytotoxic parent triterpenoid. For each series of ursane-type saponins, the most active compounds were 3-O-α-l-arabinopyranosyl ursolic acid (3h) and 3,28-di-O-α-l-rhamnopyranosyl uvaol (4f), showing IC50 values in the low micromolar range against A549 and DLD-1 cancer lines.

Background: The genus Teucrium L. is frequently employed in traditional medicine, primarily for addressing disorders of the digestive and respiratory systems. Biological investigations focused on essential oils have substantiated their antibacterial, antioxidant, anti-tumor, anti-diabetic, and anti-rheumatic properties. Objective: The aim of the study was to assess the chemical composition and biological activities of the aerial parts of the endemic species Teucrium nuchense K. Koch. Methods: The chemical composition of the essential oil was analyzed using gas chromatography-mass spectrometry (GC-MS). The antioxidant activity was evaluated through the Oxygen Radical Absorbance Capacity (ORAC) assay and tested on normal skin fibroblasts (WS-1). Additionally, the antiinflammatory efficacy was assessed by monitoring nitric oxide production. The total phenolic content in the aqueous, methanolic, and chloroformic extracts was quantified using the Folin-Ciocalteu reagent. Individual compounds were isolated using preparative high-performance liquid chromatography. Their identification was accomplished using high-resolution mass spectrometry (HRMS) with an ESI-Q-TOF detector in conjunction with nuclear magnetic resonance (NMR) spectroscopy. Results: The essential oil yield was 0.32 ml/kg. Caryophyllene oxide, constituting 15.19 %, and 1- octen-3-ol, constituting 8.75%, emerged as the primary components in the essential oil. Oxygenated sesquiterpenes dominated the terpenic compounds, representing 25.1 % of the essential oil. The aqueous and methanolic extracts displayed a notable phenolic content, with percentages of 27 ± 2 % and 35 ± 0.1 %, respectively. Both the aqueous and methanolic extracts demonstrated robust antioxidant activity in the ORAC test and in vitro assessments using WS-1 cells. The methanolic extract, at a concentration of 160 μg/ml, inhibited NO formation by 90 %, without toxicity in RAW 264.7. Individual compounds, teucrioside from the phenylethanoid glycoside class, two neo-clerodane diterpenes, teucrin A, and 6-alpha-hydroxyteuscordine, were isolated. Conclusion: The essential oil extracted from the aerial parts of Teucrium nuchense is characterized by the presence of caryophyllene oxide and 1-octen-3-ol. The methanolic extract exhibits notable antioxidant as well as anti-inflammatory properties, whereas the aqueous extract demonstrates high antioxidant activity. Additionally, three compounds of teucrioside, teucrin A, and 6-α- hydroxyteuscordine have been isolated and characterized.

The current study aimed to evaluate Tunisian Tamarix africana Poir biological activities. In this study, novel biological activities of the shoot extracts related to their phenolics investigated. Secondary metabolite contents, antioxidant, anti-inflammatory and cytotoxic activities of four extracts (hexane, dichloromethane, methanol and water) were investigated. Antioxidant activities were assessed via in vitro and ex vivo assays. Besides, anticancer activity was investigated against human lung carcinoma (A-549) and colon adenocarcinoma (DLD-1) cells. The anti-inflammatory ability was evaluated via inhibition of LPS-induced NO production in RAW 264.7 macrophage cell lines. Methanol and water extracts displayed the highest antioxidant (IC50 = 3.3 and 4.3 mu g/mL respectively), which are correlated activities correlated with phenolic contents. Hexane extract exhibited an important anti-inflammatory effect inhibiting NO ability by 100% at 80 mu g/mL. Besides, T. africana extracts were found to be active against A-549 lung carcinoma cells with IC50 values ranging from 20 to 34 mu g/mL. These results suggested that T. africana is considered as a potential source of readily accessible natural molecules with a promising effect on human health and diseases.

Methotrexate is successfully used as the gold standard for managing moderate-to-severe psoriasis. However, the low bioavailability and short half-life of the oral pills and the invasiveness of the parenteral injections make these suboptimal therapeutic options. Microneedles, bridging the advantages of the former forms, are successfully used to deliver methotrexate for different therapeutic purposes. However, the utilized dissolving microneedles demand frequent administration, potentially compromising patients' compliance. Additionally, the high toxicity of methotrexate prompts a quest for safer alternatives. Phloretin, a natural compound with confirmed antipsoriatic potential, emerges as a promising candidate. Herein, microneedle patches with separable, slow-degrading tips are developed for the sustained delivery of methotrexate and phloretin, as a comprehensive solution for long-term psoriasis management. Both compounds are individually loaded at varying doses and display sustained-release profiles. The developed microneedle patches demonstrate high mechanical strength, favorable drug delivery efficiency, and remarkable antipsoriatic potential both in vitro in keratinocytes and in vivo in a psoriasis mouse model. Comparative analysis with two subcutaneous injections reveals a similar antipsoriatic efficacy with a single patch of either compound, with prominent phloretin safety. Therefore, the developed patches present a superior alternative to methotrexate's current marketed forms and provide a viable alternative (phloretin) with comparable antipsoriatic efficacy and higher safety. As a chronic condition negatively impacting patients' overall well-being, psoriasis could greatly benefit from sustained-release drug delivery. With this in mind, herein, microneedle patches with implantable tips are developed to deliver the reference standard methotrexate and the potential alternative phloretin in a sustained way, overcoming frequent administration needs, enhancing treatment adherence, and offering an alternative to the highly toxic methotrexate. image

