PHYTOMEDICINE
·
2024
·
IF 6.7
Hui-Hui Guo,Yan-Xing Han,Xiao-Juan Rong,Zhen Shen,Hao-Ran Shen,Ling-Fei Kong,Yun-Dan Guo,Ji-Zhou Li,Bo Xu,Tian-Le Gao,Lu-Lu Wang,Cai Tie,Jian-Dong Jiang
Background Asthma affects 3% of the global population, leading to over 0.25 million deaths. Due to its complexity, asthma is difficult to cure or prevent, and current therapies have limitations. This has led to a growing demand for alternative asthma treatments. We found rosmarinic acid (RosA) as a potential new drug candidate from natural medicine. However, RosA has poor bioavailability and remains mainly in the gastrointestinal tract after oral administration, suggesting the involvement of gut microbiota in its bioactivity. Purpose To investigate the mechanism of RosA in alleviating allergic asthma by gut-lung axis. Methods We used 16S rRNA gene sequencing and metabolites analysis to investigate RosA's modulation of gut microbiota. Techniques of molecular biology and metabolomics were employed to study the pharmacological mechanism of RosA. Cohousing was used to confirm the involvement of gut microbiota in RosA-induced improvement of allergic asthma. Results RosA decreased cholate levels from spore-forming bacteria, leading to reduced 5-hydroxytryptamine (5-HT) synthesis, bronchoconstriction, vasodilation, and inflammatory cell infiltration. It also increased short-chain fatty acids (SCFAs) levels, facilitating the expression of intestinal tight junction proteins to promote intestinal integrity. SCFAs upregulated intestinal monocarboxylate transporters (MCTs), thereby improving their systemic delivery to reduce Th2/ILC2 mediated inflammatory response and suppress eosinophil influx and mucus production in lung. Additionally, RosA inhibited lipopolysaccharide (LPS) production and translocation, leading to reduced TLR4-NFκB mediated pulmonary inflammation and oxidative stress. Conclusions The anti-asthmatic mechanism of oral RosA is primarily driven by modulation of gut microbiota-derived 5-HT, SCFAs, and LPS, achieving a combined synergistic effect. RosA is a safe, effective, and reliable drug candidate that could potentially replace glucocorticoids for asthma treatment.
研究领域:
药理学
·
免疫学
·
微生物学
·
呼吸医学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Xinxin Hou,Zhaozhou Zhang,Wanqing Chen,Jinming Li,Xiangxiang Zhu,Mingjie Li,Xiaoqi Guan,Haidong Guo,Yanlei Ma,Ling Zhao
Altered gut microbiota has evidenced to be associated with colitis and colonic tumorigenesis, however bacteria-driven mechanism underlying inflammation-related colon pathologies remains undetermined. This study identifies a previously overlooked genus, Megasphaera , is highly abundant in inflammatory bowel diseases (IBD) and colorectal cancer (CRC) cohorts. A Megasphaera species, M. elsdenii reshapes colonic immunity by triggering dendritic cell (DC)-mediated Th1 and Th17 inflammation. Mechanistically, M. elsdenii and its lipopolysaccharide triggers DC activation via TLR4/NF-κB/IRF4 pathway. Accordingly, in Tlr4 −/− mice, M. elsdenii colonization cannot expand colonic infiltration of DCs and fails to induce Th1 and Th17 responses in. In a Shanghai CRC cohort with a 100% detective rate for Megasphaera , the species of Megasphaera significantly dominated in early onset CRC patients (<50 years old) rather than late-onset CRC (≥50 years old). M. elsdenii and M. elsdenii -enriched microbiota exacerbate colonic inflammation and tumorigenesis in azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced murine colitis-associated cancer model. Taken together, this study uncovers a pathogenic role of Megasphaera in developing colonic tumorigenesis via activating DC-mediated inflammation.
