JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
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2026
·Vol. 40
·期 7
·e70979
·
IF 3.6
Meng Wang,Guangwei Jiang,Xiangjun Meng,Lina Wang
Diabetic retinopathy (DR) stands as a common microvascular issue associated with diabetes mellitus, a condition defined by progressive structural decline in the retina. Although studies have reported that vitexin exhibits positive pharmacological activity in inflammatory eye diseases and has been shown to protect against neuronal damage, its efficacy in treating DR and its underlying mechanism of action remain unreported. Cellular viability was determined via the Cell Counting Kit-8 (CCK-8) approach. Oxidative stress, apoptosis, and inflammatory response in cells were assessed via flow cytometry, the thiobarbituric acid (TBA) assay, commercial kits, and western blot analysis. Combined with bioinformatics analysis (online Swiss Target Prediction, Comparative Toxicogenomics Database (CTD), online Gene Cards, and molecular docking), it was confirmed that vitexin's cytoprotection in ARPE-19 cells against damage is mediated by caspase-3 (CASP3). In HG-challenged ARPE-19 cells, vitexin successfully mitigated oxidative stress. This was evidenced by downregulated levels of malondialdehyde (MDA) and reactive oxygen species (ROS), coupled with enhanced enzymatic performance of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). It also attenuated the inflammatory response by suppressing tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) while promoting interleukin-10 (IL-10), ultimately leading to reduced apoptosis. Differential gene screening and molecular docking analysis revealed an interaction between CASP3 and vitexin. Moreover, in HG challenged ARPE-19 cells, overexpressing CASP3 significantly compromised the protective benefits conferred by vitexin. Vitexin alleviates damage to ARPE-19 cells induced by HG via CASP3, exerting a protective effect in early DR.
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PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2020
·Vol. 42
·期 7
·1101-1110
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IF 5.064
Ma Xiao-yao,Zhang Man,Fang Ge,Cheng Chuan-jing,Wang Mu-kuo,Han Yi-man,Hou Xiao-tao,Hao Er-wei,Hou Yuan-yuan,Bai Gang
Alcoholic liver disease (ALD) is one of the pathogenic factors of chronic liver disease with the highest clinical morbidity worldwide. Ursolic acid (UA), a pentacyclic terpenoid carboxylic acid, has shown many health benefits including antioxidative, anti-inflammatory, anticancer, and hepatoprotective activities. We previously found that UA was metabolized in vivo into epoxy-modified UA containing an epoxy electrophilic group and had the potential to react with nucleophilic groups. In this study we prepared an alkynyl-modified UA (AM-UA) probe for tracing and capturing the target protein of UA from liver in mice, then investigated the mode by which UA bound to its target in vivo. By conducting proteome identification and bioinformatics analysis, we identified caspase-3 (CASP3) as the primary target protein of UA associated with liver protection. Molecule docking analysis showed that the epoxy group of the UA metabolite reacted with Cys-163 of CASP3, forming a covalent bond with CASP3. The binding mode of the UA metabolites (UA, CM-UA, and EM-UA) was verified by biochemical evaluation, demonstrating that the epoxy group produced by metabolism played an important role in the inhibition of CASP3. In alcohol-treated HepG2 cells, pretreatment with the UA metabolite (10 μM) irreversibly inhibited CASP3 activities, and subsequently decreased the cleavage of PARP and cell apoptosis. Finally, pre-administration of UA (20–80 mg· kg −1 per day, ig, for 1 week) dose-dependently alleviated alcohol-induced liver injury in mice mainly via the inhibition of CASP3. In conclusion, this study demonstrates that UA is a valuable lead compound for the treatment of ALD.
研究领域:
药理学
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肝病学
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生物化学
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分子生物学
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PubMed
高影响因子
CyTA-Journal of Food
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2016
·
IF 0.769
Xu Si,Zhongkai Zhou,Dandan Bu,Jing Li,Padraig Strappe,Chris Blanchard
Polysaccharides were extracted from corn bran (CBPs) and then modified by a sulfating reaction to obtain sulfated corn bran polysaccharides (SCBPs). Synthesized sulfated polysaccharides were located in the equatorial bonds of monosaccharide residues. A more orderly and smooth surface of SCBPs was observed. Single factor experiment results showed 2.0 g of aminosulfonic acid, 60 mL of N-dimethylformamide and 2.5 h of reaction time were the optimum conditions for SCBPs preparation. Phenolic content of SCBPs significantly decreased with increasing concentration of aminosulfonic acid, while it increased with increasing DMF concentration and reaction time. SCBPs had higher DPPH, ABTS and iron chelating capacity under the optimum conditions. SCBPs significantly inhibited the proliferation of A549 and HepG2 cell lines, which was associated with the up-regulation at the mRNA expression level of pro-apoptotic genes CASP3, CASP8, CASP9 and reduced expression of p53, gene Bcl-2 and gene iNOS.
