NEUROTOXICITY RESEARCH
·
2020
·Vol. 38
·期 1
·59-73
·
IF 2.992
Wen Caiyan,Huang Cuiqin,Yang Mei,Fan Chongzhu,Li Qin,Zhao Jiayi,Gan Danhui,Li An,Zhu Lihong,Lu Daxiang
Oxidative stress is a potential pathological mechanism of Alzheimer’s disease (AD). Berberine (BBR) can improve antioxidative capacity and inhibit Aβ protein aggregation and tau protein hyperphosphorylation in AD, and stem cell therapy is also increasingly recognized as a therapy for AD. Bone marrow mesenchymal stem cells (BMSCs) have many advantages, as they exhibit antioxidant and anti-inflammatory activity and secrete a variety of neurotrophic factors, and play important roles in neurodegenerative disease treatment. In this study, we investigated the antioxidant effects of secretions from BMSCs pretreated with BBR on tert -butyl hydroperoxide ( t -BHP)–damaged neurons. We demonstrated that BBR can enhance BMSC viability and the secretion of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), both of which are vital neurotrophic factors that maintain neuronal growth. Moreover, conditioned medium from BBR-treated BMSCs (BBR-BMSC-CM) reduced reactive oxygen species (ROS) production, attenuated a decrease in the mitochondrial membrane potential, and ameliorated neuronal apoptosis by decreasing levels of the apoptotic proteins Bax/Bcl-2, cytochrome c, and cleaved caspase-3/caspase-3. In addition, increased synaptophysin (SYP) and postsynaptic density protein 95 (PSD95) levels indicated that neuronal synaptic function was restored. Further study revealed that BBR-BMSC-CM activated the antioxidant proteins Keap1, Nrf2, and HO-1. In conclusion, our results showed that BBR-BMSC-CM attenuated apoptosis and oxidative damage in neurons by activating the Keap1-Nrf2-HO-1 signaling pathway. Taken together, these results also suggest BBR as a drug to stimulate the secretion of nutritional cytokines with the potential to treat AD.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2017
·Vol. 7
·期 55
·34846-34856
·
IF 3.108
Ye Tian,Zheng Li,Bingyu Shen,Lin Wu,Lu Han,Qiaoling Zhang,Haihua Feng
Shikonin (SHK) has various biological and pharmacological activities, including anticancer, antibacterial and anti-inflammation activities. However, the protective effects and mechanism of SHK on lipopolysaccharide (LPS) and D-galactosamine (D-GalN) induced acute liver injury remain unclear. In this study, LPS/D-GalN caused acute liver injury by intraperitoneal injection. SHK was administrated for 1 h. Then, LPS/D-GalN was given to C57BL/6 mice for 3 h. Our results showed that SHK treatment distinctly decreased serum TNF-α, IL-1β, IL-6 and IFN-γ inflammatory cytokine production, reduced serum ALT, AST, hepatic MPO and ROS production levels, and tissue histology harmful effects, inhibited JNK1/2, ERK1/2, p38 and NF-κB (p65) phosphorylation, and suppressed IκBα phosphorylation and degradation. Furthermore, our research showed that SHK could dramatically increase SOD and GSH production, as well as reduce ROS production, through up-regulating the protein expression of HO-1, Nqo1, Gclc and Gclm, which was related to the induction of Nrf2 nuclear translocation. These results showed that SHK exerted anti-inflammatory activity, which was associated to the inhibition of inflammatory production via down-regulation of the MAPK and NF-κB signaling pathways, and anti-oxidative effects were connected with GSH and SOD activation through up-regulation of the Nrf2/HO-1 signaling pathways.
