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npj Biofilms and Microbiomes · 2021 ·Vol. 7 ·期 1 ·1-10 · IF 7.29

Improved functionality of Ligilactobacillus salivarius Li01 in alleviating colonic inflammation by layer-by-layer microencapsulation

Yao Mingfei,Lu Yanmeng,Zhang Ting,Xie Jiaojiao,Han Shengyi,Zhang Shuobo,Fei Yiqiu,Ling Zongxin,Wu Jingjing,Hu Yue,Ji Shouling,Chen Hao,Berglund Björn,Li Lanjuan

The low viability during gastrointestinal transit and poor mucoadhesion considerably limits the effectiveness of Ligilactobacillus salivarius Li01 (Li01) in regulating gut microbiota and alleviating inflammatory bowel disease (IBD). In this study, a delivery system was designed through layer-by-layer (LbL) encapsulating a single Li01cell with chitosan and alginate. The layers were strengthened by cross-linking to form a firm and mucoadhesive shell (~10 nm thickness) covering the bacterial cell. The LbL Li01 displayed improved viability under simulated gastrointestinal conditions and mucoadhesive function. Almost no cells could be detected among the free Li01 after 2 h incubation in digestive fluids, while for LbL Li01, the total reduction was around 3 log CFU/mL and the viable number of cells remained above 6 log CFU/mL. Besides, a 5-fold increase in the value of rupture length and a two-fold increase in the number of peaks were found in the (bacteria-mucin) adhesion curves of LbL Li01, compared to those of free Li01. Oral administration with LbL Li01 on colitis mice facilitated intestinal barrier recovery and restoration of the gut microbiota. The improved functionality of Li01 by LbL encapsulation could increase the potential for the probiotic to be used in clinical applications to treat IBD; this should be explored in future studies.

研究领域: 微生物学 · 医药科学 · 食品科学
✓ 已验证 DOI PubMed 高影响因子
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Food Bioscience · 2021 · IF 4.24

Fermented Maillard reaction product alleviates injurious effects in colon caused by Clostridium perfringens

Yujin Kim,Sejeong Kim,Heeyoung Lee,Nam-Su Oh,Min Suk Rhee,Yohan Yoon

Clostridium perfringens is an important bacterium among commensal bacteria in the gastrointestinal tract , which is known to possess potential pathogenicity during its inhabitation. In concordance with the concerns raised by its pathogenicity, this study aimed to elucidate if FMRP (fermented Maillard reaction products), the novel milk-derived material, can reduce the effect caused by the overabundance of C. perfringens in the gut. As a result, FMRP significantly reduced mRNA expression levels in the inflammatory cytokines (interleukin-10, interleukin-11, and interferon-γ) (p<0.05), and tumorigenic potential by activating the cell proliferation-suppressing factors (β-catenin, adenomatous polyposis coli , and E-cadherin) (p<0.05) and deactivation of the cell proliferation-inducing factor (cyclooxygenase-2) (p<0.05) in the colon. Moreover, the tight junction proteins (zonula occludens-1 and claudin-3) were recovered (p<0.05), and the antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) were decreased by FMRP (p<0.05). However, biochemical analyses showed no significant difference. These results indicate that C. perfringens might cause inflammation, oxidative stress , disruption of tight junctions and abnormal cell proliferation to the colon, but FMRP may reduce inflammation and generation of reactive oxygen, and recover tight junction in the colon.

研究领域: 微生物学 · 消化系统疾病 · 营养学
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International Journal of Nanomedicine · 2023 · IF 8

Short-Term Oral Administration of Mesoporous Silica Nanoparticles Potentially Induced Colon Inflammation in Rats Through Alteration of Gut Microbiota

