Frontiers in Pharmacology
·
2020
·
IF 4.225
Wei Aiwu,Xiao Huidongzi,Xu Guangli,Yu Xile,Guo Jingjing,Jing Zhuqing,Shi Shaoqi,Song Yanli
Anticardiolipin antibody (aCL), an important characterization of antiphospholipid syndrome, shows an intense association with vascular endothelial injury. Hyperoside is a flavonoid extracted from medicinal plants traditionally used in Chinese medicines, displaying anti-inflammatory, anti-cancer, and anti-oxidative properties in various diseases. Recent studies have shifted the focus on the protective effects of hyperoside on vascular endothelial injury. However, little is known about the mechanisms involved. In the present study, we investigated the effect of hyperoside on aCL-induced injury of human umbilical vein endothelial cells (HUVECs) in vitro. Our data illustrated that aCL induced HUVEC injury via inhibiting autophagy. Hyperoside reduced aCL-induced secretion of proinflammatory cytokines IL-1β and IL-8 and endothelial adhesion cytokines TF, ICAM1, and VCAM1 in HUVECs. Additionally, hyperoside activated autophagy and suppressed the mTOR/S6K and TLR4/Myd88/NF-κB signaling transduction pathways in aCL-induced HUVECs. To the best of our knowledge, this is the first study to investigate the effect of hyperoside on aCL-induced injury, as well as offer insights into the involved mechanisms, which is of great significance for the treatment of antiphospholipid syndrome.
研究领域:
免疫学
·
药理学
·
细胞生物学
·
血管生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Donglin Sui,Mingxin Li,Chunqing Ai,Shugang Li,Hong Chang,Yixuan Li,Shouhao Zhao,Huan Li,Xiaomeng Ren
This study aimed to investigate the therapeutic efficacy of Larimichthys Crocea Isinglass polysaccharide (CIP) in ameliorating DSS-induced colitis. CIP, a complex polysaccharide composed of six monosaccharides with a molecular weight of 3.97 kDa. Specifically, CIP treatment mitigated weight loss and histopathological damage in the colon, increased colon length, and by inhibiting the TLR4/MyD88/NF-κB pathway significantly downregulated the secretion levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β, while simultaneously upregulating the anti-inflammatory cytokine IL-10 and inhibition of the oxidative stress-related enzyme inducible nitric oxide synthase (iNOS). Additionally, CIP treatment enhanced intestinal barrier function by increasing the expression of intestinal tight junction proteins (TJs) and MUC2, and it promoted the production of short-chain fatty acids (SCFAs). Concurrently, CIP modulated the composition of the intestinal microbiota, inhibiting the proliferation of potentially harmful bacteria such as Bacteroidota and Campylobacter . Taken together, these findings suggest that CIP exhibits promising attributes as a functional food constituent, with a particular efficacy in modulating and maintaining intestinal health.
研究领域:
免疫学
·
营养学
·
肠道健康研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2026
·
IF 4.9
Li Ruifang,Sun Yan,Feng Mingzhi,Kelsang Drolma,Cai Hanhui,Zhang Jun
Ulcerative colitis (UC) is a chronic disease characterized by intestinal inflammation, mucosal damage, and immune dysregulation. Current treatments are often inadequate, driving the search for alternatives with fewer side effects. Isoliquiritigenin (ISL), a flavonoid from licorice, has demonstrated anti-inflammatory effects, but its efficacy in UC remains uncertain. Male C57BL/6 mice were divided into six groups: Control, DSS model, low-, medium-, and high-dose ISL (25, 50, 100 mg/kg), and 5-aminosalicylic acid (5-ASA, 100 mg/kg). UC was induced by administering 3% DSS, followed by ISL or 5-ASA treatment. Disease activity index (DAI), histopathology, real-time PCR, Western blotting, immunohistochemistry, and 16 S rRNA sequencing were used to assess inflammation, intestinal barrier integrity, and gut microbiota (GM) composition. a Caco-2 cell-based model of UC was developed. After transfection to induce the overexpression of TLR4 and its adaptor protein MyD88, the cells were incubated with ISL. The effects of this intervention were evaluated by measuring the expression of inflammatory cytokines, tight junction-associated proteins, and components of the TLR4/MyD88 signaling pathway. ISL significantly alleviated DSS-induced UC symptoms, such as weight loss and colonic shortening. ISL reduced colonic mucosal damage and inflammatory cell infiltration, downregulated TLR4, MyD88, and phosphorylated NF-κB expression, and lowered TNF-α, IL-1β, and IL-6 levels. It also improved intestinal barrier function by upregulating ZO-1, Claudin-1, and Occludin expression. ISL modulated GM by increasing beneficial bacteria (Muribaculaceae) and reducing pathogenic bacteria (Escherichia-Shigella). Overexpression of TLR4 and MyD88 in the Caco-2 cell line abrogated the protective effects of ISL, as evidenced by increased expression of inflammatory cytokines and downregulated expression of tight junction proteins. Overall, these findings suggest ISL may protects against DSS-induced UC by suppressing the TLR4/MyD88/NF-κB pathway, enhancing intestinal barrier function, and modulating GM, supporting its potential as a therapeutic supplement for UC.
