EXPERIMENTAL EYE RESEARCH
·
2023
·
IF 3.4
Jingfei Yang,Zhijuan Hua,Zhikun Zheng,Xuan Ma,Liang Zhu,Yan Li
Diabetes retinopathy (DR) is one of the most common microvascular complications of diabetes. Retinal pigment epithelial (RPE) cells exposed to a high glucose environment experience a series of functional damages, which is an important factor in promoting the progression of DR. Acteoside (ACT) has strong antioxidant and anti-apoptotic properties, but the mechanism of ACT in DR is not completely clear. Therefore, the purpose of the present study was to explore whether ACT inhibits the damage to RPE cells in a high glucose environment through antioxidative effects to alleviate the DR process. The DR in vitro cell model was constructed by treating RPE cells with high glucose, and the DR in vivo animal model was constructed by injecting streptozotocin (STZ) into the peritoneal cavity of mice to induce diabetes. The proliferation and apoptosis of RPE cells were detected by CCK-8 and flow cytometry assays, respectively. The expression changes in Nrf2, Keap1, NQO1 and HO-1 were evaluated by qRT‒PCR, Western blot and immunohistochemistry analyses. The MDA, SOD, GSH-Px and T-AOC contents were detected by kits. The changes in ROS and nuclear translocation of Nrf2 were observed by immunofluorescence assays. HE staining was used to measure the thickness of the outer nuclear layer (ONL) of the retina, and TUNEL staining was used to detect the number of apoptotic cells in the retinas of mice. In the present study, ACT effectively ameliorated outer retina damage in diabetic mice. In high glucose (HG)-induced RPE cells, ACT treatment had the following effects: improved proliferation, decreased apoptosis, inhibited Keap1 expression, promoted the nuclear translocation and expression of Nrf2, upregulated NQO1 and HO-1 (the target genes of Nrf2) expression, decreased ROS concentration, and increased the levels of the SOD, GSH-Px and T-AOC antioxidant indicators. However, knockdown of Nrf2 reversed the above phenomena, which indicated that the protective function of ACT in HG-induced RPE cells are closely related to Nrf2. In summary, the present study demonstrated that HG-induced oxidative stress injury is inhibited by ACT in RPE cells and the outer retina through the Keap1/Nrf2/ARE pathway.
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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糖尿病研究
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眼科学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Haochun Guo,Jiajia Chen,Hanxu Yu,Lei Dong,Ran Yu,Qingju Li,Jian Song,Haoyu Chen,Haijun Zhang,Juan Pu,Wanpeng Wang
Background Radiation-induced lung injury (RILI) is a common side effect of thoracic tumor radiotherapy, including early-stage radiation-induced lung injury (RP) and late-stage radiation-induced pulmonary fibrosis (RIPF). Currently, it is urgently needed to clarify the pathogenesis of RILI and find safe and effective RILI treatment methods. Irradiation causes DNA damage and oxidative stress in tissues and cells, induces cellular senescence, and promotes the occurrence and development of RILI. In recent years, Anisodamine (654-2) has shown potential therapeutic value in acute lung injury, acute kidney injury, chlamydial pneumonia, and COVID-19. However, there is currently no research on the mechanism of 654-2-mediated cellular senescence and its preventive and therapeutic effects on RILI. Purpose This study aimed to investigate the protective effect and mechanism of 654-2 on X-ray-induced RILI. Methods In vivo experiments involved a mouse RILI model with 18 Gy X-ray irradiation. Mice were divided into control, model, medication (control + 654-2), and treatment (model + 654-2) groups. And mice in medication and treatment groups were intraperitoneal injection of 5 mg/kg 654-2 every other day until being sacrificed at week 6. In vitro experiments used MLE-12 cells irradiated with 16 Gy and divided into control, model, and model + 654-2（2 μM and 10 μM） groups. Various assays were performed to evaluate lung tissue morphology, fibrosis, apoptosis, cytokine expression, cellular senescence, protein expression, and antioxidant capacity. Results 654-2 mitigated pulmonary pathological damage, inflammation, DNA damage, cellular senescence, and apoptosis in RILI mice and MLE-12 cells. It restored epithelial cell proliferation ability and enhanced antioxidant capacity. Additionally, 654-2 activated the Nrf2/ARE pathway, increased Nrf2 phosphorylation, and upregulated antioxidant gene expression. Inhibition of Nrf2 reversed the effects of 654-2 on ROS production, antioxidant capacity, and cell senescence. Conclusion 654-2 can activate the Nrf2/ARE pathway, enhance cellular antioxidant capacity, and inhibit cellular senescence, thereby exerting a protective effect against RILI.