✓ 已验证
产品关联
DOI
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Wen-lin Li,Ke Li,Wen-guang Chang,Hui Shi,Wen-xuan Zhang,Zi Wang,Wei Li
Background Although our previous work confirmed 20(R)-ginsenoside Rg3 (R-Rg3), which is an active ingredient in the Panax Ginseng C.A. Meyer, to have good anti-diabetic activity, its beneficial effect on diabetic retinal injury was found to be limited. Purpose This study aims to investigate the protective effects of R-Rg3 on diabetes-induced retinal injury and the associated molecular mechanisms of action. Methods Diabetic retinal injury was induced in mice using a combination of a high-fat diet (HFD) and intraperitoneal injection of streptozotocin (STZ). R-Rg3 (10 and 20 mg/kg) was subsequently administered for 6 weeks. The human retinal endothelial cells (HRECs) were subjected to high glucose (HG)-induced injury for the in vitro analysis and treated with R-Rg3 (4, 8, 16 μM), antioxidant N-Acetylcysteine (NAC, 1 mM) and Nrf2 inhibitor ML385 (5 μM). The mice retinas then underwent functional and histopathological analysis. Expression levels of proteins related to the Nrf2/HO-1 axis, tight junction proteins, endoplasmic reticulum (ER) stress and the apoptosis in retinal tissue and HRECs were determined by western blot. Expressions of ZO-1 and Nrf2 in the retina and HRECs were assessed by immunofluorescence. Additional evaluations included measuring body weights, fasting blood glucose (FBG), lipid levels and oxidative markers. Results The results showed 6 weeks of R-Rg3 treatment significantly restored the functional changes and redox system imbalance that was induced by HFD/STZ in mice. R-Rg3 was also found to significantly reduce retinal barrier damage and thickness changes resulting from hyperglycaemia exposure. At the same time, R-Rg3 also protected HRECs from HG-induced damage. R-Rg3 could also activate Nrf2/HO-1 axis and inhibit endoplasmic reticulum stress as a means of alleviating retinal endothelial cells apoptosis. The molecular docking results also demonstrated that R-Rg3 had a good binding ability with Nrf2. Conclusion Our study suggested Nrf2/HO-1 axis might be crucial for the ability of R-Rg3 to prevent diabetic retinal injury.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2025
·Vol. 55
·期 3
·1-15
·
IF 5.8
Congna Zi,Yulei Wei,Ying Zhu,Juan Fan
Regulator of G‑protein signaling 12 (RGS12) is a regulatory factor that is involved in various physiological processes. However, the role of RGS12 in myocardial ischemia/reperfusion injury (MIRI) currently remains unclear. The present study established a mouse model of MIRI by ligating the left main coronary artery followed by reperfusion. In addition, mouse HL‑1 cells were cultured in a hypoxic and serum‑free medium, followed by reoxygenation to establish an in vitro cell model of hypoxia/reoxygenation (H/R). Adenoviruses targeting RGS12 were subsequently used to either overexpress or silence RGS12 expression. RGS12 was highly expressed in both the myocardial tissues of mice with MIRI and HL‑1 cells subjected to H/R. The results from the in vitro experiments demonstrated that the knockdown of RGS12 reduced oxidative stress under a pathological environment, as indicated by decreased reactive oxygen species (ROS) levels and malondialdehyde activity and increased activities of superoxide dismutase and catalase. Furthermore, mice with MIRI and HL‑1 cells that underwent H/R stimulation exhibited increased ferroptosis, whereas RGS12 knockdown reversed these changes. These results showed that post‑RGS12 silencing the levels of Fe2+ and lipid ROS were decreased, the expression levels of glutathione peroxidase 4 and cystine transporter solute carrier family 7 member 11 were increased and mitochondrial structure was improved by preventing the loss of the mitochondrial crest. Mechanistically, the nuclear factor erythroid 2‑related factor 2 (Nrf2) pathway with anti‑ferroptosis and anti‑oxidative stress capacities was activated by RGS12 knockdown. Conversely, RGS12 overexpression exerted the opposite effects both in vivo and in vitro. Notably, it was demonstrated that penehyclidine hydrochloride (PHC), known to block the MIRI process, decreased RGS12 expression levels both in vivo and in vitro, and RGS12 overexpression inhibited the therapeutic effects of PHC on MIRI. In conclusion, the present study demonstrated that RGS12, a target of PHC, potentially enhanced the progression of MIRI by promoting oxidative stress and ferroptosis, and this effect may involve the regulation of the Nrf2 pathway.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Sheng Li,Shiyi Lu,Jiahui Xiong,Liang Chen,Yanting Lin,Xiaohui Chen,Xinyi Wang,Lijing Lin,Xiaoliang Cai,Xiaoyu Yang
