Toxicology Research
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2024
·Vol. 13
·期 1
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IF 2.2
Zhang Chu,Liao Yupei,Li Tangjia,Zhong Haijing,Shan Luchen,Yu Pei,Xia Chenglai,Xu Lipeng
The 2022 US Cancer Statistics show that breast cancer is one of the most common cancers in women. Epidemiology has shown that adding flavonoids to the diet inhibits cancers that arise in particular women, such as cervical cancer, ovarian cancer, and breast cancer. Although there have been research reports on apigenin (API) and breast cancer, its anti-tumor effect and potential mechanism on breast cancer have not yet been clarified. Therefore, in this study, we used 4T1 cells and a 4T1 xenograft tumor mouse model to investigate the antitumor effect of API on breast cancer and its underlying mechanism. In vitro, we used MTT, transwell, staining, and western blotting to investigate the inhibitory effect of apigenin on 4T1 and the underlying molecular mechanism. In vivo by establishing a xenograft tumor model, using immunohistochemistry, and flow cytometry to study the inhibitory effect of apigenin on solid breast tumors and its effect on the tumor immune microenvironment. The results showed that API can induce breast cancer cell apoptosis through the PI3K/AKT/Nrf2 pathway and can improve the tumor immune microenvironment in mice with breast tumors, thereby inhibiting the growth of breast cancer. Thus, API may be a promising agent for breast cancer treatment.
研究领域:
肿瘤学
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分子生物学
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免疫学
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DOI
PubMed
高影响因子
CURRENT ISSUES IN MOLECULAR BIOLOGY
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2024
·Vol. 46
·期 10
·11359-11374
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IF 2.8
Xin Li,Kai Zheng,Hao Chen,Wei Li
While Ginsenoside Re has been shown to protect the central nervous system, reports of its effects on memory in the model of scopolamine-induced memory impairment are rare. The aim of this study was to investigate the effects of Ginsenoside Re on scopolamine (SCOP)-induced memory damage and the mechanism of action. Male ICR mice were treated with SCOP (3 mg/kg) for 7 days and with or without Ginsenoside Re for 14 days. As evidenced by behavioral studies (escape latency and cross platform position), brain tissue morphology, and oxidative stress indicators after Ginsenoside Re treatment, the memory damage caused by SCOP was significantly ameliorated. Further mechanism research indicated that Ginsenoside Re inhibited cell apoptosis by regulating the PI3K/Akt/Nrf2 pathway, thereby exerting a cognitive impairment improvement effect. This research suggests that Ginsenoside Re could protect against SCOP-induced memory defects possibly through inhibiting oxidative stress and cell apoptosis.
研究领域:
神经科学
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药理学
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氧化应激
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DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2023
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IF 4.8
Wei-guang Yang,Ao Sun,Rong Zhu,Nan Liu,Wei-jie He,Lin-lin Liu
Background Artemisinin (ART) is a safe and effective antimalarial drug. In recent years, antimalarial drugs have demonstrated a good therapeutic efficacy in IgA nephropathy, suggesting that this may become a new treatment option.Purpose We aimed to evaluate the effect and mechanism of artemisinin in IgA nephropathy.Methods In this study, CMap database was used to predict the artemisinin therapeutic effect for IgA nephropathy. A network pharmacology approach was applied to explore the unknown mechanism of artemisinin in IgA nephropathy. We used molecular docking to predict the binding affinity of artemisinin with the targets. A mouse model of IgA nephropathy was established to investigate the therapeutic effect of artemisinin on IgA nephropathy. In vitro, the cell counting Kit-8 assay was used to evaluate the cytotoxicity of artemisinin. Flow cytometry and PCR assays were used to detect the effects of artemisinin on oxidative stress and fibrosis in lipopolysaccharide (LPS)-stimulated mesangial cells. Western blot and immunofluorescence were used to detect the expression of pathway proteins.Results CMap analysis showed artemisinin may reverse the expression levels of differentially expressed genes in IgA nephropathy. Eighty-seven potential targets of artemisinin in the treatment of IgA nephropathy were screened. Among them, 15 hub targets were identified. Enrichment analysis and GSEA analysis indicated that response to reactive oxygen species is the core biological process. AKT1 and EGFR had the highest docking affinity with artemisinin. In vivo, artemisinin could improve renal injury and fibrosis in mice. In vitro, artemisinin attenuated LPS-induced oxidative stress and fibrosis promoted AKT phosphorylation and Nrf2 nuclear translocation.Conclusion Artemisinin reduced the level of fibrosis and oxidative stress with IgA nephropathy through the AKT/Nrf2 pathway, which provided an alternative treatment for IgAN.
