JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Ruyi Chen,Fenfen Li,Kai Zhou,Mengyu Xing,Xiaoxi Zhang,Xinyu Zhao,Chenxi Wu,Ziwei Han,Yixuan Zhou,Li Yan,Daozong Xia
Ethnopharmacological relevance Modified sanmiao pills (MSMP), a traditional Chinese medicine (TCM) formula, is consisted of rhizome of Smilax glabra Roxb., Cortexes of Phellodendron chinensis Schneid., rhizome of Atractylodes chinensis (DC.) Koidz., and roots of Cyathula officinalis Kuan. in a ratio of 3:3:2:1. This formula has been broadly applied to treat gouty arthritis (GA) in China. Aims of the study To elaborate the pharmacodynamic material basis and pharmacological mechanism of MSMP against GA. Materials and methods UPLC-Xevo G2-XS QTOF combined with UNIFI platform was applied to qualitatively assess the chemical compounds of MSMP. Network pharmacology and molecular docking were used to identify the active compounds, core targets and key pathways of MSMP against GA. The GA mice model was established by MSU suspension injecting into ankle joint. The swelling index of ankle joint, expressions of inflammatory cytokines, and histopathological changes in mice ankle joints were determined to validate the therapeutic effect of MSMP against GA. The protein expressions of TLRs/MyD88/NF-κB signaling pathway and NLRP3 inflammasome in vivo was detected by Western blotting . Results In total, 34 chemical compounds and 302 potential targets of MSMP were ascertained, of which 28 were overlapping targets pertaining to GA. 143 KEGG enrichment pathway were obtained, of which the NOD-like receptor signaling pathway, Toll-like receptor signaling pathway, and NF-κB signaling pathway were strongly associated with GA. In silico study indicated that the active compounds had excellent binding affinity to core targets. In vivo study confirmed that MSMP observably decreased swelling index and alleviated pathological damage to ankle joints in acute GA mice. Besides, MSMP significantly inhibited the secretion of inflammatory cytokines (IL-1β, IL-6, and TNF-α) induced by MSU, as well as the expression levels of key proteins involved in TLRs/MyD88/NF-κB signaling pathway and NLRP3 inflammasome. Conclusion MSMP possessed a pronounced therapeutic effect on acute GA. Results from network pharmacology and molecular docking showed that obaculactone, oxyberberine, and neoisoastilbin might treat gouty arthritis by down-regulating TLRs/MyD88/NF-κB signaling pathway and NLRP3 inflammasome.
研究领域:
药理学
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中药学
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网络生物学
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分子生物学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2022
·
IF 5.572
Dan Su,Aitong Lei,Chunchao Nie,Yi Chen
The potential mechanism for the protective effect of Ganoderma atrum ( G. atrum ) polysaccharide (PSG-1) on acrylamide (AA) induced intestinal damage in mice was explored. Results showed that PSG-1 pretreatment prevented AA-induced injury by decreasing intestinal permeability and serum D-lactate acid (D-Lac) levels and increasing the number of small intestinal goblet cells and IgA secreting cells. In addition, PSG-1 pretreatment effectively reduced malondialdehyde (MDA) level and raised superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) activities in the intestine. Furthermore, PSG-1 administration decreased the levels of pro-inflammatory factors including IL-1β, TNF-α, and IL-6, while the anti-inflammatory factor IL-10 was elevated. Meanwhile, PSG-1 could increase the performance of tight junction (TJ) proteins such as Occludin , Claudin-1 and ZO-1. Moreover, according to the isobaric tag for relative and absolute quantitation (iTRAQ) and Western blot results, PSG-1 could reduce AA-induced intestinal injury through TLR4/MyD88/NF-κB signaling pathway. Overall, the present study suggested that PSG-1 protected intestinal permeability and barrier function in mice via reducing inflammation and oxidative stress , and effectively prevented AA-induced intestinal injury in mice.
