INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2021
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IF 6.953
Chao Xin,Shuang Liu,Hang Qu,Zhenyu Wang
Chemical liver injury threatens seriously human health, along with the shortage of efficiency and low-toxicity drugs. Herein, the novel oral nanocomplexes composed of deoxycholic acid-grafted chitosan and oleanolic acid were constructed to reverse the CCl 4 -induced acute liver damage in mice. Results indicated core-shell nanocomplexes, maintained by the hydrophobic interaction between deoxycholic acid and oleanolic acid, could be dissociated in the intestine. Notably, the nanocomplexes possessed superior hepatoprotective effect in vivo , possibly due to the synergistic effect between grafted chitosan and oleanolic acid. Mechanism investigations suggested that nanocomplexes reversed CCl 4 -induced liver injury through improving hepatic antioxidant capacity via NrF2/Keap1 pathway and regulating inflammation response via NF-κB signaling pathway. The novel oral nanocomplexes represent an effective strategy for chemical liver injury therapy.
研究领域:
药学
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毒理学
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药理学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
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IF 8.2
Jiang-Hong Luo,Wan-Shuang Zou,Jing Li,Wei Liu,Jing Huang,Hu-Wei Wu,Jian-Lin Shen,Fei Li,Jia-Shuang-Wei Yuan,An-Kang Tao,Liang Gong,Jun Zhang,Xiao-Yin Wang
This study aimed at investigating the gastroprotective effect of Evodiae fructus polysaccharide (EFP) against ethanol-induced gastric ulcer in mice. Biochemical indexes along with untargeted serum and liver metabolomics were determined. Results showed that pre-treatment of EFP alleviated ethanol-induced gastric ulcer in mice. EFP lessened oxidative stress and inflammation levels of stomachs, showing as increments of SOD and GSH-Px activities, GSH content and IL-10 level, and reductions of MDA and IL-6 levels. Meanwhile, EFP activated the Keap1/Nrf2/HO-1 signaling pathway through increasing Nrf2 and HO-1 protein expressions, and decreasing Keap1 protein expression. Serum and liver metabolomics analyses indicated that 10 metabolic potential biomarkers were identified among normal control, ulcer control and 200 mg/kg·bw of EFP groups, which were related to 5 enriched metabolic pathways including vitamin B6 metabolism, nicotinate and nicotinamide metabolism, pentose phosphate pathway, bile secretion and ascorbate and aldarate metabolism. Further pearson's correlation analysis indicated that there were some positive and negative correlations between the biomarkers and the biochemical indexes. It could be concluded that the gastroprotection of EFP might be related to anti-oxidative stress, anti-inflammation, activation of Keap1/Nrf2/HO-1 signaling pathway and alteration of metabolic pathways. This study supports the potential application of EFP in preventing ethanol-induced gastric ulcer.
研究领域:
药理学
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胃肠病学
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代谢组学
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生物化学
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产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
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2025
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IF 8
Xuanying Xin,Sungkwon Park,Wen Zhang,Jia Yu,Sun Jin Hur,Xiangzi Li,Seong-Ho Choi
Conventional identification methods for antioxidant peptides from bovine hide collagen suffer from poor specificity and high costs. This study employed an integrated approach combining peptidomics, molecular simulation, and quantum chemical calculations to identify ten highly active antioxidant peptides from 6006 candidates. Molecular docking revealed that the peptides bound strongly to the Keap1 protein (binding energies: −7.19 to −12.26 kcal/mol) Quantum chemical calculations demonstrated superior electron-donating capacity, while Fukui function analysis identified key active sites. Cellular assays showed all ten synthetic peptides (1 mg/mL) significantly reduced H₂O₂-induced ROS levels in RAW264.7 cells, enhanced SOD/GSH-Px activities, inhibited MDA accumulation, and upregulated the expression of genes in the Nrf2 signaling pathway, which was further confirmed by Western Blot analysis of key proteins in the Keap1-Nrf2 axis. Computational parameters strongly correlated with cellular antioxidant efficacy, with SGPOGPOGP showing optimal protective effects. This tripartite validation strategy provides an innovative paradigm for efficient discovery of bovine hide-derived antioxidant peptides.
