INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 19
·14771
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IF 5.6
Pan Lei,Zhiyang Li,Qiuwei Hua,Ping Song,Lun Gao,Long Zhou,Qiang Cai
The neuroinflammatory response after intracerebral hemorrhage (ICH) causes a large amount of neuronal loss, and inhibiting the inflammatory response can improve the prognosis. In previous laboratory studies and clinical trials, ursolic acid (UA) inhibited the inflammatory response, but whether it can be administered to inhibit the neuroinflammatory response after cerebral hemorrhage is unknown. The aim of this study was to investigate the effects of ursolic acid after cerebral hemorrhage. Online databases were used to obtain potential therapeutic targets of ursolic acid for the treatment of cerebral hemorrhage, and possible mechanisms were analyzed by KEGG, GO, and molecular docking. A rat model of cerebral hemorrhage was established using collagenase, and an in vitro cerebral hemorrhage model was constructed by adding hemin to BV2 cell culture medium. Enzyme-linked immunosorbent assay (ELISA), Western blotting (WB), immunofluorescence, TUNEL staining, and calcein/PI staining were used to investigate the degree of microglial M1 polarization, changes in the levels of inflammatory factors, activation of the NF-κB pathway, and changes in the indicators of cellular death after ursolic acid treatment. In addition, phorbol 12-myristate 13-acetate (PMA) was used to activate the NF-κB pathway to verify that ursolic acid exerts its anti-neuroinflammatory effects by regulating the NF-κB/NLRP3/GSDMD pathway. Network pharmacology and bioinformatics analyses revealed that ursolic acid may exert its therapeutic effects on cerebral hemorrhage through multiple pathways. Together, in vivo and in vitro experiments showed that ursolic acid inhibited microglial M1 polarization and significantly reduced the levels of p-NF-κB, GSDMD-N, cleaved caspase-1, TNF-α, IL-6, and IL-1β, which were significantly inhibited by the use of PMA. Ursolic acid inhibits microglial pyroptosis via the NF-κB/NLRP3/GSDMD pathway to alleviate neuroinflammatory responses after cerebral hemorrhage.Keywords:ursolic acid;neuroinflammation;cerebral hemorrhage;microglial;pyroptosis
研究领域:
神经科学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2024
·
IF 3.3
Jun-qi Zhan,Jun-xin Wu,Jing-jing Fu,Gao-shang Li,Fang Wu,Yue-wen Chen
BACKGROUND Giant salamander protein peptide is a peptide with rich functional properties. Giant salamander protein peptide KGEYNK (KK-6) is a peptide with both antioxidant and anti-inflammatory properties. The antioxidant and anti-inflammatory mechanisms of KK-6 are still unclear. When we studied the functional mechanism of KK-6, we found that the antioxidant property of KK-6 has a synergistic and promoting effect on anti-inflammatory properties. RESULTS KK-6 enhances cellular resistance to LPS via the MAPK/NF-κB signaling pathway, leading to increased levels of inflammatory factors: interleukin-1β (764.81 ng mL −1 ), interleukin-6 (1.06 ng mL −1 ) and tumor necrosis factor-α (4440.45 ng mL −1 ). KK-6 demonstrates potent antioxidant properties by activating the Nrf2 signaling pathway, resulting in elevated levels of antioxidant enzymes (glutathione peroxidase: 0.03 μg mL −1 ; superoxide dismutase: 0.589 μg mL −1 ) and a reduction in the concentration of the oxidative product malondialdehyde (967.05 μg mL −1 ). CONCLUSION Our findings highlight the great potential of KK-6, a peptide extracted from giant salamander protein, as a remedy for intestinal inflammation. Through its dual role as an antioxidant and anti-inflammatory agent, KK-6 offers a promising avenue for alleviating inflammation-related damage and oxidative stress. This study lays the foundation for further exploration of giant salamander products and highlights their importance in health and novel food development. © 2024 Society of Chemical Industry.
