CARDIOVASCULAR DRUGS AND THERAPY
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2024
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IF 3.1
Ye Bozhi,Cai Xueli,Liang Xiaohe,Chen Yunxuan,Dai Shanshan,Huang Zhuqi,Huang Weijian,Zhang Lei,Wang Zixuan,Xing Jincheng,Lai Xianhui,Huang Zhouqing,Jia Zhuyin
Purpose Inflammatory responses induced by NLRP3 inflammasome contribute to the progression of atherosclerosis. This study seeks to investigate the effect of emodin on the NLRP3 inflammasome in atherogenesis and to probe the underlying mechanism. Methods ApoE-knockout (ApoE −/− ) mice were treated with a high-fat diet (HFD) for 12 weeks and intragastrically with emodin for 6 weeks. Human mononuclear cell line THP-1 was pretreated with emodin or signaling pathway inhibitors and induced into macrophages using phorbol 12-myristate 13-acetate (PMA) for 48 h. The NLRP3-mediated inflammatory response was studied both in vivo and in vitro. The level of the inflammation was detected by western blot, real-time PCR analysis, and ELISA. Results Emodin attenuated atherosclerotic lesions in HFD-treated ApoE −/− mice. Emodin dramatically decreased the expression of NLRP3, GSDMD, IL-1β, and IL-18 in HFD-treated ApoE −/− mice and PMA-induced macrophages. Moreover, emodin significantly hindered the activation of nuclear factor kappa-B (NF-κB) by inhibiting the formation of the TLR4/MyD88 complex in PMA-induced macrophages. Conclusion Our data demonstrate that emodin can inhibit the development of atherosclerotic plaques by alleviating NLRP3/GSDMD-induced inflammation through repressing the TLR4/MyD88/NF-κB signaling pathway in macrophages. This finding suggests that emodin can be a potential candidate for the treatment of atherosclerosis.
研究领域:
免疫学
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心血管疾病
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药理学
✓ 已验证
DOI
PubMed
高影响因子
EXPERIMENTAL ANIMALS
·
2021
·
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
LIFE SCIENCES
·
2021
·
IF 5.037
Mengyuan Fang,Wencui Wan,Qiuming Li,Weiwei Wan,Yang Long,Hongzhuo Liu,Xin Yang
Aim This study aimed to evaluate the effects of Asiatic acid (AA), a naturally occurring compound of pentacyclic triterpenoid, on the pathological processes of diabetic retinopathy (DR). Methods SD rats were induced to develop early DR by intraperitoneal injection of STZ (60 mg/kg). Four weeks after injection, the diabetic rats were orally administrated with 37.5 mg/kg or 75 mg/kg AA every day for four weeks. The integrity of blood-retinal barrier (BRB) was measured by Evans blue staining. The polarization of microglia was determined by real-time PCR, western blot, and ELISA assays. The inner BRB (iBRB) or outer BRB (oBRB) breakdown was induced in human retinal endothelial cells or APRE19 cells through co-culture with high glucose and LPS-stimulated microglia BV2 cells. The damage to the iBRB and oBRB was measured using transendothelial/transepithelial electrical resistance (TEER/TER) and FITC-conjugated dextran cell permeability assays. Key findings Results demonstrated that AA alleviated BRB breakdown, as evidenced by decreased protein expression of occludin, claudin-5, and ZO-1. Furthermore, AA treatment suppressed inflammation and M1 polarization, while it increased M2 polarization in the retina of DR rats. In vitro , the iBRB or oBRB breakdown was alleviated by AA. LPS-induced M1-polarization of BV2 cells under high glucose condition was also repressed through AA administration. Finally, we demonstrated that AA weakened the TLR4/MyD88/NF-κB p65 signaling pathway both in vivo and in vitro . Significance AA ameliorated early DR by regulating microglia polarization via the TLR4/MyD88/NF-κB p65 pathway. These data indicate that AA is a potential candidate for DR treatment.
