Chinese Medicine
·
2024
·Vol. 19
·期 1
·1-18
·
IF 5.3
Zhen Jianhua,Li Yini,Zhang Yunan,Zhou Yali,Zhao Lu,Huang Guangrui,Xu Anlong
Background Shaoyao Decoction (SYD) is a widely recognized herbal formula utilized in traditional Chinese medicine for the treatment of diarrhea. Although it has demonstrated significant effectiveness in clinical practice for treating ulcerative colitis, the precise mechanisms by which it operates remain largely elusive. Methods The active ingredients of SYD were obtained by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), which were used to explore the potential pharmacological mechanism based on TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) and PANTHER (Protein Analysis Through Evolutionary Relationships) classification system. In a mouse model of dextran sulfate sodium (DSS)-induced colitis, mRNA sequencing, 16S rDNA sequencing and targeted metabolomics techniques were used to elucidate the mechanisms of SYD, and immunohistochemistry, immunofluorescence, enzyme linked immunosorbent assay, real time quantitative polymerase chain reaction and western blot were used to test the key targets. In addition, QGP-1 and H9 cells were performed to validate the discoveries from the animal experiments. Results In the mouse model of DSS-induced colitis, SYD effectively alleviated symptoms such as bloody stool, tissue damage, inflammation, intestinal flora dysbiosis and abnormal gene expression. Analyses of both differential expressed genes in colonic tissue and predicted 16S rDNA genes, as well as the analyses of targeted genes from TCMSP based on the active ingredients in UPLC-MS/MS of SYD, uncovered the enrichment of pathways involved in the biosynthesis and degredation of 5-hydroxytryptamine (5-HT). Interestingly, SYD suppressed the relative abundance of key genes in 5-HT synthesis, Tph1(Tryptophan hydroxylase 1) and Ddc (Dopa decarboxylase), in faeces from DSS-induced mice, leading to a reduction in the concentration of fecal 5-HT. Moreover, SYD augmented the production of butyric acid. Subsequently, increasing butyric acid influenced the metabolism of 5-HT in the organism through G protein-coupled receptor 43 by impeding its synthesis, facilitating its transport and degredation. These findings were additionally corroborated in a model utilizing enterochromaffin cell (QGP-1 cells). Furthermore, reduced levels of 5-HT hindered the activation of T lymphocytes (H9 cells) via the PKC (Protein kinase C) and NF-κB (Nuclear factor kappa-B) signaling pathways, by means of HTR1A (5-HT receptor 1A) and HTR3 (5-HT receptor 3). Additionally, diminished secretion of 5-HT resulted in reduced secretion of associated cytokines, thereby alleviating inflammation in the colon. Conclusion Through modulation of T lymphocyte activation mediated by 5-HT metabolism in the local colon via the intestinal flora and its metabolite, SYD effectively mitigated colonic inflammation in DSS-induced mice.
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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微生物学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2024
·Vol. 29
·期 5
·1-14
·
IF 3.4
Xinya Yu,Xiaoxi Li,Yunchun Xu,Yuwei Li,Ye Zhou,Junhua Zhang,Le Guo
Ulcerative colitis (UC) is a chronic idiopathic inflammatory condition affecting the rectum and colon. Inflammation and compromisation of the intestinal mucosal barrier are key in UC pathogenesis. Resveratrol (Res) is a naturally occurring polyphenol that exhibits anti‑inflammatory and antioxidant properties. Nuclear factor erythroid‑2‑related factor 2/heme oxygenase 1 (Nrf2/HO‑1) pathway regulates occurrence and development of numerous types of diseases through anti‑inflammatory and antioxidant activity. However, it is not clear whether Nrf2/HO‑1 pathway is involved in the treatment of Res in UC. Therefore, the present study aimed to investigate whether Res modulates the Nrf2/HO‑1 signaling pathway to attenuate UC in mice. Dextran sulfate sodium (DSS) was used to induce experimental UC in male C57BL/6J mice. Disease activity index (DAI) and hematoxylin eosin (H&E) staning was used to assessed the magnitude of colonic lesions in UC mice. ELISA) was utilized to quantify inflammatory cytokines (IL‑6, IL‑1β, TNF‑α and IL‑10) in serum and colon tissues. Immunohistochemistry and Western blot were used to evaluate the expression levels of tight junction (TJ) proteins [zonula occludens (ZO)‑1 and Occludin] in colon tissues. Pharmacokinetic (PK) parameters of Res were derived from TCMSP database. Networkpharmacology was employed to identify the biological function and pharmacological mechanism of Res in the process of relieving UC, and the key target was screened. The binding ability of Res and key target was verified by molecular docking. Finally, the effectiveness of key target was substantiated by Western blot. Res decreased DAI, ameliorated histopathological changes such as crypt loss, disappeatance of the mucosal epithelium, and inflammatory infiltration in mice. Additionally, Res decreased expression of pro‑inflammatory cytokines IL‑6, IL‑1β and TNF‑α and increased anti‑inflammatory factor IL‑10 expression. Res also restored the decreased protein expression of ZO‑1 and occludin after DSS treatment, increasing the integrity of the intestinal mucosal barrier. The PK properties of Res suggested that Res possesses the therapeutic potential for oral administration. Network pharmacology revealed that Res alleviated UC through anti‑inflammatory and antioxidant pathways, and confirmed that Nrf2 has a high binding affinity with Res and is a key target of Res against UC. Western blotting demonstrated that Res treatment increased the protein levels of Nrf2 and HO‑1. In conclusion, Res treatment activated the Nrf2/HO‑1 pathway to decrease clinical symptoms, inflammatory responses, and intestinal mucosal barrier damage in experimental UC mice.
