JOURNAL OF THE CHINESE CHEMICAL SOCIETY
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2020
·Vol. 67
·期 5
·874-879
·
IF 1.554
Wenjie Li,Yan Lu,Yi Cheng,Hui Luo,Zhenbin Jia,Ning Li
Curcumol (Cur), which is the primary active anti-liver cancer component of Chinese traditional medicine Rhizoma zedoariae , was encapsulated in galactosylated liposomes to enhance its liver-targeting efficacy. In this study, we optimized the preparation methods, prescription, and process of galactosylated curcumol liposomes (Gal-Cur-L). The experimental results showed that the encapsulation efficiency, particle diameter, and stability coefficient of Gal-Cur-L obtained by the two-step emulsification method were improved compared with those of it obtained by other methods. Single-factor investigation showed that two factors, pH and the amount of triolein, contribute at least partly to the encapsulation efficiency and particle diameter of Gal-Cur-L. The best prescription and process were obtained through orthogonal test: the ratio of lecithin to cholesterol was 2:1, the ratio of drug to lipid was 1:2, and the amount of ether and Twain-80 were 4 ml and 1.6 g/L, respectively, 15 min for ultrasonic time, 100 W for ultrasonic power, and 20 min for homogeneous time. Using the best method, prescription, and process mentioned earlier, the basic test results of Gal-Cur-L were obtained, which demonstrated that our methods, prescription, and process of Gal-Cur-L were applicable. The encouraging results of this study provided references for the research of liver-targeting reagents of curcumol.
研究领域:
药剂学
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肿瘤学
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DOI
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2020
·
IF 1.813
Yang Zheng,Jiahui Wang,Jiaru Wang,Haiyuan Xie,Tiejian Zhao
Objective. To study the effect of curcumol on liver sinusoidal endothelial cells (LSECs) and to analyze the mechanism of antihepatic fibrosis. Methods. The effects of drug intervention on cell proliferation rates were detected by MTT assay. The expression of NF-κB was detected by RT-PCR and WB. The NF-κB expression and entry into the nucleus were detected by immunofluorescence; scanning electron microscopy was used to observe the changes of LSECs fenestrae. Results. MTT results showed that the interference of cell proliferation in each group was small. RT-PCR showed that the expression of NF-κB in the curcumol intervention group was significantly lower than that in the positive control group (). The WB detection found that, in the curcumol intervention group, the expression of pNF-κB in the NF-κB signaling pathway was significantly lower than that in the positive control group (). Scanning electron microscopy showed that the LSEC fenestrae were significantly improved compared with the positive control group. Conclusion. Curcumol may be one of the mechanisms of antihepatic fibrosis by inhibiting the activity of the NF-κB signaling pathway and increasing the fenestrae of LSECs.
研究领域:
药理学
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肝脏病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2018
·Vol. 16
·期 2
·925-930
·
IF 1.41
Wen‑Jie Li,You‑Wen Lian,Quan‑Sheng Guan,Ning Li,Wen‑Jun Liang,Wen‑Xin Liu,Yong‑Bin Huang,Yi Cheng,Hui Luo
Liver‑targeted drug delivery improves the efficacy of anti‑liver cancer agents and reduces systemic toxicity by limiting the bioavailability of these drugs to within tumors. Liver targeting reagents with galactose residues, which selectively combine to asialoglyco protein receptors, have previously been used to improve liposome‑encapsulated drug accumulation within liver cells. They lead to a reduction in liver cancer cell growth and have been used to cure certain hepatic diseases. In the present study, curcumol, which is the primary active component of Chinese traditional medicine Rhizoma zedoariae, was encapsulated in galactosylated‑liposomes to enhance its anti‑liver cancer efficacy. Galactosylated‑liposomes and normal liposomes were labeled with propidium iodide. Galactosylated‑liposomes with increasing concentrations of galactosylated‑stearate (Gal‑s) had a notably increased level of uptake in HepG2 cells (hepatoblastoma) compared with SGC‑7901 (gastric cancer) and A549 (non‑small cell lung cancer) cells. When the percentage of Gal‑s reached 20%, liposome uptake plateaued. In the in vitro anti‑liver cancer experiment, the anti‑liver cancer efficacy of galactosylated‑curcumol‑liposomes increased significantly more compared with normal curcumol liposomes and free curcumol as indicated by cell survival rate and lactate dehydrogenase release rate. Collectively, these results demonstrate that galactosylated‑liposomes are able to enhance the in vitro liver‑targeting effect and anti‑liver cancer efficacy of curcumol.
