Development of Anti-inflammatory Probiotic Limosilactobacillus reuteri EFEL6901 as Kimchi Starter: in vitro and In vivo Evidence

The use of probiotic starters can improve the sensory and health-promoting properties of fermented foods. In this study, we developed an anti-inflammatory probiotic starter, Limosilactobacillus reuteri EFEL6901, for use in kimchi fermentation. The EFEL6901 strain was safe for use in foods and was stable under human gastrointestinal conditions. In in vitro experiments, EFEL6901 cells adhered well to colonic epithelial cells and decreased nitric oxide production in lipopolysaccharide-induced macrophages. In in vivo experiments, oral administration of EFEL6901 to DSS-induced colitis mice models significantly alleviated the observed colitis symptoms, prevented body weight loss, lowered the disease activity index score, and prevented colon length shortening. Analysis of these results indicated that EFEL6901 played a probiotic role by preventing the overproduction of pro-inflammatory cytokines, improving gut barrier function, and up-regulating the concentrations of short-chain fatty acids. In addition, EFEL6901 made a fast growth in a simulated kimchi juice and it synthesized similar amounts of metabolites in nabak-kimchi comparable to a commercial kimchi. This study demonstrates that EFEL6901 can be used as a suitable kimchi starter to promote gut health and product quality.

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Screening of an anti-inflammatory peptide from Hydrophis cyanocinctus and analysis of its activities and mechanism in DSS-induced acute colitis

Scientific Reports ◽

10.1038/srep25672 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 10

Author(s):

Zengjie Zheng ◽

Hailong Jiang ◽

Yan Huang ◽

Jie Wang ◽

Lei Qiu ◽

...

Keyword(s):

Inflammatory Diseases ◽

Activity Index ◽

Tumor Necrosis Factor Receptor ◽

Disease Activity Index ◽

Acute Colitis ◽

Surface Plasmon Resonance Analysis ◽

Tnf Α ◽

Anti Inflammatory

Abstract Snake has been used for centuries as a traditional Chinese medicine, especially for therapeutic treatment for inflammatory diseases; however, its mechanisms of action and active constituents remain controversial. In our study, a tumor necrosis factor receptor 1 (TNFR1) selective binding peptide, Hydrostatin-SN1 (H-SN1), which was screened from a Hydrophis cyanocinctus venom gland T7 phage display library, was shown to exhibit significant anti-inflammatory activity in vitro and in vivo. As a TNFR1 antagonist, it reduced cytotoxicity mediated by TNF-α in L929 fibroblasts and effectively inhibited the combination between TNF-α with TNFR1 in surface plasmon resonance analysis. H-SN1 was also shown to suppress TNFR1–associated signaling pathways as it minimized TNF-α-induced NF-кB and MAPK activation in HEK293 embryonic kidney and HT29 adenocarcinoma cell lines. We next determined the effect of H-SN1 in vivo using a murine model of acute colitis induced by dextran sodium sulfate, demonstrating that H-SN1 lowered the clinical parameters of acute colitis including the disease activity index and histologic scores. H-SN1 also inhibited TNF/TNFR1 downstream targets at both mRNA and protein levels. These results indicate that H-SN1 might represent a suitable candidate for use in the treatment of TNF-α-associated inflammatory diseases such as inflammatory bowel diseases.

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In Vitro Antioxidant, Anti-inflammatory, and In Vivo Anticolitis Effects of Combretin A and Combretin B on Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice

Gastroenterology Research and Practice ◽

10.1155/2020/4253174 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Mbiantcha Marius ◽

Dawe Amadou ◽

Atsamo Albert Donatien ◽

Ateufack Gilbert ◽

Yousseu Nana William ◽

...