研究领域:
药理学
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炎症性肠病
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分子生物学
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动物模型
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网络药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Jianqing Peng,Jia Zhou,Xing Liu,Xiaobo Zhang,Xiang Zhou,Zipeng Gong,Yi Chen,Xiangchun Shen,Yan Chen
Glucose oxidase (GOx)-based enzyme therapeutics are potential alternatives for colorectal cancer (CRC) treatment via glucose consumption and accumulation of hydrogen peroxide (H 2 O 2 ). Given that H 2 O 2 can be eliminated by cytoprotective autophagy, autophagy inhibitors that can interrupt autolysosome-induced H 2 O 2 elimination are promising combination drugs of GOx. Here, we developed a multifunctional biomimetic nanocarrier for effective co-delivery of an autophagy inhibitor-chloroquine phosphate (CQP) and GOx to exert their synergistic effect by irreversibly upregulating intracellular reactive oxygen species (ROS) levels. Poly (D, l -lactide- co -glycolide) (PLGA) nanoparticles (NPs) were used to encapsulate both GOx and CQP using a W/O/W multi-emulsion method. Calcium phosphate (CaP) was used to “fix” CQP to GOx in the internal water phase, where it served as a pH-sensitive unit to facilitate intracellular drug release. Folic acid-modified red blood cell membranes (FR) were used to camouflage the GOx/CQP/CaP encapsulated PLGA NPs (referred to as PLGA/GCC@FR). In an AOM/DSS-induced CRC mouse model, PLGA/GCC@FR exhibited improved antitumor effects, in which the number of tumor nodes were only a quarter of that in the free drug combination group. The enhanced therapeutic effects of PLGA/GCC@FR were attributed to the prolonged tumor retention which was verified by both dynamic in vivo imaging and drug biodistribution . This multifunctional biomimetic nanocarrier facilitated combined enzyme therapeutics by depleting glucose and augmenting intracellular ROS levels in tumor cells, which exerted a synergistic inhibitory effect on tumor growth. Therefore, this study proposed a novel strategy for the enhancement of combined enzyme therapeutics, which provided a promising method for effective CRC treatment.
研究领域:
癌症生物学
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药学
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纳米技术
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
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2024
·
IF 10.7
Tingting Zhang,Congcong Zhang,Xue Li,Dongfang Ren,Mingshuang Zheng,Shuo Zhang,Fangping Yuan,Xin Du,Zhenguo Zhang
Prostaglandin E2 (PGE2), an eicosane, regulates the physiological activity of inflammatory cells and represents a potential therapeutic target for facilitating tissue repair in vivo. In our work, an electrochemical immunosensor employing Ketjen black-Au nanoparticles (KB–Au) and poly tannic acid nanospheres conjugated with anti-PGE2 polyclonal antibody (PTAN-Ab) was designed to ultra-sensitively analyze PGE2 levels secreted by living cells and tissues. Antibody assembly strategies were explored to achieve signal amplification. Moreover, we studied the therapy effects of docosahexaenoic acid (DHA), arachidonic acid (AA), hyaluronic acid (HA), and small molecule 15-hydroxyprostaglandin dehydrogenase inhibitor (SW033291) on inflammation and evaluated the protective functions of HA and SW033291 in a murine model subjected to colitis induced by dextran sulfate sodium (DSS) using the developed sensor. The sensor exhibited a linear range of 10 −5 –10 6 fg/mL and a detection limit (LOD) of 10 −5 fg/mL. Fetal bovine serum (FBS) samples were used to achieve high recovery of target analytes. This study not only presents an effective strategy for ultra-sensitively monitoring PGE2 but also provides valuable insights into assessing the degree of inflammation and the therapeutic effect of related drugs. Research on human health monitoring and regenerative medicine could greatly benefit from the findings.
