Seven previously undescribed sesquiterpenoids, designated as chloranholosins N‒T (1-7), including two acorane-type sesquiterpenoids (1-2), two lindenane-type sesquiterpenoids (3-4), and three eudesmane-type sesquiterpenoids (5-7), together with six known analogues (8-13) were isolated from the whole plants of Chloranthus holostegius var. Shimianensis. Their structures and absolute configurations were elucidated by a comprehensive method including the spectroscopic data, electronic circular dichroism calculations, and single-crystal X-ray diffraction. Compounds 5 and 6 are the first instances of eudesmane-type sesquiterpenoids with tigloyl and senecioyl substitutions at C-15, respectively. Additionally, the isolates were evaluated for their inhibitory activities against LPS induced nitric oxide production in RAW 264.7 macrophage cells. Among them, compounds 5 and 10 showed significant inhibitory activities with IC values of 9.35 ± 1.49 and 3.94 ± 0.69 μM, respectively. Compounds 1, 3, 4, 6, 9, and 12 showed moderate inhibitory activities with IC values from 10.48 to 35.36 μM, compared with that of the positive drug dexamethasone at 15.01 ± 1.33 μM.

Sixteen guaiane-type sesquiterpenoids, including four undescribed 4,5-seco-guaiane derivatives (1-4) and one undescribed guaiane (6), were isolated from the volatile oil of Pogostemon cablin. Their structures were determined using extensive spectroscopic evidence, including NMR, IR, HR-ESI-MS, and ECD calculations. Their anti-depressive effects were evaluated in corticosterone (CORT)-induced PC12 cells in vitro. Compound 5 (7-epi-chabrolidione A) was previously reported by our group to exhibit neuroprotective properties. However, the present study further demonstrated that compounds 1-5 had protective effects against CORT-induced injury in PC12 cells. Hoechst 33258 staining, high-content screening, and western blot analysis revealed that compound 5 activated the CaMKII/CREB/BDNF signaling pathway, thereby reducing apoptosis in CORT-injured PC12 cells and inhibiting intracellular calcium levels. Furthermore, compound 5 effectively rescued reserpine-induced depression and cognitive impairment in zebrafish in vivo. Collectively, these findings indicate that 4,5-seco-guaiane sesquiterpenoids from Pogostemon cablin (especially compound 5) possess potential anti-depressive activity.

Sacraoxides I-Q (1-9), nine undescribed cembranoids were isolated from the gum resin of Boswellia sacra as well as two known analogues (10 and 11). Their structures were determined by the analysis of 1D/2D NMR and HRESIMS data, quantum chemical calculations, modified Mosher's method, and a single-crystal X-ray diffraction study. Compounds 1 and 2 possess an unprecedented 15,16-dioxatricyclo[7.5.1.1]hexadecane polyether skeleton. Compound 3 has been identified as the first instance of nor-cembranoid bearing a 13-oxabicyclo[8.2.1]tridecane skeleton. Meanwhile, compounds 4 and 5 have been characterized as unusual 5,6-seco- and 7,8-seco-cembranoids. Plausible biosynthetic pathways were proposed from the naturally occurring cembranoids. The isolated cembranoids were evaluated for their activation towards transient receptor potential vanilloid 3 (TRPV3) by using calcium fluorescent assay and manual whole-cell patch-clamp technique. The results revealed that sacraoxide P (8) significantly activates TRPV3 at 50 μM. Molecular docking and molecular dynamic studies preliminarily undercover that compound 8 targets TRPV3 by forming hydrophobic interactions, hydrogen bond, and van der Waals forces with residues at the nexus of the linker domain, pre-S1 and TRP helices.

