Search Results (18)

Background: Rehmannia glutinosa, a traditional Chinese herb, is commonly used to treat vascular-related disorders. Sepsis-associated vascular endothelial dysfunction is closely associated with mitochondrial damage. This study investigated the protective effects of secondary metabolites from R. glutinosa against LPS-induced mitochondrial dysfunction in endothelial cells, providing potential therapeutic insights into sepsis-related vascular complications. Methods: Phytochemical profiling of fresh R. glutinosa roots was conducted, and the structures of new secondary metabolites (1 and 2) were elucidated through comprehensive spectroscopic analysis and ECD calculations. UPLC-Q-TOF-MS/MS characterized phenylethanoid glycosides. Mitochondrial function was assessed by measuring the membrane potential, ROS levels, and TOM20/DRP1 expression in LPS-injured HUVECs. Results: Two novel eremophilane-type sesquiterpenes, remophilanetriols J (1) and K (2), along with five known phenylethanoid glycosides (3–7), were isolated from the fresh roots of R. glutinosa. UPLC-Q-TOF-MS/MS analysis revealed unique fragmentation pathways for phenylethanoid glycosides (3–7). In LPS-injured HUVECs, all compounds collectively restored the mitochondrial membrane potential, attenuated ROS accumulation, and modulated TOM20/DRP1 expression. In particular, remophilanetriol K (2) exhibited potent protective effects at a low concentration (1.5625 μM). Conclusions: This study identifies R. glutinosa metabolites as potential therapeutics for sepsis-associated vascular dysfunction by preserving mitochondrial homeostasis. This study provides a mechanistic basis for the traditional use of R. glutinosa and offers valuable insights into the development of novel therapeutics targeting mitochondrial dysfunction in sepsis. Full article

Background: Ten new sesquiterpenes, including eight eremophilane-type sesquiterpenes (1–8) and two compounds (9–10) with a cyclopentane ring, representing an undescribed subtype of sesquiterpene, along with a new abietane-type diterpenoid (11), were isolated and identified from a deep-sea-derived fungus: Eutypella sp. Methods: Their structures were elucidated on the basis of various spectroscopic analyses, mainly including nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry (HRESIMS) data, ¹³C NMR calculations with DP4+ probability analyses, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction experiments. Results: Furthermore, compound 11 exhibited potent immunosuppressive activity with IC₅₀ values of 8.99 ± 1.08 μM in a lipopolysaccharide (LPS) model and 5.39 ± 0.20 μM in a concanavalin A (ConA) model. Full article

Six new sesquiterpenes, including four eremophilane derivatives fureremophilanes A–D (1–4) and two acorane analogues furacoranes A and B (5 and 6), were characterized from the culture extract of the cold-seep derived fungus Furcasterigmium furcatum CS-280 co-cultured with autoclaved Pseudomonas aeruginosa QDIO-4. All the six compounds were highly oxygenated especially 2 and 3 with infrequent epoxyethane and tetrahydrofuran ring systems. The structures of 1–6 were established on the basis of detailed interpretation of 1D and 2D NMR and MS data. Their relative and absolute configurations were assigned by a combination of NOESY and single crystal X-ray crystallographic analysis, and by time-dependent density functional (TDDFT) ECD calculations as well. All compounds were tested the anti-inflammatory activity against human COX-2 protein, among which, compounds 2 and 3 displayed activities with IC₅₀ values 123.00 µM and 93.45 µM, respectively. The interaction mechanism was interpreted by molecular docking. Full article

The fungal strain BC17 was isolated from sediments collected in the intertidal zone of the inner Bay of Cadiz and characterized as Emericellopsis maritima. On the basis of the one strain–many compounds (OSMAC) approach, four new eremophilane-type sesquiterpenes (1–4), together with thirteen known derivatives (5–17) and two reported diketopiperazines (18, 19), were isolated from this strain. The chemical structures and absolute configurations of the new compounds were determined through extensive NMR and HRESIMS spectroscopic studies and ECD calculation. Thirteen of the isolated eremophilanes were examined for cytotoxic and antimicrobial activities. PR toxin (16) exhibited cytotoxic activity against HepG2, MCF-7, A549, A2058, and Mia PaCa-2 human cancer cell lines with IC₅₀ values ranging from 3.75 to 33.44 µM. (+)-Aristolochene (10) exhibited selective activity against the fungal strains Aspergillus fumigatus ATCC46645 and Candida albicans ATCC64124 at 471 µM. Full article