Keyword(s):

Nitric Oxide ◽

Ulcerative Colitis ◽

Protein Denaturation ◽

Antioxidant Activities ◽

Activity Index ◽

Antioxidant Properties ◽

Disease Activity Index ◽

Anti Inflammatory

Combretum fragrans (Combretaceae) is a Cameroonian medicinal plant containing various secondary metabolites and traditionally used for the treatment of several pathologies. Two cycloartane-type triterpenes, Combretin A and Combretin B, were isolated from this plant. This study was aimed at evaluating the anti-inflammatory, antioxidant, and anticolitis effects of these compounds. In vitro anti-inflammatory properties were evaluated by inhibition of cyclooxygenase, 5-lipoxygenase, and denaturation of the protein; antioxidant properties were assessed by using 1,1-diphenyl-2-picrylhydrazyl (DPPH), (2,2’-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid)) ABTS•+, capacity tests ferric reducing antioxidant (FRAP), and trapping nitric oxide. For in vivo analysis, we used the model of ulcerative colitis induced by Dextran Sulfate Sodium (DSS). Studies of the anti-inflammatory activity showed that Combretin A and Combretin B had maximal inhibitory activity on cyclooxygenase (71.92% and 89.59%), 5-lipoxygenase (76.68% and 91.21%), and protein denaturation (63.93% and 87.78%). Antioxidant activity on DPPH, ABTS•+, ferric reducing antioxidant capacity (FRAP), and nitric oxide scavenging showed that Combretin A and Combretin B showed good antioxidant activities. These compounds significantly reduced the signs of DSS-induced colitis in the treated animals by preventing the weight loss of the animals, by significantly reducing the disease activity index, improving the condition of the stool, preventing the reduction of the length of the colon, and preventing the degradation of the colon. This study revealed that Combretin A and Combretin B have anti-inflammatory, antioxidant, and curative properties against colitis experimentally induced by DSS in rats.

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Thymoquinone, a Dietary Bioactive Compound, Exerts Anti-Inflammatory Effects in Colitis by Stimulating Expression of the Colonic Epithelial PPAR-γ Transcription Factor

Nutrients ◽

10.3390/nu13041343 ◽

2021 ◽

Vol 13 (4) ◽

pp. 1343

Author(s):

Balaji Venkataraman ◽

Saeeda Almarzooqi ◽

Vishnu Raj ◽

Abdullah T. Alhassani ◽

Ahmad S. Alhassani ◽

...

Keyword(s):

Transcription Factor ◽

Activity Index ◽

Nigella Sativa ◽

Mapk Signaling ◽

Mitogen Activated Protein Kinase ◽

Ppar Γ ◽

Anti Inflammatory ◽

Ht 29

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders with increasing incidence and prevalence worldwide. Here, we investigated thymoquinone (TQ), a naturally occurring phytochemical present in Nigella sativa, for anti-inflammatory effects in colonic inflammation. To address this, we used in vivo (mice) and in vitro (HT-29 cells) models in this investigation. Our results showed that TQ treatment significantly reduced the disease activity index (DAI), myeloperoxidase (MPO) activity, and protected colon microscopic architecture. In addition, TQ also reduced the expression of proinflammatory cytokines and mediators at both the mRNA and protein levels. Further, TQ decreased phosphorylation of the activated mitogen-activated protein kinase (MAPK) signaling pathway and nuclear factor kappa B (NF-κB) proteins and enhanced colon epithelial PPAR-γ transcription factor expression. TQ significantly decreased proinflammatory chemokines (CXCL-1 and IL-8), and mediator (COX-2) mRNA expression in HT-29 cells treated with TNF-α. TQ also increased HT-29 PPAR-γ mRNA, PPAR-γ protein expression, and PPAR-γ promoter activity. These results indicate that TQ inhibits MAPK and NF-κB signaling pathways and transcriptionally regulates PPAR-γ expression to induce potent anti-inflammatory activity in vivo and in vitro models of colon inflammation.

