COLLOIDS AND SURFACES B-BIOINTERFACES
·
2019
·
IF 3.973
Menghang Zu,Heliang Song,Jiabin Zhang,Qiubing Chen,Shiqin Deng,Brandon S.B. Canup,Yi Yuan,Bo Xiao
Edible plant-derived nanoparticles (NPs) have attracted increasing attention in the treatment of ulcerative colitis (UC). Lycium barbarum (LB), a popular functional fruit, possesses various biological functions. Here, fat-soluble contents were extracted from LB and further processed into LB lipid-derived NPs (LBLNs). The resultant NPs had an average hydrodynamic diameter around 189.2 nm, narrow size distribution (polydispersity index = 0.2), and negative surface charge (-34.9 mV). Moreover, they could be efficiently taken up by UC therapy-related target cells (macrophages), and over 69.0 % of macrophages internalized LBLNs after 4 h co-incubation. We further found from the in vitro results that LBLNs had strong capacities to inhibit the secretion of the main pro-inflammatory cytokines (TNF-α and IL-12) and up-regulate the expression of the typical anti-inflammatory factor (IL-10). Finally, mice experiments confirmed that LBLNs after oral administration could specifically accumulate into inflamed colon tissues, and further attenuate UC-relevant symptoms ( e.g. , bodyweight loss, colon shortening, increase of spleen weight, and histopathological appearance, as well as ulceration). Collectively, this study demonstrates the excellent therapeutic outcomes of LBLNs against UC and provides a promising edible nanotherapeutic for UC treatment.
研究领域:
药理学
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纳米技术
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炎症性肠病
·
药物递送系统
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DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2024
·
IF 2.7
Xiaodong Liu,Tianyi Jiang,Huiyun Jin,Chenxi Yan,Yuqi Tong,Jiaquan Ding,Yaqi Li,Lian Huang,Zhaohui Zhang
Beryllium sulfate (BeSO 4 ) can cause inflammation through the mechanism, which has not been elucidated. Mitochondrial DNA (mtDNA) is a key contributor of inflammation. With mitochondrial damage, released mtDNA can bind to specific receptors (e.g., cGAS) and then activate related pathway to promote inflammatory responses. To investigate the mechanism of mtDNA in BeSO 4 -induced inflammatory response in 16HBE cells, we established the BeSO 4 -induced 16HBE cell inflammation model and the ethidium bromide (EB)-induced ρ 0 16HBE cell model to detect the mtDNA content, oxidative stress-related markers, mitochondrial membrane potential, the expression of the cGAS-STING pathway, and inflammation-related factors. Our results showed that BeSO 4 caused oxidative stress, decline of mitochondrial membrane potential, and the release of mtDNA into the cytoplasm of 16HBE cells. In addition, BeSO 4 induced inflammation in 16HBE cells by activating the cGAS-STING pathway. Furthermore, mtDNA deletion inhibited the expression of cGAS-STING pathway, IL-10, TNF-α, and IFN-β. This study revealed a novel mechanism of BeSO 4 -induced inflammation in 16HBE cells, which contributes to the understanding of the molecular mechanism of beryllium and its compounds-induced toxicity.
