Six previously undescribed 3-decalinoyltetramic acid (3-DTA) derivatives Penicitriequitins A-F (1-6), one previously undescribed meroterpenoid Sesquicillin G (7), together with three previously described meroterpenoids were isolated from rhizosphere fungus Penicillium citrinum SMUC020. Their structures were elucidated by extensive analysis of NMR spectroscopic data, modified Mosher's method, and quantum computed ECD calculations. The L-alanine in the tetramic acid moiety was established by Marfey's method. Compounds 1-6 feature an unusual oxidation pattern at C-3, which has rarely been observed in DTA related natural products. Anti-inflammatory activity screening was performed to evaluate the inhibitory effects of these compounds on the production of pro-inflammatory cytokines IL-6, IL-1β, and TNF-α in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Further mechanistic studies showed that compound 5 reduced the phosphorylation of NF-κB p65 and IκBα, while CETSA indicated an alteration in the thermal stability of NF-κB. These findings support an association between the activity of compound 5 and modulation of NF-κB/IκBα signaling, without establishing direct protein binding. This study expands the structural diversity of equisetin-type trans-DTAs and provides a basis for further exploration of their structure-activity relationships and biosynthetic mechanisms.

Twenty biphenyls including fifteen previously undescribed compounds (1-8 and 14-15) were isolated from the leaves of Garcinia pedunculata Roxb. The structures of these undescribed compounds were elucidated using high resolution electrospray ionization mass spectroscopy, ultraviolet spectrophotometry, nuclear magnetic resonance (NMR), and calculated [13]C NMR with DP4+ analysis. The absolute configurations of the compounds were determined using electronic circular dichroism. All the isolated compounds were evaluated for their cytotoxicity and inhibitory effects on nitric oxide production with lipopolysaccharides induced RAW 264.7 cells. Notably, garpedunbiphenyl C (3), mangostanone Ⅲ (9), and garciesculenbiphenyl B (12) exhibited significant anti-inflammatory properties, with IC50 values of 7.19 ± 0.38, 8.85 ± 0.62, and 13.64 ± 0.57 μM, respectively. Further assessment via enzyme-linked immunosorbent assay indicated that compounds 3, 9, and 12 dose-dependently inhibited the expression of proinflammatory cytokines IL-6 and TNF-α. At a concentration of 10 μM, compound 3 demonstrated a comparable inhibitory effect on IL-6 and TNF-α to that of dexamethason. Additionally, Western blot analysis revealed that compound 3 significantly attenuated the expressions of iNOS, COX-2, and the NF-κB signaling pathway, thereby alleviating inflammatory responses.

Five undescribed diterpenoids (1-5) and thirteen known analogues (6-18) were isolated from the roots of Euphorbia ebracteolata Hayata. The cytotoxic activity of all isolates was evaluated against MDA-MB-231, HepG2 and MC38 cancer cell lines, with IC50 values of 6.16 ± 0.85, 11.10 ± 0.13 and 6.48 ± 0.37 μM. Flow cytometry showed that compound 12 increased the apoptosis rate of MDA-MB-231 cells in a concentration-dependent manner. Western blot analysis indicated that compound 12 significantly upregulated pro-apoptotic Bax, downregulated anti-apoptotic Bcl-2, and inhibited the JAK2-STAT3 pathway. These findings demonstrated that compound 12 showed promising cytotoxic activity, warranting further investigation.

The essential oil of the underground parts of Doronicum austriacum subsp. giganteum (Griseb.) Stoj. & Stef. (Asteraceae) was studied here for the first time. Based on GC-FID peak-area normalization, neryl isobutyrate (44.2%) and neryl 2-methylbutyrate (28.8%) were the two most abundant identified constituents. Targeted chromatographic fractionation guided by GC-MS revealed a series of oxygenated acyclic monoterpene diesters that proved difficult to identify by conventional means. By combining the synthesis of authentic reference compounds with high-field NMR spectroscopy (HSQC, HMBC, NOESY) and diagnostic [13]C-[1]H coupling constants, nine previously undescribed natural products were identified, including 8- and 9-acyloxyneryl isobutyrates and the corresponding 2-methylbutyrate analogues. Systematic relationships between structure and linear retention indices on nonpolar and polar stationary phases provided transferable criteria for distinguishing C-8 vs C-9 oxygenation and neryl (Z) vs geranyl (E) geometry, and enabled estimation of chromatographic behavior for related, not-yet observed congeners. A re-evaluation of reported NMR patterns further suggests that a subset of literature "acyloxyneryl/geranyl" assignments may correspond to C-10-acylated isomers. Collectively, these findings expand the phytochemical space of acylated monoterpenes in Asteraceae roots and provide a validated spectral and retention-index reference framework for future studies of closely related metabolites.

