Cornus officinalis
fruits, an edible functional food with the tonic effect, belongs to the Cornaceae family. It is widely used in both traditional medicine and in some food production. A ...phytochemical study on the fruits of
Cornus officinalis
resulted in 20 structurally diverse compounds including 2 new lignans, named officinalignans A-B (
1–2
), and 2 new iridoids, named loganin-(4′-
O
-7″)-α-morroniside (
3
) and 2′-
O
-
p
-coumaroyl-kingiside (
4
). These structures were identified by various spectroscopic techniques and chemical methods, including NMR, high-resolution electrospray ionization mass spectrometry (HR-ESI–MS), CD spectra and acid hydrolysis. The radical scavenging effects of all isolates were investigated. Compounds
1
,
4
,
15
and
18
showed significant inhibitory activities against 2,2-diphenyl-1-picrylhydrazyl (DPPH), whereas
7
and
17
displayed good 2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical-scavenging activities that was even more potent than that of trolox. In addition, all isolates were evaluated for their anti-inflammatory activities by detecting the nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) production by the lipopolysaccharides (LPS) in macrophages cell line RAW264.7, and compounds
3
−
4
and
6
−
7
exhibited the potent inhibition. The results disclosed that the lignans and iridoids from
C. officinalis
fruits can be regarded as a potential new source of antioxidants and inflammation inhibitors.
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Inflammation caused by microglial activation is important in neurodegenerative diseases. In this research, we tried to identify safe and effective anti-neuroinflammatory agents by screening a natural ...compounds library and found that Ergosterol can inhibit the nuclear factor kappa-light-chain enhancer of the activated B cells (NF-κB) pathway induced by lipopolysaccharide (LPS) in microglia cells. Ergosterol has been reported to be an effective anti-inflammatory agent. Nevertheless, the potential regulatory role of Ergosterol in neuroinflammatory responses has not been fully investigated. We further investigated the mechanism of Ergosterol that regulates LPS-induced microglial activation and neuroinflammatory reactions both in vitro and in vivo. The results showed that Ergosterol can significantly decrease the pro-inflammatory cytokines induced by LPS in BV2 and HMC3 microglial cells, possibly by inhibiting the NF-κB, protein kinase B (AKT), and mitogen-activated protein kinase (MAPK) signaling pathways. In addition, we treated Institute of Cancer Research (ICR) mice with a safe concentration of Ergosterol following LPS injection. Ergosterol treatment significantly decreased microglial activation-associated ionized calcium-binding adapter molecule-1 (IBA-1), NF-κB phosphorylation, and pro-inflammatory cytokine levels. Moreover, Ergosterol pretreatment clearly reduced LPS-induced neuron damage by restoring the expression of synaptic proteins. Our data may provide insight into possible therapeutic strategies for neuroinflammatory disorders.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The pathogenesis of diabetes mellitus is mediated mainly by oxidative stress produced by damaged pancreatic β-cells. We identified that an ethyl-acetate fraction (EA) from a cinnamon-cortex extract ...(CCE) is rich in flavonoid, and showed no toxicity to β cells.
In this study, we evaluated the pharmacologic activities of EA on pancreatic β cells using a model of oxidative stress induced by H
O
or alloxan.
The results showed that EA could significantly reduce reactive oxygen (ROS) accumulation to improve the survival of cells. Western blot showed that EA treatment upregulated expression of nuclear factor erythroid 2 related factor 2, heme oxygenase-1, and gamma glutamylcysteine synthetase. The same model study found that EA also can protect β cells against the apoptosis induced by oxidative stress. Furthermore, EA can enhance insulin secretion in rat and mouse β cell lines treated or not with alloxan or H
O
. The expression of the insulin transcription factor PDX-1 increased in an EA concentration-dependent manner. At last, the major functional compounds of EA analysis showed that three compounds, cinnamyl alcohol, coumarin, and cinnamic acid, had similar effects as EA.
