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Natural Product Research 2023Euphorfinoids M and N ( and ), two previously undescribed -abietane diterpenoids, together with seven known analogues (-), were isolated from the roots of wild . Their...
Euphorfinoids M and N ( and ), two previously undescribed -abietane diterpenoids, together with seven known analogues (-), were isolated from the roots of wild . Their structures were elucidated by spectroscopic analysis, including extensive NMR, HR-ESIMS, ECD, and comparison with structurally related known analogues. Bioassays against proliferative effects of HeLa cell line showed that compound was the most active with IC 3.62 ± 0.31 μM.
Topics: Humans; Abietanes; Diterpenes; Euphorbia; HeLa Cells; Magnetic Resonance Spectroscopy; Plant Roots; Molecular Structure; Antineoplastic Agents, Phytogenic
PubMed: 36661108
DOI: 10.1080/14786419.2023.2169686 -
Phytochemistry Sep 2023The roots of the plant Euphorbia ebracteolata Hayata (Yue Xian Da Ji) are commonly used in traditional Chinese medicine to treat multiple diseases such as chronic liver... (Review)
Review
The roots of the plant Euphorbia ebracteolata Hayata (Yue Xian Da Ji) are commonly used in traditional Chinese medicine to treat multiple diseases such as chronic liver diseases, oedema, pulmonary diseases and cancer. It is the main ingredient of the TCM called Langdu which can be prepared also from roots of E. fischeriana Steud. and occasionally from Stellera chamaejasme species. Numerous bioactive natural products have been isolated from E. ebracteolata including a large diversity of diterpenoids with anti-inflammatory and anticancer properties. One little series of compounds has been named yuexiandajisu (A, B, C, D, D, E, F) which comprises two casbane-, one isopimarane-, two abietane-, and two rosane-type diterpenes including a dimeric molecule. The origin, structural diversity and properties of these little-known natural products is discussed here. Several of these compounds have been identified in the roots of other Euphorbia species, notably the potent phytotoxic agent yuexiandajisu C. The abietane diterpenes yuexiandajisu D-E exhibit marked anticancer properties but their mechanism of action remains unresolved. The dimeric compound, renamed yuexiandajisu D, also exhibit anti-proliferative properties against cancer cell lines, unlike the rosane diterpene yuexiandajisu F. The structural or functional analogy with other diterpenoids is discussed.
Topics: Euphorbia; Diterpenes; Plant Roots; Cell Line; Neoplasms; Molecular Structure
PubMed: 37419377
DOI: 10.1016/j.phytochem.2023.113784 -
Phytomedicine : International Journal... Aug 2023The diterpenoid alkaloids belong to a highly esteemed group of natural compounds, which display significant biological activities. It is a productive strategy to expand...
BACKGROUND
The diterpenoid alkaloids belong to a highly esteemed group of natural compounds, which display significant biological activities. It is a productive strategy to expand the chemical space of these intriguing natural compounds for drug discovery.
METHODS
We prepared a series of new derivatives bearing diverse skeletons and functionalities from the diterpenoid alkaloids deltaline and talatisamine based on a diversity-oriented synthesis strategy. The anti-inflammatory activity of these derivatives was initially screened and evaluated by the release of nitric oxide (NO), tumor necrosis factor (TNF-α), and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-activated RAW264.7 cells. Futhermore, the anti-inflammatory activity of the representative derivative 31a was validated in various inflammatory animal models, including phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mice ear edema, LPS-stimulated acute kidney injury, and collagen-induced arthritis (CIA).
RESULTS
It was found that several derivatives were able to suppress the secretion of NO, TNF-α, and IL-6 in LPS-activated RAW264.7 cells. Compound 31a, one of the representative derivatives named as deltanaline, demonstrated the strongest anti-inflammatory effects in LPS-activated macrophages and three different animal models of inflammatory diseases by inhibiting nuclear factor kappa-B (NF-κB)/mitogen-activated protein kinase (MAPK) signaling and inducing autophagy.