Here, we systematically evaluated the therapeutic efficacy and mechanisms of action of in-house synthesized hydroxyethyl starch-curcumin nanoparticles (HES-CUR NPs) in ulcerative colitis (UC). Using a dextran sodium sulfate (DSS)-induced UC mouse model, we analyzed the effect of HES-CUR NPs on colonic tissue and the gut microbiota through the assessment of organ indices and serum biochemical markers, histopathology, immunohistochemistry, Western blot, and 16S rRNA sequencing. We found that HES-CUR NPs significantly suppressed the TLR4/NF-κB inflammatory pathway (downregulated TLR4, p-IKKβ, IL-1β, IL-6, NFKB, MyD88, and p-IKKB/IKKB; p < 0.01), activated the Nrf2/HO-1 antioxidant pathway (enhanced Nrf2 nuclear translocation and HO-1 expression), and upregulated the expression of tight junction proteins (claudin-1, occludin, ZO-1), thereby restoring intestinal barrier integrity. Microbiota analysis revealed that HES-CUR NPs increased gut microbiota diversity (elevated Chao1, Shannon, and ACE indices) and enriched beneficial bacteria abundance (Ligilactobacillus murinus, Lactobacillus johnsonii). Antibiotic intervention partially attenuated the therapeutic effects of the HES-CUR NPs, confirming that their effects involved microbiota-dependent mechanisms. Compared to CUR and SASP, HES-CUR NPs exhibited significantly enhanced bioavailability and efficacy (p < 0.01), attributed to the targeted delivery and sustained-release properties of the hydroxyethyl starch nanocarrier. No toxicity was observed, as indicated by normal spleen, liver, and thymus indices and stable levels of TP, ALT, AST, ALB, GLB, and ALB/GLB. Our findings indicated that HES-CUR alleviates UC through a synergistic, multi-target mechanism involving inflammatory pathway suppression, antioxidant pathway activation, intestinal barrier repair, and microbiota modulation, providing a theoretical foundation for developing efficient and safe natural nanomedicines targeting UC.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Qiang Chu,Shuang Zhang,Lushuang Yu,Yonglu Li,Yangyang Liu,Xiang Ye,Xiaodong Zheng
The tubers of Apios americana Medikus possess high nutritional value and have been used as food in many countries for a long time. However, few researches have focused on the tuber polysaccharides. In the present study, a purified polysaccharide (ATP-1) was isolated with the average molecular weights of 12.16 kDa. ATP-1 significantly suppressed the release of nitric oxide (NO) and inflammatory cytokines from LPS-induced RAW 264.7 cells, as well as oxidative stress and mitochondrial dysfunction. Meanwhile, ATP-1 reduced oxidative damage via the NF-κB, MAPKs and Nrf2-Keap1 signaling pathways in RAW264.7 macrophages. Furthermore, autophagy was activated by HMGB1-Beclin1, Sirt1-FoxO1 and Akt-mTOR signaling pathways, leading to a relief of oxidative stress, mitochondrial dysfunction, inflammation and an expression enhancement of autophagy-related proteins, such as LC3, Beclin1, Atg4, Atg5, and Atg7. In summary, our results suggested that ATP-1 might help to activate the anti-inflammation system，resulting in prevention of LPS-induced damage in RAW264.7 cells.
研究领域:
药理学
·
免疫学
·
细胞生物学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
BIOLOGICAL TRACE ELEMENT RESEARCH
·
2026
·
IF 4.3
Ngwe Phar Ku,Zhu Jing,Ling Hao,Gao Mengmeng,Guo Chengxiang,Hu Yinan,Wang Jicang
Lead (Pb), a persistent and highly toxic environmental contaminant, induces severe multi-organ toxicity, with the liver as a primary target. Naringenin (Nar), a natural flavonoid with established antioxidant properties, shows potential in mitigating chemical-induced liver injury; however, its protective mechanism against Pb hepatotoxicity remains unclear. This study investigated the hepatoprotective effects and underlying mechanisms of Nar in Pb-exposed rats. Thirty-six five-week-old male Sprague-Dawley rats were randomly assigned to six groups ( n = 6): control, three Pb-treated groups (15, 30, and 60 mg/kg), co-treatment group (60 mg/kg Pb + 50 mg/kg Nar), and Nar-alone group (50 mg/kg). After 8 weeks, Pb exposure induced significant liver injury, evidenced by histopathological lesions (e.g., central venous congestion and inflammation), elevated serum levels of ALT, AST, and LDH, and oxidative stress (increased MDA; decreased CAT, T-SOD, and GSH). At the molecular level, Pb exposure suppressed the Nrf2/NQO1 pathway, upregulated Keap1, and impaired autophagic flux, as indicated by a decreased LC3-II/LC3-I ratio, accumulated p62, and a disrupted PINK1/Parkin pathway. Corroborating the impaired flux, transmission electron microscopy (TEM) revealed an accumulation of autophagic vacuoles, indicative of blocked autophagic degradation. Crucially, Nar co-treatment effectively mitigated these Pb-induced disturbances by activating the Nrf2/NQO1 pathway to counteract oxidative stress and restored autophagic flux, which was supported by the reversal of p62 accumulation and normalization of the LC3-II/LC3-I ratio. In conclusion, Nar protects against Pb-induced hepatotoxicity by concurrently alleviating oxidative stress and restoring autophagic function, supporting its potential as a therapeutic agent. Graphical
