JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Sumin Ge,Sihua Wu,Qin Yin,Meng Tan,Sichuan Wang,Yonghao Yang,Zixuan Chen,Lei Xu,Hui Zhang,Chuang Meng,Yufei Xia,Naoki Asakawa,Wenping Wei,Kaizheng Gong,Xin Pan
Ethnopharmacological relevance Eclipta prostrata (Linn.) is a traditional medicinal Chinese herb that displays multiple biological activities, such as encompassing immunomodulatory, anti-inflammatory, anti-tumor, liver-protective, antioxidant, and lipid-lowering effects. Ecliptasaponin A (ESA), a pentacyclic triterpenoid saponin isolated from Eclipta prostrata (Linn.), has been demonstrated to exert superior anti-inflammatory activity against many inflammatory disorders. Aim of the study Inflammation plays a critical role in acute myocardial infarction (AMI). This study aims to explore the treatment effects of ESA in AMI, as well as the underlying mechanism. Methods An AMI mouse model was established in mice via left anterior descending coronary artery (LAD) ligation. After surgery, ESA was injected at doses of 0.5, 1.25, and 2.5 mg/kg, respectively. Myocardial infarction size, cardiomyocyte apoptosis and cardiac echocardiography were studied. The potential mechanism of action of ESA was investigated by RNA-seq, Western blot, surface plasmon resonance (SPR), molecular docking, and immunofluorescence staining. Results ESA treatment not only significantly reduced myocardial infarct size, decreased myocardial cell apoptosis, and inhibited inflammatory cell infiltration, but also facilitated to improve cardiac function. RNA-seq and Western blot analysis proved that ESA treatment-induced differential expression genes mainly enriched in HMGB1/TLR4/NF-κB pathway. Consistently, ESA treatment resulted into the down-regulation of IL-1β, IL-6, and TNF-α levels after AMI. Furthermore, SPR and molecular docking results showed that ESA could bind directly to HMGB1, thereby impeding the activation of the downstream TLR4/NF-κB pathway. The immunofluorescence staining and Western blot results at the cellular level also demonstrated that ESA inhibited the activation of the HMGB1/TLR4/NF-κB pathway in H9C2 cells. Conclusion Our study was the first to demonstrate a cardiac protective role of ESA in AMI. Mechanism study indicated that the treatment effects of ESA are mainly attributed to its anti-inflammatory activity that was mediated by the HMGB1/TLR4/NF-κB pathway.
研究领域:
药理学
·
心脏病学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Qun Wang,Zhaomei Wang,Jun Song,Kangjie Xu,Wenni Tian,Xu Cai,Jiamei Mo,Yong Cao,Jie Xiao
A nanolipidcarrier (NLC) loaded homogalacturonan enriched pectin (citrus modified pectin, MCP4) hydrogel was designed as a novel colon inflammation site-specific oral delivery system for 6-gingerol (6G) (6G-NLC/MCP4 hydrogel) administration, and its colitis alleviation effect were investigated. 6G-NLC/MCP4 exhibited typical “cage-like” ultrastructure with 6G-NLC embedded in the hydrogel matrix as observed by cryoscanning electron microscope. And due to the homogalacturonan (HG) domain in MCP4 specifically combined with Galectin-3, which is overexpressed in the inflammatory region, the 6G-NLC/MCP4 hydrogel targeted to severe inflammatory region. Meanwhile, the prolonged-release characteristics of 6G-NLC provided sustained release of 6G in severe inflammatory regions. The matrix of hydrogel MCP4 and 6G achieved synergistic alleviation effects for colitis through NF-κB/NLRP3 axis. Specifically, 6G mainly regulated the NF-κB inflammatory pathway and inhibited the activity of NLRP3 protein, while MCP4 regulated the expression of Galectin-3 and peripheral clock gene Rev-Erbα/β to prevent the activation of inflammasome NLRP3.
