PHYTOMEDICINE
·
2026
·
IF 11.3
Li Zhen,Jianhong Peng,Huimin Cui,Junhong Tao,Yaping Liu,Jianxin Cao,Hesham R El-Seedi,Guiguang Cheng,Zhengxuan Wang
Background The flowers of Rosa chinensis cv. ‘JinBian’ (RCF) has been utilized as a herbal tea for millennia to prevent aging-related diseases. RCF is enriched in flavonoids and exhibits significant antioxidant effects for anti-aging potential. However, the specific bioactive compounds and their underlying anti-aging mechanisms remain unclear. Purpose This study aimed to investigate the bioactive ingredients and neuroprotective mechanisms of RCF extracts. Methods The study obtained dichloromethane (RD), ethyl acetate (RE), n-butanol (RB), and residual water (RW) fractions from RCF after liquid-liquid extraction. It investigated their neuroprotective effect in in vitro and in vivo experiments. UHPLC-ESI-HRMS/MS analysis was used to identify phytochemicals in RE. In vitro assays included measuring phenolic and flavonoid contents, ABTS⁺ and DPPH + scavenging capacities, and effects on H₂O₂-induced SHSY-5Y cells. In vivo , D-galactose-induced mice were used and assessed through the Morris water maze test and the crucifixion anxiety test. Molecular pathways and gut microbiota were analyzed. Results Among the fractions, RE had the highest phenolic and flavonoid contents, the strongest ABTS⁺ and DPPH + scavenging capacities, and significantly inhibited ROS accumulation by increasing antioxidants (glutathione, catalase, superoxide dismutase) in H₂O₂-induced SHSY-5Y cells. UHPLC-ESI-HRMS/MS analysis identified 28 phytochemicals in RE, primarily gallic acid derivatives and flavonoid derivatives. In D-galactose-induced mice, RE alleviated memory impairment and anxiety-like behavior. RE ameliorated brain damage by activating the Keap1/Nrf2-regulated antioxidant pathway (increasing T-AOC, GSH, GPX4, NQO1, SOD1, HO-1), suppressing ferroptosis, inhibiting acetylcholinesterase activity, attenuating GSK-3β/Tau/Bcl-2 axis-regulated apoptosis, and modulating AMPK-regulated autophagy. Additionally, RE improved gut microbiota diversity, particularly increasing beneficial bacteria such as Lactobacillus and Bifidobacterium . Conclusions Therefore, RE could alleviate the cognitive deficit associated with age-related neurodegenerative diseases by targeting ferroptosis-related oxidative stress, apoptosis, and autophagy, as well as modulating the gut microbiota.
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DOI
PubMed
高影响因子
Toxins
·
2022
·Vol. 14
·期 12
·876
·
IF 5.075
Yanan Wang,Jiayu Wu,Lingfeng Wang,Ping Yang,Zuhong Liu,Shahid Ali Rajput,Mubashar Hassan,Desheng Qi
Aflatoxin B1(AFB1) exists widely in feed and food with severe hazards, posing a serious threat to human and animal health. Epigallocatechin gallate (EGCG) and glutathione (GSH) have been reported as having anti-oxidative and other functions. The present study aimed to investigate the detoxification effect of EGCG and GSH alone or in combination on AFB1exposure in ducklings. Fifty one-day-old male ducklings were randomly assigned into five experimental groups (n= 10): 1. Control (CTR); 2. 0.3 mg/kg BW AFB1(AFB1); 3. 0.3 mg/kg BW AFB1+ 100 mg/kg BW EGCG (AFB1+ EGCG); 4. 0.3 mg/kg BW AFB1+ 30 mg/kg BW GSH (AFB1+ GSH); 5. 0.3 mg/kg BW AFB1+ 100 mg/kg BW EGCG + 30 mg/kg BW GSH (AFB1+ EGCG + GSH). The experiment lasted for seven days. Compared with the CTR group, AFB1reduced growth performance, total serum protein and albumin content, increased serum enzyme activity (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase), and caused pathological damage to the ducklings’ livers. AFB1exposure increased malondialdehyde content and decreased superoxide dismutase, total antioxidant capacity, catalase, glutathione peroxidase activities, and glutathione content in the liver. EGCG and GSH alone or in combination mitigated these adverse effects. Meanwhile, EGCG and GSH attenuate apoptosis of hepatocytes, and regulated AFB1-induced changes in the abundance of genes contained in the Keap1/Nrf2 signalling and apoptotic pathways. Collectively, these results suggest that EGCG and GSH alleviate the hepatocyte injury induced by AFB1by inhibiting oxidative stress and attenuating excessive mitochondria-mediated apoptosis.Keywords:aflatoxin B1;duckling;epigallocatechin gallate;glutathione;oxidative stress;Keap1/Nrf2 signalling;apoptosisKey Contribution:EGCG and GSH alleviate AFB1-induced liver injury in ducklings by increasing antioxidant capacity and antagonising apoptosis.
