Six previously undescribed alkaloids, including four C19-diterpenoid alkaloids, aemulanines A-D, and two C18-diterpenoid alkaloids, aemulanines E-F, together with five known analogues, were isolated from the whole plant of Delphinium aemulans Nevski (Ranunculaceae). Their structures were established by comprehensive spectroscopic analysis, and the absolute configuration of aemulanine A was confirmed by single-crystal X-ray diffraction. Aemulanines A-C feature a rare C19-diterpenoid alkaloid skeleton with an opened B ring and an unusually rearranged D ring, while aemulanine E represents the first naturally occurring 7,17-secolycoctonine C18-diterpenoid alkaloid bearing a C-7-O-C-17 hemiacetal linkage. A plausible biosynthetic pathway for aemulanines A-C is proposed. In the acetic acid-induced writhing test in mice, aemulanines A and B exhibited notable analgesic activity, with 83.15% and 58.00% inhibition at 5 mg/kg, respectively. All previously undescribed isolates showed no significant inhibition of hERG or CaV3.1 ion channels, nor did they exhibit notable anti-inflammatory or cytotoxic activity against HeLa, HepG2, and HT-29 cell lines. Aemulanine A moderately inhibited KV channels (IC50 69.5 μM), while aemulanine B was much less potent (IC50 1600 μM). Aemulanine A additionally showed no activity against KV1.2, α7-nAChR, or the NLRP3 inflammasome.
Seven rearranged phenylpropanoyl-phloroglucinol (PPG) dimers, xanthchrysones D-J (1-7), were isolated from the flowers of Xanthostemon chrysanthus. Their structures and absolute configurations were unambiguously established by comprehensive NMR spectroscopy, X-ray crystallography, and quantum chemical calculations. Structurally, compounds 1 and 2 represent the first examples of phenylpropanoyl-phloroglucinol dimers featuring an unprecedented 3-(cyclopentyl(phenyl)methyl)-2-styryl-4H-chromene scaffold, while compounds 3 and 4 incorporate a distinctive 5-(3-phenylpropanoyl)-3,9-dihydrocyclopenta[b]chromen-1(2H)-one backbone. These compounds possess unprecedented skeletons characterized by a unique rearrangement process involving cyclopentanone ring formation and cleavage of the phenylpropanoyl moiety, and their plausible biogenetic pathway was also proposed. All isolates exhibited potent α-glucosidase inhibitory activities, with 5- to 20-fold greater potency than the clinically used antidiabetic drug acarbose. Among them, compounds 6 and 7 showed the most pronounced inhibitory effects, and were therefore selected for subsequent enzyme kinetics studies, molecular docking, and molecular dynamics simulations. Both in vitro and in silico results consistently demonstrated that compounds 6 and 7 are promising candidates for the development of new α-glucosidase inhibitors.
Coreopsis tinctoria Nutt., a traditional edible and medicinal plant, is recognized for its bioactive compounds with potential health benefits. In this study, eight previously unreported compounds including a biflavone (1), an acylated flavonol glycoside (2), an acylated aurone glycoside (3), five phenolic bisabolane-type sesquiterpenoids (4-8), along with nine known compounds, were isolated and structurally elucidated using NMR, HRESIMS, ECD, and quantum chemical calculations. Compounds 7 and 9 showed moderate inhibition of nitric oxide production in LPS-induced RAW 264.7 cells, with IC50 values of 24.56 ± 0.62 μM and 17.72 ± 0.53 μM, respectively. In the ELISA assays, compound 9 reduced the production of pro-inflammatory cytokines, including TNF-α and IL-6. Network pharmacology and molecular docking analyses revealed that compound 9 exerted anti-inflammatory effects via multiple pathways, and exhibited high binding affinity for potential key targets associated with anti-inflammatory activity. Furthermore, molecular dynamics simulations confirmed the stability of those complexes. These findings provide preliminary evidence for the potential of bisabolane-type sesquiterpenoids as lead compounds for developing anti-inflammatory ingredients.
This review summarizes the classification, distribution, biosynthesis, and bioactivities of 381 natural oligomeric iridoids from 1980 to the end of 2025, including 314 dimeric iridoids, 40 trimeric iridoids, and 27 tetrameric iridoids.
