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
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免疫学
·
细胞生物学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
·
2023
·
IF 4.3
Guanglu Wang,Yue Xin,Kaixin Ping,Xuhui Xu,Ying Sun,Xing Li,Xinying Guan,Jingquan Dong
Avermectins, as a new type of environmental pollutant, have received significant attention in recent years. Previous research has shown that acute exposure to avermectins can induce oxidative stress and inflammation in non-target fish species, such as carp. Flavonoid lignans, particularly Silybin, have demonstrated promising biological activities, including regulation of non-alcoholic fatty liver and cerebral ischemia-reperfusion injury. This study aims to investigate the impact of dietary supplementation with Silybin on the intestinal damage in carp caused by chronic exposure to avermectins and to improve the health status and production of carp in aquaculture. Silybin was used as a dietary supplement by adding it to the experimental feed, and an animal experimental model was utilized to assess its effects on oxidative stress, inflammation, and cell apoptosis in carp intestine. Additionally, intestinal barrier integrity, digestive capacity, and fish growth were evaluated. The results indicated that dietary supplementation with Silybin effectively alleviated the oxidative stress induced by chronic exposure to avermectins in carp intestine. Furthermore, Silybin improved intestinal barrier integrity and digestive capacity by modulating the Nrf2/Keap1 pathway. This study demonstrates that dietary supplementation with Silybin can effectively mitigate the intestinal damage caused by chronic exposure to avermectins in carp, providing a sustainable solution for the aquaculture industry to enhance the overall health and production of cultured fish. The research expands our understanding of avermectin environmental pollution and offers a potential remediation approach.
研究领域:
水产养殖
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环境毒理学
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药理学
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鱼类生理学
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产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2023
·
IF 4.1
Wan-Ying Li,Jun-Yang Liu,Zi-Xian Wang,Ke-Ying Wang,Chun-Xiang Huang,Wen He,Jia-Le Song
Ulcerative colitis (UC) is a chronic gastrointestinal disease that results from repeated inflammation and serious complications. Sinapic acid (SA) is a hydroxycinnamic acid present in a variety of plants that has antioxidant, anti-inflammatory, anticancer, and other protective effects. This study investigated the antifibrotic effect of SA on chronic colitis induced by dextran sulfate sodium salt (DSS) in mice. We observed that SA could significantly reduce clinical symptoms (such as improved body weight loss, increased colon length, and decreased disease activity index score) and pathological changes in mice with chronic colitis. SA supplementation has been demonstrated to repair intestinal mucosal barrier function and maintain epithelial homeostasis by inhibiting activation of the NLRP3 inflammasome and decreasing the expression of IL-6, TNF-α, IL-17A, IL-18, and IL-1β. Furthermore, SA could induce the expression of antioxidant enzymes (Cat, Sod1, Sod2, Mgst1) by activating the Nrf2/keap1 pathway, thus improving antioxidant capacity. Additionally, SA could increase the protein expression of downstream LC3-II/LC3-I and Beclin1 and induce autophagy by regulating the AMPK-Akt/mTOR signaling pathway, thereby reducing the production of intestinal fibrosis-associated proteins Collagen-I and α-SMA. These findings suggest that SA can enhance intestinal antioxidant enzymes, reduce oxidative stress, expedite intestinal epithelial repair, and promote autophagy, thereby ameliorating DSS-induced colitis and intestinal fibrosis.
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
产品关联
DOI
PubMed
高影响因子
Antioxidants
·
2025
·Vol. 14
·期 4
·392
·
IF 6.6
Wenge Zheng,Ruiling Chen,Kewei Xu,Rui Wang,Zhiyuan Wang,Huijuan Li,Yuyo Go,Xihui Chan,Qing Huang,Jianxin Wu
Glycation is a process in which reducing sugars bind to proteins, resulting in the formation of advanced glycation end products (AGEs). These AGEs accumulate in the skin, promote excessive collagen crosslinking, and disrupt the extracellular matrix (ECM), impairing normal cellular functions and contributing to skin aging. To evaluate the anti-glycation efficacy of lotus stamen extract (LSE), we employed the BSA–fructose system and a high glucose (HG)-induced fibroblast glycation model. The results demonstrated that LSE effectively inhibited cellular glycation and also exhibited anti-inflammatory, antioxidative, and anti-senescent effects in HG-induced human skin fibroblasts (HSF). Further investigation into the anti-glycation mechanism and component analysis of the lotus stamen ethyl acetate extract (LSEE) led to the identification of 15 flavonoids. The anti-glycation results indicated that these flavonoids are likely the primary active constituents in LSE. Mechanistic studies revealed that GLO1 plays a crucial role in cellular resistance to glycation, and LSEE enhanced GLO1 expression through the Nrf2/Keap1 pro-survival pathway, thereby mitigating intracellular AGE production. In summary, LSEE and its multiple flavonoid components exhibit potent intracellular anti-glycation activity and present significant potential to be developed as a natural and organic product for cosmetic and healthcare applications.