研究领域:
药理学
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肿瘤学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
·
2014
·
IF 0.968
Ping Guo,Yue-Wu Wang,Bi-Xia Weng,Xiao-Kun Li,Shu-Lin Yang,Fa-Qing Ye
Using curcumol that was extracted from the volatile oil of Rhizoma Curcumae as the raw material, its derivatives were synthesized and purified. The structures of these compounds were confirmed by 1H, 13C NMR, and mass spectral data. The test compounds were evaluated for their in vitro anti-tumor activity against gastric cancer cell lines SGC-7901 and lung carcinoma cell line H460 by methyl thiazolyl tetrazolium chromatometry. Distinct structure–activity relationships of these curcumol derivatives were also revealed for inhibiting cell proliferation. Presence of electron-withdrawing groups or amino could increase the activity significantly, whereas esterification of 8-hydroxy diminished the anti-tumor activity. Many of the tested candidates exhibited higher inhibition efficiency than curcumol, suggesting that structural modifications could enhance its activity effectively.
研究领域:
药理学
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化学
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肿瘤学
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DOI
PubMed
高影响因子
FASEB JOURNAL
·
2022
·Vol. 36
·期 12
·e22665
·
IF 5.834
Yang Zheng,Tiejian Zhao,Jiaru Wang,Ruizhu Jiang,Jinbiao Huang,Weimin Li,Jiahui Wang
To explore the effect of curcumol on autophagy and ferroptosis of hepatic stellate cells, and to clarify the molecular mechanism of its anti-hepatic fibrosis. In the present study, we report that curcumol promotes the death of activated HSCs and reduces the deposition of extracellular matrix. Interestingly, curcumol treatment can trigger ferroptosis to eliminate activated HSCs characterized by iron overload, lipid ROS accumulation, glutathione depletion, and lipid peroxidation. Curcumol promotes HSC autophagy, which may be the key mechanism for its induction of ferroptosis. It is worth noting that the upregulation of nuclear receptor coactivator 4 (NCOA4) may play a key molecular mechanism. NCOA4 mediates the release of iron ions and induces the occurrence of ferroptosis. Overall, curcumol promotes autophagy in hepatic stellate cells, mediates the degradation of NCOA4 and FTH1 complexes, releases iron ions, leads to iron overload, and induces ferroptosis, which may be an important mechanism for its anti-hepatic fibrosis effect.
研究领域:
药理学
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细胞生物学
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分子生物学
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肝病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROPOROUS AND MESOPOROUS MATERIALS
·
2023
·
IF 5.2
Qianqian Wang,Shuo Zhang,Zhuang Deng,Yi Zhang,Zhen Jiao
A metal-organic frameworks (MOFs)-based drug delivery system was prepared by supercritical solution impregnation (SSI) technology. Firstly, core-shell structured Fe 3 O 4 @UiO-66 composite was synthesized by in situ growth of MOFs layers on the surface of carboxy-functionalized Fe 3 O 4 . The composite exhibited superparamagnetic properties with a magnetization saturation of 5.51 emu/g, allowing magnetic targeting and MR imaging along with effective drug loading and controlled release. A hydrophobic anti-cancer drug, curcumol (CUR) was encapsulated into the synthesized composite using the SSI process and ethanol impregnation. The effects of impregnating solvent, impregnation time, impregnation temperature and impregnation pressure on the drug loading content were investigated. In SSI process, the drug load reached impregnation equilibrium within 2 h. In the range of pressure 10–20 MPa and temperature 40–60 °C, the drug loading content was varied from 1.09 wt% to 5.72 wt% by adjusting the impregnation conditions. The optimal impregnation conditions were 50 °C and 20 MPa. SSI was more efficient and faster compared to conventional ethanol impregnation, and the final product can be obtained without further purification. In in vitro drug release experiment, Fe 3 O 4 @UiO-66 exhibited a sustained controlled drug release for up to 36 h. Overall, SSI technology proves to be a promising strategy to maximize the drug loading capacity of Fe 3 O 4 @UiO-66.
