INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Hend Mohamed Anwar,Gad Elsayed Mohamed Salem,Hanan M. Abd El-Latief,Amany Abd Elhameid Osman,Sahar K. Ghanem,Haroon Khan,Suchana Chavanich,Alshaymaa Darwish
The COVID-19 pandemic has drawn attention to acute lung injury and respiratory distress syndrome as major causes of death, underscoring the urgent need for effective treatments. Protease enzymes possess a wide range of beneficial effects, including antioxidant, anti-inflammatory, antifibrotic, and fibrinolytic effects. This study aimed to evaluate the potential therapeutic effects of bacterial protease and chymotrypsin in rats in mitigating acute lung injury induced by lipopolysaccharide . Molecular docking was employed to investigate the inhibitory effect of bacterial protease and chymotrypsin on TLR-4, the receptor for lipopolysaccharide. Bacterial protease restored TLR-4, Nrf2 , p38 MAPK , NF-kB, and IKK-β levels to normal levels, while chymotrypsin normalized TLR-4, IKK-β, IL-6, and IL-17 levels. The expression of TGF-β, caspase-3, and VEGF in the bacterial protease- and chymotrypsin-treated groups was markedly reduced. Our results suggest that both therapies ameliorate LPS-induced acute lung injury and modulate the TLR4/Nrf2/NF-k signaling pathway. Each protease exhibited distinct mechanisms, with bacterial protease showing a better response to oxidative stress, edema, and fibrosis , whereas chymotrypsin provided a better response in the acute phase and innate immunity. These findings highlight the potential of each protease as a promising therapeutic option for acute lung injury and respiratory distress syndrome.
研究领域:
医学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
POULTRY SCIENCE
·
2025
·Vol. 104
·期 4
·104918
·
IF 4.2
Linghuan Luo,Ming Ge,Yiming Sun,Yihan Hu,Xiaoyi Yang,Ruili Zhang
2-Ethylhexyl diphenyl phosphate ( EHDPHP ) is a pervasive environmental pollutant known to induce oxidative damage in organisms; however, its precise mechanisms of toxicity remain unclear. Furthermore, limited research has been conducted on potential therapeutic agents to counteract EHDPHP toxicity. Glycyrrhizic acid ( GA ), a triterpenoid saponin compound with recognized antioxidant, anti-inflammatory, and immunomodulatory properties, represents a promising candidate for mitigating EHDPHP-induced oxidative injury. In chickens, the thymus is the main immune organ. This study aims to investigate the mechanism of EHDPHP-induced thymus damage and the role and mechanism of GA intervention in this process. A potential ‘EHDPHP/GA-Target-Oxidative Stress ( OS )’ network was constructed using network biology. A model of EHDPHP-induced chicken thymic injury was established by continuous oral administration of EHDPHP (160 mg/kg) for 42 days. Moreover, the mechanism of action by which GA antagonizes EHDPHP-induced oxidative damage was explored using MDCC-MSB1 cells in vitro. Network biology analyses showed that ‘EHDPHP/GA-OS’ targets were mainly enriched in the adipocytokine and apoptotic signaling pathways. Molecular docking demonstrated the binding interactions of GA and EHDPHP with Kelch-like ECH-associated protein 1 ( Keap1 ), nuclear factor erythroid 2-related factor 2 ( Nrf2 ), and signal transducer and activator of transcription 3 ( STAT3 ) proteins. Both in vitro and in vivo experiments revealed that GA attenuated EHDPHP-induced damage to thymus and MDCC-MSB1 cells, as evidenced by reductions in oxidative stress markers (ROS, MDA, T-AOC, SOD, and GSH-Px), inflammation factors (NF-κB, IL-6, and TNF-α), and the apoptotic factor (Caspase 3) expression. GA treatment increased the expression of Nrf2 and HO-1 while reducing the expression of Keap1, JAK1, Phospho-JAK1 ( P-JAK1 ), STAT3, and Phospho-STAT3 ( P-STAT3 ). Furthermore, the protective effect of GA against EHDPHP-induced MDCC-MSB1 cell injury, as well as its inhibition of the JAK1/STAT3 pathway, was diminished by the Nrf2 inhibitor ML385. These findings suggest that GA exerts its protective effects through Nrf2 and mitigates EHDPHP-induced thymic injury in chickens by modulating the crosstalk between the Nrf2/ROS/STAT3 signaling pathways. Overall, this study highlights the novel role of GA in treating EHDPHP-induced injury and underscores its potential application in diseases treatable with Nrf2 activators.
