查找使用阿拉丁产品的科研文献

Biomimetic fucoidan nanoparticles with regulation of macrophage polarization for targeted therapy of acute lung injury

Weili Yang,Hui Liu,Xiaowei Liu,Yuxin Cao,Xuemei Wang,Xinxin Wang,Wenwen Cao,Chunjing Guo,Daquan Chen

Acute lung injury (ALI) is a complex acute respiratory illness with a high mortality rate. Reactive oxygen species (ROS) play a pivotal role in ALI, inducing cellular damage, inflammation, and oxidative stress, thereby exacerbating the severity of the injury. In this study, inspired by the “subtractive” strategy, we developed a fucoidan-based macrophage membrane bio-nanosystem, abbreviated as MF@CB, designed as an anti-inflammatory and antioxidant agent to alleviate lipopolysaccharide (LPS)-induced inflammation in ALI. MF@CB coated with macrophage membrane for effective targeting and accumulation in ALI lesions. In addition, MF@CB activates Nrf2 transcriptional activity in macrophages, inhibiting ROS synthesis at its origin while effectively removing ROS already present in the ALI. This dual-pronged approach demonstrates robust antioxidant properties and restores the macrophage antioxidant defense barrier. In the LPS-induced ALI mouse model, MF@CB significantly mitigated lung inflammatory damage by modulating lung macrophage polarization and inhibiting the over-secretion of pro-inflammatory cytokines by activated immune cells. More importantly, unlike most surface modification strategies because it remove the molecule, this approach is easier to apply and potentially safer and may provide useful insights into the development of more effective therapeutic strategies for ALI.

Alleviation effect of arabinogalactan on decabromodiphenyl ether (BDE-209)-stimulated intestinal epithelial barrier damage via the Nrf2/HO-1/NQO1 signaling pathway in a Caco-2 cell monolayer model

Shaoying Gong,Jiachen Zheng,Lin Wang,Ruoyu Wu,Jianchun Han,Yongxin She

Decabromodiphenyl ether (BDE-209), a widely used polybrominated diphenyl ether, is a persistent environmental pollutant with intestinal toxicity. Arabinogalactan possesses antioxidant and anti-inflammatory properties, but its ability to counteract BDE-209-induced intestinal epithelial barrier (IEB) damage remains unclear. This study examined the protective effects of arabinogalactan on BDE-209-induced IEB damage and the underlying mechanisms. Arabinogalactan significantly restored barrier integrity, as evidenced by increased transepithelial electrical resistance and reduced FITC-dextran permeability. Mechanistically, it attenuated oxidative stress by regulating the levels of reactive oxygen species, glutathione, and malonaldehyde and the activity of superoxide dismutase and reducing the secretion of inflammatory cytokines (IL-1β, IL-6, and TNF-α). Arabinogalactan also preserved tight junction protein expression (claudin-1, zonula occludens [ZO]-1, occludin), lowered intracellular Ca²⁺, and activated the Nrf2/HO-1/NQO1 pathway. Taken together, these findings suggest that arabinogalactan inhibits oxidative stress and inflammation by regulating the Nrf2/NQO1/HO-1 signaling pathway to upregulate TJ expression, thereby alleviating BDE-209-induced IEB damage.

Atraric acid alleviates high-fat diet-induced renal injury, lipid accumulation, and fibrosis in mice by regulating oxidative stress and inflammation through AMPK-dependent Nrf2 and NF-κB signaling pathways

Yannan Xiang,Tianyue Guan,Jun Wang,Shasha Zhang,Yusa Li,Jing Xia,Panpan Zhao,Lei Wang

This study explores the protective effects of Atraric Acid (AA) against chronic kidney disease (CKD) induced by a high-fat diet (HFD) and its underlying mechanisms. In vivo HFD-induced CKD mouse models and in vitro OA/PA-stimulated HK2 cells were treated with AA. AA improved kidney morphology, reduced fibrosis, lipid accumulation, and body weight. It also decreased serum TC, TG, HDL-C, Scr, BUN, and Cys-C levels, indicating improved renal function. AA alleviated oxidative stress, ROS accumulation, and inflammation, as confirmed by DHE staining, oxidative stress markers, and pro-inflammatory cytokine levels. Western blotting showed that AA activated Nrf2 and suppressed NF-κB signaling. AMPK inhibition experiments demonstrated that AA regulated Nrf2 and NF-κB via AMPKα phosphorylation. In conclusion, AA mitigates HFD-induced CKD by targeting AMPKα to regulate oxidative stress and inflammation.