研究领域:
毒理学
·
细胞生物学
·
免疫学
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产品关联
DOI
PubMed
高影响因子
Chinese Journal of Integrative Medicine
·
2024
·
IF 2.2
Liu Xiao-rong,Li Shuo-fu,Mei Wen-ya,Liu Xiang-dan,Zhou Ri-bao
Objective To investigate the effect of isorhamnetin on the pathology of rheumatoid arthritis (RA). Methods Tumor necrosis factor (TNF)- α -induced fibroblast-like synoviocytes (FLS) was exposed to additional isorhamnetin (10, 20 and 40 µ mol/L). Overexpression vectors for matrix metalloproteinase-2 (MMP2) or MMP9 or SRC were transfected to explore their roles in isorhamnetin-mediated RA-FLS function. RA-FLS viability, migration, and invasion were evaluated. Moreover, a collagen-induced arthritis (CIA) rat model was established. Rats were randomly divided to sham, CIA, low-, medium-, and high-dosage groups using a random number table ( n =5 in each group) and administed with normal saline or additional isorhamnetin [2, 10, and 20 mg/(kg·day)] for 4 weeks, respectively. Arthritis index was calculated and synovial tissue inflammation was determined in CIA rats. The levels of MMP2, MMP9, TNF-α, interleukin-6 (IL-6), and IL-1 β, as well as the phosphorylation levels of SRC, extracellular regulated kinase (ERK), and cyclic adenosine monophosphate response element-binding (CREB), were detected in RA-FLS and synovial tissue. Molecular docking was also used to analyze the binding of isorhamnetin to SRC. Results In in vitro studies, isorhamnetin inhibited RA-FLS viability, migration and invasion ( P <0.05). Isorhamnetin downregulated the levels of MMP2, MMP9, TNF-α, IL-6, and IL-1 β in RA-FLS ( P <0.05). The overexpression of either MMP2 or MMP9 reversed isorhamnetin-inhibited RA-FLS migration and invasion, as well as the levels of TNF-α, IL-6, and IL-1 β ( P <0.05). Furthermore, isorhamnetin bound to SRC and reduced the phosphorylation of SRC, ERK, and CREB ( P <0.05). SRC overexpression reversed the inhibitory effect of isorhamnetin on RA-FLS viability, migration and invasion, as well as the negative regulation of MMP2 and MMP9 ( P <0.05). In in vivo studies, isorhamnetin decreased arthritis index scores ( P <0.05) and alleviated synovial inflammation. Isorhamnetin reduced the levels of MMP2, MMP9, TNF-α, IL-6, and IL-1 β, as well as the phosphorylation of SRC, ERK, and CREB in synovial tissue ( P <0.05). Notably, the inhibitory effect of isorhamnetin was more pronounced at higher concentrations ( P <0.05). Conclusion Isorhamnetin exhibited anti-RA effects through modulating SRC/ERK/CREB and MMP2/MMP9 signaling pathways, suggesting that isorhamnetin may be a potential therapeutic agent for RA.
研究领域:
药理学
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免疫学
·
风湿病学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Natural Products and Bioprospecting
·
2024
·Vol. 14
·期 1
·1-11
·
IF 4.8
Huang Ni,Yang Yi-Na,Huang Jia,Shao Hui-Yan,Li Yan-Lang,Qin Shi-Hui,Li Han-Fen,Shen Xiao-Jiang,Yang Liu,Hu Jiang-Miao
Dictyophora rubrovalvata is a valuable fungus homologous to food and medicine, and its polysaccharide have been gaining increasing attention because of its plentiful activity. However, the structure and activity of its homogeneous polysaccharide have not been studied enough. In this study, two polysaccharides DRP-I and DRP-II were purified from D. rubrovalvata . Their structures were characterized by chemical composition, monosaccharide composition analysis, methylation analysis and nuclear magnetic resonance spectroscopy. The results showed that DRP-I and DRP-II were neutral heteropolysaccharides with molecular weights of 5.79 × 10 3 and 1.25 × 10 4 Da, respectively, which were composed of mannose, galactose, glucose, xylose and fucose. The main chains were → 6)- α -D-Gal p -(1 → 6)- α -D-Gal p -(2,1 → 6)- α -D-Man p -(2,1 → 6)- α -D-Gal p -(1, and branch chains were β -D-Xyl p -(1 → 3)- α -L-Fuc p -(1 → 4)- α -D-Man p -(1 → and α -D-Gal p -(1 → 3)- α -D-Gal p -(1 → . The in vitro immunoactivity assays on dendritic cells showed that DRP-I and DRP-II could up-regulate the expression of IL-10 and IL-6 and inhibit the expression of TNF-α in a concentration-dependent manner. This research indicated that DRP-I and DRP-II possessed immunoactivity by balancing the excessive inflammation, and molecular weight is an important factor affecting immunoactivity. Graphical Abstract
研究领域:
真菌学