研究领域:
生物化学
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免疫学
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营养学
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产品关联
DOI
PubMed
高影响因子
3 Biotech
·
2020
·Vol. 10
·期 8
·1-10
·
IF 1.798
Ge Xin,Meng Xianglin,Fei Dongsheng,Kang Kai,Wang Qiubo,Zhao Mingyan
Lung injury associated with systemic inflammatory response is a common problem affecting human health. Previous studies have shown that lycorine exerts a anti-inflammatory effect. However, whether lycorine alleviates lung injury remains unclear. To explore this issue, BALB/c mice and MLE-12 cells were treated with lipopolysaccharide (LPS) to establish lung injury mouse model and cell model, respectively. Glycyrrhizic acid, known as an inhibitor of ALI, was also used to study the effects of lycorine in vitro. Our results showed that after LPS treatment, the lung injury score, lung wet-to-dry weight ratio, and malondialdehyde (MDA) production in the lung tissues and the expression levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in bronchoalveolar lavage fluid were significantly increased, whereas their levels were decreased by lycorine. Additionally, LPS injection activated the high-mobility group box 1 (HMGB1)/Toll-like receptors (TLRs)/NF-κB pathway. However, lycorine treatment attenuated the activity of the HMGB1/TLRs/NF-κB pathway in the lung tissues. In vitro studies showed that lycorine administration significantly decreased the levels of inflammatory cytokines and MDA and attenuated the activity of the HMGB1/TLRs/NF-κB pathway in LPS-treated cells. Moreover, the inhibitory effects of lycorine on the inflammatory response and oxidative stress in LPS-treated lung cells were similar with that of glycyrrhizic acid, and this inhibition was intensified by both lycorine and glycyrrhizic acid treatment. We suggest that lycorine could alleviate LPS-induced lung injury of inflammation and oxidative stress by blocking the HMGB1/TLRs/NF-κB pathway, which gives a new perspective for ALI therapy to treat lycorine as a potential treatment clinically.
研究领域:
药理学
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免疫学
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肺病学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF DRUG TARGETING
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2019
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IF 3.277
Yan Jiang,Hongjiao Du,Xue Liu,Xi Fu,Xiaodong Li,Qian Cao
There is increasing evidence that atherosclerosis is the significant risk factor for cardiovascular diseases, which are the leading causes of morbidity and mortality worldwide. Artemisinin is a natural endoperoxides quiterpene lactone compound in Artemisia annua L with vasculoprotective effects. The primary aim of this study was to investigate whether artemisinin could be conferred an anti-atherosclerotic effect in high-fat diet (HFD)-fed ApoE–/– mice and explore the possible mechanism. We found that treatment with artemisinin (50 and 100 mg/kg) effectively ameliorated atherosclerotic lesions, such as foam cell formation, hyperplasia and fibrosis in the aortic intima. Atherosclerotic mice treated with artemisinin showed reduced inflammation by up-regulating adenosine 5′-monophosphate (AMP) activated protein kinase (AMPK) activation and by down-regulating nuclear factor-κB (NF-κB) phosphorylation and nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome expression in the aortas. In addition, artemisinin was found to promote AMPK activity in macrophages and its anti-inflammatory effect was neutralised by AMPK silence using specific siRNA. In conclusion, we demonstrate that artemisinin may protect the aortas from atherosclerotic lesions by suppression of inflammatory reaction via AMPK/NF-κB/NLRP3 inflammasomes signalling in macrophages.
研究领域:
心血管疾病
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL ANIMALS
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2021
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IF 2.319
Jianhua Wu,Lizhen Wu,Li Zhang,Huanhuan Xu,Min Wang,Lin Wang,Jie Chen,Kaiyue Sun
Inflammatory allergic reaction is the main cause of allergic rhinitis (AR). Previous studies indicated that miR-224-5p was downregulated in the nasal mucosa of patients with AR, while the function of miR-224-5p in AR remains unclear. To explore this issue, AR mouse model was established using ovalbumin (OVA). For treatment group, lentivirus (LV)-miR-224-5p or its control was intranasally administrated to AR mice. miR-224-5p expression was detected by reverse transcription-quantitative PCR, followed by assessing the immunoglobulin E (IgE) level. Pathological alterations in nasal mucosa were detected using Hematoxylin-Eosin staining and Sirius red staining, followed by assessing the levels of inflammatory cells and factors. The NLRP3 inflammasome and TLR4/MyD88/NF-κB pathway were measured by Western blot, and then the relationship between miR-224-5p and toll-like receptor 4 (TLR4) was verified. The results showed that miR-224-5p was significantly decreased in nasal mucosa of AR mice. AR mice exhibited increased sneezing and nasal rubbing events, IgE level in serum, and pathological alterations in nasal mucosa, while overexpression of miR-224-5p markedly attenuated these changes. The levels of inflammatory cells in nasal lavage fluid and pro-inflammatory factors in serum and nasal mucosa were significantly increased in AR mice, which were reduced by miR-224-5p overexpression. Of note, LV-miR-224-5p treatment remarkably suppressed the activations of NLRP3 inflammasome and the TLR4/MyD88/NF-κB pathway in AR mice. Furthermore, miR-224-5p could bind to 3’-untranslated region (3’-UTR) of TLR4 and negatively regulate TLR4 level. Overall, we conclude that miR-224-5p may relieve AR by negatively regulating TLR4/MyD88/NF-κB pathway, indicating that miR-224-5p may be a promising target for AR treatment.