In sum, our data suggested that EA fraction from CCE can protect β cells from oxidative stress, and increase insulin secretion to improve the function of β cells. This function might be due to these three compounds found in EA. Our findings provide a theoretical basis and functional molecules for the use of CCE against diabetes mellitus.
Excessive reactive oxygen species (ROS) production contributes to brain ischemia/reperfusion (I/R) injury through many mechanisms including inflammation, apoptosis, and cellular necrosis. Chebulic ...acid (CA) isolated from
has been found to have various biological effects, such as antioxidants. In this study, we investigated the mechanism of the anti-hypoxic neuroprotective effect of CA in vitro and in vivo. The results showed that CA could protect against oxygen-glucose deprivation/reoxygenation (OGD/R) induced neurotoxicity in SH-SY5Y cells, as evidenced by the enhancement of cell viability and improvement of total superoxide dismutase (T-SOD) in SH-SY5Y cells. CA also attenuated OGD/R-induced elevations of malondialdehyde (MDA) and ROS in SH-SY5Y cells. Nuclear factor-E2-related factor 2 (Nrf2) is one of the key regulators of endogenous antioxidant defense. CA acted as antioxidants indirectly by upregulating antioxidant-responsive-element (ARE) and Nrf2 nuclear translocation to relieve OGD/R-induced oxidative damage. Furthermore, the results showed that CA treatment resulted in a significant decrease in ischemic infarct volume and improved performance in the motor ability of mice 24 h after stroke. This study provides a new niche targeting drug to oppose ischemic stroke and reveals the promising potential of CA for the control of ischemic stroke in humans.
Ficus hirta Vahl. (Wuzhimaotao) is an edible functional food used for the soup cooking and health products. Seven undescribed phenolic glycosides (1–7), along with 20 analogues, were isolated from ...the roots of Ficus hirta. Their structures were determined by comprehensive spectroscopic methods (UV, IR, HRESIMS, and NMR), while the absolute configuration of 1 was established by comparison of the experimental and calculated ECD data. The antineuroinflammatory effects of all the compounds were examined by Western blot. Compounds 1 and 11 attenuated the phosphorylation of AKT, JNK, and ERK1/2. In addition, compound 11 inhibited the NF-κB p65 phosphorylation. Our results indicated that compounds 1 and 11 decreased the occurrence of neuroinflammation in BV2 microglia cells, which might be regulated by inhibiting the activity of proteins in NF-κB, MAPK (JNK and ERK1/2), or AKT signaling pathways. Thus, 1 and 11 might exhibit antineuroinflammatory activities and show promise in treating neurodegenerative diseases.
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IJS, KILJ, NUK, PNG, UL, UM, UPUK
•Theacrine augments the hypnotic effect of pentobarbital.•Theacrine shortens wakefulness time and increases NREM sleep time in the EEG and EMG recordings test.•Theacrine exerts the hypnotic property ...by both adenosine A1 receptor and adenosine A2A receptor.•Theacrine increased adenosine content in hippocampus tissues.