Eleven previously undescribed 3,4-seco-spiromeroterpenoids, penicitrinoids A-K (1-11), one revised analogue (12), and three known compounds (13-15) were isolated under HPLC-UV guidance from the marine-derived fungus Penicillium citrinum F5025. Their structures and absolute configurations were unequivocally determined through HR-ESIMS, extensive 1D and 2D NMR analysis, ECD calculations, and a single-crystal X-ray diffraction study. Notably, Penicitrinoid A (1) represents the first example of a 3,4-seco-spiromeroterpenoid incorporating a tetrahydrofuran ring. Moreover, the previously reported structure of fusariumin B was revised and corresponds to compound 12. In antiviral assays, compounds 8 and 14 exhibited activity against influenza virus (strain ZX1109) with EC50 values of 6.41 and 10.91 μM, respectively. Compound 8 also showed activity against Ross River virus (RRV) (EC50 = 51.92 μM), while compound 10 was active against dengue virus (DENV-2) (EC50 = 51.91 μM). Mechanistic studies indicated that the antiviral effects of compounds 8 and 10 against RRV and DENV-2 are primarily mediated through interference with viral RNA replication. This study not only expands the structural diversity of 3,4-seco-spiromeroterpenoids but also provides a foundation for their development as potential antiviral agents.

Five highly oxidized taccalonolides, namely taccachatrones H‒L, together with nineteen reported analogues, were characterized from the rhizomes of Tacca chantrieri André. Their structures were established on the basis of extensive spectroscopic analysis and comparison with the spectral data reported in the literature. Taccachatrones H‒L were evaluated for their cytotoxic activities against five human cancer cell lines, including HL-60, A549, SMMC-7721, MCF-7, and SW480. Taccachatrone I exhibited the strongest cytotoxic activity across all tested cell lines, with IC50 values ranging from 8.34 to 13.19 μM. The preliminary structure-activity analysis suggested that substitutions at C-1, C-11, and C-15 may play important roles in the cytotoxic activity of taccalonolides. Molecular docking suggested a possible interaction between taccachatrone I (2) and β-tubulin, providing a hypothesis for further experimental validation.

Ten undescribed dammarane-type triterpenoid saponins (1‒10), along with six known analogues (11‒16) were isolated from the dry leaves of Gynostemma pentaphyllum (Thunb.) Makino, collected from Guilin City in Guangxi, China. Their diverse structures were elucidated on the basis of comprehensive spectroscopic analysis of 1D and 2D NMR, HR-MS, and acid hydrolysis. Among the isolates, three compounds (5, 12, and 16) significantly increased intracellular ATP levels in C2C12 myotubes, reaching 153.2%, 154.7%, and 134.9%, respectively. Further investigation revealed that these regulatory effects were mediated through the modulation of mitochondrial function, among which compound 12 exhibited the strongest agonist activity on the mitochondrial ATP production, elevating it by 25.45%. These findings deepen the insight into dammarane-type saponins and underscore the potential of G. pentaphyllum in anti-fatigue applications.

Sophora flavescens Aiton (Kushen) is a widely used medicinal herb known for its rich phytochemical composition. The plant contains alkaloids, flavonoids, triterpenoid saponins, and other bioactive constituents, among which non-alkaloids are of significant research interest. From 1968 to 2025, 158 non-alkaloids have been isolated. In this review, non-alkaloids were classified according to their skeleton frameworks and substitution patterns, including poly-isopentenyl, isoflavonoids, pterocarpans, benzofuran derivatives, etc. Then this paper systematically summarizes their biological activities, structure-activity relationships (SAR), as well as their NMR spectroscopic features and the biosynthesis of the side-chain cyclization in isopentenyl flavones. Pharmacological studies have shown that non-alkaloid compounds have many biological activities, including anti-inflammation, antioxidant, cytotoxic and anti-Alzheimer disease. This review provides a comprehensive reference for the structural elucidation, pharmacological evaluation, NMR characterization and biosynthesis of non-alkaloids from Sophora flavescens.

