The Asian water plantain, Alisma orientale (Sam.) Juzep, is a traditional Chinese medicinal plant. The dried tubers of the Alisma orientale, commonly referred to as Alismatis rhizome (AR), have long been used in traditional Chinese medicine to treat a variety of diseases. Soil properties and the soil microbial composition are known to affect the quality and bioactivity of plants. Here, we sought to identify variations in soil fungal communities and soil properties to determine which would be optimal for cultivation of A. orietale. Soil properties, heavy metal content, and pesticide residues were determined from soils derived from four different agricultural regions around Shaowu City, Fujian, China, that had previously been cultivated with various crops, namely, Shui Dao Tu (SDT, rice), Guo Shu Tu (GST, pecan), Cha Shu Tu (CST, tea trees), and Sang Shen Tu (SST, mulberry). As fungi can either positively or negatively impact plant growth, the fungal communities in the different soils were characterized using long-read PacBio sequencing. Finally, we examined the quality of A. orientale grown in the different soils. Our results show that fungal community diversity of the GST soil was the highest with saprotrophs the main functional modes in these and SDT soils. Our data show that GST and SDT soils were most suitable for A. orientale growth, with the quality of the AR tubers harvested from GST soil being the highest. These data provide a systematic approach at soil properties of agricultural lands in need of replacement and/or rotating crops. Based on our findings, GST was identified as the optimal soil for planting A. orientale, providing a new resource for local farmers.

This study aimed to compare the therapeutic effects of fresh (CMF) and dried (CMD) Centipeda minima against allergic rhinitis (AR), elucidate their underlying molecular mechanisms, and identify the bioactive compounds responsible for their immunomodulatory actions. An ovalbumin-induced AR mouse model was treated with CMF or CMD extracts, followed by evaluation of nasal symptoms, serum biomarkers (IgE, histamine, cytokines), and nasal mucosa histopathology. Transcriptomics and widely targeted metabolomics were integrated with network pharmacology to identify differentially expressed genes and bioactive components, which were further validated in RAW264.7 and RBL-2H3 cells. CMF and CMD exhibited distinct anti-AR mechanisms: CMF predominantly suppressed Th2 responses (reducing IgE, IL-6, and histamine while elevating IL-10), whereas CMD enhanced Th1 activity (increasing IFN-γ). Metabolomic analysis revealed CMF was rich in amino acids while CMD contained higher flavonoids, with neocnidilide and 6-gingerol identified as key bioactive compounds that modulated TNF-α, IL-6, and IL-10 via NF-κB and JAK-STAT pathways. These findings demonstrate that CMF and CMD exert complementary anti-inflammatory effects through Th2 inhibition and Th1 activation, respectively, providing a molecular basis for the traditional use of Centipeda minima and highlighting its bioactive compounds as potential therapeutics for inflammatory diseases.

Glioblastoma (GBM) is a highly aggressive and therapy-resistant brain tumor, necessitating innovative multi-target strategies. Natural compounds like the triterpenoid Alisol B from Alisma orientale hold promise due to their polypharmacological potential, yet their system-level mechanisms are unclear. Using an integrated multi-omics approach (transcriptomics, proteomics, lysine acetyl-proteomics) in resistant GBM cells and validating findings in vitro and in AB strain zebrafish (Danio rerio) xenografts, we found that Alisol B induces endoplasmic reticulum stress and G2/M arrest, initiated by extensive lysine acetylation reprogramming on histones and metabolic enzymes (e.g., FASN, FDFT1). This epigenetic rewiring leads to disrupted cholesterol biosynthesis, characterized by transcriptional activation of the mevalonate pathway alongside post-transcriptional suppression of terminal enzymes (DHCR7, CYP51A1), suggestive of toxic intermediate accumulation. Alisol B also downregulated the oncogenic axis (BIRC5-FOXM1-ITGA4) and SCD5. This study delineates Alisol B’s novel multi-mechanistic action through concurrent epigenetic rewiring, metabolic dysfunction induction, and survival network dismantling. Our work elucidates the molecular pharmacology of a natural compound and provides a framework for developing polypharmacological therapies against resistant cancers, exemplifying natural products as tools to reveal new therapeutic paradigms.