Twelve previously undescribed compounds, including 10 naphthalene derivatives (1, 3-11), one benzo[b]oxepine derivative (2) and one anthraquinone analogue (12) were isolated from the CH2Cl2 extract of the roots and rhizomes of Rubia yunnanensis, together with 27 known ones (13-39). Their structures were elucidated on the basis of extensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Angeloylgomisin O (31) exhibited anti-neuroinflammatory activity by inhibiting lipopolysaccharide (LPS)-induced overproduction of nitric oxide (NO) in BV-2 microglial cells. Furthermore, angeloylgomisin O (31) exhibited notable neuroprotective effects against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injuries in SH-SY5Y cells. These investigation results suggested that angeloylgomisin O (31) may contribute to the anti-inflammatory effects of Rubia yunnanensis and may provide valuable insights into the discovery of novel protective agents against ischemic neuronal or microglial injuries.
The endophytic fungal genus Darksidea, one of the most abundant members of root-associated fungal communities in Eurasian and North American grasslands, was investigated for its specialized metabolites. Molecular phylogenetic analysis of 51 Darksidea isolates revealed 15 well-supported clades, including eight potentially novel species. Following a metabolite screening of the in vitro-cultivated fungal isolates, 18 characteristic metabolites of the genus were identified and isolated. Their chemical structures were elucidated by high-performance liquid chromatography coupled with high-resolution tandem mass spectrometry (HPLC-HR-MS/MS), which revealed structure-specific fragmentation patterns. The structures were subsequently confirmed by nuclear magnetic resonance (NMR) spectroscopy. These analyses also led to the identification of four previously undescribed compounds: two eremophilane-type sesquiterpenes, 1-dehydroisopetasol and 3-petason, and two polyketides, mannuronyl-epicoccamide A and mannuronyl-epicoccamide D. Plant bioassay with Lemna minor showed that ten of the 18 compounds inhibited plant growth. In addition, the polyketide quinone ascomycone A exhibited mild antibacterial activity against both methicillin-resistant and methicillin-susceptible Staphylococcus aureus strains.
Seven previously unreported oleanane-type triterpenoid saponins (1-7), along with three known compounds (8-10), were isolated from the leaves of Camellia petelotii. Their structures, including the relative configurations of the aglycone moieties, were elucidated through comprehensive spectroscopic analysis, including extensive NMR and mass spectrometry. The absolute configurations of the sugar units attached to the saponins were determined by acid hydrolysis. All isolated compounds were screened for hyaluronidase inhibitory activity. As a result, compounds 2, 3, 4, 5, 8, 9, and 10 exhibited hyaluronidase inhibitory effects, with IC50 values of 2.02 ± 0.16, 1.27 ± 0.20, 1.79 ± 0.25, 1.96 ± 0.19, 0.27 ± 0.07, 0.48 ± 0.04, and 0.86 ± 0.15 mM, respectively. Notably, compounds 8 and 9 showed inhibitory activity comparable to the positive control ascorbyl palmitate (IC50 = 0.35 ± 0.02 mM), while compound 8 was even more potent.
Employing a dual strategy combining Small Molecule Accurate Recognition Technology and bioactivity-guided approaches, the roots of Edgeworthia gardneri were investigated for the first time, leading to the isolation of seventeen previously unreported guaiane-type sesquiterpenoids, edgewolides A-Q (1-17), together with one known analogue (18). Notably, compounds 2 and 3 incorporate an unusual endoperoxide bridge, forging a 7,8-dioxabicyclo[4.2.1]nonane and a 6,7-dioxabicyclo[3.2.2]nonane scaffold, respectively. Their structures were elucidated through comprehensive spectroscopic analyses, single-crystal X-ray diffraction, and quantum chemical calculations. Anti-adipogenic screening revealed that eight members attenuated lipid accumulation in differentiated 3T3-L1 adipocytes, with 2 exhibiting the highest potency. Structure-activity relationships pinpoint an α-substituted acrolein moiety appears to be critical for activity. Preliminary mechanistic studies indicated that 2 promotes lipolysis via HSL activation and boosts thermogenesis by up-regulating UCP1 and PGC-1α.