研究领域:
环境毒理学
·
免疫学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOLIA HISTOCHEMICA ET CYTOBIOLOGICA
·
2023
·Vol. 61
·期 2
·109-122
·
IF 1.5
Jiahui Han Di Jia Hao Yao Ting Lv Xi Xu Xin Ge
Introduction. Hemorrhagic shock (HS) is an important cause of high mortality in traumatized patients. Cryptotanshinone (CTS) is a bioactive compound extracted from Salvia miltiorrhiza Bunge (Danshen). The current study aimed to explore the effect and underlying mechanism of CTS on the liver injury induced by HS. Material and methods. Male Sprague-Dawley rats were used to establish the HS model by hemorrhaging and monitoring mean arterial pressure (MAP). CTS was intravenously administered at concentration of 3.5 mg/kg, 7 mg/kg, or 14 mg/kg 30 minutes before resuscitation. Twenty-four hours after resuscitation, the liver tissue and serum samples were collected for the following examinations. Hematoxylin and eosin (H&E) staining was used to evaluate hepatic morphology changes. The myeloperoxidase (MPO) activity in liver tissue and the serum activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were examined to reveal the extent of liver injury. The protein expression of Bax and Bcl-2 in liver tissue was detected by western blot. The TUNEL assay determined the apoptosis of hepatocytes. Oxidative stress of liver tissue was assessed by the examination of reactive oxygen species (ROS) generation. The content of malondialdehyde (MDA), glutathione (GSH), and adenosine triphosphate (ATP), the activity of superoxide dismutase (SOD) and oxidative chain complexes (complex I, II, III, IV), as well as cytochrome c expression in cytoplasm and mitochondria, were also used to determine the extent of oxidative injury in the liver. Immunofluorescence (IF) was employed to estimate nuclear factor E2-related factor 2 (Nrf2) expression. The mRNA and protein levels of heme oxygenase 1 (HO-1), NAD(P)H: quinone oxidoreductases 1 (NQO1), cyclooxygenase-2 (COX-2), and nitric oxide synthase (iNOS) were assessed by real-time qPCR, western blot to investigate the mechanism of CTS regulating HS-induced liver injury. Results. H&E staining and a histological score of rat liver suggested that HS induced liver injury. The activity of ALT, AST, and MPO was significantly increased by HS treatment. After CTS administration the ALT, AST, and MPO activities were suppressed, which indicates the liver injury was alleviated by CTS. The HS-induced upregulation of the TUNEL-positive cell rate was suppressed by various doses of CTS. HS-induced ROS production was decreased and the protein expression of Bax and Bcl-2 in the HS-induced rat liver was reversed by CTS administration. In the liver of HS-induced rats, the upregulation of MDA content and the downregulation of GSH content and SOD activity were suppressed by CTS. Additionally, CTS increases ATP content and mitochondrial oxidative complexes activities and suppressed the release of cytochrome c from mitochondria to the cytoplasm. Moreover, IF and western blot demonstrated that the activation of Nrf2 blocked by HS was recovered by different doses of CTS in liver tissue. The expression of downstream enzymes of the Nrf2 pathway, including HO-1, NQO1, COX-2, and iNOS, was reversed by CTS in the HS rat model. Conclusions. The current study for the first time revealed the protective effect of CTS in HS-induced liver injury. CTS effectively recovered hepatocyte apoptosis, oxidative stress, and mitochondria damage induced by HS in the rat liver partly via regulating the Nrf2 signaling pathway.
