Five undescribed compounds, including two drimane-type sesquiterpenoids, asperdrimanes A and B (1 and 2), and three amide compounds, asperspamides A–C (3–5), together with four known metabolites 6–9, were isolated from the fungus Aspergillus spelaeus GDGJ-286. By extensively analyzing NMR, LC–MS/MS, Marfey's method, and X-ray crystallography, the structures were characterized successfully. Asperdrimanes A and B (1 and 2) are drimane-type sesquiterpenoids characterized by a spiro-β-lactone moiety. Asperspamide B (4) exhibited exceptional antioxidant capacity in ABTS, FRAP, and DPPH tests, along with significant neuroprotective effects in a hydrogen peroxide-induced PC12 cell oxidative injury model, demonstrating strong anti-apoptotic and anti-necrotic properties. These findings highlight asperspamide B’s potential as a lead compound for developing antioxidant agents.
In this study, a homogeneous polysaccharide, designated PGP-1, was successfully isolated and purified from the roots of Platycodon grandiflorus. Comprehensive structural characterization via methylation analysis, GC–MS, and NMR spectroscopy identified PGP-1 as an inulin-type fructan predominantly composed of →1)-β-D-Fruf-(2→ as the main chain with terminal β-D-Fruf-(2→ and α-D-Glcp-(1→ residues, consistent with the structural features of previously reported Platycodon grandiflorus fructans. Unlike conventional chemotherapeutic agents that rely on broad-spectrum and non-specific cytotoxicity, biological evaluations revealed that PGP-1 acts as a safe and targeted immunomodulator. Specifically, PGP-1 effectively induced M1 macrophage polarization in RAW264.7 cells through the TLR4/NF-κB signaling pathway, significantly enhancing their phagocytic capacity and promoting the robust release of tumoricidal factors, including nitric oxide (NO), TNF-α, and IL-6. Crucially, utilizing a macrophage-tumor transwell co-culture model to simulate the tumor microenvironment, it was demonstrated that PGP-1 exhibited negligible direct cytotoxicity to cancer cells but exerted potent indirect tumoricidal activity against hepatocellular (H22) and lung (LLC) carcinoma cells by augmenting macrophage-mediated immune responses. These findings provide preliminary evidence linking the polysaccharide's safety profile with its tumor-suppressive efficacy, suggesting the potential of PGP-1 as a low-toxicity natural immune enhancer for cancer immunotherapy.
A drug–drug cocrystal strategy harnessing natural product synergy was developed to address the oral delivery barriers of breviscapine (BRE), a natural flavonoid with poor solubility and extensive first-pass metabolism. BRE was integrated with the monoterpenoid permeation enhancer borneol (BO) via solvent evaporation to form a stable supramolecular assembly. Comprehensive solid-state characterization and density functional theory calculations confirmed that the cocrystal lattice is stabilized by specific hydrogen bonding between the flavonoid and terpenoid scaffolds. The optimized BRE-BO cocrystal exhibited highly synchronized release of both natural products (R2 = 0.86), in contrast to the discordant dissolution of the physical mixture, with kinetics following the Korsmeyer–Peppas model (n = 0.45) indicative of Fickian diffusion. In vivo pharmacokinetic evaluation in rats demonstrated that the synergy conferred by co-delivered BO resulted in a 1.6-fold enhancement in oral bioavailability (AUC0-24), a prolonged Tmax (from 2.3 to 3.3 h), and an elevated Cmax (1.2 vs. 0.8 mg/L) compared to bulk BRE. These findings demonstrate that drug–drug cocrystallization can simultaneously achieve dissolution synchronization and pharmacokinetic optimization, providing a viable strategy for the formulation of poorly bioavailable natural flavonoids without the use of polymeric excipients.
Avicennia marina (Forssk.) Vierh. is an important mangrove plant with high nutritional and medicinal values, featuring saccharides as its primary bioactive compounds. In this study, we successfully isolated a neutral tetrasaccharide (AMO-1) from the fruits of A. marina. Through monosaccharide composition, methylation, UPLC-ESI–MS/MS, and NMR analyses, we revealed that the structure of AMO-1 was α-D-Galp-(1 → 6)-α-D-Galp-(1 → 6)-α-D-Glcp-(1 → 2)-β-D-Fruf. Subsequently, we investigated the anti-osteoporosis (anti-OP) efficacy and underlying mechanisms of AMO-1. Our findings demonstrated that AMO-1 promoted the differentiation and mineralization of MC3T3-E1 cells. Furthermore, AMO-1 increased trabecular bone density and restored its reticular structure in dexamethasone-induced OP mice. Additionally, AMO-1 upregulated the expression levels of osteogenic factors and elevated serum levels of osteocalcin and PINP. Mechanistically, AMO-1 promoted osteogenesis through activation of the PI3K/AKT/HIF-1α signaling pathway, thus exerting anti-OP effects. Overall, these findings indicate that AMO-1 is a promising functional food ingredient with therapeutic potential for the prevention and management of OP.
The Trichoderma-produced secondary metabolite 6-pentyl-alpha-pyrone (6-PP) has demonstrated promise for agricultural applications, but cost-effective bioproduction remains limited by product inhibition during fermentation. This study aimed to evaluate the effect of media type on 6-PP production in T. atroviride IMI206040, screen production by nine New Zealand Trichoderma strains, and assess Amberlite XAD-4 in situ product removal in five strains to overcome self-inhibition. T. atroviride IMI206040 was cultured for 5 days in potato dextrose broth (PDB) or minimal media supplemented with ammonium or nitrate, and 6-PP production was assessed by thin-layer chromatography (TLC). The ten Trichoderma strains were cultured for 7 days in PDB and 6-PP production quantified by spectrophotometry. Finally, five strains were cultured in PDB for 14 days with and without Amberlite XAD-4, and 6-PP quantified by spectrophotometry and gas chromatography (GC). In T. atroviride IMI206040, PDB supported the highest 6-PP production, while ammonium-based minimal media repressed production, consistent with nitrogen catabolite repression. Screening revealed up to 14.6-fold variation among strains, with T. gamsii LU771 and T. viridescens LU1369 as the highest producers. Spectrophotometric and GC measurements showed strain-dependent disagreement, indicating GC is more reliable for cross-strain comparisons. Amberlite XAD-4 increased total 6-PP production 3- to 5.2-fold across all five strains, with > 99
