Food & Function
·
2020
·Vol. 11
·期 12
·10852-10863
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IF 4.171
Mingbao Gu,Jie Jin,Chenghao Ren,Ximiao Chen,Weiyang Gao,Xiangyang Wang,Yaosen Wu,Naifeng Tian,Zongyou Pan,Aimin Wu,Yifei Zhou,Xiaolei Zhang
As an ordinary joint vestigial disease, osteoarthritis (OA) contributes to a considerable proportion of disability cases worldwide. Inflammation, as the main pathological factor, mediates the occurrence and development of OA. Akebia Saponin D (ASD), also known as Asperosaponin VI, is one of the active components extracted from Dipsaci Radix and is rich in Dipsacus loose tea. It has shown sound therapeutic effects on various diseases; nevertheless, its role in OA therapy is not completely understood. This study demonstrated the anti-inflammatory activity of ASD in OA through a series of in vivo and in vitro experiments. In vitro experiments revealed that ASD might prohibit the production of inflammatory mediators in IL-1β treated chondrocytes such as COX-2, iNOS, NO, PGE2, IL-6, and TNF-α. Meanwhile, it may also inhibit the production of ADAMTS-5 and MMP13 and promote the production of Aggrecan and Collagen II. The mechanism study demonstrated that ASD exerted an anti-inflammatory effect by activating the NRF2 target, upregulating the expression of HO-1, and preventing P65 from binding to DNA. In vivo experiments demonstrated that ASD might improve the progression of OA in a DMM mouse model. These research results provide evidence for the potential application of ASD in OA therapy.
研究领域:
药理学
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风湿病学
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炎症研究
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骨科
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2020
·
IF 7.182
Yajuan Bai,Xuchao Jia,Fei Huang,Ruifen Zhang,Lihong Dong,Lei Liu,Mingwei Zhang
In this study, LPIIa, a purified polysaccharide from longan pulp, was isolated. Its anti-inflammatory activity and intestinal barrier protection were investigated with LPS-treated co-culture model of Caco-2 cells and RAW 264.7 macrophages. The average molecular weight LPIIa was 159.3 kDa. Its detailed structure was shown below. The backbone of LPIIa was composed of (1→3,4)-linked-α-Rha p , (1→4)-linked-β-Gal p , (1→6)-linked-β-Gal p , and (1→3,6)-linked-β-Gal p , with branches at the O-4 of Rha and O-3 of Gal, consisting of side chains of α-Ara f , β-Gal p , and α-Glc p . In LPS-induced RAW 264.7 macrophages, LPIIa suppressed the production of inflammatory mediators, including TNF-α, IL-6, NO, and PGE2, and inhibited iNOS and COX-2 gene expression. In addition, LPIIa attenuated intestinal tight-junctional channel protein Claudin-2 expression and increased tight-junctional barrier protein ZO-1 expression in Caco-2 cells. Knowing the structural features and activities of longan polysaccharide gives insights into longan polysaccharide application as an anti-inflammatory agent or adjuvant in curing the intestinal inflammation.
