BIOMEDICINE & PHARMACOTHERAPY
·
2019
·
IF 3.743
James Asenso,Jun Yu,Feng Xiao,Mingyi Zhao,Jian Wang,Yijin Wu,Chun Wang,Wei Wei
Paeoniflorin-6'-O-benzene sulfonate (CP-25), is a novel derivative of paeoniflorin (Pae) with improved anti-arthritic effects. The aim of this study was to evaluate the therapeutic effects and pharmacokinetics of CP-25 when co-administered with MTX in adjuvant-induced arthritis (AA) rats. AA rats were randomly divided into 6 groups and treated as follows: TGP (50 mg/kg/day, ig), CP-25 (50 mg/kg/day, ig), MTX (0.5 mg/kg, 3 times/week, ig), TGP (50 mg/kg/day, ig) + MTX (0.5 mg/kg, 3 times/week, ig) and CP-25 (50 mg/kg/day, ig) + MTX (0.5 mg/kg, 3 times/week, ig) from days 14 - 35 after induction. Clinical, biochemical, and histological scores were used to assess the severity of arthritis while novel ultra-performance liquid chromatography mass spectrometry (UPLC-MS/MS) was used to detect plasma concentration of CP-25. Co-administration of CP-25 and MTX significantly reduced clinical signs of inflammation, suppressed the serum production of IL-17 compared to TGP (50 mg/kg/day, ig) and MTX (0.5 mg/kg, 3 times/week, ig). Pharmacokinetics studies showed increased AUC 0-t , C max , and t 1/2 of CP-25 while V/F and CL/F decreased when co-administered with MTX. We observed an increase concentration and longer exposure with decreased clearance of CP-25 when combined with MTX, that should be further explored for clinical RA therapy.
研究领域:
药理学
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风湿病学
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药物动力学
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炎症研究
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DOI
PubMed
高影响因子
ANALYTICAL BIOCHEMISTRY
·
2023
·
IF 2.9
Sili Zheng,Dongning Zhang,Bailu Duan,Guoyan Mo,Jingjing Li,Hailing Huang,Shanshan Wang,Yan Ye,Zhuang Huang,Ping Huang,Fengyun Zhang,Fang Huang,Lintao Han
Acute enteritis (AE) is a type of digestive disease caused by biochemical factors that irritate the intestinal tract or pathogenic bacteria that infect it. In China, Ma-Mu-Ran Antidiarrheal Capsules (MMRAC) have been applied against diarrhea caused by AE and bacillary dysentery for many years, but the underlying mechanisms of their beneficial effects are not known. In the present study, network pharmacology and metabolomics were performed to clarify the active ingredients of MMRAC and explore the specific mechanism of MMRAC on AE mice. A total of 43 active components of MMRAC with 87 anti-AE target genes were identified, and these target genes were enriched in IL-17 and HIF-1 signaling pathways. Integration analysis revealed that purine metabolism was the critical metabolic pathway by which MMRAC exerted its therapeutic effect against AE. Specifically, MAPK14, MMP9, PTGS2, HIF1A, EGLN1, NOS2 were the pivotal targets of MMRAC for the treatment of AE, and Western blot analysis revealed MMRAC to decrease protein levels of these pro-inflammatory signaling molecules. According to molecular docking, these key targets have a strong affinity with the MMRAC compounds. Collectively, MMRAC relieved the colon inflammation of AE mice via regulating inflammatory signaling pathways to reduce hypoxia and improved energy metabolism.
