EUROPEAN JOURNAL OF PHARMACOLOGY
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2024
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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
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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
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2022
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IF 5.895
Xue-Yan Dai,Shi-Yong Zhu,Jian Chen,Mu-Zi Li,Milton Talukder,Jin-Long Li
Lycopene (Lyc) has anti-inflammatory and antioxidant biological functions. Di-2-ethylhexyl phthalate (DEHP) is an extremely harmful and persistent environmental pollutant and is a threat to animal health. The toll-like receptor (TLR)/MyD88 pathway is an important pathway in the inflammatory response. To illustrate the potential antagonistic action of Lyc against DEHP by the TLR/MyD88 pathway, 140 ICR mice were randomly assigned groups and continuously gavaged with corn oil, distilled water, different DEHP concentrations (500 or 1000 mg/kg BW/day), and/or Lyc (5 mg/kg BW/day) for 28 days. The data show that Lyc effectively attenuates the DEHP-induced activation of the TLR/MyD88 pathway, the upregulation of JNK expression, the content of IL-6 and TNF-α, and the downregulation of the IL-10 content, which eventually inhibit the inflammatory response and mitochondrial injuries. These findings underline the TLR/MyD88 pathway as a potential therapeutic target in DEHP and Lyc as a new therapeutic method to inhibit DEHP toxicity.
研究领域:
毒理学
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免疫学
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药理学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2024
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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
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
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2023
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IF 4.7
Zhihua Hao,Qingyu Lu,Yanyan Zhou,Yanting Liang,Yun Gao,Huanyan Ma,Yusong Xu,Huabing Wang
The widespread use of pesticides hampers the immune system of non-target organisms, however, there is a lack of common biomarkers to detect such effects. Myeloid differentiation primary response factor 88 (MyD88) is a crucial junction protein in the Toll-like receptor signaling pathway , which plays an important role in the inflammatory response. In this study, we investigated MyD88 as a potential biomarker for pesticide-induced stress. Phylogenetic analysis revealed that MyD88 was a conserved protein in the evolution of vertebrates and invertebrates. MyD88s usually have death domain (DD) and Toll/interleukin-1 receptor (TIR) domain. Bombyx mori ( B. mori ) is an important economic insect that is sensitive to toxic substances. We found microbial pesticides enhanced the expression level of MyD88 in B. mori . Transcriptome analysis demonstrated that MyD88 expression level was increased in the fatbody after dinotefuran exposure, a third-generation neonicotinoid pesticide. Moreover, the expression of MyD88 was upregulated in fatbody and midgut by imidacloprid , a first-generation neonicotinoid pesticide. Additionally, insect growth regulator (IGR) pesticides, such as methoprene and fenoxycarb , could induce MyD88 expression in the fatbody of B. mori . These results indicated that MyD88 is a potential biomarker for pesticide-induced stress in B. mori . This study provides novel insights into screening common biomarkers for multiple pesticide stresses and important implications for the development of more sustainable pest management strategies.
研究领域:
昆虫学
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毒理学
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分子生物学
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环境科学
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产品关联
DOI
PubMed
高影响因子
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
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2021
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IF 3.636
Feng-Ying Gao,Xin Zhou,Mai-Xin Lu,Miao Wang,Zhi-Gang Liu,Jian-Meng Cao,Xiao-Li Ke,Meng-Meng Yi,Deng-Gao Qiu
Toll-like receptors (TLRs) play a critical role in the innate immune response of fish. In this study, we isolated the cDNA sequence of Nile tilapia TLR1 ( On TLR1). The deduced OnTLR1 protein contains a signal peptide , 7 leucine-rich repeats (LRRs), a C-terminal LRR (LRR-CT), a transmembrane region and a highly conserved TIR domain. In healthy Nile tilapia, the On TLR1 transcript was broadly expressed in all examined tissues, with the highest expression levels in the spleen . After infection with Streptococcus agalactiae , the On TLR1 transcripts were upregulated in the gill and kidney. After stimulation with polyinosinic-polycytidylic acid (poly(I:C)), the expression levels of On TLR1 were significantly downregulated in the intestine , whereas On TLR1 transcripts were significantly upregulated in the kidney. After challenge with lipopolysaccharide (LPS), the expression levels of On TLR1 were significantly upregulated in the spleen and kidney. The subcellular localization showed that On TLR1 was expressed in the cytoplasm. TLR1 significantly increased MyD88-dependent NF-κB activity. However, the results of a pull-down assay showed that On TLR1 did not interact with MyD88 or TIRAP. Binding assays revealed the specificity of OnTLR1 for pathogen-associated molecular patterns (PAMPs) and bacteria that included S. agalactiae , Aeromonas hydrophila and poly(I:C) and LPS. Taken together, these findings suggest that OnTLR1, as a pattern recognition receptor (PRR), might play an important role in the immune response to pathogen invasion.
