Food & Function
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2024
·Vol. 15
·期 6
·3008-3022
·
IF 5.1
Danyin Yang,Qi Liu,Qiongyao Xu,Lin Zheng,Silu Zhang,Shan Lu,Guoxun Xiao,Mouming Zhao
This work aimed to investigate the protective effects of collagen hydrolysates containing different contents of Gly-Pro-Xaa tripeptides on UV-induced photoaging mice and to identify potent anti-photoaging peptides. Results showed that oral ingestion of collagen hydrolysates with a higher content of Gly-Pro-Xaa tripeptides (∼11.4%, HCH) dramatically enhanced the absorption of Pro-Hyp, Hyp-Gly, and Gly-Pro-Hyp into the body, which were 1.77-, 2.18-, and 65.07-fold higher in area under the concentration–time curve (AUC) values than that of collagen hydrolysates with a lower content of Gly-Pro-Xaa tripeptides (∼3.8%, LCH), respectively. Furthermore, the protective effects of HCH on the photo-aged skin of mice were significantly stronger than those of LCH in terms of increases in the contents of hyaluronic acid and collagen, improvement in skin elasticity and epidermal thickness, alleviation in inflammation, and decreases in the contents of matrix metalloproteinase-1 (MMP-1) and MMP-3. More importantly, Gly-Pro-Hyp displayed potent anti-photoaging activities comparable to HCH based on an equivalent amount of Hyp. Network pharmacology analysis for potential mechanisms further indicated that Gly-Pro-Hyp might interact with JUN and FOS and regulate IL-17 and TNF signaling pathways. Collectively, our results suggested that HCH had great potential to be applied in functional foods for skin health and Gly-Pro-Hyp was found to be a potent collagen-derived anti-photoaging peptide, which might contribute to the excellent anti-photoaging effects of HCH.
研究领域:
药理学
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皮肤病学
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美容护肤品
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营养保健品
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产品关联
DOI
PubMed
高影响因子
Human Cell
·
2024
·
IF 3.4
Cao Yue,Xing Ruixian,Li Qiushi,Bai Yang,Liu Xuewen,Tian Buxian,Li Xin
Reperfusion after cerebral ischemia leads to secondary damage to the nervous system, called cerebral ischemia/reperfusion injury (CIRI). The blood–brain barrier (BBB) consists of endothelial cells and tight junction (TJ) proteins, and its disruption aggravates CIRI. Two GSE datasets identified Tissue Factor Pathway Inhibitor 2 (TFPI2) as a differentially upregulated gene (Log2FC > 1, p < 0.01) in the cerebral cortex of ischemic rats, and TFPI2 affects angiogenesis of endothelial cells. Moreover, genes (c-Jun, c-Fos, FosL1) encoding subunits of Activator Protein-1 (AP-1), a transcription factor involved in IRI, were highly expressed in ischemic samples. Thus, the effects of the AP-1/TFPI2 axis on CIRI were explored. We determined increased TFPI2 expression in the cerebral cortex of rats receiving middle cerebral artery occlusion (MCAO) for 90 min and reperfusion (R) for 48 h. Then AAV2-shTFPI2 particles (5 × 10 10 vg) were injected into the right lateral ventricle of rats 3 weeks before MCAO/R. TFPI2 knockdown decreased infarct size and neuronal injury in ischemic rats. It improved BBB integrity, demonstrated by reduced FITC-dextran leakage in brain tissues of MCAO/R-operated rats. Furthermore, it increased the expression of TJ proteins (Occludin, Claudin-5, TJP-1) in the cerebral cortex of rats with CIRI. Consistently, we found that TFPI2 knockdown mitigated cell damage in mouse endothelial bEND.3 cells with oxygen and glucose deprivation (ODG) for 6 h and reoxygenation (R) for 18 h (OGD/R) treatment. High co-expression of c-Jun and c-Fos significantly elevated TFPI2 promoter activity. c-Jun knockdown inhibited TFPI2 expression in OGD/R-treated bEND.3 cell. Collectively, our findings demonstrate that inhibition of the AP-1/TFPI2 axis alleviates CIRI.