研究领域:
药理学
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免疫学
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分子生物学
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毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Nutrition
·
2022
·
IF 6.59
Qianqian Yao,Linlin Fan,Nan Zheng,Christophe Blecker,Véronique Delcenserie,Huiying Li,Jiaqi Wang
Gut microbiota dysbiosis, together with goblet cells dysfunction has been observed in ulcerative colitis cases. This study aims to evaluate the potential of 2′-fucosyllactose (2′-FL) supplementation in inhibiting intestinal inflammation through regulating gut microbiota, protecting goblet cells, and stimulating mucin secretion. 2′-FL was orally administered to C57BL/6J mice daily (400 mg/kg bw) for 21 days and 5% dextran sulfate sodium (DSS) was used to induce the colitis in the last 7 days. Meanwhile, fecal microbiota transplantation (FMT) was conducted to test the roles of gut microbiota in the remission of colitis by 2′-FL. Gut microbiota alteration was analyzed through 16S ribosomal RNA (16S rRNA) sequencing. Periodic acid-Schiff (PAS), immunofluorescence staining, as well as mucin 2 (MUC2) and NOD-like receptor family pyrin domain containing 6 (NLRP6) messenger RNA (mRNA) expression in colon fragments was performed and detected. The results showed that the DSS + 2′-FL mice were found to have a slower rate of weight loss, lower disease activity index (DAI) scores, and longer colon lengths than the DSS group ( p < 0.05), so in the FMT recipient mice which received fecal microbiota from the DSS + 2′-FL group. In addition, the data revealed that 2′-FL relieved the disorder of DSS-induced gut microbiota, including decreasing the high abundance of mucin-utilizing bacteria in the DSS group, such as Bacteroides, Lachnospiraceae NK4A136, Lachnospiraceae , and Bacteroides vulgatus . PAS and immunofluorescence staining showed that 2′-FL treatment promoted the recovery of goblet cells and enhanced MUC2 and NLRP6 expression, which was also observed in the FM (DSS + 2′-FL) group. Moreover, NLRP6, which has been proved to be a negative regulator for Toll-like receptor 4/myeloid differential protein-8/nuclear factor-kappa B (TLR4/MyD88/NF-κB) pathway, was upregulated by 2′-FL in colon tissue. In conclusion, this study suggests that 2′-FL ameliorates colitis in a gut microbiota-dependent manner. The underlying protective mechanism associates with the recovery of goblet cells number and improves MUC2 secretion through TLR4-related pathway.
研究领域:
免疫学
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微生物学
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胃肠病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2022
·
IF 9.231
Chuang Liu,Zhichang Qiu,Duanyin Gu,Fangzhou Wang,Rentang Zhang
This study explored the structural characteristics of the purified blackened polysaccharide fraction (BJP-4) and its potential to alleviate colitis. BJP-4 had a molecular weight of 1.24 × 10 5 Da and mainly consisted of → 4)- α - l -Gal p A (1→, →5)- α - l -Ara f (1 → and → 4)- β - d -Gal p (1 → residues. After the administration of BJP-4, the disease activity index of colitic mice was reduced by 40.38–50.96%, accompanied by increased colon length (30.00–62.50%) and ameliorated pathological damage. The mechanisms involved regulation of the intestinal microbiota and subsequent inhibition of the TLR4/MyD88/NF- κ B/NLRP3 pathway, balance of pro/anti-inflammatory cytokines and oxidative status, enhancement of epithelial barrier integrity and production of short-chain fatty acids. In particular, high-doses of BJP-4 significantly increased the abundance of beneficial bacteria (f_ Muribaculaceae , Lactobacillus and Lachnospiraceae _NK4A136_group, 0.78–1.04-fold) and suppressed the levels of harmful bacteria (o_ Clostridia _UCG-014, Bacteroides and Escherichia-Shigella , 32.30–90.42%). These findings revealed the anti-inflammatory effects and mechanisms of purified blackened polysaccharides, which facilitated their application in functional foods.