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l-Isoleucine Administration Alleviates DSS-Induced Colitis by Regulating TLR4/MyD88/NF-κB Pathway in Rats

Frontiers in Immunology ◽

10.3389/fimmu.2021.817583 ◽

2022 ◽

Vol 12 ◽

Author(s):

Xiangbing Mao ◽

Rui Sun ◽

Qingxiang Wang ◽

Daiwen Chen ◽

Bing Yu ◽

...

Keyword(s):

Mrna Expression ◽

Activity Index ◽

Control Diet ◽

Average Daily Gain ◽

Disease Activity Index ◽

Inflammatory Cells ◽

Feed Conversion ◽

Enterocyte Apoptosis

Inflammatory bowel disease (namely, colitis) severely impairs human health. Isoleucine is reported to regulate immune function (such as the production of immunoreactive substances). The aim of this study was to investigate whether l-isoleucine administration might alleviate dextran sulfate sodium (DSS)-induced colitis in rats. In the in vitro trial, IEC-18 cells were treated by 4 mmol/L l-isoleucine for 12 h, which relieved the decrease of cell viability that was induced by TNF-α (10 ng/ml) challenge for 24 h (P <0.05). Then, in the in vivo experiment, a total of 44 Wistar rats were allotted into 2 groups that were fed l-isoleucine-supplemented diet and control diet for 35 d. From 15 to 35 d, half of the rats in the 2 groups drank the 4% DSS-adding water. Average daily gain, average daily feed intake and feed conversion of rats were impaired by DSS challenge (P <0.05). Drinking the DSS-supplementing water also increased disease activity index (DAI) and serum urea nitrogen level (P <0.05), shortened colonic length (P <0.05), impaired colonic enterocyte apoptosis, cell cycle, and the ZO-1 mRNA expression (P <0.05), increased the ratio of CD11c-, CD64-, and CD169-positive cells in colon (P <0.05), and induced extensive ulcer, infiltration of inflammatory cells, and collagenous fiber hyperplasia in colon. However, dietary l-isoleucine supplementation attenuated the negative effect of DSS challenge on growth performance (P <0.05), DAI (P <0.05), colonic length and enterocyte apoptosis (P <0.05), and dysfunction of colonic histology, and downregulated the ratio of CD11c-, CD64-, and CD169-positive cells, pro-inflammation cytokines and the mRNA expression of TLR4, MyD88, and NF-κB in the colon of rats (P <0.05). These results suggest that supplementing l-isoleucine in diet improved the DSS-induced growth stunting and colonic damage in rats, which could be associated with the downregulation of inflammation via regulating TLR4/MyD88/NF-κB pathway in colon.

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Anti-Inflammatory Activities of Pentaherbs formula and Its Influence on Gut Microbiota in Allergic Asthma

Molecules ◽

10.3390/molecules23112776 ◽

2018 ◽

Vol 23 (11) ◽

pp. 2776 ◽

Cited By ~ 10

Author(s):

Miranda Tsang ◽

Sau-Wan Cheng ◽

Jing Zhu ◽

Karam Atli ◽

Ben Chan ◽

...

Keyword(s):

