A novel anti-inflammatory flavonoid from flowers of Hibiscus mutabilis L.

Hibiscus mutabilis L. is a Traditional Chinese Medicinal plant of significant value. However, there has been limited research focusing specifically on its flowers. In this study, we report the isolation of one novel and nine known flavonoids from the flowers of H. mutabilis L. The structures of these compounds were elucidated using chemical and comprehensive spectral analysis, involving 1D, 2D NMR, and HRESIMS. The novel compound was further evaluated for its anti-inflammatory and cytotoxic activities using in vitro assays on RAW264.7 cells. Compound 1 at the concentration of 6.25 µM significantly inhibited the production of NO and TNF-α induced by LPS in RAW264.7 cells, exhibiting superior efficacy compared to the positive control dexamethasone, thus indicating its potential as an anti-inflammatory drug candidate.

Sativene Sesquiterpenoids from the Plant Endophytic Fungus Bipolaris victoriae S27 and Their Potential as Plant-Growth Regulators.

Thirteen new sativene sesquiterpenoids (1 and 3-14), one new natural product (2), and 16 known compounds (15-30) were isolated from the endophytic fungus Bipolaris victoriae S27. Their structures were elucidated by extensive spectroscopic analysis, NMR and ECD calculations, and X-ray crystal diffractions. Compound 1 represented the first example of sativene sesquiterpenoids with a 6/5/3/5-caged tetracyclic ring system. All obtained compounds were evaluated for their plant-growth regulatory activity. The results showed that 1, 3, 4, 6, 8, 11, 12, 17, 19, 26, and 27 could suppress the growth of Arabidopsis thaliana, while 2, 5, 13, 15, 18, and 25 showed promoting effects. Among them, compound 3 showed the most potent plant-growth inhibitory activity, which is obviously superior to that of the marked herbicide glyphosate.

The Natural Alkaloid (-)-N-Hydroxyapiosporamide Suppresses Colorectal Tumor Progression as an NF-κB Pathway Inhibitor by Targeting the TAK1-TRAF6 Complex.

Colorectal cancer (CRC) is an exceptionally deadly disease, whereas effective therapeutic drugs for CRC have declined over the past few decades. Natural products have become a reliable source of anticancer drugs. Previously we isolated an alkaloid named (-)-N-hydroxyapiosporamide (NHAP), which exerts potent antitumor effects, but its effect and mechanism in CRC remain unclear. This study aimed to reveal the antitumor target of NHAP and identify NHAP as a promising lead compound for CRC. Various biochemical methods and animal models were used to investigate the antitumor effect and molecular mechanism for NHAP. These results showed that NHAP exhibited potent cytotoxicity, induced both apoptosis and autophagic cell death of CRC cells, and inhibited the NF-κB signaling pathway by blocking the interaction of the TAK1-TRAF6 complex. NHAP also markedly inhibited CRC tumor growth in vivo without obvious toxicities and possessed good pharmacokinetic characteristics. These findings identify, for the first time, that NHAP is an NF-κB inhibitor with potent antitumor activity in vitro and in vivo. This study clarifies the antitumor target of NHAP against CRC, which will contribute to the future development of NHAP as a novel therapeutic lead compound for CRC.

Eremophilane-type and xanthanolide-type sesquiterpenes from the aerial parts of Xanthium sibiricum and their anti-inflammatory activities.

The traditional Chinese medicine Xanthium sibiricum Patrin ex Widder is used to treat wind-cold headache, nasal congestion, nasal discharge, allergic rhinitis, sinusitis, urticaria, and arthritis. Our previous studies found that sesquiterpene lactones, the main bioactive constituents of X. sibiricum, relieved airway inflammation in an asthma mouse model. To obtain active sesquiterpenes, five undescribed ones, including a pair of eremophilanes and three xanthanolides, together with eight known xanthanolides were isolated from X. sibiricum. Their structures were identified by IR, UV, HR-ESI-MS and NMR spectroscopic data, and their absolute configurations were determined by X-ray crystallographic diffraction analysis and the comparison between their experimental and calculated electronic circular dichroism. All isolated compounds were evaluated for their inhibitory effects on nitric oxide production, and Tnf-α, Il-1ß, and Il-6 mRNA expression induced by lipopolysaccharide in the macrophage cell line RAW264.7. Further investigation showed that xanthsibiriolide and 11ß-hydroxyl-13-chloro-8-epi-xanthatin exerted their anti-inflammatory effects by inhibiting the PI3K/AKT/mTOR signaling pathway. Analysis of the structure-activity relationships indicated that the α,ß-unsaturated lactone ring and the 1,5-epoxide group might be the bioactive groups of xanthanolides, and these results provide a basis for further exploration of sesquiterpene-type lead compounds with anti-inflammatory activity.

Neuropyrones A-E, five undescribed α-pyrone derivatives with tyrosinase inhibitory activity from the endophytic fungus Neurospora dictyophora WZ-497.