The genus Senecio is one of the largest in Asteraceae. There are thousands of species across the globe, either confirmed or awaiting taxonomic delimitation. While the species are best known for the toxic pyrrolizidine alkaloids that contaminate honeys (as bees select pollen from the species) and teas via lateral transfer and accumulation from adjacent roots of Senecio in the rhizosphere, they are also associated with more serious cases leading to fatality of grazing ruminants or people by contamination or accidental harvesting for medicine. Surprisingly, there are significantly more sesquiterpenoid than pyrrolizidine alkaloid-containing species. The main chemical classes, aside from alkaloids, are flavonoids, cacalols, eremophilanes, and bisabolols, often in the form of furan derivatives or free acids. The chemistry of the species across the globe generally overlaps with the 469 confirmed species of Africa. A small number of species express multiple classes of compounds, meaning the presence of sesquiterpenes does not exclude alkaloids. It is possible that there are many species that express the pyrrolizidine alkaloids, in addition to the cacalols, eremophilanes, and bisabolols. The aim of the current communication is, thus, to identify the research gaps related to the chemistry of African species of Senecio and reveal the possible chemical groups in unexplored taxa by way of example, thereby creating a summary of references that could be used to guide chemical assignment in future studies. Full article

Chemical examination of a marine sponge-associated Penicillium copticola fungus resulted in the isolation of ten undescribed eremophilanes, namely copteremophilanes A–J (1–10), along with two new glycosides, 5-glycopenostatin F (11) and 5-glucopenostatin I (12). Their structures were determined by extensive spectroscopic data, in association with ECD data and chemical conversions for configurational assignments. Analogs 1, 2, and 10 represent a group of uncommon skeletons of eremophilanes with an aromatic ring and a methyl migration from C-5 to C-9, and analogs 11 and 12 are characteristic of a PKS scaffold bearing a glucose unit. The incorporation of a chlorinated phenylacetic unit in 3–9 is rarely found in nature. Analog 7 showed neuroprotective effect, whereas 8 exhibited selective inhibition against human non-small cell lung cancer cells (A549). This study enriched the chemical diversity of eremophilanes and extended their bioactivities to neuroprotection. Full article

Four new eremophilane-type sesquiterpenes, boeremialanes A–D (1–4) were obtained from solid substrate cultures of Boeremia exigua (Didymellaceae), an endophytic fungus isolated from Fritillaria hupehensis (Liliaceae). Boeremialanes A–C (1–3) are highly oxygenated eremophilanes with a benzoate unit attached at the C-13 position and are rarely found in nature. Their structures and absolute configurations were determined by extensive spectroscopic methods, electronic circular dichroism (ECD), and nuclear magnetic resonance (NMR) calculations with DP4+ analysis. Boeremialane D (4) potently inhibited nitric oxide production in lipopolysaccharide-treated RAW264.7 macrophages with an IC₅₀ of 8.62 μM and was more potent than the positive control, pyrrolidinedithiocarbamate (IC₅₀ = 23.1 μM). Full article

Five new sesquiterpenoids, citreobenzofuran D–F (1–3) and phomenone A–B (4–5), along with one known compound, xylarenone A (6), were isolated from the culture of the mangrove-derived fungus Penicillium sp. HDN13-494. Their structures were deduced from extensive spectroscopic data, high-resolution electrospray ionization mass spectrometry (HRESIMS), and electronic circular dichroism (ECD) calculations. Furthermore, the absolute structures of 1 were determined by single-crystal X-ray diffraction analysis. Citreobenzofuran E–F (2–3) are eremophilane-type sesquiterpenoids with rare benzofuran frameworks, while phomenone A (4) contains a rare thiomethyl group, which is the first report of this kind of sesquiterpene with sulfur elements in the skeleton. All the compounds were tested for their antimicrobial and antitumor activity, and phomenone B (5) showed moderate activity against Bacillus subtilis, with an MIC value of 6.25 μM. Full article

