MOLECULES
·
2023
·Vol. 28
·期 4
·1529
·
IF 4.6
Zhixiang Wang,Wentao Liu,Guohu Li,Jiacheng Wang,Bin Zhao,Peishan Huang,Wenjie Mei
Herein, two novel ruthenium(II) complexes coupled by erianinviaa flexible carbon chain, [Ru(phen)2(L1-(CH2)4-erianin)](ClO4)2(L1= 2-(2-(tri-fluoromethyphenyl))-imidazo [4,5f][1–10]phenanthroline (1) and [Ru(phen)2(L2-(CH2)4-eria)](ClO4)2(L2= 2-(4-(tri-fluoromethyphenyl))-imidazo [4,5f][1,10]phenanthroline (2), have been synthesized and investigated as a potential G-quadruplex(G4) DNA stabilizer. Both complexes, especially 2, can bind toc-mycG4 DNA with high affinity by electronic spectra, and the binding constant calculated for 1 and 2 is about 15.1 and 2.05 × 107M−1, respectively. This was further confirmed by the increase in fluorescence intensity for both complexes. Moreover, the positive band at 265 nm in the CD spectra ofc-mycG4 DNA decreased treated with 2, indicating that 2 may bind toc-mycG4 DNA through extern groove binding mode. Furthermore, fluorescence resonance energy transfer (FRET) assay indicated that the melting point ofc-mycG4 DNA treated with 1 and 2 increased 15.5 and 16.5 °C, respectively. Finally, molecular docking showed that 1 can bind toc-mycG4 DNA in the extern groove formed by base pairs G7–G9 and G22–A24, and 2 inserts into the small groove ofc-mycG4 DNA formed by base pairs T19–A24. In summary, these ruthenium(II) complexes, especially 2, can be developed as potentialc-mycG4 DNA stabilizers and will be exploited as potential anticancer agents in the future.Keywords:ruthenium(II) complexes;erianin;c-mycG-quadruplex DNA;stabilizer
研究领域:
生物化学
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药物化学
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DOI
PubMed
高影响因子
CELL BIOCHEMISTRY AND BIOPHYSICS
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2024
·
IF 1.8
Jiang Qianqian,Fan Guoxia,Wu Kaiwei
Chronic atrophic gastritis (CAG) is a critical initial step in gastric cancer tumorigenesis accompanied by high malignancy. Erianin has been proposed as a promising agent in treating precancerous lesions of gastric cancer. Considering that little work has been implemented concerning the specific role and possible regulatory mechanism of Erianin in CAG, the goal of the study is to disclose the effects and mechanism of erianin on the malignant transformation in the process of CAG. CAG cell model was generated in human gastric epithelium GES-1 cells induced by Nmethyl-N’-nitro-N-nitrosoguanidine (MNNG). CCK-8 method determined cell viability. ELISA and corresponding assay kits severally appraised the contents of inflammatory cytokines and oxidative stress markers. Cellular reactive oxygen species (ROS) formation was measured by flow cytometry analysis using DCFH-DA probe. GFP-LC3 immunofluorescence staining and Western blotting evaluated autophagy. Also, Western blotting analyzed the expression of components in mitogen activated protein kinase (MAPK)/mechanistic target of rapamycin (mTOR) signaling. The results manifested that MNNG treatment diminished the viability and autophagy whereas intensified the inflammation and oxidative stress in GES-1 cells, which were all reversed by Erianin. Besides, Erianin blocked mTOR/MAPK signaling in MNNG-exposed GES-1 cells. Autophagy inhibitor 3-methyladenine (3-MA) or p38 MAPK agonist asiatic acid partially counteracted the protection elicited by Erianin against viability loss, inflammatory reaction as well as oxidative stress in MNNG-induced GES-1 cells. Combined with the findings, Erianin might mediate autophagy to improve MNNG-elicited CAG via MAPK/mTOR signaling.