研究领域:
兽医学
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毒理学
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药理学
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DOI
PubMed
高影响因子
Food & Function
·
2023
·Vol. 14
·期 4
·1884-1896
·
IF 6.1
Huiyi Li,Qiqing Weng,Shuai Gong,Weixian Zhang,Jiaqi Wang,Yuqiao Huang,Yuanjun Li,Jiao Guo,Tian Lan
Acetaminophen (APAP)-induced liver injury (AILI) has become a growing public health problem. Ferroptosis, an iron-dependent form of cell death associated with lipid peroxide accumulation, has been recently implicated in AILI. The activation of the Nrf2 signaling pathway is a potential therapy for AILI. Kaempferol (KA), a flavonoid widely existing in edible plants, has been reported to exert profound anti-inflammatory and antioxidant activities. This study aimed to investigate whether KA exerts anti-AILI effects via the Nrf2 signaling pathway. Mice were fasted for 22 h and injected intraperitoneally with APAP (250 mg kg−1) to induce AILI. Mice were pre-injected intragastrically with KA for 2 h followed by APAP injection. The hepatic injury was observed by H&E staining. Biochemical parameters of the serum and liver were measured using kits. KA alleviated hepatic injury and inflammatory response in AILI mice and ameliorated APAP-induced hepatic iron overload and oxidative stress in mice. In addition, the protective effects of KA against APAP-induced hepatotoxicity were examined in L02 cells in vitro. Cell viability was assayed by the CCK8 assay. Mitochondrial reactive oxygen species (ROS) in L02 cells were detected by MitoSox fluorescence. KA reversed the APAP-induced decrease in cell viability and GSH levels and inhibited the accumulation of intracellular ROS. Furthermore, KA activated the Nrf2 pathway and upregulated Gpx4 in mouse livers and L02 cells to inhibit ferroptosis induced by APAP. Finally, molecular docking indicated the potential interaction of KA with Keap1. Taken together, KA ameliorated oxidative stress and ferroptosis-mediated AILI by activating Nrf2 signaling.