研究领域:
药理学
·
病理生理学
·
分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 23
·期 13
·7395
·
IF 6.208
Xiaoqin Ding,Yan Chen,Lina Zhou,Ruoyun Wu,Tunyu Jian,Han Lyu,Yan Liu,Jian Chen
Bisdemethoxycurcumin (BDMC), a principal and active component of edible turmeric, was previously found to have beneficial effects on metabolic diseases. Chronic kidney disease (CKD) may benefit from its potential therapeutic use. Using a high-fat diet (HFD)-fed mouse model, we examined the effects of BDMC on renal injury and tried to determine how its associated mechanism works. A number of metabolic disorders are significantly improved by BDMC, including obesity, hyperglycemia, hyperinsulinemia, hyperlipidemia and inflammation. Further research on renal histopathology and function showed that BDMC could repair renal pathological changes and enhance renal function. Moreover, decreased serum malondialdehyde (MDA), elevated superoxide dismutase (SOD) activity, and the inhibition of renal reactive oxygen species (ROS) overproduction revealed the alleviation of oxidative stress after BDMC administration. In addition, renal Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 (Keap1/Nrf2) pathway was activated in BDMC-treated mice. In conclusion, these findings demonstrated BDMC as a potential therapy for HFD-induced CKD via the activation of the Keap1/Nrf2 pathway.Keywords:bisdemethoxycurcumin;chronic kidney disease;high-fat diet;Keap1/Nrf2 pathway;oxidative stress
研究领域:
药理学
·
肾病学
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL BIOLOGY INTERNATIONAL
·
2022
·Vol. 47
·期 3
·598-611
·
IF 4.473
Yangyang Wu,Shuo Zhou,An Zhao,Yuling Mi,Caiqiao Zhang
Oxidative stress is a major cause of ovarian aging and follicular atresia. There is growing evidence that showed potential roles of rutin in antidiabetic, anti-inflammatory, antitumor, antibacterial and antioxidant, although it is yet unclear what the underlying mechanism is. Here, we looked into the potential effects of rutin on oxidative stress in the prehierarchical small white follicles (SWFs) from 580-day-old (D580) laying chickens. According to the findings, aging D580 layer ferroptosis was much higher than it was for laying hens during the peak period (280-day-old, D280). In both naturally aged and d -gal-induced chicken SWFs, rutin treatment concurrently boosted cell proliferation and prevented apoptosis. In addition, rutin inhibited the increased ferroptosis in aging hens. Meanwhile, rutin markedly suppressed the elevated ferroptosis and descending antioxidant capacity of D280-culture-SWFs from chicken elicited by d -gal. Rutin's activation of the Nrf2/HO-1 pathway hastened the SWFs' verbal battle with oxidative damage and reduced ferroptosis. Furthermore, activation of the ferroptosis signal increased the oxidative damage in SWFs. In conclusion, rutin alleviated oxidative stress that was induced by ferroptosis in aging chicken SWFs through Nrf2/HO-1 pathway. These findings point to a novel mechanism by which rutin protects SWFs from oxidative stress by suppressing ferroptosis, which is presumably a fresh approach to slowing ovarian aging in laying hens.