研究领域:
药理学
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放射生物学
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分子生物学
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呼吸病学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2022
·Vol. 48
·期 2
·393-403
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IF 4.414
Ma Zijian,Ma Yang,Cao Xuefeng,Zhang Yunpeng,Song Tieying
Postoperative neurocognitive impairment (POCD) is a common complication after surgery and anesthesia, especially in elderly patients. Avenanthramide-C (AVC) test is a vascular endothelial cell adhesion molecule inhibitor with strong anti-inflammatory and antioxidant effects. The aim of this study was to investigate the effect and mechanism of AVC on POCD in aged rats to clarify the effect of AVC on POCD in aged rats. The aging rat model was established by continuous 200 mg/kg propofol anesthesia. Repeated propofol anesthesia could severely impair spatial learning ability, memory and cognitive function, and could promote hippocampal apoptosis, oxidative stress injury, neuroinflammation and ferroptosis in aging rats. In addition, AVC not only improved cognitive dysfunction, but also significantly inhibited apoptosis, neuroinflammatory response, ferroptosis and oxidative stress level in the hippocampus of aging rats induced by repeated anesthesia. Further mechanistic studies manifested that the above protective effects of AVC on aging rats induced by repeated propofol anesthesia may be achieved by activating Nrf2/ARE pathway activity. AVC pretreatment has a preventive effect on cognitive dysfunction induced by repeated propofol anesthesia in aging rats, and the preventive effect of AVC may be realized by activating the Nrf2/ARE signaling pathway activity. Our results demonstrate that AVC preconditioning reduces postoperative neuronal loss and neuroinflammation, activates the Nrf2/ARE pathway, reduces oxidative stress injury, and improves POCD in aged rats.
研究领域:
神经科学
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药理学
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老年医学
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麻醉学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2018
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IF 3.61
Zhisheng Xie,Lingjun Zhong,Yanrao Wu,Xiaomeng Wan,Hua Yang,Xiaojun Xu,Ping Li
Background Diabetic nephropathy (DN), one of the most serious complications of diabetes , is the leading cause of morbidity and mortality of end-stage renal disease. Our previous research found that carnosic acid (CA) or rosemary extract can effectively improve glucose and lipid metabolism disorder by inhibiting SREBPs . Purpose In this study, we aimed to explore the therapeutic effects of CA on the DN. Methods The mice glomerular mesangial cells (mGMCs) were used to evaluate the anti-oxidative and anti-inflammation effects of CA under high glucose (HG) condition. Furthermore, db/db mice and streptozotocin (STZ)-induced diabetic mice were used to investigate the effects of CA against DN in vivo . Results The results showed that CA activated Nrf2, inhibited NF-κB pathway and regulated related downstream genes in mGMC under HG condition. A 14-week treatment of mice with CA reduced water uptake and urine volume, attenuated diabetes-induced albuminuria , increased urine creatinine , and subsequently improved the glomerular sclerosis and mesangial expansion in db/db mice. Similarly, a 20-week oral administration of CA improved kidney damage in STZ-induced diabetic mice. In addition, CA inhibited the expression of profibrotic factors, such as TGF-β1, fibronectin and E-cadherin. Compared to irbesartan , CA exerted better glucose lowering effect, and in kidney, CA was more potent to reduce fibronectin and E-cadherin expression. In all the animal experiment, CA did not lead to abnormal damages to other tissues. Conclusion These findings suggest that CA is a safe compound which exerts the protective effects on diabetes-induced kidney complications.
