BIOMEDICINE & PHARMACOTHERAPY
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2018
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IF 3.457
Lifeng Qin,Jinmei Qin,Xiumei Zhen,Qian Yang,Liyi Huang
The C-X-C motif chemokine 12/C-X-C chemokine receptor type 4 (CXCL12/ CXCR4) biological axis plays an important role in the pathogenesis of liver fibrosis . Curcumin is known to have an anti-fibrosis effect, but the specific mechanism needs to be elucidated. There is currently no evidence illustrating a connection between curcumin and the CXCL12/CXCR4 axis in liver fibrosis . Here, we investigated the contribution of curcumin on CXCL12/ CXCR4 biological axis in liver fibrosis. Our results showed that curcumin remarkably improved hepatic function and liver fibrosis, and the effects are similar as silymarin . The alleviation of liver fibrosis with curcumin treatment was associated with a reduction of CXCL12, CXCR4, α-SMA and RhoA. In addition, curcumin markedly inhibited the proliferation and migration of HSC-T6 cells. This study indicates that curcumin could protect against hepatic stellate cells activation and migration by inhibiting the CXCL12/CXCR4 biological axis in liver fibrosis.
研究领域:
药理学
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肝病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
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2023
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IF 8.8
Jian Sun,Huayi Qu,Waseem Ali,Yan Chen,Tao Wang,Yonggang Ma,Yan Yuan,Jianhong Gu,Jianchun Bian,Zongping Liu,Hui Zou
Microplastics (MPs) and cadmium (Cd) are important environmental pollutants, that damage the liver. However, the effect and mechanism of combined Cd and MPs exposure on liver fibrosis are still largely unknown. In this study investigated, Cd + MPs exposure increased superoxide anion production and promoted extracellular ATP release compared with exposure to Cd or MPs individually. Cd + MPs increased inflammatory cell infiltration , activated the P2X7-NLRP3 signaling pathway, and promoted inflammatory factor release. Cd + MPs aggravated Cd- or MPs-induced liver fibrosis and induced liver inflammation. In AML12/HSC-T6 cell in vitro poisoning model, exposure of AML12 cells to Cd + MPs increased the opening of connexin hemichannels and promoted extracellular ATP release. Treatment of HSC-T6 cells with the supernatant of AML12 cells exposed to Cd + MPs significantly promoted HSC-T6 cell activation. Treatment of HSC-T6 cells with different concentrations of ATP produced similar results. TAT-Gap19TFA, an inhibitor of connexin hemichannels, significantly inhibited the ATP release and activation of Cd + MPs-treated HSC-T6 cells. Finally, the expression of the ATP receptor P2X7 was silenced in HSC-T6 cells, which significantly inhibited their activation. In conclusion, exposure to Cd + MPs promoted liver fibrosis through the ATP-P2X7 pathway and synergistically affected liver inflammation and fibrosis.
研究领域:
环境科学
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毒理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Chinese Herbal Medicines
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2024
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IF 4.7
Xin Wu,Cuiwei Chen,Hongyan Zhang,Keda Lu,Gang Cao
Objective This study is mainly to elucidate the characteristic components, hepatoprotective effect, and the underlying anti-hepatic fibrosis molecular mechanism of the total flavonoids of Tetrastigma hemsleyanum Diels & Gilg (SYQTF). Methods The components of SYQTF were confirmed based on global natural products social molecular networking (GNPS) as well as the hepatoprotective effect on CCl 4 -induced acute liver injury. Cell toxicity and viability, cell cycle, and apoptosis analyses were then performed to determine the effects of SYQTF in transforming growth factor-β1 (TGF-β1) (10 ng/mL)-induced HSC-T6 hepatic fibrosis cell model. Finally, the lentiviral particles to package recombinant Ras-related C3 botulinum toxin substrate 1 (Rac1) over-expression and Rac1 knockdown plasmids were transfected into TGF-β1-induced HSC-T6 cells to elucidate the mechanism of anti-hepatic fibrosis of SYQTF targeting Rac1, respectively. Results Our findings demonstrated that 86 components in SYQTF were identified in MS E and FastDDA mode with the aid of GNPS. Moreover, S 15 -ZJ, the genuine functional food and medicinal materials of T. hemsleyanum , was significantly different from other regions by multivariate statistical methods based on progenesis QI. Remarkably, kaempferol-3- O -furananose7- O -rhamnosyl-glucoside, the highest response intensity in S 15 -ZJ, may act as the potential Q-marker of genuine functional food and medicinal materials of T. hemsleyanum in Zhejiang Province distinguished from other areas. In addition, the in vivo experiments revealed that SYQTF greatly alleviated CCl 4 -induced acute liver injury. Furthermore, SYQTF can reversible the activation and proliferation of HSC-T6 cells, block the cell cycle in the G 0 /G 1 phase, and promote cell apoptosis. Remarkably, the study is the first to reveal that SYQTF exhibited the anti-hepatic fibrosis effect through targeting Rac1 in the hedgehog signaling pathway. Conclusion Rac1 is an important signaling molecule for the activation of the hedgehog pathway in HSC-T6. Importantly, SYQTF exerted its anti-hepatic fibrosis effect by inhibiting the Rac1-hedgehog signaling pathway. Furthermore, kaempferol-3- O -furananose7- O -rhamnosyl-glucoside could be a potential Q-marker of T. hemsleyanum in Zhejiang Province distinguished from other areas.
