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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2021 · IF 6.953

Immunomodulatory effect of intracellular polysaccharide from mycelia of Agaricus bitorquis (QuéL.) Sacc. Chaidam by TLR4-mediated MyD88 dependent signaling pathway

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 · 真菌学 · 药理学 · 生物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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PHARMACEUTICAL BIOLOGY · 2020 · IF 2.971

Curcumin attenuates renal interstitial fibrosis of obstructive nephropathy by suppressing epithelial-mesenchymal transition through inhibition of the TLR4/NF-кB and PI3K/AKT signalling pathways

Zhaohui Wang,Zhi Chen,Bingsheng Li,Bo Zhang,Yongchao Du,Yuhang Liu,Yao He,Xiang Chen

Context Renal interstitial fibrosis (RIF) is characterized by the accumulation of inflammatory cytokines and epithelial-mesenchymal transition (EMT). Curcumin exerts antifibrogenic, anti-inflammatory and antiproliferative effects.Objective To explore the mechanisms underlying the effects of curcumin on RIF.Materials and methods Eight-week-old male C57BL/6 mice were intragastrically administered curcumin (50 mg/kg/day) for 14 days after undergoing unilateral ureteral obstruction (UUO) operations. Renal function (blood urea nitrogen [BUN] and serum creatinine [Scr]) and inflammatory cytokine levels were tested using colorimetric assays and ELISA, respectively. EMT markers were evaluated through immunohistochemistry, western blotting and qPCR. Transforming growth factor beta 1 (TGF-β1; 10 ng/mL) and lipopolysaccharides (LPS; 100 ng/mL) were used to stimulate EMT and an inflammatory response in human renal proximal tubular epithelial (HK-2) cells, respectively, for further investigation.Results In vivo, curcumin significantly improved the levels of BUN and Scr by 28.7% and 21.3%, respectively. Moreover, curcumin reduced the levels of IL-6, IL-1β and TNF-α by 22.5%, 30.3% and 26.7%, respectively, and suppressed vimentin expression in UUO mice. In vitro, curcumin reduced the expression of vimentin and α-smooth muscle actin in TGF-β1-induced HK-2 cells. In LPS-induced HK-2 cells, curcumin decreased the release of IL-6, IL-1β and TNF-α by 43.4%, 38.1% and 28.3%, respectively. In addition, curcumin reduced the expression of TLR4, p-PI3K, p-AKT, p-NF- κB and p-IκBα in both LPS- and TGF-β1-induced HK-2 cells.Discussion and conclusions Curcumin repressed EMT and the inflammatory response by inhibiting the TLR4/NF-κB and PI3K/AKT pathways, demonstrating its potential utility in RIF treatment.

CAS / MDL: 458-37-7
研究领域: 肾病学 · 药理学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BIOMEDICINE & PHARMACOTHERAPY · 2023 · IF 7.5

Eudragit-coated chitosan-tripterygium glycoside conjugate microspheres alleviate DSS-induced experimental colitis by inhibiting the TLR4/NF-κB signaling pathway

Guohui Xue,Huifang Xiong,Shixiu Wang,Yingjun Fu,Yong Xie

Objective Tripterygium glycoside (TG) is a fat-soluble extract of Tripterygium wilfordii, with anti-inflammatory properties associated with TLR signaling pathways. This study constructed a targeted delivery system for experimental colitis, namely, eudragit (EuL)-coated chitosan (Ch)-TG conjugate microspheres (Ch-TG-MS/EuL), and evaluated its therapeutic efficacy and underlying mechanisms. Methods Ch-TG-MS was fabricated using emulsification cross-linking technique and then coated with EuL to create Ch-TG-MS/EuL. Drug release properties were assessed using a dialysis model. Additionally, the therapeutic benefits of Ch-TG-MS/EuL on colonic inflammation and its specific effect on TLR4/NF-κB signaling in intestinal mucosa were evaluated in vivo using a DSS-induced murine colitis model. Results The Ch-TG-MS/EuL microspheres appeared as yellow powders with a slightly enlarged shape, rough surface, and adhesions. The Ch-TG-MS/EuL formulations also exhibited high entrapment efficiency and drug loading rate. High-performance liquid chromatography revealed that Ch-TG-MS/EuL exhibited a less intense peak than free TG, confirming that the drug is contained within the formulation. Free TG displayed explosive release within the first 5 h of administration, while Ch-TG-MS/EuL prevented the pre-mature release of TG and exhibited controllable release up to 24 h. In vivo, noticeable amelioration of intestinal mucosal tissue destruction was achieved with Ch-TG-MS/EuL compared to free TG. Additionally, immunohistochemical and western blotting results revealed that Ch-TG-MS/EuL markedly down-regulated the expression of intestinal mucosal TLR4, MyD88, and NF-κB p65. Hence, Ch-TG-MS/EuL may ameliorate the colon inflammatory response by inhibiting the hyperactivation of TLR4/NF-κB signaling. Conclusion Novel Ch-TG-MS/EuL preparation may represent a colonic delivery system for UC therapeutics by inhibiting TLR4/NF-κB hyperactivation. Data availability All experimental data supporting the conclusions of this study are available from the corresponding author on reasonable request.