研究领域:
药学
·
生物医学工程
·
炎症生物学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2018
·Vol. 23
·期 7
·1788
·
IF 3.098
Hong-Xin Cui,Ji-Hong Chen,Jing-Wan Li,Fang-Rong Cheng,Ke Yuan
Myrica rubra(MR) is rich in anthocyanins, and it has good anti-cancer, anti-aging, antioxidant, and antiviral effects. The proportion of disability and death caused by ischemic stroke gradually increased, becoming a major disease that is harmful to human health. However, research on effects of anthocyanin from MR on cerebral ischemia-reperfusion (I/R) injury is rare. In this study, we prepared eight purified anthocyanin extracts (PAEs) from different types of MR, and examined the amounts of total anthocyanin (TA) and cyanidin-3-O-glucoside (C-3-G). After one week of PAE treatment, the cerebral infarction volume, disease damage, and contents of nitric oxide and malondialdehyde were reduced, while the level of superoxide dismutase was increased in I/R mice. Altogether, our results show that Boqi1MR contained the most TA (22.07%) and C-3-G (21.28%), and that PAE isolated from Dongkui MR can protect the brain from I/R injury in mice, with the mechanism possibly related to the Toll-like receptor 4 (TLR4)/ nuclear factor-κB (NF-κB) and NOD-like receptor pyrin domain-containing 3 protein (NLRP3) pathways.Keywords:Myrica rubra;anthocyanins;cyanidin-3-O-glucoside;cerebral ischemia-reperfusion;TLR4/NF-κB;NLRP3
研究领域:
药理学
·
神经科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nutrients
·
2022
·Vol. 14
·期 13
·2765
·
IF 6.706
Xuejiao Zhang,Bowei Zhang,Bo Peng,Jin Wang,Yaozhong Hu,Ruican Wang,Shuo Wang
Sugar reduction and sugar control are advocated and gaining popularity around the world. Sucrose, as the widely consumed ingredient in our daily diet, has been reported a relation to gastrointestinal diseases. However, the role of sucrose in inflammatory bowel disease remains controversial. Hence, our study aimed to elucidate the potential role of three doses of sucrose on DSS-induced colitis in C57BL/6 mice and the underlying mechanisms. The results showed that low-dose sucrose intervention alleviated colitis in mice, reducing the expression of inflammatory cytokines and repairing mucosal damages. In contrast, high-dose sucrose intervention exacerbated colitis. Furthermore, three doses of sucrose administration markedly altered gut microbiota composition. Notably, the low-dose sucrose restored microbial dysfunction and enhanced the production of short chain fatty acids (SCFAs). Specifically, the abundance of SCFAs-producing bacteriaFaecalibaculum,Bacteroides,andRomboutsiawere increased significantly in the LOW group. Consistently, PPAR-γ, activated by SCFAs, was elevated in the LOW group, thereby inhibiting the MAPK/NF-κB pathway. Together, our study demonstrates the differential effects of sucrose on colitis at different doses, providing a scientific basis for measuring and modifying the safe intake level of sugar and providing favorable evidence for implementing sugar reduction policies.Keywords:sucrose;gut microbiota;SCFAs;PPAR-γ;MAPK/NF-κB
研究领域:
胃肠病学
·
免疫学
·
微生物学
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Shaojie Zhang,Qian Zhang,Chong Li,Na Xing,Pengfei Zhou,Yukun Jiao
Anemarrhena asphodeloides polysaccharide (AAP70–1) was reported to have immunomodulatory effects in our previous report. To further improve the immunomodulatory effects of AAP70–1, an A. asphodeloides polysaccharide-zinc complex (AAP-Zn) was synthesized using a ZnCl 2 modification method, and the potential mechanisms by which AAP-Zn activates macrophages were investigated. The results showed that the structural features of AAP-Zn were similar to those of AAP70–1 with a Zn content of 0.2 %, confirming that Zn mainly interacted with AAP70–1 by forming Zn O coordination bonds and Zn…OH bonds. In addition, the administration of AAP70–1 and AAP-Zn effectively improved the immunomodulatory effects by enhancing phagocytosis and upregulating the mRNA expression of cytokines (TNF- α , IL-6, IL-1 β , and IL-18), as well as increasing the production levels of nitric oxide (NO) and reactive oxygen species (ROS) in zebrafish embryos. The intracellular mechanism by which AAP-Zn activates macrophages was found to involve activation of the NF- κ B and MAPK signaling pathways. Our findings suggest that AAP-Zn may be a potential immunopotentiator in the field of biomedicine or functional foods.
