CURRENT MOLECULAR MEDICINE
·
2023
·
IF 2.5
Wang Qi,Zhang Aihua
Background: Oxidative stress is a key mechanism underlying arsenicinduced
liver injury, the Kelch-like epichlorohydrin-related protein 1 (Keap1)/nuclear
factor E2 related factor 2 (Nrf2) pathway is the main regulatory pathway involved in
antioxidant protein and phase II detoxification enzyme expression. The aim of the present
study was to investigate the role and mechanism of baicalein in the alleviation of
arsenic-induced oxidative stress in normal human liver cells.
Methods: Normal human liver cells (MIHA cells) were treated with NaAsO2 (0, 5, 10,
20 μM) to observe the effect of different doses of NaAsO2 on MIHA cells. In addition,
the cells were treated with DMSO (0.1%), NaAsO2 (20 μM), or a combination of NaAsO2
(20 μM) and Baicalein (25, 50 or 100 μM) for 24 h to observe the antagonistic effect
of Baicalein on NaAsO2. Cell viability was determined using a Cell Counting Kit-8
(CCK-8 kit). The intervention doses of baicalein in subsequent experiments were determined
to be 25, 50 and 100μM. The intracellular content of reactive oxygen species
(ROS) was assessed using a 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA)
probe kit. The malonaldehyde (MDA), Cu-Zn superoxide dismutase (Cu-Zn SOD) and
glutathione peroxidase (GSH-Px) activities were determined by a test kit. The expression
levels of key genes and proteins were determined by real-time fluorescence
quantitative polymerase chain reaction (qPCR) and Western blotting.
Results: Baicalein upregulated the protein expression levels of phosphorylated Nrf2
(p-Nrf2) and nuclear Nrf2, inhibited the downregulation of Nrf2 target genes induced by
arsenic, and decreased the production of ROS and MDA. These results demonstrate
that baicalein promotes Nrf2 nuclear translocation by upregulating p-Nrf2 and inhibiting
the downregulation of Nrf2 target genes in arsenic-treated MIHA cells, thereby enhancing
the antioxidant capacity of cells and reducing oxidative stress.
Conclusion: Baicalein alleviated arsenic-induced oxidative stress through activation
of the Keap1/Nrf2 signalling pathway in normal human liver cells.
研究领域:
毒理学
·
分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2025
·
IF 8.2
Hailin Wang,Yueying Wang,Xin Li,Jiayang Ma,Zhiqi Hu,Qian Qu,Yong Miao
Hair graying and loss are significant indicators of aging, and oxidative stress plays an essential role in this progression. Ergothioneine (EGT), potent antioxidant from edible fungi and certain prokaryotes, regulates the antioxidant defense system. However, its anti-aging effects on hair follicles (HFs) are remain obscure. We used dermal papilla cells (DPCs) co-culture system, HFs organ culture system, aged mice and H 2 O 2 -induced gray hair mice to explore the antioxidative functions and mechanisms of EGT on HFs. Research demonstrated that EGT mitigated H 2 O 2 -induced DPCs damage, reduced the secretion of inflammatory factors (IL-6, IL-1β, and TNF-α) and enhanced the production of pigmentation promoting factors (SCF and SDF1) through the SIRT1/Nrf2 pathway in DPCs. In vitro experiments of co-culture system indicated that EGT-treated DPCs remarkably alleviated oxidative damages and promoted cell proliferation in A-375 and HaCaT. Furthermore, it increased tyrosinase activity, melanin content and the expression of key melanin synthesis genes in A-375. Meanwhile, it promoted the expression of K19 and K14 in HaCaT. In vivo experiments revealed that EGT exhibited excellent effects on reducing pigmentation disfunction and hair loss in aged mice and H 2 O 2 -induced gray hair mice. In the HFs organ culture, the EGT promoted hair growth and pigmentation via SIRT1/Nrf2 partly. Our research indicated that EGT had potent antioxidant and anti-aging functions for HFs. This not only provided new applications for EGT but also opened up new therapeutic avenues for hair aging.
