Seven unreported compounds were isolated from dried flower buds of Ochrocarpus longifolius in this study, including an alkaloid ochrocaracid A (1), five coumarins ochrocarpins I (2), J (3), K (4), L (5), and M (6), and one styryl-2-pyranone compound iresinoacid (7) and nine known compounds (8-16). All these compounds were found in O. longifolius for the first time. Their structural elucidation was achieved through NMR, HR-ESI-MS, and ECD data. Additionally, a glucose uptake-promoting activity assay revealed that compounds 10 (128.21 μM) and 16 (123.15 μM) increased the glucose uptake capacity of L6 cells by 1.49-fold and 1.48-fold, respectively. These bioactive compounds could be potential candidates for further pharmaceutical applications.

Parrotia subaequalis, an endangered Tertiary relict tree native to China and a member of the Hamamelidaceae family, is one of several host plant species in this family that exhibit unique ecological habits, such as gall formation. Tree galls are the results of complex interactions between gall-inducing insects and their host plant organs. The formation of galls may serve to protect other regions of the plant from potential damage, often through the production of phytoalexins. In this study, a preliminary investigation was carried out on the metabolites of the 90% MeOH extract derived from the closed spherical galls on the twigs of P. subaequalis. Consequently, nine previously undescribed benzofuran-type and dibenzofuran-type phytoalexins (parrotiagallols A-I, 1-9, respectively) were isolated and characterized, along with several known miscellaneous metabolites (10-17). Their chemical structures and absolute configurations were elucidated using spectroscopic methods, a combination of calculated and experimental electronic circular dichroism data, and single crystal X-ray diffraction analyses. Among these compounds, 1 and 2 are identified as neolignan derivatives, while compounds 3-5 are classified as 9,10-dinorneolignans. Compound 6 represents a rare 2,3-seco-neolignan, and compounds 7-9 are dihydroxy-dimethyl-dibenzofuran derivatives. Parrotiagallol A (1) showed considerable antibacterial activity against Staphylococcus aureus, with an MIC value of 14 μM. Additionally, parrotiagallol E (5) and methyl gallate (17) exhibited inhibitory effects against ATP-citrate lyase (ACL), a potential therapeutic target for hyperlipidemia, with IC values of 5.1 and 9.8 μM, respectively. The findings underscore that galls not only serve as physical defense barriers but also benefit from the chemical defense system of the host plants. These insights provide avenues for exploring potential new therapeutic agents for S. aureus infections and ACL-related diseases, while also promoting scientific conservation strategies for P. subaequalis.

Seven previously undescribed dihydro-β-agarofurans (1-7) together with 28 known compounds were isolated from Celastrus orbiculatus fruits using LC-MS/MS-based molecular networking-guided purification. Their structures were elucidated through 1D and 2D-NMR, HRESIMS analysis, and ECD quantum chemical calculations. The inhibitory effects of all isolated compounds on α-MSH-induced melanin production in B16F0 melanoma cells were tested. Compounds 1, 11, 12, 19-21, 23, 29, 31, 34, and 35 showed significant inhibitory effects on melanin production with IC values ranging from 11.3 to 30.1 μM.

The four matrine-derived alkaloids, namely sophflarines B-E (1-4), with distinct skeleton types, were isolated from Sophora flavescens. Compounds 1 and 2 possess rare 1-aza-11-oxatricyclo[5.3.1.0] undecane cores, featuring unprecedented N,O-heterocyclic systems of 5/5/6/6/6 and 6/5/5/6/6, respectively. Compounds 3 and 4 exhibit two novel C units with tetracyclic skeletons of 5/6/6/6 and 6/5/6/6, respectively. The structures were elucidated through spectroscopic analyses, quantum chemical calculations, and X-ray diffraction data. A plausible biosynthetic pathway for these newly discovered compounds was proposed. Furthermore, compounds 1 and 2 showed anti-neuroinflammatory activity against the cytokines NO, TNF-α, and IL-6. Compound 2 exhibited a neuroprotective effect potentially mediated by activating the Keap1-Nrf2/HO-1 pathway to reduce inflammation and oxidative stress.