Five undescribed α-pyrone derivatives, named neuropyrones A-E, were isolated from the endophytic fungus Neurospora dictyophora WZ-497 derived from the stems of Aster tataricus L. f. The structures of these α-pyrones with absolute configurations were determined by comprehensive spectroscopic analysis and computational calculations. All isolated compounds were tested for various bioactivities, including tyrosinase inhibitory activity. The results showed that neuropyrones A-C displayed potent inhibitory effects on tyrosinase with IC50 values of 0.38 ± 0.07, 0.49 ± 0.06, and 0.12 ± 0.01 mM, respectively, which were comparable to that of the positive control, kojic acid (IC50 = 0.14 ± 0.021 mM). A molecular docking study revealed the interaction between 3 and the His263, His85, Val283, Asn260, Phe264, and Val248 residues of tyrosinase.

LncRNA NEAT1 Promotes the Malignant Progression of Colorectal Cancer by Targeting ZEB1 via miR-448.

Background: Long noncoding RNAs have been associated with various types of malignant tumors; however, the specific role of long noncoding RNAs in tumorigenesis still remains unclear in colorectal cancer. Here, we aim to elucidate the role of long noncoding RNA nuclear paraspeckle assembly transcript 1 in the malignant progression of colorectal cancer and investigate its underlying mechanisms. Methods: Real-time polymerase chain reaction was used to detect the expression of nuclear paraspeckle assembly transcript 1 in colorectal cancer tissues and cells. Cell Counting Kit-8 assay was used to determine the effect of nuclear paraspeckle assembly transcript 1 in proliferation. Transwell assay was used to explore the role of nuclear paraspeckle assembly transcript 1 in metastasis. Bioinformatics method was used to predict the core nuclear paraspeckle assembly transcript 1 interaction network. Real-time polymerase chain reaction was used to detect nuclear paraspeckle assembly transcript 1 and miR-448 expression levels. Western blotting was used to detect the expression levels of ZEB1. Luciferase assay was used to verify the relationship among nuclear paraspeckle assembly transcript 1, miR-448, and ZEB1. The effect of nuclear paraspeckle assembly transcript 1 on tumor growth was detected by tumorigenesis test in nude mice. Results: Long noncoding RNA-nuclear paraspeckle assembly transcript 1 was up-regulated in colorectal cancer tissues and cells. Knocking down of nuclear paraspeckle assembly transcript 1 can suppress colorectal cancer proliferation and invasion, and caused a reduction of ZEB1 expression and an increase of miR-448 expression. Furthermore, knockdown of nuclear paraspeckle assembly transcript 1 regulated miR-448/ZEB1 axis to inhibit the expression of ZEB1. miR-448 silencing can reverse the effect of nuclear paraspeckle assembly transcript 1 knockdown. Conclusion: Our result demonstrated that long noncoding RNA nuclear paraspeckle assembly transcript 1 promotes proliferation and invasion of colorectal cancer by targeting miR-448 to promote the expression of ZEB1, which may play a significant role in the tumorigenesis of colorectal cancer.

[Simultaneous determination of ergosterol, nucleosides and their bases from natural and cultured Cordyceps by pressurized solvent extraction and high performance liquid chromatography].

AIM: To establish a simple method for simultaneous determination of ergosterol, nucleosides and their bases in Cordyceps by HPLC coupled with pressurized solvent extraction (PSE). METHODS: The extraction was performed by using PSE and the PSE condition was optimized by using orthogonal test, the contents of ergosterol, nucleosides and their bases in Cordyceps were determined by HPLC. RESULTS: The optimized condition of PSE extraction for ergosterol, nucleosides and their bases in Cordyceps was obtained as follow: solvent, methanol; temperature, 160 degrees C; static extraction time, 5 min; pressure, 10 MPa and one extraction cycle and one time. A ZORBAX NH2 column (250 mm x 4.6 mm ID, 5 microm) and a ZORBAX NH2 guard column (12.5 mm x 4.6 mm ID, 5 microm) were used for simultaneous determination of ergosterol, nucleosides and their bases. Solvents that constituted the mobile phase were A (acetonitrile) and B (10 mmol x L(-1) ammonium acetate in water). The elution conditions applied were: 0 -5.0 min, linear gradient 0 --> 15% B; 5.0-25.0 min, linear gradient 15% --> 20% B; 25.0 - 35.0 min, linear gradient 20% --> 40% B; 35.0 - 45.0 min, linear gradient 40% --> 80% B; 45.0 -50.0 min, 80% B isocratic. The flow-rate was 0. 6 mL x min(-1) and the injection volume was 20 microL. The system operated at 25 degrees C. Ergosterol was monitored and quantified at 275 nm, nucleosides and their bases at 254 nm. CONCLUSION: High performance liquid chromatography coupled with pressurized solvent extraction is a rapid and simple method for simultaneous determination of ergosterol, nucleosides and their bases in Cordyceps.