The ameliorating effects of Guizhi Fuling Wan combined with rosiglitazone in a rat ovarian model of polycystic ovary syndrome by the PI3K/AKT/NF-κB and Nrf2/HO-1 pathways

Yongju Ye,Weimei Zhou,Yuefang Ren,Jiali Lu,Aixue Chen,Ruiying Jin,Feilan Xuan

Fresh Dendrobium Officinale Polysaccharides Combine with Penicillamine to Attenuate Copper Overload-Induced Liver Injury in a Rat Model of Wilson’s Disease Via Activation of the Nrf2/HO-1/Keap1 Signaling Pathway

Zhang Shenao,Liu Pangwei,Jiang Yuge,Wu Huan,Cao Shijian,Xuan Shujuan,Wu Hongfei,Zhou An

Wilson’s disease (WD) is characterized by pathological copper accumulation, which drives hepatocellular oxidative stress and subsequent liver injury. While the first-line chelator penicillamine (PCA) effectively eliminates copper, it is associated with significant side effects. Dendrobium officinale polysaccharides, the active components in Dendrobium officinale , exhibit significant antioxidant and hepatoprotective effects. However, their potential in ameliorating liver injury in WD and as an adjunctive therapy to PCA remains unclear. This study investigated the hepatoprotective effects and underlying mechanisms of fresh Dendrobium officinale polysaccharides (FDOP), both alone and combined with PCA, in a copper-overloaded rat model. The results showed that FDOP significantly mitigated hepatic histopathological damage and reduced serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (AKP). It also alleviated oxidative stress by decreasing hepatic malondialdehyde (MDA) and oxidized glutathione (GSSG) levels while enhancing superoxide dismutase (SOD) activity. Furthermore, FDOP promoted copper excretion and reduced copper deposition in the liver, brain, and kidneys. Mechanistically, FDOP activated the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/Kelch-like ECH-associated protein 1 (Keap1) signaling pathway, evidenced by upregulated nuclear Nrf2 and HO-1 expression and downregulated Keap1 expression, thereby enhancing the cellular antioxidant defense system. Importantly, the combination of FDOP and PCA outperformed either monotherapy in alleviating liver injury, promoting copper excretion, and activating antioxidant pathways. In conclusion, FDOP not only exhibits excellent hepatoprotective effects but also holds potential as an adjunct to PCA therapy, offering a novel combined treatment strategy for WD.

Lycii Fructus, a medicine food homology material, attenuates retinal damage in sodium iodate-induced retinal degeneration mice and inhibits oxidation-induced apoptosis of Müller cells via regulating Nrf2-HO1 signaling pathway

Cheng Cao,Yunqing Lu,Bing Li,Yang Chen,Pan Xu,Mengqiu Liu,Ziqiang Zhu,Lei Yuan,Sheng Guo,Hongjie Kang,Jin-ao Duan,Yue Zhu

Lycii Fructus (LF) is a medicinal-edible homology material frequently used for treating age-related macular degeneration (AMD) in Chinese medicine. Abundant of literatures verified the retina protection effect of LF on AMD-like animal models. However, previous studies on LF attenuating retinal damage mainly focused on its protection effect on pigment epithelial cells and optic ganglion cells while few reports on Müller cells. In the current study, we found that LF extracts attenuated oxidation damages and inhibited cell apoptosis of retina on a mouse retinal injury model induced by sodium iodate. LF extracts also increased expressions of Müller cell biomarker glutamine synthetase of eyeballs of model mice, which indicated that LF extract protected Müller cell from oxidation injury induced by sodium iodate. In Müller cell MIO-M1 cultures, LF also significantly inhibited cellular apoptosis induced by NaIO 3 by regulating Nrf2/HO-1 signaling pathway and the aqueous extracts exerted better active tendency than ethanol extracts. These data implied that the antioxidant effect of LF on protecting Müller cell might contribute to its retina repair function, thereby providing more scientific evidences for the development of LF as an alternative therapy or preventive measures for AMD.

Purified Tetrastigma hemsleyanum vines polysaccharide attenuates EC-induced toxicity in Caco-2 cells and Caenorhabditis elegans via DAF-16/FOXO pathway

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 .