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2026
·
IF 2.5
Zhen Yang,Huiying Li,Wei Zhao,Yingxia Yu,Yanling Lin,Jianxuan Liu,Xinghu Fan,Moyan Wang,Xin Teng,Zhikai Qiu
Objective Evaluation of the therapeutic effect of Tongfu Zhike Formula (TFZKF) on mice with cough variant asthma (CVA) and exploration of its mechanism of action in improving CVA. Methods The main chemical components of TFZKF were detected and analyzed using UHPLC-MS/MS. Network pharmacology was employed to investigate the potential targets of TFZKF in CVA. After grouping and drug administration, the number of coughs and cough latency were observed in CVA mice. White blood cell differential counts in BALF, serum levels of IgE, IL-4, IL-5, IL-13 and IFN-γ, as well as pathological changes in lung tissue were assessed. Western blot and RT-qPCR were used to analyze the protein expression levels and mRNA changes of TLR4, MyD88, and NF-κB in the lung tissue of CVA mice. Results A total of 495 chemical components were detected in TFZKF under both positive and negative ion modes. Network pharmacology analysis identified 199 potential targets related to TFZKF and CVA, and found close associations with the TLR4 and NF-κB signaling pathways. Animal experiments showed that, compared to the Model group, TFZKF significantly reduced the number of coughs, prolonged cough latency, decreased serum levels of IgE, IL-4, IL-5, and IL-13, reduced the total number of white blood cells, neutrophils, and eosinophils in BALF, alleviated inflammatory cell infiltration and fibrosis in lung tissue, and downregulated the protein and mRNA expression of TLR4, MyD88, and NF-κB. Conclusion The interaction within the TLR4/MyD88/NF-κB signaling pathway may be a potential key target for the treatment of cough variant asthma.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2020
·
IF 1.813
Kai-hui Zhang,Mei-qi Wang,Lu-ling Wei,Cheng-jing Feng,Yu-si Zhang,Jian-bei Teng
Objective. Gout is a chronic disease that causes inflammatory arthritis, which is closely related to urate accumulation induced by a disorder of uric acid metabolism and the consequent deposition of monosodium urate crystals. Dendrobium loddigesii Rolfe is an herbal medicine that has been used in some traditional Chinese medicine formulae in the treatment of gout. This study aimed to explore and verify the antigout activity of Dendrobium loddigesii extract (DLE) on alleviating the hyperuricaemia of mice and the acute gouty arthritis of rats. Methods. An animal model of hyperuricaemia was established using potassium oxonate (PO). We analysed the expression of uric acid transporter mRNA in the kidney in the hyperuricaemic mice after treatment with DLE. Simultaneously, a monosodium urate crystal-induced acute gouty arthritis rat model was used to evaluate the effects of DLE, according to the level of ankle swelling, as well as the protein levels of inflammatory receptors and cytokines, as assayed by WB and ELISA. Results. DLE alleviated hyperuricaemia in mice and inhibited acute gouty arthritis in rats (). Meanwhile, DLE regulated the levels of uric acid transporters mRNA transcripts, including mouse organic anion transporter 1 (mOAT1), organic anion transporter 3 (mOAT3), urate transporter 1 (mURAT1), and glucose transporter 9 (mGLUT9) in the kidney (), suggesting that DLE promoted uric acid metabolism. Furthermore, DLE significantly suppressed the protein levels of TLRs, MyD88, and NF-κB in the ankle joint’s synovium (), and the serum levels of IL-1β, IL-6, and TNF-α were also reduced, which demonstrated the anti-inflammatory effects of DLE. Conclusion. DLE alleviates hyperuricaemia by regulating the transcription level of uric acid transporters in the kidney. It also inhibits acute gouty arthritis by inhibiting the pathway of TLRs/MyD88/NF-κB in the ankle joint’s synovium. The findings of the present study imply that DLE alleviates gout by promoting uric acid metabolism and inhibiting inflammation related to the TLRs/MyD88/NF-κB pathway.
