Nanoemulsions of Jasminum humile L. and Jasminum grandiflorum L. Essential Oils: An Approach to Enhance Their Cytotoxic and Antiviral Effects

Unprecedented nanoemulsion formulations (NE) of Jasminum humile and Jasminum grandiflorum essential oils (EO) were prepared, and examined for their cytotoxic and antiviral activities. NE characterization and stability examination tests were performed to ensure formula stability. The antiviral activity was determined against hepatitis A (HAV) and herpes simplex type-1 (HSV-1) viruses using MTT assay, while the cytotoxic potential was determined against liver (HepG-2), breast (MCF-7), leukemia (THP-1) cancer cell lines and normal Vero cells. Statistical significance was determined in comparison with doxorubicin as cytotoxic and acyclovir as antiviral standard drugs. GC-MS analysis indicated twenty four compounds in the EO of J. humile and seventeen compounds in the EO of J. grandiflorum. Biological investigations of pure EOs revealed weak cytotoxic and antiviral effects. Nevertheless, their NE formulations exhibited high biological value as cytotoxic and antiviral agents. NE formulations also showed feasible selectivity index for the viral-infected and cancer cells (especially HepG-2) than normal Vero cells. Both nanoemulsions showed lower IC50 than standard doxorubicin against HepG-2 (26.65 and 22.58 vs. 33.96 μg/mL) and MCF-7 (36.09 and 36.19 vs. 52.73 μg/mL), respectively. The study results showed the dramatic effect of nanoemulsion preparation on the biological activity of EOs and other liposoluble phytopharmaceuticals

Promising anti-Helicobacter pylori and anti-inflammatory metabolites from unused parts of Phoenix dactylifera CV ‘Zaghloul’: in vitro and in silico study

AbstractContext Date palm waste is an agricultural waste that accumulates in massive amounts causing serious pollution and environmental problems.Objectives Date palm trees, Phoenix dactylifera Linn CV ‘Zaghloul’ (Arecaceae) grown in Egypt, leave behind waste products that were investigated to produce compounds with anti-Helicobacter pylori and anti-inflammatory activities.Materials and methods Chromatographic workup of P. dactylifera aqueous methanol extract derived from fibrous mesh and fruit bunch (without fruit) afforded a new sesquiterpene lactone derivative, phodactolide A (1), along with ten known compounds (2–11), primarily identified as polyphenols. Chemical structures were unambiguously elucidated based on mass and 1D/2D NMR spectroscopy. All isolated compounds were assessed for their activities against H. pylori using broth micro-well dilution method and clarithromycin as a positive control. The anti-inflammatory response of isolated compounds was evaluated by inhibiting cyclooxygenase-2 enzyme using TMPD Assay followed by an in silico study to validate their mechanism of action using celecoxib as a standard drug.Results Compounds 4, 6 and 8–10 exhibited potent anti-H. pylori activity with MIC values ranging from 0.48 to 1.95 µg/mL that were comparable to or more potent than clarithromycin. For COX-2 inhibitory assay, 4, 7 and 8 revealed promising activities with IC50 values of 1.04, 0.65 and 0.45 μg/mL, respectively. These results were verified by molecular docking studies, where 4, 7 and 8 showed the best interactions with key amino acid residues of COX-2 active site.Conclusion The present study characterizes a new sesquiterpene lactone and recommends 4 and 8 for future in vivo studies as plausible anti-ulcer remedies

In Vitro Phytobiological Investigation of Bioactive Secondary Metabolites from the <i>Malus domestica</i>-Derived Endophytic Fungus <i>Aspergillus tubingensis</i> Strain AN103

Endophytic fungi including black aspergilli have the potential to synthesize multiple bioactive secondary metabolites. Therefore, the search for active metabolites from endophytic fungi against pathogenic microbes has become a necessity for alternative and promising strategies. In this study, 25 endophytic fungal isolates associated with Malus domestica were isolated, grown, and fermented on a solid rice medium. Subsequently, their ethyl acetate crude extracts were pretested for biological activity. One endophytic fungal isolate demonstrated the highest activity and was chosen for further investigation. Based on its phenotypic, ITS ribosomal gene sequences, and phylogenetic characterization, this isolate was identified as Aspergillus tubingensis strain AN103 with the accession number (KR184138). Chemical investigations of its fermented cultures yielded four compounds: Pyranonigrin A (1), Fonsecin (2), TMC 256 A1 (3), and Asperazine (4). Furthermore, 1H-NMR, HPLC, and LC-MS were performed for the identification and structure elucidation of these metabolites. The isolated pure compounds showed moderate-to-potent antibacterial activities against Pseudomonas aeruginosa and Escherichia coli (MIC value ranged from 31 and 121 to 14.5 and 58.3 μg/mL), respectively; in addition, the time–kill kinetics for the highly sensitive bacteria against isolated compounds was also investigated. The antifungal activity results show that (3) and (4) had the maximum effect against Fusarium solani and A. niger with inhibition zones of 16.40 ± 0.55 and 16.20 ± 0.20 mm, respectively, and (2) had the best effect against Candida albicans, with an inhibition zone of 17.8 ± 1.35 mm. Moreover, in a cytotoxicity assay against mouse lymphoma cell line L5178Y, (4) exhibited moderate cytotoxicity (49% inhibition), whereas (1–3) reported weak cytotoxicity (15, 26, and 19% inhibition), respectively. Our results reveal that these compounds might be useful to develop potential cytotoxic and antimicrobial drugs and an alternative source for various medical and pharmaceutical fields