Background/Objectives: Triptolide (TP), a potent natural diterpenoid, exhibits anti-glioma activity, but faces significant clinical translation challenges, including poor water solubility, systemic toxicity such as hepatotoxicity, and inadequate tumor targeting. This study aimed to develop a novel epidermal growth factor receptor (EGFR)-targeted liposomal formula-tion, designated as TP-CTX-Lip (where CTX denotes cetuximab), to enhance the deliv-ery efficiency and therapeutic window of TP. Methods: The formulation was optimized using a uniform design approach (four factors, six levels) and prepared via thin-film hydra-tion–ultrasonication. The encapsulation of TP was supported by Fourier transform in-frared spectroscopy (FTIR) and thermal analysis (DSC/TGA), which revealed molecu-lar interactions (e.g., hydrogen bonding) with lipid components and a marked en-hancement in thermal stability, consistent with successful incorporation into the lipo-somal bilayer. The physicochemical properties, including the size, polydispersity index (PDI), zeta potential, encapsulation efficiency, and drug loading, were characterized. In vitro release kinetics were evaluated in phosphate buffer (pH 7.4), and cytotoxicity was assessed in high-EGFR (U87-MG) and low-EGFR (SW1088) glioma cells. In vivo efficacy and developmental toxicity were investigated using zebrafish models. The op-timized TP-CTX-Lip demonstrated favorable characteristics: size = 131.3 ± 4.5 nm, PDI = 0.24 ± 0.006, zeta potential = −23.37 ± 0.27 mV, encapsulation efficiency = 85.83% ± 1.81%, and drug loading = 13%. In vitro release followed first-order kinetics dominated by Higuchi diffusion (79.0% ± 4% at 24 h). After 48 h of treatment, TP-CTX-Lip exhib-ited significantly enhanced cytotoxicity in U87-MG cells (IC50 = 10.4 ± 0.2 nM), com-pared with IC50 values of 42.8 nM in SW1088 cells and 45.3 nM for non-targeted lipo-somes. In the 3T3-L1 non-cancerous cell line, the 48 h IC50 value of TP-CTX-Lip (8.433 ± 0.954µM) was higher than that of the TP solution (2.173 ± 0.181µM) but lower than that of TP-Lip (25.78 ± 2.691µM). Specifically, in 3T3-L1 cells, the 48 h IC50 of TP-CTX-Lip (8.43 µM) was approximately 4-fold higher than that of free TP (2.17 µM), confirming its substantially reduced cytotoxicity against non-cancerous cells. Results: In comparison to TP-Lip and free FITC solution, the uptake rate of TP-CTX-Lip in U87-MG cells exhibited a significantly higher level. Specifically, the uptake rate for the TP-CTX-Lip group (57.46 ± 5.44%) was statistically significantly higher than that of TP-Lip (13.7 ± 2.33%) and the free FITC solution group (20.97 ± 1.60%) (p < 0.01). In zebrafish, TP-CTX-Lip reduced developmental toxicity, with LC50 increased 1.26 times to 5.733 μg/mL, and suppressed orthotopic U87-MG xenograft growth (p < 0.001), in-dicating an improved therapeutic window as reflected by the LC50/IC50 ratio. Conclusions: the EGFR-targeted TP-CTX-Lip significantly enhances the tumor selectivity and safety of TP, providing a promising strategy for targeted glioma therapy.

Introduction: The Asian water plantain, Alisma orientale (Sam.) Juzep, is a flowering hydrophytic plant that grows in marshes. In traditional Chinese medicine, the rhizome of A. orientale is highly valued for its medicinal properties. Endophytic microbes modulate plant growth and the biosynthesis of secondary metabolites, however little is known concerning these effects in A. orientale . Methods: Here, high-throughput sequencing and culturing methods were utilized to investigate the endophytic fungal diversity in the rhizomes, flowers, roots and leaves of A. orientale . In vitro assays were employed to screen for strains exhibiting high growth-promoting abilities based on phosphate solubilization, siderophore production, oxidative stress resistance, and indole-3-acetic acid (IAA) production. Transcriptomics and whole genome sequencing were employed to investigate the underlying molecular mechanisms. Results: These data revealed that the Ascomycota and Basidiomycota were dominant phyla in all parts, with significant variation in fungal community composition observed at the genus level, as reflected in alpha and beta diversity indices. A total of 19 different endophytic fungal strains were isolated via culturing methods from the four different parts of A. orientale . In vitro assays resulted in the identification of four isolates subsequently used for co-culturing with sterile A. orientale to monitor plant-growth and terpenoid production. These latter results identified one promising strain, RT1, characterized as Pseudothielavia terricola . Isolate RT1 enhanced plant growth by 100–121% with respect to root length and plant height as compared to controls. After 21 days of treatment with strain RT1, the contents of the triterpenoids alisols B-23, C-23, and B were 4.5–5.5 times higher than those of the controls. Transcriptomics revealed enhanced expression of key enzymes involved in plant growth and bioactive compound accumulation, including 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), mevalonate diphosphate decarboxylase (MVD), farnesyl diphosphate synthase (FPPS), 1-deoxy- D -xylulose-5-phosphate reductoisomerase (DXR), 1-deoxy- D -xylulose-5-phosphate synthase (DXS), farnesyl-diphosphate farnesyltransferase (FDFT1), and squalene monooxygenase (SQLE) during RT1 interaction. Whole genome sequencing of P. terricola revealed the presence of several gene clusters involved in tryptophan synthesis. Discussion: This study establishes endophytic fungal enhancement of A. orientale growth and bioactive compound accumulation, thereby increasing crop value and utility.