研究领域:
药理学
·
免疫学
·
中医
✓ 已验证
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2022
·
IF 4.319
Bozhi Ye,Xudong Chen,Shanshan Dai,Jibo Han,Xiaohe Liang,Shuang Lin,Xueli Cai,Zhouqing Huang,Weijian Huang
Background Emodin has recently been reported to have a powerful antiinflammatory effect, protecting the myocardium against ischemia/reperfusion (I/R) injury. Pyroptosis is a proinflammatory programmed cell death that is related to many diseases. The present study investigated the effect of emodin on pyroptosis in cardiomyocytes.Materials and methods Sprague Dawley rats were randomly divided into sham, I/R, and I/R+Emodin groups. I/R model was subjected to 30 minutes’ ligation of left anterior descending coronary artery, followed by 2 hours of reperfusion. Cardiomyocytes were exposed to hypoxic conditions for 1 hour and normoxic conditions for 2 hours. The level of the pyroptosis was detected by Western blot, real-time PCR analysis, and ELISA.Results The level of gasdermin D-N domains was upregulated in cardiomyocytes during I/R or hypoxia/reoxygenation (H/R) treatment. Moreover, emodin increased the rate of cell survival in vitro and decreased the myocardial infarct size in vivo via suppressing the levels of I/R-induced pyroptosis. Additionally, the expression of TLR4, MyD88, phospho-IκBα, phospho-NF-κB, and the NLRP3 inflammasome was significantly upregulated in cardiomyocytes subjected to H/R treatment, while emodin suppressed the expression of these proteins.Conclusion This study confirms that emodin treatment was able to alleviate myocardial I/R injury and inhibit pyroptosis in vivo and in vitro. The inhibitory effect of emodin on pyroptosis was mediated by suppressing the TLR4/MyD88/NF-κB/NLRP3 inflammasome pathway. Therefore, emodin may provide an alternative treatment for myocardial I/R injury.
研究领域:
药理学
·
心脏病学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FASEB JOURNAL
·
2025
·Vol. 39
·期 5
·e70439
·
IF 4.2
Yun Li,Site Yu,Jizhang Zeng,Situo Zhou,Xu Cui,Jie Zhou,Pihong Zhang
Excessive inflammation is a prominent issue in diabetic wounds, leading to delayed healing or amputation. Corilagin (Cori) is a natural polyphenolic compound with diverse pharmacological activities, particularly its anti-inflammatory properties. The aim of this study was to evaluate the anti-inflammatory effect of Cori on diabetic wounds and to explore the potential underlying mechanisms. The impact of Cori on wound healing was assessed in streptozotocin (STZ)-induced diabetic mice through morphological observation, histological staining, and gene expression analysis. Flow cytometry, qRT-PCR, western blot analysis, and RNA sequencing were conducted to elucidate the underlying mechanisms in RAW264.7 cells. The results demonstrated that Cori accelerated wound healing, inhibited excessive inflammation, and regulated macrophage polarization in diabetic mice. In Vitro, Cori decreased M1 polarization and inhibited the expression of pro-inflammatory mediators in RAW264.7 cells. Sequencing analysis revealed that Cori exerts anti-inflammatory effects on RAW 264.7 cells through multiple targeted mechanisms. Moreover, in LPS-induced macrophages, Cori dramatically decreased the activation of TLR4, MyD88, and NF-κB. Additionally, Cori enhanced M2 polarization by promoting fatty acid oxidation. In conclusion, the findings suggest that Cori modulates macrophage polarization through various targeted mechanisms, effectively suppressing inflammation and accelerating diabetic wound healing. Graphical Diabetic ulcers are common chronic wounds marked by excessive and persistent inflammation, imposing significant healthcare and economic burdens. Corilagin (Cori) was shown to accelerate wound healing in STZ-induced diabetic mice by modulating macrophage polarization and suppressing inflammation. In vitro, Cori inhibited M1 polarization and reduced the expression of pro-inflammatory mediators via the TLR4/MyD88/NF-κB pathway, while promoting M2 polarization by enhancing fatty acid oxidation. This study highlights Cori's potential as a therapeutic agent for diabetic wound management through its multi-targeted anti-inflammatory mechanisms.
研究领域:
药理学
·
免疫学
·
分子生物学
·
糖尿病研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC GASTROENTEROLOGY
·
2025
·Vol. 25
·期 1
·1-14
·
IF 2.6
Yuan Zuohui,Yang Xiaoping,Wang Xiaochun,Shi Xinlong,Chen Jia,Huang Lijun,Yang Jie,Shi Yuping,Zhang Liping,Mai Ping
Section
Background
This study aimed to investigate the effects of melatonin on diarrhea and visceral hypersensitivity in rats with diarrhea-predominant irritable bowel syndrome (IBS-D) and to explore its potential mechanisms through modulation of the TLR4/MyD88/NF-κB pathway.