研究领域:
免疫学
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分子生物学
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鱼类生物学
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病原识别
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2021
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IF 6.953
Ximeng Lin,Wenxia Li,Hywel Yuen,Michael Yuen,Qiang Peng
Agaricus bitorquis (QuéL.) Sacc. Chaidam is a valuable edible fungus in Qinghai-Tibet plateau and ABSP is a novel intracellular polysaccharide from its mycelia. GC and NMR analysis determined ABSP is galactoglucomannan-like polysaccharide that may have immunomodulatory effect. This study used RAW264.7 as model cell to determine immunomodulatory effect of ABSP. After ABSP treatment, viability and phagocytic ability promoted, and NO, ROS, TNF-α levels also raised which proved ABSP had immune regulation to RAW264.7. WB and qRT-PCR determined the key proteins and genes expression of TLR4, MyD88, TRAF-6 and NF-κB significantly increased while protein and gene expression of TRAM had no significant increase. Also, TNF-α level extremely decreased by adding inhibitors of TLR4 and MyD88 which confirmed ABSP could immunologically regulate RAW264.7 byTLR4-MyD88 dependent pathway. This study would provide theoretical basis for further study on ABSP and be helpful for development of beneficial functionally foods and exploitation of this resource.
研究领域:
免疫学
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真菌学
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药理学
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生物化学
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产品关联
DOI
PubMed
高影响因子
NUTRITION
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2023
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IF 4.4
Jiabao Tang,Xiaohua Li,Wei Li,Chun Cao
Objective Enteral nutrition (EN) is the key therapy in septic patients. Different formulas of EN have various effects on gastrointestinal sepsis. Therefore, we investigated the effects of EN supplemented with octanoic acid (OA) on lipopolysaccharide (LPS) induced intestinal injury and explored the potential mechanism. Methods First, to investigate the effects of EN supplemented with OA on LPS-induced intestinal injury, rats were randomly divided into four groups: the sham, LPS, LPS + EN, and LPS + EN + OA groups. Then, to explore whether EN supplemented with OA can prevent LPS-induced intestinal injury via the PPARγ/STAT-1/MyD88 pathway, rats were randomly divided into five groups: the sham, LPS, LPS + EN + OA, LPS + EN + OA +SR202, and LPS + pioglitazone groups. All rats received nutritional support for three days. We examined the serum levels of inflammatory factors, pathological changes, goblet cell density, intestinal tight junction protein expression, and the PPARγ/STAT-1/MyD88 pathway in the ileum and colon. In addition, the effect of OA on intestinal epithelium injury was also explored in vitro. Results EN supplemented with OA significantly decreased the serum levels of inflammatory factors and prevented intestinal barrier dysfunction compared with EN alone (P < 0.05). Inhibiting the PPARγ/STAT-1/MyD88 pathway exacerbated effects of EN supplemented with OA on intestinal injury (P < 0.05). Activation of the PPARγ/STAT-1/MyD88 pathway prevented intestinal injury (P < 0.05). OA also exerted a similar effect on intestinal epithelium injury in vitro. Conclusion EN supplemented with OA prevents LPS-induced intestinal injury via the PPARγ/STAT-1/MyD88 pathway.