研究领域:
药理学
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代谢组学
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炎症
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胃肠病学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
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IF 7.7
Sichen Li,Huihui Peng,Yuning Sun,Jiali Yang,Juan Wang,Fuqing Bai,Chuanyi Peng,Shuzhen Fang,Huimei Cai,Guijie Chen
Yeast β-glucan intervention offers a promising strategy for managing colitis; however, the mechanisms remain unknown. In the present work, the protective effects of yeast β-glucan on DSS-induced colitis in mice was evaluated, focusing on its interaction with gut microbiota. The result showed yeast β-glucan significantly alleviated colitis symptoms, evidenced by reduced weight loss, lower disease activity index (DAI) scores, and minimized intestinal damage. It enhanced intestinal barrier integrity via upregulation of tight junction proteins, suppressed lipopolysaccharide (LPS) release, and decreased pro-inflammatory cytokines production. Additionally, yeast β-glucan boosted short-chain fatty acids (SCFAs) production, and activated their receptors, increased the relative abundances of beneficial microbes like Lactobacillus and Lachnospiraceae_UCG-006 . Transcriptomic analyses suggest that yeast β-glucan mitigates inflammation by downregulating gene expression related to IL-17 pathway. Our findings highlight potential of yeast β-glucan as a therapeutic agent for colitis through modulation of gut microbiota and inflammatory responses.
研究领域:
免疫学
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胃肠病学
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微生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Xiaoyu Tao,Yifei Gao,Zhengsen Jin,Shan Lu,Zhiqi Li,Siyu Guo,Qiqi Fan,Jiaqi Li,Chuanqi Qiao,Huiling Lei,Zhiqiang Zhang,Chongjun Zhao,Jiarui Wu
Background The combined therapeutic mechanisms of evodiamine (EVO) and berberine (BBR), which are the primary bioactive components contributing to the pharmacological effects of Euodiae Fructus and Rhizoma Coptidis , a classic herb pair used for colitis, have not yet been fully elucidated Purpose This study aimed to investigate the critical mechanisms by which co-administration EVO and BBR mitigated EVO-induced hepatotoxicity while exerting therapeutic effects against colitis. Methods Safety and therapeutic outcomes of EVO alone and combined BBR were validated in normal and colitis models. RNA-seq sequencing was performed on liver and colon tissues from different groups, while metagenomic sequencing was utilized to analysis fecal samples. An integrated bioinformatics analysis of transcriptomic and metagenomic data was conducted to reveal the mechanisms underlying EVO-induced hepatotoxicity and the protective and synergistic effects of BBR against colitis. Molecular biology experiments were employed to validate the regulatory mechanism, with a particular emphasis on the interactions within the gut- liver axis, including those related to lipid metabolism and inflammatory pathways. Results BBR attenuated EVO-induced hepatotoxicity in C57 mice by ameliorating pathological injuries and hepatic steatosis as well as inhibiting abnormal AST/ALT elevation, thereby revealing its hepatoprotective effects. In colitis mice, the combination therapy exhibited enhanced efficacy in reducing mucosal damage, restoring goblet cells populations, and suppressing pro-inflammatory cytokines production compared to monotherapy. Integrated analysis of RNA-seq combined with experimental validation revealed that EVO-induced hepatotoxicity was associated with the disrupted fatty acid β-oxidation and cholesterol synthesis homeostasis. Notably, co-administration of BBR effectively rescued metabolic disturbance through modulating core regulatory targets such as ACSL1, CPT1B, SQLE, DHCR7. Additionally, the combination treatment synergistically inhibited IL-17/NF-κB signaling, upregulated tight junction proteins, and rectified gut microbiota dysbiosis, thereby alleviating intestinal injury in colitis mice. Furthermore, ACSL3, a central regulator of fatty acid β-oxidation, was identified as a pivotal target through which the combination of EVO combined BBR suppressed lipid peroxidation-mediated activation of IL-17/NF-κB, leading to alleviate inflammation in LPS-induced NCM460 cell. Conclusion ACSL3 was identified as the critical therapeutic target through underlying the amelioration of fatty acid metabolism-mediated inflammatory injury in colitis by the combined administration of EVO and BBR, thereby offering a scientific foundation for precise and safe clinical drug administration.