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
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2024
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IF 4.8
Meimei Shan,Xingrui Xu,Chuanqi Chu,He Wang,Chengting Zhang,Shengbao Cai
Fatigue is an intricate physiological phenomenon, causing serious secondary concerns and bioregulation disorders. The objective of this research was to look into the anti-fatigue effect and potential mechanisms of natural ingredients in methanol extract of edible oil from Rhus chinensis Mill. fruits (PMRO). Results showed that a total of 18 fatty acids and 9 anacardic acids were identified by GC-MS and UHPLC-ESI-HCES/MS in PMRO. PMRO significantly increased the weight-bearing swimming time. Further investigations showed that PMRO significantly improved physiological indexes related to fatigue and regulated the oxidative stress (Keap1/Nrf2) and energy metabolism (AMPK/PGC-1α)-related proteins expression to exert anti-fatigue effects. The 16S rRNA sequence analysis indicated that a potential role of PMRO in modulating the abundance of gut bacteria and influencing the short-chain fatty acids content, thereby exerting an anti-fatigue effect. Therefore, the natural ingredients in PMRO may hold promise as a dietary supplement capable of delaying body fatigue.
研究领域:
营养学
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药理学
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微生物学
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生物化学
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产品关联
DOI
高影响因子
Materials Today Bio
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2024
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IF 8.7
Changxing Liu,Yawei Sun,Dengju Li,Fan Wang,Haojue Wang,Senbo An,Shui Sun
Osteoarthritis (OA) is characterized by progressive and irreversible damage to the articular cartilage and a consecutive inflammatory response. However, the majority of clinical drugs for OA treatment only alleviate symptoms without addressing the fundamental pathology. To mitigate this issue, we developed an inflammation-responsive carrier and encapsulated bioactive material, namely, LDH@TAGel. The LDH@TAGel was designed with anti-inflammatory and antioxidative abilities, aiming to directly address the pathology of cartilage damage. In particular, LDH was confirmed to restore the ECM secretion function of damaged chondrocytes and attenuate the expression of catabolic matrix metalloproteinases (Mmps). While TAGel showed antioxidant properties by scavenging ROS directly. In vitro evaluation revealed that the LDH@TAGel could protect chondrocytes from inflammation-induced oxidative stress and apoptosis via the Nrf2/Keap1 system and Pi3k-Akt pathway. In vivo experiments demonstrated that the LDH@TAGel could alleviated the degeneration and degradation of cartilage induced by anterior cruciate ligament transection (ACLT). The OARSI scores indicating OA severity decreased significantly after three weeks of intervention. Moreover, the IVIS image revealed that LDH@TAGel enhances the controlled release of LDH in a manner that can be customized according to the severity of OA, allowing adaptive, precise treatment. In summary, this novel design effectively alleviates the underlying pathological causes of OA-related cartilage damage and has emerged as a promising biomaterial for adaptive, cause-targeted OA therapies.
研究领域:
生物材料
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组织工程
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骨科
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药学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
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2024
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IF 18
Yulu Yang,Xianhui Zhang,Yao Yang,Pengfei Gao,Wuzhe Fan,Tao Zheng,Weihu Yang,Yu Tang,Kaiyong Cai
Postmenopausal osteoporosis (PMOP) is a prevalent condition among elderly women. After menopause, women exhibit decreased iron excretion, which is prone to osteoporosis. To design a specific titanium implant for PMOP, we first analyze miRNAs and DNA characteristics of postmenopausal patients with and without osteoporosis. The results indicate that iron overload disrupts iron homeostasis in the pathogenesis of PMOP. Further experiments confirm that iron overload can cause lipid peroxidation and ferroptosis of MSCs, thus breaking bone homeostasis. Based on the findings above, we have designed a novel Ti implant coated with nanospheres of caffeic acid (CA) and deferoxamine (DFO). CA can bind on the Ti surface through the two adjacent phenolic hydroxyls and polymerize into polycaffeic acid (PCA) dimer, as well as the PCA nanospheres with the repetitive 1,4-benzodioxan units. DFO was grafted with PCA through borate ester bonds. The experimental results showed that modified Ti can inhibit the ferroptosis of MSCs in the pathological environment of PMOP and promote osseointegration in two main ways. Firstly, DFO was released under high oxidative stress, chelating with excess iron and decreasing the labile iron pool in MSCs. Meanwhile, CA and DFO activated the KEAP1/NRF2/HMOX1 pathway in MSCs and reduced the level of intracellular lipid peroxidation. So, the ferroptosis of MSCs is inhibited by promoting the SLC7A11/GSH/GPX4 pathway. Furthermore, the remained CA coating on the Ti surface could reduce the extracellular oxidative stress and glutathione level. This study offers a novel inspiration for the specific design of Ti implants in the treatment of PMOP.
