Fourtheen undescribed oleanane-type triterpenoids (Sabialimons S-Z), including five nortriterpenoids (1-5) and nine normal triterpenoids (6-14), along with five previously described analogs (15-19) were isolated and characterized from the stems of Sabia limoniacea. Their structures were fully elucidated via extensive spectroscopic analyses, including 1D and 2D NMR, HRESIMS. Compounds 1-3 are oleanane-type triterpenoids which the rings A are broken and the carbons of position 2 are absent to form the five-membered ring-A contracted nortriterpenoids, resulting in the establishment of a 5/6/6/6/6 pentacyclic skeleton. Compounds 4 and 5 represent the interesting variation in which the C-1/C-3 bonds have been oxidatively cleaved to generate ring-A-seco triterpenoids, leading to establishment of a 0/6/6/6/6 tetracyclic skeleton. Biological evaluation revealed that compounds 9 and 10 can inhibited nitric oxide production in lipopolysaccharide stimulated RAW264.7 cells with IC values of 36.40 and 36.52 μM, respectively.

Glucagon-like peptide-1 (GLP-1) is a fascinating target for the treatment of diabetes to avoid hypoglycemia. Kaempferiae Rhizoma (KR), the dried rhizomes of Kaempferia galanga, is a famous pungent medicine used for activating Qi, warming interior, removing digestion and relieving pain in China. In order to characterize the antidiabetic effects of KR, 21 previously undescribed O-linked diarylheptanoid dimers, kaemgalangins A-A (1-4), B-B (5-17) and C-C (18-21), were isolated from the ethyl acetate fraction. Their structures were determined by extensive spectroscopic analyses, quantum computation and chemical methods. All compounds were tested for their GLP-1 stimulating effects on NCI-H716 cells, most of which showed obvious activity representing a new type of antidiabetic constituents. Especially, compounds 1, 2 and 16 showed spectacular GLP-1 stimulation with promoting rates of 146.6±31.1%, 159.0±16.6% and 142.9±2.7%, more potent than the positive control. Mechanism study manifested that kaemgalangin A (1) promoted GLP-1 secretion through up-regulating the mRNA expression of Gcg and Pc1/3, and the phosphorylation of PKA and CREB, but independent on TGR5 and GPR119 receptors. Furthermore, network pharmacology analysis suggested that the GLP-1 secretion induced by 1 was closely related to MAPK and PI3K-Akt signaling pathways. This investigation first revealed that KR was rich in diarylheptanoid dimers with GLP-1 promoting effects, which provides scientific basis for the antidiabetic application of K. galanga.

Coumarins constitute one of the most substantial classes of secondary metabolites, characterised by a fundamental α-benzopyranone skeleton, which serves as an overarching nomenclature for o-hydroxycinnamyl lactone moieties. These chemical constituents are widely distributed in various plant species. Based on the nature and loci of their substituents, these compounds can be further classified into simple coumarins, furanocoumarins, pyranocoumarins, isocoumarins, biscoumarins and other coumarins. Contemporary pharmacological research has revealed that coumarins exhibit a spectrum of properties, including antibacterial, antioxidant, anticancer, anti-inflammatory and hypoglycaemic activities. Owing to their diverse of structures and pharmacological actions, coumarins are widely used in cuisine, cosmetics and pharmaceutical industries. An extensive body of scholarly literature has been produced in this domain, although a notable paucity in the compilation and updating of references has been identified since 2019. Herein, the chemical structures and pharmacological activities of coumarins reported for the first time between 2019 and 2024 were systematically summarised. In total, 220 scholarly articles involving 574 coumarins reported for the first time in plants were included in this review. In addition, the biosynthetic pathways of some common types of coumarins (simple coumarins, furanocoumarins, and pyranocoumarins) are also preliminarily summarised in this paper. Meticulously analyzing and synthesising the published literature will lay a solid foundation for further investigation and extensive utilisation of coumarin derivatives.