研究领域:
药理学
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毒理学
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胃肠病学
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系统生物学
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生物信息学
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分子生物学
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民族药理学
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代谢
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免疫学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Ming Li,Ru Qu,Ping Li,Xuan Mo,Juan Liu,Biao Dong,Liting Liu,Zhenjiang Zech Xu
This study aimed to investigate the potential alleviating effect of Epimedium polysaccharide (EP) on intestinal inflammation aggravated by Porphyromonas gingivalis (Pg). P. gingivalis , an oral pathogen, may play a role in intestinal inflammation, highlighting the necessity to explore substances capable of inhibiting its pathogenicity. Initially, in vitro screening experiments utilizing co -culturing and quantitative polymerase chain reaction revealed that EP significantly inhibited the growth of P. gingivalis and the levels of virulence genes, including Kgp and RgpA. Subsequent mouse experiments demonstrated that EP notably ameliorated Pg-aggravated weight loss, disease activity index, histopathological lesions, and disruption of intestinal barrier integrity, evidenced by a reduction in tight junction protein levels. Flow cytometry analysis further illustrated that EP attenuated Pg-induced Th17 differentiation and Th17-related cytokines, such as IL-17 and IL-6. Additionally, 16S rRNA amplicon sequencing analysis elucidated that EP significantly mitigated Pg-induced gut microbiota dysbiosis, enriching potentially beneficial microbes, including Akkermansia and Bifidobacterium . The metabolomic analysis provided further insight, indicating that EP intervention altered the accumulation of relevant intestinal metabolites and exhibited correlations with disease indicators. In conclusion, our research suggested that EP holds promise as a prospective therapeutic agent for alleviating P. gingivalis -aggravated intestinal inflammation.
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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胃肠病学
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产品关联
DOI
PubMed
高影响因子
Antioxidants
·
2025
·Vol. 14
·期 10
·1206
·
IF 6.6
Haoyu Liu,Zhen Yang,Qian Chen,Hongjuan Zhang,Yu Liu,Di Wu,Dan Shao,Shengyi Wang,Baocheng Hao
Chronic inflammatory bowel disease, ulcerative colitis (UC), currently lacks specific drugs for clinical treatment, and screening effective therapeutic agents from natural plants represents a critical research strategy. This study aimed to investigate the therapeutic potential of the flavonoid extract of Polygonum viviparum L. (TFPV) against UC. Liquid chromatography-mass spectrometry (LC-MS) was used to identify the chemical components of TFPV, while cell and animal models were employed to evaluate its anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation. The mechanism of anti-inflammatory action was further investigated using a mouse model of UC induced by dextran sulfate sodium (DSS). The results revealed the identification of 32 bioactive components in TFPV, with major compounds such as kaempferol, luteolin, galangin, and quercetin. TFPV effectively mitigated inflammatory damage induced by LPS in IPEC-J2 cells and C57BL/6 mice. In the UC modeled by DSS, TFPV attenuated intestinal inflammation by reducing pro-inflammatory cytokines IL-1β, IL-6, and TNF-α; increasing the anti-inflammatory cytokine IL-10; up-regulating tight junction protein expression such as Claudin-1, Occludin, and ZO-1; and inhibiting the expression of PI3K, AKT, NF-κB, and IL-17 proteins. Analysis of mice fecal samples through 16S rRNA gene sequencing demonstrated that TFPV adjusted the equilibrium of gut microbiota by boosting the abundance of Dubosiella and diminishing that of Enterococcus , Romboutsia , and Enterobacter . Untargeted metabolomics analysis further revealed that TFPV reduced inosine and ADP levels while increasing dGMP levels by the regulation of purine metabolism, ultimately resulting in decreased uric acid levels and thereby alleviating intestinal inflammation. Additionally, TFPV safeguarded the intestinal mucosal barrier by enhancing the expression of tight junctions. In conclusion, TFPV alleviates UC by blocking the PI3K/AKT/NF-κB and IL-17 signaling pathways, lessening intestinal inflammation and injury, safeguarding intestinal barrier integrity, balancing gut microbiota, and lowering uric acid levels, suggesting its promise as a therapeutic agent for UC.
