Dilignans with a Chromanol Motif Discovered by Molecular Networking from the Stem Barks of Magnolia obovata and Their Proprotein Convertase Subtilisin/Kexin Type 9 Expression Inhibitory Activity

Natural products have been fundamental materials in drug discovery. Traditional strategies for observing natural products with novel structure and/or biological activity are challenging due to large cost and time consumption. Implementation of the MS/MS-based molecular networking strategy with the in silico annotation tool is expected to expedite the dereplication of secondary metabolites. In this study, using this tool, two new dilignans with a 2-phenyl-3-chromanol motif, obovatolins A (1) and B (2), were discovered from the stem barks of Magnolia obovata Thunb. along with six known compounds (3–8), expanding chemical diversity of lignan skeletons in this natural source. Their structures and configurations were elucidated using spectroscopic data. All isolates were evaluated for their PCSK9 mRNA expression inhibitory activity. Obovatolins A (1) and B (2), and magnolol (3) showed potent lipid controlling activities. To identify transcriptionally controlled genes by 1 along with downregulation of PCSK9, using small set of genes (42 genes) related to lipid metabolism selected from the database, focused bioinformatic analysis was carried out. As a result, it showed the correlations between gene expression under presence of 1, which led to detailed insight of the lipid metabolism caused by 1.

Discovery of novel obovatol-based phenazine analogs as potential antifungal agents: synthesis and biological evaluation in vitro

To explore candidate fungicides from plant secondary metabolites, 16 novel obovatol-type phenazine derivatives were semi-synthesized from obovatol isolated from the leaves of Magnolia obovata Thunb. The antifungal activity of synthesized compounds was investigated in vitro against four phytopathogenic fungi using the spore germination method. The bioassay results showed that eight derivatives (8b, 8g, 8h–k, 8i′, and 8k′) exhibited better antifungal activity against Fusarium solani than two positive controls, especially compounds 8b (IC50 = 64.61 μg mL−1) and 8i′ (IC50 = 79.97 μg mL−1) showed pronounced inhibition of spore germination activity against F. solani. They could be used as lead compounds for further structural optimization. Additionally, the preliminary structure-activity relationships (SARs) illustrated that the introduction of a benzene ring monosubstituted with electron-withdrawing groups into the obovatol scaffold could lead to potentially antifungal compounds.

Suppressive Effects of Hot-water Extract of Magnolia obovata on Clostridium perfringens Enterotoxin-induced Cytotoxicity in Human Intestinal Caco-2 Cells

The physiological functions of the leaves of Japanese big-leaf magnolia (Magnolia obovata) against enterotoxins produced by foodborne pathogens remain unclear. In this study, we evaluated the protective effects of M. obovata leaf extract (MLE) against the cytotoxicity of Clostridium perfringens enterotoxin (CPE), which causes the symptoms of C. perfringens type A food poisoning. The protective effects of MLE against CPE-induced cytotoxicity were evaluated in human intestinal epithelial Caco-2 cells. Pre-treatment with MLE significantly suppressed the cytotoxicity induced by CPE in undifferentiated and differentiated human intestinal Caco-2 cells at a pH range of 4.0 – 7.0. This CPE-suppressive effect was due to a hydrophilic sugar-containing compound without phenolic and protein structures but not the hydrophobic biologically active neolignans, honokiol and magnolol. MLE had a protective effect against cytotoxicity caused by type A C. perfringens. Our results provide novel insight regarding the usage of M. obovata in managing food poisoning.

Influence of short-term hyperthermia on relict plants Ginkgo L. and Magnolia L.

In connection with global climatic changes, which are accompanied by sharp temperature fluctuations, it is important to study the heat resistance of relict plants in order to improve the understanding of the mechanisms of adaptation and survival of organisms in these conditions. Identification of rare and useful plant species more resistant to high temperatures will make it possible to recommend them for use in landscaping, agriculture, medicine, and the like. The work was carried out on magnolias and ginkgo, since these plants are not only important for landscape design all over the world, but are also valued for the content of biologically active substances that are used in medicine and agriculture. Plants of Ginkgo biloba L., Magnolia obovata Thunb., Magnolia kobus DC. and Magnolia denudata Desr. warmed up for three hours at + 40 ° C, the control group was at + 26 ° C. The stress response was analyzed for the level of lipid peroxidation, superoxide dismutase and peroxidase activity, as well as the content of flavonoids and photosynthetic pigments in the studied plants. The photosynthesizing system of all studied species did not undergo any damaging effects due to the action of hyperthermia. Ginkgo biloba plants have shown very high resistance to high temperatures and stability of the antioxidant and pigment systems. Representatives of all the species of magnolia that we have considered can be positioned in the direction of decreasing resistance to sudden increases in temperature: Magnolia kobus → Magnolia obovata → Magnolia denudata. A higher resistance to hyperthermia was found in plants native to Japan. M. denudata was the least resistant species, possibly due to insufficient activity of antioxidant enzymes.