PHYTOTHERAPY RESEARCH
·
2023
·
IF 7.2
Huihui Wang,Baoping Xie,Shuotao Shi,Rong Zhang,Qi Liang,Zhongqiu Liu,Yuanyuan Cheng
Myocardial infarction (MI) is a common disease with high morbidity and mortality. Curdione is a sesquiterpenoid from Radix Curcumae . The current study is aimed to investigate the protective effect and mechanism of curdione on ferroptosis in MI. Isoproterenol (ISO) was used to induce MI injury in mice and H9c2 cells. Curdione was orally given to mice once daily for 7 days. Echocardiography, biochemical kits, and western blotting were performed on the markers of cardiac ferroptosis. Curdione at 50 and 100 mg/kg significantly alleviated ISO-induced myocardial injury. Curdione and ferrostatin-1 significantly attenuated ISO-induced H9c2 cell injury. Curdione effectively suppressed cardiac ferroptosis, evidenced by decreasing malondialdehyde and iron contents, and increasing glutathione (GSH) level, GSH peroxidase 4 (GPX4), and ferritin heavy chain 1 expression. Importantly, drug affinity responsive target stability, molecular docking, and surface plasmon resonance technologies elucidated the direct target Keap1 of curdione. Curdione disrupted the interaction between Keap1 and thioredoxin1 (Trx1) but enhanced the Trx1/GPX4 complex. In addition, curdione-derived protection against ISO-induced myocardial ferroptosis was blocked after overexpression of Keap1, while enhanced after Keap1 silence in H9c2 cells. These findings demonstrate that curdione inhibited ferroptosis in ISO-induced MI via regulating Keap1/Trx1/GPX4 signaling pathway.
研究领域:
药理学
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心脏病学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS
·
2019
·Vol. 34
·期 5
·297-305
·
IF 1.894
Zhiyuan Li,Xiaohui Sun,Xiaoming Liu,Ziyuan Sun,Jingwei Li
Background: Ruyiping is an effective traditional Chinese herbal medicine formula for preventing postoperative recurrence and metastasis of breast cancer. However, the exact function and underlying mechanism of Ruyiping in breast cancer remain unclear.Materials and Methods: After breast cancer cell lines MDA-MB-231 and MDA-MB-468 were treated with Ruyiping, the CCK8, colony formation, wound-healing, and transwell invasion assays were used to examine cell proliferation, migration, and invasion, respectively. Flow cytometry was performed to examine the effect of Ruyiping on cell cycle distribution. Western blot was performed to examine the expression of related proteins, and the activity of MMP9 was detected using Gelatin zymography assay.Results: Ruyiping treatment significantly inhibited cell proliferation and viability of MDA-MB-231 and MDA-MB-468 cells. Ruyiping was also revealed to trigger cell cycle arrest at the G2 phase in MDA-MB-231 and MDA-MB-468 cells. Moreover, Ruyiping suppressed the migration and invasion abilities of MDA-MB-231 and MDA-MB-468 cells in vitro. Furthermore, Ruyiping blocked the activity of MMP9 in MDA-MB-231 and MDA-MB-468 cells. Additionally, western blotting showed that Ruyiping attenuated epithelial-to-mesenchymal transition (EMT) of breast cancer through downregulation of N-cadherin, Vimentin, Snail1, and Snail2 and upregulation of E-cadherin. The authors observed that the components of Ruyiping Pseudobulbus Cremastra seu pleiones polysaccharide and curcumol showed significant suppression in the growth and invasion of breast cancer cell.Conclusions: The observations of this study suggest the antitumor properties of Ruyiping in cell growth and invasion of breast cancer, which are modulated by induction of cell cycle arrest and reduction of MMP9 and EMT.