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Xiao-Lu Jie,Zi-Rui Luo,Jin Yu,Zhe-Ren Tong,Qiao-Qiao Li,Jia-Hui Wu,Yi Tao,Pei-Shi Feng,Ji-Ping Lan,Ping Wang
Ethnopharmacological relevance Pi-Pa-Run-Fei-Tang (PPRFT) is an empirical TCM prescription for treating asthma. However, the underlying mechanisms of PPRFT in asthma treatment have yet to be elucidated. Recent advances have revealed that some natural components could ameliorate asthma injury by affecting host metabolism. Untargeted metabolomics can be used to better understand the biological mechanisms underlying asthma development and identify early biomarkers that can help advance treatment. Aim of the study The aim of this study was to verification the efficacy of PPRFT in the treatment of asthma and to preliminarily explore its mechanism. Materials and methods A mouse asthma model was built by OVA induction. Inflammatory cell in BALF was counted. The level of IL-6, IL-1β, and TNF-α in BALF were measured. The levels of IgE in the serum and EPO , NO , SOD , GSH-Px, and MDA in the lung tissue were measured. Furthermore, pathological damage to the lung tissues was detected to evaluate the protective effects of PPRFT. The serum metabolomic profiles of PPRFT in asthmatic mice were determined by GC-MS. The regulatory effects on mechanism pathways of PPRFT in asthmatic mice were explored via immunohistochemical staining and western blotting analysis. Results PPRFT displayed lung-protective effects through decreasing oxidative stress, airway inflammation , and lung tissue damage in OVA-induced mice, which was demonstrated by decreasing inflammatory cell levels, IL-6, IL-1β, and TNF-α levels in BALF, and IgE levels in serum, decreasing EPO, NO, and MDA levels in lung tissue, elevating SOD and GSH-Px levels in lung tissue and lung histopathological changes. In addition, PPRFT could regulate the imbalance in Th17/Treg cell ratios, suppress RORγt, and increase the expression of IL-10 and Foxp3 in the lung. Moreover, PPRFT treatment led to decreased expression of IL-6, p-JAK2/Jak2, p-STAT3/STAT3, IL-17, NF-κB, p-AKT/AKT, and p-PI3K/PI3K. Serum metabolomics analysis revealed that 35 metabolites were significantly different among different groups. Pathway enrichment analysis indicated that 31 pathways were involved. Moreover, correlation analysis and metabolic pathway analysis identified three key metabolic pathways: galactose metabolism; tricarboxylic acid cycle; and glycine, serine , and threonine metabolism. Conclusion This research indicated that PPRFT treatment not only attenuates the clinical symptoms of asthma but is also involved in regulating serum metabolism. The anti-asthmatic activity of PPRFT may be associated with the regulatory effects of IL-6/JAK2/STAT3/IL-17 and PI3K/AKT/NF-κB mechanistic pathways.
研究领域:
药理学
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免疫学
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代谢组学
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中医
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Jing Liu,Bocun Li,Xiaohong Zhou,Guangya Liu,Chao Li,Zhaoduan Hu,Rui Peng
Ethnopharmacological relevance Zhubi Decoction (ZBD) is a modified formulation derived from the classic traditional Chinese medicine prescription “Er-Xian Decoction” documented in the esteemed “Clinical Manual of Chinese Medical Prescription”. While the utilization of ZBD has exhibited promising clinical outcomes in treating rheumatoid arthritis (RA), the precise bioactive chemical constituents and the underlying mechanisms involved in its therapeutic efficacy remain to be comprehensively determined. Aim of the study This study aims to systematically examine ZBD's pharmacological effects and molecular mechanisms for RA alleviation. Materials and methods Utilizing the collagen-induced arthritis (CIA) rat model, we comprehensively evaluated the anti-rheumatoid arthritis effects of ZBD in vivo through various indices, such as paw edema, arthritis index, ankle diameter, inflammatory cytokine levels, pathological conditions, and micro-CT analysis. The UPLC-MS/MS technique was utilized to analyze