研究领域:
细胞生物学
·
医学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Discovery Medicine
·
2024
·Vol. 36
·期 181
·266-277
·
IF 2
Luo X,Liao H,Peng J,Jiang X
Background Osteoarthritis (OA) is a common disease that causes pain to many older adults. Because the pathogenesis is not fully elucidated, effective drug therapies are currently lacking. This study aimed to determine how salidroside (Sal)-mediated reduction of osteoarthritis development in mice worked and to identify the underlying mechanism. Methods Using in vitro experiments, ATDC5 cells were treated with various concentrations of Sal and interleukin (IL)-1β for 24 hours to mimic OA. An enzyme-linked immunosorbent assay (ELISA) was conducted to detect the production of pro-inflammatory cytokines and reactive oxygen species (ROS). Western blotting was performed to observe the nuclear factor-kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways. In in vivo experiments, pathological examination was used to assess the effects of Sal on alleviating OA progression in mice. Nrf2 signaling and its downstream proteins were further tested by immunofluorescence analysis. Results The results showed that both pro-inflammatory cytokines and ROS were significantly reduced following Sal treatment in a concentration-dependent manner. Western blotting revealed that Sal could inhibit the expression of the NF-κB/hypoxia-inducible factor-2α pathway and activate the Nrf2/heme oxygenase-1 pathway. In vivo experiments showed that the cartilage surface in the saline-treated group eroded to a greater extent than the Sal-treated groups ( p < 0.001). Immunohistochemistry analysis revealed that matrix metallopeptidase (MMP) 9, MMP13, and a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5) decreased expression level. In contrast, collagen-II and aggrecan increased in the Sal-treated groups compared to the saline-treated group. Conclusions Our findings indicate that Sal can alleviate OA progression by promoting anti-oxidant expression and inhibiting degradation enzyme expression. These findings suggest that Sal inhibits the NF-κB pathway and its downstream targets through up-regulating the Nrf2 pathway.
研究领域:
医学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Yan-Ling Qian,Bang-Yin Tan,Shi-Shi Qin,Xian-Run Wu,Zhuo-Qi Shi,Yun-Li Zhao,Xiao-Dong Luo
Ethnopharmacological relevance Crotalari a assamica Benth, one of the folk medicinal plants in the "Dai" of China, is commonly used to treat liver and bile related diseases. However, its bioactive compounds and the mechanism related to traditional use remain unclear. Aim of the study To investigate the protective compounds and mechanism of C . assamica on drug-induced liver injury. Materials and methods The acetaminophen (APAP)-induced mice and cell model were carried out to reveal the liver protection of the extract of C . assamica (ECA) and bioactive compounds in vitro and in vivo . The protective pathway was explored using transcriptome analysis, and binding targets were predicted by structure-based binding prediction and dynamic simulation, which were further supported by qPCR and Western Blot experiments on the livers of treated mice. Results ECA reduced the contents of serum lactate dehydrogenase, aspartate transaminase, and alanine transaminase significantly, adjusted the oxidative indices of serum and liver tissues, and ameliorated inflammation and necrosis of liver tissues, as well as up-regulated expressions of NQO1, HO-1, Nrf2, p-AKT, BCL-2, AKT, and IL-6 in vivo . Moreover, its bioactive compound sarosiensin V increased the viability of APAP-induced HepG2 cells, and restored liver function activity, accompanied by enhanced antioxidation and mitochondrial membrane potential significantly. Conclusion C. assamica and its bioactive compound sarosiensin V inhibited oxidative stress, inflammation, apoptosis and necrosis of liver tissues, which was associated with the upregulation of the Nrf2 pathway, and then supporting its traditional use for liver protection.