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INFLAMMATION
·
2021
·Vol. 44
·期 5
·1993-2005
·
IF 4.092
Wu Yuqin,Fan Lin,Wang Yun,Ding Jing,Wang Rongfu
This study is aimed at exploring the potential of isorhamnetin in protection against diabetes-exacerbated ischemia/reperfusion-induced brain injury and elucidating its action mechanism. After establishment of the model of high glucose (HG)-aggravated oxygen-glucose deprivation and reoxygenation (OGD/R), HT22 cell viability was detected by CCK-8. Lactate dehydrogenase (LDH) activity, casapase-3 activity, and oxidative stress-related markers in HT22 cells were detected by corresponding commercial kits. The apoptosis of HG-treated HT22 cells following OGD/R was observed with TUNEL staining. The level of pro-inflammatory cytokines was examined by ELISA. The expression of Akt/SIRT1/Nrf2/HO-1 signaling-related proteins was assayed by Western blot. The results showed that HG noticeably worsened the OGD/R-induced apoptosis of HT22 cells. Isorhamnetin relieved the HG-aggravated OGD/R-induced apoptosis, inflammatory response, and oxidative stress of HT22 cells. Isorhamnetin alleviated the HG-aggravated OGD/R injury in HT22 cells through Akt/SIRT1/Nrf2/HO-1 signaling pathway. Meanwhile, treatment with Akt inhibitor LY294002 reversed the protective effects of isorhamnetin against HG-aggravated OGD/R injury in HT22 cells. In a conclusion, Isorhamnetin alleviates HG-aggravated OGD/R in HT22 hippocampal neurons through Akt/SIRT1/Nrf2/HO-1 signaling pathway.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Ovarian Research
·
2024
·Vol. 17
·期 1
·1-17
·
IF 3.8
Sui Xue,Gao Bingqing,Zhang Liu,Wang Yanmin,Ma Junnan,Wu Xingchen,Zhou Chenyu,Liu Min,Zhang Lin
Background Cisplatin (DDP) is one of the most effective anticancer drugs, commonly used to treat advanced ovarian cancer (OC). However, DDP has significant limitations of platinum-based drugs, including chemical resistance and high-dose toxic side effects. Traditional Chinese medicines (TCMs) often presented in the form of formula, in which the herb pair was the basic unit. Scutellaria barbata D.Don and Hedyotis diffusa Willd (SB-HD) are famous TCMs herb pair that have been shown to help treat multiple types of cancers. However, the synergistic effects and mechanism of combination of SB-HD and DDP to enhance DDP chemosensitivity in OC are still unknown.Results In vitro, we found that the optimal proportion of SB-HD to inhibit the proliferation of OC cells was 2:1, SB-HD and DDP were shown to synergistically reduce the viability of OC cells, inhibit the colony formation, promote cell cycle arrest and apoptosis, as well as inhibit cell migration and invasion. In vivo, combination treatment significantly inhibited the growth of subcutaneous tumors in BALB/c nude mice and reduced the toxic side effects of DDP. Mechanistically, SB-HD and DDP combination treatment significantly promoted oxidative stress response, decreased MMP, inhibited ATP production, decreased ROS levels and increased SOD activity, increased the expression of NRF2, HO-1, ATG5 and LC3, decreased the expression of p62 and FTH1 both in OC cells and tumor tissue of mice. Inhibitor 3-MA (Methyladenine, autophagy inhibitor) and Fer-1 (Ferrostatin-1, iron ion inhibitor) can effectively reverse the expression changes of the key target proteins, but not ZnPP (Zinc protoporphyrin, HO-1 inhibitor). Through bioinformatics analysis, it was found that the abnormal expression level of NRF2 and FTH1 mRNA has a high prognostic value, at the same time, the other four key proteins respectively or interacting with NRF2 and FTH1, also play important roles in the occurrence and development of OC.Conclusion Our findings uncover a synergistic effect of SB-HD and DDP against OC through modulating oxidative stress via NRF2-FTH1 autophagic degradation pathway, which may provide an important theoretical foundation for the use of SB-HD and a new strategy for enhancing DDP chemosensitivity as well as reducing toxic side effects.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Foods
·
2025
·Vol. 14
·期 10
·1707
·
IF 5.1
Li Li,Ying Hu,Yu-Mei Wang,Xiao-Xue Wu,Si-Tong Lin,Hang Li,Ji Zhang,Guo-Rong Fan,Zong-De Wang,Bin Wang,Shang-Xing Chen