研究领域:
药学
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材料科学
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产品关联
DOI
高影响因子
ONCOLOGY REPORTS
·
2017
·Vol. 38
·期 6
·3583-3591
·
IF 2.662
Shilei Zang,Qiling Tang,Fangrui Dong,Huan Liu,Lili Li,Fang Guo,Xuediao Pan,Haorong Lin,Weibin Zeng,Zhaoxu Cai,Qibin Zhong,Ning Zang,Linquan Zang
Curcumol, a polyphenol compound derived from the rhizome of Curcuma, has been established as an antitumor compound against multiple types of cancer, including gastric (GC), lung, liver and breast cancer. However, the molecular mechanisms undelying its anticancer activity in GC are still unclear. In this study, the antitumor efficacy of curcumol was ascertained in human gastric adenocarcinoma MGC-803 cells. An MTT assay was used to assess the viability of the MGC-803 cells treated by curcumol. The results of the Annexin V/propidium iodide (PI) staining followed by fluorescence activated cell sorting (FACS) analysis demonstrated that the cell cycle was arrested in the G2/M phase by curcumol. Annexin V-FITC/PI double staining followed by FACS analysis revealed that curcumol induced apoptosis of MGC-803 cells. FACS analysis after the cells were loaded with a DFCH-DA probe revealed that the level of reactive oxygen species (ROS) increased after the cells were treated with curcumol. In adittion, FACS analysis after the cells were loaded with JC-1 revealed that the level of mitochondrial membrane potential (MMP) decreased after the cells were treated with curcumol. Furthermore, the downregulation of isocitrate dehydrogenase 1 (IDH1) was observed in the MGC-803 cells after being treated with curcumol as determined by western blotting and RT-qPCR. In conclusion, we elucidated the antitumor effect of curcumol on MGC-803 cells and the involved mechanisms related to the induction of apoptosis, the increase of ROS, the decrease of MMP and the downregulation of IDH1.
研究领域:
肿瘤学
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细胞生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2022
·
IF 7.419
Yang Zheng,Jiahui Wang,Jiaru Wang,Ruizhu Jiang,Tiejian Zhao
Objective Liver fibrosis is a reversible pathological process, and its prevention and treatment hold great significance for patients with chronic liver disease. This study combined 16S rRNA analysis of gut microbiota and serum metabolomics to explore the mechanism of curcumol’s effect on liver fibrosis in mice. The results clarified the relationship between the gut microbiota and metabolites in the process of liver fibrosis. Materials and methods In this study, we randomly divided mice into a control group, a model group, and a curcumol treatment group to analyze the pathological changes in the liver tissue as well as the activities of the toll-like receptor 4 (TLR4)/nuclear factory kappa B (NF-κB) signaling pathway and inflammatory factors, such as tumor necrosis factor (TNF), interleukin 6 (IL-6), and IL-8. The gut microbiota were analyzed by 16 S rRNA sequencing, and serum metabolites were examined by liquid chromatography-mass spectrometry (LC-MS) metabolomic analysis. Results Molecular biological testing found that curcumol could significantly improve the pathological changes of the liver tissue and inhibit the occurrence of liver inflammation. Intestinal flora testing found that curcumol could significantly change the abundances of Veillonellaceae, Prerotella_oulorum, and Alistipes_finegoldii. Metabolomics analysis found that curcumol’s antihepatic fibrosis effect may be related to its regulation of arachidonic acid metabolism. Correlation analysis suggested that curcumol regulated the abundances of Bacteroidota and Bacteroides and participated in the metabolism of Prostaglandin B2. Conclusions When liver fibrosis occurs, the intestinal flora and metabolic network are altered. The effect of curcumol on liver fibrosis may be related to its regulation of intestinal flora and the resulting interference with metabolic pathways, thereby reducing liver inflammation.