研究领域:
动物科学
·
分子生物学
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Current Research in Food Science
·
2022
·
IF 6.269
Yong Chen,Jiajun Wang,Ziheng Jing,Jose M. Ordovas,Jing Wang,Lirong Shen
Demands for dietary supplements with anti-fatigue effects are growing fast due to increasing societal demands. Moreover, in highly physically active individuals, there are also significant needs for supplements to improve exercise performance. The present study evaluated the potential anti-fatigue and anti-oxidant effects of curcumin in mice using exhaustive swimming test. Male C57BL/6J mice were randomized into six groups: blank control (Rest), swimming control (Con), Vitamin C (Vc), low-dose curcumin (C 50 ), middle-dose curcumin (C 100 ), and high-dose curcumin (C 200 ). After a 4-week intervention, the mice in all groups except the Rest group were subject to an exhaustive swimming test. Then, mice were sacrificed to examine serum biochemical markers and fatigue-related enzymes. Moreover, the gene and protein expressions of signal transduction factors involved in the Nrf2/Keap1 signaling pathway were measured. The results indicated that curcumin significantly enhanced the exercise tolerance of mice in the exhaustive swimming test. Particularly, the swimming time of mice in the C 100 group was increased by 273.5% when compared to that of mice in the Con group. The levels of blood urea nitrogen, blood ammonia, lactic acid, creatine kinase and lactate dehydrogenase in the C 100 group were decreased by 13.3%, 21.0%, 18.6%, 16.7% and 21.9%, respectively, when compared to those of mice in the Con group. Curcumin alleviated exercise-induced oxidative stress and significantly enhanced the activities of superoxide dismutase, catalase and glutathione peroxidase by activating the Nrf2 signaling. These findings indicated that curcumin supplementation exerted remarkable anti-oxidant and anti-fatigue effects in mice, providing additional evidence supporting the use of curcumin as functional food, especially by those engaged in sports-related activities.
研究领域:
营养学
·
运动生理学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICAL RESEARCH
·
2025
·Vol. 30
·期 1
·1-14
·
IF 3.4
Guan Pin,Cai Wentao,Zhong Chunrong,Wu Chunmei
Background Nuclear factor erythroid-2-related factor 2 ( Nrf2 ) could alleviate chronic obstructive pulmonary disease (COPD)-induced muscle dysfunction, and this study aimed to explore the specific mechanisms involved. Methods We successfully established a 12-week cigarette smoke-induced mouse model to replicate COPD-related sarcopenia. The Nrf2 agonist sulforaphane (SFN) and inhibitor ML385 were used to comprehensively assess the regulatory function of Nrf2 in COPD-related sarcopenia. Lung function tests, muscle tension measurements, flow cytometry, H&E staining, qRT-PCR, Western blotting, and biochemical assays were performed to evaluate changes in inflammation, oxidative stress, autophagy, and the Nrf2 /Keap1 axis, so as to verify the pivotal role of Nrf2 signaling in modulating immune responses and skeletal muscle injury from multiple perspectives. Results In the COPD model group, FEV 0.1 /FVC was significantly decreased ( p < 0.05), along with markedly reduced quadriceps muscle mass and grip strength ( p < 0.05). Additionally, the numbers of neutrophils, monocytes, and macrophages in the lung tissues were notably increased ( p < 0.05), accompanied by elevated levels of inflammatory cytokines IL-1b, IL-6, and IL-18 ( p < 0.05). The level of Malondialdehyde (MDA) was increased ( p < 0.05), while that of heme oxygenase 1 (HO-1), glutathione-S-transferase (GST), and total superoxide dismutase (T-SOD) was decreased ( p < 0.05). SFN treatment significantly upregulated Nrf2 and downregulated Keap1 expression ( p < 0.05), reversed the changes in inflammatory and oxidative stress markers ( p < 0.05), and inhibited the protein levels of ATG7 and LC3 ( p < 0.05). In contrast, the ML385-treated group showed opposite trends. Conclusion The present study demonstrated that the Nrf2 pathway played a key role in the regulation of inflammatory response, oxidative stress and autophagy in COPD-associated sarcopenia.
