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The identification of novel anti-infective agents of synthetic and natural origin represents one of the main aims of contemporary drug discovery. In the current work, four different varieties of Nicotiana tabacum, namely, K399, SPG28, Swat No. 1, and Swat No. 2, were studied to assess the antibacterial and antifungal properties of their extracts. The extracts contain anthraquinones, alkaloids, saponins, terpenoids, tannins, resins, steroids, proteins, and carbohydrates, and the antibacterial and antifungal activities were evaluated toward four bacterial and four fungal strains. N. tabacum K399 showed the highest zone of inhibition against E. coli. Similarly, K399 showed the highest antifungal potential, as the highest zone of inhibition for the set was detected against C. albicans. Then, the underlying molecular mechanism was further investigated, and the extracts were tested for their inhibitory potential against urease, an enzyme which is conserved in bacteria and fungi. Additionally, computational tools were enrolled to assess the role of rutin and chlorogenic acid, which are among the main constituents of N. tabacum leaves, in interacting with urease through molecular docking. Combined together, the computational and experimental results support the antibacterial and antifungal potential of N. tabacum extracts, particularly, that obtained from K399 variety.

The usage of Pistacia chinensis subsp. integerrima (J.L. Stewart) Rech. f. and its extracts in traditional medicine is well-documented, since this plant is known for its anti-infective, antidiabetic and antioxidant properties. Additionally, recent studies described the antiproliferative activity of its extracts on cancer cell models. Nevertheless, the mechanisms of action underlying this biological effect still have to be fully elucidated. In this study, we focused our attention on the characterization of the bioactivity profile of the flavonoids spinacetin (1) and patuletin (2) and of the triterpene pistagremic acid (3) extracted from the galls of P. integerrima. The compounds were tested in vitro against aldose reductase and thymidine phosphorylase, two targets that are attracting growing attention in the field of drug discovery due to their involvement in metabolism regulation and angiogenesis. Computational studies were used to rationalize experimental data, and the results support the potential of spinacetin (1) as a promising bioactive multi-target anticancer agent. [Display omitted] • P. integerrima is a source of anticancer compounds. • Spinacetin, patuletin and pistagremic acid inhibit aldose reductase and thymidine phosphorylase. • Molecular docking studies paralleled experimental results. [ABSTRACT FROM AUTHOR]

Iphiona grantioides (Boiss) Anderb. is a medicinal plant featuring several traditional uses. Nevertheless, this plant has not been widely investigated by modern medicinal chemistry yet, as also the properties of its extracts. In this study, we report the extraction of the essential oil by hydrodistillation from the leaves of I. grantioides. This was characterised by GC-MS analysis and ten chemical constituents were identified. Our findings demonstrate that the essential oil is effective in inhibiting the growth of bacterial strains, and of Klebsiela pneumonia and Staphylococcus aureus in particular. Additionally, its antioxidant properties were evaluated, and it showed radical scavenging activity in vitro. [ABSTRACT FROM AUTHOR]

Pistacia chinensis subsp. integerrima is a valuable medicinal plant as its parts and extracts found application for treating diarrhea, fever, liver disorders, asthma, and inflammation. In this study, we report the leishmanicidal activity of sakuranetin, spinacetin, and patuletin extracted from P. chinensis. The tested compounds revealed a strong anti-leishmanial activity in vitro against Leishmania major showing IC50 values of 7.98 ± 0.16 µM, 9.23 ± 0.23 µM 11.09 ± 0.87 µM for sakuranetin, spinacetin, and patuletin, respectively. Moreover, to explore the potential mechanism(s) by which the compounds may act, computational docking studies were performed against dihydrofolate reductase and pteridine reductase, showing that the flavonoids could target these two key enzymes to exploit their leishmanicidal activity. In accordance with in vitro results, patuletin was highlighted as the most promising compound of the set, and binding energy values of −6.72 and −6.74 kcal/mol were computed for the two proteins, respectively. [ABSTRACT FROM AUTHOR]