The formation of artefacts during the extraction and isolation of specialised metabolites is a significant issue in phytochemical research and related areas, including marine chemistry, and microbial metabolites studies. Artefacts arise when genuine natural products undergo chemical transformations induced by mechanical stress, heat, extraction, purification, storage conditions, enzymatic activity, and/or analytical procedures. Common transformation pathways include hydrolysis, oxidation, isomerisation, solvolysis, rearrangement, polymerisation, and alkylation (e.g., O-methylation). These processes are discussed using representative examples from major phytochemical classes, such as iridoids, sesquiterpene lactones, alkaloids, glucosinolates, and phenolic compounds. Considering these mechanisms of artefact formation, a best practice workflow is proposed in order to minimise artefact formation. The workflow includes systematic control strategies to reduce artefact generation and guidelines for defining appropriate control experiments prior to publishing natural products as genuine compounds. In this way, the reliability of the phytochemical literature can be enhanced. The proposed workflow covers recommendations for extraction planning, solvent selection, temperature and pH control, protection from light, oxygen and enzymes, stability testing, and transparent, systematic analytical validation. Awareness of the feasibility of artefact formation, together with transparent control experiments, will improve reproducibility, ensure structural accuracy, and facilitate more reliable interpretation of phytochemical data. Finally, guidance is provided on how to detect artefacts in previous publications and how to check for their occurrence in one's own work.

The outer skins of potato tubers undergo healing after the wounding that occurs during cultivation and processing of this major food crop, but the macromolecular structure of the suberized cell wall barriers that mitigate drought and infection has remained elusive. Because many prior models have drawn upon top-down analyses of depolymerization treatments that are known to be incomplete, we devised a comprehensive strategy of bottom-up monitoring of wound-healing metabolites at several time points, solid-state NMR (ssNMR) compositional analysis of the suberized cell wall, and top-down chemical analysis of soluble chemical depolymerization products. Liquid and gas chromatography - mass spectrometry (LC-MS and GC-MS) metabolite profiling were conducted for extracts from wound tissues in four potato cultivars with differing skin morphologies at 0, 1, 2, 3, and 7 days post wounding. In parallel, [13]C ssNMR was used to characterize the suberin-enriched polymeric material. Finally, the biopolymer composite was subjected to mild chemical breakdown followed by LC-MS and GC-MS analyses. By coordinating these phytochemical analyses, we found new glycoalkaloid, sterol, and phenolic amine compounds that are incorporated within the biopolymer composite. These findings enrich our picture of the suberin macromolecular structure that develops after wounding or in native skins to protect potato tubers from environmental threats.

As part of our ongoing investigation of the Cotinus coggygria flavonoid complex, five previously undescribed compounds, namely, heterodimers of flavanonol (-)-fustin and aurone sulfuretin 6-8, named fusturetins A, B and C, respectively, and cyclobutane tetramers of sulfuretin 9 and 10, named tetrasulfuretins A and B, respectively, were isolated from the heartwood and structurally characterized using 1D and 2D NMR, HRMS, UV, ECD and IR spectroscopy. In addition, three known homodimers, bis-sulfuretins (3-5), were isolated for the first time from natural sources. Their structures were elucidated by comparison of their spectroscopic data with those of the same compounds obtained by synthesis in our laboratory via laccase-mediated dimerization of sulfuretin using the enzyme from Trametes versicolor. The linkage between fustin and sulfuretin in heterodimers 6-8, and between two sulfuretin molecules in 3-5, could be rationalized by oxidative coupling involving the sulfuretin double bond and the catechol moiety of fustin or sulfuretin, respectively. The final stage of tetramers 9 and 10 biosynthesis, formation of cyclobutane ring, was proposed to be a [2 + 2] cycloaddition of 2(10)-double bonds in 3. Cytotoxicity screening of compounds 3-10 against human cervical adenocarcinoma HeLa, breast adenocarcinoma MDA-MB-231, and myelogenous leukemia K562 cell lines, as well as normal fibroblasts MRC-5, revealed moderate activity of tetramer 9 and dimer 4 against K562 cells, with moderate selectivity.