研究领域:
药理学
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免疫学
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胃肠病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2022
·
IF 6.656
Ying-kun Zhi,Jing Li,Lang Yi,Rui-li Zhu,Jin-fang Luo,Qing-ping Shi,Sha-sha Bai,Yan-wu Li,Qun Du,Jia-zhong Cai,Liang Liu,Pei-xun Wang,Hua Zhou,Yan Dong
Background Sinomenine (SIN) is an anti-inflammatory drug that has been used for decades in China to treat arthritis . In a previous study, SIN acted on α7 nicotinic acetylcholine receptor (α7nAChR) to inhibit inflammatory responses in macrophages, which indicates a new anti-inflammatory mechanism of SIN. However, the level of α7nAChR was increased in the inflammatory responses and was downregulated by SIN in vitro, so the underlying mechanisms of SIN acting on α7nAChR remain unclear. Purpose To analyze the role of α7nAChR in inflammation and the effect and mechanism of SIN regulation of α7nAChR. Methods The effects of SIN on α7nAChR in endotoxemic mice and LPS-stimulated macrophages were observed. Nicotine (Nic) was used as a positive control, and berberine (Ber) was used as a negative control targeting α7nAChR. The antagonists of α7nAChR, α-bungarotoxin (BTX) and mecamylamine (Me), were used to block α7nAChR. In RAW264.7 macrophage cells in vitro , α7nAChR short hairpin RNA (shRNA) was used to knock down α7nAChR. Macrophage polarization was analyzed by the detection of TNF-α, IL-6, iNOS, IL-10, Arg-1, and Fizz1. U0126 was used to block ERK phosphorylation. The cytokines α7nAChR, ERK1/2, p-ERK1/2 and Egr-1 were detected. Results SIN decreased the levels of TNF-α, IL-6 and the expression of α7nAChR increased by LPS in endotoxemic mice. The above effects of SIN were attenuated by BTX. In the α7nAChR shRNA transfected RAW264.7 cells, compared with the control, α7nAChR was knocked down, and M1 phenotype markers (including TNF-α, IL-6, and iNOS) were significantly downregulated, whereas M2 phenotype markers (including IL-10, Arg-1, and Fizz1) were significantly upregulated when stimulated by LPS. SIN inhibited the expression of p-ERK1/2 and the transcription factor Egr-1 induced by LPS in RAW264.7 cells, and the above effects of SIN were attenuated by BTX. The expression of α7nAChR was suppressed by U0126, which lessened the expression of p-ERK1/2 and Egr-1. Conclusions SIN acts on α7nAChR to inhibit inflammatory responses and downregulates high expression of α7nAChR in vivo and in vitro . The increase of α7nAChR expression is correlated with inflammatory responses and participates in macrophage M1 polarization. SIN downregulates α7nAChR via a feedback pathway of α7nAChR/ERK/Egr-1, which contributes to inhibiting macrophage M1 polarization and inflammatory responses.
研究领域:
免疫学
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药理学
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细胞生物学
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炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
·
IF 5.7
Jiahui Wang,Wei Liu,Jia Lu,Mengyue Zhu,Yanni Wu,Wenhui Pan,Boyi Fan,Yan Song,Wenli Wang,Guangtong Chen
The prevalence of neurodegenerative diseases has increased in recent decades. Its exact pathogenesis is not yet fully understood, and only a few drugs can be used clinically to alleviate disease symptoms. Increasing evidence highlights plant-derived compounds are becoming a promising resource for mitigating the onset and progression of neurodegenerative diseases. Uvaol (1) is an ursane-type triterpenoid commonly found in olive leaves, fruits, and virgin olive oil. It is one of the rare compounds in olive oil that can penetrate the blood–brain barrier. Despite its potential neuroprotective activity, research on its structural variations and antineuroinflammatory properties remains sparse. This study explored the biotransformation of uvaol using three fungal species: Actinomucor elegans, Aspergillus flavus, and Circinella muscae. This process yielded 15 new compounds along with seven known ones. Their structures were determined through comprehensive spectroscopic analysis. Furthermore, the antineuroinflammatory activities of compounds were evaluated by using MTT and Griess assays. Notably, compound 9 was found to markedly suppress the transcriptional levels of inflammation-associated elements such as TNF-α, IL-1β, IL-6, iNOS, and COX-2 in BV-2 cells stimulated by lipopolysaccharides (LPS). Moreover, compound 9 also facilitated autophagy by upregulating ULK1 mRNA expression and downregulating the p62 protein. These results suggested that biotransformation was an effective approach for rapidly diversifying uvaol and providing a basal material for the discovery of candidates in treating neurodegenerative diseases.