研究领域:
微生物学
·
免疫学
·
肿瘤学
·
胃肠病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
iScience
·
2024
·
IF 4.6
Chenming Zou,Ruihua Cai,Yunbing Li,Yu Xue,Guoguang Zhang,Gulimiran Alitongbieke,Yutian Pan,Sanguo Zhang
Recently, increasing evidence has shown the association between liver abnormal inflammation and cognition impairment, yet their age-related pathogenesis remains obscure. Here, our study provides a potential mechanistic link between liver macrophage excessive activation and neuroinflammation in aging progression. In aged and LPS-injected C57BL/6J mice, systemic administration of β-chitosan ameliorates hepatic macrophage-driven inflammation and reduces peripheral accumulations of TNF-α and IL-1β. Downregulation of circulatory pro-inflammatory cytokines then decreases vascular VCAM1 expression and neuroinflammation in the hippocampus, leading to cognitive improvement in aged/LPS-stimulated mice. Interestingly, β-chitosan treatment also exhibits the beneficial effects on the behavioral recovery of aged/LPS-stimulated zebrafish and Caenorhabditis elegans . In our cell culture and molecular docking experiments, we found that β-chitosan prefers shielding the MD-2 pocket, thus blocking the activation of TLR4-MD-2 complex to suppress NF-κB signaling pathway activation. Together, our findings highlight the extensive therapeutic potential of β-chitosan in reversing aged-related/LPS-induced cognitive impairment via the liver-brain axis.
研究领域:
免疫学
·
神经科学
·
老年学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2024
·
IF 3.8
Jiahao Liao,Jianyu Huang,Xiaoyi Chi,Xiaoqiong Li,Jian Kuang,Jianqiang Li,Xiangyu Bian,Jinzhu Pang,Jinjun Li,Weiwei Wang
In this study, D-mannose-modified nanoliposomes (MLipo@OVA) were developed to facilitate the targeted delivery of ovalbumin (OVA) to macrophages. The subsequent anti-inflammatory, antioxidant, and macrophage-polarizing effects of OVA were investigated. The nanoliposomes were designed with DSPE-PEG and DPPC to enhance the bioavailability and stability of OVA. In vitro analysis showed that MLipo@OVA significantly increased macrophage uptake, with D-mannose further enhancing this effect. MLipo@OVA reduced pro-inflammatory cytokines (TNF-α, IL-1β) and increased anti-inflammatory IL-10 levels in LPS-induced macrophages, primarily via the inhibition of the TLR4/NF-κB pathway. Furthermore, ROS levels were decreased, SOD and GSH activity was enhanced, the Nrf2/HO-1 pathway was activated, and the compound exhibited strong antioxidant activity. MLipo@OVA also promoted M2 macrophage polarization by upregulating CD206 and Arg-1 and downregulating iNOS. Overall, these results indicate that MLipo@OVA could be used as a nanomedicine to facilitate targeted anti-inflammatory and antioxidant therapies.
研究领域:
药学
·
免疫学
·
纳米技术
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Sujuan Wang,Wenqing Li,Wenxiu Liu,Lei Yu,Fu Peng,Junyuan Qin,Lin Pu,Yunli Tang,Xiaofang Xie,Cheng Peng
Background: Penthorum chinense Pursh (PCP) is widely utilized in China to treat a variety of liver diseases. It has been shown that flavonoids inhibit inflammation and have the potential to attenuate tissue damage and fibrosis. However, the mechanisms underlying how total flavonoids isolated from PCP (TFPCP) exert their anti-fibrotic effects remain unclear. Methods: The chemical composition of TFPCP was determined using UHPLC–Q-Orbitrap HRMS. Subsequently, rats were randomly assigned to a control group (Control), a carbon tetrachloride (CCl 4 )-induced hepatic fibrosis model group (Model), a positive control group [0.2 mg/(kg∙day)] of Colchicine), and three TFPCP treatment groups [50, 100, and 150 mg/(kg∙day)]. All substances were administered by gavage and treatments lasted for 9 weeks. Simultaneously, rats were intraperitoneally injected with 10%–20% CCl 4 for 9 weeks to induce liver fibrosis. At the end of the experiment, the liver ultrasound, liver histomorphological, biochemical indicators, and inflammatory cytokine levels were tested respectively. The underlying mechanisms were assessed using Western blot, immunohistochemistry, immunofluorescence, RT-qPCR, and metabolomics. Results: Fourteen flavonoids were identified in TFPCP. Compared with control animals, CCl 4 -treated rats demonstrated obvious liver injury and fibrosis, manifested as increases in gray values, distal diameter of portal vein (DDPV) and a decrease in blood flow velocity (VPV) in the ultrasound analysis; increased biochemical index values (serum levels of ALT, AST, TBIL, and ALP); marked increases in the contents of fibrotic markers (PC III, COL4, LN, HA) and inflammatory factors (serum TNF-α, IL-6, and IL-1β); and significant pathological changes. However, compared with the Model group, the ultrasound parameters were significantly improved and the serum levels of inflammatory cytokines were reduced in the TFPCP group. In contrast, the expression of TGF-β 1 , TLR4, and MyD88, as well as the p-P65/P65 and p-IκBα/IκBα ratios, were considerably reduced following TFPCP treatment. In addition, we identified 32 metabolites exhibiting differential abundance in the Model group. Interestingly, TFPCP treatment resulted in the restoration of the levels of 20 of these metabolites. Conclusion: Our findings indicated that TFPCP can ameliorate hepatic fibrosis by improving liver function and morphology via the inactivation of the TLR4/MyD88-mediated NF-κB pathway and the regulation of liver metabolism.