Seven undescribed iridoids, identified as valeriridoids A-E (compounds 1, 5, 18, 19a, 19b, 20a, and 20b), were isolated from the roots and rhizomes of Valeriana officinalis L., along with sixteen known iridoids and nine known lignans. The structures were elucidated using NMR and MS spectroscopy, and the absolute configurations of the undescribed iridoids were determined through ECD calculations. Valeriridoids D and E were found to be epimeric and scalemic mixtures, which were successfully resolved through a chiral column. These isolated iridoids were evaluated for their antiproliferative activities, with valeriridoid A, jatamanvaltrates P, and Q showing significant effects against human non-small cell lung cancer cells, with IC values of 14.68, 8.77, and 10.07 μM, respectively. Furthermore, the antihyperglycemic properties of the compounds were investigated in insulin-resistant human hepatoblastoma cells induced by palmitic acid treatment, revealing that valeriridoid A, jatamanvaltrates P, and Q at a concentration of 10 μM led to a notable increase in glucose consumption.

Daphne mezereum L. (Thymelaeaceae) was an important medicinal plant in Norway during the 18th and 19th centuries and used against diseases such as diarrhea, swelling, stomach pain, and tuberculosis. Five previously undescribed phenolic compounds, including two biflavonoids with a catechin core structure, two tricoumarins, and one bicoumarin, together with ten known compounds were isolated from a 50% EtOH extract of the bark of D. mezereum. Using NMR, HRESIMS, acid hydrolysis, and circular dichroism spectra, the biflavonoids were identified as 3'-hydroxygenkwanol A and 3'-hydroxydihydrodaphnodorin B, and the coumarins were identified as 3‴-O-acetyltriumbellin, triumbellin 4‴-O-β-d-glucopyranoside, and daphnogitin-7-O-β-d-glucopyranoside. The absolute configuration of dihydrodaphnodorin B was for the first time established as 2R, 3S, 2″S, 3″S. Daphnin, syringin, 3'-hydroxydihydrodaphnodorin B, dihydrodaphnodorin B, and neochamaejasmin A and B were identified as the major secondary metabolites in the extract. Neochamaejasmin A and B showed the most potent inhibition of TNF-α secretion in Con A stimulated peripheral blood mononuclear cells (PBMCs) with 71.3 ± 3.4 and 83.5 ± 11.5% inhibition, respectively, at 50 μM.

Euphohelinodes D-I (1-6), six previously unreported ent-abietane lactones, along with two known analogues (7 and 8), were isolated from the anti-inflammatory fraction extracted from E. helioscopia by a bioactivity-guided isolation. Their structures were characterized using a combination of spectroscopic data interpretation, single-crystal X-ray diffraction and ECD analysis. The anti-inflammatory activity of these compounds was evaluated by measuring their inhibitory effects on NO production in LPS-stimulated RAW264.7 macrophages. The most active candidate, euphohelinode H (5), had better inhibitory activity against NO production with an IC value of 30.23 ± 2.33 μM. Further study revealed that 5 significantly suppressed the expressions of iNOS and COX-2 through the NF-κB signaling pathway.

Chemical investigation on the rice fermentation of the fungus Physisporinus vitreus led to the isolation of ten previously undescribed lanostane triterpenoids, physivitrins I-R, and three known analogues. The new structures were elucidated on the basis of extensive spectroscopic methods, including 1D & 2D NMR, HRESIMS, UV and ECD. Physivitrins I and P exhibited significant inhibitory activities against NO production in LPS-activated RAW267.4 macrophages with IC values of 8.2 and 11.5 μM, respectively. The comprehensive data indicated that P. vitreus is rich in lanostane triterpenes and has potential anti-inflammatory application prospects.

