CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
·
2025
·Vol. 52
·期 4
·e70033
·
IF 2.5
Xin Zhang,Xinliu Wang,Yuanyuan Wang,Xingyou Ma,Yunyun Geng,Shuxian Zang,Ziyun Ban,Yugai Jia,Yonggang Gao
Norisoboldine (NIB) displays beneficial effects on cardiovascular diseases, although its protective role and underlying mechanisms in myocardial ischemia (MI) injury remain elusive. The aim of this study is to explore the potential cardioprotective mechanism of NIB on MI injury caused by isoproterenol (ISO). We administered NIB to SD rats at 20 and 40 mg/kg daily for 7 days in this study; this was followed by an ISO injection to induce MI injury. Parameters such as electrocardiogram readings, heart rate, serum concentrations of creatine kinase (CK) and creatine kinase-MB (CK-MB), levels of inflammatory markers, some histopathological assessments and oxidative stress markers were evaluated. We conducted Western blot analyses to evaluate protein expression related to apoptosis and the TLR4–MyD88-mediated NF-κB activation pathway. The L-type Ca 2+ current (ICa-L) and contraction of isolated ventricular cells from rats were identified using patch-clamp methods and the IonOptix detection system. The treatment with NIB resulted in improvements in heart rate and ST-segment changes, a reduction in CK and CK-MB levels, the restoration of superoxide dismutase, catalase and glutathione levels and a decrease in malondialdehyde accumulation. Furthermore, NIB reduced the expression of inflammatory markers, lowered Ca 2+ levels and reactive oxygen species production and improved myocardial tissue morphology. It also countered ISO-induced alterations in apoptosis and the TLR4–MyD88-dependent NF-κB activation pathway. Additionally, NIB considerably attenuated ICa-L and reduced the contractile function of cardiomyocytes. These results suggest that NIB effectively mitigates ISO-induced MI injury through anti-inflammatory, antioxidative, and anti-apoptotic mechanisms, potentially involving the TLR4–MyD88-dependent NF-κB activation pathway and calcium balance.
研究领域:
药理学
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心血管疾病
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分子生物学
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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.
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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
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肝病学
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分子生物学
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DOI
PubMed
高影响因子
CELL CYCLE
·
2021
·
IF 4.534
Zhensong Jiang,Jianru Zhang
EXs (Exosomes) secreted by mesenchymal stem cells (MSCs) have the potential to treat spinal cord injury (SCI), this study aimed to further explore the therapeutic effect of EXs on SCI. Firstly, EXs were extracted from MSCs and analyzed with a transmission electron microscope. Next, MSCs with or without the miR-145-5p plasmid were injected into the SCI rat model, and then rat damage was evaluated by BBB score, HE staining and Nissl staining. And then Luciferase experiment verified the targeting relationship between miR-145-5p and TLR4. Furthermore, LPS-induced PC12 cells were established and incubated with Dil-labeled MSC-EXs to explore their effects on cell viability, apoptosis and inflammation through MTT, flow cytometry and ELISA, respectively. In addition, expressions of TLR4/NF-κB signaling pathway related factors were measured by qRT-PCR and Western blot. The results showed that after MSCs were successfully isolated, the existence of EXs in MSCs was confirmed. Moreover, MSC-EXs containing miR-145-5p improved functional recovery and reduced histopathological injury and inflammation in SCI rats. And MSC-EXs promoted miR-145-5p expression in spinal cord tissue and inhibited TLR4/NF-κB pathway activation in SCI rats. MSC-EXs inhibited LPS-induced inflammatory response and activation of the TLR4/NF-κB pathway in PC12 cells. In addition, we also found that miR-145-5p specifically targeted TLR4. TLR4 overexpression significantly reversed the effect of EX-miR-145-5p on maintaining PC12 cell viability, inhibiting apoptosis and inflammatory response, and activating TLR4/NF- κB pathway. In conclusion, mesenchymal stem cell-derived EXs containing miR-145-5p reduce inflammation in spinal cord injury by regulating the TLR4/NF-κB signaling pathway.