研究领域:
药理学
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眼科学
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免疫学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2025
·Vol. 29
·期 14
·e70659
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IF 4.2
Hao Wang,Chi Zhang,Jinyue He,Zhuoen He,Shihua Yan,Yuan Zhang,Shiyin Huang,Yangtian Yan,Yuchi Chen,Zhiqiang Xian,Rong Hu,Yanjing Wang,Wei Xiao,Mingqing Wang
Skeletal muscle atrophy is a prevalent complication in chronic kidney disease (CKD), and its pathogenesis is closely related to inflammation and oxidative stress. P-Coumaric acid (PCA) is a phenolic acid with anti-inflammatory and antioxidant pharmacological actions. This research aims to investigate the effect of PCA on CKD-induced muscle atrophy and its underlying mechanism. In our study, in vivo and in vitro models were established by using 5/6 nephrectomized rats and LPS-induced C2C12 myoblasts. The experimental results showed that PCA ameliorated kidney injury in CKD rats and increased skeletal muscle weight and the cross-sectional area of muscle fibres. In both CKD rats and LPS-induced C2C12 myoblasts, PCA also exhibited anti-inflammatory and antioxidant effects, reduced the levels of pro-inflammatory cytokines and enhanced the activity of antioxidant enzymes. Network pharmacology studies have identified 165 common targets between PCA and skeletal muscle atrophy. Furthermore, the experimental results also demonstrated that PCA decreased the expression of TLR4, MyD88, NF-κB p65, MurF1 and MAFbx at both the protein and mRNA levels. Additionally, in vitro experiments showed that the use of TLR4 agonists could reverse the muscle-protective effect of PCA. In summary, this study illustrated that PCA ameliorated skeletal muscle atrophy in CKD rats by inhibiting the TLR4/MyD88/NF-κB pathway.
研究领域:
药理学
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分子生物学
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肾脏病学
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生物化学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
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2023
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IF 3.8
Yiheng Quan,Pengchao Su,Chenhong Shangguan,Hao Hao,Lijuan Yue,Chen Chen
Bergenin (BG) is a polyphenolic substance which has therapeutic potential in the treatment of diabetic nephropathy (DN), a common complication of type II diabetes. However, the mechanisms underlying these effects remain unclear. We studied the protective effects and mechanisms of BG in DN mice, focusing on the TLR4/MyD88/NF-κB signalling pathway. C57BL/6J mice were used as experiments (n=60), and 10 animals were randomly selected as normal control. The DN model was developed by administering an intraperitoneal injection of streptozotocin (40 mg/kg BW for three days) and a high-fat diet (n=50). BG (20, 40, and 80 mg/kg BW, once a day) was administered orally for four weeks. After BG treatment, the food and water intake of DN mice decreased, blood glucose levels decreased, and insulin resistance reduced. As a result, serum LDL-C, TC, and TG levels decreased; HDL-C levels increased; SOD, CAT, and GSH-Px levels decreased; and MDA levels increased. BG administration reduced AST, ALT, BUN, and CRE levels and inflammatory factors (including TNF-α, MCP-1, IL-1β, and IL-6). Histopathology revealed a significant improvement in pathological damage to the liver, kidney, and spleen of mice treated with BG, and TLR4, MyD88, and NF-κB p65 were down-regulated at both mRNA and protein levels in the BG-treated group. Based on these results, BG therapeutic type II DN by hypoglycaemia, improving liver and kidney function, and anti-oxidative stress; reducing inflammation; and inhibiting the TLR4/MyD88/NF-κB signalling pathway. The results of this study suggest that BG can be used as an effective treatment for type II DN.
