Journal of Functional Foods
·
2019
·
IF 3.197
Yanbei Tu,Kai Wang,Jian-Bo Wan,Chengwei He
Glycine tabacina (Labill.) Benth, a renowned Chinese medicinal herb, has been used for treatment of rheumatoid arthritis (RA) and joint infection. This study aimed to investigate inhibitory effect of its ethanol extract (GTE) on RA-associated inflammation. Nine isoflavonoids of twelve ones which were found in G. tabacina roots were identified by UHPLC-DAD-MS/MS. GTE treatment suppressed lipopolysaccharide-stimulated overproduction of nitric oxide, TNF-α and IL-6, and iNOS expression in macrophages. GTE blocked the activation of NF-κB and MAPK pathways, as indicated by reduced levels of phosphorylation of IKKα/β, IκBα, p38, ERK and JNK, and the suppressed nuclear translocation of NF-κB p65. Additionally, GTE administration decreased swelling of arthritic paw and serum TNF-α and IL-1β levels in collagen-induced arthritis (CIA) mice. These results demonstrated that GTE exhibited strong anti-inflammatory and anti-arthritic activities through suppressing NF-κB and MAPK pathways activation in activated macrophages and CIA mice, suggesting the potential applications of this species in RA prevention and treatment as functional food or therapeutic agent.
研究领域:
药理学
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免疫学
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炎症研究
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风湿病学
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产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2024
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IF 10
Saisai Ge,Xinyue Wang,Xinru Zhao,Lingling Yuan,Xuewei Bao,Caidie Sun,Zehua Gong,Jun Guo,Siyu Yuan,Danyou Hu,Jing Yang,Bin Yuan,Guiyang Zhang
Rheumatoid arthritis (RA) is a chronic immune disease characterized by the infiltration of immune cells and the proliferation of fibroblast-like synoviocytes (FLS) at the joint site, leading to inflammation and joint destruction. However, the available treatment options targeting both inflammatory and proliferative FLS are limited. Herein, this work presents three covalent organic frameworks (COFs) photothermal composite systems modified with multi-armed polyethylene glycols (PEG) for the treatment of RA. These systems exhibit a dual response under low pH and high reactive oxygen species (ROS) conditions at the site of inflammation, with a specific focus on delivering the protein drug ribonuclease A (RNase A). Notably, molecular docking studies reveal the interaction between RNase A and NF-κB p65 protein, and Western blotting confirm its inhibitory effect on NF-κB activity. In vitro and in vivo experiments verify the significant reduction in joint swelling and deformities in adjuvant-induced arthritis (AIA) rats after treatment with RNase A delivered by multi-armed PEG-modified COF ligands, restoring joint morphology to normal. These findings underscore the promising therapeutic potential of COFs for the treatment of RA, highlighting their unique capabilities in addressing both inflammatory and proliferative aspects of the disease and expanding the scope of biomedical applications for COFs.