研究领域:
化妆品科学
·
生物化学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Xiong Zhao,Shuai Wu,Sheng Ni,Yuan Zhong,Xian Qin,Kun Zhang,Kai Qu,Li Zhu,Wei Wu
Rheumatoid arthritis (RA) is a chronic disease characterized by immune cell infiltration and cartilage damage. The local lesion of RA shows severe oxidative stress and proinflammatory cytokine secretion. For drug therapy, the efficacy of agents, such as methotrexate (MTX), may be greatly limited, resulting from the low bioavailability, immune clearance, and toxic side effects. A nanocarrier (TA-PBA NPs) was developed with anti-inflammatory and antioxidant activities, combined with MTX to prepare nanomedicine (MTX NPs) for synergistic treatment of RA. Moreover, inspired by the biological functions homing to inflammation lesion of macrophages, the biomimetic nanomedicine camouflaged with macrophage membrane (MM@MTX NPs) was constructed. TA-PBA NPs could timely promote MTX release in response to the overaccumulated ROS to exhibit high anti-inflammatory and antioxidant activities for alleviating RA progression. The experimental results confirmed that MM@MTX NPs could significantly reduce the secretion of proinflammatory cytokines (TNF-α) while significantly increasing the typical anti-inflammatory cytokines (IL-10), promote the phenotype transformation of macrophages from M1 to M2, and up-regulate the Nrf2-keap1 pathway-related proteins (HO-1 and NRF2) to positively regulate the local inflammation for effectively inhibiting RA development. Thus, MM@MTX NPs represent a possible candidate as a safe and efficient nanotherapy platform for RA management.
研究领域:
纳米技术
·
药学
·
免疫学
·
风湿病学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2022
·
IF 5.895
Ji Wang,Meihe Li,Yawen Gao,Hongmei Li,Li Fang,Chunlei Liu,Xiaoting Liu,Weihong Min
This study investigated the effects of the exopolysaccharide from Lactiplantibacillus plantarum JLAU103 (EPS103) on the intestinal immune response, oxidative stress, intestinal mucosal barrier, and microbial community in cyclophosphamide-induced immune-suppressed mice. The results showed that EPS103 promoted the secretion of cytokines and the generation of secretory immunoglobulin A and mucin-2 in the small intestine of mice, which might be related to the activation of the MAPK pathway. Additionally, EPS103 protected against oxidative stress by activating antioxidation enzymes and Nrf2/Keap1 pathways. It also improved the intestinal physical barrier functions via regulating the ratio of villous height to crypt depth and upregulating the expression of tight-junction proteins. Meanwhile, EPS103 promoted the generation of short-chain fatty acids (SCFAs) and modulated the constituents of gut microbiota. These results suggested that EPS103 may modulate the intestinal immunoresponse relying on the regulation of SCFA production and gut microbiota in immunosuppressed mice, resulting in the activation of systemic immunity.
