INTERNATIONAL JOURNAL OF NEUROSCIENCE
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2024
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IF 1.7
Qiannan Li,Yinghui Lu,Jinfeng Shang,Qi Song,Jiakang Jiao,Lei Bi,Tingyue Jiang,Xin Liu
Background To explore the effect of Ganshuang granule on anti-alcoholic and anti-hangover and its potential mechanism.Methods SPF SD rats’ drunken model and SPF Kunming mice’s hangover model were used as models.Results Ganshuang granule could significantly reduce sleep time, the time to climb in mice, and significantly prolong the tolerance time and shorten sleep time in rats (p < 0.05). The blood ethanol concentration of rats in each administration group was lower than that in the model group at each time point (p < 0.05). Compared with the control group, the activities of ADH and ALDH in the liver of the model group were significantly decreased (p < 0.05); the content of DA and 5-HT in the striatum of the model group was significantly increased (p < 0.05); and the activity of AchE in the hippocampus was significantly decreased (p < 0.05). The above processes could be improved and regulated in the drug administration group. Compared with the control group, there was no significant difference between ADH and ALDH in the serum of the model group (p > 0.05). However, the activities of ADH and ALDH in the liver of drunk rats could be upregulated by Ganshuang granule (p < 0.05).Conclusion Ganshuang granule has the pharmacological effects of anti-alcoholic and anti-hangover, which is related to regulating the activities of ADH and ALDH in the liver, the contents of DA and 5-HT in striatum, and the activity of AchE in the hippocampus.
研究领域:
药理学
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生物化学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Ginseng Research
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2025
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IF 5.6
Weimin Wang,Kaixuan Zhou,Zengshuai Fu,Yucheng Huang,Jianjun Deng,Daidi Fan,Haixia Yang
Background Alcohol-induced liver injury contributes to various liver diseases, with dietary interventions of ginsenosides being a promising solution. Ginsenosides, the major active compounds of Panax ginseng Meyer , are divided into protopanaxadiol (PPD) and protopanaxatriol (PPT) based on C-3 or C-6 glycosylation, which have anti-inflammatory and antioxidant effects, but structure-activity relationships remain unclear. Methods Using C57BL/C mice with alcohol-induced liver injury, we evaluated Rg5 and F4 effects on liver function, inflammation, lipid deposition, apoptosis, alcohol metabolism, and lipid synthesis. Results Rg5 (60 mg/kg) demonstrated significantly superior efficacy to F4 in alleviating alcohol-induced liver injury, reducing lipid deposition through 33.9% and 25.8% decreases in serum triglyceride (TG) and total cholesterol (TC) levels versus the F4 group. Additionally, Rg5 attenuated hepatic apoptosis by reducing BAX and cleaved-CASPASE-3 protein expression by 26.3% and 28.4% compared to F4. Rg5 enhanced alcohol metabolism through activation of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH), thereby restoring AMP-activated protein kinase (AMPK) phosphorylation by 26.1% while reducing sterol regulatory element-binding protein 1 (SREBP-1) expression by 27.8% (compared to F4), with efficacy approaching that of positive control silymarin. Molecular docking revealed that the C-6 sugar moiety of F4 induced hydrogen bond donor repulsion, increasing hydrogen bond length and weakening binding stability with ADH, ALDH and AMPK, providing a structural basis for Rg5's superior hepatoprotective activity. Conclusion These findings highlight the critical influence of glycosylation position on hepatoprotective activity of ginsenosides, and provide insights into the structural modification of ginsenosides, which could contribute to the treatment of alcohol-related liver disease.
研究领域:
药理学
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生物化学
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药物化学
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分子生物学
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营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Protein & Cell
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2024
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IF 13.6
Ma Wei,Zhang Lu,Chen Weilong,Chang Zhaoxia,Tu Juchuanli,Qin Yuanyuan,Yao Yuwen,Dong Mengxue,Ding Jiajun,Li Siqin,Li Fengkai,Deng Qiaodan,Yang Yifei,Feng Tingting,Zhang Fanrong,Shao Xiying,He Xueyan,Zhang Lixing,Hu Guohong,Liu Quentin,Jiang Yi-Zhou,Zhu Shu,Xiao Zhi,Su Dan,Liu Tong,Liu Suling
Tumor-resident microbiota in breast cancer promote cancer initiation and malignant progression. However, targeting microbiota to improve the effects of breast cancer therapy has not been investigated in detail. Here, we evaluated the microbiota composition of breast tumors and found that enterotoxigenic Bacteroides fragilis (ETBF) was highly enriched in the tumors of patients who did not respond to taxane-based neoadjuvant chemotherapy. ETBF, albeit at low biomass, secreted the toxic protein BFT-1 to promote breast cancer cell stemness and chemoresistance. Mechanistic studies showed that BFT-1 directly bound to NOD1 and stabilized NOD1 protein. NOD1 was highly expressed on ALDH+ breast cancer stem cells (BCSCs) and cooperated with GAK to phosphorylate NUMB and promote its lysosomal degradation, thereby activating the NOTCH1-HEY1 signaling pathway to increase BCSCs. NOD1 inhibition and ETBF clearance increases the chemosensitivity of breast cancer by impairing BCSCs.