CONCLUSION
Deltanaline is a new structural compound derived from natural diterpenoid alkaloids, which may serve as a new lead compound for the treatment of inflammatory diseases.
Topics: Mice; Animals; Tumor Necrosis Factor-alpha; Interleukin-6; Lipopolysaccharides; Anti-Inflammatory Agents; NF-kappa B; Alkaloids; RAW 264.7 Cells; Diterpenes; Nitric Oxide
PubMed: 37295024
DOI: 10.1016/j.phymed.2023.154907 -
Advanced Healthcare Materials Nov 2023To strengthen the antitumor efficacy and avoid toxicity to normal cells of cisplatin and triptolide, herein, an acid and glutathione (GSH) dual-controlled nanoplatform...
To strengthen the antitumor efficacy and avoid toxicity to normal cells of cisplatin and triptolide, herein, an acid and glutathione (GSH) dual-controlled nanoplatform for enhanced cancer treatment through the synergy of both "1+1" apoptosis and "1+1" ferroptosis is designed. Remarkably, ZIF8 in response to tumor microenvironment enhances drug targeting and protects drugs from premature degradation. Meanwhile, the Pt center can be easily reduced to cisplatin because of the large amount of GSH, thus liberating the triptolide as the coordinated ligand. The released cisplatin and hemin in turn boost the tumor cell "1+1" apoptosis through chemotherapy and photodynamic therapy, respectively. Furthermore, GSH reduction through Pt weakens the activation of glutathione peroxidase 4 (GPX4) effectively. The released triptolide can inhibit the expressions of GSH by regulating nuclear factor E2 related factor 2 (Nrf2), further promoting membrane lipid peroxidation, thus "1+1" ferroptosis can be achieved. Both in vitro and in vivo results demonstrate that the nanosystem can not only perform superior specificity and therapeutic outcomes but also reduce the toxicity to normal cells/tissues of cisplatin and triptolide effectively. Overall, the prodrug-based smart system provides an efficient therapeutic strategy for cancer treatment by virtue of the effect of enhanced "1+1" apoptosis and "1+1" ferroptosis therapies.
Topics: Humans; Female; Cisplatin; Breast Neoplasms; Prodrugs; Diterpenes; Cell Line, Tumor; Tumor Microenvironment
PubMed: 37392128
DOI: 10.1002/adhm.202301328 -
Cell Biology and Toxicology Dec 2023Hepatic sinusoidal obstruction syndrome (HSOS) is a death-dealing liver disease with a fatality rate of up to 67%. In the study present, we explored the efficacy of...
Hepatic sinusoidal obstruction syndrome (HSOS) is a death-dealing liver disease with a fatality rate of up to 67%. In the study present, we explored the efficacy of andrographolide (Andro), a diterpene lactone from Andrographis Herba, in ameliorating the monocrotaline (MCT)-induced HSOS and the underlying mechanism. The alleviation of Andro on MCT-induced rats HSOS was proved by biochemical index detection, electron microscope observation, and liver histological evaluation. Detection of hepatic ATP content, mitochondrial DNA (mtDNA) copy number, and protein expression of nuclear respiratory factor-1 (NRF1) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A) demonstrated that Andro strengthened mitochondrial biogenesis in livers from MCT-treated rats. Chromatin immunoprecipitation assay exhibited that Andro enhanced the occupation of nuclear factor erythroid 2-related factor 2 (NFE2L2, also known as NRF2) in the promoter regions of both PPARGC1A and NRF1. Andro also activated the NRF2-dependent anti-oxidative response and alleviated liver oxidative injury. In Nrf2 knock-out mice, MCT induced more severe liver damage, and Andro showed no alleviation in it. Furthermore, the Andro-activated mitochondrial biogenesis and anti-oxidative response were reduced in Nrf2 knock-out mice. Contrastingly, knocking out Kelch-like ECH-associated protein 1 (Keap1), a NRF2 repressor, reduced MCT-induced liver damage. Results from co-immunoprecipitation, molecular docking analysis, biotin-Andro pull-down, cellular thermal shift assay, and surface plasmon resonance assay showed that Andro hindered the NRF2-KEAP1 interaction via directly binding to KEAP1. In conclusion, our results revealed that NRF2-dependent liver mitochondrial biogenesis and anti-oxidative response were essential for the Andro-provided alleviation of the MCT-induced HSOS. Graphical Headlights: 1. Andro alleviated MCT-induced HSOS via activating antioxidative response and promoting mitochondrial biogenesis. 2. Andro-activated antioxidative response and mitochondrial biogenesis were NRF2-dependent. 3. Andro activated NRF2 via binding to KEAP1.