The first phytochemical investigation of the leaves of Fissistigma fulgens (Hook.f. & Thomson) Merr. led to the isolation and identification of five previously undescribed dihydrochalcone derivatives, including two dimeric dihydrochalcones, fissisfulgenones A and B (1 and 2), and three monomeric dihydrochalcones, fissisfulgenones C-E (3-5), along with three known compounds. Their structures were elucidated by spectroscopic analysis. The dimeric structure of fissisfulgenone A (1) was confirmed by single-crystal X-ray diffraction analysis using Cu-Kα radiation. The pure enantiomers of the scalemic mixtures of 1-3 were successfully resolved using chiral-phase HPLC, and their absolute configurations were determined by comparing experimental and calculated ECD spectra. Fissisfulgenones A (1), C (3), and D (4) were evaluated for biological activities, including cytotoxicity against human breast adenocarcinoma (MDA-MB231), human lung carcinoma (A549), human hepatocellular carcinoma (Huh7), and human colorectal adenocarcinoma (SW480 and HT29), antiviral activity against dengue virus (DENV), and nitric oxide production inhibitory activity in LPS-stimulated RAW 264.7 macrophages. Among them, fissisfulgenone C (3) exhibited the highest cytotoxicity against SW480 and HT29 cells with IC values of 40.6 and 68.0 μM, respectively, whereas fissisfulgenone D (4) showed cytotoxicity against MDA-MB231, A549, and Huh7 cell lines with IC values of 48.7, 38.3, and 21.2 μM, respectively. Notably, fissisfulgenone A (1) significantly reduced virus production in DENV-infected Huh7 cells at a sub-toxic dose of 50.0 μM. Regarding anti-inflammatory activity, fissisfulgenone C (3) exhibited strong nitric oxide inhibition, markedly reducing LPS-induced levels with an IC value of 5.27 μM and preserving normal macrophage morphology. Fissisfulgenone A (1) also showed similar effects at lower, non-toxic concentrations.

Five undescribed sesquiterpenes, including a dimeric sesquiterpene lactone with an unreported rare framework, neoversicolactone (1), and four sesquiterpenes, yunnadolins A-D (3-6), and a reidentified dimeric sesquiterpene lactone, versicolactone D (2), were obtained from the roots of Isotrema yunnanense, together with twelve known compounds. Their structures were established by spectroscopic analysis, single-crystal X-ray diffraction, and calculated electronic circular dichroism. Moreover, their analgesic and anti-inflammatory activities were evaluated in vivo and in vitro. All compounds exhibited significant anti-nociceptive activity, up to 59.5 % inhibition, except compounds 1 and 2. Meanwhile, compounds 6 and 15-17 showed better NO inhibition effects with IC values of 17.4 ± 2.9, 14.1 ± 2.0, 18.4 ± 0.3, and 12.8 ± 3.0 μM, respectively. Further investigation of the anti-inflammatory effect and mechanism shows that 6 exhibits a distinct anti-inflammatory effect by inhibiting the activation of MAPK/NF-κB pathways. Additionally, it also demonstrated effective anti-rheumatoid arthritis activity.

Genome mining of eight Kibdelosporangium genomes revealed previously untapped biosynthetic potential of diverse natural products. Among these, azicemicins, characterized by a unique aziridine moiety, drew considerable attention. Further genomic and metabolic analysis facilitated the identification of previously undescribed compounds from the K. phytohabitans XY-R10, including two angucyclines (1-2) and six azicemicins (3-8). Their structures were elucidated using comprehensive spectroscopic analyses, single-crystal X-ray diffraction, and electronic circular dichroism. Compounds 3-8 exhibited a distinctive ring-opened aziridine, likely originating from an acetylated aziridine precursor. Notably, compound 3 exhibited significant ferroptosis inhibition by decreasing RSL3-induced HMOX1 gene expression and upregulating GCH1 gene expression.