研究领域: 药学 · 药理学 · 免疫学 · 药物递送系统 · 炎症性肠病
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF ANIMAL PHYSIOLOGY AND ANIMAL NUTRITION · 2024 · IF 2.2

Asiatic Acid Alleviates LPS-Induced Pyroptosis and Endoplasmic Reticulum Stress-Mediated Apoptosis via Inhibiting the HMGB1/TLR4/NF-κB Pathway in Broiler Hepatocytes

Wenyue Qiu,Wenxin Jiang,Yiman Su,Hui Huang,Jiali Ye,Rongmei Wang,Zhaoxin Tang,Rongsheng Su

Lipopolysaccharides (LPS) is the major compoent of Gram-negative bacteria and an important factor in inducing inflammation, which usually leads to multiple organ failure in broilers, seriously affecting the growth performance of broilers and hindering the development of poultry farming. Under the policy of prohibiting antibiotics in feed, it has become more urgent to find natural drugs to prevent liver damage caused by LPS in broilers. Asiatic acid (AA) is a pentacyclic triterpene that has been proven to have anti-inflammatory and antioxidant effects. However, the protective effects of AA in LPS-induced liver damage in broilers still need to be clarified. This study aims to explore the complete mechanism of AA against LPS-induced acute liver injury (ALI) in broilers. A total of 60 broilers (1 day old) were randomly divided into the control group, LPS group, LPS+AA (15, 30 and 60 mg/kg) group and control+AA (60 mg/kg) group. At 16, 18 and 20 days of age, the broilers were attacked with LPS (0.5 mg/kg) to construct liver injury model. H&E staining assessed liver pathological changes. The mRNA and protein expression levels related to the HMGB1/TLR4/NF-κB pathway, pyroptosis, and ERS-mediated apoptosis in the liver tissue were detected. Our results founded that intraperitoneal injection of LPS in broilers increased the activities of AST and ALT, as well as raising the related gene and protein expression of the HMGB1/TLR4/NF-κB pathway, pyroptosis, and ERS-mediated apoptosis. Interestingly, AA improved LPS-induced liver damage and decreased the activities of AST and ALT in broilers. Additionally, AA mitigated LPS-induced ALI by reducing the mRNA levels and protein expressions of the HMGB1/TLR4/NF-κB pathway, pyroptosis and ERS-mediated apoptosis. In conclusion, the present study investigated that AA mitigated LPS-induced ALI in broilers by reducing pyroptosis and ERS-mediated apoptosis via inhibition of the HMGB1/TLR4/NF-κB pathway. Therefore, AA may serve as a potential feed additive for the prevention of LPS-induced ALI in broilers.

CAS / MDL: 506-32-1
研究领域: 兽医学 · 药理学 · 免疫学 · 动物科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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PHYTOMEDICINE · 2024 · IF 6.7

ESL Attenuates BLM-induced IPF in Mice: Dual Mediation of the TLR4/NF-κB and TGF-β1/PI3K/Akt/FOXO3a Pathways

Canchao Jia,Minjuan Yang,Guanlin Xiao,Zhihao Zeng,Lingjie Li,Yangxue Li,Jieyi Jiang,Aili Xu,Jinyan Qiu,Ruiyin Tang,Dongmei Li,Dezheng Jia,Canhui Xie,Guangying Wu,Dake Cai,Xiaoli Bi