Yue Yu,Zhou Wang,Ran Wang,Jing Jin,Yi Zhun Zhu

Purpose Mesoporous silica (MSNs) have attracted considerable attention for its application in the field of drug delivery and biomedicine due to its high surface area, large pore volume, and low toxicity. Recently, numerous studies revealed that gut microbiota is of critical relevance to host health. However, the toxicological studies of MSNs were mainly based on the degradation, biodistribution, and excretion in mammalian after oral administration for now. Here in this study, we explored the impacts of oral administration of three kinds of MSNs on gut microbiota in rats to assess its potential toxicity.Methods Forty rats were divided into four groups: control group; Mobil Composition of Matter No. 41 type mesoporous silica (MCM-41) group; Santa Barbara Amorphous-15 type mesoporous silica (SBA-15) group, and biodegradable dendritic center-radial mesoporous silica nanoparticle (DMSN) group. Fecal samples were collected 3 days and 7 days after the intake of MSNs and analyzed with high throughput sequencing. Gastric tissues in rats were obtained after dissection for the histological study.Results Three different MSNs (MCM-41, SBA-15, and DMSN) were successfully prepared in this study. The pore size of three MSNs was calculated similarly as (3.54 ± 0.15) nm, (3.48 ± 0.21) nm, and (3.45 ± 0.17) nm according to the BET & BJH model, respectively, while the particle size of MCM-41, SBA-15 and DMSN was around 209.2 nm, 1349.56 nm, and 244.4 nm, respectively. In the gene analysis of 16S rRNA, no significant changes in the diversity and richness were found between groups, while Verrucomicrobia decreased and Candidatus Saccharibacteria increased in MCM-41 treated groups. Meanwhile, no inflammatory and erosion symptoms were observed in the morphological analysis of the colons, except the MCM-41 treated group.Conclusion Three different MSNs, MCM-41, SBA-15, and DMSN were successfully prepared, and this study firstly suggested the impact of MSNs on the gut microbiota, and further revealing the potential pro-inflammatory effects of oral administration of MCM-41 was possibly through the changing of gut microbiota.

CAS / MDL: 78-10-4
研究领域: 纳米技术 · 毒理学 · 微生物学 · 药学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Food & Function · 2024 · IF 5.1

Glycosylation of oyster peptides by COS ameliorates zinc deficiency-induced syndromes: intestinal inflammation and imbalance of the gut microbiota in vivo

Xuening Yu,Guang Li,Shuling Zhou,Xiaoyang Liu,Fawen Yin,Deyang Li,Dayong Zhou

Zinc is essential for maintaining the integrity and repair of small intestinal epithelial cells while zinc deficiency could induce the inflammatory infiltration and imbalance of intestinal flora in the intestine. In this study, glycosylation between oyster protein hydrolysate (OPH) and chitosan oligosaccharide (COS) was conducted and used as the carrier of zinc ions (OCZn). The results of zeta potential and particle size distribution showed that the OPH-COS successfully bound to zinc ions to form OCZn with a surface zinc content of 0.56% (scanning electron microscopy). In addition, OCZn was found to exhibit good intestinal digestion by in vitro simulated digestion microscopy, while TSQ fluorescence staining revealed the presence of free zinc ions released from OCZn in the intestinal cells. In the zinc deficiency-induced mouse model, a moderate dose of OCZn (zinc: 6.96 mg kg−1) showed significant restorative effects on colonic inflammation (IL-1β: 28.20 pg per mg·protein, IL-6: 27.73 pg per mg·protein), protein expressions of HO-1 and ZO-1, oxidative stress (the liver and kidneys), and imbalance of the gut microbiota, increasing microbial diversity and abundance (ratio of Firmicutes/Bacteroides). Zinc deficiency triggered the abundance of Proteobacteria (risk of diseases), while the dominant bacteria were mainly restored to Bacteroides, Parabacteroides, Alistipes, Alloprevotella, and Muribaculaceae following the administration of OCZn. This study provided a theoretical basis for improving the inflammatory infiltration of the colon and the imbalance of intestinal flora caused by zinc deficiency.

CAS / MDL: 302-17-0
研究领域: 营养学 · 微生物学 · 免疫学 · 胃肠病学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BIOMACROMOLECULES · 2021 · IF 6.988

Broad-Spectrum Reactive Oxygen Species Scavenging and Activated Macrophage-Targeting Microparticles Ameliorate Inflammatory Bowel Disease

Jiawei Li,Huiqiang Qiu,Hengtai Gong,Weijun Tong

Inflammatory bowel disease (IBD) is a refractory chronic inflammatory disease. An excessively high level of reactive oxygen species (ROS) in the colon is one of the characteristics and pathogenic factors of IBD. Therefore, scavenging excessive ROS is a feasible method to treat IBD. Because ROS include many types of species, scavenging a single kind of ROS is not enough to reduce the ROS level and cure IBD effectively. Herein, broad-spectrum ROS scavenging and activated macrophage-targeting microparticles (MPs) are successfully fabricated by coprecipitation of catalase (CAT) and bovine serum albumin into a MnCO3 template followed by deposition of polydopamine (PDA), assembly of targeting molecules on the surface, and finally removal of MnCO3. The CAT content of MPs is about 34.1%. The obtained MPs can effectively scavenge the broad spectrum of ROS and retain 88% of the radical scavenging activity even after the treatment of simulated gastric fluid. The surface-modified dextran sulfate endows MPs with the targeting ability toward activated macrophages, achieving a better therapeutic effect. The MPs with components mostly derived from natural substances exhibit good biocompatibility and can show excellent ROS scavenging ability in cell experiments. In animal experiments, oral administration of a proper dosage of MPs can substantially mitigate colonic inflammation, as evidenced by disease activity index scores reduced by ∼40%, reduced body weight loss, and the production of typical proinflammatory cytokines in the inflammatory colon. This kind of MP can also be utilized for the treatment of other inflammatory diseases.