研究领域:
药理学
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免疫学
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微生物学
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营养学
✓ 已验证
产品关联
DOI
高影响因子
Food & Function
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2023
·Vol. 14
·期 5
·2313-2325
·
IF 6.1
Sibo Zhao,Shanshan Hu,Kang Sun,Liyong Luo,Liang Zeng
Blue light emitted by smartphones and tablets at night increases the risk of depression. Pu-erh tea has been reported to reduce the risk of depression by regulating tryptophan metabolism, but its underlying protective mechanism on depression induced by blue light at night (BLAN) remains unclear. In this work, two groups of C57BL6/J mice were given water or 0.25% (w/v) Pu-erh tea for 120 days, followed by a 45-day BLAN treatment (400 lux blue light between 21:00 and 23:00) to simulate blue light emitted from electronic equipment. Our results indicated that BLAN induced depression-like behaviors and gut microbiota disorders in healthy mice. Pu-erh tea intake significantly reshaped the gut microbiome (especially Bifidobacterium) and regulated the metabolism of short-chain fatty acids (SCFAs) which protected the integrity of the intestinal barrier. This improvement further reduced blood–brain barrier (BBB) damage and alleviated neuroinflammation by inhibiting MyD88/NF-κB pathways which finally regulated neurotransmitters such as brain-derived neurotrophic factor (BDNF) and serotonin (5-hydroxytryptamine, 5-HT). Collectively, 0.25% (w/v) Pu-erh tea has the potential to prevent BLAN-induced depression-like behaviors by reshaping the gut microbiota and increasing the generation of SCFAs via the gut–brain axis.
研究领域:
神经科学
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药理学
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微生物学
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行为科学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
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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
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免疫学
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微生物学
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分子生物学
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胃肠病学
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植物学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2021
·
IF 7.963
Weike Shaoyong,Wanrong Zhang,Chenyang Wang,Zhongyun Kou,Wenlong Yong,Junheng Jiao,Wenyong Yan,Weijun Pang
Decabromodiphenyl ether (BDE-209), a congener of polybrominated diphenyl ethers (PBDEs), is used as a flame retardant and accounts for over 82% of total PBDE usage. BDE-209 has been found to be persistent in indoor and outdoor environments and has adverse health effects on humans. This study aimed to investigate the effects of BDE-209 on mouse intestinal tissues and reveal the underlying toxicological mechanisms. In this study, C57BL/6J male mice were administered BDE-209 intragastrically (200 mg/kg bodyweight) once a day for 4 weeks, after which intestinal tissues, blood samples, and fecal samples were collected for analysis. The results showed that BDE-209 exposure significantly decreased body weight ( P < 0.01) and promoted intestinal oxidative stress, apoptosis, autophagy, and inflammation. Additionally, BDE-209 reduced the intestinal mucus barrier and increased gut permeability. Importantly, BDE-209 decreased the levels of intestinal short-chain fatty acids (SCFAs), including acetic acid ( P < 0.05) and butyric acid ( P < 0.01), which protect gut health. Mechanistically, BDE-209 triggered apoptosis by damaging mitochondrial function, increasing both the release of mitochondrial cytochrome c (Cyt c) into the cytosol and the Bax/Bcl-2 ratio, as well as inducing activation of caspase-3, caspase-9, and PARP. Moreover, BDE-209 exposure induced intestinal inflammation via the TLR4/MyD88/NF-κB signaling pathway and promoted intestinal autophagy by upregulating Beclin 1, leading to the accumulation of LC3-I to LC3-II. Therapeutically, N -acetyl-L-cysteine (NAC) attenuated the effects of BDE-209 on gut toxicity, including intestinal permeability, apoptosis, and inflammation through the oxidative stress pathway. Overall, we suggest that BDE-209 causes gut toxicity by modulating the intestinal barrier, permeability, oxidative stress, autophagy, apoptosis, and inflammation, and BDE-209 exposure could be partly reversed by antioxidant NAC supplementation. Our findings provide new insights into the intestinal response to BDE-209 exposure.