In this study, we systematically investigated the mechanisms of the antioxidation and anti-lipid accumulation effects of antioxidant peptides fromLitsea cubebaon a free fatty acid (FFA)-induced NAFLD model of HepG2 cells. The NAFLD cell model was constructed by inducing the HepG2 hepatocellular carcinoma cell line with 0.5 mmol/L FFAs, and AQRDAGLL, QEGPFVR, and DVPPPRGPL were given to the culture to study their lipid-lowering and antioxidant activities on NAFLD cells. The lipid-lowering activities of the three antioxidant peptides were evaluated by Oil Red O staining and TG and TC content assays, and the results showed that all three peptides had strong ameliorating effects on FFA-induced lipid accumulation in NAFLD cells. The intracellular antioxidant protease (CAT, GSH, and SOD) activity levels and lipid peroxidation (MDA) content were measured and intracellular ROS levels were detected. The results showed that after intervention with the antioxidant peptides, the intracellular ROS levels in the NAFLD model cells were significantly reduced, the SOD and CAT activities were increased, the GSH content was elevated, and the MDA content was reduced, which indicated that AQRDAGLL, QEGPFVR, and DVPPPRGPL were able to inhibit the oxidative stress of the cells effectively and to achieve the effect of intervening in NAFLD. JC-1 fluorescence staining experiments showed that the mitochondrial membrane potential function of NAFLD cells was restored under the effect of the antioxidant peptides. Molecular dynamics simulations revealed that the main driving force between QEGPFVR and Keap1 protein was van der Waals forces, ΔG = −62.11 kcal/mol, which indicated that QEGPFVR was capable of spontaneously binding to Keap1 protein.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Wan Wang,Hang Shang,Jinzhe Li,Yue Ma,Cong Xu,Jiage Ma,Juncai Hou,Zhanmei Jiang
Polyphenols have received attention as dietary supplements for the relief of alcoholic liver disease (ALD) due to various bioactivities. Ethanol-induced rat small intestinal epithelial cell 6 (IEC-6) and alpha mouse liver 12 (AML-12) cell models were pretreated with four dietary polyphenols with different structures to explore their effects on cytotoxicity and potential protective mechanisms. The results showed that polyphenols had potential functions to inhibit ethanol-induced AML-12 and IEC-6 cell damage and oxidative stress, and restore ethanol-induced IEC-6 permeability and tight junction gene expression. Especially, dihydromyricetin (DMY) had the best protective effect on ethanol-induced cytotoxicity, followed by apigenin (API). Western blot results showed that DMY and API had the best ability to inhibit CYP2E1 and Keap1, and promote nuclear translocation of Nrf2, which might be the potential mechanism by which DMY and API attenuate ethanol-induced cytotoxicity. Moreover, the molecular docking results predicted that DMY and API could bind more tightly to the amino acid residues of CYP2E1 and Keap1, which might be one of the inhibitory modes of dietary polyphenols on CYP2E1 and Keap1. This study provided a rationale for the subsequent protective effect of dietary polyphenols on alcohol-induced liver injury in animal models and provided new clues on bioactive components for ALD-protection based on the gut-liver axis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Qian Ren,Tingting Tian,Bin Wang,Jun Pan,Yong Huang,Li Zhong,Yehong Wang,Xia Wang,Xiao Huang
Photodynamic therapy (PDT) remains underutilized as a primary cancer treatment due to the limited lethality of reactive oxygen species (ROS) and poor targeting efficiency of traditional photosensitizers. This the aim of the study is to develop a Fe₃O₄@ZnO nanoparticle photosensitizer co-loaded with anti-EGFR antibody, brusatol, and Nrf2-siRNA to improve the therapeutic effect of PDT. This system can be guided to tumors by a magnetic field and further targets cancer cells through EGFR-specific binding. Under UVA light, brusatol and Nrf2-siRNA are released, enabling combined chemo-, gene, and photodynamic therapy. With the photosensitizer treatment, ROS levels in cutaneous squamous cell carcinoma cells were elevated by 191.09 ± 10.02 % through suppression of Nrf2 and its associated antioxidant defenses, significantly enhancing cell lethality and reducing cell viability by 80.43 ± 9.37 %. In vivo studies further demonstrated a tumor suppression rate of 76.30 ± 5.12 % in nude mice, highlighting the robust anti-tumor efficacy of the photosensitizer and its potential for clinical application in targeted cancer therapy. The biocompatibility and high therapeutic efficacy of this photosensitizer highlight its promise as a safer and more effective option for treating cutaneous squamous cell carcinoma.
✓ 已验证
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）