Eight previously undescribed and one fully characterized isopimarane diterpenoids, hymenocraterol (A-I), were isolated from n-hexane extract of the aerial parts of Hymenocrater elegans. Their structures were elucidated using HRMS, 1D and 2D-NMR, and electronic circular dichroism calculation techniques. Hymenocrater species are used traditionally for the treatment of different conditions such as inflammation. On this basis, the anti-inflammatory potential of the isolated compounds was evaluated in vitro using J774A.1 murine macrophages. Our results indicated that the majority of these compounds possess anti-inflammatory properties, among which compound 6 was identified as the most promising. Compound 6 significantly inhibited proinflammatory parameters in J774A.1 macrophages in inflammatory conditions, such as nitric oxide release and oxidative stress parameters. These results were additionally confirmed in mouse peritoneal primary macrophages. Our results support the reported anti-inflammatory properties and traditional use of H. elegans, presenting it as an interesting source of anti-inflammatory and antioxidant compounds.
A collection of presently unnamed nitrogen-containing compounds belonging to the classes of alkaloids and nucleosides was compiled from primary literature sources (journal articles and patents) related to Organic Chemistry, Medicinal Chemistry and Natural Product Chemistry. Their interesting structures and bioactivities are highlighted and, based on both their origin and structural characteristics, an attempt is made to propose trivial names for them. Moreover, this review article is enriched with basic information about the host plant, including its phytochemical content, traditional uses, and modern studies relating the plant or its parts to biological activity, with particular emphasis on nitrogen-containing compounds. When available, the total synthesis of these natural products is presented. Alternatively, the search for synthetic procedures of closely related key scaffolds provides an initial hint for an organic chemist who may intend to synthesize them.
Piper longum L. (Piperaceae), a distinctive spice, is extensively utilized in traditional cuisines across different countries. Despite the rich content in P. longum fruits, studies on isolation and biological activity of hydroxyamide alkaloids are limited. An NMR-guided analytical strategy was applied to rapidly isolate and identify 42 hydroxyamide alkaloids, including 34 previously unreported compounds. The absolute configurations of the uncharacterized compounds were determined based on spectrascopic data, ECD and quantum calculations, together with chemical derivatization. Additionally, bioactivities of these compounds were assessed. Six compounds exhibited weak anti-inflammatory activity, and five compounds presented anti-proliferative effects on cancer cell lines including HeLa (human cervical carcinoma cells), HT-29 (human colorectal adenocarcinoma cells), and MCF-7 (human breast adenocarcinoma cells), with the most pronounced effects observed against HT-29 cells. These unique phytochemicals show promise for the development of functional products derived from P. longum fruits.
A methanol extract of the roots of Sophora flavescens Aiton, which is used as a crude drug Sophora Root (Sophorae Radix; "Kujin" in Japanese) and is listed in the Japanese Pharmacopoeia XIX, exerted antiallergic effects on ear passive cutaneous anaphylaxis (PCA) reactions in mice. From the extract, we isolated three previously undescribed prenylflavonoids, kujinfulavanonols A (1) and B (2) and kujinflavanone A (3), along with 34 known compounds (4-37). The absolute stereostructures of 1-3 were established by comparing experimental and predicted ECD data as well as through DP4+ analysis using the calculated 13C NMR chemical shifts. Among the isolates, principal prenylflavonoide sophoraflavanone G (4) and matrine-type alkaloid oxymatrine (30) showed in vivo antiallergic activity at a dose of 50 mg/kg, p.o. To determine the mechanisms of this antiallergic effect, hyaluronidase inhibitory activity and antigen-induced degranulation inhibitory activity were examined in vitro. The results showed that i) sophoraflavanone G (4, IC50 = 34.1 μM), isoxanthohumol (12, 49.1 μM), and kushenols X (14, 22.9 μM) and I (15, 40.1 μM) and ii) sophoraflavanone G (4, IC50 = 48.9 μM), leachianone A (5, 28.9 μM), kushenol U (6, 32.9 μM), (-)-kurarinone (7, 90.5 μM), (2S)-2'-methoxykurarinone (8, 34.4 μM), and isoxanthohumol (12, 58.5 μM), (2R)-3β,7,4'-trihydroxy-5-methoxy-8-prenylflavanone (17, 50.8 μM), and (2R)-3α,7,4'-trihydroxy-5-methoxy-8-prenylflavanone (19, 66.6 μM) were the active constituents.