研究领域:
肿瘤学
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药理学
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中医药
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细胞生物学
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DOI
PubMed
高影响因子
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
·
2024
·Vol. 43
·期 1
·1-20
·
IF 11.4
Xu Wenjing,Li Yingqiu,Liu Lumei,Xie Jing,Hu Zongren,Kuang Shida,Fu Xinying,Li Bonan,Sun Tiansong,Zhu Congxu,He Qinghu,Sheng Wen
Background Prostate cancer (PCa) incidence and mortality rates are rising. Our previous research has shown that the combination of icariin (ICA) and curcumol (CUR) induced autophagy and ferroptosis in PCa cells, and altered lipid metabolism. We aimed to further explore the effects of the combination of ICA and CUR on gut microbiota, metabolism, and immunity in PCa. Methods A mouse subcutaneous RM-1 cell tumor model was established. 16 S rRNA sequencing was performed to detect changes in fecal gut microbiota. SCFAs in mouse feces, and the effect of ICA-CUR on T-cell immunity, IGFBP2, and DNMT1 were examined. Fecal microbiota transplantation (FMT) was conducted to explore the mechanism of ICA-CUR. Si-IGFBP2 and si/oe-DNMT1 were transfected into RM-1 and DU145 cells, and the cells were treated with ICA-CUR to investigate the mechanism of ICA-CUR on PCa development. Results After treatment with ICA-CUR, there was a decrease in tumor volume and weight, accompanied by changes in gut microbiota. ICA-CUR affected SCFAs and DNMT1/IGFBP2/EGFR/STAT3/PD-L1 pathway. ICA-CUR increased the positive rates of CD3 + CD8 + IFN-γ, CD3 + CD8 + Ki67 cells, and the levels of IFN-γ and IFN-α in the serum. After FMT (with donors from the ICA-CUR group), tumor volume and weight were decreased. SCFAs promote tumor development and the expression of IGFBP2. In vitro, DNMT1/IGFBP2 promotes cell migration and proliferation. ICA-CUR inhibits the expression of DNMT1/IGFBP2. Conclusions ICA-CUR mediates the interaction between gut microbiota and the DNMT1/IGFBP2 axis to inhibit the progression of PCa by regulating immune response and metabolism, suggesting a potential therapeutic strategy for PCa.
研究领域:
肿瘤学
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免疫学
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微生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Kun Hu,Shaojun Wu,Jiaxin Xu,Yongzhen Zhang,Yanan Zhang,Xinyuan Wu,Jie Miao,Yongxu Yao,Susu Zhu,Guangtong Chen,Jie Ren
Alzheimer’s disease (AD), one of the neurodegenerative disorders, is highly correlated with the abnormal hyperphosphorylation of Tau and aggregation of β-amyloid (Aβ). Oxidative stress, neuroinflammation, and abnormal autophagy are key drivers of AD and how they contribute to neuropathology remains largely unknown. The flavonoid compound pongamol is reported to possess a variety of pharmacological activities, such as antioxidant, antibacterial, and anti-inflammatory. This study investigated the neuroprotective effect and its mechanisms of pongamol in lipopolysaccharide (LPS)-induced BV2 cells, d-galactose/sodium nitrite/aluminum chloride (d-gal/NaNO2/AlCl3)-induced AD mice, and Caenorhabditis elegans models. Our research revealed that pongamol reduced the release of inflammatory factors IL-1β, TNF-α, COX-2, and iNOS in LPS-induced BV2 cells. Pongamol also protected neurons and significantly restored memory function, inhibited Tau phosphorylation, downregulated Aβ aggregation, and increased oxidoreductase activity in the hippocampus of AD mice. In addition, pongamol reversed the nuclear transfer of NF-κB and increased the levels of Beclin 1 and LC3 II/LC3 I. Most importantly, the anti-inflammatory and promoter autophagy effects of pongamol may be related to the regulation of the Akt/mTOR signaling pathway. In summary, these results showed that pongamol has a potential neuroprotective effect, which greatly enriched the research on the pharmacological activity of pongamol for improving AD.
研究领域:
神经科学
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2026
·
IF 6.2
Yao Wang,Junhua Qiu,Chengwei Wang,Ruiyu Yang,Fuyou Guo,Tian Li,Shili Li,Lei Yang,Wei Ding
Plant-derived terpenoids are essential secondary metabolites exhibiting broad-spectrum antibacterial properties. However, the bioactivities of terpenoids against Ralstonia solanacearum remain unexplored. Herein, the bioactivities of 30 terpenoids against R. solanacearum were assessed, and trans-anethole (TAN) was identified as a potent antibacterial agent with a minimum inhibitory concentration and minimum bactericidal concentration of 50 and 75 mg/L, respectively. TAN was low-toxic to silkworms, earthworms, seeds, and E. coli. Furthermore, TAN (>25 mg/L) significantly impeded the R. solanacearum growth, blocked ATP and exopolysaccharide (EPS) synthesis, caused DNA damage and cell rupture, and affected swimming motility and biofilm formation, and suppressed expressions of related genes. Compared with thiodiazole copper, and ethylicin, 100 mg/L TAN had a significantly greater control efficiency in both greenhouse and field tests. Importantly, TAN enhanced the abundance of the beneficial bacteria Bacillus and Sphingomonas. These findings highlight TAN as a potential bacterial wilt control agent.