A phytochemical investigation of the roots of Premna herbacea Roxb. led to the isolation and characterization of ten abietane-type diterpenoids, including five previously undescribed compounds: premnaherbietones A and B (1 and 4), and premnaherbietanes A-C (5-7). Structural elucidation was achieved using comprehensive spectroscopic analysis (1D and 2D NMR, HRESIMS) and confirmed by electronic circular dichroism (ECD) calculations. The previously undescribed compounds possess diverse carbon skeletons, including quinonemethide abietane, 20(10 → 5)-abeo-abietane, and seco-4,5-abietane frameworks. Selected compounds (2, 3, 9, and 10) were evaluated for their α-glucosidase inhibitory and cytotoxic activities. Salvilenone (10) exhibited α-glucosidase inhibition with an IC value of 34.6 μM, significantly outperforming the positive control, acarbose (IC = 190.4 μM). In silico molecular docking revealed that compound 10 interacts with key active site residues of α-glucosidase through hydrogen bonding and π-π interactions, supporting its inhibitory potential. Bharangin (2) demonstrated notable cytotoxicity against A549 human lung adenocarcinoma cell lines with an IC value of 19.4 μM. A plausible biosynthetic pathway for the isolated diterpenoids is also proposed.

Eight previously undescribed cyclopentanoid monoterpene glycosides, paedosides A-H (1-8), and 19 known analogues were isolated from the aerial parts of Paederia foetida L. The structures of these compounds, especially their absolute configurations, were unequivocally established by comprehensive spectroscopic analysis, various quantum chemical calculations, and single-crystal X-ray diffraction analysis. Compound 1 contains a thiocarbonate group, with the aglycone C-1 linked via O-glycosidic bonds to both sugar C-1' and C-6', thereby forming a 7-membered ring. Compounds 2-4 feature a skeleton with three ortho-fused five-membered rings. Proposed biosynthetic pathways for compounds 1-4 are shown in Scheme 1. Compounds 1-27 were tested for cytotoxicity, hepatoprotective activity, and inhibitory effects on NO production in LPS-activated microglia, but all were inactive (IC > 10 μM or the compounds showed no significant cell protection at 10 μM).

Ten previously undescribed nor-clerodane diterpenoids, teuvinoids A-J (1-10), were isolated from the whole plants of Teucrium viscidum. Comprehensive structural elucidation, including unambiguous determination of absolute configurations, was accomplished using spectroscopic analysis, electronic circular dichroism, and single-crystal X-ray diffraction. Teuvinoids A (1) and B (2) are particularly noteworthy for featuring an unusual 2,3,4,5-tetrahydroxylated tetrahydrofuran moiety. Compounds 1 and 2 exhibited anti-hepatic fibrosis effects in TGF-β1-induced LX-2 hepatic stellate cells, as demonstrated by downregulation of key fibrotic biomarkers including fibronectin, collagen I, and α-smooth muscle actin.

The genus Sedum is recognized for its diverse biological activities; however, the potential anti-depressive properties of Sedum kamtschaticum Fisch. & C. A. Mey. and S. takesimense Nakai, along with their bioactive constituents, remain unexplored. Therefore, this study was conducted to profile the phytochemicals of SK and ST and evaluate their antioxidant, anti-aging, and anti-monoamine oxidase potential in vitro. The 70 % ethanolic extracts of SK and ST showed radical-scavenging, anti-aging, and monoamine oxidase inhibitory activities. Through ultra-performance liquid chromatography-electrospray ionization-high-resolution quadrupole time-of-flight mass spectrometry, three phenolic acids, 12 phenolic glucosides, one ellagic acid, and 14 flavonoids were identified. Notably, four flavonoids were reported for the first time: gossypetin-3,5-di-O-β-d-glucopyranoside-8-O-β-d-xylopyranoside (7), gossypetin-3,5-di-O-β-d-glucopyranoside-8-O-α-l-arabinopyranoside (8), herbacetin-3,5-di-O-β-d-glucopyranoside-8-O-β-d-xylopyranoside (10), and herbacetin-3,5-di-O-β-d-glucopyranoside-8-O-α-l-arabinopyranoside (11), as characterized through mass spectrometry, ultraviolet, electronic circular dichroism, and nuclear magnetic resonance analyses. The biological activity assay revealed that most flavonoids exhibited significant antioxidant and lifespan-extending activities. Moreover, their aglycones-gossypetin and herbacetin-exhibited potent and selective inhibition of monoamine oxidase-B. These findings suggest that gossypetin- and herbacetin-based flavonols, the main active compounds in S. kamtschaticum Fisch. & C. A. Mey. and S. takesimense Nakai, may be employed as lead structures in the development of functional foods or drugs to prevent diseases caused by aging and neurotransmitter imbalances.