研究领域:
药理学
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神经科学
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药物化学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
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2020
·
IF 4.831
Jiawei Zuo,Shi-Meng Wang,Xia Jiang,Mengxin Cao,Ziwen Zhang,Tianlu Shi,Hua-Li Qin,Wenjian Tang
Acute kidney injury (AKI) is associated with a strong inflammatory response, and inhibiting the response effectively prevents or ameliorates AKI. A series of novel arylpropionic esters were designed, synthesized and evaluated their biological activity in LPS-stimulated RAW264.7 cells. Novel arylpropionic esters bearing multi-functional groups showed significant anti-inflammatory activity, in which, compound 13b exhibited the most potent activity through dose-dependent inhibiting the production of nitric oxide (NO, IC 50 = 3.52 μM), TNF-α and IL-6 (84.1% and 33.6%, respectively), as well as suppressing the expression of iNOS, COX-2 and TLR4 proteins. In C57BL/6 mice with cisplatin-induced AKI, compound 13b improved kidney function, inhibited inflammatory development, and reduced pathological damage of kidney tissues. In brief, this arylpropionic ester scaffold may be developed as anti-inflammatory agents.
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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肾脏生理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
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2022
·Vol. 74
·期 9
·1241-1250
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IF 4.81
Huang Wenwen,Zhou Xiaoying
ObjectivesTo examine the possible anti-histamine effects of dipotassium glycyrrhizinate (DG), a dipotassium salt of glycyrrhizic acid, on histamine-mediated lung fibroblast activation, differentiation and proliferation; to investigate the potential and underlying mechanisms for pulmonary fibrosis (PF) treatment.MethodsRat primary lung fibroblasts were extracted to establish cell models; histamine, DG and loratadine (LTD, a histamine receptor antagonist) were applied. Cell proliferation, migration and cell cycle were explored; intracellular signal proteins were detected; mitochondrial membrane potential was examined.Key findingsThe anti-histamine effects of DG were found in a similar pattern of LTD on lung fibroblasts. DG inhibited histamine-induced cell activation, proliferation and migration; DG altered histamine-mediated mitochondrial membrane potentials. DG reduced the histamine-induced PAR-2 (a tryptase receptor) expression to impair mast cell tryptase co-working. Histamine-induced expressions of MMP-2, FAK, TNF-α, P38, iNOS were decreased by DG, while Bax and caspase-3, P53 were increased by DG against histamine effects. Histamine drove cells from G0/G1 to S phases, whereas DG rested cells by inhibiting G0/G1 and G2/M phases.ConclusionsThis study provided the evidences that DG can inhibit histamine-induced effects on lung fibroblasts and promote apoptosis of abnormally activated lung fibroblasts, implicating its potential therapeutic mechanisms against PF development, also for those histamine-related diseases.
研究领域:
药理学
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呼吸医学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2022
·
IF 6.656
Shuang Luo,Jinrong He,Shaowei Huang,Xiaojing Wang,Yulin Su,Yanyang Li,Yanping Chen,Guanghua Yang,Bin Huang,Shaoju Guo,Lian Zhou,Xia Luo
Background Emodin is an active ingredient of traditional Chinese medicine Rheum palmatum L. and Polygonum cuspidatum , which possesses anti-inflammatory and intestinal mucosal protection effects. Our previous study found that emodin significantly alleviated ulcerative colitis induced by sodium dextran sulfate (DSS). In this study, we found the underlying mechanism of emodin on ulcerative colitis (UC). Purpose We aimed to further explore the mechanism of emodin in the treatment of ulcerative colitis from the perspective of metabolism and intestinal flora . Methods Ulcerative colitis was induced by 3% sodium dextran sulfate (DSS) on mice, and the mice were respectively treated with mesalazine , rosiglitazone , emodin, and emodin combined with GW9662 (PPARγ inhibitor) simultaneously. Weight changes , the disease activity index (DAI), colonic length, and pathologic changes in colon were used to evaluate the efficacy of emodin. LC-MS/MS was performed for metabolomics analysis of colon. In addition, intestinal flora was assessed using 16S rDNA sequencing. A vector-based short hairpin RNA (shRNA) method was used to silence PPARγ gene expression in Caco-2 cells. Results Emodin binds to the active site of PPARγ protein and forms hydrogen bond interaction with ARG288 and CYS285 amino acids. Furthermore, Emodin significantly promotes the protein expression of PPARγ, while inhibiting iNOS and NF-kB p65 in UC mice, however, this effect is hardly shown when it is combined with GW9662 (the inhibitor of PPARγ). Meanwhile, emodin suppresses the expression of iNOS in Caco-2 cells induced with IFNγ and IL-22, but has no effect on its expression in shPPARγ-Caco-2 cells. In addition, through activating PPARγ signal pathway , emodin is capable of regulating colonic metabolism including oxidative phosphorylation and citrulline metabolism and effecting luminal availability of oxygen and nitrate. This promotes the recovery of anoxic environment of colon epithelial cells, which strains the growth and expansion of Enterobacteriaceae . Conclusion The mechanism of Emodin in the treatment of ulcerative colitis relies on its regulation of PPARγ signal pathway, which could modulate colonic metabolism and restore intestinal homeostasis .