研究领域: 药理学 · 生物技术 · 医学 · 免疫学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL IMMUNOPHARMACOLOGY · 2024 · IF 4.8

Fraxin (7-hydroxy-6-methoxycoumarin 8-glucoside) confers protection against ionizing radiation-induced intestinal epithelial injury in vitro and in vivo

Feng-Ling Tang,Li-Wei Xie,Lin-Feng Tang,Hai-Yan Lu,Rui-Qiu Zhu,Di-Fan Wang,Ye Tian,Shang Cai,Ming Li

The small intestine exhibits remarkable sensitivity to ionizing radiation (IR), which significantly hampers the effectiveness of radiotherapy in the treatment of abdominal and pelvic tumors. Unfortunately, no effective medications are available to treat radiation-induced intestinal damage (RIID). Fraxin (7-hydroxy-6-methoxycoumarin 8-glucoside), is a coumarin derivative extracted from the Chinese herb Cortex Fraxini. Several studies have underscored the anti-inflammatory, antibacterial, antioxidant, and immunomodulatory properties of fraxin. However, the efficacy of fraxin at preventing or mitigating RIID remains unclear. Thus, the present study aimed to investigate the protective effects of fraxin against RIID in vitro and in vivo and to elucidate the underlying mechanisms. The study findings revealed that fraxin markedly ameliorated intestinal injuries induced by 13 Gy whole abdominal irradiation (WAI), which was accompanied by a significant increase in the population of Lgr5 + intestinal stem cells (ISCs) and Ki67 + progeny. Furthermore, fraxin mitigated WAI-induced intestinal barrier damage, and reduced oxidative stress and intestinal inflammation in mice. Transcriptome sequencing of fraxin-treated mice revealed upregulation of IL-22, a pleiotropic cytokine involved in regulating the function of intestinal epithelial cells. Moreover, in both human intestinal epithelial cells and ex vivo cultured mouse intestinal organoids, fraxin effectively ameliorated IR-induced damage by promoting the expression of IL-22. The radioprotective effects of fraxin were partially negated in the presence of an IL-22-neutralizing antibody. In summary, fraxin is demonstrated to possess the ability to alleviate RIID and maintain intestinal homeostasis , suggesting that fraxin might serve as a strategy for mitigating accidental radiation exposure- or radiotherapy-induced RIID.

CAS / MDL: 524-30-1
研究领域: 放射生物学 · 药理学 · 分子生物学 · 免疫学 · 胃肠病学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ANALYTICAL BIOCHEMISTRY · 2023 · IF 2.9

Metabolomics integrated network pharmacology reveals the mechanism of Ma-Mu-Ran Antidiarrheal Capsules on acute enteritis mice

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.

CAS / MDL: 9011-18-1
研究领域: 药理学 · 代谢组学 · 炎症 · 胃肠病学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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LIFE SCIENCES · 2025 · IF 5.1

NVP-AUY922 relieves radiation-induced intestinal injury via regulating EPHX1

Wenzhe Kong,Xudong Ding,Zhaoyu Wang,Lu Lu,Saijun Fan

As a common side effect of radiotherapy, radiation-induced intestinal injury (RIII) greatly affects the prognosis of patients and the efficacy of radiotherapy. Current therapeutic strategies for RIII are still very limited. Thus, the identification of effective radioprotective agents is of great importance. NVP-AUY922 is an HSP90 inhibitor with favorable anti-inflammatory and antioxidant activities. It has been proven to mitigate radiation-induced lung injury. However, its effects on the alleviation of RIII remain unclear. In this study, our data indicated that NVP-AUY922 remarkably increased the survival rate after radiation exposure. NVP-AUY922 treatment could enhance the viability of intestinal stem cells (ISCs) and promote the recovery of the small intestine. In addition, it also inhibited intestinal inflammation and reshaped the gut microbiota structure. We found that the radioprotective effect of NVP-AUY922 is partially dependent on EPHX1. In addition, NVP-AUY922 could attenuate dextran sulfate sodium (DSS)-induced colitis and promote intestinal barrier recovery. Thus, our results suggest that NVP-AUY922 contributes to the amelioration of intestinal injury after radiation exposure, which offers a new approach for the prevention of RIII.