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免疫学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Journal of Applied Biomedicine
·
2023
·Vol. 21
·期 4
·193-199
·
IF 1.3
Hongji Wang,Lisha Chen,Juping Xing,Xiangchao Shi,Changshui Xu
Naringin inhibits inflammation and oxidative stress, the P2 purinoreceptor X4 receptor (P2X4R) is associated with glial cell activation and inflammation, the purpose of this study is to investigate the effects of naringin on P2X4 receptor expression on satellite glial cells (SGCs) and its possible mechanisms. ATP promoted the SGC activation and upregulated P2X4R expression; naringin inhibited SGC activation, decreased expression of P2X4R, P38 MAPK/ERK, and NF-κB, and reduced levels of Ca2+, TNF-α, and IL-1β in SGCs in an ATP-containing environment. These findings suggest that naringin attenuates the ATP-induced SGC activation and reduces P2X4R expression via the Ca2+-P38 MAPK/ERK-NF-κB pathway.
研究领域:
神经科学
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药理学
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细胞生物学
·
炎症研究
✓ 已验证
DOI
PubMed
高影响因子
Purinergic Signalling
·
2020
·Vol. 16
·期 4
·585-599
·
IF 3.065
Ge Huixiang,Sun Mengyun,Wei Xingyu,Zhang Mingming,Tu Hongcheng,Hao Yuanzhen,Chen Ruxin,Ye Miao,Gao Yun
Activated astrocytes play a key role in diabetic neuropathic pain and depression. We aimed to assess the protective effects of dihydromyricetin (DHM) on primary hippocampal astrocytes cultured with high glucose (HG), substance P (SP), and corticosterone (CORT). Culturing with HG + SP + CORT resulted in damage to primary hippocampal astrocytes, which simulates the clinical damage caused by comorbidity of diabetic neuropathic pain and depression. Western blot, qPCR, and immunofluorescence analyses revealed that HG + SP + CORT increased P2X 7 receptor expression in primary hippocampal astrocytes, which was reversed by DHM treatment. Further, HG + SP + CORT elevated TNF-α, IL-1β, free Ca 2+ , and ERK1/2 phosphorylation levels, which was inhibited by DHM or P2X 7 shRNA treatment. Moreover, DHM significantly reduced the P2X 7 agonist-activated currents in HEK293 cells transfected with the P2X 7 receptor. These findings suggest that DHM can protect primary hippocampal astrocytes cultured with HG + SP + CORT from P2X 7 receptor-mediated damage. Culturing cells with HG + SP + CORT might be a viable cell model for cellular injury exploration of diabetic comorbid pain and depression.
研究领域:
神经科学
·
药理学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2018
·
IF 3.831
Shang Xiaofei,Miao Xiaolou,Yang Feng,Li Bing,Guo Xiao,Pan Hu,Zhang Yu,Zhang Jiyu
Dihuang powder (DHP) has been used in the traditional Chinese medicine for the treatment of diarrhea in some regions of China. But up to now, the anti-diarrheal activity of DHP haven’t been performed with modern pharmacological technology. This study aims to investigate the quality control, the potential toxicity and anti-diarrheal activity of Dihuang powder in mice. High performance liquid chromatography (HPLC) and thin layer chromatography (TLC) were used to detect five active compounds in DHP for quality control, and the acute toxicity and sub-acute toxicity for 28-day oral administration of DHP were then evaluated. The anti-diarrheal activity was investigated using mouse model. Results showed that the levels of quercetin and berberine in DHP were 0.054 and 0.632 mg/g, respectively, and atractylodin, matrine, and patehouli aleohal were also detected in DHP. At the given doses, DHP was safe in terms of acute and sub-acute toxicity. Meanwhile, DHP exhibited strong anti-diarrheal effects as well as decreased gastrointestinal motility and the secretions induced by Sennae and castor oil in a dose-dependent manner. It could decrease the content of IL-1β, IL-6, and TNF-α in the small intestine, and improve the histopathological changes of small intestine and large intestine induced by Sennae. The antinociceptive and anti-inflammatory activities in vivo also were presented. Based on all of the results, we thought that DHP has anti-diarrheal activity, and could be used to treat diarrhea as well as alleviate the pain and inflammation induced by diarrhea. This study provides a theoretical basis for the clinical use of DHP and may assist in the development of new drugs for the treatment of diarrhea. The mechanism of the anti-diarrheal activity should be investigated in the future.