研究领域:
免疫学
·
药理学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BASIC RESEARCH IN CARDIOLOGY
·
2016
·Vol. 112
·期 1
·1-15
·
IF 6.038
Han Jibo,Zou Chunpeng,Mei Liqin,Zhang Yali,Qian Yuanyuan,You Shengban,Pan Yong,Xu Zheng,Bai Bin,Huang Weijian,Liang Guang
Angiotensin II (Ang II) induces cardiac inflammation and remodeling. Emerging evidence indicates that Ang II may utilize the Toll-like receptor 4 (TLR4) signaling pathway in mediating pro-inflammatory and pro-fibrotic activities. However, the precise mechanism is poorly understood. Myeloid differentiation 2 (MD2), a molecule that physically binds to TLR4, confers lipopolysaccharide responsiveness and may also be involved in mediating the actions of Ang II. We hypothesize that MD2 plays an essential role in cardiac inflammation and remodeling induced by local Ang II, and inhibition of MD2 can attenuate Ang II-induced cardiac dysfunction. Using a specific small molecule MD2 blocker L6H21 and the MD2 knockout mice, we show that MD2 deficiency significantly reduces cardiac inflammation and subsequent fibrosis, hypertrophy, and dysfunction in mice challenged with subcutaneous injection of Ang II. In rat cardiomyocyte-like H9c2 cells as well as rat primary cardiomyocytes, inhibition of MD2 by L6H21 or siRNA knockdown suppressed the Ang II-induced TLR4 signaling pathway activation including MyD88 recruitment, and reduced cardiomyocyte hypertrophy and matrix protein expression. These pro-inflammatory activities of Ang II were independent of the AT1 receptor. Finally, we demonstrated the direct interaction between Ang II and MD2 protein via hydrogen bonds on Arg-90, Glu-92, and Asp-100. Ang II produces an inflammatory response and cardiac remodeling by directly binding to MD2, activating MD2/TLR4 complex, and recruiting MyD88. MD2 may be a new therapeutic target for Ang II-mediated cardiac inflammation and remodeling.
研究领域:
心脏病学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Zhehuan Wang,Huiru Zhang,Caihong Qi,Hui Guo,Xiangyue Jiao,Jia Yan,Yifei Wang,Qiangsheng Li,Mingming Zhao,Xinhao Guo,Baoluo Wan,Xiaotian Li
Background Ursolic acid (UA) is a triterpenoid compound found in natural plants. It has been reported to have anti-inflammatory, antioxidant, and immunomodulatory properties. However, its role in atopic dermatitis (AD) is unknown. This study aimed to evaluate the therapeutic effect of UA in AD mice and explore the underlying mechanisms. Methods Balb/c mice were treated with 2, 4-dinitrochlorobenzene (DNCB) to induce AD-like lesions. During modeling and medication administration, dermatitis scores and ear thickness were measured. Subsequently, histopathological changes, levels of T helper cytokines, and oxidative stress markers levels were evaluated. Immunohistochemistry staining was used to assess changes in the expression of the nuclear factor of kappa B (NF-κB) and NF erythroid 2-related factor 2 (Nrf2). Furthermore, CCK8 assay, reactive oxygen species (ROS) assay, real-time PCR, and western blotting were employed to evaluate the effects of UA on ROS levels, inflammatory mediator production, and the NF-κB and Nrf2 pathways in TNF-α/IFN-γ-stimulated HaCaT cells. Results The results showed that UA significantly reduced dermatitis score and ear thickness, effectively inhibited skin proliferation and mast cell infiltration in AD mice, and decreased the expression level of T helper cytokines. Meanwhile, UA improved oxidative stress in AD mice by regulating lipid peroxidation and increasing the activity of antioxidant enzymes. In addition, UA inhibited ROS accumulation and chemokine secretion in TNF-α/IFN-γ-stimulated HaCaT cells. It might exert anti-dermatitis effects by inhibiting the TLR4/NF-κB pathway and activating the Nrf2/HO-1 pathway. Conclusion Taken together, our results suggest that UA may have potential therapeutic effects on AD and could be further studied as a promising drug for AD treatment.