研究领域:
免疫学
·
微生物学
·
胃肠病学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Qiang Chu,Ruoyi Jia,Wen Chen,Yangyang Liu,Yonglu Li,Xiang Ye,Yong Jiang,Xiaodong Zheng
Ethyl Carbamate (EC), as a carcinogen widely found in fermented foods, was verified that its cytotoxicity was associated with oxidative stress. Polysaccharides from natural sources due to their antioxidative capacity have attracted great attention in the past time. In this study, purified polysaccharide from Tetrastigma hemsleyanum vines (TVP) with 64.89 kDA was extracted and conducted multiple analysis to identify its structural information. It could be discovered that TVP was composed of mannose, rhamnose, glucuronic acid, glucose, galactose, and arabinose. In vitro , TVP could inhibit cytotoxicity and genotoxicity, attenuate oxidative damage and mitochondrial dysfunction induced by EC in Caco-2 cells. Meanwhile, TVP could suppress apoptosis by mTOR and Bcl-2 signaling pathways, ameliorate oxidative via Sirt1-FoxO1 and Nrf2-Keap1 signaling pathways. In vivo , EC as well triggered the decline of survival and athletic ability in Caenorhabditis elegans ( C. elegans ) and TVP could reverse the decline. In the meantime, TVP could ameliorate oxidative damage in N2 and daf-2 (-) mutant but fail in daf-16 (-) mutant, which suggested that DAF-16 (FOXO) might affect the antioxidative protection of TVP in C. elegans . In brief, our results manifested that TVP could attenuate EC-induced cytotoxicity both in vitro and in vivo .
研究领域:
药理学
·
毒理学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Qin Chen,Fen-Sheng Qiu,Wei Xie,Wen-Ying Yu,Zhao-An Su,Guang-Ming Qin,You-Kun Kang,Song-Lin Jiang,Chen-Huan Yu
Diabetic retinopathy (DR) is one of the chronic microvascular complications of type 2 diabetes mellitus (T2DM), which will cause retinal detachment and blindness without ideal therapies. Gypenoside A (GPA) are the main bioactive compound from Gynostemma pentaphyllum , and have various pharmacological effects. However, it suffered from poor bioavailability and potential cardiotoxicity in the clinical application. To overcome those limitations, in this study, nearly spherical nanoparticles (GPA-NP) with a mean particle size of 140.6 ± 22.4 nm were prepared by encapsulating GPA into mPEG-PLGA. This encapsulation efficiency was 84.4 ± 6.9 %, and the drug load was 4.02 %±0.35 %. The results showed that GPA-NP displayed more prolonged GPA release and higher bioavailability in vitro than GPA. GPA-NP obviously reduced the levels of oxidative stress markers and inflammatory cytokines in both retinal tissues of DR mice and high glucose-exposed HRMEC better than GPA alone. Mechanismly, GPA blocked the Nrf2-Keap1 interaction by binding with Kelch domain of Keap1 via alkyl and hydrogen bonds. Therefore, GPA-NP exerted more potent protectivity effects against high glucose-induced retinal microvascular endothelial ferroptosis in vitro and in vivo by activating Nrf2/HO-1/GPX4 pathway. It could be a promising therapeutic agent for preventing DR.
研究领域:
药理学
·
纳米技术
·
糖尿病
·
眼科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOFACTORS
·
2023
·
IF 6
Yongli Han,Lingling Luo,Hongli Li,Lijun Zhang,Yingxuan Yan,Minglv Fang,Jing Yu,Xiaoyan Gao,Ying Liu,Cheng Huang,Shengjie Fan
Nonalcoholic steatohepatitis (NASH) and hepatic fibrosis are leading causes of cirrhosis with rising morbidity and mortality worldwide. Currently, there is no appropriate treatment for NASH and hepatic fibrosis. Many studies have shown that oxidative stress is a main factor inducing NASH. Nomilin (NML) and obacunone (OBA) are limonoid compounds naturally occurring in citrus fruits with various biological properties. However, whether OBA and NML have beneficial effects on NASH remains unclear. Here, we demonstrated that OBA and NML inhibited hepatic tissue necrosis, inflammatory infiltration and liver fibrosis progression in methionine and choline-deficient (MCD) diet, carbon tetrachloride (CCl 4 )-treated and bile duct ligation (BDL) NASH and hepatic fibrosis mouse models. Mechanistic studies showed that NML and OBA enhanced anti-oxidative effects, including reduction of malondialdehyde (MDA) level, increase of catalase (CAT) activity and the gene expression of glutathione S-transferases ( GSTs ) and Nrf2-keap1 signaling. Additional, NML and OBA inhibited the expression of inflammatory gene interleukin 6 ( Il-6 ), and regulated the bile acid metabolism genes Cyp3a11 , Cyp7a1 , multidrug resistance-associated protein 3 ( Mrp3 ). Overall, these findings indicate that NML and OBA may alleviate NASH and liver fibrosis in mice via enhancing antioxidant and anti-inflammation capacity. Our study proposed that NML and OBA may be potential strategies for NASH treatment.