Gut Microbiota ◽

Allergic Asthma ◽

Herbal Medicines ◽

Oral Intake ◽

Allergic Diseases ◽

Short Chain Fatty Acids ◽

Mice Model ◽

Anti Inflammatory

Allergic asthma is a highly prevalent airway inflammatory disease, which involves the interaction between the immune system, environmental and genetic factors. Co-relation between allergic asthma and gut microbiota upon the change of diet have been widely reported, implicating that oral intake of alternative medicines possess a potential in the management of allergic asthma. Previous clinical, in vivo, and in vitro studies have shown that the Pentaherbs formula (PHF) comprising five traditional Chinese herbal medicines Lonicerae Flos, Menthae Herba, Phellodendri Cortex, Moutan Cortex, and Atractylodis Rhizoma possesses an anti-allergic and anti-inflammatory potential through suppressing various immune effector cells. In the present study, to further investigate the anti-inflammatory activities of PHF in allergic asthma, intragastrical administration of PHF was found to reduce airway hyperresponsiveness, airway wall remodeling and goblet cells hyperplasia in an ovalbumin (OVA)-induced allergic asthma mice model. PHF also significantly suppressed pulmonary eosinophilia and asthma-related cytokines IL-4 and IL-33 in bronchoalveolar lavage (BAL) fluid. In addition, PHF modulated the splenic regulatory T cells population, up-regulated regulatory interleukin (IL)-10 in serum, altered the microbial community structure and the short chain fatty acids content in the gut of the asthmatic mice. This study sheds light on the anti-inflammatory activities of PHF on allergic asthma. It also provides novel in vivo evidence that herbal medicines can ameliorate symptoms of allergic diseases may potentially prevent the development of subsequent atopic disorder such as allergic asthma through the influence of the gut microbiota.

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Galangin Protects against Symptoms of Dextran Sodium Sulfate-Induced Acute Colitis by Activating Autophagy and Modulating the Gut Microbiota

Nutrients ◽

10.3390/nu12020347 ◽

2020 ◽

Vol 12 (2) ◽

pp. 347 ◽

Cited By ~ 3

Author(s):

Hongzhuan Xuan ◽

Aiqun Ou ◽

Shengyu Hao ◽

Jiajun Shi ◽

Xiaolu Jin

Keyword(s):

Gut Microbiota ◽

Activity Index ◽

Disease Activity Index ◽

Short Chain Fatty Acids ◽

Control Group ◽

Necrosis Factor Alpha ◽

Bowel Diseases ◽

Pre Treatment ◽

Related Proteins

Galangin is a natural flavonoid that has been reported to provide substantial health benefits. Nevertheless, little is known about the potential effects of galangin against inflammatory bowel diseases. Here, an in vivo study was performed to investigate the preventive effects of galangin against dextran sulphate sodium (DSS)-induced acute murine colitis, which mimics the symptoms of human ulcerative colitis (UC). Pre-treatment with galangin (15 mg/kg, p.o.) resulted in a significant decreased in the macroscopic signs of DSS-induced colitic symptoms, including a decreased disease activity index, prevention of the colon length shortening, and alleviation of the pathological changes occurring in the colon. Colonic pro-inflammatory mediators, including tumor necrosis factor-alpha, interleukin (IL)-1 beta, and IL-6, as well as myeloperoxidase activities were decreased following galangin pre-treatment when compared with the DSS control group. Moreover, galangin pre-treatment significantly increased the expressions of autophagy-related proteins and promoted the formation of autophagosome in the colon. Galangin pre-treatment increased the diversity of the gut microbiota, and this was accompanied by increased levels of short-chain fatty acids. These observed changes could involve the modulating effects conferred by galangin in relation to some specific bacteria populations, including the recovery of Lactobacillus spp., and increased Butyricimonas spp. Overall, these results support the use of galangin in the prevention of UC.

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Dietary Alaska Pollock Protein Attenuates the Experimental Colitis Induced by Dextran Sulfate Sodium via Regulation of Gut Microbiota and Its Metabolites in Mice

Metabolites ◽

10.3390/metabo12010044 ◽

2022 ◽

Vol 12 (1) ◽

pp. 44

Author(s):

Genki Tanaka ◽

Nozomi Hagihara ◽

Ryota Hosomi ◽

Takaki Shimono ◽

Seiji Kanda ◽

...