研究领域:
毒理学
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药理学
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分子生物学
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环境科学
✓ 已验证
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Dan Han,Meihua Wang,Ningyu Dong,Jiaxing Zhang,Dingran Li,Xiaoling Ma,Ying Ma,Siliang Wang,Yun Zhu,Cheng Wang
Lipid nanoparticles (LNPs) hold great promise as carriers for developing drug delivery systems (DDSs) aimed at managing ischemic stroke (IS). Previous research has highlighted the vital role played by the lipid composition and biophysical characteristics of LNPs, influencing their interactions with cells and tissues. This understanding presents an opportunity to engineer LNPs tailored specifically for enhanced IS treatment. We previously introduced the innovative concept of reconstituted lipid nanoparticles (rLNPs), which not only retain the advantages of conventional LNPs but also incorporate lipids from the originating cell or tissue. Brain-derived rLNPs (B-rLNPs) exhibit significantly superior accumulation within the cerebral ischemic region when compared to liver-derived rLNPs (L-rLNPs). The homing effect of B-rLNPs was then employed to construct 3-n-butylphthalide (NBP) loaded DDS (B-rLNPs/NBP) for the treatment of IS. Our results demonstrated that compared with free NBP, B-rLNPs/NBP can significantly reduce infarct volume, neurological deficits, blood-brain barrier (BBB) leakage rate, brain water content, neutrophil infiltration, alleviate pathological structures, and improve the motor function in MCAO/R model. We also proved that B-rLNPs/NBP showed further reinforced protective effects on the same model than free NBP through the regulation of TLR4/MyD88/NF-κB (anti-inflammation) and Bax/Bcl-2 (anti-apoptosis) pathways. This study offers a promising tool towards improved IS treatment.
研究领域:
神经科学
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药学
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生物技术
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2022
·
IF 5.895
Shanshan Hu,Liyong Luo,Xintong Bian,Rui Hai Liu,Sibo Zhao,Yu Chen,Kang Sun,Jielin Jiang,Zhonghua Liu,Liang Zeng
Pu-erh tea is a healthy beverage rich in phytochemicals, and its effect on the risk of inducing circadian rhythm disorders (CRD) is unclear. In this study, healthy mice were given water or 0.25% (w/v) Pu-erh tea for 7 weeks, followed by a 40 day disruption of the light/dark cycle. CRD caused dysregulation of neurotransmitter secretion and clock gene oscillations, intestinal inflammation, and disruption of intestinal microbes and metabolites. Pu-erh tea boosted the indole and 5-hydroxytryptamine pathways of tryptophan metabolism via the gut–liver–brain axis. Furthermore, its metabolites (e.g., IAA, Indole, 5-HT) enhanced hepatic glycolipid metabolism and down-regulated intestinal oxidative stress by improving the brain hormone release. Tryptophan metabolites and bile acids also promoted liver lipid metabolism and inhibited intestinal inflammation (MyD88/NF-κB) via the enterohepatic circulation. Collectively, 0.25% (w/v) Pu-erh tea has the potential to prevent CRD by promoting indole and 5-HT pathways of tryptophan metabolism and signaling interactions in the gut–liver–brain axis.
研究领域:
营养学
·
药理学
·
分子生物学
·
胃肠病学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Nutrition
·
2022
·
IF 6.59
Yin Wei,Xiao Du,Yangbian Guo,Mingchang Chang,Bing Deng,Jingyu Liu,Jinling Cao
Dry fruiting bodies of Cordyceps militaris (CMF) have been widely used in folk tonic foods and traditional herbal medicine in East Asia. Drying treatment serves as the last step in CMF industrial processes. In this work, the physicochemical properties of polysaccharides from C. militaris fruiting bodies (CMFPs) with hot air drying (HD), far-infrared radiation drying (ID) and vacuum freeze-drying (FD) treatments were analyzed, and their effects on ulcerative colitis (UC) were further investigated in oxazolone-induced zebrafish. The results showed that physicochemical properties of CMFP-H, CMFP-I and CMFP-F were obvious different. CMFPs could repair the intestinal mucosal barrier, inhibit ROS generation and the activities of MDA and MPO, and improve the activities of SOD, CAT, ACP, AKP and LZM. Further detection indicated that CMFPs could better improve UC via activating the MyD88/NF-κB signaling pathway in vivo . However, CMFP-H, CMFP-F and CMFP-I exhibited diverse regulation effects on specific immune-related enzymes and cytokines. The data would be helpful for finding practical and rapid drying methods for macro-fungi and further exploring CMFPs as functional food ingredients or complementary medicines for the treatments of UC.