Twelve undescribed meroterpenoids possessing bicyclic polyprenylated acylphloroglucinol (BPAP) scaffold, (±)-lancasternoids A-D and lancasternoids E-H, together with fourteen known analogues, were isolated from Hypericum lancasteri (Hypericaceae) and structurally characterized. (±)-Lancasternoids A-D are the first examples of bicyclo[3.2.1]octane-type BPAP meroterpenoids present as enantiomeric pairs, while (±)-lancasternoids A-C incorporate an unprecedented 5-oxatetracyclo[7.5.1.0.0]pentadecane system. Lancasternoids E-H are two pairs of epimers with [3.3.1]-type BPAP scaffold. Some of the isolates showed inhibition in hypoxia-inducible factor-1α (HIF-1α) responsive element (HRE) luciferase assay, and uraloidin A further decreased the lipopolysaccharide (LPS)-induced pro-inflammatory factor IL-1β expression level in RAW 264.7 cells.

Twelve previously undescribed dihydroagarofuran sesquiterpenes, hypogricins I-XII (1-12), were isolated from the fruits of Tripterygium hypoglaucum, along with 14 known dihydro-β-agarofuran-type sesquiterpenoids. The structural elucidation of these previously undescribed compounds was achieved through using comprehensive spectroscopic analysis, single-crystal X-ray diffraction studies, and electronic circular dichroism (ECD) calculations. All the compounds were evaluated for their effects on HaCaT cell viability and their potential to inhibit tumor necrosis factor α (TNF-α)- and interleukin 17A (IL-17A)-induced inflammation. Biological assays revealed that compounds 2, 7, 8, 9, 10, 12, 13 and 26 at a concentration of 25 μM downregulated the expression of the relevant inflammatory factors S100 calcium-binding protein A8 (S100A8), defensin beta 4 (DEFB4A), and C-C motif chemokine ligand 2 (CCL-2) induced by TNF-α and IL-17A in HaCaT cells to varying extents. Furthermore, this work presents initial findings indicating that petroleum ether extracts from fruits exhibit low toxicity and significant anti-inflammatory activity. This study also includes the first evaluation of the cytotoxicity and anti-inflammatory effects of sesquiterpenoids on keratinocytes, thereby providing a scientific basis for the treatment of skin inflammation.

Eight previously undescribed epipolythiodioxopiperazines (ETPs), asperstrins A-H (1-8), and three known analogues, dethiosecoemestrin (9), secoemestrin C (10), and secoemestrin D (11), were isolated from the endophytic fungus Aspergillus nidulans. Their structures and configurations were elucidated based on HRESIMS, one-dimensional and two-dimensional nuclear magnetic resonance spectroscopic data, electronic circular dichroism calculations, and X-ray crystallography. Asperstrins A-C (1-3) represent the first examples of O-methyl or O-ethyl derivatives of emestrin-type ETPs, respectively. Asperstrin C (3) showed moderate cytotoxic activities with IC values ranging from 3.00 to 4.60 μM; asperstrins F (6) and G (7) displayed potent butyrylcholinesterase inhibitory activities with IC values of 9.49 ± 0.51 and 2.03 ± 0.55 μM, respectively.

Seven previously undescribed triterpenoid saponins, oleiferasaponins G-G (1-7), along with two known congeners (8 and 9) were isolated from seeds of Camellia oleifera Abel. Their structures were determined by extensive spectroscopic data. All isolated compounds are decorated with an aglycone and tetrasaccharide moiety. Compounds 1-5 were characterized by an uncommon acylation at C-16 instead of hydroxylation among the identified triterpenoid saponins in Camellia plants. Importantly, compounds 6-9 exhibited excellent antiproliferation effects against HCT-116, HL-60 and HepG2. According to preliminary structure-activity relationship investigations, a free hydroxyl group at the C-16 position of saponins was beneficial for their antiproliferation activity. Interestingly, compounds 1-5 displayed neither antiproliferation nor hemolytic activity, which suggests that the hemolytic and antiproliferation activity of the test saponins exhibit a relatively consistent pattern in their structure-activity relationships.