研究领域:
药理学
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肝病学
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微生物学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
European Journal of Integrative Medicine
·
2023
·
IF 2.5
Xuelin Duan,Tiejian Zhao,Jiaru Wang,Jiahui Wang,Yang Zheng
Introduction : Curcuma is used as an herbal remedy for the treatment of chronic liver diseases, and its main active ingredient is curcumol. This study explored the molecular mechanism of curcumol in regulating glutamine metabolism. Methods : The current investigation used lipopolysaccharide(LPS) to activate hepatic stellate cells (HSCs) and then analyzed the effects of curcumol on glutamine metabolism and cell proliferation. The effects of curcumol on glutaminase 1 (GLS1), senescence-related proteins, and extracellular matrix (ECM) expression were examined by western blotting and reverse transcription-quantitative polymerase chain reaction(RT-PCR). The effect of curcumol on the cell cycle was detected by flow cytometry. Furthermore, after overexpression of GLS1, we observed the effects of curcumol on glutamine metabolism, the expression of related molecules, and the cell cycle. Results : Curcumol significantly inhibited cell proliferation, glutamine metabolism, and GLS1 and ECM expression, and also significantly promoted cell senescence. With GLS1 overexpression, the inhibitory effects of curcumol on glutamine metabolism and on promoting cell senescence were rescued. Conclusion : Curcumol targets GLS1, inhibits glutamine metabolism, and induces senescence in HSCs. GLS1 may be an important target for the pharmacological effects of curcumol.
研究领域:
药理学
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细胞生物学
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肝病学
✓ 已验证
产品关联
DOI
高影响因子
Chinese Journal of Integrative Medicine
·
2021
·Vol. 28
·期 11
·992-999
·
IF 1.978
Zheng Yang,Wang Lei,Wang Jia-hui,Liu Lu-lu,Zhao Tie-jian
Objective To investigate the effect of curcumol on NOD-like receptor thermoprotein domain 3 (NLRP3) inflammasomes, and analyze the mechanism underlying curcumol against liver fibrosis. Methods Thirty Kunming mice were divided into a control group, a model group and a curcumol group according to a random number table, 10 mice in each group. Mice were intraperitoneally injected with 40% carbon tetrachloride (CCl 4 :peanut oil, 2:3 preparation) at 5 mL/kg for 6 weeks, twice a week, for developing a liver fibrosis model. The mice in the control group were given the same amount of peanut oil twice a week for 6 weeks. The mice in the curcumol group were given curcumol (30 mL/kg) intragastrically, and the mice in the model and control groups were given the same amount of normal saline once a day for 6 weeks. Changes in liver structure were observed by hematoxylin and eosin (HE) and Masson staining. Liver function, liver fiber indices, and the expression of interleukin (IL)-10 and tumor necrosis factor-α (TNF-α) levels were determined by automatic biochemical analyzer and enzyme linked immunosorbent assay kit. Immunoblotting and reverse transcription-quantitative PCR (RT-qPCR) were performed to detect the expression of NLRP3 inflammasome-related molecules, TGF-β and collagen. Results HE and Masson staining results showed that the hepatocytes of the model group were arranged irregularly with pseudo-lobular structure and a large amount of collagen deposition. The mice in the curcumol group had a significant decrease in liver function and liver fibers indices compared with the model group ( P <0.05); RT-qPCR and Western blotting results reveal that, in the curcumol group, the mRNA and protein expression levels of NLRP3, IL-1 β, Caspase 1 and gasdermin D decreased significantly compared with the model group ( P <0.05); immunohistochemical results showed that in the curcumol group, the protein expression levels of NLRP3 and IL-1 β decreased significantly compared with the model group ( P <0.05). Conclusion A potential anti-liver fibrosis mechanism of curcumol may be associated with the inhibition of NLRP3 inflammasomes and decreasing the downstream inflammatory response.