研究领域:
药理学
·
食品科学
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免疫学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2023
·
IF 8.4
Guichun Wang,Chengjun Peng,Maomao Tang,Yuxiao Wang,Jiaxin Li,Hairong Chen,Xiangwei Chang,Zixuan Shu,Ning He,Jian Guo,Shuangying Gui
Currently, the antibiotics-loaded hydrogels have not shown an over standard of clinical effects on periodontitis treatment. Abnormal crosstalk between macrophages and periodontal ligament stem cells (PDLSCs) is a key factor for unexpected clinical efficacy. Here, we reported a therapeutic strategy for the programmed intervention of macrophages and PDLSCs based on folic acid-modified liposome hydrogel composites loaded with genistein (FA-GEN-Lip@Gel). FA-GEN-Lip@Gel exhibited excellent thermos-sensitivity and injectability, could sustained-release genistein for more than 120 h. Flow cytometry showed that FA-GEN-Lip@Gel shifted macrophages from the M1 to M2 phenotype. We further confirmed the anti-inflammatory mechanisms that FA-GEN-Lip@Gel regulate TLR4/MyD88/NF-κB axis in macrophages. In addition, FA-GEN-Lip@Gel could promote osteogenic differentiation of PDLSCs via remodeling of cytokine secretion of IL-6, IL-17, TNF-α and IL-10 in macrophages, as verified by conditioned culture system. Therefore, FA-GEN-Lip@Gel significantly reduced periodontal inflammation in vivo according to ELISA, H&E and immunofluorescence staining. Meanwhile, FA-GEN-Lip@Gel promoted alveolar bone regeneration by remodeling RANKL/OPG balance and increasing osteogenic markers of ALP, BMP2 and RUNX2. Altogether, this study develops a novel liposome-hydrogel composites that can be efficiently simultaneously boost inflammation resolution and osteogenic differentiation in periodontitis via modulating the crosstalk between macrophages and PDLSCs.
研究领域:
牙科学
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药学
·
生物医学工程
·
免疫学
✓ 已验证
产品关联
DOI
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Zhichang Qiu,Lu Xiang,Yanhui Han,Bin Zhang,Xuguang Qiao,Zhenjia Zheng,Hang Xiao
The present study identified the protective effects of garlic oligo/poly-saccharides of different chain lengths against dextran sulfate sodium (DSS)-induced colitis in mice and elucidated the structure-function relationships. The results showed that oral intake of garlic oligo/poly-saccharides decreased disease activity index, reduced colon shortening and spleen enlargement, and ameliorated pathological damage in the mouse colon. The dysregulation of colonic pro-/anti-inflammatory cytokines was significantly alleviated, accompanied by up-regulated antioxidant enzymes, blocked TLR4-MyD88-NF- κ B signaling pathway, enhanced intestinal barrier integrity, and restored SCFA production. Garlic oligo/poly-saccharides also reversed gut microbiota dysbiosis in colitic mice by expanding beneficial bacteria and suppressing the growth of harmful bacteria. High-molecular-weight polysaccharides exhibited stronger alleviating effects on DSS-induced colitic symptoms in mice than low-molecular-weight oligo/poly-saccharides did, probably due to their greater ability to be fermented in the colon. Taken together, this study demonstrated the anti-inflammatory effects of garlic oligo/poly-saccharides and revealed that high-molecular-weight polysaccharide fractions were more effective in alleviating DSS-induced colitis.
研究领域:
药理学
·
免疫学
·
胃肠病学
·
微生物学
✓ 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）