研究领域:
神经科学
·
干细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2020
·Vol. 72
·期 7
·956-968
·
IF 2.571
Wang Youpeng,Jing Weichao,Qu Wanying,Liu Zhiwei,Zhang Di,Qi Xiaoyu,Liu Lujia
ObjectivesThe aim of this study was to evaluate the effect of tectorigenin on treating allergic asthma model of guinea pigs and investigate the underlying mechanisms.MethodsAllergic asthma model of guinea pigs was established by sensitizing with ovalbumin (OVA). Then OVA-sensitized guinea pigs were injected with 10 mg/kg tectorigenin, 25 mg/kg tectorigenin or dexamethasone to investigate the effect of tectorigenin.Key findingsHigh dose of tectorigenin effectively decreased the number of coughs, the number of inflammatory cells and the levels of pro-inflammatory factors. Moreover, tectorigenin could inhibit pulmonary fibrosis in guinea pigs sensitized with OVA. In addition, the functions of tectorigenin were realized through downregulating profibrotic factors of transforming growth factor (TGF)-β1, phosphorylated (p)-Smad2/3 and Smad4, upregulating fibrosis-inhibitor of Smad7 and decreasing pro-inflammatory factors of vascular endothelial growth factor A (VEGFA), tumour necrosis factor-α (TNF-α), Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), p-inhibitor of nuclear factor-kappa B (NF-κB) kinase β (p-IKKβ) and NF-κB.ConclusionsTectorigenin could inhibit pulmonary fibrosis and airway inflammation through TGF-β1/Smad signalling pathway and TLR4/NF-κB signalling pathway. Therefore, tectorigenin might be a promising medicine to treat allergic asthma.
研究领域:
药理学
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免疫学
·
呼吸医学
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2020
·
IF 7.182
Qingxia Yuan,Xiandong Zhang,Mingyang Ma,Tao Long,Chulei Xiao,Jing Zhang,Jikai Liu,Longyan Zhao
In this study, a glucuronoxylomannan named TAP-3 was obtained from high-value Tremella aurantialba Bandoni et Zang. Physicochemical analysis revealed that TAP-3, which had a molecular weight of ∼624 kDa, mainly consisted of d -mannose (Man), d -xylose (Xyl), and d -glucuronic acid (GlcA) in a molar ratio of 3.0:1.0: 1.0. Structural analyses of its depolymerized fragments clarified that TAP-3 contained a (1 → 3) and (1 → 2)-linked α-Man p backbone, side chains formed by β-Xyl p and β-Glc p A linked to the C -2 position of α-Man p , and acetyl groups connected to the sixth hydroxyl positions of Man p . TAP-3 showed marked immune enhancement activity, promoting NO, IL-1β and TNF-α secretion from macrophages. The critical membrane receptor of TAP-3 was identified to be TLR4 , and the chain length was essential for its immunoregulatory activity. These findings expand knowledge of the structural types of glucuronoxylomannan and illustrate its biological activity as an immunopotentiator.
研究领域:
免疫学
·
生物化学
·
真菌学
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DOI
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2024
·
IF 10.8
Qing Xia,Yuan Wei,Long-ji Hu,Fan-mei Zeng,Yu-wei Chen,Dan Xu,Yuan Sun,Lu-wei Zhao,Yi-fei Li,Guan-hua Pang,Wen Peng,Miao He
Previous studies have detected microplastics (MPs) in human biological samples, such as lungs, alveolar lavage fluid, and thrombus. However, whether MPs induce health effects after inhalation are unclear. In this study, fluorescent polystyrene microplastics (PS-MPs) were found in the thymus, spleen, testes, liver, kidneys, and brain on day 1 or day 3 after one intratracheal instillation. Furthermore, mice showed inflammation in multiple organs, manifested as obvious infiltration of neutrophils and macrophages, increased Toll-like receptors (TLRs), myeloid differentiation primary response protein 88 (MyD88) and nuclear factor-κB (NF-κB), as well as proinflammatory cytokines (tumor necrosis factor (TNF)-α and interleukin (IL)-1β) in the lungs, thymus, spleen, liver, and kidneys after four intratracheal instillations of PS-MPs at once every 2 weeks. Hepatic and renal function indexes were also increased. Subsequently, the inflammatory response in multiple murine organs was significantly alleviated by TLR2 and TLR4 inhibitors. Unexpectedly, we did not find any elevated secretion of monocyte chemotactic protein (MCP)-1 or TNF-α by RAW264.7 macrophages in vitro. Thus, PS-MPs induced inflammatory injuries in multiple murine organs via the TLRs/MyD88/NF-κB pathway in vivo, but not macrophages in vitro. These results may provide theoretical support for healthy protection against PS-MPs and their environmental risk assessment.