3D engineered neural co-culture model and neurovascular effects of marine fungi-derived citreohybridonol

Marine-based biomolecules are emerging metabolites that have gained attention for developing novel biomaterials, drugs, and pharmaceutical in vitro platforms. Here, we developed a 3D engineered neural co-culture model via a 3D prototyped sliding frame-platform for multi-step UV lithography and investigated the neurovascular potential of citreohybridonol in neuroblastoma treatment. Citreohybridonol was isolated from a sponge-derived fungus Penicillium atrovenetum. The model was characterized by Fourier-transform infrared spectroscopy and scanning electron microscopy analysis. Human umbilical cord vein endothelial cells (HUVECs) and neuroblastoma (SH-SY5Y) cell lines were encapsulated in gelatin methacrylate (GelMA) with and without citreohybridonol. The effect of citreohybridonol on the proliferation capacity of cells was assessed via cell viability and immunostaining assays. GelMA and 3D culture characterization indicated that the cells were successfully encapsulated as axenic and mixed with/without citreohybridonol. The cytotoxic test confirmed that the 3D microenvironment was non-toxic for cultural experiments, and it showed the inhibitory effects of citreohybridonol on SH-SY5Y cells and induced the proliferation of HUVECs. Finally, immunohistochemical staining demonstrated that citreohybridonol suppressed SH-SY5Y cells and induced vascularization of HUVECs in mixed 3D cell culture.Tubitak 2232 International Fellowship for Outstanding Researchers Award [118C391]; Alexander von Humboldt Research Fellowship for Experienced Researchers; Marie Sklodowska-Curie Individual Fellowship [101003361]; Science Academy's Young Scientist Awards Program (BAGEP); Bilim Kahramanlari Dernegi Young Scientist Award; Royal Academy NewtonKatip Celebi Transforming Systems Through Partnership Award [120N019]; Outstanding Young Scientists Awards (GEB.IP)S.T. acknowledges the Tubitak 2232 International Fellowship for Outstanding Researchers Award (Grant No. 118C391), the Alexander von Humboldt Research Fellowship for Experienced Researchers, the Marie Sklodowska-Curie Individual Fellowship (Grant No. 101003361), and the Royal Academy NewtonKatip Celebi Transforming Systems Through Partnership Award (Grant No. 120N019) for financial support of this research. This work was partially supported by the Science Academy's Young Scientist Awards Program (BAGEP), the Outstanding Young Scientists Awards (GEB.IP), and the Bilim Kahramanlari Dernegi Young Scientist Award. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the TUB.ITAK

Pyrone derivatives from Helichrysum italicum

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Tetrahydroanthroquinone derivatives from the mangrove-derived endophytic fungus Stemphylium globuliferum

Two new tetrahydroanthraquinone derivatives, altersolanol Q (1) and 10-methylaltersolanol Q (2), and the new dimer alterporriol X (3), together with 13 known analogues were isolated from white bean solid culture media of the endophytic fungus, Stemphylium globuliferum, obtained from the Egyptian mangrove plant Avicennia marina. The present study resulted in the production of a large diversity of secondary metabolites including new derivatives. Their structures were elucidated using one- and two-dimensional NMR spectroscopy as well as HRESIMS. The absolute configurations of the new compounds 1–3 were determined by TDDFT-ECD calculations or by comparing ECD data with those of known analogues. Compounds 1–3 were tested against the L5178Y mouse lymphoma cell line but proved to be inactive in contrast to some of the known compounds such as altersolanol A (6) that were likewise isolated in this study

Cytotoxic secondary metabolites from the endophytic fungus Aspergillus versicolor KU258497

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Alkaloids and Polyketides from <i>Penicillium citrinum</i>, an Endophyte Isolated from the Moroccan Plant <i>Ceratonia siliqua</i>

The endophytic fungus <i>Penicillium citrinum</i> was isolated from a fresh stem of the Moroccan plant <i>Ceratonia siliqua</i>. Extracts of <i>P</i>. <i>citrinum</i> grown on rice and white bean media yielded five new compounds, namely, citriquinochroman (<b>1</b>), tanzawaic acids G and H (<b>2</b> and <b>3</b>), 6-methylcurvulinic acid (<b>4</b>), 8-methoxy-3,5-dimethylisoquinolin-6-ol (<b>5</b>), and one new natural product, 1,2,3,11b-tetrahydroquinolactacide (<b>6</b>), which had previously been described as a synthetic compound. In addition, 13 known compounds including seven alkaloids and six polyketides were isolated. The structures of the new compounds were unambiguously determined on the basis of one- and two-dimensional NMR spectroscopy as well as by high-resolution mass spectrometry. Citriquinochroman (<b>1</b>) features a new skeleton, consisting of quinolactacide and (3<i>S</i>)-6-hydroxy-8-methoxy-3,5-dimethylisochroman linked by a C–C bond. 1,2,3,11b-Tetrahydroquinolactacide (<b>6</b>) may be a biogenetic precursor of quinolactacide. Citriquinochroman (<b>1</b>) showed cytotoxicity against the murine lymphoma L5178Y cell line with an IC₅₀ value of 6.1 μM, while the other compounds were inactive (IC₅₀ >10 μM) in this assay