研究领域:
药理学
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胃肠病学
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分子生物学
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免疫学
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
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2022
·
IF 8.786
Zhang Nan,Gao Xiaochen,Zhang Weijia,Xiong Junyao,Cao Xiaojian,Fu Zhen F.,Cui Min
Japanese encephalitis virus (JEV) is one of the most important members of the flavivirus family. It is a typical zoonotic pathogen that has caused substantial social and economic losses worldwide. The relation between JEV-induced immunosuppression and inflammatory responses has not been thoroughly investigated. In this study, cells infiltrating the brain tissue of JEV-infected mice were mainly identified as monocytic myeloid-derived suppressor cells (M-MDSCs), which subsequently differentiated into CD3+ macrophages. Co-culture with T cells showed that both splenic M-MDSCs and brain infiltrated M-MDSCs isolated from JEV-infected mice inhibited T cell proliferation through ARG1 and iNOS. The splenectomy model revealed that JEV-induced M-MDSCs were mainly derived from bone marrow and migrated to the spleen and central nervous system (CNS). The results of the transcriptome analysis and IRF7-deficient mice indicated that the ZBP1-IRF7 signaling pathway stimulated by JEV RNA played a central role in the induction of M-MDSCs. M-MDSCs migrated into the CNS through the chemokine CCL2/N-CCL2 derived from astrocytes and brain infiltrated M-MDSCs differentiated into CD3+ macrophages through a mechanism mediated by M-CSF, IL-6 and IFN-γ in the brain microenvironment. These findings provide evidence for the mechanism that JEV regulates the differentiation of M-MDSCs and thereby exacerbates pathogenicity, which represents a potential therapeutic target for Japanese encephalitis (JE).
研究领域:
免疫学
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神经病毒学
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病毒学
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致病机制
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
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2023
·
IF 5.1
Jie Liu,Ailing Hui,Jinghe Wang,Qingfeng Hu,Shengnan Li,Yuanli Chen,Zeyu Wu,Wencheng Zhang
Neuroinflammation is considered as an important pathological mechanism in neurodegenerative diseases. The natural isoquercitrin (IQ) was reported to have potential anti-neuroinflammatory activity. The acylation of glycoside in IQ enhanced its hydrophobicity, which was expected to enhance the protective effect against inflammation. In this study, three carboxylic acids with anti-neuroinflammatory effects including cinnamic acid, ibuprofen (IBU) and acetylsalicylic acid were introduced into the 6''-OH of IQ through the corresponding vinyl esters intermediates ( 8a-8c ). Ultimately, the acylated IQ derivatives (Compound 9a-9c ) were obtained with 35–42% yields using immobilized lipase Novozym 435 as catalyst. Subsequently, their anti-neuroinflammatory activities were evaluated in lipopolysaccharide (LPS)-induced BV2 cells. Compound 9b improved cell viability in the range of ≤50 μM and significantly decreased NO, PGE 2 production and TNF-α, IL-1β release and oxidative stress level with a concentration-dependent manner. Also, it could downregulate iNOS, COX-2, TNF-α and IL-1β expression levels, approximately 40% reduction were achieved when 15 μM compound 9b was employed. In addition, compound 9b resisted phosphorylation and degradation of IkBαs, suppressing the activation of NF-κB signaling pathway, exhibiting excellent neuroinflammatory inhibition. Moreover, the administration of compound 9b (30, 60 mg/kg) alleviated behavioral disorders and neuronal damages in LPS-induced neuroinflammatory mice. Meanwhile, the decreased TNF-α, IL-1β release, expression and the inhibited glial cells activation were obtained in compound 9b -treated group, which was superior to that of IQ or IBU. Overall, these findings demonstrated that compound 9b , formed by the introduction of ibuprofen into IQ, can serve as a novel promising therapeutic agent for anti-neuroinflammation.