the compounds of ZBD. The potential therapeutic targets and signaling pathways of ZBD in the management of RA were predicted using network pharmacology. To analyze comprehensive metabolic profiles and identify underlying metabolic pathways, we conducted a serum-based widely targeted metabolomics analysis utilizing LC-MS technology. Key targets and predicted pathways were further validated using immunofluorescent staining, which integrated findings from serum metabolomics and network pharmacology analysis. Additionally, we analyzed the gut microbiota composition in rats employing 16 S rDNA sequencing and investigated the effects of ZBD on the microbiota of CIA rats through bioinformatics and statistical methods. Results ZBD exhibited remarkable efficacy in alleviating RA symptoms in CIA rats without notable side effects. This included reduced paw redness and swelling, minimized joint damage, improved the histopathology of cartilage and synovium, mitigated the inflammatory state, and lowered serum concentrations of cytokines TNF-α, IL-1β and IL-6. Notably, the effectiveness of ZBD was comparable to MTX. Network pharmacology analysis revealed inflammation and immunity-related signaling pathways, such as PI3K/AKT, MAPK, IL-17, and TNF signaling pathways, as vital mediators in the effectual mechanisms of ZBD. Immunofluorescence analysis validated ZBD's ability to inhibit PI3K/AKT pathway proteins. Serum metabolomics studies revealed that ZBD modulates 170 differential metabolites, partially restored disrupted metabolic profiles in CIA rats. With a notable impact on amino acids and their metabolites, and lipids and lipid-like molecules. Integrated analysis of metabolomics and network pharmacology identified 6 pivotal metabolite pathways and 3 crucial targets: PTGS2, GSTP1, and ALDH2. Additionally, 16 S rDNA sequencing illuminated that ZBD mitigated gut microbiota dysbiosis in the CIA group, highlighting key genera such as Ligilactobacillus , Prevotella_9 , unclassified_Bacilli , and unclassified_rumen_bacterium_JW32 . Correlation analysis disclosed a significant link between 47 distinct metabolites and specific bacterial species. Conclusion ZBD is a safe and efficacious TCM formulation, demonstrates efficacy in treating RA through its multi-component, multi-target, and multi-pathway mechanisms. The regulation of inflammation and immunity-related signaling pathways constitutes a crucial mechanism of ZBD's efficacy. Furthermore, ZBD modulates host metabolism and intestinal flora. The integrated analysis presents experimental evidence of ZBD for the management of RA.
研究领域:
药理学
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免疫学
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代谢组学
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微生物学
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中医药
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2023
·
IF 5.4
Hupo Zhan,Ruixin Chen,Mei Zhong,Guowei Wang,Guihua Jiang,Xingbao Tao,Min Chen,Yunbin Jiang
Ethnopharmacological relevance Lamiophlomis rotata (Benth.) Kudo (LR, Lamiaceae) is a traditional Tibetan medicinal material in China. Tibetan medicine classic and research report suggested that LR could be used to cure rheumatoid arthritis (RA). However, the anti-RA active ingredients and pharmacological mechanisms of LR have not been elucidated. Aim of the study To explore the mechanisms and key active ingredients of total flavonoids from LR (TFLR) against RA. Materials and methods First, the mechanisms of TFLR against RA were investigated on collagen-induced arthritis (CIA) rat model by analyzing paw appearance, paw swelling, arthritis score, spleen index, thymus index, inflammatory cytokine (TNF-α, IL-1β, IL-6 and IL-17) levels in serum, histopathology of ankle joint and synovium from knee joint (hematoxylin-eosin, safranin O-fast green and DAB-TUNEL staining), and apoptosis-related protein (PI3K, Akt1, p-Akt, Bad, p-Bad, Bcl-xL and Bcl-2) levels in the synovium of ankle joints (Western blot). Then, the crucially active ingredients of TFLR against RA were explored by network pharmacology , ingredient