✓ 已验证
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.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2017
·
IF 4.44
Shudi Yang,Zhaoxiang Ren,Mengtian Chen,Ying Wang,Bengang You,Weiliang Chen,Chenxi Qu,Yang Liu,Xuenong Zhang
In this article, a novel graft polymeric micelle with targeting function ground on aptamer AS1411 was synthesized. The micelle was based on chitosan-ss-polyethylenimine-urocanic acid (CPU) with dual pH/redox sensitivity and targeting effects. This micelle was produced for codelivering Toll-like receptor 4 siRNA (TLR4–siRNA) and doxorubicin (Dox). In vitro investigation revealed the sustained gene and drug release from Dox–siRNA-loaded micelles under physiological conditions, and this codelivery nanosystem exhibited high dual pH/redox sensitivity, rapid intracellular drug release, and improved cytotoxicity against A549 cells in vitro. Furthermore, the micelles loaded with TLR4–siRNA inhibited the migration and invasion of A549. Excellent tumor penetrating efficacy was also noted in the A549 tumor spheroids and solid tumor slices. In vivo, multiple results demonstrated the excellent tumor-targeting ability of AS1411-chitosan-ss-polyethylenimine-urocanic acid (ACPU) micelle in tumor tissues. The micelles exhibited excellent antitumor efficacy and low toxicity in the systemic circulation in lung-tumor-bearing BALB/c mice. These results conclusively demonstrated the great potential of the new graft copolymer micelle with targeting function for the targeted and efficient codelivery of chemotherapeutic drugs and genes in cancer treatment.
研究领域:
药学
·
生物医学工程
·
癌症研究
·
药物递送系统
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Xue Bai,Jianjun Deng,Zhiguang Duan,Rongzhan Fu,Chenhui Zhu,Daidi Fan
Background Gastrointestinal mucositis stands as one of the most severe side effects of irinotecan (CPT-11). however, only palliative treatment is available at present. Therefore, there is an urgent need for adjunctive medications to alleviate the side effects of CPT-11. Purpose In this study, our objective was to explore whether ginsenoside Rh4 could serve as a modulator of the gut microbiota and an adjunctive agent for chemotherapy, thereby alleviating the side effects of CPT-11 and augmenting its anti-tumor efficacy. Study design A CPT-11-induced gastrointestinal mucositis model was used to investigate whether ginsenoside Rh4 alleviated CPT-11-induced gastrointestinal mucositis and enhanced the anti-tumor activity of CPT-11. Methods In this study, we utilized CT26 cells to establish a xenograft tumor model, employing transcriptomics, genomics, and metabolomics techniques to investigate the impact of ginsenoside Rh4 on CPT-11-induced gastrointestinal mucositis and the effect on the anti-tumor activity of CPT-11. Furthermore, we explored the pivotal role of gut microbiota and their metabolites through fecal microbiota transplantation (FMT) experiments and supplementation of the key differential metabolite, hyodeoxycholic acid (HDCA). Results The results showed that ginsenoside Rh4 repaired the impairment of intestinal barrier function and restored intestinal mucosal homeostasis in a gut microbiota-dependent manner. Ginsenoside Rh4 treatment modulated gut microbiota diversity and upregulated the abundance of beneficial bacteria, especially Lactobacillus_reuteri and Akkermansia_muciniphila , which further regulated bile acid biosynthesis, significantly promoted the production of the beneficial secondary bile acid hyodeoxycholic acid (HDCA), thereby alleviating CPT-11-induced gut microbiota dysbiosis. Subsequently, ginsenoside Rh4 further alleviated gastrointestinal mucositis through the TGR5-TLR4-NF-κB signaling pathway. On the other hand, ginsenoside Rh4 combination therapy could further reduce the weight and volume of colon tumors, promote tumor cell apoptosis, and enhance the anti-tumor activity of CPT-11 by inhibiting the PI3K-Akt signaling pathway, thus exerting a synergistic anti-tumor effect. Conclusion In summary, our findings confirm that ginsenoside Rh4 can alleviate CPT-11-induced gastrointestinal mucositis and enhance the anti-tumor activity of CPT-11 by modulating gut microbiota and its related metabolites. Our study validates the potential of ginsenoside Rh4 as a modulator of the gut microbiota and an adjunctive agent for chemotherapy, offering new therapeutic strategies for addressing chemotherapy side effects and improving chemotherapy efficacy.