研究领域:
神经科学
·
分子生物学
·
细胞生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2023
·
IF 3.4
Yao Wang,Lili Liu,Cheng Cheng,Shuxuan Wang,Qirui Zhai,Yunyang Song,Ronghua Dai
Zishen Pill (ZSP) is a traditional Chinese medicine that is frequently used to treat Benign Prostatic Hyperplasia (BPH), however its specific mechanism of action and active ingredients are yet unknown. We used a combination of serum pharmacochemistry and network pharmacology and a series of biochemical assays to explore the action mechanism of ZSP in the treatment of BPH. The BPH rat model was created using testosterone propionate , and following oral ZSP administration, the components of ZSP in rat serum were detected by UPLC-Q-Exactive Orbitrap/MS method. A "component-target-disease" network and PPI networks were constructed on this foundation. The primary mechanism of ZSP decreasing BPH in rats was studied by KEGG pathway and GO analysis. Finally, the potential pathways and key targets were further verified in vivo by molecular biology and immunological methods . 46 substances were charactered from rat serum, and 164 anti-BPH targets were screened from the database. According to network pharmacology, the primary targets were CASP3, STAT3, JUN, and PTGS2/COX2. Three related pathways (PI3K/Akt signaling pathway, AGE-RAGE signaling pathway and EGFR tyrosine kinase inhibitor resistance) were closely related to the therapeutic effects of ZSP. The findings of molecular biology demonstrated that ZSP may bring Bcl-2, BAX, CASP3, COX2, and 5LOX protein and gene expression in BPH rats appreciably closer to that of normal rats. Additionally, ZSP can lessen the expression of inflammatory cytokines in BPH rats, including VEGF, TNF-α, CCL5, and interleukin. Conclusion The above results suggest that ZSP may reduce BPH through inflammation/immunity and apoptosis/proliferation-related pathways. This study offers a fresh approach to investigate the basic pharmacological effects and mechanism of ZSP in the treatment of BPH.
研究领域:
药理学
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中医药
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2018
·
IF 3.04
Yuxin Wang,Linyao Li,Yawen Wang,Xiaokang Zhu,Mingdong Jiang,Erqun Song,Yang Song
A large population of drug candidates have failed “from bench to bed” due to unwanted toxicities. We intend to develop an alternative approach for drug discovery, that is, to seek candidates from “safe” compounds. Rebaudioside A (Reb-A) is an approved commercial sweetener from Stevia rebaudiana Bertoni. We found that Reb-A protects against carbon tetrachloride (CCl 4 )-induced oxidative injury in human liver hepatocellular carcinoma (HepG2) cells. Reb-A showed antioxidant activity on reducing cellular reactive oxygen species and malondialdehyde levels while increasing glutathione levels and superoxide dismutase and catalase activities. Reb-A treatment induced nuclear factor erythroid-derived 2-like 2 (Nrf2) activation and antioxidant response element activity, as well as the expression of heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). Further mechanistic studies indicated that c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), mitogen-active protein kinase (MAPK) and protein kinase C epsilon (PKCε) signaling was upregulated. Thus, the present in vitro study conclusively demonstrated that Reb-A is an activator of Nrf2 and is a potential candidate hepatoprotective agent. More importantly, the present study illustrated that seeking drug candidates from “safe” compounds is a promising strategy.