研究领域:
生物材料
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骨科
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材料科学
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细胞生物学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2019
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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
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细胞生物学
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生物化学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2024
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IF 5.3
Gang Wang,Xiao-Na Xu,Zhu Zhi-Min,Kun Wang,Fei Li
This study tried to develop the α-Hederin/Oxaliplatin (OXA) dual-loaded rHDL (α-Hederin-OXA-rHDL) modified liposomes to improve the therapeutic index on colon adenocarcinoma (COAD). The α-Hederin-OXA-rHDL were prepared and evaluated for characterizations, accumulate to tumor tissues, and antitumor activity. A thorough investigation into oxaliplatin resistant and KRAS-mutant related hub keg genes were identified and performed to assess the prognosis role of the genetic signature in COAD. The potential immune signatures and molecular docking for verifing the predicted targets of α-Hederin-OXA-rHDL in tumor-bearing mice. Results suggested that α-Hederin-OXA-rHDL could enhance the sensitivity of oxaliplatin in HCT116/L-OHP cells via the regulation of KEAP1/NRF2 -mediated signaling and HO1 or GPX4 proteins. Furthermore, α-Hederin-OXA-rHDL regulated the predicted targets of PRDM1 interaction with miR-140-5p, efficient activing CD8 T cell to improve therapeutic response in vivo . Collectively, this work provides drug delivery with rHDL dual-loaded α-Hederin and oxaliplatin synergistically targets cancer cells and effectory T cells combating COAD.
研究领域:
药学
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癌症生物学
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
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2024
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IF 4.8
Jia-Yi Weng,Jia-Yu Yang,Ishimwe Steven Papy,Bu-Tao Yu,Yu-Feng Ke,Bing-Yu Bai,Mitchell N. Muskat,Qian Wu,Xiang-Rong Cheng
Cinnamaldehyde (CA) is the key component of the essential oil derived from cinnamon bark and recommended as a health factor in foods for the prevention and intervention of metabolic disorders. This research aims to reveal the association between the difference in the electrophilic abilities of functional groups in CA and 3-phenylpropionaldehyde (PA), and their regulation of lipid peroxidation as well as energy metabolism in free fatty acids (FFAs) overloaded HepG2 cells. CA treatment reduced lipid accumulation and synthesis-related factors, increased levels of factors associated with fatty acid β-oxidation, decreased reactive oxygen species (ROS) content, and restored mitochondrial function and was superior to PA. Moreover, CA treatment increased nuclear Nrf2 protein levels and regulated the nuclear/cytoplasmic Nrf2 ratio, which suggested that CA effectively upregulated the Nrf2 signaling pathway. Furthermore, molecular docking showed that CA possessed an electrophilic index of 2.45 covalently bound to Nrf2-associated Keap1 protein with an affinity of −3.6 kcal/mol, which was much stronger than PA, and HPLC-MS/MS analysis further confirmed that CA covalently modified Cys151 on Keap1 protein. In conclusion, CA has the capacity to attenuate hepatic steatosis and cellular oxidative response via Nrf2 signaling pathway, which is closely related to its strong electrophilic ability.