研究领域:
药理学
·
免疫学
·
皮肤科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CTS-Clinical and Translational Science
·
2024
·Vol. 17
·期 3
·e13748
·
IF 3.1
Chenyu Song,Kaiyang Wang,Bangping Qian,Jingshun Lu,Mu Qiao,Yong Qiu,Bin Wang,Yang Yu
Ankylosing spondylitis (AS) is an immune chronic inflammatory disease, resulting in back pain, stiffness, and thoracolumbar kyphotic deformity. Based on the reported anti-inflammatory and antioxidant capacities of cynarin (Cyn), this study explored its protective role and molecular mechanisms in mesenchymal stem cells (MSCs) from AS. The target pathways and genes were verified using Western blotting, quantitative real-time polymerase chain reaction, and immunofluorescent staining, while molecular docking analysis was conducted. In AS-MSCs, we found that the expression levels of p-NF-κB, IL-6, IL-1β, and TNF-α were higher and IκB-α, Nrf-2, and HO-1 were lower compared with healthy control (HC)-MSCs. With molecular docking analysis, the biding affinities between Cyn and Keap1-Nrf-2 and p65-IκB-α were predicted. The mRNA and protein expression of p-NF-κB, IL-6, IL-1β, and TNF-α and the reactive oxygen species (ROS) generation were downregulated following Cyn administration. Meanwhile, the expression level of IκB-α, Nrf-2, and HO-1 were significantly increased after Cyn pretreatment. The results suggested that the protective mechanisms of Cyn in AS-MSCs were based on enhancing the antioxidation and suppression of excessive inflammatory responses via Nrf-2/ROS/NF-κB axis. Our findings demonstrate that Cyn is a potential candidate for alleviating inflammation in AS.
研究领域:
免疫学
·
干细胞生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROBIAL PATHOGENESIS
·
2024
·
IF 3.3
Zhikun Zhang,Dawei Shi,Haiwei Dou,Ruijie Wan,Qing Yuan,Peng Tu,Deli Xin
In previous study, lower levels of serum GP130 were reported in children with MPP. GP130 is an important signal transducer, the down regulation of which may influence host immune responses. In this study, we aimed to analyze the regulatory mechanism of GP130 during MP infection. Firstly, the mRNA and protein levels of GP130 both decrease and then increase with increasing multiplicity of infection (MOI: 1 to 40) of MP. The lowest levels of GP130 were detected at MOI of 5. Then, heat treated MP but not trypsin treated MP or MP extracted proteins show regulatory effect to the expression of GP130. These indicate that the down regulation of GP130 is related to protein mediate adhesion process of MP. Gene expression analysis revealed that MP affected apoptosis and the TLR4 pathway in infected cells, and the mRNA level of IL-6 was correlated with that of GP130. Further, Z-VAD-FMK (pan-caspase inhibitor) can suppress the apoptosis induced by MP infection and restore GP130 at protein level. Further studies revealed that MP infection promoted TLR4 internalization but did not activate the NF-κB pathway. The levels of surface TLR4 showed correlation with the transcription of IL-6 and GP130. TAK242 (TLR4 inhibitor) and PS341 (proteasome inhibitor) can restore the decreased transcription of GP130, both of which were able to promote NF-κB pathway activation in MP-infected cells. These suggested that the regulation of TLR4/NF-κB pathway and induced apoptosis post MP infection are involved in the down-regulation of GP130 at transcription and protein levels, respectively.
研究领域:
微生物学
·
免疫学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
PHARMACEUTICAL BIOLOGY
·
2023
·
IF 3.8
Shouhai Wu,Meixia Yan,Junyi Liu,Yizhen Li,Ruimin Tian,Chuang Li,Lihuang Huang,Zhisheng Lu,Peng Xu,Wei Mao
Context Clerodendranthus spicatus Thunb. (Labiatae) (CS), a perennial traditional Chinese medicinal herb that can reduce serum uric acid (sUA) levels and ameliorate renal function is widely used to treat hyperuricaemic nephropathy (HN).Objective To investigate the molecular mechanism of action of CS in HN treatment using in vivo and in vitro experiments.Materials and methods Sprague-Dawley rats were randomly divided into control, HN, CS and positive control allopurinol groups. The HN group was intraperitoneally injected with 750 mg/kg oxonic acid potassium (OA), whereas the CS group was injected with OA along with a gavage of CS (low dose 3.125 g/kg, high dose 6.25 g/kg) for five weeks. For in vitro studies, uric acid-treated HK2 cells were used to verify the therapeutic mechanism of CS in HN.Results HN rats exhibit pathological phenotypes of elevated sUA levels and renal injury. CS significantly improved these symptoms and sUA (p < 0.05) and blood urea nitrogen (p < 0.01) levels, and dramatically improved renal tubular injury in HN rats. The IC50 value of UA (uric acid) in HK2 cells was 826.32 ± 3.55 μg/mL; however, 120 ng/mL CS had no significant cytotoxicity on HK2 cells. In vivo and in vitro studies showed that CS inhibited NF-κB phosphorylation and inhibited α-smooth muscle actin (α-SMA) and vimentin expression while increasing E-cadherin expression, suggesting that CS inhibited the fibrotic process in renal cells, thus protecting renal function.Discussion and conclusions These findings provide a fundamental understanding of the application of CS in HN treatment to better guide clinical interventions.