研究领域:
药理学
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内分泌学
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肾病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Food & Function
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2022
·Vol. 13
·期 5
·2618-2630
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IF 6.317
Xin Hao,Jiahong Xie,Yuting Li,Wei Chen
Anthocyanins are natural products that display diverse bioactivities but are limited in their applications by low stability and bioavailability. Acylated anthocyanins are found to possess higher stability, while their bioactivities are still obscure. In this study, acetylation of pelargonidin-3-O-glucoside (Pg3G) was catalyzed by Candida antarctica lipase B (CALB) for the first time, with a conversion rate up to 88.77% over 48 h. The acetylated product was identified as pelargonidin-3-O-(6′′-acetyl)-glucoside and its properties were detected. Notably, acetylated Pg3G (Ace Pg3G) possessed better thermostability and lipophilicity than Pg3G, indicating a longer retention time at physiological pH and facilitating penetration into the lipophilic medium as well as the cell membrane. Most importantly, Ace Pg3G exerted better alleviation effects against H2O2-induced oxidative hepatic damage than parent Pg3G via activating the Nrf2/ARE signaling pathway and upregulating the expressions of the downstream phase II detoxification enzymes GCLC and HO-1, thereby reversing redox imbalance and enhancing cell survival. Overall, our research unveiled the better health benefits of Ace Pg3G and also provided new insights about the applications of acetylated anthocyanins in food, cosmetic, and pharmaceutical products.
研究领域:
食品科学
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药理学
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生物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2020
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IF 4.679
Hang Qu,Shuang Liu,Cuilin Cheng,Haitian Zhao,Xin Gao,Zhenyu Wang,Juanjuan Yi
Previously, we obtained a purified polysaccharide (PNP40c-1) from Pinus koraiensis pine nut and reported its protective effect on carbon tetrachloride (CCl 4 )-induced liver injury in vitro . The object of this study is to investigate its hepatoprotective activity in vivo and elucidate the mechanism underlying the hepatoprotection . PNP40c-1 effectively prevented the accumulation of serum liver injury biomarkers including alanine aminotransferase , aspartate aminotransferase, alkaline phpsphatase and total bilirubin stimulated by CCl 4 . The pathological changes in PNP40c-1-treated mice livers were also markedly ameliorated. Results showed that PNP40c-1 suppressed the production of reactive oxygen species (ROS) and lipid peroxidation, upregulated Nrf2/ARE pathway and enhanced the antioxidant capacity of hepatocytes. Furthermore, the reaction between Nrf2 and ARE promoted the generation of Mkp1 , which inhibited the activation of JNK induced by CCl 4 , and suppressed hepatocytes apoptosis by regulating the protein expression of Bax, cleaved-Caspase-3 and Bcl2, exerting hepatoprotective activity. Taken together, upregulation of Nrf2/ARE pathway and suppression of JNK activation via Nrf2/ARE/Mkp1/JNK signaling pathways are the main mechanisms underlying the hepatoprotective effect of PNP40c-1 against CCl 4 -induced mice liver injury. These results indicated that PNP40c-1 has potential to serve as a hepatoprotective agent against chemical induced hepatotoxicity.
研究领域:
药理学
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毒理学
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生物化学
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分子生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
CELLULAR SIGNALLING
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2021
·
IF 4.315
Hao Huang,Xielan Kuang,Xiaobo Zhu,Hao Cheng,Yuxiu Zou,Han Du,Han Tang,Linbin Zhou,Jingshu Zeng,Huijun Liu,Jianhua Yan,Chongde Long,Huangxuan Shen
Retinal ischemia-reperfusion (I/R) often results in intractable visual impairments, where blood retinal barrier (BRB) homeostasis mediated by retinal pigment epithelium (RPE) and retinal microvascular endothelium (RME) is crucial. However, strategies targeting the BRB are limited. Thus, we investigated the inconclusive effect of lycopene (LYC) in retinal protection under I/R. LYC elevated cellular viability and reversed oxidative stress in aRPE-19 cells/hRME cells under I/R conditions based on oxygen-glucose deprivation (OGD) in vitro . Molecular analysis showed that LYC promoted NRF2 expression and enhanced the downstream factors of the KEAP1/NRF2/ARE pathway: LYC increased the activities of antioxidants, including SOD and CAT , whereas it enhanced the mRNA expression of HO-1 ( ho-1 ) and NQO-1 ( nqo-1 ). The activation resulted in restrained ROS and MDA. On the other hand, LYC ameliorated the damage to retinal function and morphology in a mouse I/R model, which was established by unilateral ligation of the left pterygopalatine artery/external carotid artery and reperfusion . LYC promoted the expression of NRF2 in both the neural retina and the RPE choroid in vivo . This evidence revealed the potential of LYC in retinal protection under I/R, uncovering the pharmacological effect of the KEAP1/NRF2/ARE pathway in BRB targeting. The study generates new insights into scientific practices in retinal research.
