Two previously undescribed chain diarylheptanoid derivatives (2-3), five previously undescribed dimeric diarylheptanoids (4–8), together with one known cyclic diarylheptanoid (1) were isolated from ...Zingiber officinale. Their structures were elucidated by extensive spectroscopic analyses (HR-ESI-MS, IR, UV, 1D and 2D NMR) and ECD calculations. Biological evaluation of compounds 1–8 revealed that compounds 2, 3 and 4 could inhibit nitrite oxide and IL-6 production in lipopolysaccharide induced RAW264.7 cells in a dose-dependent manner.
Seven previously undescribed and one known diarylheptanoids were identified from Zingiber officinale. Bioactivity assays revealed that some isolates showed significant anti-inflammatory activity. Display omitted
•Seven previously undescribed diarylheptanoid derivatives were isolated.•Five dimeric diarylheptanoids were rarely found in Zingiberis officinale.•Compounds 2–4 could inhibit NO and IL-6 production and iNOS expression.
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Seven new diarylheptanoids, kravanhols C−I (1–7), along with two known analogues (8 and 9), were isolated from the fruits of Amomum kravanh. The structures of compounds 1–7 were ...elucidated by analysis of spectroscopic data, and the absolute configurations of selective ones were determined by time-dependent density functional theory (TD-DFT) based electronic circular dichroism (ECD) calculations. All compounds were evaluated for their inhibitory effects on the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in murine RAW264.7 macrophage cells. Compounds 2, 5, 6 and 9 exhibited moderate inhibitory activity with IC50 values in the range of 17.4–26.5 μM, being more potent than the positive control dexamethasone (IC50 = 32.5 μM).
In neurodegenerative diseases, such as Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and multiple sclerosis, neuroinflammation induced by the microglial activation plays a crucial ...role. In effort to develop effective anti-neuroinflammatory compounds, different new linear polyoxygenated diarylheptanoids were synthesized. In LPS-triggered BV-2 microglial cells their ability to reduce the concentration of IL-6 and TNF-α pro-inflammatory cytokines was evaluated. Moreover, their effect on NF-κB and ATP citrate lyase (ACLY), a recently emerged target of metabolic reprogramming in inflammation, was assessed. Finally, we turned our attention to inflammatory mediators derived from the cleavage of citrate catalyzed by ACLY: prostaglandin E2, nitric oxide and reactive oxygen species. All compounds showed null or minimal cytotoxicity; most of them had a great anti-neuroinflammatory activity. Diarylheptanoids 6b and 6c, bearing a halide atom and benzyl ether protective groups, exhibited the best effect since they blocked the secretion of all inflammatory mediators analyzed and reduced NF-κB and ACLY protein levels.
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•New linear polyoxygenated diarylheptanoids were synthesized by cross metathesis.•New diarylheptanoids reduce IL-6, TNF-α, PGE2, ROS and NO in LPS-induced microglia.•New diarylheptanoids inhibited NF-κB transcription factor and its target gene ACLY.•Diarylheptanoids 6b and 6c were the best in reducing microglial neuroinflammation.•Halide atom and benzyl ether strengthen anti-neuroinflammatory activity.
Diarylheptanoids from the barks of
ssp.
(green alder) and
(black alder) were explored for anti-quorum sensing activity. Chemicals with anti-quorum sensing activity have recently been examined for ...antimicrobial applications. The anti-quorum sensing activity of the selected diarylheptanoids was determined using two biosensors, namely
PAO1 and
CV026. Although all of the investigated compounds negatively influenced the motility of
PAO1, four were able to inhibit biofilm formation of this human opportunistic pathogen for 40-70 %. Three of the diarylheptanoids (
, and
) negatively influenced the biosynthesis of pyocyanin, which is under the control of quorum sensing. Platyphyllenone (
) and hirsutenone (
) were able to inhibit the biosynthesis of violacein in
CV026, with
being able to inhibit the synthesis of both biopigments. Only one of the tested diarylheptanoids (
) was shown to significantly decrease the production of acyl homoserine lactones (AHL) in
PAO1, more specifically, production of the long chain N-(3-oxododecanoyl)-l-HSL. On the other side, four diarylheptanoids (
-
) significantly reduced the synthesis of 2-alkyl-4-quinolones, part of the
quinolone-mediated signaling system. To properly assess therapeutic potential of these compounds, their
antiproliferative effect on normal human lung fibroblasts was determined, with doses affecting cell proliferation between 10 and 100 µg/mL. This study confirms that the barks of green and black alders are rich source of phytochemicals with a wide range of biological activities that could further be exploited as natural agents against bacterial contaminations and infections.