研究领域:
药理学
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内分泌学
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分子生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
Cell Host & Microbe
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2022
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IF 31.316
Haiyang Lu,Xiaoqiang Xu,Di Fu,Yubei Gu,Rong Fan,Hongmei Yi,Xiangyi He,Chaofu Wang,Binshen Ouyang,Ping Zhao,Li Wang,Pengpeng Xu,Shu Cheng,Zhifeng Wang,Duowu Zou,Lizhong Han,Weili Zhao
Summary Microbiota-induced tumorigenesis is well established in solid tumors of the gastrointestinal tract but rarely explored in hematologic malignancies. To determine the role of gut microbiota in lymphoma progression, we performed metagenomic sequencing on human primary gastrointestinal B cell lymphomas. We identified a distinct microbiota profile of intestinal lymphoma, with significantly decreased symbiotic microbes, particularly the genus Eubacterium and notably butyrate-producing Eubacterium rectale . Transfer of E. rectale -deficit microbiota of intestinal lymphoma patients to mice caused inflammation and tumor necrosis factor (TNF) production. Conversely, E. rectale treatment reduced TNF levels and the incidence of lymphoma in sensitized Eμ-Myc mice. Moreover, lipopolysaccharide from the resident microbiota of lymphoma patients and mice synergizes with TNF signaling and reinforces the NF-κB pathway via the MyD88-dependent TLR4 signaling, amalgamating in enhanced intestinal B cell survival and proliferation. These findings reveal a mechanism of inflammation-associated lymphomagenesis and a potential clinical rationale for therapeutic targeting of gut microbiota.
研究领域:
肿瘤学
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免疫学
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微生物学
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分子生物学
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DOI
PubMed
高影响因子
Natural Products and Bioprospecting
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2024
·Vol. 14
·期 1
·1-12
·
IF 4.8
Shi Yuru,Zhang Xiaoqian,Pei Shengji,Wang Yuhua
Adenosma buchneroides Bonati, also known as fleagrass, is an important medicinal plant used by the Akha (Hani) people of China for treating inflammation-related skin swelling, acne, and diarrhoea, among other conditions. In this study, we aimed to evaluate the anti-inflammatory activities and explore the molecular mechanisms of fleagrass on treating skin swelling and acne. The results demonstrated that fleagrass inhibited the enzymatic activities of 5-LOX and COX-2 in vitro, and decreased the release of NO, IL-6, TNF-α, and IL-10 in the LPS-induced RAW264.7 macrophages. The levels of proteins associated with the nuclear factor-kappa B (NF-κB) pathway were examined by western blotting and immunofluorescence, demonstrating that fleagrass downregulated the expression of TLR4, MyD88, NF-κB/p65, and iNOS and blocked the nuclear translocation of NF-κB/p65. Furthermore, fleagrass exhibited acute anti-inflammatory activity in paw oedema models. The results confirm that fleagrass exhibits remarkable anti-inflammatory activity and can be used in alleviating inflammation, suggesting that fleagrass has the potential to be a novel anti-inflammatory agent. Graphical Abstract
研究领域:
民族药理学
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药理学
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炎症
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药用植物
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2024
·
IF 4.2
Ruyi Zhu,Yaling Zhang,Weitai He,Yanan Sun,Xin Zhao,Yaping Yan,Qian Zhang
Wogonoside (WG) is a natural flavonoid extracted from Scutellariae Radix, recognized for its established anti-inflammatory properties. However, the role of WG in the context of neuroinflammation after spinal cord injury (SCI) remains inadequately elucidated. This study employed in silico , in vitro , and in vivo methodologies to investigate the impact of WG on microglia-mediated neuroinflammation after SCI. In the in silico experiment, we identified 15 potential target genes of WG associated with SCI. These genes were linked to the regulation of inflammatory response and immune defense. Molecular docking maps revealed toll-like receptor 4 as a molecular target for WG, demonstrating binding through a hydrogen bond (Lys263, Ser120). In lipopolysaccharide-stimulated BV2 cells and SCI mice, WG significantly attenuated microglial activation and facilitated a phenotype shift from M1 to M2. This was evidenced by the reversal of the increased expressions of Iba1, GFAP, and iNOS, as well as the decreased expression of Arg1. WG also suppressed the production of pro-inflammatory mediators (NO, TNF-α, IL-6, IL-1α, IL-1β, C1q). WG exerted these effects by suppressing the TLR4/MyD88/NF-κB signaling axis in microglia. Furthermore, by reducing levels of TNF-α, IL-1α, and C1q in supernatant of LPS-induced microglia, WG indirectly induced astrocytes change to A2 phenotype, evidenced by transcriptome sequencing result of primary mouse astrocytes. All these events above collectively created a favorable microenvironment, contributing to a significant alleviation of weight loss and neuronal damage at the lesion site of SCI mice. Our findings substantiate the efficacy of WG in mitigating neuroinflammation after SCI, thereby warranting further exploration.