Abiotic stress severely limits plant growth and productivity. Taraxacum kok-saghyz Rodin (TKS), known for its environmental resilience, represents a valuable resource for identifying stress-tolerant genes to improve stress-adaptive crops. Plant AT-rich protein and zinc-binding protein (PLATZ) transcription factors serve as core regulators of plant growth, developmental processes, and adaptive responses to various stress conditions; however, they remain uncharacterized in TKS. Here, we identified 10 TksPLATZ genes through a whole-genome analysis. Phylogenetically, these genes were grouped into five distinct evolutionary branches. Promoter sequence analysis revealed multiple types of cis-acting regulatory elements that are connected with hormonal signal responses and environmental stress adaptation. Integrated analysis of transcriptome datasets and RT-qPCR validation demonstrated that TksPLATZ genes display tissue-specific expression profiles and show distinct responsive patterns to drought and salt stress treatments. Among them, TksPLATZ1, TksPLATZ2 and TksPLATZ7 were markedly induced under both stressors and were selected for further functional study. We demonstrated that TksPLATZ1, TksPLATZ2 and TksPLATZ7 localize to the cell nucleus and act as transcriptional activators and repressors, respectively. Phenotypic data from overexpression experiments in plants confirm that heterologous expression of TksPLATZ1, TksPLATZ2, and TksPLATZ7 enhances the tolerance of Arabidopsis to salt and osmotic stress. These findings provide valuable genetic resources for improving plant tolerance to environmental stresses.
The chemical profiles of propolis and their botanical origins do not entirely match. Recent studies have shown that propolis has an active native microbiota that may contribute with its antimicrobial properties. The aim of the present investigation was to compare the native microbiota and the metabolome of two types of Brazilian green propolis occurring at distinct biomes, Cerrado (GP) and Caatinga (CP). Additionally, the native microbiota and the metabolome of the respective potential botanical origin of these propolis, Baccharis dracunculifolia (BD) and Mimosa tenuiflora (MT) was investigated. Bacterial and fungal communities were assessed by 16S rRNA and ITS regions sequencing, respectively, and the metabolomic profiles from green propolis and plant resins were analyzed by UPLC-ESI-QToF-MS/MS. Unique DNA sequences assigned to 465 bacteria and 829 fungi were found. Principal component analysis combined with K-means clustering analysis showed that the native microbiota of propolis types were significantly different, while the microbiota of the plant resins was similar (p < 0.05). Chemometric analyses showed high similarity between the metabolomes of GP and BD, while a lower similarity was observed between CP and MT, despite the presence of MT biomarkers in both of them. It indicates that MT was not the unique plant resin source for CP. Nevertheless, molecular networking analyses showed exclusive features for each propolis type derived from known flavonoids present in their respective potential botanical origins. Such flavonoid modifications could be attributed to microbial activity, although further research must be encouraged to confirm the effect of native microbiota on propolis’ metabolome.
Silphion, a ferulaceous plant endemic to the Libyan steppe, produced the most valuable spice of the Greco-Roman world, and is considered the first case of man-related plant extinction in written history. Based on ancient sources and iconographic documentation, Silphion was identified as a plant from one of the genera Ferula, Margotia, Thapsia or Cachrys, and has been at the center of recent debates on its controversial use as a contraceptive and its alleged rediscovery in a remote Anatolian area. The identification of Silphion will be discussed combining botanical considerations with current knowledge on the phytochemistry and bioactivity of its various modern candidates. Ambiguities and inconsistencies in the ancient sources complicate the identification of Silphion with a modern plant species. Based on morphological fit, Margotia gummifera (Desf.) Lange seems its closest living relative, as suggested already in the early 19th century by the German botanist Link. A greedy land management policy, presumably exacerbated by previous overexploitation, was blamed by historical sources as the ultimate cause of extinction of Silphion in the first century AD. The pre-extinction documentation does not support its use as a contraceptive or as an aphrodisiac, rather showing that Silphion was basically a luxury culinary delicacy, only occasionally used for medicinal purposes. Later references to an abortifacient activity could actually refer to asafoetida (Silphium parthicum), its culinary post-extinction replacement from various Ferula species, for which ethnopharmacological association with sexuality could have a foundation, due to the occurrence of the powerful estrogenic compound ferutinin (35a).