研究领域:
分析化学
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生物化学
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免疫学
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药理学
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再生医学
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产品关联
DOI
PubMed
高影响因子
Nature Sustainability
·
2024
·
IF 25.7
Wang Ruimin,Yang Shouzhi,Wang Mengfei,Zhou Yan,Li Xvelian,Chen Wei,Liu Wanshan,Huang Yida,Wu Jiao,Cao Jing,Feng Lei,Wan Jingjing,Wang Jiayi,Huang Lin,Qian Kun
Over a billion people across the world experience a high rate of missed disease diagnosis, an issue that highlights the need for diagnostic tools showing increased accuracy and affordability. In addition, such tools could be used in ecologically fragile and energy-limited regions, pointing to the need for developing solutions that can maximize health gains under limited resources for enhanced sustainability. Metabolic diagnosis holds promise but faces challenges due to the applicability of biospecimens and limited robustness of analytical tools. Here we present a diagnostic method coupling dried serum spots (DSS) and nanoparticle-enhanced laser desorption/ionization mass spectrometry (NPELDI MS). Our approach allows diagnosis of multiple cancers within minutes at affordable cost, environmental friendliness, serum-equivalent precision and user-friendly protocol. Our assessment shows that the implementation of this tool in less-developed regions could reduce the estimated proportion of undiagnosed cases of colorectal cancer from 84.30% to 29.20%, gastric cancer from 77.57% to 57.22% and pancreatic cancer from 34.56% to 9.30%—an overall reduction in the range of 20.35–55.10%. This work provides insights into delivering more sustainable metabolic diagnosis with maximum health gains.
研究领域:
医学诊断
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癌症研究
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可持续健康解决方案
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质谱分析
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公共卫生
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
·
2024
·Vol. 2024
·期 1
·5552747
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IF 3.5
Ying Zheng,Tianjiao Li,Xi Luo,Mengnan Jia,Liying Han,Hao Yu,Yongrui Bao,Shuai Wang,Xiansheng Meng
Inflammation is a well-known risk factor for tumor development. Intervening in chronic inflammation may be an effective approach to inhibit the progression of ulcerative colitis (UC) to colitis-associated colon cancer (CAC). Sophora japonica is a medicinal and food plant commonly used to treat hemorrhoids, bleeding, and inflammation, symptoms that coincide with those of patients with CAC. However, studies on using Sophora japonica to treat CAC are scarce. Therefore, this study aimed to investigate the anti-inflammatory and antitumor effects of Sophora japonica extract (SJE) using dextran sodium sulfate (DSS)-induced UC and azoxymethane (AOM)/DSS-induced CAC models. Furthermore, we employed ultraperformance liquid chromatography–quadrupole time-of-flight–tandem mass spectrometry (UPLC–QTOF–MS/MS) technology to explore the metabolomics mechanism through which SJE inhibited the progression of UC to CAC. The results demonstrated that SJE significantly inhibited UC and CAC and alleviated symptoms such as bloody stools, colon shortening, inflammation, and intestinal tissue damage in model mice. Further, 57 differential metabolites were identified by UPLC–QTOF–MS/MS, which were composed mainly of lipids (fatty acids, glycerophospholipids, sterol lipids, pregnenolone lipids, etc.) and peptides (amino acids). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggested that SJE might inhibit the progression of UC to CAC by regulating lipid metabolic pathways such as arachidonic acid metabolism, primary bile acid biosynthesis, and linoleic acid metabolism. This study, for the first time, substantiated the inhibitory effect of SJE on CAC. Employing metabolomics techniques, the research delved into the potential pathways through which SJE may exert its inhibitory effects on CAC by suppressing the progression of UC. These findings contribute scientific evidence to the application of Sophora japonica in functional foods and the development of natural drugs for the prevention and treatment of UC and CAC.