Six aloe-emodin derivatives, anthractones A-F (1-6), along with the known compound N-phenethylacetamide (7), were obtained from the biotransformation of aloe-emodin by Fusarium citricola HPU-L64, a fungus isolated from the Yellow River wetland. The structures of 1-7 were elucidated by comprehensive analysis of NMR spectroscopy, HRESIMS data, and X-ray crystallography. Anthracetones possess a distinctive fused 6/6/6/6/6 pentacyclic ring system, contrasting with the typical 6/6/6 tricyclic scaffold of previously reported aloe-emodin derivatives. Anthractone D exhibited enhanced antibacterial activity against Bacillus subtilis (MIC = 2.6 μM), demonstrating greater potency than aloe-emodin (MIC = 14.8 μM).

Natural products have made important contributions to the fight against human diseases, including infectious diseases. However, research on natural products still faces many challenges, such as technical barriers to in-depth screening of biomaterials. The genus Keetia is a valuable source of flavonoids, although the specific types and complete profile of most of its species remain undisclosed. The flavonoid profile of the methanol crude extract and derived extracts from Keetia venosa (Oliv.) Bridson leaves was unveiled using a feature-based molecular networking-guided fractionation strategy. This approach enables a comprehensive exploration of the plant chemical diversity, including the detection of minor components often missed out during traditional isolation and characterisation. Four previously undescribed kaempferol glycosides were isolated, together with sixteen known compounds. Their structures were elucidated by examining their physical, mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopic data. Fourteen additional already reported compounds were putatively identified from a comparative analysis of their MS features with similar analogues available in well-known databases. Furthermore, crude extract, extracts and isolated compounds were evaluated for their antibacterial activity against both Gram-positive and -negative bacteria, including Salmonella enterica, Pseudomonas aeruginosa and Klebsiella pneumoniae. The n-butanol extract, kotschyanoside A, and kaempferol 7-O-α-L-rhamnopyranoside displayed promising antibacterial activity against Gram-negative bacteria such as S. enterica, P. aeruginosa and K. pneumoniae with MIC values of 3.9-62.5 μg/mL.

Chemical investigation of the cold-seep-sourced fungus Talaromyces trachyspermus CS-106 resulted in the isolation of six previously undescribed phenolic glucopyranosides, talarosides A-F (1-6), two previously undescribed phenolic cysteine derivatives, talacysteines A and B (7 and 8), and five known congeners 9-13. The results from in vitro bioassay indicated that compounds 3, 6, and 9 displayed potent activities against several tested phytopathogenic fungal strains. Specially, the chloroquinone derivative, 2-chloro-5-methoxy-3-methylcyclohexa-2,5-diene-1,4-dione (compound 9), exhibited a broad spectrum of fungicidal activity against Alternaria brassicae, Colletotrichum gloeosporioides, Fusarium graminearum, and F. oxysporum, with MIC values ranging from 0.5 to 4 μg/mL. In vivo testing on tomato fruits showed that 9 displayed considerable curative efficacy against F. oxysporum. Both scanning electron microscopy and cryo-SEM analysis indicated that 9 possessed a strong ability to destroy the surface morphology of mycelia and seriously interfere with the growth of the fungal pathogen. Compound 9 also exhibited pronounced succinate dehydrogenase (SDH) inhibitory activity from the in vitro SDH inhibitory assay. Molecular docking simulations were performed to explore the intermolecular interaction of 9 with SDH enzyme from F. oxysporum. These findings presented a promising lead compound such as compound 9 for the discovery of SDH inhibitor as antifungal agents.