Topics: Mice; Rats; Animals; Hepatic Veno-Occlusive Disease; Antioxidants; Monocrotaline; NF-E2-Related Factor 2; Kelch-Like ECH-Associated Protein 1; Molecular Docking Simulation; Organelle Biogenesis; Diterpenes; Oxidative Stress; Mice, Knockout; DNA, Mitochondrial
PubMed: 37816928
DOI: 10.1007/s10565-023-09832-7 -
Phytochemistry Jul 2024Cembranoids and labdanes are two important types of diterpenes in tobacco (Nicotiana genus) that are predominantly found in the leaf and flower glandular trichome... (Review)
Review
Cembranoids and labdanes are two important types of diterpenes in tobacco (Nicotiana genus) that are predominantly found in the leaf and flower glandular trichome secretions. This is the first systematic review of the biosynthesis, chemical structures, bioactivities, and utilisation values of cembranoid and labdane diterpenes in tobacco. A total of 131 natural cembranoid diterpenes have been reported in tobacco since 1962; these were summarised and classified according to their chemical structure characteristics as isopropyl cembranoids (1-88), seco-cembranoids (89-103), chain cembranoids (104-123), and polycyclic cembranoids (124-131). Forty natural labdane diterpenes reported since 1961 were also summarised and divided into epoxy side chain labdanes (132-150) and epoxy-free side chain labdanes (151-171). Tobacco cembranoid and labdane diterpenes are both formed via the methylerythritol 4-phosphate pathway and are synthesised from geranylgeranyl diphosphate. Their biosynthetic pathways and the four key enzymes (cembratrienol synthase, cytochrome P450 hydroxylase, copalyl diphosphate synthase, and Z-abienol cyclase) that affect their biosynthesis have been described in detail. A systematic summary of the bioactivity and utilisation values of the cembranoid and labdane diterpenes is also provided. The agricultural bioactivities associated with cembranoid and labdane diterpenes include antimicrobial and insecticidal activities as well as induced resistance, while the medical bioactivities include cytotoxic and neuroprotective activities. Further research into the cembranoid and labdane diterpenes will help to promote their development and utilisation as plant-derived pesticides and medicines.
Topics: Diterpenes; Trichomes; Nicotiana; Molecular Structure; Humans
PubMed: 38697243
DOI: 10.1016/j.phytochem.2024.114117 -
Phytochemistry Nov 2023Fifteen undescribed diterpenoid quinones salviamilthone A-O (1-15), together with three known diterpenoid quinones (16-18), were isolated from the roots of Salvia...
Fifteen undescribed diterpenoid quinones salviamilthone A-O (1-15), together with three known diterpenoid quinones (16-18), were isolated from the roots of Salvia miltiorrhiza Bunge. Their structures were elucidated using 1D and 2D NMR data, while the relative and absolute configurations were confirmed by NOESY correlations and comparison between experimental and calculated ECD spectra. In the evaluation of bioactivities, salviamilthone J (10), salviamone (18) (10 μM) significantly increased cell viability and decreased the expression of IL-1β in lipopolysaccharide-induced BEAS-2B cells. These data provide the molecular justification for the usage of Salvia miltiorrhiza in treating acute lung injury.