Keyword(s):

Gut Microbiota ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Activity Index ◽

Body Weight Loss ◽

Disease Activity Index ◽

Experimental Colitis ◽

Short Chain Fatty Acids ◽

Spleen Weight ◽

Reduced Body

Protein derived from fish has not only nutritional properties but also health-promoting properties. Few studies have examined the effect of dietary Alaska pollock protein (APP) on the anticolitis effect reported to be associated with metabolic syndrome (MetS). This study investigated the effect of APP intake on colitis symptoms, gut microbiota, and its metabolites in the experimental colitis mouse model induced by dextran sulfate sodium (DSS). Male C57BL/6J mice were divided into three groups: (1) DSS-untreated mice fed an American Institute of Nutrition (AIN) 93G diet (protein source is casein), (2) DSS-treated mice fed an AIN93G diet, and (3) DSS-treated mice fed an APP diet. After the mice were fed the diets for 21 days, experimental colitis was induced by three cycles of 2% DSS administration for 5 days followed by washouts over the course of 5 days. APP-reduced body weight loss increased the disease activity index, and elevated spleen weight and alleviated colon length shortening and colonic tissue damage. Furthermore, APP altered the structure and composition of the microbiota and short-chain fatty acids in feces. Since APP intake alleviates experimental colitis induced by DSS administration through alterations in the gut microbiota and its metabolites, we deduced that APP would inhibit MetS progression via colitis suppression.

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Tryptophol acetate and tyrosol acetate, metabolites secreted by a probiotic yeast, halt cytokine storm

10.1101/2021.12.16.472991 ◽

2021 ◽

Author(s):

orit malka ◽

ravit malishev ◽

marina bersudsky ◽

manikand rajendran ◽

mathumathi krishnamohan ◽

...

Keyword(s):

Immune Modulation ◽

Ex Vivo ◽

Fermented Foods ◽

Cytokine Storm ◽

Immune Functions ◽

Therapeutic Benefits ◽

Probiotic Yeast ◽

Anti Inflammatory

Probiotic fermented foods are perceived as contributing to human health and capable of protecting against inflammation, however solid mechanistic evidence for the presumptive therapeutic benefits is lacking. Here we report that tryptophol acetate and tyrosol acetate, small molecule metabolites secreted by the probiotic milk-fermented yeast Kluyveromyces marxianus exhibit remarkable anti-inflammatory properties. Comprehensive in vivo, ex vivo and in vitro experiments, employing LPS-induced 'cytokine storm' models, reveal dramatic effects of the two molecules, added in tandem, on mice morbidity, laboratory parameters and mortality. In parallel, significant attenuation of pro-inflammatory cytokines including IL-6, IL-1α, IL-1β and TNF-κB, and reduction of reactive oxygen species were recorded. Importantly, tryptophol acetate and tyrosol acetate did not completely suppress cytokine generation, but rather brought their concentrations back to baseline levels, further maintaining core immune functions, including phagocytosis. The anti-inflammatory effects of tryptophol acetate and tyrosol acetate were mediated through downregulation of TLR4, IL-1R, and TNFR signaling pathways and increased A20 expression, attenuating NF-kB level. In addition, the two molecules had a significant impact on mice microbiome, increasing the abundance of the genus Bactericides, known to exhibit anti-inflammatory properties. Overall, this work illuminates pronounced and broad-based immune modulation properties of probiotic yeast-secreted metabolites, uncovering their mechanism of action and underscoring potential new therapeutic avenues for severe inflammation.

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Intestinal inflammation increases convulsant activity and reduces antiepileptic drug efficacy in a mouse model of epilepsy

Scientific Reports ◽

10.1038/s41598-019-50542-0 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 9

Author(s):

Carmen De Caro ◽

Antonio Leo ◽

Valentina Nesci ◽

Carla Ghelardini ◽

Lorenzo di Cesare Mannelli ◽

...