研究领域:
营养学
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胃肠病学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2023
·
IF 10.8
Hongbing Liu,Muse Ji,Yuti Bi,Peifu Xiao,Jiansong Zhao,Jingxin Gou,Tian Yin,Haibing He,Huaiwei Ding,Xing Tang,Yu Zhang
Excessive reactive oxygen species (ROS) and stressed inflammatory response are major characteristics of ulcerative colitis , which cause disease progression and aggravation. Herein, a novel mesoporous cerium oxide nanozymes (MCN) was designed and then loaded with Myeloid differentiation factor-88 (MyD88) inhibitor for synergistic treatment of colitis by scavenging ROS and regulating inflammation. This innovative MCN with average particle size of 200.7 nm , specific surface area of 119.78 m 2 /g and mesopores of 4.47 nm not only exhibited excellent SOD-like and CAT-like activities to scavenge ROS but also could act as a carrier to load MyD88 inhibitor, TJ-M2010–5, (abbreviated as TJ-5) into their mesopores, achieving the effect of ‘two birds with one stone’. Besides, the modification of dextran sulfate sodium (TJ-5/MCN/DSS) increased the internalization of nanozymes into activated macrophages and enhanced in vitro anti-inflammatory ability. To enhance colon targeting, we coated TJ-5/MCN/DSS with the enteric material Eudragit S100 , preventing premature release or absorption of the drug in the gastrointestinal tract after oral administration. The results demonstrated that TJ-5/MCN/DSS/Eudragit not only achieved delayed drug release and improved colon targeting but also exhibited optimal therapeutic efficacy in colitis mice. Mechanistically, the MCN-mediated ROS scavenging and TJ-5-mediated MyD88 blockade synergistically inhibited the NF-κB signaling pathway, thereby reducing the inflammatory response. Importantly, TJ-5/MCN/DSS/Eudragit did not induce systemic toxicity. In conclusion, our work not only presents a novel carrier capable of scavenging ROS but also provides proof of concept for the synergistic treatment of colitis using this carrier in combination with MyD88 inhibitors. This study proposes a safe and efficient strategy for targeting ROS-associated inflammation.
研究领域:
药学
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纳米技术
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炎症性肠病
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药物递送系统
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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
MICROBIAL PATHOGENESIS
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2023
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IF 3.8
Shun Wang,Xiaodi Jin,Hao Chen,Mingdong Han,Jiaxin Bao,Dong Niu,Yikang Wang,Rui Li,Zhiyong Wu,Jichang Li
Chronic respiratory disease (CRD) caused by Mycoplasma gallisepticum (MG) in chickens leads to enormous economic damage to the poultry industry yearly. The active components and mechanism of action of the traditional herbal remedy Ephedra houttuynia powder (EHP), which had been approved for clinical treatment against MG infection in China, remain unknown. In this study, the active components of EHP against MG were screened using a network pharmacological method, additionally, we studied the mechanism of action of the screened results (quercetin (QUE)). The findings demonstrated that QUE was an essential element of EHP against MG infection, effectively attenuating MG-induced oxidative stress and activation of the TLR2/MyD88/NF-κB pathway. Following QUE therapy, IL-1, IL-6, and TNF-α content and expression were downregulated, whereas IL-4 and IL-10 expression were upregulated, eventually suppressing the inflammatory response both in vitro and in vivo . Together, this study presents a strong rationale for using QUE as a therapeutic strategy to inhibit MG infection-induced inflammatory damage and oxidative stress.
研究领域:
兽医学
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药理学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
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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
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DOI
PubMed
高影响因子
Bioengineered
·
2022
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IF 6.832
Kenan Zheng,Baojiang Lv,Lulu Wu,Chen Wang,Haoyou Xu,Xiaojun Li,Zhibing Wu,Yuanqi Zhao,Zequan Zheng
Experimental autoimmune encephalomyelitis (EAE) is characterized by demyelination of the central nervous system. Emodin is an anthraquinone derivative with comprehensive anti-inflammatory, anti-cancer, and immunomodulatory effects and is widely used in the treatment of inflammatory, tumor, and immune system diseases. However, none of the clinical or experimental studies have explored the therapeutic efficacy of emodin in EAE/multiple sclerosis (MS). Thus, we evaluated the protective effect of emodin on EAE mediated via inhibition of microglia activation and inflammation. Wild-type mice were randomly divided into the normal control, EAE, low-dose emodin, and high-dose emodin groups. Clinical scores and pathological changes were assessed 21 days after immunization. The network pharmacology approach was used to elucidate the underlying mechanisms by using an online database. Molecular docking, polymerase-chain reaction tests, western blotting, and immunofluorescence were performed to verify the network pharmacology results. An in vivo experiment showed that high-dose emodin ameliorated clinical symptoms, inflammatory cell infiltration, and myelination. Pharmacological network analysis showed AKT1 was the main target and that emodin played a key role in MS treatment mainly via the PI3K–Akt pathway. Molecular docking showed that emodin bound well with PI3K, AKT1, and NFKB1. Emodin decreased the expression of phosphorylated(p)-PI3K, p-Akt, NF-κB, and myeloid differentiation factor 88 and the levels of markers (CD86 and CD206) in M1- and M2-phenotype microglia in EAE. Thus, the emodin inhibited microglial activation and exhibited anti-inflammatory and neuroprotective effects against EAE via the Myd88/PI3K/Akt/NF-κB signalling pathway. In conclusion, emodin has a promising role in EAE/MS treatment, warranting further detailed studies.
研究领域:
神经科学
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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
危险品化学品经营许可证（带存储）