研究领域:
药理学
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肾病学
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分子生物学
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生物信息学
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DOI
PubMed
高影响因子
JOURNAL OF FOOD SCIENCE
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2020
·Vol. 85
·期 6
·1752-1763
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IF 2.479
Shilian Zheng,Zeyuan Deng,Fang Chen,Liufeng Zheng,Yao Pan,Qian Xing,Rong Tsao,Hongyan Li
Phenolics and carotenoids coexist in fruits and vegetables and could possess interaction effects after consumption. The present study aims to elucidate the possible mechanisms of the antioxidant interactions between anthocyanins and carotenoids using petunidin and lycopene as examples in hydrogen peroxide (H 2 O 2 )-induced heart myofibroblast cell (H9c2) line model. The results revealed that petunidin and lycopene showed antioxidant effects and petunidin in a larger proportion mixed with lycopene, for example, petunidin: lycopene = 9:1 significantly protected against the loss of the cell viability (8.98 ± 1.03%) and intracellular antioxidant enzyme activities of superoxide dismutase (SOD, 27.07 ± 3.51%), catalase (CAT, 29.51 ± 6.12%), and glutathione peroxidase (GSH-Px, 20.33 ± 2.65%). Moreover, the messenger RNA (mRNA) and protein expressions of NAD(P)H quinone reductase (NQO1) and heme oxygenase (HO-1) of the nuclear factor erythrocyte 2-related factor 2 (Nrf2) signaling pathway were significantly induced in petunidin, lycopene, and synergistic combinations, suggesting that the antioxidant action was through activating the Nrf2 antioxidant response pathway. This was further validated by Nrf2 siRNA, and the results that petunidin significantly induced more of NQO1 expression and lycopene more of HO-1 suggested that the synergism may be a result of concerted actions by the two compounds on these two different target genes of the Nrf2 pathway. The two compounds also significantly increased the phosphorylation of Akt in synergistic combinations. Findings of the present study demonstrated that petunidin and lycopene exerted synergistic antioxidant effects when petunidin in a larger proportion in the combinations and contribute to the prevention of cellular redox homeostasis, which might provide a theoretical basis for phenolics and carotenoids playing beneficial effects on the cardiovascular risk. Practical Application In this study, we revealed that the combined treatments of petunidin and lycopen inhibited H 2 O 2 -induced oxidative damage in myocardial cells. Moreover, the treatments contributed to the Nrf2 pathway and the restoration of cellular redox homeostasis might provide a theoretical basis for phenolics and carotenoids playing beneficial effects on the cardiovascular risk.
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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营养学
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DOI
PubMed
高影响因子
NEUROSCIENCE
·
2024
·
IF 2.9
Xinyue Zhang,Xiao Wang,Le Yin,Dan Wang,Hong Jiao,Xiaodan Liu,Jiaolin Zheng
HECT domain and Ankyrin repeat-containing E3 ubiquitin protein ligase 1 (HACE1) is an E3 ubiquitin ligase involving oxidative stress, an important contributor in cerebral ischemia–reperfusion injury (CIRI). It was proposed to be associated with the PI3K/AKT pathway and Nrf2 nuclear translocation, which are important players of oxidative stress. Therefore, we supposed that HACE1 might affect CIRI by regulating the PI3K/AKT/Nrf2 pathway. Here, we used the transient middle cerebral artery occlusion-reperfusion (tMCAO/R) model to induce CIRI in rats and found lower HACE1 expression in ischemic rats compared with the control. To explore the exact role of HACE1, the lentivirus vector carrying the HACE1 sequence was administrated to rats by intracerebroventricular injection (1 × 10 9 TU/mL, 9 μL) one week before tMCAO/R operation. HACE1 overexpression alleviated tMCAO/R-induced brain damage in rats. Further studies revealed that it reduced oxidative stress via activating the PI3K/AKT/Nrf2 pathway, thereby inhibiting neuronal apoptosis in the ischemic penumbra of rats with CIRI. Then, differentiated PC12 cells were cultured in oxygen-glucose deprivation-reoxygenation (OGD/R) conditions (OGD: 1 % O 2 , 94 % N2, and 5 % CO 2 ; R: normal atmosphere) to simulate CIRI in vitro . Similarly, HACE1 overexpression inhibited neuronal apoptosis caused by OGD/R treatment. The PI3K inhibitor LY294002 reversed the inhibitory effects of HACE1 overexpression on oxidative stress in OGD/R-injured cells, accompanied by the inactivated AKT/Nrf2 pathway. Altogether, our results suggest that HACE1 protects against oxidative stress-induced neuronal apoptosis in CIRI by activating the PI3K/AKT/Nrf2 pathway, providing a new insight into the CIRI treatment.
