Plant diseases caused by phytopathogenic fungi are a serious threat in the process of crop production and cause large economic losses to global agriculture. To obtain high-antifungal-activity compounds with novel action mechanisms, a series of 4-substituted mandelic acid derivatives containing a 1,3,4-oxadiazole moiety were designed and synthesized. In vitro bioassay results revealed that some compounds exhibited excellent activity against the tested fungi. Among them, the EC50 values of E13 against Gibberella saubinetii (G. saubinetii), E6 against Verticillium dahlia (V. dahlia), and E18 against Sclerotinia sclerotiorum (S. sclerotiorum) were 20.4, 12.7, and 8.0 mg/L, respectively, which were highly superior to that of the commercialized fungicide mandipropamid. The morphological studies of G. saubinetii with a fluorescence microscope (FM) and scanning electron microscope (SEM) indicated that E13 broke the surface of the hyphae and destroyed cell membrane integrity with increased concentration, thereby inhibiting fungal reproduction. Further cytoplasmic content leakage determination results showed a dramatic increase of the nucleic acid and protein concentrations in mycelia with E13 treatment, which also indicated that the title compound E13 could destroy cell membrane integrity and affect the growth of fungi. These results provide important information for further study of the mechanism of action of mandelic acid derivatives and their structural derivatization.
Aralia chinensis L. has shown potential in breast cancer treatment, yet its pharmacodynamically active components and mechanisms remain undefined. To systematically identify the bioactive constituents absorbed into the bloodstream and elucidate their multi-target mechanisms against breast cancer, we employed ultra-high-performance liquid chromatography in conjunction with Q Exactive Orbitrap mass spectrometry (UHPLC-Q Exactive Orbitrap-MS) alongside serum pharmacochemistry to analyze the chemical constituents of total saponins derived from A. chinensis (TSAC) and to identify the blood-absorbed prototypes in a rat model. Network pharmacology predicted targets and pathways of serum prototypes, validated by molecular docking and in vitro experiments. We identified 38 triterpenoid saponins, 3 steroidal saponins, and 8 triterpenoids in TSAC, with 22 prototype compounds detected in serum. An integrative analysis encompassing 486 compound targets and 1747 genes associated with breast cancer elucidated critical pathways, notably the PI3K-Akt signaling pathway and resistance mechanisms to EGFR tyrosine kinase inhibitors. Molecular docking confirmed strong binding of araloside A and elatoside L to SRC, PIK3R1, PIK3CA, STAT3, and EGFR. In MCF-7 cells, TSAC suppressed proliferation and migration while downregulating Src, PI3K, and EGFR expression at the gene and protein levels. This study successfully identified TSAC’s serum-absorbed bioactive components and demonstrated their anti-breast cancer effects via multi-target mechanisms involving the Src/PI3K/EGFR axis, providing a crucial pharmacological foundation for developing A. chinensis-derived breast cancer therapies.
Gerbera piloselloides (L.)Cass. is an important ethnomedicinal plant. Wild populations are steadily declining, however, posing a risk of failure to meet future market demand. Investigating suitable habitats for this plant and key influencing factors is crucial for its artificial cultivation. In this study, we implemented an optimized MaxEnt to project suitable habitats for the target species in five different periods and explored the impact of different environmental variables on its distribution. Our study findings provide confirmation of the following: (1) The current and future potential distributions of Gerbera piloselloides are primarily located in the areas south of the Qinling–Huaihe boundary in China, with future expansions expected to shift northward and westward. (2) Notably, there was a contraction in the junction regions of the provinces of Jiangxi, Anhui, Hunan, and Hubei. (3) The number of highly suitable habitats in Fujian, Guangdong, Yunnan, and Guangxi is expanding; in comparison, the number in Guizhou, Sichuan, and Hainan is declining. (4) The primary environmental determinants shaping its range, together with the threshold values for highly suitable habitats, are the minimum temperature of the coldest month (bio6, 0.88–22.58 °C) and the temperature seasonality (bio4, 461.54–763.9). The findings presented in this work provide support for the artificial cultivation and conservation of this plant.