研究领域:
免疫学
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分子生物学
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过敏
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药理学
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产品关联
DOI
PubMed
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
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2021
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IF 3.228
Jianqing Chen,Bing Shao,Jinliang Wang,Zhiqiang Shen,Honggui Liu,Shu Li
Chlorpyrifos (CPF) is an organophosphate insecticide and can cause cell death of animals. In the study, the common carp were exposed to CPF at 0 μg/L (the control group), 1.16 μg/L (the low dose group), 11.6 μg/L (the medium dose group), and 116 μg/L (the high dose group), respectively. The carp were euthanized at the 30th day and gills were collected immediately. The ultrastructural and histopathological observations showed obvious necrosis characteristics and inflammatory injury in the CPF-treated groups. CPF exposure activated the MAPK pathway, in which the mRNA and protein expressions of extracellular signal-regulated (ERK), p38 MAP kinase (p38), and c-Jun N-terminal kinase (JNK) were increased; the mRNAs and proteins of NF-κB and TNF-α were activated; and the mRNAs and proteins of necroptosis related genes were changed (the mRNA and protein expression of RIPK1 , RIPK3 , MLKL, and FADD were increased and caspase-8 was decreased) with concentration dependency. Taken together, we concluded that CPF exposure activated the MAPK/NF-κB/TNF-α pathway, promoted inflammatory injure and evoked necroptosis in common carp gills. In addition, CPF-induced inflammation and necroptosis was concentration dependency. The toxic effects of CPF on gills provided data for both aquaculture and toxicological studies.
研究领域:
环境毒理学
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鱼类生理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INDUSTRIAL CROPS AND PRODUCTS
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2023
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IF 5.9
Meixia Xie,Jiale Cai,Xiaoting Zhong,Jiayin Liang,Shengwang Liang,Minghua Xian,Chunyan Yan,Shumei Wang
Rehmannia glutinosa Libosch is a useful crop for both industrial and medical use. Polysaccharide is one of the rich components, while its separation, purification and structural characteristics are rarely reported. In this work, two new natural polysaccharides, RGP90–1–1 and RGP90–1–2 (molecular weights 13.2 kDa and 6.2 kDa, respectively), were obtained from Rehmannia glutinosa . The structural characteristics, including monosaccharide composition, linkage, and configuration, were analyzed by HPLC, FT-IR, GC-MS NMR spectroscopy , and so on. The main component of RGP90–1–1 was arabinose , with trace amounts of glucose and xylose , with the linkages L-Ara f -(1→, →3)-L-Ara f -(1→, →5)-L-Ara f -(1→, D-Glc p -(1→, →3, 5)-L-Ara f -(1→, →2, 5)-L-Ara f -(1→, →6)-D-Glc p -(1→ and →2, 3, 4)-D-Xyl p -(1→. RGP90–1–2 consisted of large amounts of arabinose and a small amount of glucose, with linkages including L-Ara f -(1→, →3)-L-Ara f -(1→, →5)-L-Ara f -(1→, →3,5)-L-Ara f -(1→ and →6)-D-Glc p -(1→. Furthermore, inhibition experiments of α-glucosidase and α-amylase activities showed that RGP90–1–1 and RGP90–1–2 had potential hypoglycemic effects. In vitro, RGP90–1–2 dose-dependently attenuated the secretion of nitric oxide and the expression of iNOS in LPS-induced RAW264.7 inflammation model and exerted significant anti-inflammatory effects via NF-κB/IκBα pathway. The findings suggest that RGP90–1–1 and RGP90–1–2 have the potential for development into new hypoglycemic drugs or health food . It offers a scientific foundation for increasing the planting applications and public awareness of Rehmannia glutinosa .