A phytochemical investigation of the aerial parts of Euphorbia monostyla Prokh., an endemic species of Turkmenistan, led to the isolation of twelve previously undescribed myrsinane-type diterpenoids, euphomonophanes F-Q (1-12). Their structures were elucidated through comprehensive spectroscopic analyses, including 1D, 2D NMR, and HRESIMS. Relative configurations were established by NOESY correlations, while absolute configurations were determined by a combination of ECD calculations and single-crystal X-ray diffraction analysis. All compounds were evaluated for their cytotoxicity against HeLa (human cervical carcinoma), HCT-8 (human ileocecal adenocarcinoma), and MCF-7 (human breast cancer) cell lines using the MTT assay with doxorubicin and docetaxel as positive controls, followed by preliminary structure-activity relationship analysis. Among them, euphomonophane F (1) and K (6) exhibited the strongest cytotoxicity against HeLa cells with IC50 values of 15.37 ± 0.52 and 26.86 ± 1.86 μM, respectively, while euphomonophanes H (3) and L (7) showed activity with IC50 values of 43.10 ± 2.41 and 37.23 ± 2.21 μM, respectively. Euphomonophane H (3) also demonstrated activity against MCF-7 and HCT-8 cells with IC50 values of 24.66 ± 1.25 and 30.76 ± 2.03 μM. These findings highlight the potential of the myrsinane scaffold as a valuable framework for further structural optimization and investigation toward anticancer agents.
Forty-one constituents, including ten previously undescribed erythropalumins A-J (1, 3-11) were obtained from Erythropalum scandens stems. Their structures were elucidated using comprehensive spectroscopic analyses combined with computational methods. Compounds 1, 7, 14-17, 23, 25, 26, 32-35, and 39 exhibited moderate antioxidant effects, while compounds 1, 6, 11-16, 22, 23, and 27 showed pronounced anti-inflammatory activity, in some cases exceeding that of the positive control. No significant antibacterial activity was observed. Structure-activity relationship of antioxidant was analyzed. Network pharmacology, pathway enrichment, molecular docking, and molecular dynamics simulations, indicated that the observed activities are associated with modulation of inflammation-related pathways. Overall, these findings expand the known chemical diversity of E. scandens and offer preliminary insights into the possible pharmacological basis of its traditional "clear-heat" use.
A phytochemical investigation of Manglietia chevalieri (Magnoliaceae), an ornamental species has remained largely unexplored for its chemical constituents and pharmacological potential, led to the isolation and identification of 51 structurally diverse compounds. These include 20 phenylpropanoids, 12 terpenoids, and 19 alkaloids. Among them, 14 previously undescribed structures, named manglianins A-N (1-11, 12b, 13, 14), were characterized. Notably, the 3,3'-biphenyl neolignans 1-3 feature unprecedented fusions with an additional C2 or C3 unit, leading to the formation of dioxane or benzofuran rings. Compound 13 is the first sesquiterpenoid featuring a rare 3-oxabicyclo[3.3.0]octane ring. The undescribed structures and their absolute configurations were determined by extensive spectroscopic data analysis, computational calculations, and the modified Mosher's method. Given the role of chronic inflammation in driving idiopathic pulmonary fibrosis (IPF), all isolates were initially evaluated for their anti-inflammatory activity in LPS-stimulated RAW 264.7 macrophages by measuring the mRNA expression levels of CCL-2, IL-1β, and IL-6. At 1 μM, 17 isolates reduced expression of the three cytokines by more than 50%. Notably, compounds 14, 15, 28, and 40 retained significant anti-inflammatory effect at concentrations as low as 0.1 μM. Subsequent anti-fibrotic assays evaluating the expression of fibrosis markers (collagen I, fibronectin, and α-SMA) identified compounds 14, 28, 31, 33, and 40-43 as potential anti-IPF agents.
A thorough phytochemical study of a 50% MeOH/CH2Cl2 extract of Croton argyratus (Euphorbiaceae) yielded 17 furylethyl clerodanes, crotargyric acids A-L (1-12), ent-heteroscyphsic acids B, C, and F (13-15), crotargyrol (16), and biscrotargyric acid A (17). In these metabolites, the C-9 methyl group of the original clerodane scaffold was oxidized to a carboxylic acid in compounds 1-15 and 17 or to a hydroxymethyl in compound 16. Compounds 1-15 and 17 represent rare examples of clerodanes with a furylethyl moiety and a carboxylic acid at C-9. Other notable structural features include the A-ring rearranged cyclopentene in 1 and the ester-linkage in hetero-clerodane dimer 17, which is the first such example reported from Euphorbiaceae. The isolated compounds 5-12, 13-15, and 18-22 exhibited no cytotoxicity; however, 13 showed significant antifungal activity against Candida albicans, C. tropicalis, C. neoformans, and Rhizopus oryzae, with R. oryzae being the most sensitive species.