Topics: Salvia miltiorrhiza; Quinones; Diterpenes; Plant Roots; Salvia
PubMed: 37648044
DOI: 10.1016/j.phytochem.2023.113840 -
Bioorganic Chemistry Nov 2023Eleven new abietane-type diterpene lactones, salpratlactones D-N (1-11), including five 11,12-seco-11-nor-abietane diterpenes (1-5), four 11,12-seco-abietane diterpenes...
Eleven new abietane-type diterpene lactones, salpratlactones D-N (1-11), including five 11,12-seco-11-nor-abietane diterpenes (1-5), four 11,12-seco-abietane diterpenes (6-9), two 20(10 → 5)-abeo-4,5;11,12-bis-seco-abietane diterpenes (10-11), and two known analogues (12-13), were characterized from Salvia prattii. Notably, compounds 1-3 were characterized by a unique linear 6/6/6 tricyclic skeleton. The structures were established by spectroscopic data interpretation, calculated NMR-DP4+ and electronic circular dichroism analysis, as well as single-crystal X-ray diffraction. A bioactivity study showed that 1, 2, 5, 11, and 12 can potently inhibit platelet aggregation induced by arachidonic acid (AA), with IC values of 5.66-16.10 μg/ml, stronger than aspirin. In addition, the lactate dehydrogenase assay showed that they had no effect on platelet integrity. Structurally, the same 1,2-benzopyrone fragments of 1, 2, and 5 should be the important pharmacophore for antiplatelet activity.
Topics: Abietanes; Aspirin; Lactones; Salvia; Enzyme Assays; Platelet Aggregation Inhibitors
PubMed: 37677855
DOI: 10.1016/j.bioorg.2023.106834 -
Fitoterapia Oct 2023A phytochemical investigation of the medicinal plant Callicarpa macrophylla resulted in the characterization of two rare rearrangement abietane-type diterpenoids,...
A phytochemical investigation of the medicinal plant Callicarpa macrophylla resulted in the characterization of two rare rearrangement abietane-type diterpenoids, macrophypene F-G (1-2), and three abietane diterpenoids, named macrophypene H-J (3-5). Additionally, five known diterpenoids (6-10) were identified. The structures of the newly discovered compounds were fully established through extensive analysis of HRESIMS, 1D and 2D NMR data. The absolute configurations of the isolated compounds were determined using CD comparison, chemical methods, and X-ray crystal diffraction experiments. Subsequently, all isolated diterpenoids were evaluated for their inhibitory effects on extracellular PCSK9 protein levels by PCSK9 AlphaLISA screening. Jiadfenoic acid B (6, 56.80% inhibition at 20 μM) and holophyllin F (10, 43.18% inhibition at 20 μM) significantly decreased PCSK9 protein levels in medium of HepG2 cells.
Topics: Abietanes; Proprotein Convertase 9; Callicarpa; Molecular Structure; Plant Leaves; Diterpenes
PubMed: 37524125
DOI: 10.1016/j.fitote.2023.105629 -
Chinese Journal of Natural Medicines Dec 2023Six new abietane diterpenoids (1-6) and five undescribed iridoids (7-11) have been isolated from the aerial parts of Caryopteris mongolica. The intricate structural...
Six new abietane diterpenoids (1-6) and five undescribed iridoids (7-11) have been isolated from the aerial parts of Caryopteris mongolica. The intricate structural characterization of these compounds was meticulously undertaken using an array of advanced spectroscopic techniques. This process was further enhanced by the application of DP4+ probability analyses and electronic circular dichroism (ECD) calculations. Following isolation and structural elucidation, the cytotoxicity of these compounds was evaluated. Among them, compound 3 stood out, displaying significant cytotoxic activity against HeLa cells with an IC value of 7.83 ± 1.28 μmol·L. Additionally, compounds 1, 2, 4, 9, and 10 manifested moderate cytotoxic effects on specific cell lines, with IC values ranging from 11.7 to 20.9 μmol·L.
Topics: Humans; Abietanes; HeLa Cells; Lamiaceae; Circular Dichroism; Diterpenes; Molecular Structure
PubMed: 38143106
DOI: 10.1016/S1875-5364(23)60409-1