Biodegradable polymeric nanoparticles (NPs) such as poly(lactic-co-glycolic acid) (PLGA) and polyvinyl alcohol (PVA) have been used as drug delivery systems for natural and synthetic compounds and are designed to control the loading and release of biodegradable materials to target cells, tissues, and organs. Eremophilane-type sesquiterpenes have anti-inflammatory properties but are lipophilic, cytotoxic, and not biocompatible with many cells. To determine whether biodegradable PLGA/PVA could improve the biocompatibility of sesquiterpenes, sesquiterpene-loaded NPs were synthesized and their effects on human mast cells (LAD2), the major effector cells of allergic inflammation, were determined. NPs composed of PLGA/PVA and two types of sesquiterpenes (fukinone, PLGA/PVA-21 and 10βH-8α,12-epidioxyeremophil-7(11)-en-8β-ol, PLGA/PVA-22) were produced using a microfluidic synthesis method. The NPs’ size distribution and morphology were evaluated by dynamic light scattering and cryogenic transmission electron microscopy (TEM). PLGA/PVA-21 and PLGA/PVA-22 were 60 to 70 nm and were readily internalized by LAD2 as shown by flow cytometry, fluorescence microscopy, and TEM. While unencapsulated sesquiterpenes decreased LAD2 cell viability by 20%, PLGA/PVA-21 and PLGA/PVA-22 did not alter LAD2 viability, showing that encapsulation improved the biocompatibility of the sesquiterpenes. PLGA/PVA-21 and PLGA/PVA-22 decreased the expression of genes encoding the subunits of the high affinity immunoglobulin E receptor (FcεR1α, FcεR1β, FcεR1γ) and the stem cell factor receptor (Kit,), suggesting that hybrid NPs could alter mast cell responses to antigens and shift their maturation. Similarly, PLGA/PVA-21 and PLGA/PVA-22 inhibited tryptase expression but had no effect on chymase expression, thereby promoting a shift to the tryptase-positive phenotype (MC_T). Lastly, PLGA/PVA-21 and PLGA/PVA-22 inhibited mast cell degranulation when the LAD2 cells were activated by IgE crosslinking and FcεRI. Overall, our results suggest that PLGA/PVA-21 and PLGA/PVA-22 alter human mast cell phenotype and activation without modifying viability, making them a more biocompatible approach than treating cells with sesquiterpenes alone. Full article

Alpinia oxyphylla Miquel (Zingiberaceae) has been reported to show antioxidant, anti-inflammatory, and neuroprotective effects. In this study, two new eudesmane sesquiterpenes, 7α-hydroperoxy eudesma-3,11-diene-2-one (1) and 7β-hydroperoxy eudesma-3,11-diene-2-one (2), and a new eremophilane sesquiterpene, 3α-hydroxynootkatone (3), were isolated from the MeOH extract of dried fruits of A. oxyphylla along with eleven known sesquiterpenes (4–14). The structures were elucidated by the analysis of 1D/2D NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), and optical rotation data. Compounds (1–3, 5–14) were evaluated for their protective effects against tert-butyl hydroperoxide (tBHP)-induced oxidative stress in adipose-derived mesenchymal stem cells (ADMSCs). As a result, treatment with isolated compounds, especially compounds 11 and 12, effectively reverted the damage of tBHP on ADMSCs in a dose-dependent manner. In particular, 11 and 12 at 50 µM improved the viability of tBHP-toxified ADMSCs by 1.69 ± 0.05-fold and 1.61 ± 0.03-fold, respectively. Full article