研究领域:
药理学
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细胞生物学
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代谢紊乱
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产品关联
DOI
高影响因子
ACS Applied Nano Materials
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2023
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IF 5.9
Qiang Feng,Hongting Xu,Xiaoyu Pan,Siqi Geng,Huifeng Qian,Chujie Wang,Ying Li,Jiaying Qin,Yiting Wu,Bangyi Zhou,Xiaoyu Liu,Zhiqiu Ye,Yingchun Xu,Zhangsen Yu
Acetaminophen (APAP), a common antipyretic and analgesic drug, is considered the most common cause of drug-induced liver injury (DILI). The mechanism of liver injury induced by APAP is mainly related to oxidative stress and inflammatory reaction. Herein, we report a simple and efficient one-step synthesis of Prussian blue (PB) nanozymes with multiple antioxidant enzymatic activities that effectively treat APAP-induced DILI. At the cellular level, reaching 10 μg/mL PB nanozymes can effectively scavenge intracellular reactive oxygen species (ROS), reduce mitochondrial membrane potential drop, and inhibit hepatocyte apoptosis. According to in vivo experimental studies, the levels of serum biochemical indicators and histopathological examination of DILI mice livers showed that 12.5 mg/kg PB nanozymes could effectively inhibit liver necrosis and 25 mg/kg PB nanozymes achieved the same therapeutic effect as 300 mg/kg NAC. More importantly, compared with NAC, PB nanozymes can still attenuate APAP-induced acute liver injury in mice after APAP-induced acute liver injury in mice for 3 h. Therefore, PB nanozymes can effectively prolong the therapeutic time window, revealing the potential of PB nanozymes in clinical applications for advanced DILI treatment. Furthermore, the therapeutic mechanism studies have shown that PB nanozymes with abundant and variable valence states could not only directly scavenge ROS but also through the Keap1-Nrf2/HO-1 pathway to reduce oxidative stress. Moreover, the decreased expression levels of myeloperoxidase and F4/80 in the liver, which are markers of neutrophil and macrophage infiltration, indicated that the Prussian blue nanozymes modulates inflammation to protect against APAP-induced acute liver injury. Consequently, our findings suggested that PB nanozymes have excellent clinical application prospects for acetaminophen-induced acute liver injury.
研究领域:
药理学
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纳米医学
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肝病学
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生物化学
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毒理学
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产品关联
DOI
高影响因子
Food Bioscience
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2021
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IF 4.24
Qiang Chu,Ruoyi Jia,Chaowei Chen,Yaxuan Wang,Xin Yu,Yiru Zhang,Tao Wu,Xiaodong Zheng
Apios americana Medik leaves are rich in polyphenols and prevent glucose-induced damage in organisms. Polyphenols are a group of natural antioxidants. Therefore, a H 2 O 2 induced oxidative stress model of HepG2 cells was used to explore the protective effects of the Apios americana Medik leaves water extract (ALWE) against oxidative stress. Nine compounds were identified in ALWE using HPLC-TOF-MS including C 18 H 24 O 13 , which had not previously been reported. Fluorescence staining assays showed that the ALWE significantly decreased apoptosis, intracellular ROS generation, mitochondrial membrane potential (MMP) dissipation and mitochondrial membrane lipid peroxidation after ALWE pretreatment. Data from western blots showed that Keap1-Nrf2 and Sirt1-FoxO1 signaling pathways were involved in preventing H 2 O 2 induced oxidative stress. Transmission electron microscope and Western blot analyses indicated that autophagy contributed to the regulation of the oxidative balance. These results together indicated that ALWE is a potential antioxidant and autophagy activator, and it protects HepG2 cells against H 2 O 2 damage through activation of autophagy.
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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DOI
高影响因子
INTERNATIONAL JOURNAL OF FOOD SCIENCE AND TECHNOLOGY
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2024
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IF 2.6
Wangxiang Huang,Chen Wang,Qianzi Chen,Feng Chen,Haohan Hu,Jianfei Li,Jingling Kang,Qiyi He,Xiaodong Yu
Summary This study aims to identify novel antioxidant peptides within black soldier fly larvae protein (BSFLP) using simulated gastrointestinal processes, LC–MS/MS analysis, and virtual screening. Two peptides, PFCPK and ADFW, exhibited significant antioxidant properties in both in vitro radical scavenging experiments and in vivo evaluations using zebrafish embryos induced with 2,2′-azobis(2-methylpropionamidine) dihydrochloride. Treatment with 25 μg mL −1 of PFCPK or ADFW significantly ( P < 0.05) enhanced zebrafish embryo survival, reduced abnormal heartbeats and lowered ROS generation rate by 62.98% and 83.44%, lipid peroxidation by 52.54% and 68.35%, and cell death rate by 86.92% and 97.54%, respectively. Moreover, they restored antioxidant enzyme activities and MDA levels to near-normal values, demonstrating significant therapeutic effects. The observed antioxidant effects may potentially be linked to the modulation of the Keap1/Nrf2 pathway. This study provides valuable insights for developing novel natural antioxidants and maximising the high-value applications of BSFLP.
研究领域:
食品科学
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生物化学
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分子生物学
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药理学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）