研究领域:
药理学
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中医
·
胃肠病学
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产品关联
DOI
PubMed
高影响因子
Journal of Natural Medicines
·
2020
·Vol. 75
·期 1
·37-47
·
IF 2.055
Han Jieru,Shi Guangyu,Li Wenhao,Xie Ying,Li Fuzhen,Jiang Deyou
Monosodium urate (MSU)-mediated inflammation is closely related to gouty arthritis (GA). Dioscin, an active ingredient, has been reported to possess anti-inflammatory property. Nevertheless, the role of dioscin in GA and the underlying mechanism have not been fully understood. In the present study, we investigated the anti-inflammatory effect of dioscin on MSU-induced GA through in vivo and in vitro experiments. Histopathological analysis showed that dioscin alleviated the severity of GA concomitant with the lowered uric acid and creatinine levels. Moreover, the increasing IL-1β, IL-6, and TNF-α levels induced by MSU were decreased via administration of dioscin in mice and human synoviocytes. Western blotting results suggested that dioscin inhibited the activation of NLRP3 through down-regulating the protein expressions of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), cleaved-caspase-1, as well as IL-1β. In addition, TLR4, myeloid differentiation primary response gene 88 (MyD88), p-IKKβ, p-p65, and NF-κB p65 in nuclei levels were significantly reduced by dioscin. Importantly, dioscin remarkably lowered the NF-κB p65-DNA activity in MSU-treated mice utilizing electrophoretic mobility shift assay (EMSA) analysis. Taken together, dioscin had a protective effect against MSU-initiated inflammatory response via repressing the production of inflammatory cytokines and the activation of inflammasome NLRP3 and TLR4/NF-κB signaling pathway. The above findings revealed that dioscin could be a potential drug for the treatment of GA.
研究领域:
药理学
·
免疫学
·
风湿病学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Guangming Chen,Nan Jiang,Junping Zheng,Haiming Hu,Huabing Yang,Aizhen Lin,Baifei Hu,Hongtao Liu
In this study, two homogeneous polysaccharides (APS-A1 and APS-B1) were isolated from Astragalus membranaceus by DEAE-52 cellulose and Sephadex G-100 column chromatography. Their chemical structures were characterized by molecular weight distribution, monosaccharide composition, infrared spectrum, methylation analysis, and NMR. The results revealed that APS-A1 (2.62 × 10 6 Da) was a 1,4-α-D-Glc p backbone with a 1,4,6-α-D-Glc p branch every ten residues. APS-B1 (4.95 × 10 6 Da) was a heteropolysaccharide composed of glucose, galactose, and arabinose (75.24:17.27:19.35). Its backbone consisted of 1,4-α-D-Glc p , 1,4,6-α-D-Glc p , 1,5-α-L-Ara f and the sidechains composed of 1,6-α-D-Gal p and T-α/β-Glc p . Bioactivity assays showed that APS-A1 and APS-B1 had potential anti-inflammatory activity. They could inhibit the production of inflammatory factors (TNF-α, IL-6, and MCP-1) in LPS-stimulated RAW264.7 macrophages via NF-κB and MAPK (ERK, JNK) pathways. These results suggested that the two polysaccharides could be potential anti-inflammatory supplements.