研究领域:
药理学
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毒理学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
Antioxidants
·
2026
·Vol. 15
·期 9
·1207
·
IF 8.2
Kaiwen You,Yixuan Li,Wanqing Zhong,Jie Yu,Yamei Wu,Yuqi Guo,Haoyang Liu,Haiping Xie,Kai Yuan,Yihong Chen,Lei Wang
Due to the hypoxic environment caused by global warming and intensive aquaculture process, fish are susceptible to oxidative damage and death.Eucommia ulmoidesextract (EUE) has demonstrated antioxidant and anti-inflammatory properties. However, whether EUE can mitigate hypoxia-induced negative effects remains uninvestigated in fish. This study investigated the effect of 0 and 1.0 g/kg EUE on acute hypoxia-induced damage in largemouth bass and its potential mechanisms. The results showed that EUE alleviated the deterioration of plasma activities (ALT and AST) induced by acute hypoxic stress, decreased the number of macrophages and increased the total number of blood cells. EUE was effective in reducing the level of apoptosis and the content of ROS, Ca2+, and NO in blood cells. Additionally, EUE alleviated liver tissue injury caused by acute hypoxic stress, which could be associated with increased total antioxidant capacity and antioxidant enzyme activities (SOD, CAT and GSH-Px). Furthermore, EUE up-regulated the expression levels ofNrf2andCAT, activatedXBP1andIREexpression and down-regulatedGRP78expression, relieving the endoplasmic reticulum (ER) stress response. The down-regulation ofCaspase3andCaspase9is evidence that EUE inhibited apoptosis in acute hypoxic stress. In summary, EUE reduced oxidative damage, ER stress, and apoptosis caused by hypoxic stress via the Nrf2/Keap1 signaling pathway in largemouth bass. This study presents a part of the theoretical foundation for the EUE to resist damage caused by hypoxic stress, thereby establishing a basis for sustainable development in aquaculture.
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DOI
高影响因子
Experimental and Therapeutic Medicine
·
2021
·Vol. 22
·期 6
·1-10
·
IF 2.447
Qian Li,Zhaoyan Qiu,Yan Wang,Chunyan Guo,Xu Cai,Yandong Zhang,Li Liu,Hongkun Xue,Jintian Tang
Tea polyphenols (TPs) are the major bioactive extract from green tea that have been extensively reported to prevent and treat oxidative stress damage. In previous studies, TPs have been demonstrated to protect cells against oxidative injury induced by hydrogen peroxide (H2O2). However, the underlying mechanism remains unclear. The aim of the current study was to investigate whether the protective and regulatory effects of TPs on oxidative stress damage were dependent on the mammalian STE20‑like protein kinase (Mst)/nuclear factor (erythroid‑derived 2)‑like 2 (Nrf2) axis and the Kelch‑like ECH‑associated protein 1 (Keap1)/Nrf2/heme oxygenase 1 (HO‑1) pathway in RAW264.7 cells, a murine macrophage cell line. Maintaining a certain range of intracellular reactive oxygen species (ROS) levels is critical to basic cellular activities, while excessive ROS generation can override the antioxidant capacity of the cell and result in oxidative stress damage. The inhibition of ROS generation offers an effective target for preventing oxidative damage. The results of the present study revealed that pretreatment with TPs inhibited the production of intracellular ROS and protected RAW264.7 cells from H2O2‑induced oxidative damage. TPs was also demonstrated to attenuate the production of nitric oxide and malondialdehyde and increase the levels of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase). In addition, following TPs treatment, alterations in Mst1/2 at the mRNA and protein level inhibited the production of ROS and promoted the self‑regulation of antioxidation. TPs‑induced Keap1 gene downregulation also increased the expression of Nrf2 and HO‑1. Collectively, the results of the present study demonstrated that TPs provided protection against H2O2‑induced oxidative injury in RAW264.7 cells.