Hydrofluoric acid (HF) is a ubiquitous industrial chemical that is particularly hazardous because of the potential for systemic effects and the induction of severe cutaneous necrosis after contact with the skin. Minimizing skin injury requires decontaminating the affected area promptly with an emergency rinsing solution. Few experimental studies have objectively characterized rinsing solutions such as Diphoterine (DP). Here we develop an ex vivo pigskin model to study and compare the efficacy of rinsing solutions as initial decontaminating agents to stop the progression of skin lesions after HF splashing. The pigskin model shows an immediate local response to HF at varying concentrations and exposure times. We then exposed the pigskin biopsies to 3.75% HF for 1 min and rinsed them with different solutions, including water, 0.9% NaCl solution (saline), 10% calcium gluconate (CaG), Hexafluorine (HXF), and DP. We found DP to be a more effective agent for decontaminating HF lesions than water, saline, and CaG. DP had a similar efficacy as HXF, an emergency rinsing solution used specifically for decontaminating HF-exposed skin. This study shows that skin exposed to HF must be treated quickly from the first minute of exposure.

Three original derivatives of the cytotoxic betulinic acid 3-O-α-l-rhamnopyranoside featuring a monomethylated rhamnoside residue were synthesized. An improved catalytic procedure was involved to functionalize the O-3 position of the monosaccharide in a site-selective fashion. The cytotoxicity of the novel compounds was evaluated in vitro to highlight the moderate impact of carbohydrate monomethylation on the biological activity of betulinic acid 3-O-α-l-rhamnopyranoside.

The aim of this study was to investigate the antioxidant, anti-inflammatory, and anticancer properties of Tunisian Suaeda mollis specie after fractionation by increasing polarity of several extracts (Hexane, Dichloromerthane, Methanol and water). Water and methanol extracts of S. mollis exhibited the best in vitro antioxidant ability (2.92±0.19 and 2.77±0.21 µmol TE/mg, respectively), while, dichloromethane extract displayed the highest ex vivo antioxidant activity with an IC50 equal to 1.73 µg/ml. Besides, hexane extract showed an important anti-inflammatory effect inhibiting NO with 55.9% at 160 µg/ml. Finally, dichloromethane extract displayed a potent anticancer activity against cancerous cells A-549 with an IC50 equal to 70±7 µg/ml as well as non cancerous cells Detroit-551 and WS1 (IC50=81±1 and 62±5 µg/ml, respectively) using resazurin test. Moreover, hexane extract is efficient against Caco-2 (IC50=122 µg/ml). Overall, the results suggested that biological activities are influenced by solvent polarity and extractability.

Lycium europaeum is used as a medicinal herb in many countries. In this study, cyclohexane, dichloromethane, ethyl acetate, methanol and water were used as solvents in the extraction of L. europaeum fruits. The contents of total phenolics, total flavonoids, total tannins and condensed tannins as well as the biological activities of these extracts were investigated using various in vitro and ex vivo assays. Results showed that all solvent extracts of L. europaeum had no anticancer activity against cancerous (A-549 and DLD-1) and non-cancerous (WS-1) human cells. Methanol and ethyl acetate were the most effective solvent for extraction of phenolic compounds and also exhibited the highest antioxidant and anti-inflammatory activities. The methanol extract of L. europaeum fruits was the richest in phenolic compounds with the predominance of ferulic acid, catechin and narengin. These results supported the use of L. europaeum fruit as natural source of bioactive compound for pharmaceutical applications.

The chemical compositions of eleven wild species of aromatic and medicinal plants indigenous to Algeria, including Thymus, Mentha, Rosmarinus, Lavandula, and Eucalyptus, were analyzed. The identification of the chemical composition of each oil was conducted using GC-FID and GC-MS capillary gas chromatography. The study investigated the chemical variability of the essential oils based on several parameters. These included the impact of the vegetative cycle on oil composition, variations among subspecies of the same species, variations among species within the same genus, the influence of environmental factors on composition variations within a species, chemo typing, and the genetic factors (such as hybridization) contributing to chemical variability. The concepts of chemotaxonomy, chemotype, and chemical markers were examined to understand their limitations and emphasize the importance of regulating the use of essential oils derived from wild plants. The study advocates for an approach that involves the domestication of wild plants and screening their chemical compositions according to more specific standards for each commercially available oil. Lastly, the nutritional implications and the variability of nutritional impact based on the chemical composition of the essential oils will be discussed.