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产品关联
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
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真菌学
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农业科学
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药理学
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产品关联
DOI
PubMed
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
PHARMAZIE
·
2014
·Vol. 69
·期 5
·362-366
·
IF 1.003
Kong L.M.,Xu S.Y.,Hu H.H.,Zhou H.,Jiang H.D.,Yu L.S.,Zeng S.
The aim of the present study was to develop the recombinant insect cell-expressed protein as an in vitro model for inhibitors screening for human cytochrome P450 2C19 (CYP2C19), and to use the model to investigate the inhibition effect of three phytochemicals on CYP2C19 in
vitro. Omeprazole was applied as the probe substrate. The estimated inhibitory constant (Ki) of ticlopidine and fluvoxamine were 0.64 ± 0.025 M and 0.29 ± 0.090 M, respectively. After co-incubation with ticlopidine or fluvoxamine, the mean omeprazole Michaelis-Menten
constant (Km) increased from 4.99 ± 0.22 M to 16.25 ± 1.22 M or 19.20 ± 1.73 M, respectively, while omeprazole's mean Vmax did not vary much. Both ticlopidine and fluvoxamine were competitive inhibitors of CYP2C19. The IC50 of three phytochemicals,
isoalantolactone, curcumol and schisandrin A was determined as 38.91 M, 121.0 M and 86.41 M, and the Ki as 5.02 ± 1.04 M, 35.84 ± 8.95 M, and 4.46 ± 0.017 M, respectively. The in vitro model for inhibitor screening established using recombinant CYP2C19
could be used to assess the inhibition potential of drug candidates. Isoalantolactone and schisandrin A are potent inhibitors of CYP2C19, while curcumol is a moderate potent inhibitor of CYP2C19.
研究领域:
药理学
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分子生物学
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产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2021
·
IF 4.36
Yang Zheng,Jiaru Wang,Tiejian Zhao,Lei Wang,Jiahui Wang
Ethnopharmacological relevance Curcuma is a common Chinese herbal medicine that is used in the clinical treatment of chronic liver disease . Studies have found that curcumol is the main active ingredient of curcuma and has good hepatoprotective and anti-inflammatory effects. However, there are few reports on the molecular mechanism underlying the anti-liver fibrosis effect of curcumol. Aim To explore the effect of curcumol on liver angiogenesis, and to reveal the mechanism of curcumol against liver fibrosis . Materials and methods We used liver collagenase perfusion combined with Percoll density gradient sedimentation to separate primary liver sinusoidal endothelial cells, and then applied a leptin-activated cell pathological model. The cells were divided into four treatment groups as follows: blank group, model group, curcumol group, and solafini group. MTT was used to detect the cell proliferation rate in each group, and RT-PCR and western blotting were used to detect the expressions of VEGF, AKT, eNOS , CD31, and vWF. A fluorescent probe was used to detect NO expression, and scanning electron microscopy was used to observe changes in the cell fenestration structure. Angiogenesis assays were used to observe blood vessel formation in each group. Results The results of the MTT test found that the proliferation rate of each group was higher. The results of the molecular biology tests found that curcumol inhibited the activity of the VEGF/AKT/eNOS pathway, thereby increasing fenestration of sinusoidal endothelial cells and inhibiting liver angiogenesis. These differences were statistically significant compared with the model group. Conclusions Curcumol inhibits the activity of the VEGF/AKT/eNOS signaling pathway, regulates the structure of hepatic sinusoidal endothelial cells, and inhibits liver angiogenesis, which together may explain its anti-liver fibrosis mechanism.
研究领域:
药理学
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分子生物学
·
肝病学
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民族药理学
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产品关联
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
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
·
细胞生物学
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分子生物学
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肝病学
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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
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）