研究领域:
药理学
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神经科学
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炎症
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Cancer Cell International
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2021
·Vol. 21
·期 1
·1-14
·
IF 5.722
Li Chunyang,Yang Shuangqing,Ma Huaqing,Ruan Mengjia,Fang Luyan,Cheng Jing
Background Cervical cancer is a type of the most common gynecology tumor in women of the whole world. Accumulating data have shown that icariin (ICA), a natural compound, has anti-cancer activity in different cancers, including cervical cancer. The study aimed to reveal the antitumor effects and the possible underlying mechanism of ICA in U14 tumor-bearing mice and SiHa cells.Methods The antitumor effects of ICA were investigated in vivo and in vitro. The expression of TLR4/MyD88/NF-κB and Wnt/β-catenin signaling pathways were evaluated.Results We found that ICA significantly suppressed tumor tissue growth and SiHa cells viability in a dose-dependent manner. Also, ICA enhanced the anti-tumor humoral immunity in vivo. Moreover, ICA significantly improved the composition of the microbiota in mice models. Additionally, the results clarified that ICA significantly inhibited the migration, invasion capacity, and expression levels of TGF-β1, TNF-α, IL-6, IL-17A, IL-10 in SiHa cells. Meanwhile, ICA was revealed to promote the apoptosis of cervical cancer cells by down-regulating Ki67, survivin, Bcl-2, c-Myc, and up-regulating P16, P53, Bax levels in vivo and in vitro. For the part of mechanism exploration, we showed that ICA inhibits the inflammation, proliferation, migration, and invasion, as well as promotes apoptosis and immunity in cervical cancer through impairment of TLR4/MyD88/NF-κB and Wnt/β-catenin pathways.Conclusion sTaken together, ICA could be a potential supplementary agent for cervical cancer treatment.
研究领域:
肿瘤学
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免疫学
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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
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2024
·
IF 4.2
Fengjiao Liu,Yaxin Jia,Liwei Zhao,Li-na Xiao,Xizhen Cheng,Yingying Xiao,Ying Zhang,Yuling Zhang,Huimin Yu,Qiao-en Deng,Yuanyuan Zhang,Yimeng Feng,junfang Wang,Yonggang Gao,Xuan Zhang,Yunyun Geng
Major depressive disorder (MDD) is a prevalent psychiatric disorder associated with brain inflammation and neuronal damage. Derived from the Aesculus chinensis Bunge fruit, escin has shown anti-inflammatory and neuroprotective effects. However, its potential as a treatment for MDD is unclear. This study investigates the antidepressant properties of escin using in vivo experimentation. The chronic unpredictable mild stress (CUMS) model was used to analyze the potential antidepressant effects and underlying mechanisms of escin. Wistar rats were exposed to CUMS for 35 consecutive days to induce MDD. The rats were then given either escin (1, 3, and 10 mg/kg) or fluoxetine (2 mg/kg) on a daily basis. Notably, escin significantly alleviated the depressive behaviors induced by CUMS, as evaluated through a series of behavioral assessments. Moreover, escin administration reduced TNF-α, IL-1β, and IL-6 levels in the hippocampus. It also decreased serum adrenal cortical hormone (ACTH) and corticosterone (CORT) levels while increasing 5-HT and Brain-derived neurotrophic factor (BDNF) levels in the CUMS rats, as measured by the enzyme-linked immunosorbent assay (ELISA). Pathological changes in the hippocampal regions were identified through Nissl staining, and Western blotting was used to quantify the protein levels of BDNF, TrkB, CREB, TLR4, MyD88, and NF-κB. Escin mitigated neuronal injury, elevated TrkB, BDNF, and CREB, and reduced TLR4, MyD88, and NF-κB protein levels in CUMS rats. The data from this study suggest that escin holds the potential for alleviating depression-like symptoms induced by CUMS. This effect may be mediated through the modulation of two signaling pathways, BDNF/TrkB/CREB and TLR4/MyD88/NF-κB.