Keyword(s):

Antiepileptic Drug ◽

Intestinal Inflammation ◽

Activity Index ◽

Disease Activity Index ◽

Drug Efficacy ◽

Seizure Threshold ◽

Seizure Susceptibility ◽

Gut Health ◽

Anti Inflammatory ◽

Animal Models Of Epilepsy

Abstract We studied the effects of intestinal inflammation on pentylenetetrazole (PTZ)-induced seizures in mice and the effects thereon of some antiepileptic and anti-inflammatory treatments to establish if a link may exist. The agents tested were: alpha-lactoalbumin (ALAC), a whey protein rich in tryptophan, effective in some animal models of epilepsy and on colon/intestine inflammation, valproic acid (VPA), an effective antiepileptic drug in this seizure model, mesalazine (MSZ) an effective aminosalicylate anti-inflammatory treatment against ulcerative colitis and sodium butyrate (NaB), a short chain fatty acid (SCFA) normally produced in the intestine by gut microbiota, important in maintaining gut health and reducing gut inflammation and oxidative stress. Intestinal inflammation was induced by dextran sulfate sodium (DSS) administration for 6 days. Drug treatment was started on day 3 and lasted 11 days, when seizure susceptibility to PTZ was measured along with intestinal inflammatory markers (i.e. NF-κB, Iκ-Bα, COX-2, iNOS), histological damage, disease activity index (DAI) and SCFA concentration in stools. DSS-induced colitis increased seizure susceptibility and while all treatments were able to reduce intestinal inflammation, only ALAC and NaB exhibited significant antiepileptic properties in mice with induced colitis, while they were ineffective as antiepileptics at the same doses in control mice without colitis. Interestingly, in DSS-treated mice, VPA lost part of its antiepileptic efficacy in comparison to preventing seizures in non-DSS-treated mice while MSZ remained ineffective in both groups. Our study demonstrates that reducing intestinal inflammation through ALAC or NaB administration has specific anticonvulsant effects in PTZ-treated mice. Furthermore, it appears that intestinal inflammation may reduce the antiepileptic effects of VPA, although we confirm that it decreases seizure threshold in this group. Therefore, we suggest that intestinal inflammation may represent a valid antiepileptic target which should also be considered as a participating factor to seizure incidence in susceptible patients and also could be relevant in reducing standard antiepileptic drug efficacy.

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3-(3-Pyridylmethylidene)-2-indolinone Reduces the Severity of Colonic Injury in a Murine Model of Experimental Colitis

Oxidative Medicine and Cellular Longevity ◽

10.1155/2015/959253 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 9

Author(s):

Kun-Ping Wang ◽

Chao Zhang ◽

Shou-Guo Zhang ◽

En-Dong Liu ◽

Lan Dong ◽

...

Keyword(s):

Inflammatory Response ◽

Activity Index ◽

Body Weight Loss ◽

Sodium Sulphate ◽

Histopathological Analysis ◽

Dependent Manner ◽

Colon Tissue ◽

Colonic Injury ◽

Anti Inflammatory

Nrf2 is the key transcription factor regulating the antioxidant response which is crucial for cytoprotection against extracellular stresses. Numerousin vivostudies indicate that Nrf2 plays a protective role in anti-inflammatory response. 3-(3-Pyridylmethylidene)-2-indolinone (PMID) is a synthesized derivative of 2-indolinone compounds. Our previous study suggested that PMID induces the activation of Nrf2/ARE pathway, then protecting against oxidative stress-mediated cell death. However, little is known regarding the anti-inflammatory properties of PMID in severe inflammatory phenotypes. In the present study we determined if PMID treatment protects mice from dextran sodium sulphate- (DSS-) induced colitis. The result suggests that treatment with PMID prior to colitis induction significantly reduced body weight loss, shortened colon length, and decreased disease activity index compared to control mice. Histopathological analysis of the colon revealed attenuated inflammation in PMID pretreated animals. The levels of inflammatory markers in colon tissue and serum were reduced associated with inhibition of NF-κB activation. The expression levels of Nrf2-dependent genes such as HO-1, NQO1, and Nrf2 were increased in PMID pretreated mice. However, PMID pretreatment did not prevent DSS-induced colitis in Nrf2 knockout mice. These data indicate that PMID pretreatment in mice confers protection against DSS-induced colitis in Nrf2-dependent manner, suggesting a potential role of PMID in anti-inflammatory response.

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