研究领域:
肿瘤学
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胃肠病学
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药理学
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细胞生物学
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DOI
PubMed
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 19
·6328
·
IF 4.927
Huanan Yu,Yuanqi Liu,Fang Zheng,Wenyu Chen,Kun Wei
Psoriasis is a chronic inflammatory skin disorder accompanied by excessive keratinocyte proliferation. Erianin (Eri) is an ideal drug candidate for inhibiting proliferation and inducing apoptosis in the treatment of psoriasis. However, Eri’s poor water solubility and low penetration activity across the skin hinder its application in local medicine. In this study, we developed a novel photo-responsive dendritic mesoporous silica nanoparticle-based carrier to deliver erianin, improved its bioavailability, and achieved sustained-release effects. Spiropyran (SP), 3-aminopropyltriethoxysilane (APTES), and perfluorodecyltriethoxysilane (PFDTES) were conjugated to the outer surface, which allowed Eri to be released in response to UV radiation. The physicochemical properties of photo-responsive dendritic mesoporous silica nanoparticles ([email protected]) were characterized via multiple techniques, such as using a Fourier-transform infrared spectrometer, a high-resolution transmission electron microscope, and nuclear magnetic resonance (NMR) spectroscopy. The anti-proliferative properties and light-triggered release of erianin-loaded photo-responsive dendritic mesoporous silica nanoparticles were assessed via the MTT assay and a drug release study in vitro. Erianin-loaded photo-responsive dendritic mesoporous silica nanoparticles (UV) exhibit a significantly enhanced HaCat cell-inhibiting efficacy compared to other formulations, as demonstrated by their extremely low cell viability of 10.0% (concentration: 500 mg/mL), indicating their capability to release a drug that responds to UV radiation. The cellular uptake of photo-responsive dendritic mesoporous silica nanoparticles ([email protected]) was observed via confocal laser scanning microscopy (CLSM). These experimental results show that[email protected]could be effectively endocytosed into cells and respond to ultraviolet light to release Eri, achieving a more effective psoriasis treatment. Therefore, this drug delivery system may be a promising strategy for addressing the question of Eri’s delivery and psoriasis therapy.Keywords:erianin;mesoporous silica nanoparticles;photo-responsive;psoriasis;drug delivery
研究领域:
药学
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纳米技术
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皮肤病学
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产品关联
DOI
PubMed
高影响因子
ChemMedChem
·
2023
·
IF 3.4
Yawen Yang,Qingqing Liu,Xinyi Wang,Shaohua Gou
Graphical The dominant skeleton of the natural product erianin or its derivatives were used to design and synthesize a series of novel HDAC inhibitors. Among these, some compounds were found to show stronger in vitro antitumor activity than erianin and SAHA with potent inhibition on HDAC. Multi-target histone deacetylase (HDAC) inhibitors can be designed by introducing dominant structures of natural products to enhance activity and efficacy while avoiding the toxicity from other targets. In this study, we reported a series of novel HDAC inhibitors based on erianin and amino erianin upon pharmacophore fusion strategy. Two representative compounds, N-hydroxy-2-(2-methoxy-5- (3,4,5-trimethoxyphenethyl)phenoxy)acetamide and N-Hydroxy-8-((2-methoxy-5- (3,4,5-trimethoxyphenethyl)phenyl)amino)octanamide, possessed good inhibitory effect against five cancer cells tested (IC 50 =0.30–1.29 μΜ, 0.29–1.70 μΜ) with strong HDAC inhibition, and low toxicity toward L02 cells, which were selected for subsequent biological studies in PANC-1 cells. They were also found to promote the intracellular generation of reactive oxygen species, cause DNA damage, block the cell cycle at G2/M phase, and activate the mitochondria-related apoptotic pathway to induce cell apoptosis, which are significant for the discovery of new HDAC inhibitors.