Section
Methods
Adult male Sprague-Dawley (SD) rats were used to establish an IBS-D model through a combination of chronic and acute stress. The rats were randomly divided into four groups: healthy control (HC), IBS-D, IBS-D + melatonin 5 mg/kg (M-L), and IBS-D + melatonin 10 mg/kg (M-H), with six rats in each group. Visceral sensitivity was assessed using the abdominal withdrawal reflex (AWR). The expression levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in colon tissue were measured using enzyme-linked immunosorbent assay (ELISA). Western blotting and immunohistochemistry were employed to detect the expression of TLR4, MyD88, and NF-κB proteins in colon tissue. Additionally, 16 S rRNA sequencing was used to analyze the composition of the intestinal microbiota.
Section
Results
Compared to the HC group, the IBS-D group exhibited colonic inflammatory injury, increased AWR scores, elevated levels of TNF-α, IL-6, TLR4, MyD88, and NF-κB in the colon, and altered intestinal microbiota composition. Melatonin treatment reduced colonic inflammatory injury, decreased AWR scores, and lowered the levels of TNF-α, IL-6, TLR4, MyD88, and NF-κB in a dose-dependent manner. The intestinal microbiota composition in melatonin-treated groups showed a trend towards that of the HC group.
Section
Conclusion
Melatonin improved diarrhea and visceral hypersensitivity in IBS-D rats, potentially through the modulation of the TLR4/MyD88/NF-κB pathway and partial restoration of the intestinal microbiota.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
·
2026
·Vol. 19
·期 2
·275
·
IF 5.7
Zhongnan Hu,Hui Liu,Weihua Wu,Tayyab Ali,Adam Junka,Farukh S. Sharopov,Xuan Zou,Shisong Fang,Yanfang Sun
Background: Influenza A virus is an acute respiratory virus that spreads quickly, affects a broad range of populations, and can lead to many complications and mortality.ArtemisiaL. species are widely used in traditional medicine, but their antiviral potential against H1N1 remains uncertain.Methodology: Network pharmacology and molecular docking were used to computationally explore their potential function in this domain, and to investigate how their invasion mechanisms and adsorption occur. UPLC-MS/MS analysis identified the main components of the extracts. The anti-H1N1 mechanism ofArtemisiaL. extracts was studied in vitro.Results: Network pharmacology identified 95 key targets betweenArtemisiaL. and IAV, with quercetin and luteolin as core active compounds. Molecular docking predicted strong binding affinities between these compounds and influenza virus proteins. UPLC-MS/MS analysis identified 75, 100, and 64 chemical components inACBE,AALE, andACTE, respectively, mainly flavonoids and terpenoids.ArtemisiaL. extracts exhibited both preventive and therapeutic effects against H1N1, reducing progeny virus NP mRNA and protein levels. In vitro experiments showed that higher concentrations of the extracts prevent virus attachment to MDCK cells by denaturing the HA protein. NA plays an essential role in progeny virus release. We found that a high concentration of ACTE can inhibit NA up to 85%, and ACBE showed a low inhibitory effect on NA.Conclusions: In terms of therapeutic effects,ArtemisiaL. extracts can regulate intracellular inflammatory factors via the TLR4/NF-κB/MyD88 signaling pathways and reduce the expression of IL-1β, IL-6, TNF-α, TLR4, NF-κB, p65, and MyD88 at the mRNA level, thereby inhibiting H1N1 virus replication. These results suggest that bioactive components inArtemisiaL. extracts may inhibit H1N1, potentially leading to the development of natural-product-based anti-influenza agents.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2022
·
IF 6.51
Tengteng Yuan,Shujie Lv,Wei Zhang,Yanan Tang,Hong Chang,Zihan Hu,Liang Fang,Jiaojiao Du,Sifan Wu,Xinli Yang,Yangfu Guo,Ruihan Guo,Zongrui Ge,Lei Wang,Caiyun Zhang,Rulin Wang,Weidong Chen
Paeoniflorin (PF) has a certain therapeutic effect on cholestasis liver injury. To further improve the bioavailability of PF and play its pharmacological role in liver protection, PF-phospholipid complex micelles (PF-PLC micelles) were prepared based on our previous research on PF-PLC. The protective effects of PF and PF-PLC micelles on cholestasis liver injury induced by 17α-ethynylestradiol (EE) were compared, and the possible mechanisms were further explored. Herein, we showed that PF-PLC micelles effectively improved liver function, alleviated liver pathological damage, and localized infiltration of inflammatory cells. Mechanism studies indicated that PF-PLC micelles treatment could suppress the TLR4/MyD88/NF-κB pathway, and further reduce the levels of pro-inflammatory factors. Meanwhile, our experimental results demonstrated that the beneficial effect of PF-PLC micelles on EE-induced cholestasis may be achieved by the upregulation of nuclear receptors and metabolic enzymes (PXR/CAR/UGT1A1). All these results indicate that PF-PLC micelles have great potential in the treatment of cholestatic liver disease.