研究领域:
肿瘤学
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微生物学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Food Bioscience
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2023
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IF 5.2
Zixu Wang,Lujuan Xing,Jiaming Cai,Fidel Toldrá,Yuejing Hao,Wangang Zhang
Alcoholic liver disease (ALD) is a worldwide disease caused by excessive ethanol consumption. In current study, hepatoprotective peptides were isolated from the porcine liver while their activities and interactions with ethanol metabolizing enzymes (alcohol dehydrogenase: ADH/acetaldehyde dehydrogenase: ALDH) were analyzed. The alcalase digested porcine liver hydrolysate (PLH) was confirmed to possess ADH/ALDH activation ability in a dose-dependent manner. The peptide sequences of PLH were identified by mass spectrometry. Molecular docking and in silico analysis were federatively used for screening. NTLPHPTAP had the lowest binding energy with ADH (−0.88 kcal/mol) and low toxicity. Fluorescence quenching data showed a dynamic fluorescence quenching constant (Kq) for NTLPHPTAP interacting with ADH/ALDH (ADH: 1.57 × 10 −10 M −1 s −1 ; ALDH:1.961 × 10 −10 M −1 s −1 ). Circular dichroism (CD) spectra and infrared spectrometer (FTIR) revealed that the enzyme secondary structures became flexible and disordered after interaction with NTLPHPTAP. Meanwhile, the ADH/ALDH was speculated to bind NTLPHPTAP via amido and carbonyl groups, respectively. These results indicated that the formation of ADH/ALDH-NTLPHPTAP complexes expanded the overall structure of the original enzymes and further increased the possibility of enzyme-substrate binding. In conclusion, the study proposed a method for the extraction of porcine liver hepatoprotective peptides and suggested further explanation for the interaction between NTLPHPTAP and ADH/ALDH in vitro .
研究领域:
生物化学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
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2016
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IF 8.387
Rong Sun,Song Shen,Yun-Jiao Zhang,Cong-Fei Xu,Zhi-Ting Cao,Long-Ping Wen,Jun Wang
Cancer stem cells (CSCs) have garnered increasin g attention over the past decade, as they are believed to play a crucial role in tumor initiation, progression and metastasis, relapse and drug resistance. Therapeutic strategies which simultaneously exterminate both bulk tumor cells and the rare CSC subpopulation may produce striking response and result in long-term tumor remission. Accumulating evidence provides insight into the function of autophagy in maintenance, plasticity and survival of CSCs. The role of autophagy in the susceptibility of breast CSCs to chemotherapeutics was investigated in the present work, reduced ‘stemness’ and increased susceptibility to chemotherapy drugs (doxorubicin, DOX and docetaxel, DTXL) were observed after chloroquine (CQ)-mediated autophagy inhibition in sorted ALDH hi cells of breast cancer cell line MDA-MB-231. We further proved that nanoparticle-mediated autophagy inhibition promoted the efficacy of chemotherapeutics against ALDH hi MDA-MB-231 cells in vitro . Administration of drug delivery systems significantly prolonged the circulation half-life and augmented enrichment of two different drugs in tumor tissues and ALDH hi cells. More importantly, compared with single treatment, the combined delivery systems NP CQ /NP DOX and NP CQ/DOX (NP CQ /NP DTXL and NP CQ/DTXL ) showed most effective and persistent tumor growth inhibitory effect by eliminating bulk tumor cells as well as CSCs ( p < 0.01) in an MDA-MB-231 orthotopic tumor murine model. Therefore, our research provides new insights into the nanoparticle-facilitated combination of autophagy inhibition and chemotherapy for effective therapy of breast cancer.
研究领域:
肿瘤学
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药理学
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纳米技术
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癌症生物学
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药物递送系统
✓ 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）