Xiu-Li Wu

The present study investigated the effects of hierarchical molecular weights and iron chelation on the in vivo absorption and the inflammatory bioactivity of chondroitin sulfate (CS). Firstly, CS, chondroitin sulfate-iron complex (CS-Fe), and low-molecular-weight chondroitin sulfate-iron complex (LCS-Fe) were fluorescently labeled and characterized. Then, the plasma concentration–time profiles and fluorescence imaging results demonstrated that LCS-Fe was more efficiently absorbed into the bloodstream and showed a higher Cmax (415.16 ± 109.50 μg/mL) than CS-Fe (376.60 ± 214.10 μg/mL) and CS (135.27 ± 236.82 μg/mL), and it clearly accumulated in the liver. Furthermore, the anti-inflammatory effect of CS-Fe and LCS-Fe was assayed in LPS-induced macrophages, and LCS-Fe and CS-Fe both showed a better inhibitory effect on NO production, COX-2 and IL-1β gene expression levels compared to CS. Additionally, targeted metabolic analysis of macrophages using LC-MS/MS revealed that CS, CS-Fe, and LCS-Fe could reverse approximately one quarter of the LPS-induced differential metabolites, and the biosynthesis of valine, leucine, and isoleucine was the most significantly involved metabolic pathway. Notably, the molecular weight reduction and iron chelation could both enhance the bioavailability and anti-inflammatory efficacy of CS.

Hispidin ( 1 ) is a polyphenolic compound with a wide range of pharmacological activities that is distributed in both plants and fungi. In addition to natural extraction, hispidin can be obtained by chemical or enzymatic synthesis. In this study, the identification and characterization of an undescribed enzyme, PheG, from Phellinus igniarius ( P. igniarius ), which catalyzes the construction of a key C─C bond in the enzymatic synthesis of hispidin are reported. It is demonstrated in vitro that PheG generates hispidin by catalyzing C─C bond formation in the aldol condensation reaction. Based on these results, a plausible pathway for hispidin biosynthesis is proposed by utilizing the primary triacetic acid lactone (TAL, 2 ) and 3,4‐dihydroxybenzaldehyde ( 3 ). The mechanisms for the aldol condensation reaction of PheG are investigated using molecular dynamics (MD) simulations, molecular mechanics/generalized Born surface area (MM/GBSA) binding free energy calculations, density functional theory, and site‐specific mutations. The locations of the key amino acid residues that catalyze the conversion of substrates 2 and 3 to hispidin at the active site of PheG‐1 are identified. This study provides a new method for preparing hispidin with high efficiency and low cost.

Microorganisms produce a wealth of structurally diverse specialized metabolites with a remarkable range of biological activities. The Phomopsis sp. LGT‐5 was obtained through tissue block and repeatedly crossed methods from Tripterygium wilfordii Hook. F. The antibacterial experiments of LGT‐5 showed that it has high inhibitory activity against Staphylococcus aureus and Pseudomonas aeruginosa, and moderate inhibitory activity against Candida albicans. To research the generation of the antibacterial phenomenon of LGT‐5 and provide support for further research and application, the whole genome sequencing (WGS) of LGT‐5 was obtained by single‐molecule real‐time DNA sequencing platform Pacific Biosciences (PacBio) sequencing and Illumina paired‐end sequencing. The final assembled LGT‐5 genome is 54.79 Mb with a contig N50 of 290.07 kb; in addition, its secondary metabolites were detected through HPLC‐Q‐ToF‐MS/MS. By comparing its MS/MS data, the secondary metabolites were analyzed based on visual network maps obtained on the Global Natural Products Social Molecular Networking (GNPS). The analysis results showed that the secondary metabolites of LGT‐5 were triterpenes and various cyclic dipeptides.

Celastrol (1), obtained from the roots of Tripterygium wilfordii Hook F., is most likely to become an antitumor drug, but with severe cytotoxicity. Due to the lack of modifiable sites in the structure of celastrol, the structural diversity of the modified products obtained by synthesis in the previous studies is insufficient, which hinders the pace of its patent medicine. This study describes a method of microbial transformation to increase the modification site of celastrol and reduce its toxicity. The screening of endophytes from native plants was introduced in this context, which led to two novel stereoselective oxidation products such as S-16-hydroxyl celastrol (2) and A-ring aromatized S-16-hydroxyl celastrol (3), along with a rare 7,9-octadecadienoic acid ester of celastrol (4). Their structures were determined by extensive spectroscopic data analysis, especially 1D and 2D NMR. Compared with 1, compounds 3 and 4 exhibited similar antitumor activity in U251, A549, KG-1, and B16 cell lines. Compound 2 had slightly decreased antitumor activity when compared with compound 1. Furthermore, compound 2–4 showed lower cytotoxicity against BV-2 (about 21-fold lower, 2: 92.82 μM, 3: 34.25 μM, and 4: 74.75 μM vs. celastrol: 4.35 μM), and also identical trends against H9c2 and PC12 cell lines.

Trace amounts of components in traditional Chinese medicine are considered pharmacological active substances used for treating many serious diseases. However, purifying all the trace substances and making clear their structures are not easy. In this context, high‐performance liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry based molecular networking was applied to investigate the chemical constituents of the roots of Aconitum kusnezoffii Reichb., which led to the identification of 33 nodes in different groups (N1–N33). Based on the excremental fragmentation pathway of known diterpenoid alkaloids (1–9) and comparisons of characteristic ions and characteristic loss of analogs in literature, the structures of unknown ions were deduced. This work lays a foundation for the evaluation of the clinical basis and mechanism of traditional Chinese medicine from the aspects of chemistry. In this paper, the method speculation of unknown natural products by means of molecular network method is expected to be applied in the discovery and change law of relevant active components in clinical pharmacology and the change of complex systems caused by trace active compounds.

Mining structural novel and bioactive natural products from traditional Chinese drugs and folk medicines have attracted attention from pharmacologists and pharmaceutical chemists for a long time. In this study, the chemical constituents of Asplenium ruprechtii Sa. Kurata was systematically studied based on the evaluation of neuroprotective activity on hydrogen peroxide (H₂O₂)-induced damage of SH-SY5Y cell lines. Sixteen chemical monomers (1–16), including two new structures of 9,19-cycloartane-triterpenoid saponins (1,2), were discovered. Their chemical structures were established based on extensive spectroscopic data analysis, including the one- and two-dimensional (1D and 2D) nuclear magnetic resonance (NMR) data and high-resolution electrospray ionization mass spectrometry (HRESIMS). All monomer compounds were docked with an “active pocket” at the N-terminal of the GluN2B protein, where compounds 13–16 were found to possess high binding scores, which warrant further study on the molecular mechanism. Our findings provide insight and research techniques for discovering new drugs based on neuroprotective activity.