研究领域:
药理学
·
免疫学
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肝病学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2024
·
IF 4.2
Jingjing Yang,Hai Zhu,Wenhao Liang,Xingzeng Zhao,Min Yin,Xu Feng,Bi Wang
Phytophthora capsici is an infamously soil-borne pathogen that poses a serious threat to agricultural production. Curcumol is a natural plant-derived sesquiterpene lactone, whose antimicrobial effect against plant pathogens remains unclear. In this study, curcumol exhibited pronounced antifungal activity against a diverse range of plant pathogens, particularly against plant pathogenic oomycetes, which including P. capsici , Phytophthora infestans , Phytophthora parasitica , and Phytophthora sojae . The median effective concentration values of curcumol against P. capsici for spore germination and mycelial growth were 4.75 and 2.11 μg mL −1 , respectively. After treatment with curcumol, mycelia of P. capsici exhibited morphological and ultrastructual defects, which included swelling, hyperbranching, dissolution of plasma membrane, and loss of organelles. In addition, curcumol effectively inhibited the synthesis of phosphatidylcholine (PC), a primary component of cell membrane, by downregulating the expression levels of genes participated in PC synthesis such as Phospholipid N-methyltransferase and Cholinephosphotransferase . This inhibition decreased the accumulation of PC and phospholipids within the cell, thereby increasing the cell membrane permeability and damaging its integrity. In the in vivo antifungal tests, curcumol reduced the disease incidence of P. capsici on tomato leaves as well as pepper seedlings. The systemicity tests further validated the strong phloem and xylem mobility of curcumol in both upward and downward directions. Taken together, these results indicated that curcumol could effectively combat diseases caused by P. capsici and had the potential for development into a novel fungicide for P. capsici management.
研究领域:
植物病理学
·
真菌学
·
农业科学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2026
·
IF 8.1
Jing Qin,Huanhuan Huang,Mengzhen Xu,Lin Zhu,Haoli Liu,Xinyu Qian
Laminin promotes tumor progression, but its role in small-cell lung cancer (SCLC) remains unclear. Curcumol, a natural compound from Curcumae Rhizoma, has anti-tumor activity. Here, we tested the hypothesis that Curcumol disrupts Laminin–Integrin β1 interaction to suppress SCLC. SBC-2 and H69 cells were cultured on Laminin-coated substrates. Cell functions were assessed by Transwell migration, colony formation, and MTT assays. Molecular mechanisms were investigated through qRT-PCR, Western blot, molecular docking, Co-IP, and Dot blot assays. Target specificity was confirmed by Integrin β1 mutagenesis. The therapeutic efficacy of Curcumol was evaluated in xenograft mouse models. Laminin enhanced malignant phenotypes in SCLC cells, accompanied by the activation of FAK/ERK and TGF-β/Smad2/3 pathways. Curcumol inhibited the laminin-promoted malignant phenotypes and epithelial–mesenchymal transition (EMT) in SCLC cells and suppressed the expression of related proteins. Mechanistic studies revealed that Curcumol directly bound to Integrin β1, competitively inhibiting the binding of Laminin to Integrin β1 and the activation of downstream signaling. Target specificity was validated through mutagenesis studies, where Curcumol exhibited reduced efficacy in Integrin β1-mutant cells. In vivo, Curcumol (100 mg/kg, oral) attenuated Laminin-driven tumor growth, suppressed EMT and FAK/ERK signaling, with no detectable toxicity. Integrin β1 is a key mediator of Laminin's pro-tumorigenic effects in SCLC. Curcumol disrupts Laminin–Integrin β1 interaction, inhibits FAK/ERK signaling and EMT, and suppresses tumor progression, representing a promising therapeutic strategy.
✓ 已验证
DOI
PubMed
高影响因子
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