Backgrounds Idiopathic pulmonary fibrosis (IPF) is a persistent and advanced pulmonary ailment. The roles of innate immunity and adaptive immunity are pivotal in the evolution of IPF. An ill-adjusted interaction between epithelial cells and immune cells is responsible for initiating the epithelial–mesenchymal transition (EMT) process and sustaining chronic inflammation, thereby fostering fibrosis progression. The intricacy of IPF pathogenesis has hindered the availability of efficacious agents. Elephantopus scaber Linn. (ESL) is a canonical Chinese medicine with significant immunoregulatory effects, and its aqueous extract has been proven to attenuate IPF symptoms in bleomycin (BLM)-induced mice. However, the underlying mechanism through which ESL relieves IPF remains unclear. Aim To validate whether ESL reverses IPF by mediating the immune response and EMT. Methods : Ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) and UPLC were used to identify the components and determine the concentrations of the specific compounds in the ESL. Network pharmacology and molecular docking were applied to predict the potential mechanism underlying the anti-IPF effect of ESL. BLM-induced IPF mice were used to validate the anti-IPF effect of ESL, and lung tissue was collected to test putative pathways involved in inflammation and EMT via immunohistochemistry (ICH), real-time quantitative polymerase chain reaction (RT–qPCR) and Western blotting. Results Sixty-one compounds were identified, and thirteen main ingredients were quantified in the ESL. In silico experiments predicted that the IPF-mediated reversal of adverse effects by ESL would be related to interruption of the Toll-like receptor 4 (TLR4)/nuclear factor-k-gene binding (NF- ĸ B) inflammatory pathway and the transforming growth factor-beta l (TGF-β1)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/forkhead box O3 (FOXO3a) fibrosis pathway. In vivo experiments showed that ESL alleviates BLM-induced lung inflammation and fibrosis by reducing neutrophil aggregation and fibroblast foci, similar to the effects of the positive control drug pirfenidone (PFD). ESL markedly inhibited the transcription of TNF-α, IL-1 β, and IL-6, which are downstream genes of the NF-κB signaling pathway. Furthermore, the protein levels of TLR4 and p-NF- κ B were correspondingly inhibited in response to ESL treatment. Additionally, ESL reverses BLM-induced changes in the expression of EMT-related biological characteristic indicators (collagen I [COLIA1], E-cadherin, and alpha smooth muscle actin [ α -SMA]) at the messenger ribonucleic acid (mRNA) level and markedly inhibits the expression of EMT-related upstream proteins (TGF- β 1, p-PI3K, p-Akt, and p-FOXO3a). Conclusion Our research suggested that ESL attenuates BLM-induced IPF through mediating the EMT process via the TGF-β1/PI3K/Akt/FOXO3a signaling pathway and inhibiting inflammation through the TLR4/NF-κB signaling pathway, highlighting that ESL can serve as an immunoregulator for relieving the abnormal immune response and reversing the EMT in IPF.

CAS / MDL: 53179-13-8
研究领域: 药理学 · 免疫学 · 呼吸医学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Food & Function · 2023 ·Vol. 14 ·期 14 ·6678-6689 · IF 6.1

Apple peel polyphenol alleviates antibiotic-induced intestinal dysbiosis by modulating tight junction proteins, the TLR4/NF-κB pathway and intestinal flora

Ziqian He,Na Deng,Bisheng Zheng,Yingjie Gu,Jian Chen,Tong Li,Rui Hai Liu,Ling Yuan,Wenzhi Li

The intestine and its flora have established a strong link with each other and co-evolved to become a micro-ecological system that plays an important role in human health. Plant polyphenols have attracted a great deal of attention as potential interventions to regulate the intestinal microecology. In this study, we investigated the effects of apple peel polyphenol (APP) on the intestinal ecology by establishing an intestinal ecological dysregulation model using lincomycin hydrochloride-induced Balb/c mice. The results showed that APP enhanced the mechanical barrier function of mice by upregulating the expression of the tight junction proteins at the transcriptional and translational levels. In terms of the immune barrier, APP downregulated the protein and mRNA expression of TLR4 and NF-κB. As for the biological barrier, APP promoted the growth of beneficial bacteria as well as increasing the diversity of intestinal flora. In addition, APP treatment significantly increased the contents of short-chain fatty acids in mice. In conclusion, APP can alleviate intestinal inflammation and epithelial damage as well as inducing potentially beneficial changes in the intestinal microbiota, which helps to reveal the potential mechanisms of host–microbial interactions and polyphenol regulation of intestinal ecology.