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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生物化学
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DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2025
·
IF 4.5
Yulu Wang,Minghao Yuan,Sihui Li,Jiamei Tang,Yan Wan,Xue Liang,Yiping Guo,Li Guo
Alcohol liver disease (ALD) is a chronic liver disorder resulting from long-term heavy alcohol consumption. The pathogenesis of ALD is multifactorial, and existing therapeutic agents primarily target specific aspects of the disease while presenting significant side effects, including drug-induced liver injury and hepatobiliary disease. Silibinin (SLB) has attracted widespread attention for its hepatoprotective effects and favorable safety profile. However, inherent limitations associated with SLB, such as poor solubility and bioavailability, have significantly limited its clinical application. Drug delivery systems, including liposomes, offer promising potential for the delivery of hydrophobic drugs. However, the selection of an appropriate delivery vehicle requires optimization. Ursodeoxycholic acid sodium (UAS) serves as a promising alternative to cholesterol in liposomal formulations, offering a potential strategy to mitigate the health risks associated with cholesterol. In this study, UAS was employed as the liposomal membrane material to prepare a UAS liposome loaded with SLB (SUL), and its efficacy and mechanism of action in alcoholic-induced liver injury were subsequently evaluated. The experimental results demonstrated that SUL exhibited a uniform particle size distribution, good stability, and an effective release profile in vitro. Following oral administration, SUL effectively inhibited alcohol-induced liver damage, oxidative stress, and fat accumulation. In addition, SUL regulated the expression of the kelch-1ike ECH- associated protein l (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1) proteins, thereby exerting antioxidative stress effects. Furthermore, it also modulated apoptosis-related factors, including B-cell lymphoma-2 (Bcl-2), BCL-2-associated X (Bax), cysteinyl aspartate specific proteinase-3 (Caspase-3), and cleaved caspase-3, to mitigate hepatocyte apoptosis. In summary, SUL demonstrates enhanced therapeutic efficacy against ALD, offering a novel approach for the clinical application of SLB in the prevention and treatment of ALD.
研究领域:
药理学
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肝病学
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药物递送系统
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分子生物学
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DOI
PubMed
高影响因子
ACS Omega
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2024
·
IF 3.7
Chenxin Xu,Yinghua Chen,Zhuoen Zhou,Ying Yan,Wenying Fu,Peng Zou,Daoyong Ni
Lung cancer is one of the leading causes of death. Celastrol is a natural product that has shown anticancer activity but has not yet been applied in clinical settings due to its narrow therapeutic window. In this study, we discovered that celastrol stimulates an abnormal rise in the reactive oxygen species (ROS) level in lung cancer cells and that the ROS scavenger N-acetylcysteine (NAC) could counteract the cell death caused by celastrol. At the same time, celastrol upregulated the expression of cytoprotective transcription factor Nrf2 and its downstream proteins, which are effective in preventing the oxidative damage caused by ROS accumulation. Notably, we found that the overexpression of Nrf2 enhances the tolerance of lung cancer cells to celastrol and that lung cancer cells H460 with a Keap1 mutation are insensitive to celastrol. This indicates that the increase in Nrf2 contributes to the survival of lung cancer cells. Thus, we brought in an Nrf2 inhibitor ML385 to suppress the activation of Nrf2. We found that when ML385 and celastrol were added together the survival rates of lung cancer cells decreased more and the detected ROS level became much higher compared to treatment with celastrol alone. We also discovered that ML385 suppressed the expression of HO-1 and GCLC, which amplified celastrol-induced ATF4/CHOP-dependent endoplasmic reticulum stress (ER stress). Above all, our study found that ML385 enhanced celastrol-induced increases in ROS and ER stress, leading to lung cancer cell death. This research provides a potential strategy for the preclinical investigation of celastrol.
研究领域:
肿瘤学
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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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DOI
PubMed
高影响因子
Probiotics and Antimicrobial Proteins
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2022
·Vol. 14
·期 4
·741-750
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IF 5.265
Gao Xiaoxi,Zhang Yuhong,Mu Guangqing,Xu Yunpeng,Wang Xinmiao,Tuo Yanfeng,Qian Fang
The aim of the present study was to investigate the in vitro antioxidant potential of Bacillus coagulans T242. B. coagulans T242 showed better antioxidant activities, including the 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging ability, lipid peroxidation inhibiting ability and reducing ability, than those exerted by Lactobacillus rhamnosus GG (LGG). B. coagulans T242 positively regulated the expression of the nuclear factor erythroid 2-relatedfactor 2/Kelch-like ECH-associated protein-1 (Nrf2/Keap1) pathway-related proteins (Nrf2, Keap1, heine oxygenase-1 (HO-1)); increased antioxidant enzymes (glutathione peroxidase (GSH-Px), catalase (CAT), superoxide dismutase (SOD)); reduced the content of malondialdehyde (MDA) level; decreased the expression of inflammatory-related cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α); and thus increased the survival rate in 2,2′-azobis (2-methylpropionamidine) dihydrochloride (AAPH)-damaged HT-29 cells. This study proved that B. coagulans T242 exerted antioxidative effects by quenching oxygen free radicals and activating the Nrf2 signaling pathway in HT-29 cells.