Eleven undescribed sesquiterpenes, vachanins A-K covering types of germacrane, eudesmane, guaiacane, and cadinane, along with fifteen known analogs were isolated from the aerial parts of Artemisia vachanica Krasch. ex Poljakov. Their structures were established on the basis of HRMS and NMR data, and their absolute configurations were successfully determined by single-crystal X-ray diffraction analysis, C-NMR calculations and DP4+ probability analysis, and ECD data in corporation with quantum chemical calculations. Vachanin A is the first example of germacrane bearing an uncommon C, C-oxygen bridge. All isolated compounds were assayed for anti-inflammatory and anti-diabetic activities. Compounds 15 and 22 presented weak anti-inflammatory activity by inhibiting the release of NO in RAW 264.7 cells induced by LPS with IC values of 42.82 ± 1.43, and 63.37 ± 3.28 μM.

Orthosiphon wulfenioides is a medicinal plant to treat arthritis, vascular inflammation, edema, and dyspepsia. To explore the anti-inflammatory components and their mechanism of action, 12 previously undescribed highly oxidized diterpenes, wulfenioidones L-W (1-12), were isolated from O. wulfenioides by bioactivity orientation. Their structures were elucidated using HRESIMS, NMR, specific rotation, single-crystal X-ray diffraction, and ECD spectra analysis. Compounds 1-4 exhibited significant inhibition on LDH release by preventing macrophage J774A.1 pyroptosis. Compound 1 showed the most potent inhibitory effect with an IC value of 5.81 μM. It was revealed in the western blot experiment that compound 1 not only significantly and dose-dependently decreased the activation of CASP1 and IL-1β, but also prevented GSDMD-FL from splitting into GSDMD-NT, the membrane pore-forming protein to release inflammatory factors, thus blocking the extracellular release of IL-1β. More interestingly, compound 1 not only blocked the activation of NLRP3 inflammasome, but also strikingly enhanced the orange fluorescence of JC-1 aggregates, thus showing the activity of maintaining mitochondrial membrane potential and reversing mitochondria damage.

Gentidelasides A-G (1-7) seven unreported loganin derivatives and fourteen known compounds (8-21) were isolated from the flowers of Gentiana delavayi Franch. Their structures including absolute configurations were unambiguously elucidated by analysis of extensive NMR spectroscopy, ECD, and HRESIMS, as well as enzymatic hydrolysis. In vitro bioassay, compound 7 showed obvious inhibitory effects on the production of Aβ40 and Aβ42, with IC values of 0.052 ± 0.0023 nM and 1.52 ± 0.95 nM, respectively, which probably exert their prevention of Alzheimer's disease by inhibiting the expression of β-site amyloid precursor protein cleaving enzyme 1. The molecular docking simulation revealed that compound 7 inhibited BACE1 through hydrophilic and hydrophobic interactions in the active site cavities.

Nine previously undescribed (1-9) and seven known (10-16) cycloartane-type triterpenoids were isolated and characterized from Combretum quadrangulare Kurz using physicochemical and spectroscopic methods. The absolute configurations of these compounds were determined through modified Mosher's method and quantum chemical calculation of electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) spectra. Their inhibitory activities against PCSK9 secretion were assessed, and a plausible structure-activity relationship was delineated. Compounds 2, 14, and 15 exhibited notable inhibitory effects on PCSK9 mRNA and protein levels, and significant PCSK9 mRNA inhibition was observed when co-treated with atorvastatin. Compound 15 showed the most potent activity, markedly enhancing LDL uptake compared to the negative control. In vivo pharmacokinetic studies confirmed that compound 15 exhibited higher distribution in the liver than plasma, where PCSK9 is predominantly synthesized. These findings emphasize the potential significance of the cycloartane-type triterpenoid scaffold in discovering PCSK9 inhibitors.

Twelve neomanoalide derivatives (1-12) and two halisulfate derivatives (13 and 14), nine of which are unprecedented (4-9, 11, 12, and 14; coscilides A-H and halisulfate 11, respectively), were isolated from the sponge Coscinoderma bakusi. The previously unreported neomanoalide derivatives show distinct features in their 6,7-double bond geometry (4 and 9) or terpenoid moieties (5-8, 11, and 12) compared to the reported ones, as elucidated using NMR spectroscopy and HRMS analysis. Among these derivatives, compounds 11 and 12 contain terpenoid moieties that are rarely found in marine natural products. The isolated compounds showed low activity against hTRPA1, six pathogenic bacterial strains, 10 cancer cell lines, except in the case of 7, which exhibited activity against hTRPA1 (IC, 34.5 μM) and Staphylococcus aureus (MIC, 32.0 μg/mL). The halisulfate derivative 14 inhibited NO production in LPS-activated RAW 246.7 macrophage by 45% at a concentration of 10.0 μM. Although no significant activity was observed for the compounds in this study, the compounds reported herein would contribute to the chemical diversity of marine sesterterpenoids.