研究领域:
生物化学
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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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高影响因子
JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY
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2026
·
IF 4.1
Jingchun Wang,Mingzheng Han,Jingling Yu,Bohao Chen,Shuaihao Guo,Ziqi Wu,Hai Huang,Zhaoxin Tang,Jianzhao Liao,Jianying Guo
Copper (Cu) exposure poses significant threats to renal health yet effective mitigation strategies remain scarce. Kaempferol (Kae) is a naturally occurring flavonoid with well-documented antioxidant and anti-apoptosis activities. Nevertheless, its protective effects in renal copper poisoning and the underlying molecular mechanisms have not been fully elucidated. This study integrated network toxicology, pharmacology, molecular docking, molecular dynamics simulation and a broiler model preliminarily revealed the mechanism of Kae alleviates Cu-induced nephrotoxicity (CuN). The potential targets of CuN scanned from Comparative Toxicogenomics Database (CTD), GeneCards database (GC) and the targets of Kae scanned from SwissTargetPrediction, PharmMapper database were used to perform GO and KEGG enrichment analysis. STRING and Cytoscape were employed to constructed PPI networks and locked on core targets. Molecular docking and dynamics simulations were used to investigate the binding affinity and stability of Kae with the core targets. A broiler model to further validate the impact of Kae on key signaling pathways. Notably, Kae effectively ameliorated histopathological damage caused by excess Cu and restored renal function ( P < 0.05). Network results revealed the involvement of apoptosis and MAPK signaling pathway, with Caspase-3 (CASP3) and Mitogen-activated protein kinase 8 (MAPK8) identified as core targets. In vivo experiments demonstrated that Cu significantly up-regulated the levels of Cleaved-CASP3 and phosphorylated MAPK8 and the expression of genes and proteins involved in promoting endogenous apoptosis ( P < 0.05), while Kae markedly reversed these effects and reduced TUNEL staining positive rate from 43.83% to approximately 12.84% ( P < 0.05). In summary, our findings demonstrate that Kae alleviates CuN by targeting the apoptotic process and the MAPK/JNK signaling axis, highlighting its potential as a natural therapeutic agent against heavy metal-induced nephrotoxicity in agricultural settings.
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高影响因子
INTERNATIONAL JOURNAL OF FOOD SCIENCE AND TECHNOLOGY
·
2017
·Vol. 52
·期 5
·1176-1184
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IF 1.64
Jing Li,Wenting Shang,Xu Si,Dandan Bu,Padraig Strappe,Zhongkai Zhou,Chris Blanchard
Summary Corn bran polysaccharides were extracted using an ultrasonic-assisted method with a yield of 33.50% and then carboxymethylated. The occurrence of modification was confirmed using Fourier transform infrared spectral analysis. The surface of polysaccharide particles became loosened following the carboxymethylation. The effect of sodium hydroxide concentration, reaction temperature, and the reaction time on the degree of substitution was investigated, and the relationship among the substitution degree, total phenolic content and antioxidant activity were studied. With sodium hydroxide concentration of 6.0 mol L −1 , keeping the reaction temperature of 60 °C and reaction time of 5.0 h, the modified polysaccharides possessed the highest degree of substitution and antioxidant activity. Cell culture model indicated that the carboxymethylated polysaccharide significantly inhibited the proliferation of A549 and HepG-2 cells, and these antitumour characteristics may be associated with the elevated expression of CASP3 , CASP8 , CASP9 , and p53 , as well as the significantly decreased expression of Bcl-2 and iNOS genes. The excellent antioxidant capacity and strong antitumour activity of these polysaccharides might provide a potential application as a naturally functional ingredient.