研究领域:
分子生物学
·
药理学
·
呼吸医学
·
免疫学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 19
·14721
·
IF 5.6
Yue Wang,Shixiang Wei,Hui Lian,Lingling Tong,Linhui Yang,Bo Ren,Dongsheng Guo,He Huang
Ophiocordyceps gracilis(O. gracilis) is a parasitic fungus used in traditional Chinese medicine and functional foods. In this study, a neutral heteropolysaccharide (GSP-1a) was isolated from spores ofO. gracilis, and its structure and antioxidant capacities were investigated. GSP-1a was found to have a molecular weight of 72.8 kDa and primarily consisted of mannose (42.28%), galactose (35.7%), and glucose (22.02%). The backbone of GSP-1a was composed of various sugar residues, including →6)-α-D-Manp-(1→, →2,6)-α-D-Manp-(1→, →2,4,6)-α-D-Manp-(1→, →6)-α-D-Glcp-(1→, and →3,6)-α-D-Glcp-(1→, with some branches consisting of →6)-α-D-Manp-(1→ and α-D-Gal-(1→. In vitro, antioxidant activity assays demonstrated that GSP-1a exhibited scavenging effects on hydroxyl radical (•OH), 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radical cation (ABTS•+), and 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•). Moreover, GSP-1a was found to alleviate H2O2-induced oxidative stress in HepG2 cells by reducing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), while enhancing the activities of superoxide dismutase (SOD). Furthermore, GSP-1a upregulated the mRNA expression of antioxidant enzymes such asHo-1,Gclm, andNqo1, and regulated the NRF2/KEAP1 and FNIP1/FEM1B pathways. The findings elucidated the structural types of GSP-1a and provided a reliable theoretical basis for its usage as a natural antioxidant in functional foods or medicine.Keywords:Ophiocordyceps gracilis;spores;polysaccharide;structural characterization;antioxidant activity
研究领域:
药理学
·
生物化学
·
分子生物学
·
传统中药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2023
·
IF 5.1
Xi Wang,Wenjing Zhu,Miao Xing,Haiyan Zhu,Enqing Chen,Jie Zhou
Matrine (MT) is an alkaloid isolated from Sophora flavescens with various bioactivities and is widely used clinically. However, the broader its clinical use, the greater its toxicity concerns. We investigate the role of ferroptosis in MT-induced liver injury caused by an imbalance in the antioxidant pathway. Our results showed that MT could cause pathological changes in liver tissues and lead to a significant reduction in L02 cell viability. MT also reduced superoxide dismutase (SOD) and glutathione (GSH), increased malondialdehyde (MDA), reactive oxygen species (ROS), and lipid peroxidation levels, and disrupted iron homeostasis , leading to ferroptosis. In addition, MT decreased the protein levels of FTH, Nrf2 , xCT, GPX4, HO-1 and ferroptosis suppressor protein 1 (FSP1) and increased the protein levels of TRF1 and DMT1 , characteristic indicators of ferroptosis. Interestingly, the cytotoxic effects of MT were alleviated by ferroptosis inhibitor, Nrf2 agonist, or selenium supplementation. These results revealed that MT triggers hepatocyte ferroptosis by inhibiting the Nrf2/GPX4 antioxidant system.
研究领域:
药理学
·
毒理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Xiaocui Jiang,Xiaoming Yu,Zhongyi Zhu,Yinjuan Lyu,Xinyu Jiang,Zihao Liu,Jigang Cao,Min Xiao
Ethnopharmacological relevance The effect of hyperuricemia (HUA) on testicular spermatogenesis cannot be ignored. The classical Chinese medicine compound Shenling Baizhu San (SLBZS) can reduce uric acid and improve testicular spermatogenesis, while researchers have not well explored the related pathology and pharmacodynamic mechanism have. Aims of study To investigate whether the dysfunction of testicular spermatogenesis caused by HUA and the therapeutic effect of SLBZS are related to testicular cell ferroptosis. Materials and methods C57BL/6 mice and C57BL/6 background Sirt3 -/- mice were induced by oxazinate potassium (OXO), and HUA spermatogenic dysfunction mice model were constructed and treated with SLBZS. Sperm quality detection and testicular histopathology served for evaluating the protective mechanism of SLBZS against testicular spermatogenesis in HUA mice. Biochemical detection, transmission electron microscopy, immunohistochemistry and immunofluorescence were used to evaluate ferroptosis level of testicular cells. Western blot analysis assisted in verifying the expression of the corresponding pathway proteins. Results The testes of mice with HUA spermatogenic dysfunction were subjected to OXO-induced oxidative stress and ferroptosis, and the Sirt3/Nrf2 pathway-related protein expressions were changed. SLBZS improved the testes of mice with HUA spermatogenic dysfunction in terms of their spermatogenic function, oxidative stress and ferroptosis, and promoted Sirt3/Nrf2 antioxidant pathway-related proteins to be expressed. The analysis of Sirt3 -/- mice was modeled and dosed, and it was found that SLBZS could not improve the spermatogenic function, oxidative stress and ferroptosis of Sirt3-deficient model mice’ testes. Conclusions OXO-induced spermatogenic dysfunction in HUA is associated with ferroptosis of testicular cells. SLBZS can be used for treating spermatogenic dysfunction in HUA possibly by activating Sirt3/Nrf2 signaling pathway, which inhibits ferroptosis due to oxidative stress.
