Effects of Limosilactobacillus reuteri ID-D01 Probiotic Supplementation on Exercise Performance and Gut Microbiota in Sprague-Dawley Rats.

The gut microbiota composition in animals and humans has recently been found to be influenced by exercise. Although Limosilactobacillus reuteri strains have notable probiotic properties that promote human health, understanding of its effects in combination with exercise and physical activity is limited. Therefore, this study examined the effects of L. reuteri ID-D01, a human-derived probiotic, on exercise performance and fatigue in Sprague-Dawley rats. Organ weight, maximal running distance, serum biochemistry, muscle performance, microbial community composition, and short-chain fatty acid (SCFA) levels were assessed. Results indicated that ID-D01 supplementation significantly improved endurance performance. Rats in the probiotic group demonstrated a significant increase in maximal running distance compared with that in the control group (p < 0.05). Additionally, levels of fatigue markers, such as lactate and creatine phosphokinase, were significantly reduced in the ID-D01-administered groups, suggesting its potential to alleviate exercise-induced fatigue. Microbiome analysis revealed a distinct shift in gut microbiota composition in response to ID-D01 administration. The group that received ID-D01 probiotics exhibited a significant increase in the abundance of SCFA-producing bacteria, particularly Akkermansia spp., compared with that in the control groups. Furthermore, they showed elevated production of SCFAs, such as acetate and butyrate. In conclusion, this study demonstrated that ID-D01 can enhance exercise performance and reduce fatigue. Herein, we highlighted that human-derived probiotics could improve physical performance, as observed by changes in gut microbiota composition and SCFA production.

Evaluation of purine-nucleoside degrading ability and in vivo uric acid lowering of Streptococcus thermophilus IDCC 2201, a novel antiuricemia strain.

This study evaluated 15 lactic acid bacteria with a focus on their ability to degrade inosine and hypo-xanthine-which are the intermediates in purine metabolism-for the management of hyperuricemia and gout. After a preliminary screening based on HPLC, Lactiplantibacillus plantarum CR1 and Lactiplantibacillus pentosus GZ1 were found to have the highest nucleoside degrading rates, and they were therefore selected for further characterization. S. thermophilus IDCC 2201, which possessed the hpt gene encoding hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and exhibited purine degradation, was also selected for further characterization. These three selected strains were examined in terms of their probiotic effect on lowering serum uric acid in a Sprague-Dawley (SD) rat model of potassium oxonate (PO)-induced hyperuricemia. Among these three strains, the level of serum uric acid was most reduced by S. thermophilus IDCC 2201 (p < 0.05). Further, analysis of the microbiome showed that administration of S. thermophlilus IDCC 2201 led to a significant difference in gut microbiota composition compared to that in the group administered with PO-induced hyperuricemia. Moreover, intestinal short-chain fatty acids (SCFAs) were found to be significantly increased. Altogether, the results of this work indicate that S. thermophilus IDCC 2201 lowers uric acid levels by degrading purine-nucleosides and also restores intestinal flora and SCFAs, ultimately suggesting that S. thermophilus IDCC 2201 is a promising candidate for use as an adjuvant treatment in patients with hyperuricemia.

Blending Three Probiotics Alleviates Loperamide-Induced Constipation in Sprague-Dawley (SD)-Rats.

BIOVITA 3 bacterial species (BIOVITA 3), a probiotic blend powder containing Clostridium butyricum IDCC 1301, Weizmannia coagulans IDCC 1201 and Bacillus subtilis IDCC 1101, has been used as a food ingredient for gut health. However, its efficacy in improving constipation has not been reported. Therefore, we aimed to investigate the functional effects of oral administration of BIOVITA 3 as well as its component strains alone (at 1.0×109 CFU/day) in Sprague-Dawley (SD) rats with loperamide-induced constipation. The study included fecal analysis, gastrointestinal transit ratio, histopathological analysis, short chain fatty acids (SCFAs), and metagenome analysis. As results, the BIOVITA 3 group showed significant improvements in fecal number, water content, gastrointestinal transit ratio, and thickening of the mucosal layer. In the SCFAs analysis, all probiotic-treated groups showed an increase in total SCFAs compared to the loperamide-constipated group. Changes in microbial abundance and the diversity index of three groups (normal, constipated, and BIOVITA 3) were also defined. Of these, the BIOVITA 3 showed a significant improvement in loperamide-constipated SD-rats. This study suggests the possibility that BIOVITA 3 can be applied as an ingredient in functional foods to relieve constipation.