研究领域:
食品科学
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生物化学
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药理学
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分子生物学
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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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PubMed
高影响因子
JOR Spine
·
2024
·Vol. 7
·期 4
·e70020
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IF 3.4
Xiaoqiang Wang,Chao Song,Daqian Zhou,Yongliang Mei,Weiye Cai,Rui Chen,Jiale Lv,Houyin Shi,Zongchao Liu
Intervertebral disc degeneration (IVDD) stands as a prevalent chronic orthopedic ailment, profoundly impacting patients' well‐being due to incapacitating low back pain. Studies have highlighted a close correlation between IVDD and the programmed cell death of nucleus pulposus (NP) cells orchestrated by interleukin‐1 beta (IL‐1β), tumor necrosis factor‐alpha (TNF‐α), and caspase‐3 (CASP3). Puerarin, renowned for its anti‐inflammatory attributes and its influence on IL‐1β and TNF‐α, emerges as a promising candidate for IVDD treatment. However, the precise mechanism by which it regulates apoptosis via these pathways remains ambiguous. This investigation utilizes bioinformatics to unveil the molecular intricacies of puerarin‐mediated apoptosis regulation in IVDD, substantiated by preliminary in vitro experiments. Analysis exposes aberrant expression of pivotal apoptosis‐associated proteins (IL‐1β, TNF‐α, CASP3, CASP8, and BCL2) in IVDD patients, with network pharmacology indicating puerarin's potential efficacy in IVDD treatment by modulating apoptosis and cellular senescence pathways. Further experiments elucidate puerarin's capacity to stimulate NP cell proliferation while inhibiting apoptosis, potentially contributing to IVDD mitigation. Western blot and PCR outcomes reveal escalated expression of apoptosis‐related proteins (IL‐1β, TNF‐α, and CASP3) in lipopolysaccharide‐treated NPCs, ameliorated by puerarin intervention. Molecular docking simulations demonstrate favorable binding properties of puerarin with apoptotic proteins, while flow cytometry analysis indicates its ability to diminish NPC apoptosis. These discoveries imply that puerarin might alleviate NPC apoptosis by modulating key targets, thereby potentially ameliorating IVDD. In summary, this study unveils the intrinsic mechanism of puerarin in regulating NPC apoptosis to alleviate IVDD, underscoring its therapeutic promise. Network pharmacology and bioinformatics analyses suggest that puerarin may mitigate intervertebral disc degeneration (IVDD) by inhibiting nucleus pulposus (NP) cell apoptosis. This hypothesis was validated through in vitro experiments, which demonstrated that puerarin significantly reduces apoptosis in NPCs.
研究领域:
骨科
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药理学
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分子生物学
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生物信息学
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PubMed
高影响因子
MATERIALS & DESIGN
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2022
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IF 9.417
Yuqin Yang,Desheng Cai,Yisong Shu,Zhihua Yuan,Wenmin Pi,Yaozhi Zhang,Jihui Lu,Jingyi Jiao,Xuehao Cheng,Feifei Li,Penglong Wang,Haimin Lei
It is crucial to inhibit tumor growth and distant metastasis for breast cancer (BC) therapy. However, the treatment primarily dependent on surgery, chemotherapy, and radiotherapy is far from satisfactory. It had been demonstrated that the CXCL1/2-S100A8/9 axis played an essential role in BC therapy. Therefore, we constructed a natural product hydrogel for BC therapy by blocking CXCL1 signaling. The GK-GA (phytochemicals of Genkwa Flos -glycyrrhizic acid) hydrogel was designed in a one-step “green” approach. The pharmacodynamics study showed GK-GA exhibited significant anti-tumor and anti-lung metastasis activities, resulting in the inhibition rate of tumor growth (IRG) over 90 % at 6.25 mg·kg −1 , and did not display any obvious toxicity. In addition, the potent antitumor efficiency was also attributed to aggregation/assembly-induced retention (AIR) property. RNA sequencing analysis revealed the gene expression was significantly down-regulated in the GK-GA group, which were BCL2, CASP3, CXCL1, CXCL2, CXCR2, S100A8, S100A9, and confirmed further by western blot (WB). Our findings indicated natural product GK-GA hydrogel inhibited tumor growth and lung metastasis via the BCL2-CASP3 mitochondrial apoptosis pathway as well as the CXCL1/2-S100A8/9 pathway. This study provides inspiration for the fabrication of new excipients-free nano-dispersion in a one-step, no‐carrier‐added, organic solvent-free, “green” approach, particularly for small molecular antitumor agents.