研究领域:
肿瘤学
·
药理学
·
微生物学
·
分子生物学
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Feifan Liu,Yuanmei Bai,Xue Wu,Yan Wan,Shifang Luo,Linao Zhang,Tao Li,Hua Tang,Xianjin Tang,Rong Chen,Qinghua Chen,Yuhuan Xie,Peixin Guo
Ethnopharmacological relevance Allergic rhinitis (AR) stands as a non-infectious inflammatory condition affecting the nasal mucosa, marked by bouts of sneezing, nasal itching, and congestion. This ailment afflicts individuals across all age groups and poses challenges for effective treatment due to its chronic nature. Cangerzisan (CEZS), documented in the Jishengfang compendium, represents a traditional Chinese medicinal formula long utilized for AR management. Aim of the study : Investigating mechanism beneath therapeutic effect of CEZS in alleviating AR. Materials and methods The main active components in CEZS were determined by High Performance Liquid Chromatography (HPLC).The active constituents of CEZS and their corresponding targets were identified through an exhaustive screening process employing TCMSP database. To identify targets relevant to AR, GeneCards, OMIM, and DisGeNET databases were thoroughly applied. Protein-protein interaction (PPI) network was assembled utilizing STRING platform. Potential signaling pathways influenced by CEZS were delineated through GO and KEGG enrichment analyses. Subsequently, an AR model was induced by administering aluminum hydroxide (Al(OH)3) and ovalbumin (OVA) for affecting basal and local sensitization, respectively, facilitating experimental validation of the principal signaling pathways. Results There were 61 active constituents identified within CEZS, targeting a pool of 129 entities associated with AR treatment. Pathways analysis of KEGG revealed that CEZS potentially inhibits AR advancement via modulating TLR4 signaling pathway. Animal experiments demonstrated that CEZS effectively alleviated symptom scores in guinea pigs with AR. Moreover, it exhibited notable improvements in serum immune and inflammatory factors levels, as well as reduced inflammatory infiltration within nasal mucosa, including goblet and mast cells. CEZS was found to enhance GATA-3 expression while reducing T-bet expression, thereby modulating the TH1/TH2 immune balance. Additionally, CEZS downregulated HMGB1, TLR4, and p–NF–κB/NF-κB protein expressions within nasal mucosa of guinea pigs. Conclusions The therapeutic mechanism of CEZS against AR involves rectifying TH1/TH2 immune imbalance and upregulating inflammatory and immune factors through modulating key proteins expression within TLR4 pathway. This targeted regulation effectively impedes AR progression.
研究领域:
民族药理学
·
药理学
·
免疫学
·
传统中药
·
生物信息学
·
实验验证
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Meng Ding,Yuan Zhu,Xiaoting Xu,Hui He,Tianyu Jiang,Xiaochuan Mo,Zhuting Wang,Wenfeng Yu,Hailong Ou
Macrophage inflammation and oxidative stress promote atherosclerosis progression. Naringenin is a naturally occurring flavonoid with antiatherosclerotic properties. Here, we elucidated the effects of naringenin on monocyte/macrophage endothelial infiltration and vascular inflammation. We found naringenin inhibited oxidized low-density lipoprotein (oxLDL)-induced pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α toward an M2 macrophage phenotype and inhibited oxLDL-induced TLR4 (Toll-like receptor 4) membrane translocation and downstream NF-κB transcriptional activity. Results from flow cytometric analysis showed that naringenin reduced monocyte/macrophage infiltration in the aorta of high-fat-diet-treated ApoE-deficient mice. The aortic cytokine levels were also inhibited in naringenin-treated mice. Further, we found that naringenin reduced lipid raft clustering and acid sphingomyelinase (ASMase) membrane gathering and inhibited the TLR4 and NADPH oxidase subunit p47phox membrane recruitment, which reduced the inflammatory response. Recombinant ASMase treatment or overexpression of ASMase abolished the naringenin function and activated macrophage and vascular inflammation. We conclude that naringenin inhibits ASMase-mediated lipid raft redox signaling to attenuate macrophage activation and vascular inflammation.