研究领域:
微生物学
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细胞生物学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Marine Drugs
·
2025
·Vol. 23
·期 8
·294
·
IF 5.4
Jing Lu,Pujing Shi,Yutian Cao,Bingxin Shi,Huilin Shen,Shuai Zhao,Yuchen Gao,Huibing Chi,Lei Wang,Yawei Shi
Mussels are nutrient-rich but perishable, resulting in substantial resource loss. A protease-producing strain (Bacillus velezensisZ-1,Mytilus edulis) isolated from marine sludge was used to hydrolyze mussels, producing Y-1, a hydrolysate with antioxidant activity. In this study, ultrafiltration, gel chromatography, and LC-MS/MS were employed to isolate and identify bioactive peptides from the hydrolysate. The results revealed that the hydrolysate exhibited antioxidant activity, pancreatic cholesterol esterase inhibitory activity, pancreatic lipase inhibitory activity, and α-glucosidase inhibitory activity. Molecular docking using AutoDock Tools 1.5.6 was performed to analyze the interactions of peptides with CD38 and Keap1, leading to the identification of five potentially bioactive peptides: VPPFY, IMLFP, LPFLF, FLPF, and FPRIM. These peptides formed hydrogen bonds and hydrophobic interactions with CD38 and Keap1, demonstrating strong DPPH radical scavenging and superoxide anion radical scavenging capacities. This study highlights the multifunctional bioactive potential of these peptides, offering insights into their therapeutic applications. The findings provide a novel approach for the effective utilization of mussel resources and highlight their potential application value in the development of functional foods.
研究领域:
海洋生物技术
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食品科学
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生物化学
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药理学
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生物技术
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产品关联
DOI
PubMed
高影响因子
Food Frontiers
·
2023
·
IF 9.9
Pengde Lu,Jinfen Chen,Ying Chen,Xingping Quan,Jiayue Liu,Yan Han,Yiyang Li,Li Yang,Jian-Bo Wan,Yonghua Zhao
Ulcerative colitis (UC) is a digestive disease with a high incidence and is difficult to be cured due to its complex etiology. It has evidenced that intestinal barrier dysfunction plays a predominant role in UC. 20( S )-protopanaxadiol saponins (PDS) isolated from Panax notoginseng possess anti-inflammatory and antioxidative activities, suggesting its potential of treating UC. Herein, the therapeutic effects of PDS against UC and underlying mechanisms in the aspect of intestinal barrier dysfunction were investigated in vivo and in vitro. The results showed PDS had protective effects against dextran sulfate sodium–induced colitis, including attenuating weight loss, disease activity index score elevation, colon length shortening, and histological lesions. Additionally, PDS reduced the colonic activity of myeloperoxidase and the cytokine levels of TNF-α, IL-6, and IL-1β, decreased MDA production, and elevated colonic activities of SOD and GSH-Px in the colitis mice. The expressions of proteins related to tight junction (TJ), including ZO-1, claudin-5, occludin, caveolin-1 (Cav-1), and Nrf2 were downregulated, whereas that of Keap1 was upregulated after colitis induction. These changes were reversed by PDS. Cav-1 expression was downregulated in lipopolysaccharides (LPS)- and H 2 O 2 -induced HCT116 cells, and the expressions of ZO-1, claudin-5, and occludin were suppressed in HCT116 cells stimulated by LPS and H 2 O 2 combined with Cav-1 small interfering RNA transfection, which were ameliorated by PDS, suggesting PDS targeted Cav-1 against intestinal barrier damage. Collectively, PDS alleviates inflammatory injury and oxidative stress by regulating the Nrf2/Keap1 pathway, contributing to targeting Cav-1 against intestinal epithelial TJ proteins loss. It suggests PDS might be a promising therapeutic natural product for UC treatment.