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
TOXICOLOGY
·
2023
·
IF 4.5
Xinyu Wu,Yeyun Ma,Xueqing Li,Nana He,Tianmeng Zhang,Feixue Liu,Huimiao Feng,Jingquan Dong
Indiscriminate use of pesticides not only leads to environmental pollution problems, but also causes poisoning of non-target organisms. Abamectin (ABM), a widely used insecticide worldwide, is of wide concern due to its persistence in the environment and its high toxicity to fish. The kidney, as a key organ for detoxification, is more susceptible to the effects of ABM. Unfortunately, few studies investigated the mechanisms behind this connection. In this study, carp was used as an indicator organism for toxicological studies to investigate renal damage caused by ABM residues in carp. In this work, carp were exposed to ABM (0, 3.005, and 12.02 μg/L) for 4 d and the nephrotoxicity was assessed. Histopathological findings revealed that ABM exposure induced kidney damage in carp, as well as an increase Creatinine and BUN levels. Meanwhile, ABM as a reactive oxygen species (ROS) stimulator, boosted ROS bursts and lowered antioxidant enzyme activity while activating the body's antioxidant system, the Nrf2-Keap1 signaling pathway. The accumulation of ROS can also lead to the imbalance of the body's oxidation system, leading to oxidative stress. At the same time, NF-κB signaling pathway associated with inflammation was activated, which regulated expression levels of inflammatory cytokines ( TNF-α , IL-6 , IL-1β , and iNOS increased, while IL-10 and TGF-β1 decreased). In addition, ABM exposure caused structural damage to kidney mitochondria of carp, resulting in decreased mitochondrial membrane potential and ATP production capacity, and mediated apoptosis through endogenous pathways Bax/Bcl-2/Caspase-9/Caspase-3. In conclusion, ABM caused kidney damage in carp by inducing oxidative stress, inflammation, and apoptosis through mitochondrial pathway. These findings will be useful for future research into molecular mechanisms of ABM-induced nephrotoxicity in aquatic organisms.
研究领域:
毒理学
·
环境科学
·
水生生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Yue Tang,Yueyue Kang,Xinru Zhang,Caiyi Cheng
Oxidative stress-induced retinal pigment epithelial (RPE) cell damage is a major factor in the pathogenesis of dry age-related macular degeneration (AMD). Although the therapeutic effect of mesenchymal stem cell (MSC) exosomes on dry AMD has been preliminarily discussed, the underlying mechanism has yet to be reported. Here, we demonstrate that MSC exosomes, acting as a nanodrug, can effectively reduce the incidence of dry AMD by regulating Nrf2/Keap1 signaling pathway. In the in vitro study, MSC exosomes relieved the damage of ARPE-19 cells, suppressed the activity of lactate dehydrogenase (LDH), decreased the level of reactive oxygen species (ROS) and upregulated the activity of superoxide dismutase (SOD). In the in vivo study, MSC exosomes were administered via intravitreal injection. MSC exosomes effectively protected RPE layer, photoreceptor outer segment/inner segment (OS/IS) layer and outer nuclear layer (ONL) from NaIO 3 -induced damage. Western blotting results showed that the ratio of Bcl-2/Bax was increased after pre-administration of MSC exosomes in both in vitro and in vivo studies. Moreover, MSC exosomes were found to upregulate the expressions of Nrf2, P-Nrf2, Keap1 and HO-1, while the antioxidant effect of MSC exosomes was blocked by ML385 (a Nrf2 inhibitor). Besides, immunofluorescence results showed that MSC exosomes upregulated the expression of P-Nrf2 in the nucleus compared to the oxidant group. These results indicate that MSC exosomes protect RPE cells from oxidative damage by regulating Nrf2/Kepa1 signaling pathway. In conclusion, MSC exosomes are promising nanotherapeutics for the treatment of dry AMD.
研究领域:
眼科学
·
干细胞生物学
·
分子生物学
·
细胞生物学
·
药理学
✓ 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）