Sixteen previously undescribed sesquiterpenoid glycosides (1-16), bearing eudesmane-type (1-4) and cadinane-type skeletons (5-16), were obtained from the stems of Cissampelopsis spelaeicola. The structural elucidation and absolute configuration assignment of compounds 1-16 were accomplished through multiple spectroscopic analyses, computed ECD/NMR, and X-ray crystallography. Furthermore, anti-neuroinflammatory effects of all isolates were assessed by NO inhibition in LPS-stimulated BV-2 microglia. Compounds 12 and 14-16 exhibited potent NO inhibitory effects (IC = 5.62-19.29 μM), outperforming the positive control L-NMMA (IC = 21.20 ± 0.57 μM). Further evaluation revealed that compound 15 (IC = 5.62 ± 0.37 μM) effectively attenuated LPS-stimulated overexpression of IL-1β, IL-6, iNOS, and TNF-α in BV-2 cells.

Three previously undescribed citrinin dimers, penicitrones A-C (1-3), and one previously unreported tetramic acid derivative, penipyrrone A (4), along with fourteen previously known compounds (5-18) were isolated from the crude extract of the mangrove-derived fungus Penicillium citrinum WHUF05149. The structures of compounds 1-4 were elucidated through comprehensive spectroscopic analyses and their absolute configurations were determined by the modified Snatzke's method and ECD calculations. Compound 3 demonstrated moderate antifungal activities against three strains of Cryptococcus gattii (3284G14, R265 and 3271G1). Compound 15 displayed antibacterial effects against Bacillus subtilis, Bacillus paranthracis and methicillin-resistant Staphylococcus aureus (MRSA) along with anti-biofilm effects against these pathogens. In addition, compound 15 exhibits anti-MRSA activity by disrupting cell membrane integrity, inducing the leakage of intracellular constituents and reducing intracellular ATP levels.

Lobane- and prenyleudesmane-type diterpenoids represent structurally unique and biologically diverse natural products, predominantly isolated from soft corals in the genera Lobophytum and Sinularia. This review comprehensively covers the literature from 1978 to 2025, isolation methods, structural elucidation, biological evaluations, and proposed biosynthetic pathways. Based on their reported bioactivities, the compounds were systematically classified, and their potential biosynthetic pathways were proposed. Additionally, a structure-activity relationship (SAR) analysis was conducted to further elucidate the functional groups responsible for their anti-inflammatory, toxicity and anti-fungal properties. To address the challenge of insufficient supply for biological assays, recent total syntheses of representative compounds were also highlighted, providing alternative solutions for future drug discovery and mechanistic studies. This review not only consolidates current knowledge but also provides perspectives for future biosynthetic studies and the development of marine-derived diterpenoids as therapeutic leads.

Emerging evidence indicates that metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with gut microbial dysbiosis and disruption of the intestinal mucosal barrier function. Scutellaria baicalensis extract (SBE) has anti-inflammatory and hepatoprotective effects. In this study, the investigation conducted explored whether SBE can alleviate MASLD and the possible mechanism involving the gut-liver axis. Qualitative and quantitative analyses of SBE using UPLC-Q-Orbitrap-MS and UPLC-QqQ-MS revealed that the major component of SBE was Baicalin, which accounted for approximately 94.12 %. A mice model of MASLD was established by feeding mice a high-fat diet (HFD) and administering SBE intragastrically. The effects of SBE on liver biochemical parameters, intestinal histopathology, intestinal integrity, and gut microbiota were evaluated. SBE restored the expression of TJs in the intestine and ameliorated the increased permeability of the intestinal mucosa induced by the HFD, thereby enhancing the function of the intestinal barrier. In addition, SBE altered the composition of the gut microbiota in mice with MASLD, decreasing the abundance of Helicobacter and increasing the abundance of Bacteroidota. The results of fecal metabolomics showed that medium-dose SBE significantly upregulated the levels of 11 metabolites, including cholic acid, and downregulated the levels of 13 metabolites, including allantoic acid. Moreover, SBE may reverse HFD-induced hepatic steatosis in mice, suggesting that SBE could serve as a potential therapeutic strategy for MASLD.