研究领域:
肿瘤学
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药学
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分子生物学
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癌症治疗
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高影响因子
Frontiers in Pharmacology
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2023
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IF 5.6
Cao Xu,Zhang Ningyi,Chen Hening,Wang Wei,Liang Yijun,Zhang Jiaxin,Liu Ruijia,Li Shuo,Yao Yuhao,Jin Qian,Guo Ziwei,Chen Yue,Gong Yuanyuan,Li Xiaoke,Zao Xiaobin,Ye Yong’an
The JiGuCao capsule formula (JCF) has demonstrated promising curative effects in treating chronic hepatitis B (CHB) in clinical trials. Here, we aimed to investigate JCF’s function and mechanism in diseases related to the hepatitis B virus (HBV). We used mass spectrometry (MS) to identify the active metabolites of JCF and established the HBV replication mouse model by hydrodynamically injecting HBV replication plasmids into the mice’s tail vein. Liposomes were used to transfect the plasmids into the cells. The CCK-8 kit identified cell viability. We detected the levels of HBV s antigen (HBsAg) and HBV e antigen (HBeAg) by the quantitative determination kits. qRT-PCR and Western blot were used to detect the genes’ expression. The key pathways and key genes related to JCF on CHB treatment were obtained by network pharmacological analysis. Our results showed that JCF accelerated the elimination of HBsAg in mice. JCF and its medicated serum inhibited HBV replication and proliferation of HBV-replicating hepatoma cells in vitro. And the key targets of JCF in treating CHB were CASP3, CXCL8, EGFR, HSPA8, IL6, MDM2, MMP9, NR3C1, PTGS2, and VEGFA. Furthermore, these key targets were related to pathways in cancer, hepatitis B, microRNAs in cancer, PI3K-Akt signaling, and proteoglycans in cancer pathways. Finally, Cholic Acid, Deoxycholic Acid, and 3′, 4′, 7-Trihydroxyflavone were the main active metabolites of JCF that we obtained. JCF employed its active metabolites to perform an anti-HBV effect and prevent the development of HBV-related diseases.
研究领域:
药理学
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病毒学
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分子生物学
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网络药理学
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肝病学
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PubMed
高影响因子
BMC Complementary Medicine and Therapies
·
2024
·Vol. 24
·期 1
·1-15
·
IF 3.3
He Yu,Liu Fei,He Mingjuan,Long Fayu,Hu Ding,Chen Jingwen,Fang Miao,Wang Zhenlong
The purpose of this study was to investigate the mechanism by which resveratrol (Res) inhibits apoptosis and promotes proliferation and differentiation of pre-osteoblastic MC3T3-E1 cells, laying the groundwork for the treatment of osteoporosis (OP). The TCMSP database was used to find the gene targets for Res. The GeneCards database acquire the gene targets for OP. After discovering the potential target genes, GO, KEGG, and Reactome enrichment analysis were conducted. Verifying the major proteins involved in apoptosis can bind to Res using molecular docking. CCK8 measured the proliferative activity of mouse pre-osteoblasts in every group following Res intervention. Alkaline phosphatase staining (ALP) and alizarin red staining to measure the ability of osteogenic differentiation. RT-qPCR to determine the expression levels of Runx2 and OPG genes for osteogenic differentiation ability of cells. Western blot to measure the degree of apoptosis-related protein activity in each group following Res intervention. The biological processes investigated for GO of Res therapeutic OP involved in cytokine-mediated signaling pathway, negative regulation of apoptotic process, Aging, extrinsic apoptotic signaling pathway in absence of ligand, according to potential therapeutic target enrichment study. Apoptosis, FoxO signaling pathway, and TNF signaling pathway are the primary KEGG signaling pathways. Recactome pathways are primarily engaged in Programmed Cell Death, Apoptosis, Intrinsic Apoptotic Pathway, and Caspase activation via extrinsic apoptotic signaling pathways. This research established a new approach for Res treatment of OP by demonstrating how Res controls the apoptosis-related proteins TNF, IL6, and CASP3 to suppress osteoblast death and increase osteoclastogenesis.
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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生物信息学
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骨生物学
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网络医学
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高影响因子
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