INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
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2023
·Vol. 52
·期 6
·1-11
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IF 5.4
Su-Ji Jeon,Eun-Young Choi,Eun-Ji Han,Sang-Woo Lee,Jun-Mo Moon,Soo-Hyun Jung,Ji-Youn Jung
Piperlongumine (PL) is an amide alkaloid with diverse pharmacological effects against cancer, bronchitis and asthma; however, research on its efficacy against melanoma is lacking. The present study investigated the anticancer effects of PL on A375SM and A375P human melanoma cells. PL decreased the survival rate of A375SM and A375P cells, as shown by MTT assay, increase of apoptotic cells by DAPI staining. And PL induced apoptosis by decreasing the expression of the anti‑apoptotic protein Bcl‑2 and increasing that of the pro‑apoptotic proteins cleaved‑PARP and Bax. PL also induced apoptosis in A375SM and A375P cells via the MAPK pathway, increasing expression of the MAPK pathway proteins, phosphorylated‑(p‑ERK), p‑JNK p‑p38. These proteins were confirmed by western blot. In addition, A375SM and A375P cells treated with PL showed an increased number of acidic vesicular organelles by acridine orange staining. Also, autophagy induced by the expression of 1A/1B‑light chain 3, Beclin 1and mTOR was investigated through western blot. When PL was applied following treatment with autophagy inhibitors 3‑methyladenine and hydroxychloroquine, autophagy exhibited a cytoprotective effect against apoptosis in MTT assay. Pretreatment of A375P cells with the ERK inhibitor PD98059 and the JNK inhibitor SP600125 followed by treatment with PL confirmed that apoptosis and autophagy were mediated via the MAPK/ERK pathway by western blot. In summary, the present study provided empirical evidence supporting the anticancer effects of PL on human melanoma cells and indicated the potential of PL as a treatment for melanoma.
研究领域:
肿瘤学
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细胞生物学
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药理学
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DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 16
·6014
·
IF 4.6
Shanbin Chen,Dong Zhao,Chunguang Luan,Jia Zheng,Wei Liu,Zheng Feng,Ruiqi Luo,Xinglin Han,Deliang Wang
Ferulic acid (FA) is a bioactive compound found in traditional Chinese herbal medicine; for example, it is present in Xinjiang Ferula, but also in strong-flavor Chinese baijiu. FA has been shown to play a crucial role in treating oxidative stress, skin whitening, and eye diseases. In this study, the potential role of FA as a means of inducing apoptosis and inhibiting colon cancer induced by the transplantation of CT26 cells was investigated. The results show that FA adjuvant treatment caused an upregulation in the expression of genes related to autophagy while simultaneously suppressing the expression of inflammatory response elements and improving the bodyweight, glutamic pyruvic transaminase (ALT), and glutamic oxaloacetic transaminase (AST) in vivo. Furthermore, FA inhibited the proliferation of CT26 cells and induced apoptosis, specifically by activating the phosphorylation of ERK and JNK to enhance the essential proteins BCL-2 and BAX in the apoptosis pathway. These results suggest that FA could be a promising auxiliary therapeutic agent for the treatment of colon cancer. Further research is needed to better understand the mechanisms underlying the beneficial effects of FA and its synergistic effects with other compounds.Keywords:ferulic acid;apoptosis;autophagy;MAPK pathway
研究领域:
药理学
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肿瘤学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ACTA HISTOCHEMICA
·
2025
·
IF 2.4
Xiaorui Dong,Xixi Chen,Mengling Xue,Yina Zhang,Peiyue Jiang
Background Cervical cancer (CC) is a common gynecological disease that seriously threatens women’s health. This study aims to explore key genes and pathways related to CC prognosis through bioinformatics, providing new insights for further treatment of CC. Methods CC patient data were analyzed from the public databases. The enrichment analyses explored the roles and pathways of CC-related differentially expressed genes (DEGs). A prognostic key gene was identified using Venn diagrams and subjected to survival analysis. Gene Set Enrichment Analysis (GSEA) was employed to investigate the potential pathways of key genes. Correlations between the key gene and clinical features were examined. The function of the key gene was validated through immunohistochemistry, flow cytometry, transwell, MTT, and Western blot assays in vitro and in vivo . Results Our research identified 2459 upregulated genes among DEGs between healthy and tumor cervical tissues. These DEGs were primarily enriched in the PI3K-AKT and MAPK pathways. Moreover, EFNA1 was recognized as a key prognostic gene in CC, with elevated expression compared to normal tissue. A negative correlation between EFNA1 levels and patient survival rates was corroborated by Kaplan-Meier analysis. Furthermore, EFNA1 expression correlated with the cancer stage and was linked to antigen presentation, folate synthesis, and IL-17 signaling. Knockdown of EFNA1 enhanced apoptosis and reduced migration, invasion, and proliferation in vitro and in vivo , inhibiting EMT and MAPK pathways. Conclusion This study revealed the key signaling pathways in CC progression and identified EFNA1 as a crucial prognostic biomarker, potentially impacting CC treatment.