研究领域:
药理学
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肿瘤学
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药物化学
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2024
·
IF 10.5
Jiaxing Lei,Lei Wang,Chen Yang,Dongdong Li,Jiaxue Zhang,Jia Ma,Peipei Zhang,Qingqing Li,Jiye Zhang
Corneal neovasularization (CNV) is one of the leading causes for visual impairment. Dasatinib is a multi-target tyrosine kinase inhibitor, which can inhibit both platelet derived growth factor receptor and Src family kinases. Erianin exhibits excellent anti-inflammatory and anti-angiogenic effects. In this study, dasatinib and erianin were found to synergically inhibit the proliferation, migration and tube formation of Ea.hy926 cells, the three most important cellular processes of CNV. Next, dasatinib and erianin were co-encapsulated in nanostructured lipid carriers (dasa-eri-NLC), which increased the solubility of dasatinib by about 1790 times, increased the solubility of erianin by about 3 times. To improve its retention time on the ocular surface, dasa-eri-NLC was mixed with gellan gum (dasa-eri-NLC-gel), which achieved a sol-gel transformation when got in contact with tears. The dasa-eri-NLC-gel exhibited good rheological properties with shear thinning properties, extended the ocular residence time by more than 6 times, sustained the drug release, improved the corneal permeability of drug and exhibited good biocompatibility. Finally, the in vivo anti-CNV effect was evaluated in an alkaline burned mouse model of CNV, in which, the dasa-eri-NLC-gel significantly impeded the development and pathological changes of CNV, inhibited the expression of TNF-α, VEGF-A, HIF-1α, Src, p Src in the cornea. In summary, dasa-eri-NLC-gel safely and efficiently delivered dasatinib and erianin to the cornea and exhibited significantly anti-CNV effect via inhibiting various angiogenesis related cytokines or factors. Dasa-eri-NLC-gel showed a great promise for the treatment of CNV and our study laid a solid foundation for future clinical transformation.
研究领域:
药理学
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眼科
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生物材料科学
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2020
·Vol. 18
·期 1
·1-14
·
IF 6.518
Mo Canlong,Lu Lulu,Liu Danyang,Wei Kun
Background Psoriasis is a malignant skin disease characterized as keratinocyte hyperproliferation and aberrant differentiation. Our previous work reported that a bibenzyl compound, erianin, has a potent inhibitory effect on keratinocyte proliferation. To improve its poor water-solubility, increase anti- proliferation activity, and enhance the skin delivery, erianin loaded dendritic mesoporous silica nanospheres (E/DMSNs) were employed.Results In this work, DMSNs with pore size of 3.5 nm (DMSN1) and 4.6 nm (DMSN2) were fabricated and E/DMSNs showed pore-size-dependent, significantly stronger anti-proliferative and pro-apoptotic effect than free erianin on human immortalized keratinocyte (HaCaT) cells, resulting from higher cellular uptake efficiency. In addition, compared to free erianin, treatment with E/DMSNs was more effective in reducing mitochondrial membrane potential and increasing cytoplasmic calcium levels, which were accompanied by regulation of mitochondria and endoplasmic reticulum stress (ERS) pathway. Porcine skin was utilized in the ex vivo accumulation and permeation studies, and the results indicated higher drug retention and less drug penetration in the skin when administered as the E/DMSNs-loaded hydrogel compared to the erianin-loaded hydrogel.ConlusionsThis work not only illustrated the further mechanisms of erianin in anti-proliferation of HaCaT cells but also offer a strategy to enhance the efficiency of erianin and the capacity of skin delivery through the DMSNs drug delivery systems.
研究领域:
药学
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纳米技术
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皮肤病学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
CELL BIOLOGY INTERNATIONAL
·
2021
·Vol. 45
·期 12
·2420-2428
·
IF 3.612
Chang Su,Shaoqun Liu,Xiaoying Ma,Jiajun Liu,Jianwen Liu,Ming Lei,Yiou Cao
Multidrug resistance (MDR) is the main cause of chemotherapy failure in the treatment of colon cancer and the high expression of drug efflux protein P-gp is one of the main factors of MDR. P-gp expression is regulated by the signal transducer and activator of transcription 3 (STAT3) signaling pathway. In this study, human colon cancer oxaliplatin-resistant cells were treated with oxaliplatin combined with the natural product erianin. Then, we evaluated the impact of erianin on drug resistance, and explored the relationship between erianin-related oxaliplatin resistance and the Janus kinase 2/STAT3 signaling pathway in vitro. Our research showed that erianin could significantly inhibit the proliferation of human colon cancer oxaliplatin-resistant cells, and suppress the cell cycle of oxaliplatin-resistant cells in the G2/M phase, indicating that erianin could regulate the MDR phenotype of oxaliplatin-resistant cells, and its mechanism might be the inhibition of STAT3 signaling pathway and the significant reduction of P-gp expression. However, this study provides a theoretical basis for the clinical application of erianin in platinum-based chemotherapy for colon cancer.
研究领域:
肿瘤学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
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