研究领域:
药理学
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神经科学
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精神病学
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免疫学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
·
IF 7.7
Jiqi Huang,Yifan Su,Qianyu Wang,Mingxiao Feng,Dawei Zhang,Qian Yu,Chunyan Yan
Ganoderma lucidum spores are tiny mature germ cells ejected from the abaxial side of the pileus and were responsible for multiple pharmacological properties. The defatted G. lucidum spores are the byproducts after the extraction of G. lucidum spores oil by supercritical fluid extraction technology, which have not been given sufficient attention. In order to fully utilize the resources of G. lucidum spores, a glucomannan (SGL90–1, 6.4 kDa) was isolated from the defatted G. lucidum spores. SGL90–1 was composed of mannose, glucose, galactose, and fucose in a molar ratio of 23.9:28.7:9.0:1.0. The backbone of SGL90–1 was consisted of →2,4)- α -D-Man p -(1→, →6)- β -D-Man p -(1→, →2,6)- α -D-Man p -(1→, →2)- α -D-Glc p -(1→, and →3,6)- β -D-Glc p -(1 → with seven side chains, and terminated with β -D-Man p -(1→, β -D-Glc p -(1→, α -L-Fuc p -(1→, and β -D-Gal f -(1→. Moreover, SGL90–1 could significantly elevate the phagocytic capability of RAW264.7 macrophages and promote the levels of nitric oxide (NO), tumor necrosis factor- α (TNF- α ), and interlrukin-6 (IL-6) through activating the TLR4/MyD88/NF-κB signaling pathway. Collectively, these findings demonstrated the potential of SGL90–1 as a natural functional food with strong immune-enhancing effect.
研究领域:
真菌学
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免疫学
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药理学
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生物化学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Yiyang Du,Tingxu Yan,Bo Wu,Bosai He,Ying Jia
Ethnopharmacological relevance Increased inflammatory response and disruption of neuroplasticity are important mechanisms in the hypothesis of the pathogenesis of depression. Thus, these two aspects are conducive to the development of treatments for depression. Suanzaoren Decoction (SZRD) is a classic traditional Chinese medicine compound for the treatment of insomnia, which can clinically relieve depression symptoms, but its antidepressant pharmacological mechanism remains to be elucidated. Aim of this study Based on the hypothesis of inflammation and neuroplasticity in depression, this study aimed to investigate the antidepressant effect of SZRD and its specific molecular mechanism through chronic unpredictable mild stress (CUMS) induced SD rat model and lipopolysaccharide (LPS) induced BV2 cell neuroinflammation model. Materials and methods The body weight and behavioral indexes of CUMS model rats treated with orally or without oral SZRD for 4 weeks were detected. Hematoxylin and eosin staining was used to observe brain pathological damage. Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) staining was used to observe neuronal apoptosis. Immunofluorescence, ELISA kit and Western blotting were used to detect the inflammatory index Iba-1 and inflammatory factors, as well as the important inflammatory pathway TLR4/MyD88/NF-κB. Enzyme linked immunosorbent assay (ELISA) and western blotting were used to detect neuroplasticity indexes proteins-brain-derived neurotrophic factor (BDNF), presynaptic membrane protein-synaptophysin (SYP), and postsynaptic protein- 95(PSD95), and the key pathway Wnt/β-catenin. The possible mechanism of SZRD antidepressant was further explored in LPS-induced BV2 cells. Results In vivo and in vitro experiments showed that SZRD treatment significantly reversed the depression-like behaviors in rats, decreased the levels of inflammatory factors and increased the expression levels of BDNF, SYP, PSD95 in depression model rats. Furthermore, SZRD treatment inhibited the activation of TLR4/MyD88/NF-κB and Wnt/β-catenin pathways and reduced the massive nuclear translocation of NF-κB and β-catenin. The addition of NF-κB pathway agonists could partially offset the inhibitory effect of SZRD on the Wnt pathway, and the addition of Wnt pathway agonists could also partially offset the inhibitory effect of SZRD on the TLR4 pathway. Conclusion This study suggestted that SZRD may exert its antidepressant effect by regulating TLR4/MyD88/NF-κB pathway and Wnt/β-catenin pathway in combination.
研究领域:
药理学
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神经科学
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中医
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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