Andrograpalides A-N (1-14), fourteen previously undescribed ent-labdane-type diterpenoids, together with a previously undescribed naturally occurring diterpenoid (15) and two known analogues (16-17), were isolated from the leaves of Andrographis paniculata. Their structures were unambiguously elucidated via extensive spectroscopic analysis, electronic circular dichroism analysis, and X-ray crystallographic studies. Structurally, compounds 1-8 and 16 are rare cases of 19-nor labdane-type diterpenoids with an unusual C carbon skeleton. Notably, compounds 1 and 2 feature an unusual hydroperoxy group at C-4. In addition, the isolated compounds were evaluated for their anti-inflammatory effects in lipopolysaccharide-induced RAW 264.7 cells. Compound 12 exhibited the most significant anti-inflammatory activity, as indicated by the lowest nitric oxide production rate, and the remarkable reduced protein expression of inducible nitric oxide synthase and cyclooxygenase-2.

Nine undescribed meroterpenoids, named ircindrimanes A-I (1-9), were isolated from the marine sponge Ircinia sp. collected in the South China Sea. Their planar structures were determined by NMR, HRESIMS, UV spectroscopic data. The absolute configurations were established through DP4+ analysis, ECD calculations and single crystal X-ray diffraction. Biological evaluation indicated that compounds 7 and 8 exhibited moderate to strong cytotoxic activities towards several cancer cell lines.

Verticillins, epipolythiodioxopiperazine alkaloids that were first described over 50 years ago, have undergone extensive cytotoxic and pharmacological evaluations over the last decade. However, of the 27 verticillin analogues in the literature, the chemistry of verticillin D, which has two additional secondary hydroxy moieties, relative to verticillin A, has remained largely unexplored since its discovery in 1999. With the goal of advancing our understanding of verticillin D, there were three main objectives with this study: improving production, streamlining purification, and assigning absolute configuration via X-ray crystallography. To begin, the production of verticillin D was analyzed across seven fungal strains, and the top producer was further assessed under two fermentation conditions. Clonostachys rosea (strain MSX51257) biosynthesized the highest amount of verticillin D, with production peaking between 15 and 25 days on rice media. Interestingly, in contrast to similar studies that yield verticillin A, the biosynthesis of verticillin D was not accompanied by a suite of structurally related verticillin analogues. As such, the purification of verticillin D was more rapid and could be accomplished without the use of HPLC. These materials were used, in part, to determine the absolute configuration of verticillin D via X-ray crystallography, allowing for assignment of the asymmetric centers at both the 13 and 13' positions as R, which has never been accomplished. This is only the third report of an X-ray structure of a verticillin analogue.

Sixteen indole alkaloids were isolated from the hook-bearing stems of Uncaria rhynchophylla (Rubiaceae family), including seven undescribed ones, uncarialines F-L (1-5, 7, and 8), and a naturally occurring alkaloid, 3-epicorynanthine (6). Among them, alkaloids 1 and 2 were identified as rare quaternary ammonium alkaloids, and alkaloid 7 exhibited an unprecedented indole alkaloid framework. Their structures were characterized by a comprehensive analysis of NMR, MS, ECD and single-crystal X-ray diffraction. Notably, alkaloid 5 demonstrate potent inhibitory activity against α-glucosidase, with an IC value of 18.45 ± 0.77 μM. Furthermore, the inhibitory kinetics of α-glucosidase revealed that alkaloid 5 belong to the mix inhibition type. Molecular docking analysis showed that alkaloid 5 possessed superior binding affinity with α-glucosidase (-10.7 kcal/mol).