研究领域:
药理学
·
分子生物学
·
肾脏病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLACENTA
·
2025
·
IF 2.5
Caiqun Huang,E Fen Cheng,Jinping Ni,Ying Lyu
Introduction Unexplained recurrent spontaneous abortion (URSA) involves multifactorial etiologies, with regulatory T cells (Tregs) playing a pivotal role in maintaining immune tolerance during pregnancy. Baicalein, a flavonoid from Scutellaria baicalensis, exhibits anti-inflammatory and immunomodulatory properties. This study evaluates baicalein's therapeutic potential in mitigating URSA via the TLR4/NF-κB signaling pathway. Methods A URSA mouse model was used, and baicalein was administered intraperitoneally. Pregnancy outcomes, abortion rates, and placental morphology were assessed on gestational day 14 (G14). Treg cells were quantified via flow cytometry, and gene/protein expression levels were analyzed by immunohistochemistry, Western blotting, and real-time PCR. In vitro experiments on ihESCs further investigated the role of the TLR4/NF-κB pathway. Results Baicalein reduced abortion rates from 33.3 % in URSA mice to 21.6 % (low dose) and 14.8 % (high dose), improved embryonic development by altering placental structure and decidual morphology, and reduced inflammation at the maternal-fetal interface. It expanded Treg cells and enhanced the expression of IGFBP-1 and PRL, markers of endometrial decidualization, and decreased TLR4, p-P65, and P65 expression. In vitro, baicalein's effects were abrogated by TLR4 inhibition, confirming pathway specificity. Discussion Baicalein improved pregnancy outcomes by enhancing Treg function and promoting decidualization via TLR4/NF-κB pathway inhibition. These findings highlight baicalein's potential as a therapeutic agent for URSA.
研究领域:
生殖医学
·
免疫学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2022
·
IF 5.572
Zheng Cao,Jinsong Gao,Wanyue Huang,Juli Yan,Anshan Shan,Xiang Gao
Deoxynivalenol (DON) induces intestinal epithelial barrier disruption, posing a threat to the body. Curcumin (Cur) possesses pharmacological bioactivities such as antioxidant and anti-inflammatory effects that help maintain intestinal health. Here, the protective effects of Cur against DON-induced intestinal epithelial barrier disruption were explored. Cur (75 or 150 mg/kg body weight [B.W.]) alleviated DON-induced (2.4 mg/kg B.W.) inhibition of growth performance and morphological damage to intestinal epithelium in mice. Cur also significantly attenuated DON-induced intestinal epithelial barrier disruption and structural damage to the tight junctions (TJs), as assessed by ultrastructure observation, serum FITC-dextran concentrations and diamine oxidase activity. Cur mitigated the DON-induced increase in reactive oxygen species , malondialdehyde and 8-hydroxy-2′-deoxyguanosine levels; p53, cytoplasmic cytochrome c , Bax , and Bcl-2 expression; and TUNEL-positive cell rate and caspase-3 activity. It decreased the total antioxidant capacity and expression of nuclear Nrf2 and its downstream target genes. Lastly, Cur attenuated the DON-induced increase in MLCK , p-MLC, nuclear NF-κB p65 expression, and the NF-κB downstream target genes; decrease in the expression of TJs proteins (claudin-1, occludin , and zonula occludens-1 [ZO-1]); and abnormal ZO-1 distribution. Overall, Cur mitigated the DON-induced disruption of the intestinal epithelial barrier by regulating the Nrf2/p53-mediated apoptotic pathway and NF-κB/MLCK-mediated TJs pathway in mice.
研究领域:
药理学
·
毒理学
·
胃肠病学
·
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）