研究领域:
环境科学
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免疫学
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毒理学
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病理学
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DOI
PubMed
高影响因子
Scientific Reports
·
2017
·Vol. 7
·期 1
·1-13
·
IF 4.259
Wang Hetong,Song Laiyu,Ju Wenhui,Wang Xuguang,Dong Lu,Zhang Yining,Ya Ping,Yang Chun,Li Fasheng
PM 2.5 is the main particulate air pollutant whose aerodynamic diameter is less than 2.5 micron. The inflammation of various respiratory diseases are associated with PM 2.5 inhalation. Pro-inflammatory cytokine IL-1β generated from effected cells usually plays a crucial role in many kinds of lung inflammatory reactions. The exacerbation of Th immune responses are identified in some PM 2.5 related diseases. To elucidate the underlying mechanism of PM 2.5 -induced acute lung inflammation, we exposed Balb/c mice to PM 2.5 intratracheally and established a mice model. Acute lung inflammation and increased IL-1β expression was observed after PM 2.5 instillation. Regulatory factors of IL-1β (TLR4/MyD88 signaling pathway and NLRP3 inflammasome) participated in this lung inflammatory response as well. Treatment with compound essential oils (CEOs) substantially attenuated PM 2.5 -induced acute lung inflammation. The decreased IL-1β and Th immune responses after CEOs treatment were significant. PM 2.5 may increase the secretion of IL-1β through TLR4/MyD88 and NLRP3 pathway resulting in murine airway inflammation. CEOs could attenuate the lung inflammation by reducing IL-1β and Th immune responses in this model. This study describes a potentially important mechanism of PM 2.5 -induced acute lung inflammation and that may bring about novel therapies for the inflammatory diseases associated with PM 2.5 inhalation.
研究领域:
免疫学
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呼吸医学
·
环境健康
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DOI
PubMed
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
·
2022
·Vol. 66
·期 7
·2100950
·
IF 6.575
Kun-Ping Li,Min Yuan,Yong-Lin Wu,Miguel Pineda,Chu-Mei Zhang,Yan-Fen Chen,Zhi-quan Chen,Xiang-Lu Rong,Jeremy E. Turnbull,Jiao Guo
Scope Ample evidence supports the prominent role of gut-liver axis in perpetuating pathological networks of high-fat high-fructose (HFF) diet induced metabolic disorders, however, the molecular mechanisms are still not fully understood. Herein, this study aims to present a holistic delineation and scientific explanation for the crosstalk between the gut and liver, including the potential mediators involved in orchestrating the metabolic and immune systems. Methods and Results An experimental obesity-associated metaflammation rat model is induced with a HFF diet. An integrative multi-omics analysis is then performed. Following the clues illustrated by the multi-omics discoveries, putative pathways are subsequently validated by RT-qPCR and Western blotting. HFF diet leads to obese phenotypes in rats, as well as histopathological changes. Integrated omics analysis shows that there exists a strong interdependence among gut microbiota composition, intestinal metabolites, and innate immunity regulation in the liver. Some carboxylic acids may contribute to gut-liver communication. Moreover, activation of the hepatic LPS-TLR4 pathway in obesity is confirmed. Conclusion HFF-intake disturbs gut flora homeostasis. Crosstalk between gut microbiota and innate immune system mediates hepatic metaflammation in obese rats, associated with LPS-TLR4 signaling pathway activation. Moreover, α-hydroxyisobutyric acid and some other organic acids may play a role as messengers in the liver-gut axis.