研究领域:
药理学
·
肝脏病学
·
分子生物学
·
天然产物化学
·
氧化应激
·
药物代谢
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2017
·
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
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2025
·
IF 9.8
Zaheer Abbas,Jing Zhang,Yucui Tong,Baseer Ahmad,Junyong Wang,Haosen Zhang,Zhenzhen Li,Xubiao Wei,Rijun Zhang,Dayong Si
The objective of this study was to isolate and characterize antioxidant peptides from mulberry leaves fermented with Bacillus subtilis H4 and Bacillus amyloliquefaciens LFB112. The results indicated that fraction F4 (<1 kDa) exhibited superior DPPH activity compared to the F1 (>10 kDa), F2 (3–10 kDa), and F3 (1–3 kDa) fractions, and cytoprotective effect against lipopolysaccharides (LPS)-induced oxidative stress in RAW264.7 cells. Three novel peptides, FRFDP, RFGG, and GPPLAFGGGP, were identified in the F4 fraction of the mulberry leaf ferment, and docking results showed that these peptides could form stable carbon (covalent) and hydrogen bonds to the active sites of Keap1, thus regulating the Keap1-Nrf2 pathway by blocking the Nrf2 binding sites on Keap1. These peptides significantly upregulated the mRNA expression of Nrf2 , HO-1 , and NQO1 , providing indirect evidence of their potential to enhance cellular antioxidant defense via the possible activation of Keap1-Nrf2 pathway. Furthermore, these peptides showed good DPPH and ABTS scavenging activities, indicating their potential as antioxidant peptides. This study offers valuable insights into the integration of these novel peptides in developing mulberry leaf ferment as a functional food and their potential use as a feed additive.
研究领域:
食品科学
·
生物化学
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DOI
PubMed
高影响因子
Frontiers of Chemical Science and Engineering
·
2023
·Vol. 17
·期 7
·976-989
·
IF 4.5
Yan Bowen,Lu Geng,Wang Rong,Kang Shixiong,Huang Caoxing,Wu Hao,Yong Qiang
Lignin exhibits antioxidative and various other biological properties. However, its neuroprotection capability has rarely been studied. In this study, three types of lignin with different structures were prepared from grape seeds by using different isolation techniques. The antioxidative and neuroprotective effects of the lignin fractions were evaluated with the apoptosis model of murine neuroectodermal (NE-4C) neural stem cells stimulated with bisphenol AF. The results demonstrated that the half maximal inhibitory concentration for scavenging 2,2-diphenyl-1-picrylhydrazyl with water-soluble lignin (L-W, 58.19 µg·mL −1 ) was lower than those of lignin in the autohydrolyzed residue of grape seeds (84.27 µg·mL −1 ) and original lignin in grape seeds (99.44 µg·mL −1 ). BPAF exposure had negative effects on the reactive oxygen species, malondialdehyde content, and superoxide dismutase and glutathione peroxidase activities in NE-4C cells, which can be reversed by using the prepared lignin to reduce oxidative stress. An immunofluorescence assay demonstrated that grape seed lignin induced protective effects on BPAF-injured NE-4C cells via the nuclear factor erythroid 2-related Factor 2 pathway. In addition, correlational analyses showed that lignin (L-W) with lower molecular weights and noncondensed phenolic hydroxyl group content and higher contents of COOH groups effectively prevented cell apoptosis, scavenged reactive oxygen species, and ensured protection from nerve injury. This study demonstrated that grape seed lignin can be used as a neuroprotective agent and serves as a demonstration of active lignin production from grape seed waste.
研究领域:
神经科学
·
植物化学
·
毒理学
✓ 已验证
DOI
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2023
·
IF 4.5
Yuhong Kou,Yongping Chen,Tongtong Feng,Luomeng Chen,Hui Wang,Ning Sun,Shuping Zhao,Tianyuan Yang,Wenjing Jiao,Guofeng Feng,Honggang Fan,Yuan Zhao
Glufosinate-ammonium (GLA) is a widely used herbicide, but less research has been done on its harmful effects on non-target organisms, especially aquatic organisms. In this study, 600 adult zebrafish were exposed to different concentration of GLA (0, 1.25, 2.5, 5, 10, and 20 mg/L) for 7 days, and the livers were dissected on the eighth day to examine the changes in liver structure, function, oxidative stress, inflammation, apoptosis, and Nrf2 pathway, and finally to clarify the mechanism of GLA induced liver injury in zebrafish. The levels of alanine aminotransferase, aspartate aminotransferase, reactive oxygen species, malondialdehyde, inflammatory factors (IL-6 and TNF-α), and caspase-3 gradually increased, while the levels of superoxide dismutase, catalase, glutathione, and glutathione peroxidase gradually decreased with the increase of GLA concentration. The Nrf2 pathway was activated at low concentrations (1.25–5 mg/L) and significantly inhibited at high concentrations (10 and 20 mg/L). These results suggested that GLA could cause oxidative stress, inflammation, and apoptosis in zebrafish liver. Therefore, GLA can cause liver injury in zebrafish, and at high concentrations, the inhibition of Nrf2 pathway is one of the important causes of liver injury.