研究领域:
肿瘤学
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生物信息学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2017
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IF 3.154
Fujie Yan,Yunyun Yang,Lushuang Yu,Xiaodong Zheng
Main components of Apios americana leaves extract (ALE) were flavonoid C-glycosides, including vitexin (46.7%), schaftoside (18.9%), and orientin (4.32%). In vitro, ALE restored glucose consumption, glucose uptake, and glycogen content in glucose-induced hepatic cells. Exposure of HepG2 cells to high glucose resulted in reactive oxygen species and O2– accumulation, while ALE alleviated these increases by 47 ± 0.68 and 68 ± 0.74%, respectively. Glucose increased c-Jun N-terminal kinase (JNK) and decreased extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 phosphorylation, while ALE reduced p-JNK and p-p38 but not p-ERK1/2, accompanied by nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1, and NAD(P)H quinine oxidoreductase 1 downregulation. In vivo, the lifespan of Caenorhabditis elegans was more violently shortened by paraquat under hyperglycemia, while ALE protected this damage in N2 worms (2.6 times extension) but not in daf-16 mutants. Furthermore, p38/PMK-1 and Nrf2/SKN-1 expressions in worms were suppressed by glucose, which were reversed by ALE treatment. These results suggest that ALE prevents glucose-induced damage via regulating specific mitogen-activated protein kinases and Nrf2 pathways.
研究领域:
药理学
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分子生物学
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DOI
PubMed
高影响因子
American Journal of Translational Research
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2017
·
IF 2.829
Yuanfeng Zhu,Shijun Fan,Ning Wang,Xiaoli Chen,Yongjun Yang,Yongling Lu,Qian Chen,Jiang Zheng,Xin Liu
Activation of NADPH oxidase 2 (NOX2) triggers reactive oxygen species (ROS) generation, both of which are essential for robust microbial clearance by phagocytes. However, it is unknown whether inhibition of NOX2 activation or ROS generation affects cellular phagocytosis. Here, we found that the classic NOX2 inhibitor diphenyleneiodonium (DPI) induced uptake of E. coli by murine peritoneal macrophages through enhancing phagocytosis, and this effect was temperature-sensitive and attenuated by cytochalasin D as well as chemical inhibition of Syk and PLCγ, two downstream kinases involved in actin polymerization during phagocytosis. DPI also decreased the production of TNF-α and IL-6 resulting from E. coli stimulation. The DPI-induced enhancement of phagocytosis was independent of NOX2 inhibition or ROS generation but depended on increased intracellular calcium and activation of the p38 MAPK signaling pathway. Furthermore, DPI enhanced bacterial elimination and ameliorated inflammation in E. coli -infected mice, leading to improved survival. Our results demonstrate that DPI facilitates ROS-independent bacterial phagocytosis by macrophages through activation of calcium and p38 MAPK signaling pathways.