The iron overload caused by non-enzymatically glycated transferrin triggers oxidative stress and ferroptosis by regulating the PI3/AKT signalling pathway and the expression of Nrf2 to promote renal damage in diabetes

Pingping Zhao,Binjing Pan,Xiaoyu Lv,Lihua Ma,Jingfang Liu

Non-enzymatic glycation is an important post-translational modification of proteins, ultimately forming advanced glycation end products (AGEs). In a high-glucose environment, the glycation degree of transferrin (Tf) increases, leading to elevated levels of AGE-modified transferrin (AGE-Tf), which reduces the binding capacity of Tf for iron. However, the role of AGE-Tf-associated iron dysregulation in diabetic nephropathy remains unclear. In this study, human podocytes were treated in vitro with AGE-Tf prepared by incubating Tf with 5.6 or 33.3 mM glucose (hereafter termed 5.6-Glc-AGE-Tf and 33.3-Glc-AGE-Tf, respectively) in combination with iron. Additionally, plasmids encoding Tf with mutations at three glycation sites (K206 A/K296 A/K534A; MT-Tf) or wild-type Tf (WT-Tf) were packaged into adeno-associated viral vectors and administered to diabetic rats. Compared with podocytes treated with 5.6-Glc-AGE-Tf, podocytes treated with 33.3-Glc-AGE-Tf exhibited reduced viability and greater oxidative stress. After ferric-citrate addition, intracellular Fe 2+ was also higher in the 33.3-Glc-AGE-Tf group than in the 5.6-Glc-AGE-Tf group. The 33.3-Glc-AGE-Tf group showed decreased GPX4, Nrf-2, and SLC7A11 expression and increased ACSL4 expression. In vivo, diabetic rats receiving an empty vector (DM-empty-vector) or a wild-type Tf vector (DM-WT-Tf-vector) exhibited higher renal AGE-Tf, Fe 2+ , and oxidative stress levels; lower nephrin and podocin expression; ferroptosis-related alterations; mesangial cell proliferation and matrix expansion; increased interstitial collagen deposition; and focal nodular sclerosis. These alterations were attenuated in diabetic rats receiving the glycation-resistant mutant Tf vector (DM-MT-Tf-vector). Deferoxamine (DFO) or TBHQ (an Nrf-2 activator) ameliorated oxidative stress, iron dysregulation, and ferroptosis in AGE-Tf-treated podocytes and in the kidneys of diabetic rats receiving the WT-Tf vector, whereas LY294002 (a PI3K/AKT pathway inhibitor) primarily alleviated oxidative stress. These findings identify AGE-Tf-associated iron dysregulation as a potential therapeutic target in diabetic kidney disease.

Involvement of the inhibition of mitochondrial apoptotic, p53, NF-κB pathways and the activation of Nrf2/HO-1 pathway in the protective effects of curcumin against copper sulfate-induced nephrotoxicity in mice

Chongshan Dai,Meng Li,Yue Liu,Diem Hong Tran,Haiyang Jiang,Shusheng Tang,Jianzhong Shen

Chronic copper exposure could cause potential nephrotoxicity and effective therapy strategies are limited. This study investigated the protective effects of curcumin on copper sulfate (CuSO 4 )-induced renal damage in a mouse model and the underlying molecular mechanisms. Mice were administrated orally with CuSO 4 (100 mg/kg per day) in combination with or without curcumin (50, 100 or 200 mg/kg per day, orally) for 28 days. Results showed that curcumin supplementation significantly reduce the Cu accumulation in the kidney tissues of mice and improved CuSO 4 -induced renal dysfunction. Furthermore, curcumin supplantation also significantly ameliorated Cu exposure-induced oxidative stress and tubular necrosis in the kidneys of mice. Moreover, compared to the CuSO 4 alone group, curcumin supplementation at 200 mg/kg per day significantly decreased CuSO 4 -induced the expression of p53, Bax, IL-1β, IL-6, and TNF-α proteins, levels of NF-κB mRNA, levels of caspases-9 and − 3 activities, and cell apoptosis, and significantly increased the levels of Nrf2 and HO-1 mRNAs in the kidney tissues. In conclusion, for the first time, our results reveal that curcumin could trigger the inhibition of oxidative stress, mitochondrial apoptotic, p53, and NF-κB pathways and the activation of Nrf2/HO-1 pathway to ameliorate Cu overload-induced nephrotoxicity in a mouse model. Our study highlights that curcumin supplementation may be a promising treatment strategy for treating copper overload-caused nephrotoxicity.