研究领域: 药理学 · 微生物学 · 免疫学 · 营养学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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RESEARCH IN VETERINARY SCIENCE · 2022 · IF 2.554

Dimethyl itaconic acid improves viability and steroidogenesis and suppresses cytokine production in LPS-treated bovine ovarian granulosa cells by regulating TLR4/nfkβ, NLRP3, JNK signaling pathways

Mohammad Reza Tabandeh,Sadegh Jozaie,Zohre Ghotbedin,Saad Gorani

The stimulation of pro-inflammatory pathways by lipopolysaccharide (LPS) endotoxins is a key player in the pathological mechanisms involved in the development of ovarian dysfunctions in dairy cows. Dimethyl itaconate acid (DMIA) is a novel immunometabolite that has recently emerged as a regulator of inflammatory responses in mammals. The present study was undertaken to determine the anti-inflammatory effects of DMIA on bovine granulosa cells (GCs) and to explore its possible molecular mechanisms. The ovarian GCs were obtained from small follicles of dairy cows. The GCs were stimulated with 1 μg/mL LPS for 4 h and then treated with 250 μM DMIA for 12 h. The viability, production of pro-inflammatory cytokines, activation of inflammatory signaling pathways and synthesis of steroid hormones were evaluated in treated GCs. Our results showed that DMIA reduced the inflammatory responses in LPS stimulated GCs by down-regulating the expression of nod-like receptor family pyrin domain containing 3 inflammasome , and toll-like receptor 4 and by suppressing the phosphorylation of nuclear factor kappa B and c-Jun N-terminal kinase proteins . DMIA also attenuated the increased production of pro inflammatory cytokines (interleukin 6, tumor necrosis factor α and interleukin 1 beta ( p  < 0.01) in LPS stimulated GCs. Exposure of LPS stimulated GCs to DMIA improved the impaired steroidogenesis by up-regulation of steroid synthesis genes including 3-beta-hydroxysteroid dehydrogenase, follicle stimulating hormone receptor and cytochrome P450 aromatase . The results of the present study highlight the potential role of itaconic acid for the improvement of GCs inflammation in dairy cows with ovarian dysfunctions.

研究领域: 动物科学 · 免疫学 · 生殖生物学
✓ 已验证 DOI PubMed 高影响因子
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NEUROPHARMACOLOGY · 2025 · IF 4.6

Baicalin ameliorates neuroinflammation by targeting TLR4/MD2 complex on microglia via PI3K/AKT/NF-κB signaling pathway

Yufang Lu,Ruiying Zhou,Ruyi Zhu,Xue Wu,Jin Liu,Yue Ma,Xin Zhang,Yaling Zhang,Luting Yang,Yanhua Li,Yuan Zhang,Yaping Yan,Qian Zhang

This study aims to elucidate the target and mechanism of baicalin, a clinically utilized drug, in the treatment of neuroinflammatory diseases. Neuroinflammation, characterized by the activation of glial cells and the release of various pro-inflammatory cytokines, plays a critical role in the pathogenesis of various diseases, including spinal cord injury (SCI). The remission of such diseases is significantly dependent on the improvement of inflammatory microenvironment. Toll-like receptor 4/myeloid differentiation protein 2 (TLR4/MD2) complex plays an important role in pathogen recognition and innate immune activation. baicalin, a natural flavonoid, is renowned for its potent anti-inflammatory property. In this study, we discovered that baicalin significantly reduced the activation of glial cells and the levels of pro-inflammatory cytokines at the lesion site of SCI mice, thereby mitigating demyelination and neuronal damage. By directly occupying the active pocket of TLR4/MD2 complex on microglia, baicalin inhibited PI3K/AKT/NF-κB pathway, thereby exerting its anti-inflammatory effect. These findings were corroborated in mice induced by lipopolysaccharide, a TLR4 agonist. Furthermore, baicalin indirectly altered phenotype of astrocytes by reducing secretion of TNF-α, IL-1α, and C1q levels from microglia. Our work demonstrated that baicalin effectively alleviated neuroinflammation by directly targeting microglia and indirectly modulating astrocytes phenotype. As a natural flavonoid, baicalin holds significant potential as a therapeutic candidate for diseases characterized by neuroinflammation.