研究领域:
免疫学
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分子生物学
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医学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
·
IF 8.5
Rong Huang,Wenyu Zhang,Yueqi Hu,Junjie Xu,Zhihui Dong,Jikai Liu,Li Zhou
Atopic dermatitis (AD), a prevalent inflammatory skin condition, significantly impacts patients' quality of life due to the multifaceted etiology and the lack of targeted therapeutic options. As the “Chinese herbal antibiotic”, Houttuynia cordata is renowned for its diverse pharmacological attributes. This study aims to investigate the therapeutic potential of Houttuynia cordata polysaccharides (HCP) in treating AD and to elucidate the mechanisms involved. HCP alleviated AD in MC903-induced mice by reducing epidermal thickness, skin lesions, mast cell infiltration, inflammatory cytokines, and restoring barrier proteins. It also suppressed inflammatory cytokines/chemokines via the mitogen-activated protein kinase (MAPK) pathway in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and tumor necrosis factor-alpha (TNF-α)/ interferon-γ(IFN-γ)-induced human keratinocytes cells (HaCaT). Moreover, HCP modulated inflammation-related metabolic pathways, especially restored lipid metabolic homeostasis through upregulating phosphatidylcholine (PC) and downregulating triglyceride (TG), lysophosphatidylcholine (LPC), potentially alleviating AD-like lesions and restoring barrier function. Our findings underscore the promising potential of HCP as a topical therapeutic candidate for AD treatment, offering a new direction for the development of targeted AD therapies.
研究领域:
皮肤病学
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药理学
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免疫学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2025
·
IF 8.2
Ruoting Xian,Hongyi Xian,Hao Dong,Jiating Lin,Xianxian Zhuang,Yue Zou,Qinkai Xie,Youde Liang,Shaobing Li
Repair and regeneration of oral and maxillofacial tissue defects remain significant challenges, mainly due to the limitations of existing treatment approaches. Conventional methods such as transplantation, tissue scaffolds, growth factors, and stem cell therapies often face obstacles, including donor shortages, insufficient vascularization, and safety concerns. There is an urgent need for innovative therapeutic strategies to effectively promote vascular regeneration while minimizing complications. Black phosphorus nanosheets (BPNSs) and hydrogels present significant advantages and broad application potential as tissue regeneration carriers due to their biocompatibility, degradability, and controlled drug release properties. By combining various characterization techniques and detection methods, we conducted a thorough analysis of BPNSs and gelatin methacryloyl (GelMA) scaffolds loaded with BPNSs (BP-GelMA). The results indicate that this study successfully prepared BPNSs with uniform size, good dispersion, and intact structure. Moreover, the BP-GelMA composite demonstrated excellent swelling behavior and structural stability while effectively enabling the controlled release of BPNSs. This study investigated the angiogenic effects of BP-GelMA at concentrations of 0, 12.5, and 25.0 μg/mL. In vitro experiments showed that BP-GelMA significantly enhanced endothelial cell proliferation, migration, and tube formation. In vivo results demonstrated that 12.5 μg/mL and 25.0 μg/mL BP-GelMA did not induce significant developmental toxicity in zebrafish and effectively promoted neovascularization. RNA-Seq analysis revealed that BP-GelMA activates angiogenesis-related biological processes. Mechanistic studies identified PEAK1 as a central regulator, driving vascular formation through activation of the MAPK signaling pathway. These findings highlight the potential of BP-GelMA as a therapeutic strategy for promoting angiogenesis and underscore the importance of optimizing BP-GelMA concentrations to achieve maximum therapeutic efficacy and safety in clinical applications.