研究领域:
药理学
·
生殖医学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
·
2015
·
IF 3.529
Chuanyang Su,Pu Zhang,Xiufang Song,Qiong Shi,Juanli Fu,Xiaomin Xia,Huiyuan Bai,Lihua Hu,Demei Xu,Erqun Song,Yang Song
Tetrachlorobenzoquinone (TCBQ), a metabolite of industrial herbicide pentachlorophenol, showed hepatotoxicity and genotoxicity through reactive oxygen species (ROS) mechanism in vivo and in vitro models. Nuclear factor erythroid-derived 2-like 2 (Nrf2) is a cellular sensor of oxidative or electrophilic stress, which controls the expression of detoxifying enzymes and antioxidant proteins. Using the human hepatoma HepG2 cell line as an in vitro model, we demonstrated a significant induction of Nrf2 but not its negative regulator Kelch-like ECH-associated protein 1 (Keap1), following exposure to TCBQ. Also, our results clearly demonstrated the translocation of cytosolic Nrf2 into the nucleus. After translocation, Nrf2 subsequently binds to the antioxidant response element (ARE), up-regulated heme oxygenase-1 (HO-1), and NADH quinone oxidoreductase subunit 1 (NQO1), which may be considered as an antioxidative response to TCBQ-intoxication. The luciferase reporter assay confirmed the formation of the Nrf2-ARE complex. Furthermore, mechanism studies proposed that TCBQ promoted the formation of the Keap1 cross-linking dimer, a ubiquitination switch from Nrf2 to Keap1 but not the dissociation of the Keap1-Cullin3 (Cul3) complex.
研究领域:
毒理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY LETTERS
·
2023
·
IF 3.5
Zhang Qian,Chuwei Li,Wei Zhao,Zhaowanyue He,Mengqi Xue,Shuxian Wang,Xi Cheng,Rujun Ma,Xie Ge
As a widespread environmental contaminant, short chain chlorinated paraffins (SCCPs) has attracted great attention. However, the toxicity of SCCPs on male reproductive system remains ambiguous. In this study, we treated mice with SCCPs by gavage and investigated the toxic effects of SCCPs on testis . According to the results, the sperm parameters of mice were significantly reduced after exposure to 1, 10, 100 mg/kg body mass per day SCCPs for 35 days. SCCPs resulted in disorderly arranged seminiferous epithelium and increased apoptotic cells in testes. Both in vivo and in vitro experiments indicated that the oxidative stress was induced after SCCPs exposure, and dysfunction of nuclear factor erythroid-related factor (NRF2) signaling pathway played a role in this process. Moreover, resveratrol , an NRF2 activator, could alleviate the damage of SCCPs onmale reproductive system. Our study indicated that oxidative stress is the key point for explaining the testicular toxicity caused by SCCPs, and NRF2 could be used as a potential target for clinical treatment to alleviate the reproductive toxicity induced by SCCPs.
研究领域:
环境毒理学
·
生殖生物学
·
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）