The genus Cryptocarya is renowned for producing characteristic content of alkyl or alkenyl α-pyrones with intriguing stereochemical complexity and diverse pharmacological properties. In this study, four unprecedented dimeric alkenyl α-pyrones featuring an unusual pentacyclo[8.4.2.0.0.0]hexadecane core scaffold, named crypcalcones A-D (1-4), were isolated from Cryptocarya calcicola, an unexplored endemic Chinese species. Their structures were established through a combination of extensive NMR spectroscopic analysis, single-crystal X-ray crystallography, and electronic circular dichroism (ECD) spectroscopy. This is the first report of α-pyrone dimers from the genus Cryptocarya, expanding the known structural diversity of α-pyrones. Compounds 1-4 are proposed to arise from an initial 8π-6π e electrocyclization of a polyene α-pyrone precursor, followed by an intramolecular [4 + 2] cycloaddition. Notably, these compounds demonstrated selective cytotoxicity against HCT-116 colorectal cancer cells, with IC values ranging from 2.02 to 7.00 μM.

A phytochemical investigation into the low-polarity fraction of Artemisia capillaris facilitated the isolation of twenty-two natural compounds. These compounds, termed Artemicapillasin O-X (1a/1b-4a/4b, 5a, 6a/6b-8a/8b, 9a, 10b, 11b, 12a, and 12b), were identified as previously undescribed 2,3-dihydrobenzofuran (2,3-DHB) derivatives. Their structures were elucidated using NMR analysis, which included coupling constant analysis, chiroptical characterization (electronic circular dichroism [ECD] and optical rotatory dispersion [ORD]), computational approaches (DP4+ probability analysis and dJ/iJ-DP4 protocol), and X-ray diffraction. Subsequent analyses identified that for 2,3-DHB derivatives featuring only two chiral centers at C-2 and C-10, the determination of absolute configuration relies on coupling constants, Cotton effects in CD spectra, and ORD measurements. A novel rule, termed Chen's Rule, was established to facilitate rapid discrimination of stereochemical relationships between H-2 and H-10 in 2,3-DHB derivatives. This rule prompted structural revisions of similar compounds reported in the prior literature. Furthermore, all compounds were assayed at a concentration of 100 μM for their inhibitory activity against xanthine oxidase (XOD) in vitro, where compounds 7a and 7b displayed moderate effects, whereas the others demonstrated negligible activity.

Chemical investigation of the plant pathogen Alternaria solani, associated with Hypoestes phyllostachya, led to the isolation of alternsolain A (1), an unprecedented alternariol-zinnol hybrid, and alternsolains B-G (2-7), six previously undescribed zinnol derivatives containing two pairs of enantiomers, (±)-alternsolains E (5) and F (6), along with five known compounds (8-12). Their structures were elucidated using comprehensive spectral analysis, single-crystal X-ray diffraction, NMR computational techniques, and electronic circular dichroism calculations. Compound 1 possessed a previously unreported carbon skeleton formed through the linkage of alternariol and zinnol via C-8-C-4' bond. Compound 2 featured a rare dimeric skeleton composed of two zinnol units connected by an ether bond. Plausible biosynthetic pathways for 1 and 2 were also postulated. Additionally, compound 9 showed potent cytotoxic activities against HL-60, MDA-MB-231, and SW480 human cancer cell lines, with IC values of 10.73 ± 0.08, 19.40 ± 0.97, and 29.72 ± 1.61 μM, respectively. These results enrich the diversity of zinnols and may provide active compounds for the development of new anticancer drugs.