研究领域:
药理学
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肿瘤学
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胃肠病学
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代谢组学
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药物化学
✓ 已验证
DOI
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Fanghua Guo,Dongying Chen,Rong Tsao,Fereidoon Shahidi,Hua Xiong,Hua Zhang,Li Jiang,Yong Sun
Lentil hulls, a by-product of lentil processing, are rich in polyphenols and dietary fiber. In this study, a mouse model of nonalcoholic fatty liver disease (NAFLD) induced by dextran sulfate sodium (DSS) and high-fat diet (HFD) was used to investigate the intervention effect of green lentil hulls (GLH) from the perspective of intestinal and hepatic metabolism. Results suggest that DSS-induced gut inflammation and barrier disruption aggravate NAFLD; GLH intervention lowered body weight, liver weight gain and lipid deposition. It also inhibited liver fat accumulation and inflammation as well as intestinal inflammation. In addition, it enhanced liver antioxidant capacity, glucose tolerance and intestinal barrier integrity. Analysis of intestinal flora indicated that GLH advanced the abundance of Akkermansia-muciniphila and Verrucomicrobiaceae , which led to increased content of short-chain fatty acids (SCFAs) and inhibited the Firmicutes and Proteobacteria . Moreover, GLH intervention regulated taurine and hypotaurine metabolism, as well as the biosynthesis of unsaturated and saturated fatty acids in the liver. The relief by GLH on NAFLD may be a comprehensive effect of its rich dietary fiber and polyphenols on intestinal and hepatic metabolism via the gut-liver axis. This research also suggests that the low-value lentil hulls can serve as a valuable food supplement for enhanced gut health and reduced risk of NAFLD.
研究领域:
营养学
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胃肠病学
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肝病学
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微生物学
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代谢学
✓ 已验证
产品关联
DOI
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2024
·
IF 7
Yue Su,Zhengying Cui,Xinyan Yang,Yujun Jiang,Wei Zhang,Yu Zhang,Chaoxin Man
Ulcerative colitis (UC) is an immune-mediated intestinal disease without a comprehensive cure, and the alleviation of UC has become an urgent problem. The results showed that JY062 with its EPS group (JEC) alleviated the intestinal barrier damage caused by LPS. After JEC intervention on Caco-2 cells, resulted in upregulation of ZO-1, Claudin-1, Occludin and MUC2 transcript levels and decreased mRNA expression of Claudin-2 (p < 0.05). JEC effectively attenuated the inflammatory response in UC mice and restoration of immunoglobulin levels (IgG, IgM and IgA), which resulted in shortening and swelling of the colon, disappearance of goblet cells, infiltration of inflammatory cells and mucosal damage were alleviated in mice. Similarly, changes in the expression of MUC2 and tight junction proteins after JEC intervention also occurred in UC mice. Administration of JEC significantly inhibited the differentiation of pro-inflammatory Th17 cells in the thymus and peripheral blood, promoted the differentiation of CD4+ T cells to Treg cells, and effectively regulated DSS-induced macrophage imbalance, which was manifested by the polarization of pro-inflammatory M1 macrophages to anti-inflammatory M2 macrophages. This study clearly demonstrates that JEC could significantly prevent intestinal barrier on DSS-induced experimental colitis and could be applied as a potential symbiotic strategy to assist in the alleviation of UC.
研究领域:
微生物学
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免疫学
·
胃肠病学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2021
·
IF 4.384
Ziqing Wang,Wenwen Mu,Pengxiao Li,Guoyun Liu,Jie Yang
Curcumin was reported as an anti-inflammatory agent. However, curcumin's poor bioavailability limited its clinical utility. Here, thirty ortho -substituted mono-carbonyl curcumin derivatives, containing acetone, cyclopentanone, cyclohexanone or 4-piperidione ( N H, N -methyl or N -acrylyl) moieties replacing β-diketone moiety of curcumin, were investigated for anti-inflammatory activity. Two active ortho -trifluoromethoxy-substituted 4-piperidione-containing derivatives 22 and 24 owned good cell uptake ability, and displayed excellent anti-inflammatory activity in both lipopolysaccharide-induced Raw264.7 macrophages and a dextran sulfate sodium (DSS)-induced mouse model of colitis . They inhibited the production of nitric oxide , reactive oxygen species , malonic dialdehyde and cyclooxygenase-2; and the expression of pro-inflammatory cytokines interleukin-1β, tumor necrosis factor-α and myeloperoxidase ; the phosphorylation of mitogen-activated protein kinases; and the nucleus translocation of p65. What's more, 22 or 24 oral administered reduced the severity of clinical symptoms of ulcerative colitis (body weight and disease activity index), and reduced obviously DSS-induced colonic pathological damage (the colon length and histopathology analysis). These results suggested that ortho -trifluoromethoxy-substituted 4-piperidione-containing mono-carbonyl curcumin derivatives 22 and 24 were potential anti-inflammatory agents; and offered the important information for design and discovery of more potent anti-inflammatory drug candidates.
研究领域:
药理学
·
炎症研究
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药物化学
✓ 已验证
DOI
PubMed
高影响因子
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