研究领域:
药理学
·
免疫学
·
生物化学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Biochemistry and Biophysics Reports
·
2023
·
IF 2.7
Ke Zhang,Youyang Liu,Yunlu Zhao,Qi Guo,Shengjun An,Shuhui Wu
Many chronic inflammatory diseases, such as autoimmune inflammation, are associated with M1 macrophages, and the key to their treatment is blocking inflammation. Oxymatrine (OMT), a traditional Chinese medicine, has a marked anti-inflammatory effect. However, its anti-inflammatory target and mechanism in M1 cells remain unclear, which limits its clinical application. In this study, we investigated the anti-inflammatory effects of oxymatrine (OMT) on the M1 inflammatory response. We also determined the relationship between OMT treatment and the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) pathway with OMT treatment. To this end, we induced the differentiation of human peripheral blood monocytes (THP-1) into M1 cells. THP-1 cells were induced with a phorbol ester (phorbol-12-myristate-13-acetate (PMA)) and differentiated into naïve M0 macrophages. M0 cells were induced into M1 cells using lipopolysaccharide (LPS). The experimental groups were divided into the M0 macrophage group (NC), M1 inflammatory response group (LPS group), and M1 group treated with different concentrations of OMT (LPS + OMT-L, LPS + OMT-M, LPS + OMT-H). The cells in the OMT-treated groups were treated with OMT for 6 h, followed by LPS for 24 h, and the LPS group was treated with LPS only. The resulting supernatants and cells were collected. The secretion levels of NO were detected by the Griess method and the secretion levels of TNF-α and IL-1β in the supernatants were detected by the ELISA method. The secretion levels of these inflammatory factors were reduced in every OMT-treated group compared to the LPS group (P < 0.01), and the most significant reductions were found in the OMT-H group (P < 0.0001). By western blotting, the protein expression levels of TLR4, NF-κB, NLRP3, and Caspase-1 were all found to be downregulated in the cells of OMT-treated groups compared to the LPS group (P < 0.0001). In situ changes in NLRP3 expression were observed using immunofluorescence. The fluorescence intensity of NLRP3 in M1 cells was weaker in all OMT intervention groups than in the LPS group (P < 0.001). In conclusion, OMT has significant anti-inflammatory effects on the M1 inflammatory responses, and the TLR4/NF-κB/NLRP3 pathway was blocked proportional to the concentration of OMT.
研究领域:
免疫学
·
药理学
·
细胞生物学
·
炎症性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Current Drug Delivery
·
2023
·
IF 2.4
Li Chenglong,Lu Guanting,Jiang Yue,Su Huaiyu,Li Chen
Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease (AD), and the
global incidence rate is 0.5 ~ 1%. Existing medications might reduce symptoms, however, there is no
known cure for this illness. Etanercept (EN) can competitively inhibit TNF-α binding to the TNF receptor
on the cell surface to treat RA. However, subcutaneous injection of free EN predisposes to systemic
distribution and induces immune system hypofunction. Draining lymph nodes (LNs) play a significant
role in the onset, maintenance, and progression of RA as they are the primary sites of aberrant immune
response and inflammatory cytokine production.
Aim: The purpose of this study was to successfully treat RA with etanercept by encapsulating it in nanoemulsions
(NEs/EN) and then delivering it specifically to draining LNs. The EN-loaded NEs were prepared
by high-pressure homogenization method and modified with DSPE-mPEG2000 and Ca(OH)2.
Methods: A novel nano-emulsion (NE) was constructed to deliver EN (NE/EN) to RA-draining LNs. To
decrease aggregation and load EN, DSPE-mPEG2000 and Ca(OH)2 were successively decorated on the
surface of the lipid injectable emulsions. The hydrodynamic diameter and morphology of NEs/EN were
investigated by using a laser particle size analyzer and transmission electron microscopy, respectively.