CAS / MDL: 21967-41-9
研究领域: 神经科学 · 药理学 · 免疫学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF ANIMAL PHYSIOLOGY AND ANIMAL NUTRITION · 2023 · IF 2.7

Tert-butylhydroquinone attenuates LPS-induced pyroptosis of IPEC-J2 cells via downregulating HMGB1/TLR4/NF-κB axis

Wenyue Qiu,Xinting Zhang,Xiaoyue Pang,Jianjia Huang,Shuilian Zhou,Ruixia Wu,Rongmei Wang,Zhaoxin Tang,Rongsheng Su

Inflammatory response induced by biological stress usually occurs in weaning piglets, it reduces the production performance of piglets and even causes death. Tert-butylhydroquinone (TBHQ) is a food additive that has the effect of anti-inflammation and anti-oxidation. However, there are few reports related to the protective mechanisms of TBHQ on lipopolysaccharide (LPS) induced injury in intestinal porcine epithelial (IPEC-J2) cells. Quantitative real-time polymerase chain reaction and western blot analysis, respectively, detected the mRNA levels and protein expressions related to pyroptosis, tight junction (TJ) protein and high-mobility group box 1/toll-like receptor 4/nuclear factor kappa-B (HMGB1/TLR4/NF-κB) axis. Localisation and expression of NOD-like receptor pyrin domain containing 3 (NLRP3), HMGB1 and P-NF-κB proteins detected by immunofluorescence. The results showed that TBHQ (12.5 and 25 μM) can increase cell activity and reduce intracellular lactate dehydrogenase (LDH) levels in a dose-dependent manner. LPS significantly decreases cell viability and increases the LDH level. However, pretreatment with TBHQ evidently increases cell viability and decreases the LDH level of IPEC-J2 cells. In addition, treatment with LPS decreased the mRNA level and protein expression of zonula occludens-1, occludin and claudin-1, and increased the mRNA level and protein expression of pyroptosis and HMGB1/TLR4/NF-κB axis. Interestingly, pretreatment with TBHQ increased the TJ protein expressions as well as decreased the mRNA level and protein expressions of pyroptosis and HMGB1/TLR4/NF-κB axis. Moreover, the results of immunofluorescence showed that TBHQ significantly reduced the expression of NLRP3, HMGB1 and P-NF-κB in LPS-induced injury of IPEC-J2 cells. Therefore, we come to the conclusion that TBHQ attenuates LPS-induced pyroptosis in IPEC-J2 cells through downregulation of the HMGB1/TLR4/NF-κB axis, TBHQ may become a potential feed additive for preventing inflammatory diarrhoea in piglets.

CAS / MDL: 1948-33-0
研究领域: 兽医学 · 细胞生物学 · 免疫学 · 动物营养学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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PHYTOTHERAPY RESEARCH · 2023 · IF 7.2

Stigmasterol regulates microglial M1/M2 polarization via the TLR4/NF-κB pathway to alleviate neuropathic pain

Waimei Si,Xin Li,Bei Jing,Shiquan Chang,Yachun Zheng,Zhenni Chen,Guoping Zhao,Di Zhang

(Switching from the microglial M1 phenotype to the M2 phenotype is a promising therapeutic strategy for neuropathic pain (NP). This study aimed to investigate the potential use of stigmasterol for treating NP. In animal experiments, 32 male Sprague–Dawley rats were randomly divided into the sham operation group, chronic constriction injury (CCI) group, CCI + ibuprofen group, and CCI + stigmasterol group. We performed behavioral tests, enzyme-linked immunosorbent assay, hematoxylin-esoin staining (H&E) staining and immunohistochemistry, immunofluorescence, and Western blotting. In cell experiments, we performed flow cytometry, immunofluorescence, Western blotting, and qRT-PCR. Stigmasterol reduced thermal and mechanical hyperalgesia and serum IL-1β and IL-8 levels and increased serum IL-4 and TGF-β levels in CCI rats. Stigmasterol reduced IL-1β, COX-2, and TLR4 expression in the right sciatic nerve and IL-1β expression in the spinal cord. Stigmasterol reduced the expression of Iba-1, TLR4, MyD88, pNF-κB, pP38 MAPK, pJNK, pERK, COX-2, IL-1β, and CD32 in the spinal cord of CCI rats while increasing the expression of IL-10 and CD206. Stigmasterol decreased M1 polarization markers and increased M2 polarization markers in lipopolysaccharide (LPS)-induced microglia and decreased the expression of Iba-1, TLR4, MyD88, pNF-κB, pP38 MAPK, pJNK, pERK, iNOS, COX-2, and IL-1β in LPS-treated microglia while increasing the expression of Arg-1 and IL-10. Stigmasterol regulates microglial M1/M2 polarization via the TLR4/NF-κB pathway to alleviate NP.