CAS / MDL: 747412-49-3
研究领域: 肿瘤学 · 放射生物学 · 药理学 · 胃肠病学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Food & Function · 2023 · IF 6.1

Xylooligosaccharides from corn cobs alleviate loperamide-induced constipation in mice via modulation of gut microbiota and SCFA metabolism

Hong Song,Rui Guo,Xianbao Sun,Yuxing Kou,Xuan Ma,Yinan Chen,Lihua Song,Chunmei Yuan,Yan Wu

This study aimed to optimize the structure and efficacy of xylooligosaccharides (XOSs) from corn cobs in constipated mice. Structural analysis revealed that XOSs from corn cobs were composed of β-Xyl-(1 →4)-[β-Xyl-(1→4)]n-α/β-Xyl (n = 0–5) without any other substituents. XOS administration significantly reduced the defecation time, increased the gastrointestinal transit rate, restored the gastrointestinal neurotransmitter imbalance, protected against oxidative stress, and reversed constipation-induced colonic inflammation. Fecal metabolite and microbiota analysis showed that XOS supplementation significantly increased short chain fatty acid (SCFA) levels and improved the gut microbial environment. These findings highlighted the potential of XOSs from corn cobs as an active ingredient for functional foods or as a therapeutic agent in constipation therapy.

研究领域: 营养学 · 胃肠病学 · 微生物学 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Acta Biomaterialia · 2025 · IF 9.6

Dual-mechanism mucoadhesive hydrogel integrating pH-independent barriers and autophagy-driven immunotherapy for the treatment of ulcerative colitis

Jie Wang,Shenyuan Ouyang,Gaolong Lin,Dingwei Li,Bingyu Ding,Yumo Chen,Bingjie Tong,Ting Ouyang,Helin Xu,Wenzhi Wu

Current therapies for ulcerative colitis (UC) face critical challenges, including systemic toxicity and inadequate mucosal regeneration. Herein, we present a pioneering dual-mechanism therapeutic platform integrating pH-independent acid-treated sucralfate (ASF) with autophagy-inducing spermidine (Spd) to synergistically address UC pathogenesis. Unlike conventional pH-dependent barrier therapies, ASF forms a mechanically tunable, injectable hydrogel that adheres robustly to colonic mucosa regardless of local pH. Spermidine was easily mounted into ASF hydrogel matrix via electrostatic interaction, with more than 90 % encapsulation efficiency. Moreover, the mechanical strength of ASF hydrogel was precisely modulated by adjusting spermidine amount in formula, making it suitable for effective gut mucosa coverage. Importantly, in vitro permeability test showed that spermidine-loaded ASF hydrogel (Spd-ASF) demonstrated the selective barrier functionality, blocking > 80 % of Escherichia coli and LPS penetration while allowing nutrient permeability. Moreover, micro-CT images demonstrated that rectally infused Spd-ASF hydrogel was uniformly adhered to the colon wall at least for 8 h. In DSS-induced colitis mice, rectally administrating Spd-ASF hydrogel uniquely restored colon length to near-normal levels ( vs. 30 % shortening in controls), reduced proinflammatory cytokines (TNF-α, IL-6, IL-1β) by 60–75 %, and doubled goblet cell density. Mechanistically, Spd-ASF reprogrammed macrophage behavior by activating autophagy and enhancing efferocytosis, driving M2 polarization to resolve inflammation. Notably, Spd-ASF uniquely reversed dysbiosis, elevating beneficial Lactobacillus while suppressing colitis-associated Muribaculaceae and Clostridia . This study is the first to combine mucoadhesive biomaterial engineering with autophagy-mediated immunomodulation, offering a paradigm shift in UC therapy by simultaneously shielding the mucosa and reprogramming inflammatory pathways. Statement of significance Here, autophagy-inducing spermidine (Spd) and pH-independent acid-treated sucralfate (ASF) were combined to create the novel dual-mechanism hydrogel (Spd-ASF), which works in concert to combat UC pathogenesis. The selective barrier functioning of Spd-ASF hydrogel was established by its capacity to permit nutritional permeability while preventing the transfer of toxins (LPS) and pathogenic bacteria ( E. coli ). Additionally, rectally infused Spd-ASF hydrogel was consistently attached on the colon wall for at least eight hours, as seen by micro-CT images. Spd-ASF therapy doubled the density of goblet cells, decreased proinflammatory cytokines (TNF-α, IL-6, and IL-1β) by 60–75 %, boosted helpful Lactobacillus , and lowered pathogenic Muribaculaceae and Clostridia . It also restored colon length in DSS-induced colitis animals. Spd-ASF's therapeutic action was closely linked to promoting cellular efferocytosis and triggering macrophage autophagy.