Theacrine (l,3,7,9-tetramethyluric acid), a purine alkaloid from Camellia assamica var. kucha, has diverse pharmacological properties, including sedative and hypnotic activities, anti-inflammatory and analgesic activities, antidepressant effects, and a protective effect against stress-provoked liver damage. The present study aims to investigate the possible mechanism of the hypnotic activity of theacrine. The results revealed that theacrine significantly enhanced pentobarbital-induced sleep at a dose of 3.0mg/kg (i.g.) in mice. Sleep parameter analysis by EEG and EMG showed that theacrine obviously shortened wake time and increased NREM sleep time and that theacrine almost had no effect on REM sleep. Meanwhile, theacrine markedly attenuated caffeine (a nonselective antagonist of adenosine receptor)-induced insomnia. In pretreatment with the adenosine A1 receptor antagonist DPCPX and the A2A receptor antagonist SCH 58261, theacrine significantly reversed the decrease in sleeping time in pentobarbital-treated mice. In addition, theacrine also markedly increased the adenosine content in the hippocampus of rats. These results suggested that theacrine might mediate the adenosine system to augment pentobarbital-induced sleep.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Cell entry of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) depends on specific host cell proteases, which are the key targets for preventing and treating viral infections. Herein, we ...describe miyabenol C and trans-ε-viniferin, two resveratrol oligomers that specifically inhibit SARS-CoV-2 entry by targeting host protease cathepsin L. Several cell-based assays were used to demonstrate the effect of resveratrol oligomers, and their target was identified via screening of antiviral targets. Molecular docking analysis suggested that the oligomers could occupy the active cavity of cathepsin L. The surface plasmon resonance assay showed that the equilibrium dissociation constant (K D) values of miyabenol C–cathepsin L and trans-ε-viniferin-cathepsin L were 5.54 and 8.54 μM, respectively, indicating their excellent binding ability for cathepsin L. Our study demonstrated the potential application of resveratrol oligomers as lead compounds in controlling SARS-CoV-2 infection by targeting cathepsin L.
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IJS, KILJ, NUK, PNG, UL, UM, UPUK
Two novel phenylpropanoids (compounds 1 and 2) and 11 known compounds were isolated from Smilax china L. Their structures were determined by NMR (1D and 2D) and high-resolution electrospray ...ionization mass spectrometry. Further, the cytotoxic activity of all the isolated compounds against HeLa, 4T1, and U251 tumor cells was evaluated using the cell counting kit-8 assay, revealing that compound 13 showed significant cytotoxicity toward HeLa cells. Further investigations explored the impact of compound 13 on the mitochondrial membrane potential, concentration of reactive oxygen species, wound-healing distance, and cell cycle of HeLa cells. Notably, compound 13 significantly decreased mitochondrial membrane potential, suppressed cell migration, and increased intracellular reactive oxygen species levels in HeLa cells. Furthermore, compound 13 inhibited HeLa cell-cycle progression in the S phase. These findings indicate that compound 13 is a potential drug lead for the treatment of cervical cancer.Two novel phenylpropanoids (compounds 1 and 2) and 11 known compounds were isolated from Smilax china L. Their structures were determined by NMR (1D and 2D) and high-resolution electrospray ionization mass spectrometry. Further, the cytotoxic activity of all the isolated compounds against HeLa, 4T1, and U251 tumor cells was evaluated using the cell counting kit-8 assay, revealing that compound 13 showed significant cytotoxicity toward HeLa cells. Further investigations explored the impact of compound 13 on the mitochondrial membrane potential, concentration of reactive oxygen species, wound-healing distance, and cell cycle of HeLa cells. Notably, compound 13 significantly decreased mitochondrial membrane potential, suppressed cell migration, and increased intracellular reactive oxygen species levels in HeLa cells. Furthermore, compound 13 inhibited HeLa cell-cycle progression in the S phase. These findings indicate that compound 13 is a potential drug lead for the treatment of cervical cancer.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Twelve undescribed jatrophane diterpenoids, euphpepluones A–L (1–12), together with seven known analogues (13–19), were isolated from the whole plant of Euphorbia peplus, and their structures were ...elucidated by spectroscopic studies. The absolute configurations of 1 and 4 were assigned by X-ray crystallographic analysis. All isolates were investigated for their inhibitory effects against the ATR-Chk1 pathway using a Western blotting assay. As a result, 1, 2, 5, 8, 10, and 16 were found to suppress the camptothecin (CPT)-induced phosphorylation of Chk1, indicating that these compounds inhibit the activation of the ATR-Chk1 pathway. A preliminary structure–activity relationship (SAR) study of the isolates was conducted. When compound 10 and CPT were combined, apoptosis was induced in A549 cells with PARP cleavage, while there was no apoptotic effect by treatment with CPT or 10 alone. The data obtained indicate that 10 potentiates the chemotherapeutic sensitivity of A549 cells to CPT.
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IJS, KILJ, NUK, PNG, UL, UM