研究领域:
药理学
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神经科学
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炎症
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Lingxian Liu,Haibo Li,Zhenzhong Wang,Xinsheng Yao,Wei Xiao,Yang Yu
ABSTRACT Background Migraine is widely recognized as the third most prevalent medical condition globally. Tianshu capsule (TSC), derived from “Da Chuan Xiong Fang” of the Jin dynasty, is integral in the clinical treatment of migraines. However, the chemical properties and therapeutic mechanisms of TSC different portions remain unclear. Purpose This study was designed to investigate the effects of TSC different portions (including small molecular TSCP-SM and polysaccharides TSC-P) on migraines and explore the underlying mechanisms. Study design and methods First of all, migraine rats were established by nitroglycerin injection and treated with TSC, TSC-P, and TSC-SM. ELISA, qPCR, and immunofluorescence were used to evaluate the pharmacological effects on migraine rats. Secondly, UPLC-Q/TOF-MS and GC-MS were employed to detect the components of TSCP-SM. PMP-HPLC, NMR, FT-IR, UV-Vis, AFM, and SEM were used for the chemical profiling of polysaccharides. Thirdly, the metabolic behavior profile of TSC-P was characterized by oral administrated fluorescence-labeled TSC-P and detected by NIR imaging. Finally, the anti-migraine mechanisms were explored by determining the composition of gut microbiota, analyzing colonic short-chain fatty acids (SCFAs), and examining serum tryptophan-related metabolites. Results Both small molecules (45 volatiles and 114 small molecules) and polysaccharides (including Glc, Ara, Gal, and Gal A) have exhibited effectiveness in alleviating migraines, and this efficacy is associated with reduced CGRP and iNOS levels, along with increased β -EP expressions. Further mechanistic exploration revealed that small-molecules exhibited effectiveness in migraines treatment by exerting antioxidative actions, while polysaccharides demonstrated superior therapeutic effects in regulating 5-HT levels. By monitoring the metabolic behavior of polysaccharides with fluorescent labeling, it was observed that TSC-P exhibited poor absorption. Instead, TSC-P demonstrated its therapeutic effects by modulating the aberrations in gut microbiota (including Alloprevotella, Muribaculaceae_ge , and Ruminococcaceae_UCG-005 ), cecum short-chain fatty acids (such as isobutyric, isovaleric, and valeric acids), and serum tryptophan-related metabolites (including indole-3-acetamide, tryptophol, and indole-3-propionic acid). Conclusion This research provides innovative insights into chemical composition, metabolic behavior, and proposed anti-migraine mechanisms of TSC from a polarity-based perspective, and pioneering an exploration focused on the polysaccharide components within TSC for the first time.