研究领域:
营养学
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微生物学
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免疫学
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代谢组学
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病理生理学
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产品关联
DOI
PubMed
高影响因子
MEDIATORS OF INFLAMMATION
·
2021
·
IF 4.711
Huan Lan,Lu-Ying Zhang,Wen He,Wan-Ying Li,Zhen Zeng,Bo Qian,Chengqiang Wang,Jia-Le Song
The integrity and permeability of the intestinal epithelial barrier are important indicators of intestinal health. Impaired intestinal epithelial barrier function and increased intestinal permeability are closely linked to the onset and progression of various intestinal diseases. Sinapic acid (SA) is a phenolic acid that has anti-inflammatory, antihyperglycemic, and antioxidant activities; meanwhile, it is also effective in the protection of inflammatory bowel disease (IBD), but the specific mechanisms remain unclear. Here, we evaluated the anti-inflammatory of SA and investigated its potential therapeutic activity in LPS-induced intestinal epithelial barrier and tight junction (TJ) protein dysfunction. SA improved cell viability; attenuated epithelial permeability; restored the protein and mRNA expression of claudin-1, ZO-1, and occludin; and reversed the redistribution of the ZO-1 and claudin-1 proteins in LPS-treated Caco-2 cells. Moreover, SA reduced the inflammatory response by downregulating the activation of the TLR4/NF-κB pathway and attenuated LPS-induced intestinal barrier dysfunction by decreasing the activation of the MLCK/MLC pathway. This study demonstrated that SA has strong anti-inflammatory activity and can alleviate the occurrence of high intercellular permeability in Caco-2 cells exposed to LPS.
研究领域:
药理学
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免疫学
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细胞生物学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2021
·Vol. 26
·期 18
·5698
·
IF 4.412
Sennan Qiao,Hansi Zhang,Fei Sun,Zhenyan Jiang
Artemisinin (also known as Qinghaosu), an active component of the Qinghao extract, is widely used as antimalarial drug. Previous studies reveal that artemisinin and its derivatives also have effective anti-inflammatory and immunomodulatory properties, but the direct molecular target remains unknown. Recently, several reports mentioned that myeloid differentiation factor 2 (MD-2, also known as lymphocyte antigen 96) may be the endogenous target of artemisinin in the inhibition of lipopolysaccharide signaling. However, the exact interaction between artemisinin and MD-2 is still not fully understood. Here, experimental and computational methods were employed to elucidate the relationship between the artemisinin and its inhibition mechanism. Experimental results showed that artemether exhibit higher anti-inflammatory activity performance than artemisinin and artesunate. Molecular docking results showed that artemisinin, artesunate, and artemether had similar binding poses, and all complexes remained stable throughout the whole molecular dynamics simulations, whereas the binding of artemisinin and its derivatives to MD-2 decreased the TLR4(Toll-Like Receptor 4)/MD-2 stability. Moreover, artemether exhibited lower binding energy as compared to artemisinin and artesunate, which is in good agreement with the experimental results. Leu61, Leu78, and Ile117 are indeed key residues that contribute to the binding free energy. Binding free energy analysis further confirmed that hydrophobic interactions were critical to maintain the binding mode of artemisinin and its derivatives with MD-2.Keywords:molecular dynamics simulation;myeloid differentiation factor 2;artemisinin;anti-inflammatory;binding free energy
研究领域:
药理学
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免疫学
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分子生物学
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计算化学
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PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2023
·Vol. 20
·期 6
·e202201145
·
IF 2.9
Huiying Bai,Zhen Cao,Sha Meng,Rui Ge,Shurong Ban,Yuanlin Zhang,Li Tang,Qing-Shan Li
Myeloid differentiation protein 2 (MD2), a key TLR4 adaptor protein for sensing LPS, plays an important role in inflammatory process and has been identified as a promising target for the treatment of a variety of inflammatory diseases. In our study, a series of benzoxazolone derivatives were synthesized, characterized and tested for anti-inflammatory activity in vitro . The compounds 3c , 3d and 3g demonstrated the greatest anti-inflammatory activity against IL-6 with IC 50 values of 10.14±0.08, 5.43±0.51 and 5.09±0.88 μM, respectively. Furthermore, the bis-ANS displacement assay revealed that these compounds competitively inhibited the binding between the probe bis-ANS and the MD2 protein. The most active compound 3g , revealed a directly bind with MD2 protein via Arg90 binding and a dissociation constant value of 1.52×10 −6 mol L −1 as determined by the biological layer interference (BLI) assay. Our finding suggested that compounds 3g could be a promising lead compound as MD2 inhibitor for further anti-inflammatory agent development.
研究领域:
药理学
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药物化学
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炎症研究
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DOI
PubMed
高影响因子
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