Phytochemical investigation of the roots of Eurycoma longifolia led to the discovery of eighteen structurally diverse quassinoids (1‒18), including fourteen previously undescribed ones (1, 3‒5, and 7‒16). Among the isolated compounds, compounds 1‒6 are three pairs of unusual C-20 epimeric C25 quassinoids. Compounds 7‒15 are nine C19 quassinoids belonging to three distinct carbon skeleton types. Compounds 16‒18 are three C18 quassinoids; notably, compound 16 features an unprecedented lactone bridge between C-9 and C-14. The chemical structures of the compounds, including absolute configurations, were elucidated by comprehensive spectroscopic analysis, single-crystal X-ray diffraction experiments, and quantum-chemical electronic circular dichroism calculations. Biological evaluations revealed that compounds 7 and 18 significantly inhibited nitric oxide production, interleukin-1β secretion, and inducible nitric oxide synthase expression in lipopolysaccharide-stimulated RAW264.7 cells, suggesting their potential anti-inflammatory activity.

Phytochemical investigation of the seeds of Caesalpinia minax Hance led to the isolation and characterization of twenty-six cassane-type diterpenoids, including eight previously undescribed compounds (1-8). Their structures were elucidated through comprehensive spectroscopic analyses of UV, HR-MS, and NMR data, together with ECD calculations and gauge-including atomic orbital (GIAO) NMR calculations combined with DP4+ probability analysis. Considering the previously reported lipid-lowering and inflammation-related activities of cassane-type diterpenoids, all isolated compounds were evaluated for their effects on proprotein convertase subtilisin/kexin type 9 (PCSK9) secretion in HepG2 cells, as well as glucocorticoid receptor (GR)-, NRF2-, and NF-κB-related reporter assays in A549 cells. Among them, caesalpin T (5) showed a notable inhibitory effect on PCSK9 secretion, with activity comparable to that of the positive control berberine at the tested concentration. In contrast, no significant activities were observed in the reporter assays.

Six previously undescribed coumarins (1-6), including one pair of enantiomers, along with 23 known coumarin derivatives (7-29), were isolated from the branches and leaves of Zanthoxylum dimorphophyllum var. spinifolium. Their structures were elucidated through comprehensive spectroscopic analysis, including HR-ESIMS, NMR, and ECD. These compounds were subsequently evaluated for their antileukemic activity. Among them, the previously undescribed compound 5 exhibited significant antiproliferative activity against three cancer cell lines: erythroleukemia (HEL), promyelocytic (HL-60), and chronic myelogenous leukemia (K562), with IC50 values of 30.5 ± 1.2, 10.2 ± 0.7, and 19.8 ± 1.2 μM, respectively. HL-60 cells were the most sensitive to compound 5, exhibiting the lowest IC50 value of 10.2 ± 0.7 μM. Flow cytometric analysis revealed that compound 5 induced apoptosis in HL-60 cells in a dose-dependent manner and induced significant cell cycle arrest at the S phase. Furthermore, in a zebrafish xenograft model, compound 5 significantly inhibited the proliferation of HL-60 cells in vivo.

Cleistanthane diterpenoids represent an important class of bioactive natural products widely distributed within the Phyllanthaceae family. In this study, a systematic phytochemical investigation of two medicinal plants from this family, Actephila merrilliana Chun and Phyllanthus reticulatus Poir., led to the isolation of thirteen previously undescribed ent-cleistanthane diterpenoids, encleistoids A-M (1-13), along with a known analogue (14). Their structures were established by extensive spectroscopic analysis, quantum chemical calculations, and single-crystal X-ray diffraction. All isolates share an aromatized C-ring. Notably, compounds 1 and 2 are rare rearranged ent-cleistanthane diterpenoids featuring a seven-membered B-ring formed by ring expansion; compounds 3-8 are uncommon tetranor-, trinor-, or nor-derivatives; and compounds 12 and 13 bear an unusual (tetrahydrofuran-2-yl)oxy substituent. Bioactivity evaluation revealed that several isolates exhibited significant anti-HIV-1 activity, with compound 14 being the most potent (IC50 = 0.56 ± 0.25 μM). This study substantially expands the structural repertoire of cleistanthane diterpenoids from the Phyllanthaceae family and highlights their potential for anti-HIV drug discovery.