Osmotic shock is the first step of high salt or drought action that involves biochemical and molecular changes during plant response to these unfavorable conditions. Indole-3-acetyl-aspartate (IAA-aspartate, IAA-Asp) is the main amide conjugate of auxin in pea (Pisum sativum L.) tissues. Although the exact molecular mechanism of the IAA-Asp action is unknown, this conjugate's indole-3-acetic acid (IAA)-independent biological activity has been observed during physiological and stress conditions. In this work, we investigated the effect of IAA-Asp alone, as well as in combination with NaCl or polyethylene glycol (PEG) (osmotic shock) on reduced/oxidized glutathione (GSH/GSSG) ratio, activities of enzymes modulating glutathione concentration, protein S-glutathionylation, and IAA homeostasis. We did not observe the hydrolysis of IAA-Asp to IAA in pea seedlings, which, together with other results, suggests that IAA-Asp modulates plant response to abiotic stimuli independently of IAA. Moreover, despite the effect of IAA-Asp on the enzymes responsible for IAA conjugation, no changes in this phytohormone level were visible. Furthermore, 3h plant treatment with IAA-Asp increased the activity of glutathione reductase (GR), which correlates with an elevated GSH/GSSG ratio. On the contrary, more extended (48h) incubation with IAA-Asp diminished the GSH/GSSG ratio and increased the activity of glutathione peroxidase (GPX). IAA-Asp reduced GR activity during salt treatment but did not affect the GSH/GSSG ratio. Similarly, under plant incubation with PEG, IAA-Asp did not change the GSH/GSSG ratio but increased glutathione S-transferase (GST) activity. We also analyzed the effect of IAA-Asp on pea protein S-glutathionylation. Increased S-glutathionylation of heat shock 70 kDa protein (HSP70) was observed after plant treatment with IAA-Asp, PEG, or IAA-Asp combined with PEG. The proteomic analysis also revealed that IAA-Asp diminished S-glutathionylation of lipoxygenase during plant incubation with PEG. Thus, we suggest that IAA-Asp modulates redox status in pea during oxidative stress and under normal physiological conditions.

Twelve bufadienolides and six 19-norbufadienolides were isolated from the aerial parts of Helleborus foetidus. They consist of aglycons and glucosides and include nine previously undescribed compounds and a compound reported for the first time as a genuine natural product. Their structures were established by extensive spectroscopic analysis and the structure and absolute configuration of two previously unreported 3,4-epoxy derivatives were confirmed by single crystal X-ray diffraction analysis. The compounds were tested for their cytotoxicity on MCF-7 human breast cancer cells. They show differential cytotoxic activity with IC values in the range of 2.4 nM - >10 μM. The potency of the activity strongly correlates with the presence of a C-19 aldehyde group. The data complement the scientific basis underpinning the use of H. foetidus in anthroposophic medicine for the integrative treatment of cancer.

Chemical investigation of the native medicinal plant Tabernaemontana bovina led to the isolation of five previously unreported monoterpenoid indole alkaloids tabernovinaines A-E (1-5) together with twenty-seven known analogs (6-32), including a bisindole alkaloid 1 with the (E)-4-aminobut-3-en-2-one fragment, as well as a unique cage skeleton 2 containing 6/5/8/6/6 ring system. The chemical structures of these unreported compounds were elucidated using mass spectrometry, NMR spectroscopy, circular dichroism, density functional theory calculations, and derivatizations. The activity evaluation shows that the bisindole alkaloid 1 revealed a potential cytotoxic effect by inducing HepG2 cell apoptosis and damaging clonal sphere expansion.