研究领域:
眼科学
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药理学
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分子生物学
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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 AGRICULTURAL AND FOOD CHEMISTRY
·
2018
·
IF 3.412
Fuqiang Liang,Yajing Fang,Weiwei Cao,Zhuo Zhang,Siyi Pan,Xiaoyun Xu
The current study evaluates the protective effects of tangeretin, a representative polymethoxyflavone (PMF) mainly isolated from the peels of citrus fruits, against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in HepG2 cells and the potential mechanisms of this protection. Tangeretin suppressed t-BHP-induced oxidative damage, as evaluated by cell viability, reactive-oxygen-species (ROS) levels, lactate dehydrogenase (LDH) leakage and glutathione (GSH) levels. Further mechanistic studies showed that tangeretin up-regulated the expression of heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). Moreover, tangeretin induced antioxidant-responsive-element (ARE)-dependent luciferase activation, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nuclear translocation, and mitogen-activated-protein-kinase (MAPK) phosphorylation. Results in the study indicate that the protective effects of tangeretin may be at least partly due to its capacity to up-regulate the antioxidant enzymes NQO1 and HO-1 via the MAPK–Nrf2–ARE signaling pathway. Tangeretin may play an effective protective role in liver injury.
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2020
·Vol. 11
·期 4
·3043-3052
·
IF 4.171
Wenli Yan,Guimei Lin,Rong Zhang,Zhen Liang,Wenjuan Wu
Two novel effective antioxidative tripeptides GWY and QWY were designed based on 3D-QSAR models. Their activities were confirmed by an improved TEAC assay. The experimental results showed that GWY and QWY possessed good antioxidant activity, equaling 3.32 mM TE and 2.97 mM TE respectively. This indicated that 3D-QSAR models possessed significant predictive capacity for drug design. In addition, molecular docking and molecular dynamics simulation were applied to reveal the potential molecular mechanism of antioxidant peptides. The result showed that GWY and QWY could enhance the stability of Keap1 by interacting with the key residues Arg415, Arg483, Arg380 and Ser555 in the active sites. Interestingly, the key residues were exactly the binding site of Nrf2 in the active pocket of Keap1. Thus, GWY and QWY could compete with Nrf2 for binding to Keap1. This demonstrated that the new tripeptides might have the ability to activate the signaling pathway Keap1–Nrf2–ARE and improve the antioxidant defense system of the body as well.
研究领域:
生物化学
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药物设计
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AQUACULTURE RESEARCH
·
2020
·Vol. 51
·期 4
·1592-1601
·
IF 1.748
Xiao-Bo Yu,Kai Hao,Fei Ling,Bin Zhu,Gao-Xue Wang
Our previous studies have verified that moroxydine hydrochloride (Mor) could inhibit replication of grass carp reovirus (GCRV) and suppress apoptosis of Ctenopharyngodon idella kidney cells, but be lack of information whether exists on antiviral activity in vivo. The paper was undertaken to explore the antiviral response of Mor against GCRV in grass carp and investigate the safety of drug for aquatic organisms. The results showed that injection treatment of Mor could more effectively inhibit GCRV replication than immersion administration. All the RNA systheses of vp3 and vp6 on day 7 in head kidney, gill, hepatopancreas and dorsal muscle in the Mor injection group were lesser than 0.07-fold than that of in control group. And the GCRV-inducing grass carp mortality was effectively controlled within 7 days post Mor injection therapy. Additionally, the reduction of superoxide dismutase activity, total antioxidant capacity and catalase activity in serum was effectively controlled by Mor. Moreover, drug safety assessment results showed that 500 mg/L of Mor was safe to C. idella , Bacillus subtilis , Chlorella vulgaris and Tetrahymena thermophila , which was far higher than the therapeutic concentration. The present study proved Mor as harmless formulations or products had potential value in the control of GCRV in aquaculture, with the advantage of super in vivo antiviral activity and environmental safety.