研究领域:
药理学
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分子生物学
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肝病学
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天然产物化学
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产品关联
DOI
高影响因子
MACROMOLECULAR BIOSCIENCE
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2017
·Vol. 17
·期 9
·1700143
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IF 3.238
Shan Yan,Lin-Yan Wan,Xiao-Jie Ju,Jiang-Feng Wu,Lei Zhang,Ming Li,Zhuang Liu,Wei Wang,Rui Xie,Liang-Yin Chu
In this work, a novel type of block copolymer micelles with K + -responsive characteristics for targeted intracellular drug delivery is developed. The proposed smart micelles are prepared by self-assembly of poly(ethylene glycol)- b -poly( N -isopropylacry-lamide- co -benzo-18-crown-6-acrylamide) (PEG- b -P(NIPAM- co -B18C6Am)) block copolymers. Prednisolone acetate (PA) is successfully loaded into the micelles as the model drug, with loading content of 4.7 wt%. The PA-loaded micelles display a significantly boosted drug release in simulated intracellular fluid with a high K + concentration of 150 × 10 −3 m , as compared with that in simulated extracellular fluid. Moreover, the in vitro cell experiments indicate that the fluorescent molecules encapsulated in the micelles can be delivered and specifically released inside the HSC-T6 and HepG2 cells responding to the increase of K + concentration in intracellular compartments, which confirms the successful endocytosis and efficient K + -induced intracellular release. Such K + -responsive block copolymer micelles are highly potential as new-generation of smart nanocarriers for targeted intracellular delivery of drugs.
研究领域:
药学
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纳米技术
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药物递送系统
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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 ETHNOPHARMACOLOGY
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2022
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IF 5.195
Min Hao,Zhouhui Yao,Mengting Zhao,Ziyan Chen,Pingping Wang,Xianan Sang,Qiao Yang,Kuilong Wang,Xin Han,Gang Cao
Ethnopharmacological relevance Curcumae Rhizoma-Sparganii Rhizoma (CR-SR) is a classic herbal pair to promote blood circulation and remove blood stasis in ancient China. However, the molecular mechanism is still unclear. Aim of study To screen out the anti-liver fibrosis active ingredients in CR-SR. Moreover, preliminary exploration the molecular mechanism of CR-SR to ameliorates liver fibrosis . Materials and methods In this research, plant taxonomy has been confirmed in the “The Plant List” database ( www.theplantlist.org ). The chemical components of CR-SR were analysed by ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS). “Component-Target-Pathway-Disease” network of CR-SR components were built by network pharmacology . Then, the interaction between primary components and predicted protein targets based on network pharmacology were validated by molecular docking. The pharmacological actions of CR-SR were verified by blood biochemical indexes, histopathologic examination of CCL 4 induced rats’ model. The core protein targets were verified by Western blot . The effects of screened active components by molecular autodocking were verified by HSC-T6 cell experiment. Results The result shows that 57 chemical constituents in CR-SR herbal pair were identified by UPLC-Q/TOF-MS, in which, 27 compounds were closely connected with liver fibrosis related protein targets. 55 protein targets screened out by “component-target-pathway-disease network” maybe the underlying targets for CR-SR to cure liver fibrosis. Moreover, the 55 protein targets are mainly related to RNA transcription, apoptosis , and signal transduction. The molecular autodocking predicted that ten components can bond well with PTGS2 and RELA protein targets. The blood biochemical indexes, histopathologic examination of CCL 4 induced rats experiment showed that CR-SR has well intervention effect of liver fibrosis. The Western blot analysis indicated that CR-SR could significantly inhibit RELA, PTGS2, IL-6, SRC, and AKT1 protein expression to exert the anti-fibrosis effect. The HSC-T6 cell experiment indicated that both formononetin (FNT) and curdione could significantly inhibit the activation of HSC and reduce the expression of PTGS2, and p-AKT1 which was accordance with the molecular autodocking results. Conclusion This study proved the molecular mechanism of CR-SR multi-component and multi-target anti-liver fibrosis effect through mass spectrometry, network pharmacology, and western blotting technology. The research provides a theoretical evidence for the development and utilization of CR-SR herbal pair.
研究领域:
药理学
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分子生物学
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网络药理学
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中药学
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肝病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）