研究领域:
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
高影响因子
MOLECULAR NEUROBIOLOGY
·
2022
·Vol. 59
·期 11
·6903-6917
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IF 5.682
Zhao Maofang,Cheng Yuan,Wang Xiaoxuan,Cui Xiaoying,Cheng Xiaojing,Fu Qian,Song Yilin,Yu Peiquan,Liu Yi,Yu Yinghua
Obesity has become a public health epidemic worldwide and is associated with many diseases with high mortality including hypertension, diabetes, and heart disease. High-fat diet (HFD)-induced energy imbalance is one of the primary causes of obesity, but the underlying mechanisms are not fully elucidated. Our study showed that HFD reduced the level of hydrogen sulfide (H 2 S) and its catalytic enzyme cystathionine β-synthase (CBS) in mouse hypothalamus and plasma. We found that HFD activated mTOR, IKK/NF-κB, the main pathway regulating inflammation. Activation of inflammatory pathway promoted the production of pro-inflammatory cytokines including IL-6, IL-1β, and TNF-α, which caused cell damage and loss in the hypothalamus. The disturbance of the hypothalamic neuron circuits resulted in body weight gain in HFD-induced mice. Importantly, we also showed that restoration of H 2 S level with NaHS or activation of CBS with SAMe attenuated HFD-induced activation of mTOR, IKK/NF-κB signaling, which reduced the inflammation and the neuronal cell loss in the hypothalamus, and also inhibited body weight gain in mice. The same effects were obtained by inhibiting mTOR or NF-κB, which suggested that mTOR and NF-κB were the critical molecular factors involved in hypothalamic inflammation. Taken together, this study identified that HFD-induced hypothalamus inflammation plays a critical role in the development of obesity. Moreover, the inhibition of hypothalamic inflammation by regaining H 2 S level could be a potential therapeutic to prevent the development of obesity. Graphical abstract
研究领域:
营养学
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内分泌学
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免疫学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
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2023
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IF 5.1
Di Jia,Jiahui Han,Jimin Cai,Zhirong Huan,Yan Wang,Xin Ge
Mesenchymal stem cells (MSCs) have favourable outcomes in the treatment of kidney diseases. Pre-B-cell leukaemia transcription factor 1 (PBX1) has been reported to be a regulator of self-renewal of stem cells. Whether PBX1 is beneficial to MSCs in the treatment of haemorrhagic shock (HS)-induced kidney damage is unknown. We overexpressed PBX1 in rat bone marrow-derived mesenchymal stem cells (rBMSCs) and human bone marrow-derived mesenchymal stem cells (hBMSCs) to treat rats with HS and hypoxia-treated human proximal tubule epithelial cells (HK-2), respectively. The results indicated that PBX1 enhanced the homing capacity of rBMSCs to kidney tissues and that treatment with rBMSCs overexpressing PBX1 improved the indicators of kidney function, alleviated structural damage to kidney tissues. Furthermore, administration with rBMSCs overexpressing PBX1 inhibited HS-induced NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and the release of proinflammatory cytokines, and further attenuated apoptosis. We then determined whether NF-κB, an important factor in NLRP3 activation and the regulation of inflammation, participates in HS-induced kidney damage, and we found that rBMSCs overexpressing PBX1 inhibited NF-κB activation by decreasing the p-IκBα/IκBα and p-p65/p65 ratios and inhibiting the nuclear translocation and decreasing the DNA-binding capacity of NF-κB. hBMSCs overexpressing PBX1 also exhibited protective effects on HK-2 cells exposed to hypoxia, as shown by the increase in cell viability, the mitigation of apoptosis, the decrease in inflammation, and the inhibition of NF-κB and NLRP3 inflammasome activation. Our study demonstrates that MSCs overexpressing PBX1 ameliorates HS-induced kidney damage by inhibiting NF-κB pathway-mediated NLRP3 inflammasome activation and the inflammatory response.
研究领域:
干细胞生物学
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肾生理学
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炎症
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Oncology
·
2021
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IF 6.244
Heng Yongqing,Liang Yupei,Zhang Junqian,Li Lihui,Zhang Wenjuan,Jiang Yanyu,Wang Shiwen,Jia Lijun
The neddylation pathway is overactivated in esophageal cancer. Our previous studies indicated that inactivation of neddylation by the NAE inhibitor induced apoptosis and autophagy in cancer cells. Camptothecin (CPT), a well-known anticancer agent, could induce apoptosis and autophagy in cancer cells. However, whether CPT could affect the neddylation pathway and the molecular mechanisms of CPT-induced autophagy in esophageal cancer remains elusive. We found that CPT induced apoptosis and autophagy in esophageal cancer. Mechanistically, CPT inhibited the activity of neddylation and induced the accumulation of p-IkBa to block NF-κB pathway. Furthermore, CPT induced the generation of ROS to modulate the AMPK/mTOR/ULK1 axis to finally promote protective autophagy. In our study, we elucidate a novel mechanism of the NF-κB/AMPK/mTOR/ULK1 pathway in CPT-induced protective autophagy in esophageal cancer cells, which provides a sound rationale for combinational anti-ESCC therapy with CPT and inhibition AMPK/ULK1 pathway.