研究领域:
兽医学
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水产养殖
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药理学
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病毒学
✓ 已验证
DOI
高影响因子
AQUACULTURE RESEARCH
·
2021
·Vol. 52
·期 6
·2528-2539
·
IF 2.082
Jiabao Hu,Qijun Le,Man Zhang,Siwen Kuang,Weiwei Gu,Yibo Sun,Kimran Jean Jacques,Youyi Zhang,Yaya Li,Jiachu Sun,Yang Yang,Yajun Wang,Shanliang Xu,Xiaojun Yan
Silver pomfret ( Pampus argenteus ) performs a significant appetite for jellyfish, and amino acids are common components of the natural prey of fish, so we investigated the effect of aspartic acid, glycine and cysteine (high-content amino acid in jellyfish) on olfactory-related receptors regulating appetite in silver pomfret. The fish showed significant attractant responses to these amino acids in water, which were also observed to improve the ingestion rates of the fish. Next, we conducted transcriptomes of the olfactory epithelium (OE) and identified 34 olfactory-related receptor genes were including olfactory receptors, trace amine-associated receptors and vomeronasal receptors genes, and we examined these genes in the OE and appetite-related genes (ghrelin and leptin in gut/stomach and neuropeptide Y, agouti-related protein and proopiomelanocortin in brain) by qRT-PCR. The olfactory-related receptor genes significantly expressed in amino acid groups, and the expression level of appetite-related genes was highest in aspartic acid group. Thus, olfactory-related receptors induced by amino acids might regulate appetite in fish through the OE–brain–gut and stomach axis. Using these data, we identified some effective amino acid phagostimulants which could be supplied in silver pomfret diet, and the results improved our understanding of the mechanism of olfactory-related receptors regulating appetite in fish.
研究领域:
海洋生物学
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鱼类生理学
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分子生物学
✓ 已验证
DOI
高影响因子
AQUACULTURE RESEARCH
·
2021
·Vol. 52
·期 7
·2963-2979
·
IF 2.082
Qin Ni,Chunfang Cai,Shengjie Ren,Junbiao Zhang,Yijun Zhao,Xinyi Wei,Yiyang Ge,Chengrui Wang,Wenjian Li,Ping Wu,Yuantu Ye,Xiamin Cao
This study aimed to reveal the impact of excessive dietary fibre (DF) intake on inflammatory responses and bile acid (BA) homeostasis in largemouth bass ( Micropterus salmoides ) and the potential mechanism. In vitro BA binding capacity was compared, and the results showed that the BA binding capacity to chenodeoxycholic acid and glycocholic acid by pectin and soybean meal was higher than cellulose and cottonseed meal respectively. An in vivo trial was conducted using a diet without DF as a control (CON diet), while test diets contained 150 g/kg cellulose (CEL diet) or pectin (PEC diet), 500 g/kg soybean meal (SBM diet) or cottonseed meal (CSM diet). Fish were overfed and ate ad libitum . Compared to fish fed the CON diet, fish fed the PEC and SBM diets showed high expression of inflammatory factor genes and BA synthesis factor genes and obvious histopathological damage in the gut and liver, while the responses of fish fed the CEL and CSM diets were mild. Whole-body BA contents in fish fed all test diets were lower than those in fish fed the CON diet ( p < 0.05). These results support the hypothesis that excessive DF intake induces inflammatory responses and dysregulation of BA homeostasis, which might be attributed to their binding capacity to BAs.
研究领域:
水产养殖
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营养学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）