研究领域:
纳米技术
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药学
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免疫学
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生物医学工程
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治疗学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
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IF 5.6
Jirui Lang,Li Li,Yunyun Quan,Ruirong Tan,Jinbiao Zhao,Min Li,Jin Zeng,Shilong Chen,Ting Wang,Yong Li,Junning Zhao,Zhujun Yin
Wuwei Shexiang Pill (WSP) is a Tibetan traditional medicine, which has been demonstrated to exhibit potent anti-inflammatory and anti-gout effects. However, the specific pharmacological mechanism is not elucidated clearly. In the present study, liquid chromatography-mass spectrometry (LC-MS)-based metabolomics was applied to investigate the alteration of serum metabolites induced by WSP treatment in MSU-induced gouty rats. Subsequently, bioinformatics was utilized to analyze the potential metabolic pathway of the anti-gout effect of WSP. The pharmacodynamic data discovered that WSP could ameliorate ankle swelling and inflammatory cell infiltration, as well as downregulate the protein expression of IL-1β, p-NF-κB p65, and NLRP3 in the synovial membrane and surrounding tissues of gouty ankles. LC-MS-based metabolomics revealed that there were 30 differential metabolites in the serum between sham-operated rats and gouty ones, which were mainly involved in the metabolism of fructose and mannose, primary bile acid biosynthesis, and cholesterol metabolism. However, compared to the model group, WSP treatment upregulated 11 metabolic biomarkers and downregulated 31 biomarkers in the serum. KEGG enrichment analysis found that 27 metabolic pathways contributed to the therapeutic action of WSP, including linoleic acid metabolism, phenylalanine metabolism, and pantothenate and CoA biosynthesis. The comprehensive analysis-combined network pharmacology and metabolomics further revealed that the regulatory network of WSP against gout might be attributed to 11 metabolites, 7 metabolic pathways, 39 targets, and 49 active ingredients of WSP. In conclusion, WSP could ameliorate the inflammation of the ankle in MSU-induced gouty rats, and its anti-gout mechanism might be relevant to the modulation of multiple metabolic pathways, such as linoleic acid metabolism, phenylalanine metabolism, and pantothenate and CoA biosynthesis. This study provided data support for the secondary development of Chinese traditional patent medicine.
研究领域:
药理学
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代谢组学
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传统中药
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炎症生物学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
·
2021
·Vol. 77
·期 2
·221-227
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IF 6.053
Qin Juan,Chen Junlin,Xu Haopeng,Xia Yi,Tang Wentao,Wang Wei,Li Chongyan,Tang Yilin,Wang Yan
Women with premature ovarian insufficiency (POI) may be more vulnerable to a variety of health risks. To seek a new method to treat the disease, the effects of low-intensity pulsed ultrasound (LIPUS) on promoting repair of ovarian injury in female SD rats induced by 4-vinylcyclohexene diepoxide (VCD) were explored in this research. A total of 24 female SD rats were subjected to intraperitoneal injection of VCD to induce POI. Successful modeling was achieved in 22 rats, which were then randomized into VCD + LIPUS group (n = 13) and VCD group (n = 9). The control group (n = 5) was injected with equal normal saline. Hematoxylin and eosin staining, enzyme-linked immunosorbent assay, Western blot analysis, scanning electron microscope, immunohistochemistry, and terminal deoxynucleotidyl transferase-mediated nick end labeling assay were applied to detect the results. The results indicated that rats in the VCD group showed disorder in the estrous cycle, the number of atresia follicles and apoptosis granulosa cells increased (p < .05). After the LIPUS treatment, the estrous cycle recovered, the number of follicles increased (p < .05), the level of E2 and anti-Müllerian hormone enhanced (p < .05), and the follicle-stimulating hormone decreased (p < .05). The expression of NF-κB p65, TNFα, Bax, ATF4, and caspase-3 in ovarian tissue was significantly decreased (p < .05). These findings showed that LIPUS could promote the repair of the VCD-induced ovarian damage in SD rats, which has the potential to be further applied in the clinic.
研究领域:
生殖生物学
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超声治疗
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内分泌学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2017
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IF 3.154
Jiarui Nie,Yaning Chang,Yujia Li,Yingjun Zhou,Jiawen Qin,Zhen Sun,Haibin Li
Caffeic acid phenethyl ester (CAPE), extracted from propolis, was evaluated for the ameliorative effects on insulin resistance and the mechanisms were identified, using non-insulin-dependent diabetes mellitus (NIDDM) model mice and insulin resistance (IR) model cells. After 5 weeks of CAPE supplementation, insulin sensitivity, hyperlipidemia, and peroxisome proliferator-activated receptor-α (PPAR-α) levels were improved in mice. Proinflammatory cytokines in serum and the expressions of tumor necrosis factor-alpha (TNF-α) mRNA in tissues were markedly downregulated from CAPE-treated mice. In vitro, CAPE supplement significantly improved glucose consumption, glucose uptake, glycogen content, and oxidative stress and decreased expression of glucose-6-phosphatase (G6Pase) mRNA in cells. Both in vivo and in vitro, CAPE enhanced p-Akt (Ser473) and p-insulin receptor substrate (IRS)-1 (Tyr612), but inhibited p-JNK (Thr183/Tyr185), p-NF-κB p65 (Ser536), and nuclear translocation of p-NF-κB p65 (Ser536). In summary, CAPE can ameliorate insulin resistance through modulation of JNK and NF-κB signaling pathway in mice and HepG2 cells.