研究领域:
药理学
·
肝病学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2026
·Vol. 51
·期 1
·73
·
IF 4.5
Zhou Juan,Li Haipeng,Wen Ying,He Lingli,He Yangli,Meng Heng
Neuromyelitis optica spectrum disorder (NMOSD) is a rare but serious inflammatory demyelinating disease. A key characteristic of NMOSD is the presence of a pathogenic autoantibody in serum called aquaporin-4 immunoglobulin G (AQP4-IgG). This study investigates the mechanism of astrocyte-derived small extracellular vesicles (EVs) carrying mitochondrial DNA (mtDNA) to promote AQP4-IgG-induced microglial activation in neuromyelitis optica (NMO) via the toll-like receptor 9 (TLR9)/myeloid differentiation primary response 88 (MyD88)/nuclear factor-kappa B (NF-κB) pathway. Serum IgG was isolated from NMOSD patients (AQP4-IgG) and healthy controls (Con-IgG). Astrocytes were treated with AQP4-IgG or Con-IgG. EVs were isolated via ultracentrifugation, characterized, and examined for internalization. Microglia were exposed to EVs, and mtDNA levels were assessed. An NMO mouse model was established, with neurological damage, mouse behaviors, tissue damage, and microglial characterization evaluated using modified neurological severity score, open-field test, rotarod test, luxol fast blue staining, and flow cytometry. Inflammatory cytokines, TLR9, MyD88, p65, IκBα, p-p65, and p-IκBα in BV2 cells and spinal cord tissues were analyzed via ELISA, RT-qPCR, and western blot. AQP4-IgG-induced astrocyte-derived EVs increased Iba1-high-expressing and CD86/tumor necrosis factor-α-high-expressing cells, reduced CD206/transforming growth factor-β-high-expressing cells, and boosted inflammatory responses. AQP4-IgG-induced EVs carried mtDNA to activate microglia via the TLR9/MyD88/NF-κB pathway. TLR9/MyD88/NF-κB pathway inhibition reversed AQP4-IgG-induced EVs’ promotion on microglial activation. In vivo, AQP4-IgG-induced EVs-mtDNA exacerbated microglial activation and NMO through the TLR9/MyD88/NF-κB pathway. AQP4-IgG-induced EVs carried mtDNA to upregulate TLR9, further activating the MyD88/NF-κB pathway, thereby promoting microglial activation and transition toward pro-inflammatory gene-high-expressing cells to drive NMO progression.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2024
·
IF 5.1
Bufan Xu,Luyao Zhang,Di Wu,Zihe Qi,Juanjuan Cao,Wenrui Li,Lihua Fan,Yiheng Shi,Yongning Wu,Guoliang Li
Copper II oxide nanoparticles (CuO NPs), a kind of widely used nanomaterial, have been detected in food and the environment, which has aroused widespread public concern. Recently, increasing data have suggested that intestinal microecology is closely related to immune homeostasis. However, the intestinal immunotoxicity induced by CuO NPs through intestinal microbiota is still unknown. Therefore, in this study, zebrafish were exposed to CuO NPs to explore intestinal immunotoxicity by evaluating physiological indicators, intestinal tissue injury, antioxidant enzyme activities, gene expression of immune factors, and changes in intestinal microbiota and its metabolites (short-chain fatty acids (SCFAs) and lipopolysaccharides (LPS)). The results revealed that the intestinal immunotoxicity of CuO NPs was mediated by the impact on intestinal microbiota and its metabolite levels. Specifically, changes were observed in the abundance of microbes that participated in the metabolism of SCFAs and LPS. The reduction in acetic acid, propionic acid and valeric acid upregulated GPR84 expression, and the decline in LPS levels further resulted in the suppression of the key immune regulatory pathways TLR4/MyD88/NF-κB, ultimately leading to intestinal immunotoxicity. This study would provide a scientific basis for the risk assessment of CuO NPs and a new perspective for research on the immunotoxicity of nanoparticles.
研究领域:
环境科学
·
毒理学
·
微生物学
·
免疫学
·
水生生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）