研究领域:
肿瘤学
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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
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2018
·
IF 2.559
Fan Zhang,Chenhong Zhang
Intracerebral hemorrhage (ICH) is reported as a common and often fatal type of stroke accompanied with high morbidity and mortality, and it frequently results in long-lasting neurological dysfunctions. However, the pathogenesis that contributes to ICH has not been fully understood. Rnf112, also known as Znf179, is a member of the RING finger protein family. The expression of Rnf112 is abundant in the brain and is modulated during brain progression and development. The study aimed to explore the role of Rnf112 in brain injury after ICH, as well as the underlying molecular mechanisms. The results indicated that ICH led to a significant decrease in Rnf112, which was confirmed in oxyhemoglobin (oxyHb)-incubated astrocytes and microglial cells. Moreover, the Rnf112 knockout (Rnf112 −/− ) mice and wild type (WT) mice induced by ICH were further employed. Compared to the WT/ICH group, Rnf112 −/− mice exhibited accelerated brain injury, as evidenced by the increased brain water contents and neurological deficit scores (NDS). In comparison to WT/ICH group, a remarkable up-regulation in the release of pro-inflammatory cytokines, including tumor necrotic factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β, was observed in perihematoma tissues of Rnf112 −/− mice on day 3 post-ICH. The process was along with promoted glial fibrillary acidic protein (GFAP) and Iba1 expression and reduced NeuN levels. Furthermore, ICH-induced increases in toll-like receptor (TLR)-4 and myeloid differentiation primary response protein (MyD88) expression were exacerbated by the loss of Rnf112. The phosphorylated expression of IKKα, inhibitor of NF-κB (IκBα) and nuclear factor-kappa B (NF-κB) induced by ICH in perihematoma tissues of mice was markedly enhanced in Rnf112 −/− mice. Rnf112 repression-induced inflammatory response was verified in lipopolysaccharide (LPS)-incubated glial cells . In contrast, over-expressing Rnf112 markedly attenuated ICH-induced brain injury by restraining inflammation via inactivating TLR-4/NF-κB pathway. In summary, our findings suggested that Rnf112 expression was highly involved in the progression of ICH, and targeting Rnf112 signaling might be a promising therapeutic strategy against ICH development.
研究领域:
神经科学
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分子生物学
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病理学
✓ 已验证
DOI
PubMed
高影响因子
Natural Product Communications
·
2021
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IF 0.986
Wenyu Xin,Ming Jing,Junjie Yang,Meiling Wang,Guige Hou,Qiaoyun Wang,Leiming Zhang,Chunhua Wang
Emerging evidence indicates that NOD-like receptor protein 3 (NLRP3) inflammasome-induced inflammation plays a critical role in the pathogenesis of Parkinson’s disease (PD). Baicalein has been considered as a possible option for PD treatment based on its anti-neuroinflammatory effects. However, no studies have elucidated the precise mechanisms underlying the anti-neuroinflammatory activity of baicalein, particularly inflammasome-mediated effects. In this present study, rotenone-induced PD mice and BV2 microglia were used to investigate the anti-neuroinflammatory effects of baicalein and explore its underlying mechanism in vivo and in vitro. The results demonstrated that baicalein alleviated motor impairments and attenuated several inflammatory responses in rotenone-induced PD mice. Also, baicalein inhibited the expression of NLRP3 and activated caspase-1 in brain tissues. Correspondingly, baicalein prominently suppressed the inflammatory response in BV2 microglia induced by rotenone. Furthermore, in vitro data showed that baicalein suppressed the expression of NLRP3 and activated caspase-1 by abrogating the upregulation of ROS, as well as by inhibiting the TLR4/NF-κB signaling cascade. Overall, the results of the present study indicated that baicalein exerted anti-neuroinflammatory effects partly by inhibiting activation of the NLRP3 inflammasome, and targeting NLRP3 inflammasome signaling offers a novel therapeutic strategy for PD treatment.
研究领域:
神经科学
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药理学
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炎症
✓ 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）