研究领域:
生物材料学
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再生医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2025
·
IF 4.7
Xingfang Zhang,Liang Gao,Jianv Wang,Wei Zhang,Dong Xu,Yanhua Wang,Tianlong Liu,Kai Gao,Zhen Ren,Yi Ding
β-Bisabolene, a bioactive sesquiterpene extracted from myrrh—a substance utilized for ischemic stroke treatment—has known therapeutic potential. Nevertheless, the exact mechanisms underlying its beneficial effects on ischemic stroke, along with its potential targets, remain to be fully elucidated. This study aimed to investigate the therapeutic potential of β-Bisabolene in ameliorating ischemic stroke, identify its potential targets and interactions, and explore the underlying pathways involved. Bioinformatics analyses, including network pharmacology and analysis of GEO transcriptomic datasets, were performed to predict the potential targets and mechanisms of β-Bisabolene in ischemic stroke treatment. Preliminary computational validation was achieved through molecular similarity comparisons, molecular docking studies, and molecular dynamics simulations. In vitro experiments were then conducted to confirm the protective effects of β-Bisabolene on microglia injured by oxygen‒glucose deprivation and to validate the findings from the bioinformatics analyses. The results revealed that β-Bisabolene reduces the levels of the proinflammatory cytokines TNF-α, IL-1β and NO; decreases reactive oxygen species levels; and decreases the expression of COX-2, P38, ERK and Keap1. Moreover, it increases the expression of Arg-1, Nrf2, NQO1 and HO-1. These effects are associated with improved survival rates of oxygen–glucose deprivation–damaged microglia. In conclusion, β-Bisabolene may exert anti-inflammatory and antioxidant effects to ameliorate microglial injury induced by ischemic stroke by antagonizing COX-2 and mediating the MAPK signaling pathway and Keap1/Nrf2 pathway. This study provides valuable insights into the therapeutic potential of β-Bisabolene for the treatment of ischemic stroke.
研究领域:
药理学
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神经科学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
PeerJ
·
2025
·
IF 2.4
Jia Song,Jinyu Qiao,Mingxue Chen,Jiahui Li,Jixia Wang,Dayong Yu,Huachuan Zheng,Liying Shi
Chaetoglobosin A (ChA) is an antitumor compound produced by Chaetomium globosum . However, the mechanism of its antitumor effect has been rarely reported. In this study, we evaluated the anti-proliferative effect of ChA on T-24 human bladder cancer cells and explored its mechanism of action. ChA was found to have a good inhibitory effect on T-24 cells by MTT assay with an IC50 value of 48.14 ± 10.25 μΜ. Moreover, it was found to have a migration inhibitory ability and a sustained proliferation inhibitory effect on tumor cells by cell aggregation assay and cell migration assay. The cells morphological changes were determined by Hoechst33342 assay. While Annexin V-FITC/PI double-staining assay also demonstrated that the number of apoptotic cells increased with the increase of drug concentration. Flow cytometry results showed that ChA treatment increased reactive oxygen species (ROS) and decreased mitochondrial membrane potential (MMP) in T-24 cells and inhibited cell mitosis, resulting in an increase in the number of sub-G1 phase cells. Further western blot experiments demonstrated that MAPK and PI3K-AKT-mTOR pathways were activated after drug treatment in addition to endogenous and exogenous apoptotic pathways. The addition of the ROS inhibitor N-acetylcysteine (NAC) upregulated the expression level of Bcl-2 protein, decreased p38 phosphorylation, increased ERK phosphorylation and restored the levels of PI3K and p-mTOR after ChA treatment. These suggest that ChA induces apoptosis by regulating oxidative stress, MAPK, and PI3K-AKT-mTOR signaling pathways in T-24 cells.
研究领域:
肿瘤学
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2022
·
IF 5.714
Lei Wang,Wan-Yang Xu,Yi-Wen Tang,Feng Hu
Pulmonary fibrosis is common in the development of inflammatory lung diseases with no effective clinical drug treatment currently. As an essential redox enzyme, thioredoxin (Trx) has been reported to be involved in pulmonary fibrosis, but the mechanism is to be revealed. Therefore, in bleomycin-indued pulmonary fibrosis model in C57 mice, Trx activity and nitrated Trx were examined.,p38-MAPK apoptosis pathway was determined in lung tissues. Additionally, before BLM administration, C57/BL6 mice were treated with aminoguanidine (AG, a peroxynitrite scavenger), recombinant human Trx-1 (rhTrx-1), or SIN-1 (a peroxynitrite donor) nitrated Trx-1 ( N -Trx-1). In bleomycin (BLM)-induced pulmonary fibrosis model in C57/BL6 mice, we observed that nitrated Trx increased, while its activity decreased, with the increase of alveolar epithelial cells (AECs)apoptosis by p38-MAPK pathway. We demonstrated that AG or rhTrx-1, but not N -Trx-1 significantly reduced pulmonary fibrosis. Taken together, the results above revealed that blockade of Trx-1 nitration, or supplementation of exogenous rhTrx-1, might represent novel therapies to attenuate pulmonary fibrosis in idiopathic pulmonary fibrosis patients.