研究领域:
药理学
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胃肠病学
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免疫学
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分子生物学
✓ 已验证
DOI
高影响因子
Journal of Cosmetic Dermatology
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2024
·
IF 2.3
Xing-Li-Shang He,Ning Wang,Xi Teng,Nan-Nan Wang,Zhi-Yi Xie,Ying-Jie Dong,Min-Qiu Lin,Ze-Hua Zhang,Mei Rong,Yi-Gong Chen,Bo Li,Gui-Yuan Lv,Su-Hong Chen
Background Dendrobium officinale flowers (DOF) have the effects of antiaging and nourishing yin, but it lacks pharmacological research on skin aging. Objective Confirming the role of DOF in delaying skin aging based on the “in vitro animal–human” model. Methods In this experiment, three kinds of free radical scavenging experiments in vitro, D-galactose-induced aging mouse model, and human antiaging efficacy test were used to test whether DOF can improve skin aging through anti-oxidation. Results In vitro experiment shows that DOF has certain scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical, hydroxyl free radical, and superoxide free radical, and its IC 50 is 0.2090 μg/mL, 15.020, and 1.217 mg/mL respectively. DOF can enhance the activities of T-AOC, SOD, CAT, and GSH Px in the serum of aging mice, increase the content of GSH, and reduce the content of MDA when administered with DOF of 1.0, 2.0, and 4.0 g/kg for 6 weeks. In addition, it can enhance the activity of SOD in the skin of aging mice, increase the content of Hyp, and decrease the content of MDA, activated Keap1/Nrf2 pathway in the skin of aging mice. Applying DOF with a concentration of 0.2 g/mL on the face for 8 weeks can significantly improve the skin water score and elasticity value, reduce facial wrinkles, pores, acne, and UV spots, and improve the facial brown spots and roughness. Conclusion DOF can significantly improve skin aging caused by oxidative stress, and its mechanism may be related to scavenging free radicals in the body and improving skin quality.
研究领域:
药理学
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化妆品科学
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衰老研究
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生物化学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2018
·Vol. 19
·期 4
·1135
·
IF 3.687
Maiquan Li,Tao Xu,Fei Zhou,Mengmeng Wang,Huaxin Song,Xing Xiao,Baiyi Lu
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor against oxidative stress and neurodegenerative disorders. Phenylethanoid glycosides (PhGs; salidroside, acteoside, isoacteoside, and echinacoside) exhibit antioxidant and neuroprotective bioactivities. This study was performed to investigate the neuroprotective effect and molecular mechanism of PhGs. PhGs pretreatment significantly suppressed H2O2-induced cytotoxicity in PC12 cells by triggering the nuclear translocation of Nrf2 and reversing the downregulated protein expression of heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), glutamate cysteine ligase-catalytic subunit (GCLC), and glutamate-cysteine ligase modifier subunit (GCLM). Nrf2 siRNA or HO-1 inhibitor zinc protoporphyrin (ZnPP) reduced the neuroprotective effect. PhGs showed potential interaction with the Nrf2 binding site in Kelch-like ECH-association protein 1 (Keap1). This result may support the hypothesis that PhGs are activators of Nrf2. We demonstrated the potential binding between PhGs and the Keap1-activated Nrf2/ARE pathway, and that PhGs with more glycosides had enhanced effects.Keywords:Keap1;Nrf2;Neuroprotective;PC12 cells;PhGs
研究领域:
神经科学
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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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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）