研究领域:
药理学
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内分泌学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2022
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IF 6.656
Yule Wang,Huimin Wu,Zhu Han,Hongda Sheng,Yuhan Wu,Yingchao Wang,Xinran Guo,Yan Zhu,Xuecai Li,Yi Wang
Background As a leading cause of death and disability, alternative therapies for stroke are still limited by its complicated pathophysiological manifestations. Guhong injection (GHI), consisting of safflower aqueous extract and aceglutamide, has been widely applied for the clinical treatment of cerebrovascular diseases , especially ischemic stroke and post-stroke recovery, in China. Recently, a series of studies have reported the positive effect of GHI against cerebral ischemia/reperfusion injury via targeting various molecular mechanisms. However, questions remain on whether treatment with GHI contributes to better functional recovery after stroke and if so, the potential mechanisms and active substances. Purpose The aim of this work was to explore the potential therapeutic possibilities of GHI for the neurological and behavioral recovery after stroke and to investigate the underlying molecular mechanisms as well as active substances. Methods The neural and motor deficits as well as cortical lesions after GHI treatment were investigated in a mouse model of transient ischemic stroke. Based on the substance identification of GHI, network pharmacology combined with an experimental verification method was used to systematically decipher the biological processes and signaling pathways closely related to GHI intervention in response to post-stroke functional outcomes. Subsequently, ingenuity pathway analysis (IPA) analysis was performed to determine the anti-stroke active substances targeting to the hub targets involved in the significant molecular pathways regulated by GHI treatment. Results Therapeutically, administration of GHI observably ameliorated the post-stroke recovery of neural and locomotor function as well as reduced infarct volume and histopathological damage to the cerebral cortex in subacute stroke mice. According to 26 identified or tentatively characterized substances in GHI, the compound-target-pathway network was built. Bioinformatics analysis suggested that inflammatory and apoptotic pathways were tightly associated with the anti-stroke effect of GHI. Based on protein-protein interaction network analysis, the hub targets (such as NF-κB p65, TNF-α, IL-6, IL-1β, Bax, Bcl-2, and Caspase-3) involved in inflammation and apoptosis were selected. On the one hand, immunofluorescence and ELISA results showed that GHI (10 ml/kg) treatment obviously reduced NF-κB p65 nuclear translocation as well as decreased the abnormally elevated concentrations of proinflammatory cytokines (TNF-α, IL-6, and IL-1β) in damaged cortex tissues. On the other hand, GHI (10 ml/kg) treatment significantly downregulated the number of TUNEL-positive apoptotic cells in ischemic cortex and effectively restored the abnormal expression of Bax, Bcl-2, and Caspase-3. Based on the results of IPA, hydroxysafflor yellow A, baicalin , scutellarin , gallic acid , syringin , chlorogenic acid , kaempferol , kaempferol-3-O-β-rutinoside, and rutin acted synergistically on core targets, which could be considered as the active substances of GHI. Conclusion Overall, the current findings showed that the beneficial action of GHI on improving post-stroke functional recovery of subacute stroke mice partly via the modulation of cortical inflammation and apoptosis. These findings not only provide a reliable reference for the clinical application of GHI, but also shed light on a promising alternative therapeutic strategy for ischemic stroke patients .
研究领域:
神经病学
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药理学
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分子生物学
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中风研究
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产品关联
DOI
PubMed
高影响因子
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