There is only limited information available on the chemical composition of the non-edible parts of Corylus avellana, source of the Italian PGI product “Nocciola di Giffoni” (hazelnut). An initial ...LC-MS profile of the methanolic extract of the male flowers of C. avellana, cultivar ‘Tonda di Giffoni’ led to the isolation of 12 compounds, of which the structures were elucidated by NMR spectroscopy. These were identified as three previously undescribed diarylheptanoids, named giffonins Q-S, along with nine known compounds. Furthermore, the quantitative determination of the main compounds occurring in the methanolic extract of C. avellana flowers was carried out by an analytical approach based on LC-ESI(QqQ)MS, using the Multiple Reaction Monitoring (MRM) experiment. In order to explore the antioxidant ability of C. avellana flowers, the methanolic extract and the isolated compounds were evaluated for their inhibitory effects on human plasma lipid peroxidation induced by H2O2 and H2O2/Fe2+, by measuring the concentration of TBARS.
Three diarylheptanoids named giffonins Q-S (10–12) along with nine known compounds were isolated from the MeOH extract of the flowers ofCorylusavellana, cultivar ‘Tonda di Giffoni’. The quantitative determination of the main compounds and the evaluation of their inhibitory effects on human plasma lipid peroxidation induced by H2O2and H2O2/Fe2+were carried out. Display omitted
•A LC-MS profile of the MeOH extract of the flowers of C. avellana, cultivar ‘Tonda di Giffoni’, was carried out.•Three diarylheptanoids never reported before along with nine known flavonoid derivatives were isolated.•A LC-ESI(QqQ)MS method for quantitative analysis of the main compounds was developed.•The MeOH extract and most of the isolated compounds showed promising activity in the TBARS assay.
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•Curcumin and demethoxycurcumin are different because of the phenylmethoxy group.•Curcumin and demethoxycurcumin have different in vivo ...bioavailability.•Phospholipid/hydroxypropyl-β-cyclodextrin complexes (PHSC) were prepared.•PHSC had enhanced in situ gastrointestinal absorption and oral bioavailability.•PHSC are promising candidates for efficient oral delivery of curcuminoids.
Curcumin (Cur) and demethoxycurcumin (Dcur) are two natural analogues of phenol extracted from turmeric, possessing various pharmacological properties. However, their therapeutic potentials are substantially limited by their rather poor aqueous solubility and bioavailability. Herein, novel soluble supramolecular complexes of the two curcuminoids were firstly prepared by integrating phospholipid (PC) compound technology and a hydroxypropyl-β-cyclodextrin (HPβCD) inclusion technique to enhance the bioavailability of the curcuminoids. The PC-HPβCD supramolecular complexes were demonstrated to show improved solubility, augmented drug release, enhanced in situ gastrointestinal absorption, and increased oral bioavailability. The significantly increased bioavailability might be attribute to the appropriate particle sizes (<200 nm), the near-neutral suface charges as well as the additional effects of PC and HPβCD. Overall, the PC-HPβCD supramolecular complexes may be considered as promising candidates for the efficient oral delivery of the curcuminoids; moreover, they are inexpensive, simple to prepare, and have good market prospects. Interestingly, the two natural analogues were found to be different in their in vivo bioavailability with or without supramolecular complexing, probably owing to the difference in the phenylmethoxy group. Therefore, Dcur may have a broader prospect in the pharmaceutical industry, based on its remarkable improvement in bioavailability and reported physiological activity.
The papain-like protease (PLpro), which controls replication of the severe acute respiratory syndrome coronavirus (SARS-CoV), has been identified as a potential drug target for the treatment of SARS. ...An intensive hunt for effective anti-SARS drugs has been undertaken by screening for natural product inhibitors that target SARS-CoV PLpro. In this study, diarylheptanoids 1-9 were isolated from Alnus japonica, and the inhibitory activities of these compounds against PLpro were determined. Of the isolated diarylheptanoids, hirsutenone (2) showed the most potent PLpro inhibitory activity, with an inhibitory concentration (IC50) value of 4.1 µM. Structure-activity analysis showed that catechol and α,β-unsaturated carbonyl moiety in the molecule were the key requirement for SARS-CoV cysteine protease inhibition.