研究领域:
医学
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药理学
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病理学
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2025
·
IF 6.1
Wei Wei,Siting Pu,Chengxin Yan,Hongzao Yang,Hongwei Chen
The rapid growth of lithium (Li)-related industrial activities and the application of Li-containing products have become an emerging human health concern. Li has been employed to treat human mental disorders; however, excessive Li salt accumulation can lead to brain damage. The mechanism of toxicity of long-term exposure to Li in the brain warrants further investigation. This research study established a network toxicology strategy to evaluate the molecular mechanisms and putative toxicity of lithium chloride (LiCl). The analysis of online databases identified 80 intersection targets for LiCl-induced neurotoxicity. Further refinements via STRING and Cytoscape software highlight 10 core targets. Furthermore, phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT), apoptosis pathways, and mitogen-activated protein kinase (MAPK) were enriched. Molecular docking validated the robust interaction of core targets with Li + . In vivo analyses of mice brains revealed substantial pathological alterations, neuronal degeneration, and nerve cell apoptosis. LiCl elevated the mRNA level of core genes. Further, the phosphorylation status of core proteins was primarily modulated by LiCl. Our investigation employs novel strategies for assessing the environmental pollutant toxicity and gives theoretical basis for elaborating the LiCl-induced neurotoxicity-related molecular mechanism. This may be employed to guide risk assessment of environmental Li exposure.
研究领域:
毒理学
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神经科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
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IF 4.8
Yancen Li,Chengyu Wan,Fan Li,Guang Xin,Tao Wang,Qilong Zhou,Tingyu Wen,Shiyi Li,Xiaoting Chen,Wen Huang
Background: Isatidis Folium, a botanical drug widely used in traditional medicine, is known for its anti-inflammatory properties, including heat-clearing, detoxifying, and blood-cooling effects. Although its potential in sepsis treatment has been suggested, the bioactive metabolites and underlying mechanisms remain poorly understood.Methods: Network pharmacology and molecular docking were employed to identify the therapeutic effects and mechanisms of Indirubin, the major bioactive metabolite of Isatidis Folium, in sepsis treatment. In vivo, a cecal ligation and puncture (CLP)-induced mouse sepsis model was used to evaluate the protective effects of Indirubin through histopathological analysis, ELISA, and biochemical assays. In vitro, RAW264.7 cells were stimulated with LPS and treated with varying concentrations of Indirubin. The anti-inflammatory effects of Indirubin were assessed using ELISA, apoptosis assays, and Western blotting.Results: Network pharmacology analysis identified Indirubin as the major bioactive metabolite of Isatidis Folium and EGFR and SRC as its key molecular targets. Experimental validation demonstrated that Indirubin significantly improved survival rates, alleviated tissue injury, and suppressed inflammatory responses in sepsis models. Mechanistically, Indirubin inhibited LPS-induced activation of the EGFR/SRC/PI3K and NF-κB/MAPK pathways in macrophages, significantly reducing cell death and inflammation in RAW264.7 cells.Conclusion: Indirubin, the primary bioactive metabolite of Isatidis Folium, exerts protective effects against sepsis by targeting the EGFR/SRC/PI3K and NF-κB/MAPK signaling pathways in macrophages. These findings provide a mechanistic basis for the development of Indirubin as a multi-target therapeutic agent for sepsis treatment.
研究领域:
药理学
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免疫学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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