研究领域:
水生毒理学
·
环境科学
·
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
·
神经科学
·
生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2020
·Vol. 11
·期 6
·5156-5165
·
IF 4.171
Yu-Sheng Shi,Xiao-Xing Li,Hao-Tian Li,Yan Zhang
Liver fibrosis is a histological change that often occurs due to hepatic stellate cell (HSC) activation and excessive formation of an extracellular matrix in the liver. Pelargonidin (PEL) is a natural anthocyanidin existing in blueberries, berries, strawberries, and red radishes and has been demonstrated to possess health beneficial effects. Herein, we investigated the effect of PEL on liver fibrosis induced by CCl4 and hepatic stellate cells induced by transforming growth factor-β (TGF-β). We found that PEL administration prevented liver injury and liver fibrosis induced by CCl4 in a dose-dependent manner. Further data revealed that PEL increased liver nuclear factor E2-related factor 2 (Nrf2) and reduced liver oxidative stress and the expression levels of NLRP3, caspase-1 and IL-1β. In TGF-β-challenged HSCs (LX-2 cells), PEL effectively inhibited the LX-2 cell activation. In addition, the anti-fibrosis effects of PEL in LX-2 cells were abolished by Nrf2 knockdown. In summary, our study demonstrated that PEL ameliorated CCl4-induced liver fibrosis and HSC activation induced by TGF-β. The possible molecular mechanisms of PEL in liver fibrosis may be attributed to its suppression of ROS-NLRP3-IL-1β signaling by Nrf2 activation.
研究领域:
药理学
·
肝病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOLOGICAL & PHARMACEUTICAL BULLETIN
·
2023
·Vol. 46
·期 11
·1527-1534
·
IF 2
Bowen Li,Wentao Yu,Lan Yang
Osmundacetone (DHBAc) is an antioxidant compound that has been shown to have neuroprotective and immunomodulatory activities. However, few studies have estimated its effect on cerebral ischemia–reperfusion (I/R) injury. In this study, we investigated the protective effect of DHBAc on the brain tissue of rats with cerebral I/R injury. Rats were respectively given nimodipine (NI), low dose (L-DHBAc) and high dose (H-DHBAc) Osmundacetone, and they were killed under anesthesia after 24 h of reperfusion. And neurological impairment scores, cerebral infarct size and cerebral pathological changes were respectively detected, and mRNA expression of recombinant kelch like ECH associated protein 1 (Keap1) and nuclear factor erythroid 2-related factor 2 (Nrf2), protein expression levels of caspase 3, cleaved caspase 3, heme oxygenase-1 (HO-1) and quinone oxidoreductase1 (NQO1) in ischemic brain tissue were measured. Compared with the I/R group, neurological impairment scores of the DHBAc groups were significantly decreased, and their infarct sizes were significantly smaller. DHBAc could improve the pathological status of brain tissue with cerebral I/R injury, including reducing number of inflammatory cells and area of vacuoles and restoring number of normal neurons. Expression levels of Keap1 mRNA and proteins of cleaved caspase3 were significantly decreased in the DHBAc groups than those of the I/R group, while expression levels of Nrf2 mRNA, HO-1 and NQO1 proteins were remarkably increased. The effect of H-DHBAc was similar to those of NI. These results suggest that DHBAc could mitigate damage to brain tissue in rats with cerebral I/R injury.
研究领域:
神经科学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Toxicology Research
·
2024
·Vol. 13
·期 1
·
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
·
分子生物学
·
免疫学
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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）