研究领域:
药理学
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神经科学
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分析化学
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代谢组学
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微生物学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
·
2022
·
IF 14.026
Xiaojuan Jiang,Yihua Lin,Yunlong Wu,Caixia Yuan,Xuli Lang,Jiayun Chen,Chunyan Zhu,Xinyi Yang,Yu Huang,Hao Wang,Caisheng Wu
Glycyrrhizae Radix et Rhizoma, a traditional Chinese medicine also known as Gan Cao (GC), is frequently included in clinical prescriptions for the treatment of pneumonia. However, the pharmacological components of GC for pneumonia treatment are rarely explored. Gan An He Ji oral liquid (GAHJ) has a simple composition and contains GC liquid extracts and paregoric, and has been used clinically for many years. Therefore, GAHJ was selected as a compound preparation for the study of GC in the treatment of pneumonia. We conducted an in vivo study of patients with pneumonia undergoing GAHJ treatments for three days. Using the intelligent mass spectrometry data-processing technologies to analyze the metabolism of GC in vivo, we obtained 168 related components of GC in humans, consisting of 24 prototype components and 144 metabolites, with 135 compounds screened in plasma and 82 in urine. After analysis of the metabolic transformation relationship and relative exposure, six components (liquiritin, liquiritigenin, glycyrrhizin, glycyrrhetinic acid, daidzin, and formononetin) were selected as potential effective components. The experimental results based on two animal pneumonia models and the inflammatory cell model showed that the mixture of these six components was effective in the treatment of pneumonia and lung injury and could effectively downregulate the level of inducible nitric oxide synthase (iNOS). Interestingly, glycyrrhetinic acid exhibited the strongest inhibition on iNOS and the highest exposure in vivo. The following molecular dynamic simulations indicated a strong bond between glycyrrhetinic acid and iNOS. Thus, the current study provides a pharmaceutical basis for GC and reveals the possible corresponding mechanisms in pneumonia treatment.
研究领域:
药理学
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中药学
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质谱学
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炎症
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分子动力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Heliyon
·
2023
·
IF 4
Ran Tu,Cheng Zhou,Wenfeng Huang,Zhengping Feng,Qiufang Zhao,Xiaofei Shi,Langjun Cui,Keke Chen
Rationale and objectives Fuzi, the dried root of Aconitum carmichaelii Debx, is one of the widely used traditional Chinese medicines. Fuzi polysaccharides are considered the most bioactive compounds with immunomodulatory functions, however, the mechanisms have not been evaluated. This study aims to systematically investigate the effects of Fuzi polysaccharides on the gut microbiota and immune function using a mouse model immunosuppressed with cyclophosphamide. Methods The short-chain fatty acid levels in cecal contents were measured by gas chromatography-mass spectrometry. The gut microbiota 16S rRNA gene were sequenced by next generation sequencing. The mRNA expression levels of NF-κB, IL-6, TNF-α, iNOS and COX-2 were measured using quantitative real-time polymerase chain reaction. The protein expression of occludin and zonula occludens-1 were analyzed by Western blot. The white blood cells were counted using automated hematology analyzer, and CD4 + FOXP3 + /CD4 + ratio was measured by flow cytometry. Results and Conclusions Fuzi polysaccharides had the function of elevating the concentration of acetic acid, propionic acid, isobutyric acid, and n-butyric acid in the cecum. Meanwhile, Fuzi polysaccharides could decrease the relative abundance of Helicobacter , Anaerotruncus , Faecalibacterium , Lachnospira , Erysipelotrichaceae _UCG-003, Mucispirillum , and Mycoplasma , and increase the relative abundance of Rhodospirillales , Ruminococcaceae _UCG-013, Mollicutes _RF39, Ruminococcus _1, Christensenellaceae _R-7_group, and Muribaculaceae in the gut. Furthermore, Fuzi polysaccharides exhibited the function of increasing spleen and thymus indices and number of white blood cells and lymphocytes. Fuzi polysaccharides could reverse the decreased mRNA expression of NF-кB, IL-6, and iNOS, differentiation of CD4 + FOXP3 + regulatory T cells as well as protein expression of occludin and zonula occludens-1 induced by cyclophosphamide. In addition, the mRNA and protein expression of cytokines were significantly correlated with the abundance of gut microbiota under Fuzi polysaccharides treatment. Collectively, the above results demonstrated that Fuzi polysaccharides could regulate inflammatory cytokines and gut microbiota composition of immunosuppressive mice to improve immunity, thereby shedding light on revealing the molecular mechanism of polysaccharides of traditional Chinese medicines in the future.
研究领域:
免疫学
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微生物学
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药理学
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中药学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）