analysis, in vitro metabolism and TNF-α-induced human RA synovial fibroblast MH7A proliferation assays. Network pharmacology was applied to predict the key active ingredients of TFLR against RA. The ingredient analysis and in vitro metabolism of TFLR were performed on HPLC, and MH7A proliferation assay were applied to evaluate the predicted results of network pharmacology. Results TFLR shown excellently anti-RA effect by reducing paw swelling, arthritis score, spleen index, thymus index and inflammatory cytokine (IL-1β, IL-6 and IL-17) levels, and improving the histopathological changes of ankle joint and synovium from knee joint in CIA rats. Results of Western blot indicated that TFLR reversed the changes of PI3K, p-Akt, p-Bad, Bcl-xL and Bcl-2 levels in the ankle joint synovium of CIA rats. Results of network pharmacology exhibited that luteolin was identified as the pivotal active ingredient of TFLR against RA. The ingredient analysis of TFLR indicated that the main ingredient in TFLR was luteoloside . The in vitro metabolism study of TFLR suggested that luteoloside could be converted to luteolin in artificial gastric juice and intestinal juice. Results of MH7A proliferation assay showed that there was no significant difference between TFLR and equal luteoloside on the viability of MH7A cells, indicating that luteoloside was the key active ingredient of TFLR against RA. Additionally, the luteolin (same mol as luteoloside) showed better inhibitory effect on the viability of MH7A cells than luteoloside. Conclusion TFLR showed anti-RA effect, and the mechanism was related to promoting synovial cell apoptosis mediated by PI3K/Akt/Bad pathway. Meanwhile, this work indicated that luteoloside was the key active ingredient of TFLR against RA. This work lays a foundation for providing TFLR product with clear mechanism and stable quality to treat RA.
研究领域:
药理学
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民族药理学
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网络药理学
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炎症
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风湿病学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-27
·
IF 10.6
Pu Chaoyu,Wang Yong,Xiang Honglin,He Jiangtao,Sun Qiyuan,Yong Yuan,Chen Lu,Jiang Ke,Yang Hanfeng,Li Yuling
Background In diabetic wounds, hyperglycemia-induced cytotoxicity and impaired immune microenvironment plasticity directly hinder the wound healing process. Regulation of the hyperglycemic microenvironment and remodeling of the immune microenvironment are crucial.Results Here, we developed a nanozymatic functionalized regenerative microenvironmental regulator (AHAMA/CS-GOx@Zn-POM) for the effective repair of diabetic wounds. This novel construct integrated an aldehyde and methacrylic anhydride-modified hyaluronic acid hydrogel (AHAMA) and chitosan nanoparticles (CS NPs) encapsulating zinc-based polymetallic oxonate nanozyme (Zn-POM) and glucose oxidase (GOx), facilitating a sustained release of release of both enzymes. The GOx catalyzed glucose to gluconic acid and (H₂O₂), thereby alleviating the effects of the hyperglycemic microenvironment on wound healing. Zn-POM exhibited catalase and superoxide dismutase activities to scavenge reactive oxygen species and H₂O₂, a by-product of glucose degradation. Additionally, Zn-POM induced M1 macrophage reprogramming to the M2 phenotype by inhibiting the MAPK/IL-17 signaling diminishing pro-inflammatory cytokines, and upregulating the expression of anti-inflammatory mediators, thus remodeling the immune microenvironment and enhancing angiogenesis and collagen regeneration within wounds. In a rat diabetic wound model, the application of AHAMA/CS-GOx@Zn-POM enhanced neovascularization and collagen deposition, accelerating the wound healing process.Conclusion sTherefore, the regenerative microenvironment regulator AHAMA/CS-GOx@Zn-POM can achieve the effective conversion of a pathological microenvironment to regenerative microenvironment through integrated control of the hyperglycemic-immune microenvironment, offering a novel strategy for the treatment of diabetic wounds.