Guanine-rich sequences of nucleic acids, including DNA and RNA, are known to fold into non-canonical structures named G-quadruplexes (G4s). Such arrangements of these macromolecular polymers are mainly located in telomeres and in promoter regions of oncogenes and, for this reason, they represent a potential target for compounds with therapeutic applications. In fact, the ligand-mediated stabilization of G4s inhibits telomerase and the activity of transcriptional machinery and counteracts cancer cell immortalization. Flavonoids, along with other classes of small molecules, have been previously tested for their ability to stabilize G4s, but the mechanism of their interaction has not been fully elucidated. In the current work, we report a multi-technique investigation on the binding of tosylated isoflavones obtained by the B-ring modification of compounds from Maclura pomifera to a telomeric DNA sequence. Our study demonstrates that such derivatization leads to compounds showing lower binding affinity but with an increased selectivity toward G4 with respect to double-stranded DNA. The binding mode to the macromolecular target G4 was studied by combining results from electrospray mass spectrometry binding studies, nuclear magnetic resonance experiments and computational simulations. Overall, our findings show that tosylation influences the selectivity toward the macromolecular target by affecting the interaction mode with the nucleic acid. [ABSTRACT FROM AUTHOR]

Gamma-oryzanol (ORY), found in rice (Oryza sativa L.), is a mixture of ferulic acid esters with triterpene alcohols, well-known for its antioxidant and anti-inflammatory properties. Our past research demonstrated its positive impact on cognitive function in adult mice, influencing synaptic plasticity and neuroprotection. In this study, we explored whether ORY can exert neuro-differentiating effects by using different experimental models. For this purpose, chemical characterization identified four components that are most abundant in ORY. In human neuroblastoma cells, we showed ORY's ability to stimulate neurite outgrowth, upregulating the expression of GAP43, BDNF, and TrkB genes. In addition, ORY was found to guide adult mouse hippocampal neural progenitor cells (NPCs) toward a neuronal commitment. Microinjection of ORY in zebrafish Tg (-3.1 neurog1:GFP) amplified neurog1-GFP signal, islet1, and bdnf mRNA levels. Zebrafish nrf2a and nrf2b morphants (MOs) were utilized to assess ORY effects in the presence or absence of Nrf2. Notably, ORY's ability to activate bdnf was nullified in nrf2a-MO and nrf2b-MO. Furthermore, computational analysis suggested ORY's single components have different affinities for the Keap1-Kelch domain. In conclusion, although more in-depth studies are needed, our findings position ORY as a potential source of bioactive molecules with neuro-differentiating potential involving the Nrf2 pathway. [ABSTRACT FROM AUTHOR]

An editorial is presented which expresses the views on the antioxidant potential of polyphenolic and flavonoid compounds, showcasing their role in health promotion and disease management. Topics include the antioxidant and anti-inflammatory activities of various plant-derived compounds, the comprehensive evaluation of these compounds in both in vitro and in vivo studies, and the implications of these findings for developing new therapeutic approaches.

Cyclooxygenase 2 (COX-2) and 5-lipoxygenase (5-LOX) are overexpressed in gastric cancer cells, the dual inhibitors of which exhibit potential against metastasis and invasion with fewer side effects. To discover inhibitors targeting COX-2 and 5-LOX, we conducted ultrafiltration and enrichment calculation to screen candidates in quaternary alkaloids (QAs) from Zanthoxylum simulans through LC and LC-Q-TOF. For intensive peaks, peaks 19 (berberine) and 21 (chelerythrine) were observed as the most potent dual candidates and showed selective affinity to 5-LOX over COX-2. Peak 19 showed an enrichment at 4.36 for COX-2 and 22.81 for 5-LOX, while peak 21 showed an enrichment at 7.81 for COX-2 and 24.49 for 5-LOX. Molecular docking results revealed chelerythrine as a better dual inhibitor, showing time- and dose- dependent anti-proliferation against AGS cells. Bio-informatics strategies, such as Gene Expression Omnibus (GEO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG), suggested that hormone pathways in gastric cancer cells might be mediated by chelerythrine. Further reviews and summaries helped outline the mechanisms by which COX-2/5-LOX inhibitors might promote apoptosis in gastric cancer cells via estrogen, thyroid, and oxytocin signaling pathways. Chelerythrine was also added to gastric cancer cells to verify the regulation of these three signaling pathways. As a result, significant calling back of thyroid-stimulating hormone receptor (TSHR), thyroid hormone α3 (TRa3), and thyroid hormone receptor β1 (TRß1) and suppressing estrogen receptor a36 (ER-a36)-Src could benefit the anti- proliferation of chelerythrine. However, it was disappointing that regulation of estrogen receptor α66 (ER-a66), estrogen receptor β (ER-β), and oxytocin receptor (OTR) contributed inversely negative effects on anti-gastric cancer ceüs. At present, the integrative study not only revealed chelerythrine as the most potent dual COX- 2/5-LOX inhibitor from QAs but also generally highlighted that comprehensive regulation of the estrogen, thyroid, and oxytocin pathway should be noted once gastric cancer cells were treated with inflammatory inhibitors. [ABSTRACT FROM AUTHOR]