CAS / MDL: 749886-87-1
研究领域: 药理学 · 神经科学 · 免疫学 · 疼痛研究
✓ 已验证 产品关联 DOI PubMed 高影响因子
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EUROPEAN JOURNAL OF PHARMACOLOGY · 2023 · IF 5

Astragalus polysaccharide attenuates bleomycin-induced pulmonary fibrosis by inhibiting TLR4/ NF-κB signaling pathway and regulating gut microbiota

Yi Wei,Ming Qi,Chao Liu,Lujia Li

Purpose Astragalus polysaccharide (APS) is a naturally-occurring compound derived from Astragalus membranaceus with anti-inflammatory and antioxidant properties. However, its beneficial effects and mechanisms on pulmonary fibrosis are unknown. Gut microbiota impact lung diseases via the gut-lung axis. Herein, we investigated APS progression to intervene in pulmonary fibrosis via the toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) signaling pathway and gut microbiota homeostasis regulation. Methods We used bleomycin (BLM) to construct an idiopathic pulmonary fibrosis (IPF) mouse model and assessed the pathology with Masson, hematoxylin-eosin (HE), and Sirius red staining . Enzyme-linked immunosorbent assay (ELISA) kits were employed to evaluate the inflammatory cytokine levels. Western blot evaluated TLR4/NF-κB signaling pathway expression. TUNEL staining to detect apoptosis. Mice feces samples were gathered for 16S rRNA gene sequencing. Results Our findings revealed that APS ameliorated the extent of damage and collagen deposition in lung tissues, reduced inflammatory cytokines TNF-α, IL-6, and IL-1β levels, and decreased apoptosis. APS might attenuate the inflammatory response through TLR4/NF-κB signaling pathway inhibition. Meanwhile, the IPF mice model exhibited dysregulation of gut microbiota, and these changes were restored after APS intervention. APS may increase the proportion of probiotics , decrease that of harmful bacteria, and balance the gut microbiota via regulating metabolic pathways. Conclusion APS ameliorated lung tissue injury in the IPF mice model, inhibited TLR4/NF-κB signaling pathway, suppressed inflammatory cytokines activation, and reduced apoptosis. Moreover, APS regulated the metabolism of gut microbiota besides beneficial bacteria content elevation.

CAS / MDL: 7727-54-0
研究领域: 药理学 · 免疫学 · 肺科学 · 微生物学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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NEUROREPORT · 2024 · IF 1.6

Electroacupuncture improves the learning and memory abilities of rats with PSCI by attenuating the TLR4/NF-κB/NLRP3 signaling pathway on the hippocampal microglia

Bian Jing,Liu Chunxu,Li Xiang,Qin Xiaoye,Wang Feng,Xuan Lina,Zhang Weimin

This study aims to investigate how electroacupuncture regulates the learning and memory abilities of poststroke cognitive impairment (PSCI) rats through the TLR4/NF-κB/NLRP3 signaling pathway on the hippocampal microglia. Thirty male rats were randomly divided into three groups: sham surgery group, PSCI model group, and electroacupuncture group, with 10 rats in each group. Middle cerebral artery occlusion was used to establish the PSCI model. The Zea Longa method was used to score the rats’ neurological function. Electroacupuncture was utilized for 21 days to improve PSCI. The learning and memory abilities of rats were tested using the Morris water maze. Hematoxylin–eosin staining and immunofluorescence were used to find the hippocampus’ pathological changes. The concentration of interleukin-1β, interleukin-6, tumor necrosis factor-α, and interleukin-18 were detected by ELISA. The mRNA expression levels of associated inflammatory corpuscles were measured by quantitative real-time PCR. The protein expression levels of TLR4, MyD88, NF-κB, and NLRP3 were measured using western blotting. Electroacupuncture improved not only the learning and memory abilities of PSCI rats but also hippocampal morphology. Electroacupuncture inhibited the activation of microglia and the TLR4/NF-κB/NLRP3 signaling pathway. Electroacupuncture also reduced proinflammatory factors and restrained the mRNA levels of NLRP3-associated inflammatory cytokines. Its mechanism was related to inhibiting the expression of the TLR4/NF-κB/NLRP3 signaling pathway, attenuating the release of inflammatory factors, and regulating the activation of hippocampal microglia in the brain.

研究领域: 神经科学 · 针灸 · 认知障碍 · 炎症
✓ 已验证 DOI PubMed 高影响因子
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