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•Design of a new class of isoxazole-tethered diarylheptanoid analogs.•Stereo-conserved access to syn and anti-1,3-diol features starting from d-glucose.•Significantly improved in ...vitro drug-like properties compared to curcumin-I.•Structurally distinct and phytochemical based PAR2 antagonist scaffold.•Highlighted analog 4a with PAR2 IC50: 6 μM (HEK293 cells, trypsin agonist).
A new class of isoxazole-tethered diarylheptanoids having characteristic 1,3-syn-diol and 1,3-anti-diol chemophoric moieties, e.g. 4a–d and 5a–c respectively, have been designed and synthesized starting from d-glucose following a stereo-conserved general synthetic strategy. The isoxazole heterocycle was installed using our recently elaborated methodology deploying Magtrieve™ as a selective oxidizing agent. Two of these new analogs 4a and 5a exhibited significantly improved in vitro drug-like properties including solubility, metabolic stability, cell permeability and lack of nonspecific cytotoxicity when compared with curcumin-I. In a HEK293 cell-based intracellular calcium Ca2+i release assay, 4a and 5a, when tested at 30 μM, inhibited the trypsin agonist induced protease-activated receptor-2 (PAR2) activity by 80% and 70% respectively. IC50 of 4a (SB70) has been determined as 6 μM which is in the same range of current benchmarks for PAR2 antagonists.
Curcuminoids and their complexes continue to attract attention in medicinal chemistry, but little attention has been given to their metabolic derivatives. Here, the first examples of (arene)Ru(II) ...complexes with curcuminoid metabolites, tetrahydrocurcumin (THcurcH), and tetrahydrobisdesmethoxycurcumin (THbdcurcH) were prepared and characterized. The neutral complexes Ru(arene)(THcurc)Cl and Ru(arene)(THbdcurc)Cl (arene = cymene, benzene, or hexamethylbenzene) were characterized by NMR spectroscopy and ESI mass spectrometry, and the crystal structures of the three complexes were determined by X-ray diffraction analysis. Compared to curcuminoids, these metabolites lose their conjugated double bond system responsible for their planarity, showing unique closed conformation structures. Both closed and open conformations have been analyzed and rationalized by using density functional theory (DFT). The cytotoxicity of the complexes was evaluated in vitro against human ovarian carcinoma cells (A2780 and A2780cisR), human breast adenocarcinoma cells (MCF-7 and MCF-7CR), as well as against non-tumorigenic human embryonic kidney cells (HEK293) and human breast (MCF-10A) cells and compared to the free ligands, cisplatin, and RAPTA-C. There is a correlation between cellular uptake and the cytotoxicity of the compounds, suggesting that cellular uptake and binding to nuclear DNA may be the major pathway for cytotoxicity. However, the levels of complex binding to DNA do not strictly correlate with the cytotoxic potency, indicating that other mechanisms are also involved. In addition, treatment of MCF-7 cells with Ru(cym)(THcurc)Cl showed a significant decrease in p62 protein levels, which is generally assumed as a noncisplatin-like mechanism of action involving autophagy. Hence, a cisplatin- and a noncisplatin-like concerted mechanism of action, involving both apoptosis and autophagy, is possible.
•Sunflower oil was enriched with curcuminoids.•Curcuminoid-enriched oil was gelled with different gelators.•Obtained oleogels differed for rheological properties and firmness.•Lypolysis kinetic ...during in vitro digestion was affected by gel structure.•The type of gelator, instead of gel strength, affected curcuminoid bioaccessibility.
Sunflower oil enriched with curcuminoid compounds (CUs) was gelled by adding 5% (w/w) saturated monoglycerides (MG), rice bran waxes (RW) or a mixture of β-sitosterol and γ-oryzanol (PS). The resulting oleogels differed for rheological properties and firmness due to the difference in gel network structure. PS oleogel was the firmest sample followed by RW and MG ones. Upon in vitro digestion, fatty acid release as a function of digestion time was greatly affected by oleogel structure: the extent of lipolysis decreased as oleogel strength increased (PS < RW < MG). On the other hand, the nature of the oleogelator affected CUs bioaccessibility, which was lower in oleogels containing crystalline particles (MG and RW). These findings appear interesting in the attempt to develop oleogels able to control lipid digestion as well as to deliver bioactive molecules in food systems.
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