Involvement of the activation of Nrf2/HO-1, p38 MAPK signaling pathways and endoplasmic reticulum stress in furazolidone induced cytotoxicity and S phase arrest in human hepatocyte L02 cells: modulation of curcumin

Chongshan Dai,Lei Lei,Bin Li,Yang Lin,Xilong Xiao,Shusheng Tang

Furazolidone (FZD) is extensively used as the antiprotozoal and antibacterial drug in clinic. The previous study has shown that curcumin pretreatment could improve FZD induced cytotoxicity by inhibiting oxidative stress and mitochondrial apoptotic pathway. The current study aimed to investigate the potential roles of endoplasmic reticulum (ER) stress, p38 mitogen-activated protein kinases (p38 MAPK) signaling pathway in curcumin against FZD cytotoxicity by using human hepatocyte L02 cells. The results showed that curcumin could markedly attenuate FZD induced cytotoxicity. Compared with FZD alone group, curcumin pretreatment significantly reduced the expression of phospho (p)-p38, cyclin D1, p-checkpoint kinase 1 (ChK1) and breast cancer associated gene 1 (BRCA1) protein, followed to attenuate S phase arrest. Meanwhile, curcumin pretreatment prevented FZD induced ER stress, evidenced by the inhibition of glucose-regulated protein 78 and DNA damage inducible gene 153/C/EBP-homologous protein (GADD153/CHOP) protein expression. Moreover, compared with the control, FZD exposure activated the protein and mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1), which were further activated by curcumin treatment. These results reveal that curcumin could prevent FZD induced cytotoxicity and S phase arrest, which may involve the activation of Nrf2/HO-1 pathway and the inhibition of p38 MAPK pathway and ER stress.

Oligoasthenozoospermia is alleviated in a mouse model by [Gly14]-humanin-mediated attenuation of oxidative stress and ferroptosis

Yumeng Liu,Qiwen Feng,Liping Zou,Changhong Zhu,Wei Xia

Background Oligoasthenozoospermia is a common cause of male infertility, for which effective treatments are urgently needed. Humanin (HN) is a peptide associated with this condition. Objectives To investigate the ameliorative effect of [Gly14]-Humanin (HNG) on oligoasthenozoospermia and the mechanisms. Materials and methods Mice were treated with cyclophosphamide (CP) to construct a mice model of oligoasthenozoospermia. The resulting model mice were treated with saline or HNG. Subsequently, the testis weights, organ indices, testicular structure, sperm counts and motilities, litter sizes, and serum testosterone concentrations of the mice were determined. Differential gene expression in testicular tissues was determined by RNA sequencing. TM3, TM4, GC1, and GC2 cells were exposed to erastin to induce ferroptosis, followed by treatment with HNG or HNG + ML385 (a nuclear factor erythroid 2-related factor 2 inhibitor). Levels of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and ferrous ions (Fe 2+ ) were determined and their expression of ferroptosis-related proteins was determined by immunofluorescence and western blot. Results The HNG treatment improved testis and sperm parameters and increased litter size and serum testosterone concentrations in model mice. Kyoto Encyclopaedia of Genes and Genomes pathway enrichment analysis revealed significant differential expression of ferroptosis-related genes. The expression of ferroptosis-related proteins increased in testicular tissues after the HNG treatment. The concentrations of ROS, MDA, and Fe 2+ decreased and the concentrations of GSH increased in testicular tissues and in TM3 and TM4 cells after HNG treatment. In vitro experiments confirmed that HNG activated the nuclear factor erythroid 2-related factor 2/glutathione peroxidase 4 (Nrf2/GPX4) pathway. However, these effects of HNG were blocked by ML385 treatment. Discussion and conclusion HNG demonstrated a therapeutic effect on oligoasthenozoospermia in a mouse model by reducing oxidative stress and ferroptosis. In TM3 and TM4 cells, HNG attenuated cellular oxidative stress and inhibited ferroptosis via the Nrf2/GPX4 pathway.

Free and Bound Phenolics of Laird Lentil (Lens culinaris) Hulls and the Anti-inflammatory Activity of their Digestive Products via Crosstalk between NF-κB and Keap1-Nrf2 Signaling Pathways in HT-29 Cells

Fanghua Guo,Li Peng,Hua Xiong,Jiaqi Wang,Rong Tsao,Xin Peng,Li Jiang,Yong Sun

Polyphenol-rich Laird lentil hulls are a byproduct of lentil processing. In the present study, free and bound polyphenols in lentil hulls were analyzed with UHPLC-LTQ-OrbiTrap-MS2, and the anti-inflammatory mechanism of their digestive products was explored based on the NF-κB and Keap1-Nrf2 signaling pathways in the HT-29 cell model. In summary, a total of 27 polyphenols and 5 nonphenolic constituents were identified in free and bound fractions, and among them, catechin glucoside, kaempferol tetraglucoside, procyanidin dimer, and dihydroxybenzoic acid-O-dipentoside were the main polyphenols in the digestive products. These digestive products could reduce inflammatory mediators and exert anti-inflammatory activity by inhibiting NF-κB and activating Keap1-Nrf2 signaling pathways, and there was crosstalk between them, which was a mutual inhibition effect. The results show that polyphenols in lentil hulls are a good source of anti-inflammatory ingredients and have a promising development potential.