研究领域:
药理学
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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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药物发现
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Zijie Wang,Anan Jiang,Hongmei Xiao,Xiaofan Yuan,Shaoru Zhang,Xinyue Qin
Objective: To study the potential targets and molecular mechanisms of Fritiliariae Irrhosae Bulbus (FIB) in the treatment of ischemic strokes based on a network pharmacology strategy, with a combination of molecular docking and animal experiments.Methods: The active components and targets of FIB were screened by TCMSP database and TCMIP database, and the related targets of ischemic strokes were screened by GeneCards, OMIM, CTD, and DrugBank, then the intersection targets of the two were taken. The protein interaction network was constructed by STRING, the PPI network diagram was drawn by using Cytoscape software, and the key targets of FIB treatment of ischemic strokes were analyzed by MCODE. The DAVID database was used for GO and KEGG enrichment analysis, and the potential pathway of FIB against ischemic strokes was obtained. Molecular docking was performed by using AutoDock Tools 1.5.6 software. Finally, a mouse model of ischemic stroke was established, and the results of network pharmacology were verified by in vivo experiments. Realtime Polymerase Chain Reaction was used to detect the expression levels of relevant mRNAs in the mouse brain tissue. Western blot was used to detect the expression levels of related proteins in the mouse brain tissue.Results: 13 kinds of active components of FIB were screened, 31 targets were found in the intersection of FIB and ischemic strokes, 10 key targets were obtained by MCODE analysis, 236 biological processes were involved in GO enrichment analysis, and key targets of KEGG enrichment analysis were mainly concentrated in Neuroactive light receptor interaction, Calcium signaling pathway, Cholinergic synapse, Hepatitis B, Apoptosis—multiple specifications, Pathways in cancer and other significantly related pathways. There was good binding activity between the screened main active components and target proteins when molecular docking was performed. Animal experiments showed that the infarct volume of brain tissue in the FIB treatment group was considerably reduced. RT-qPCR and the results of Western Blot showed that FIB could inhibit the expression of active-Caspase3, HSP90AA1, phosphorylated C-JUN, and COX2.Conclusion: Based on network pharmacology, the effect of FIB in the treatment of ischemic strokes was discussed through the multi-component-multi-target-multi-pathway. The therapeutic effect and potential mechanisms of FIB on ischemic strokes were preliminarily explored, which provided a ground work for further researches on the pharmacodynamic material basis, mechanism of action and clinical application.
研究领域:
药理学
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神经科学
·
分子生物学
·
生物信息学
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实验医学
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产品关联
DOI
PubMed
高影响因子
Signal Transduction and Targeted Therapy
·
2024
·Vol. 9
·期 1
·1-17
·
IF 40.8
Peng Fu,Liao Minru,Jin Wenke,Liu Wei,Li Zixiang,Fan Zhichao,Zou Ling,Chen Siwei,Zhu Lingjuan,Zhao Qian,Zhan Gu,Ouyang Liang,Peng Cheng,Han Bo,Zhang Jin,Fu Leilei
Sirtuin 3 (SIRT3) is well known as a conserved nicotinamide adenine dinucleotide + (NAD + )-dependent deacetylase located in the mitochondria that may regulate oxidative stress, catabolism and ATP production. Accumulating evidence has recently revealed that SIRT3 plays its critical roles in cardiac fibrosis, myocardial fibrosis and even heart failure (HF), through its deacetylation modifications. Accordingly, discovery of SIRT3 activators and elucidating their underlying mechanisms of HF should be urgently needed. Herein, we identified a new small-molecule activator of SIRT3 (named 2-APQC) by the structure-based drug designing strategy. 2-APQC was shown to alleviate isoproterenol (ISO)-induced cardiac hypertrophy and myocardial fibrosis in vitro and in vivo rat models. Importantly, in SIRT3 knockout mice, 2-APQC could not relieve HF, suggesting that 2-APQC is dependent on SIRT3 for its protective role. Mechanically, 2-APQC was found to inhibit the mammalian target of rapamycin (mTOR)-p70 ribosomal protein S6 kinase (p70S6K), c-jun N-terminal kinase (JNK) and transforming growth factor-β (TGF-β)/ small mother against decapentaplegic 3 (Smad3) pathways to improve ISO-induced cardiac hypertrophy and myocardial fibrosis. Based upon RNA-seq analyses, we demonstrated that SIRT3-pyrroline-5-carboxylate reductase 1 (PYCR1) axis was closely assoiated with HF. By activating PYCR1, 2-APQC was shown to enhance mitochondrial proline metabolism, inhibited reactive oxygen species (ROS)-p38 mitogen activated protein kinase (p38MAPK) pathway and thereby protecting against ISO-induced mitochondrialoxidative damage. Moreover, activation of SIRT3 by 2-APQC could facilitate AMP-activated protein kinase (AMPK)-Parkin axis to inhibit ISO-induced necrosis. Together, our results demonstrate that 2-APQC is a targeted SIRT3 activator that alleviates myocardial hypertrophy and fibrosis by regulating mitochondrial homeostasis, which may provide a new clue on exploiting a promising drug candidate for the future HF therapeutics.