The in vivo fluorescence imaging system was used to study the in vivo LN targeting ability of the formulation.
In the therapeutic experiment, NEs/EN was subcutaneously administrated to inhibit the development
of the mouse arthritis model.
Results: Circular dichroism spectrum and L929 cell experiment confirmed that NEs encapsulation had
no impact on the biological activity of EN. In vivo investigation on collagen-induced arthritis (CIA)
mouse model showed that NEs/EN have good inguinal lymph node targeting capabilities, as well as,
anti-inflammatory effect against RA. Compared with the free group, the paw thickness and arthritic
score in NEs/EN group were significantly alleviated. Moreover, the concentration of pro-inflammatory
cytokines TNF-α and IL-1β in NEs/EN-treated mice was lower than that in free EN.
Conclusion: NEs/EN effectively improve the effectiveness of EN in the treatment of RA. Our work
provides an experimental foundation for expanding the clinical application of EN.
研究领域:
药理学
·
免疫学
·
纳米技术
·
风湿病学
✓ 已验证
DOI
PubMed
高影响因子
CURRENT MEDICINAL CHEMISTRY
·
2024
·
IF 3.5
Liu Wei,Zheng Yi-nan,Jiang Shuang,Ren Shen,Tang Shan,Zhang Jing,Wang Zi,Li Wei
Background: Based on the Maillard reaction principle of red ginseng, this
study innovatively synthesized a new amino acid derivative by combining arginine with
lactose through simulated synthesis and was separated and purified through repeated silica
gel and polyacrylamide gel (Bio-gel P-II) column chromatography.
Purpose: The work was aimed at elucidating the synthesis of a novel amino acid derivative
and investigating the intestinal protective activity of the novel amino acid derivative
and possible molecular mechanism by establishing the intestinal injury model induced
by cisplatin in mice.
Methods: The purity and molecular weight of the amino acid derivatives were determined
to be by electrospray ionization mass spectrometry (ESI-MS). Subsequently, by
establishing cisplatin (20 mg/kg)-induced intestinal injury in vivo for 10 days and IEC-6
cell model. The biochemical indexes and histopathological analysis were used to evaluate
the oxidative stress and inflammatory and pathological changes of intestinal tissue in
mice. The protein expression levels of p-Nuclear transcription factor-κB (p-NF-κB),
cleaved caspase 3/caspase 3, cleaved caspase 9/caspase-9, Bcl-2, Bax, cytochrome C,
phosphatidylinositol 3-kinase (PI3K), Protein Kinase B (Akt), p-PI3K, p-Akt were quantified
through immunofluorescence staining and western blot analysis.
Results: The new amino acid derivatives of chemical structure were identified to be 1-
(arginine-Nαgroup)-1-deoxy-4-O-(β-D-galactopyranosyl)-D-fructose, named Argininylfructosyl-
galactose (AFGA, C18H34N4O12). The results showed that pretreatment with a
single AFGA dose remarkably alleviated cisplatin-evoked intestinal oxidative stress injury,
and the levels of reactive oxygen species (ROS) were lessening in IEC-6 cells
(p<0.05, p<0.01) and could effectively reduce the secretion of TNF-α and IL-1β in
serum and the expression level of NF-κB protein in intestinal tissues (p<0.01). Meantime,
AFGA also significantly suppressed the caspase 3, caspase 9, cytochrome C and
Bax protein expression in intestinal tissue in mice (p<0.01), and regulated the PI3K/Akt
pathway (p<0.05, p<0.01). Importantly, the molecular docking results of AFGA also
suggested a better binding ability with the above-mentioned related target proteins.
Conclusion: The results clearly revealed AFGA as a potential multifunctional therapeutic
agent with a clear protective effect against cisplatin-induced intestinal injury may be
related to the PI3K/Akt signaling pathway.
研究领域:
药理学
·
毒理学
·
分子生物学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
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