A systematic investigation of the whole plant of Juncus alatus Franch. et Sav. resulted in the identification of seven novel phenanthrene dimers named alatusins A-G (1-7) and 11 undescribed monomers (8-9, 11-14 and 18-22), in addition to six known analogues (10, 15-17 and 23-24). The structures of new compounds were fully characterized through comprehensive analysis of HRESIMS, 1D and 2D NMR spectroscopic data, single-crystal X-ray diffraction experiment, and time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculation. Compounds 1-4 feature a methylene tethering two phenanthrene/9,10-dihydrophenanthrene monomers, while 5 possesses an undescribed linkage of C-5/C-5'. Compound 6 was constructed by forming a six-membered ring spiroed at C-5'. Compound 7 possesses a furan ring to connect two monomeric halves. All the connection patterns have never or rarely been reported before. The racemates of compounds 5, 6, 7, and 14 were separated via chiral HPLC, and their stereochemistry was characterized on-line by circular dichroism (CD) spectroscopy (LC-CD coupling) and comparison of the calculated and experimental ECD spectra. Most compounds were tested for their inhibition of NO on LPS stimulated murine RAW 264.7 cells. Compounds 13 and 18-21 exhibited potent inhibitory activity, with IC values of 4.11 ± 0.59, 2.89 ± 0.90, 5.98 ± 1.86, 5.77 ± 1.36, and 5.68 ± 0.14 μM, respectively. In the ELISA assays, compound 18 significantly redused the production of pro-inflammatory cytokines, including TNF-α, IL-6, and MCP-1, in LPS-stimulated macrophages. Possible biosynthetic pathways of new dimeric compounds 1-7 were proposed.

A total of eight previously undescribed pentasaccharide resin glycosides, named ipomofins I-VIII (1-8), along with five known ones (9-13), were isolated from the whole plants of Ipomoea biflora. Their structural elucidation was achieved through a comprehensive application of spectroscopic and chemical techniques. All these resin glycosides were characterized as partially acylated pentasaccharides, originating from operculinic acids A or D, containing l-rhamnose, d-glucose, d-xylose or d-fucose units, and 11S-hydroxyhexadecanoic acid serving as the aglycone. Notably, compounds 1 and 2 represent the first resin glycosides with operculinic acid D as their core structure, while compounds 3 and 4 are the first derivatives of operculinic acid A featuring a 23-membered ring. Compounds 1, 2, and 4-6 exhibited apparent cytotoxic effects against certain cancer cell lines. Particularly, compound 5 demonstrated the ability to impair colony formation, reduce the proportion of EdU-positive cells, and enhance the expression of proteins related to endoplasmic reticulum stress (ERS) in HCT-15 cells, indicating that its cytotoxicity might be driven by the activation of ERS pathways. Collectively, this research identified 13 resin glycosides from I. biflora, including eight previously undescribed compounds, with compound 5 emerging as a potential anticancer agent due to its induction of ERS.

Four undescribed meroterpenoids, peniclactone D (1) and penichrodrimanins A-C (5-7), along with five known analogues (2-4, 8, and 9), were isolated from the fungus Penicillium sp. GDGJ-285. Their structures and absolute configurations were established on the basis of spectroscopic analyses and single-crystal X-ray diffraction. Compound 1 represents a highly oxygenated 6/5/6/5/5/5 polycyclic ring system, and 7 is a chrodrimanin-type meroterpenoid with a rare ether linkage between rings A and B via C-3 and C-9. Compound 5 exhibited notable inhibitory effect on nitric oxide (NO) production in LPS-induced RAW 264.7 cells, with the IC value of 18.50 ± 1.26 μM compared to dexamethasone (33.61 ± 4.45 μM). The further investigation indicated that 5 could suppress LPS-induced TNF-α, IL-1β, and iNOS expression via inhibition of NF-κB signaling pathway.