研究领域:
材料科学
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生物医学工程
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药学
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伤口愈合
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免疫学
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纳米技术
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DOI
PubMed
高影响因子
Nature Microbiology
·
2023
·Vol. 8
·期 5
·919-933
·
IF 28.3
Han Ji-Xuan,Tao Zhi-Hang,Wang Ji-Lin,Zhang Lu,Yu Chen-Yang,Kang Zi-Ran,Xie Yuanhong,Li Jialu,Lu Shiyuan,Cui Yun,Xu Jia,Zhao Enhao,Wang Ming,Chen Jinxian,Wang Zheng,Liu Qiang,Chen Hui-Min,Su Wenyu,Zou Tian-Hui,Zhou Cheng-Bei,Hong Jie,Chen Haoyan,Xiong Hua,Chen Ying-Xuan,Fang Jing-Yuan
Epidemiological studies have indicated an association between statin use and reduced incidence of colorectal cancer (CRC), and work in preclinical models has demonstrated a potential chemopreventive effect. Statins are also associated with reduced dysbiosis in the gut microbiome, yet the role of the gut microbiome in the protective effect of statins in CRC is unclear. Here we validated the chemopreventive role of statins by retrospectively analysing a cohort of patients who underwent colonoscopies. This was confirmed in preclinical models and patient cohorts, and we found that reduced tumour burden was partly due to statin modulation of the gut microbiota. Specifically, the gut commensal Lactobacillus reuteri was increased as a result of increased microbial tryptophan availability in the gut after atorvastatin treatment. Our in vivo studies further revealed that L. reuteri administration suppressed colorectal tumorigenesis via the tryptophan catabolite, indole-3-lactic acid (ILA). ILA exerted anti-tumorigenic effects by downregulating the IL-17 signalling pathway. This microbial metabolite inhibited T helper 17 cell differentiation by targeting the nuclear receptor, RAR-related orphan receptor γt (RORγt). Together, our study provides insights into an anti-cancer mechanism driven by statin use and suggests that interventions with L. reuteri or ILA could complement chemoprevention strategies for CRC.
研究领域:
肿瘤学
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胃肠病学
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微生物学
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药理学
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DOI
PubMed
高影响因子
Foods
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2024
·Vol. 13
·期 22
·3543
·
IF 4.7
Yajie Li,Nan Huang,Qiulan Liu,Ying Sun,Kaidi Peng,Xueyu Jiang,Yang Yi
Despite the interaction between polyphenols and polysaccharides in food products, their specific non-covalent interactions and effects on macrophage functions are not well understood. Therefore, the interaction and mechanism of purified lotus root polysaccharide (PLRP) with polyphenols, and the regulatory mechanisms of the PLRP-polyphenol complex on the macrophage functionals were studied. By combining ferulic acid (FA) and chlorogenic acid (CHA) with PLRP, the complexes PLRP-FA, PLRP-CHA and the physical mixtures PLRP&FA and PLRP&CHA were prepared, where their mass ratios of polyphenols to PLRP were 143.97 and 601.67 mg g−1. Nuclear magnetic resonance (NMR), Fourier-transform infrared (FTIR), Ultraviolet (UV), and Transmission electron microscopy (TEM) analyses confirmed that PLRP and polyphenols may engage in non-covalent interactions via hydrogen bonds and hydrophobic interactions. We confirmed that non-covalent interactions led to high molecular weight, dense complexes. Both PLRP and its polyphenol complexes stimulated NO production by macrophages to varying degrees without exacerbating lipopolysaccharide-induced inflammatory responses. PLRP and PLRP-polyphenol complexes repaired cells with impaired antioxidant capacity, depending on doses. Those results indicated that after the combination of lotus root polysaccharide and polyphenol, the molecular weight and conformation changed significantly, which influenced the biological activity. RNA-seq analysis suggested that the regulatory mechanism of PLRP-polyphenol complex in macrophages may mainly involve oxidative phosphorylation, FoxO, TNF, IL-17, MAPK, NF-kappa B, and other signaling pathways. This study investigated the effects of polyphenol binding on the physicochemical characteristics and functional activities of polysaccharides, which provided references for the development of polysaccharide functional products and the control of nutritional quality.
研究领域:
食品科学
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免疫学
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分子生物学
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药学
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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）