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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产品关联
DOI
PubMed
高影响因子
CURRENT ISSUES IN MOLECULAR BIOLOGY
·
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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产品关联
DOI
PubMed
高影响因子
NEUROSCIENCE
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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
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