Agarwood and agarwood essential oils are commodities with great commercial value. In Vietnam, the agarwood industry has been growing, with more than 10,000 ha of forest land reserved for the cultivation of Aquilaria crassna, an agarwood-producing tree. The aim of this study was to present a hydrodistillation process to recover agarwood essential oil and to compare chemical compositions of agarwood samples harvested from various locations in Vietnam. Three agarwood samples representing products from A. crassna trees cultivated in the provinces of Bac Giang and Khanh Hoa, and on the Phu Quoc island (Kien Giang province) of Vietnam were subjected to hydrodistillation, resulting in essential oil yields of 0.32%, 0.27%, and 0.25% (w/w), respectively. Using GC–MS analysis, a total of 44 volatile compounds were identified in the obtained oils. Most of the constituents were oxygenated sesquiterpenes and had been previously found in other agarwood oil samples. Notable compounds of other chemical classes were aromatics and fatty acids. The three oil samples showed a common volatile profile, which is characterized by the dominance of eremophilane, agarofurans, and eudesmane sesquiterpenes, while vetispirane and guaiane sesquiterpenes were found in smaller quantities. Desired compounds, such as neopetasane (7.47–8.29%), dihydrokaranone (2.63–3.59%), β-agarofuran (3.04–6.18%), and agarospirol (2.98–3.42%), were present in substantial quantities, suggesting that the essential oils could be commercialized as fragrant materials of high value. Full article

The diversity in root chemicals and evolutionally neutral DNA regions in the complex of Ligularia duciformis, L. kongkalingensis, and L. nelumbifolia (the d/k/n complex) was studied using eight samples collected in central and northern Sichuan Province of China. Cacalol (14) and epicacalone (15), rearranged eremophilanes, were isolated from the complex for the first time. Two new phenylpropanoids were also obtained. Seven of the eight samples produced phenylpropanoids and the other produced lupeol alone. Two of the seven samples also produced furanoeremophilanes or their derivatives and one produced oplopanes. The geographical distribution of the sesquiterpene-producing populations suggests that the production of sesquiterpenes evolved independently in separate regions. L. limprichtii collected in northern Sichuan was also analyzed and its chemical composition and the sequence of internal transcribed spacers (ITSs) in the ribosomal RNA gene cluster were found to be similar to that in the d/k/n complex and L. yunnanensis, which are morphologically similar. Full article

Chemical epigenetic manipulation was applied to a deep marine-derived fungus, Aspergillus sp. SCSIOW2, resulting in significant changes of the secondary metabolites. Three new eremophilane-type sesquiterpenes, dihydrobipolaroxin B (2), dihydrobipolaroxin C (3), and dihydrobipolaroxin D (4), along with one known analogue, dihydrobipolaroxin (1), were isolated from the culture treated with a combination of histone deacetylase inhibitor (suberohydroxamic acid) and DNA methyltransferase inhibitor (5-azacytidine). 1–4 were not produced in the untreated cultures. 2 and 3 might be artificial because 1 could form 2 and 3 spontaneously in water by intracellular acetalization reaction. The absolute configurations of 1 and 2 were assigned based on ECD spectroscopy combined with time-dependent density functional theory calculations. All four compounds exhibited moderate nitric oxide inhibitory activities without cytotoxic effects. Full article

Five sesquiterpene-related metabolites (1–5), including two new eremophilane-type compounds, philippinlins C and D (1 and 2) and a 4,5-seconeolemnane philippinlin E (3), were isolated from the organic extract of a Taiwanese soft coral Lemnalia philippinensis. The structures of the new metabolites were determined on the basis of extensive spectroscopic analysis and by comparison of NMR data with those of related metabolites. Compound 3 was suggested to be derived from the neolemnane skeleton. Full article

A new chloro-trinoreremophilane sesquiterpene 1, three new chlorinated eremophilane sesquiterpenes 2–4, together with a known compound, eremofortine C (5), were isolated from an Antarctic deep-sea derived fungus, Penicillium sp. PR19N-1. Structures were established using IR, HRMS, 1D and 2D NMR techniques. In addition, the plausible metabolic network of these isolated products is proposed. Compound 1 showed moderate cytotoxic activity against HL-60 and A549 cancer cell lines. Full article