研究领域:
心血管药理学
·
分子生物学
·
细胞生理学
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DOI
高影响因子
Cureus Journal of Medical Science
·
2024
·
IF 1
Ye-Ran Mao,Ling-Yi Zhu,Ruo-Fei Du,Xiao-Yu Liu,Zhidan Liu,Li Li
Background and objectives: In ancient China, bee venom was widely used to treat various diseases. Although using bee venom is not currently a mainstream medical method, some have applied it to treat certain conditions, including idiopathic facial paralysis (IFP). Recently, melittin (Mel), the main active component of bee venom, has been shown strong anti-inflammatory and analgesic effects. However, how bee venom improves neurological dysfunction in facial paralysis remains unknown. This study aimed to investigate the anti-neurotraumatic effect of Mel on Schwann cells (SCs), the main cells of the neuron sheath, injured by oxidative stress. Methods: A model of hypoxic SCs was established, and CCK-8 assay, siRNA transfection, enzyme-linked immunosorbent assay, quantitative reverse transcription-polymerase chain reaction, western blot, immunofluorescence, and cell ultrastructure analyses were conducted to investigate the mitigation of hypoxia-induced damage to SCs in vitro, revealing the effects of Mel on oxidative stress injury in SCs. Results: The overexpression of HIF-1α in CoCl 2 -induced SCs (p < 0.05) indicated the establishment of an SCs hypoxia model. The proliferation and regeneration process of the hypoxic SCs enhanced in the Mel-treated group compared to the CoCl 2 group has been proven through the CCK-8 experiment (p < 0.0001) and S-100 mRNA expression detection (p < 0.0001). The increased level of reactive oxygen species (ROS) (p < 0.001) and decreased superoxide dismutase (SOD) levels (p < 0.05) in the CoCl 2 -induced SCs indicated that Mel can alleviate the oxidative stress damage to SCs induced by CoCl 2 . Mel alleviated oxidative stress and inflammation in hypoxic SCs by reducing pro-inflammatory cytokines IL-1β (p < 0.0001) and TNF-α (p < 0.0001). In addition, Mel augmented cellular vitality and regulated indicators related to oxygen metabolism, cell repair, neurometabolism, and vascular endothelial formation after hypoxia, such as C-JUN (p < 0.05), glial cell line-derived neurotrophic factor (GDNF; p < 0.001), vascular endothelial growth factor (VEGF; p < 0.05), hypoxia-inducible factor 1-alpha (HIF-1α; p < 0.05), interleukin-1 receptor type 1 (IL-1R1; p < 0.05), enolase1 (ENO1; p < 0.05), aldose reductase (AR; p < 0.01), SOD (p < 0.05), nerve growth factor (NGF; p < 0.05), and inducible nitric oxide synthase (iNOS; p < 0.05). In terms of its mechanism, Mel inhibited the expression of proteins associated with the NF-κB pathway such as IKK (p < 0.01), p65 (p < 0.05), p60 (p < 0.001), IRAK1 (p < 0.05), and increased IKB-α (p < 0.0001). Moreover, knocking out of IL-1R1 in the si-IL-1R1 group enhanced the therapeutic effect of Mel compared to the Mel-treated group (all of which p < 0.05). Conclusion: This research provided evidence of the substantial involvement of IL-1R1 in oxidative stress damage caused by hypoxia in SCs and proved that Mel alleviated oxidative stress injury in SCs by targeting IL-1R1 to downregulate the NF-κB-mediated inflammatory response. Mel could potentially serve as an innovative therapeutic approach for the treatment of IFP.
研究领域:
神经科学
·
药理学
·
细胞生物学
·
分子生物学
·
炎症
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氧化应激
·
面瘫
✓ 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）