The mushroom Tricholoma matsutake is renowned in East Asia for its distinctive flavour and nutritional value. However, its chemical composition remains largely unexplored. This study aimed to identify potential lead compounds from wild mushrooms, with a focus on the specialised metabolite profiles of T. matsutake. As a result, 10 rare (-)-(14-nor)longifolane-type sesquiterpenoids, designated matsulongifolins A-J (1-10), were isolated from the fruiting bodies of T. matsutake collected in the Tibet Autonomous Region, China. Matsulongifolins G (7)/H (8) and I (9)/J (10) were obtained as inseparable mixtures. The structures, including their absolute configurations, were determined through extensive spectroscopic analyses, single-crystal X-ray diffraction and electronic circular dichroism calculations. Matsulongifolin A (1) features a unique, rigid, cage-like 5/6/7/5/5 polycyclic system, while matsulongifolin B (2), an anhydride derivative, contains a 5/6/7/5 tetracyclic ring system. Matsulongifolins I (9) and J (10) are each distinguished by a succinyl group, a rare feature typically found in bacterial natural products. Bioassay results revealed that matsulongifolins B-F (2-6) exhibited weak inhibitory activity against Staphylococcus aureus subsp. aureus. This study represents the first identification of longifolane-type sesquiterpenes from a mushroom source and advances the understanding of the specialised metabolites present in T. matsutake.

This study reports the isolation of 11 previously undescribed sesquiterpenoids from the root bark of Lycium chinense Mill, including a 1,10-secoeudesmane-type sesquiterpene (1), a 9,10-secoeudesmane-type sesquiterpene (2) and nine rearranged eudesmane sesquiterpenes (3-11). Structures elucidation of these compounds was established using 1D/2D NMR, electronic circular dichroism calculations along with DP4 probability analysis, and X-ray diffraction analysis of single crystals. Lyciiterpenoid E (1), a eudesmane sesquiterpenoid, is characterised by a bond cleavage between C-1 and C-10 while, lyciiterpenoid F (2) exhibits a bond cleavage between C-9 and C-10. All compounds (1-11) were evaluated for neuroinflammatory inhibitory activity in LPS-induced BV-2 cells. Among them, compound 5 exhibited potent anti-neuroinflammatory effects, with an EC of 2.1 ± 0.07 μM, exceeding the effectiveness of curcumin, a standard positive control. Furthermore, compound 5 may inhibit the synthesis of LPS-induced TNF-α and IL-1β/6 in BV-2 cells while downregulating iNOS and COX-2 gene and protein expression in a dose-dependent manner. This study provides the first evidence of natural anti-neuroinflammatory agents from the root bark of L. chinense for the treatment of neurodegenerative disorders.

Changes in the contents of coumarin and its precursors were monitored during the post-harvest drying process of Galium odoratum (L.) Scop. (Rubiaceae) to get scientific support for the traditional preparation of "Maibowle" (an alcoholic beverage made of white wine, sparkling wine, and G. odoratum shoots and sometimes additional ingredients) in Germany, which involves pre-drying of the freshly harvested herb for two to 24 h. The contents of coumarin, cis-melilotoside, and trans-melilotoside in G. odoratum were determined over a period of 72 h after harvesting using quantitative UHPLC-DAD analysis. The drying process was finished after 48 h, and afterwards no further weight loss of the plant material was detectable. During this 48-h-period, trans-melilotoside seemed to isomerize gradually to cis-melilotoside. For the first time, we demonstrated that coumarin decreases during drying due to sublimation, which supports the use of fresh or minimally air-dried material in traditional recipes with specific drying times. Moreover, we demonstrated for the first time that reduction in coumarin during prolonged periods of drying is explained by sublimation of coumarin. Flavonoid glycosides, quercetin 3-O-[α-l-rhamnosyl-(1 →6)-β-d-glucosyl]-7-O-β-D-glucoside 12 and kaempferol 3-O-[α-l-rhamnosyl-(1→6)-β-d-glucosyl]-7-O-β-D-glucoside 13 as well as coumarin precursors cis-melilotoside 9 and trans-melilotoside 10 were for the first time isolated from G. odoratum. Moreover, monotropein 1, geniposidic acid 2, scandoside 3, asperulosidic acid 4, deacetylasperuloside 5, asperuloside 6, 3-O-caffeoylquinic acid (neochlorogenic acid) 7, and 5-O-caffeoylquinic acid (chlorogenic acid) 8, which were already known from this source species, were isolated from a methanolic extract of G. odoratum.