Fourteen benzofuran compounds were identified in the fruits of Psoralea corylifolia L., with four previously undescribed compounds (4, 9-11) being discovered. Their chemical structures were definitively determined through comprehensive spectral data analysis. The compounds were investigated for their antioxidant, anti-tumor, and anti-inflammatory properties, revealing that benzofuran compounds exhibit significant anti-inflammatory effects. Compound 2 demonstrated the most potent anti-inflammatory effect, surpassing that of the positive control drug. The potential anti-inflammatory mechanism of 2 was extensively explored through network pharmacology research. Subsequent validation of the selected targets via Western blot analysis confirmed that 2 exerts its anti-inflammatory effects by activating the TLR4/NF-κB pathway. These findings offer a novel perspective on the development of benzofuran glycoside compounds and Psoralea fructus.

Endophytic actinomycetes exhibit considerable potential for the production of biologically active metabolites due to their coevolution with plant hosts. In this study, an endophytic Streptomyces chartreusis M7 was isolated from Houttuynia cordata Thunb. Bioactivity-guided investigation of the metabolites produced by this strain led to the identification of thirteen anthracycline-derived polyketides, including five unreported anthraquinones designated streptoquinones A-E (1-5) and two undescribed angular polyketides named chartins A and B (6-7) along with six knowns. Their structures were elucidated through comprehensive spectroscopic analysis and ECD calculations. Notably, chartins A (6) and B (7) feature angular tetracyclic and pentacyclic skeletons, respectively, which have undergone several oxidative rearrangements. Moreover, streptoquinone A (1) exhibited moderate cytotoxicity against A549 cells, with an IC value of 4.8 μM.

Thuwalamides A-E (1, 3, 5, 6 and 8), previously undescribed polychlorinated amides, along with ten previously reported related compounds (2, 4, 7 and 9-15), were isolated from the organic extract of the marine sponge Lamellodysidea herbacea (Keller), collected off the village of Thuwal in the Red Sea at Saudi Arabia. The structures of the isolated compounds have been determined through extensive analysis of their NMR and MS data, while their absolute stereochemistry was unequivocally established via single crystal X-ray diffraction. Additionally, the absolute stereochemistry of the previously reported compounds 2 and 4, whose configuration was not determined, has also been established using single-crystal X-ray crystallographic analysis. The antibacterial activity of compounds 1-15 was evaluated against Escherichia coli and Staphylococcus aureus. Among them, compound 14 displayed activity against S. aureus comparable to vancomycin that was used as a positive control with a MIC value of 4 μg/mL.

Multiple spectroscopic, chromatographic, and chemical reaction methods were combined to investigate the chemical components in the fruits of Elaeagnus angustifolia L. As results, thirty-two compounds were obtained from it as natural products. Six of them, elangphenosides A (1), B (2), C (3) and D (4), elangmegastigmanoside A (5), and elangorganic acid A (6) were retrieved by Scifinder as previously undescribed ones. Additionally, a previously undescribed artificial product, elangorganic acid A, as well as a known artificial one, (3R) 5-ethoxy-3-(ethoxycarbonyl)-3-hydroxy-5-oxopentanoic acid, were yielded. Following the phytochemical investigation, LC-MS analysis was employed to conduct a systematical characterization of the constituents from E. angustifolia fruits. Ultimately, fifty-six compounds, including seventeen phenols, one ionone, twenty-four triterpenes, and fourteen other ones, were unambiguously detected and identified. Moreover, in vitro anti-inflammatory activity screening of forty-four natural compounds presented in E. angustifolia fruits was performed by using the LPS-induced RAW264.7 cell model. Twenty-six compounds, including phenols, organic acids, and other compounds, showed assignable activity. Furthermore, their structure-activity relationships were summarized. Combined with the previous research work in our lab, triterpenes, phenols, and organic acids were speculated to be key components during the E. angustifolia fruits exerting anti-inflammatory activity. In summary, this article fully explored the chemical composition of E. angustifolia fruits, assayed their in vitro NO production inhibitory effects, greatly expanding its material foundation and laying a solid foundation for further research and development.