研究领域:
神经科学
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分子生物学
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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
·
2025
·
IF 4.7
Lianhua Tang,Juan Deng,Pi Shi,Siyuan Zou,Hongyan Ran,Fei Yin,Jianhui Liu
Rosmarinic acid (RA), a polyphenolic compound, exhibits diverse pharmacological activities, including anti-inflammatory, antioxidant, and antitumor effects. Despite its therapeutic potentials, the mechanisms underlying its efficacy in ulcerative colitis (UC), a chronic inflammatory bowel disease characterized by intestinal epithelial barrier dysfunction, remain incompletely elucidated. This study investigates RA's protective effects in UC using complementary in vivo and in vitro models. In a dextran sulfate sodium (DSS)-induced murine colitis model, RA administration significantly attenuated disease severity, mitigating weight loss, preventing colon shortening, and reducing histopathological inflammatory infiltration. RA restored intestinal barrier integrity via upregulation of key tight junction proteins such as ZO-1, occludin, claudin-1 in colonic tissues. Mechanistic analyses in lipopolysaccharide (LPS)-stimulated NCM460 human colonic epithelial cells revealed that RA inhibited phosphatidylinositol 3-kinase (PI3K)/AKT pathway activation, as evidenced by reducing AKT phosphorylation (p-AKT), while enhancing nuclear factor erythroid 2-related factor 2 (Nrf2) expression. Pharmacological PI3K inhibition with LY294002 abolished RA-induced upregulation of Nrf2 and TJPs, confirming the PI3K/AKT/Nrf2 axis as the central signaling cascade mediating RA's protective effects. Collectively, these findings elucidate a novel mechanism by which RA preserves intestinal barrier integrity through PI3K/AKT/Nrf2 axis modulation and propose a targeted therapeutic strategy for UC management.
研究领域:
药理学
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分子生物学
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胃肠病学
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免疫学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF SURGICAL RESEARCH
·
2022
·
IF 2.417
Ming Deng,Ping Xie,Junqi Liu,Yan Zhou,Zhonghui Chen,Yonggang Ma,Jianwei Yang
Introduction α-Cyperone has anti-inflammatory activities, but its effects on spinal cord injury (SCI) remain obscure. Thus, this study attempts to investigate the effects and modulatory mechanisms of α-Cyperone on SCI. Materials and methods An SCI model was established in rats which were further treated with α-Cyperone. Basso-Beattie-Bresnahan (BBB) scoring was used to assess motor rehabilitation of rats modeled with SCI. The spinal cord tissues were collected, and the effect of α-Cyperone on the histopathology of rats modeled with SCI was detected by hematoxylin-eosin staining. Rat primary cortical neuron was stimulated with H 2 O 2 and further treated with α-Cyperone and nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor ML385. The levels of Nrf2, interleukin-6 (IL-6), nuclear factor kappa B (NF-κB), Akt, toll-like receptor 4 (TLR4), and tumor necrosis factor-alpha (TNF-α) were detected by immunofluorescence staining and western blotting . Results α-Cyperone elevated the BBB score and ameliorated the damage of spinal cord tissue in rats modeled with SCI. The levels of IL-6, Nrf2, NF-κB, TLR4, and TNF-α were upregulated, whereas that of Akt was downregulated in rats and cells modeled with SCI. Furthermore, α-Cyperone diminished the levels of IL-6, NF-κB, TLR4, and TNF-α, while augmenting those of Nrf2 and Akt in rats and cells modeled with SCI. ML385 inhibited the Nrf2 level that had been promoted by α-Cyperone in the nucleus and elevated the Nrf2 level that had been suppressed by α-Cyperone in the cytosol of cells modeled with SCI. ML385 increased the levels of IL-6, NF-κB, TLR4, and TNF-α that had been inhibited by α-Cyperone and decreased the Akt level that had been enhanced by α-Cyperone in cells modeled with SCI. Conclusions α-Cyperone suppressed SCI-induced inflammation and spinal cord tissue damage via activating Akt/Nrf2 and suppressing NF-κB pathways.
研究领域:
神经科学
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药理学
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分子生物学
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病理学
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DOI
PubMed
高影响因子
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