The stems of Dendrobium chrysotoxum Lindl are used as medicinal herbs and for nutraceutical beverages and functional food products. In order to obtain an in-depth understanding of the bioactive compounds in the stems of D. chrysotoxum Lindl, an exhaustive chemical examination was carried out. A total of 20 undescribed compounds (1-20) along with 40 known ones (21-60) were isolated. The structures of 1-20 were elucidated based on spectroscopic analysis and theoretical quantum calculations. The unreported compounds consist of 7 spirophenanthrenes (1-7), 4 diphenanthrenes (8-11), 1 9,10-dihydrophenanthrene derivative (12), 1 phenanthropyran (13), 2 monophenanthrenes (14 and 15), 1 dimeric bibenzyl (16), and 3 bibenzyls (17-20). Six compounds 1b, 3b, 4a, 4b, 8, and 16 exhibited remarkable cytotoxic activity against HCCLM3 cancer cells with IC values of 1.68 μM-6.60 μM. Compounds 10, 15, and fimbriadimerbibenzyl D displayed significant anti-pulmonary fibrosis with IC values of 1.82 ± 0.02 μM to 3.68 ± 0.03 μM.

Using together HSQC NMR-guided fractionation and an invivo screening zebrafish model for bioactivity-guided fractionation, four previously undescribed butenolides, perbutanolides A-D (1-4), were isolated from the marine-derived Aspergillus sp. NBU4698. HSQC NMR-based Small Molecule Accurate Recognition Technology (SMART 2.0) was used to simplify the process of discovering and characterizing these structurally related natural products. The structures and absolute configurations were determined by HRESIMS, NMR, polarimetry, and ECD calculations. All the compounds were evaluated for multidrug resistance (MDR) reversing activity in a zebrafish model, and compound 1 induced significant MDR reversal activity by inhibiting PXR-regulated efflux transporters. In addition, compounds 1-3 exhibited a moderate inhibitory effect on pro-inflammatory mediators in RAW264.7 macrophage cells. This is the first report of MDR reversal activity for marine-derived fungal butenolides. These results provide new insights for designing and developing probes and new drugs that can inhibit MDR.

Salcastaniols A-G (1-7), seven undescribed diterpenoids, together with 29 known ones, were isolated from Salvia castanea Diels f. tomentosa Stib. Their structures, including absolute configurations, were elucidated by NMR spectroscopy analysis, ECD experiments and quantum chemical calculation. The in vitro cholinesterase inhibitory activities of all isolates were evaluated using modified Ellman's method. Ten compounds exhibited AChE inhibitory activities with IC values ranging from 0.15 ± 0.01-5.36 ± 0.25 μM. Among them, compound 1 significantly inhibited in vitro AChE. Furthermore, 1 had the highest affinity (-7.15 kcal/mol) in comparison to the positive control (galantamine, -6.00 kcal/mol) with activity site of AChE in molecular docking experiment. These studies supported the possibilities for the development of new anti-Alzheimer's drugs.

Two rearranged prenyllabdane sesterterpenoids nudiflorawus A-B (1-2) with a previously unreported carbon skeleton, and five undescribed 3,4-seco-labdane diterpenoids, nudiflorawus C-G (3-7), along with two known diterpenoids (8-9), were isolated from the leaves of Callicarpa nudiflora. Compounds 1-2 exhibited the first example of 3,4-seco-prenyllabdane sesterterpenoids with a unique six-membered ring in the side chain. Their structures were established via various spectroscopic methods. NMR calculations with DP4+ analysis and ECD were further adopted to confirm their relative and absolute configurations. Compound 6 showed significant Zika virus (ZIKV) inhibitory activity with an EC value of 25.35 ± 0.742 μM. Western blot, quantitative real-time PCR, and immunofluorescence results further indicated that compound 6 could block ZIKV infection and replication by inhibiting the expression of ZIKV-envelope protein.