研究领域:
心血管疾病
·
药理学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Xialin Sun,Tingwen Zhang,Yan Zhao,Han Yang,Yawei Li,Xin Sun,Xingbo Bian
Background Ulcerative colitis (UC) involves intestinal barrier dysfunction, immune dysregulation, and microbiota imbalance. Bletilla striata polysaccharide (BSP) shows anti-inflammatory potential, but its UC mechanisms remain unclear. Purpose To purify Bletilla striata polysaccharide (BSP-1), characterize its structure, and elucidate its multi-target UC therapeutic mechanisms. Methods This study purified a novel structure of neutral glucomannan with a small amount of acetylation (BSP-1). Together with tight junction protein analysis, oxidative stress markers, 16S rRNA sequencing, cytokine quantification, and molecular ecological network examination, the team used a UC mouse model created using dextran sodium sulfate (DSS). Results BSP-1 alleviated colitis by inhibiting TLR4/MyD88/NF-κB signaling (elevating IL-10; lowering IL-6, TNF-α, and IL-1β) and restoring integrity of the intestinal barrier via upregulating Occludin, ZO-1, MUC2, and Claudin-1. It reduced oxidative stress (lower MDA; higher SOD) and modulated gut microbiota (enriched Lactobacillus , suppressed Escherichia - Shigella ). Molecular ecological network analysis showed that BSP-1 restored microbial community stability by enhancing bacterial competition. Conclusion BSP-1 exerts integrated anti-inflammatory, barrier-repairing, and microbiota-regulating effects, highlighting its potential as a multi-target UC therapy and intestinal microecological regulator.
研究领域:
药理学
·
免疫学
·
微生物学
·
分子生物学
·
胃肠病学
·
植物学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2024
·
IF 4.7
Lei Zhang,Wei Zhu,Cong Zhang
Background DaYuan Yin (DYY), a traditional Chinese medicine for lung diseases, requires further study to understand how it improves acute lung injury (ALI). This study seeks to elucidate the material basis and molecular mechanisms underlying the treatment of ALI with DYY through network pharmacology, molecular docking, and experimental validation.Methods DYY’s active components and targets were identified using TCMSP and UHPLC-MS/MS, and a herb-component-target network was created with Cytoscape 3.7.2. ALI target genes were sourced from GeneCards, DisGeNET, and DrugBank. A PPI network was built, with core targets analyzed through GO and KEGG enrichment via Metscape. The therapeutic effects and mechanisms of DYY on LPS-induced ALI in rats were explored, and molecular docking evaluated the interactions between Nrf2, HO-1, TLR4, and the components.Results The study identified 95 active compounds, 234 therapeutic targets, and 2529 ALI-related genes, with 111 shared targets between DYY and ALI. KEGG analysis indicates that the PI3K-AKT, MAPK, and oxidative stress pathways are associated with DYY’s anti-ALI effects. Network pharmacology and UHPLC-MS/MS analysis revealed active ingredients like quercetin, Magnolol, and Wogonin. Compared with the model group, DYY reduced the lung dry–wet ratio (W/D) of ALI rats from (5.31 ± 0.51) to (4.47 ± 0.73)(P < 0.05). Meanwhile, the contents of IL-6 and TNF-α in bronchoalveolar lavage fluid (BALF) and MDA, NO and ROS in lung tissue were also significantly decreased. Notably, DYY enhances UCP2 mRNA expression, boosts Nrf2 and HO-1 expression, and inhibits TLR4-mediated pro-inflammatory mediators. Molecular docking analysis showed that the main components of DYY had strong binding ability with HO-1.Conclusion DYY can alleviate inflammation, oxidative stress, and ALI-related changes by targeting the Nrf2/HO-1 mediated TLR4 pathway, providing insights for developing effective ALI treatments.
研究领域:
药理学
·
分子生物学
·
中医中药
·
网络分析
·
炎症研究
·
氧化应激
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）