Xiao Ding

Five new Daphniphyllum alkaloids, daphmacropomines A–E (1–5), were isolated from Daphniphyllum macropodum Miq. and structurally characterized. Compound 1 is an unprecedented Daphniphyllum alkaloid that features a unique 6/9/7/5/5 ring with a rare N-nitroso group. Compound 2 is the second Daphniphyllum alkaloid featuring a highly rearranged 6/6/6/7/5/6-fused skeleton. Compounds 3 and 4 are new yuzurimine-type alkaloids, and their structures were determined by extensive techniques including HRESIMS, NMR, ECD, and single-crystal X-ray. A plausible biosynthetic pathway for 1–4 is proposed. Furthermore, compounds 3 and 4 can induce lysosomal biogenesis and promote autophagic flux.

Monomeric compounds from Humulus scandens that effectively inhibit Phytophthora nicotianae were isolated, and their antimicrobial effects were analyzed. Methanol extracts were isolated using a combination of activity tracking and chemical separation methods. Compound structures were identified using NMR and other techniques. Antimicrobial activity against P. nicotianae was assessed via the mycelial growth rate method with mycelial morphology further observed using optical microscopy and scanning electron microscopy. Five compounds were isolated from the ethyl acetate (EtOAc) layer of H. scandens , namely, chromone (compound 1), tectochrysin (compound 2), isorhamnetin (compound 3), hyperoside (compound 4), and Apigenin 7-glucoside (compound 5). All compounds exhibited varying degrees of antimicrobial activity. Compounds 1 and 5 demonstrated superior inhibitory effects, with EC ₅₀ values of 51.70 and 31.71 μg/ml and MIC values of 400 and 200 μg/mL, respectively. Microscopic examination revealed that compounds 1 and 5 induced distortion, deformation, shrinkage, collapse, and damage in P. nicotianae mycelia. Additionally, they increased membrane permeability and inhibited mycelial growth by disrupting cellular integrity. This study provides lead compounds for developing green botanical pesticides against tobacco black shank disease and offers data to support green agriculture initiatives.

Three new polyacetylene glycosides, pilosulynosides A–C (1–3), along with 15 known analogues (4–18), were isolated from the roots of Codonopsis pilosula (Franch.) Nannf. Their structures were determined by 1D and 2D NMR, HRESIMS, and DP4+ probability analysis based on uncalibrated NMR chemical shifts. The promoting effects of all isolated compounds on lysosomal biogenesis were evaluated in HepG2 cells using the LysoTracker Red staining assay. Compounds 1 (pilosulynoside A) and 18 (9-(tetrahydropyran-2-yl)-nona-trans-8-nonene-4,6-diyn-1-ol) showed strong activities in promoting lysosomal biogenesis without cytotoxicity. Mechanistic studies revealed that these effects were independent of the classical TFEB/TFE3 pathways. Furthermore, compounds 1 and 18 displayed anti-senescence activity in a senescence model of rat cardiac microvascular endothelial cells (CMECs). These findings indicate that polyacetylenes from C. pilosula can promote lysosomal biogenesis via a TFEB/TFE3-independent mechanism and exert anti-senescence effects, offering new lead compounds for therapeutic interventions in senescence and lysosome-related diseases.

Transcriptional control of lysosome biogenesis is an important mechanism underlying cellular adaptation to stress. It is largely unclear how cell surface changes or signals induce alteration in lysosome numbers. By developing a Caenorhabditis elegans-based heterologous TFE3 activation system, we here identify the non-receptor tyrosine kinases SRC-1/-2 (C. elegans) and FGR (mammals) as critical regulators of lysosome biogenesis. In C. elegans, inactivation of src-1/-2 leads to nuclear enrichment of ectopically expressed TFE3 and increased intensity of lysosomal markers. In mammalian cells, FGR inhibition or deficiency similarly results in TFEB/TFE3-dependent lysosomal increase. FGR acts through AKT2 by promoting the activation of the latter. FGR associates with the plasma membrane but is internalized onto endosomes and reaches lysosomes along the endosome–lysosome pathway following endocytosis. Lysosomal FGR promotes AKT2 recruitment to lysosomes, where it phosphorylates TFEB/TFE3 to prevent their activation. Together, these findings reveal a plasma membrane-to-lysosome signaling axis that is required for endocytosis-associated lysosome homeostasis.

Friedelin, a pentacyclic triterpene, has been reported to inhibit potential reactive oxygen species (ROS)-scavenging activity. Accordingly, we modified the structure of this compound with the aim of obtaining derivatives. A new derivative (compound 4), with an α,β-unsaturated ketone moiety, was synthesized via an aldol condensation. Structural characterization of this compound was performed using nuclear magnetic resonance (NMR) spectroscopy and high-resolution electrospray ionization mass spectrometry.

The phytochemical diversity of plants represents a valuable reservoir for novel agrochemical agents. Our preliminary investigations identified pronounced antifungal efficacy in Laggera pterodonta extracts, although this species remains critically understudied. Herein, six eudesmane-type sesquiterpenes (1–6) were isolated from L. pterodonta and structurally characterized through spectroscopic analysis. Additionally, the antifungal activity of these compounds against six plant-pathogenic fungal species was evaluated: Phytophthora nicotianae, Fusarium oxysporum, Alternaria alternata, Gloeosporium fructigenum Berk, Colletotrichum fructicola, and Botrytis cinerea. The results showed that the six compounds exhibited varying degrees of inhibitory effects on the six plant pathogens. Compound 1 showed the strongest antifungal effect in a dose-dependent way, with half-maximal effective concentration (EC₅₀) values of 12.56, 51.29, and 47.86 μg/mL against P. nicotianae, F. oxysporum, and G. fructigenum Berk, respectively. Compound 3 and compound 6 also showed notable inhibitory effects against F. oxysporum and P. nicotianae at 100 μg/mL, with inhibition rates of 58.82% and 73.92%, respectively. The minimum inhibitory concentrations (MICs) of compound 1 against P. nicotianae and F. oxysporum were 200 and 400 μg/mL, respectively. Mechanistic analysis revealed that compound 1 induced pronounced ultrastructural deformations in P. nicotianae and F. oxysporum, compromising membrane integrity and elevating permeability in both pathogens. Notably, the three bioactive compounds exhibited favorable ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiles, demonstrating promising candidacy as novel herbicidal agents. These findings underscore their potential to advance phytogenic fungicide discovery.