CAS / MDL: 124-20-9
研究领域: 生物医学工程 · 免疫学 · 胃肠病学 · 药物递送系统 · 生物材料 · 炎症性肠病(IBD)
✓ 已验证 产品关联 DOI PubMed 高影响因子
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AAPS PHARMSCITECH · 2023 ·Vol. 24 ·期 4 ·1-15 · IF 3.3

Self-Double-Emulsifying Drug Delivery System Enteric-Coated Capsules: A Novel Approach to Improve Oral Bioavailability and Anti-inflammatory Activity of Panax notoginseng Saponins

Wang Yaru,Shang Yunxia,Tang Fengyu,Qiu Kun,Wei Xiaohui,Wang Zhengtao

In this work, self-double-emulsifying drug delivery system enteric-coated capsules (PNS-SDE-ECC) were used to enhance the oral bioavailability and anti-inflammatory effects of Panax notoginseng saponins (PNS), which are rapidly biodegradable, poorly membrane permeable, and highly water-soluble compounds. The PNS-SDEDDS formulated by a modified two-step method spontaneously emulsified to W/O/W double emulsions in the outer aqueous solution, which significantly promoted the absorption of PNS in the intestinal tract. The release study revealed that PNS-SDE-ECC exhibited sustained release of PNS within 24 h and the stability study indicated that PNS-SDE-ECC were stable at room temperature for up to 3 months. Furthermore, compared to PNS gastric capsules, the relative bioavailability of NGR1, GRg1, GRe, GRb1, and GRd in PNS-SDE-ECC was increased by 4.83, 10.78, 9.25, 3.58, and 4.63 times, respectively. More importantly, PNS-SDE-ECC significantly reduced OXZ-induced inflammatory damage in the colon by regulating the expression of TNF-α, IL-4, IL-13, and MPO cytokines. Overall, the prepared PNS-SDE-ECC may serve as a viable vehicle for increasing the oral bioavailability of PNS and its anti-inflammatory action on ulcerative colitis. Graphical Abstract

CAS / MDL: 9005-65-6 1338-43-8
研究领域: 药剂学 · 药理学 · 药物递送系统 · 药学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2024 ·Vol. 25 ·期 23 ·12810 · IF 4.9

A Potential Use of Vidarabine: Alleviation of Functional Constipation Through Modulation of the Adenosine A2A Receptor-MLC Signaling Pathway and the Gut Microbiota

Xiaoyu Gao,Kaifeng Guo,Shuangfeng Liu,Weixing Yang,Jun Sheng,Yang Tian,Lei Peng,Yan Zhao

Vidarabine (VID) is an antiviral medication that is commonly utilized to treat conditions such as hand, foot, and mouth disease and herpes. Constipation is a prevalent complication of these diseases. Could VID treat these diseases by influencing defecation behavior? To date, no studies have been conducted on the potential of VID to relieve constipation. Therefore, a systematic investigation was conducted into the laxative effects and mechanisms of VID using loperamide-induced functional constipated mice. The findings indicate that the oral administration of VID promoted gastrointestinal peristalsis, improved fecal properties, facilitated defecation, and demonstrated a significant laxative effect on functional constipated mice. It has been demonstrated that VID may increase the water content of feces by regulating the expression of aquaporins (AQP3, AQP4, andAQP8) in the colon and promote intestinal motility by regulating the expression of neurotransmitters (AChE and VIP) and the adenosine A2A receptor–myosin light chain (A2AR-MLC) signaling pathway in constipated mice. Concurrently, VID may also reduce colonic inflammation in constipated mice, reinforce the gut barrier function, and alter the composition and structure of the gut microbial community. Some microbial taxa, including Firmicutes andLactobacillus, were found to be associated with the alleviation of constipation, while other taxa, including Bacteroidetes, Proteobacteria, Muribaculaceae,Muribaculum,norank__f__Desulfovibrionaceae, andParasutterella, were found to be associated with constipation. These results indicate that the gut microbiota may play a significant role in the alleviation of constipation by VID. These findings confirm the efficacy of VID in a constipated animal model, which justifies further investigation into its potential clinical applications.

CAS / MDL: 77-09-8 717824-30-1
研究领域: 药理学 · 胃肠病学 · 微生物学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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