Isolation of bioactive limonoids from the fruits of Melia azedarach.

Two previously undescribed limonoids, 1-O-benzoyl-3-O-deactylnimbolinin C (1) and a pair of epimers named toosendalactonins A and B (12a and 12b), together with ten known compounds (2-11) were isolated from the fruits of Melia azedarach L. Their structures were determined by extensive spectroscopic methods, including 1D-, 2D-nuclear magnetic resonance, and mass spectrometry. All the isolated compounds were evaluated for their nitric oxide (NO) inhibition in lipopolysaccharide-activated microglia and nerve growth factor (NGF) production in astrocytes. Compounds 1-2 and 5-8 significantly inhibited NO production, which is comparable to the positive control, L-NMMA. Previously undescribed limonoid, compound 12, and two known limonoids, munronin K (3) and 12-O-methyl-1-O-deacetyl-nimbolinin B (4), showed the highest potency to increase the NGF production in C6 astrocytes. [Formula: see text].

Anti-inflammatory activity of compounds isolated from Astragalus sinicus L. in cytokine-induced keratinocytes and skin.

Inflammation is a part of the complex biological responses of a tissue to injury that protect the organ by removing injurious stimuli and initiating the healing process, and is considered as a mechanism of innate immunity. To identify biologically active compounds against pathogenic inflammatory and immune responses, we fractionated water, aqueous methanol and n-hexane layers from nine kinds of leguminosae and examined anti-inflammatory activity of the fractions in human keratinocytes and mouse skin. Among the fractions, rf3 and rf4, isolated from the aqueous methanol layer of Astragalus sinicus L., exhibited the strongest reactive oxygen species (ROS)-scavenging and anti-inflammatory activities as measured by inhibition of the intracellular ROS production, nuclear factor-kappaB (NF-κB), janus kinase (JAK)/signal transducer and activator of transcription (STAT), and phosphatidylinositol 3-kinase/Akt signaling in cytokine-stimulated human keratinocytes, as well as by effects on T-cell differentiation in mouse CD4(+) T cells. In addition, topical application of rf3 and rf4 suppressed the progression of psoriasis-like dermatitis and expression of pro-inflammatory mediators in interleukin (IL)-23-injected mouse ears. Our results suggest that Astragalus sinicus L. may ameliorate chronic inflammatory skin diseases due to its antioxidant and anti-inflammatory activities via regulation of the intracellular ROS production, NF-κB, JAK/STAT and PI3/Akt signaling cascades as well as immune responses, and these results are the first report that Astragalus sinicus L. exhibits pharmacological activity.

Rhododendrin ameliorates skin inflammation through inhibition of NF-κB, MAPK, and PI3K/Akt signaling.

A wide range of active compounds isolated from nature is used in clinical applications and as a source of lead compounds for drug development. Rhododendron brachycarpum has been used as an oriental herbal medicine for skin inflammatory diseases. In this study, we isolated rhododendrin from Rhododendron brachycarpum leaves and investigated its molecular mechanisms for anti-inflammatory effect. Rhododendrin showed intracellular reactive oxygen species scavenging activity and suppressed nuclear translocation of nuclear factor-κB (NF-κB) by inhibiting phosphorylation of NF-κB, inhibitor of NF-κB(IκBα), and IκBα kinase(IKKα/ß). Furthermore, rhododendrin inhibited mitogen-activated protein kinases (MAPKs), including ERK1/2, p38, and decreased c-Jun N-terminal kinase (JNK) and phosphoinositide 3-kinase (PI3K)/Akt signaling. As a result, rhododendrin reduced expression of pro-inflammatory mediators, such as cyclooxygenase-2 (COX-2), intracellular adhesion molecule-1 (ICAM-1), interleukin-1α (IL-1α), IL-1ß, IL-6, IL-8, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), chemokine (C-X-C) motif ligand 1 (CXCL1), and chemokine (C-C motif) ligand 17 (CCL17) in TNF-α/IFN-γ-stimulated keratinocytes. Notably, we demonstrated that topically applied rhododendrin alleviated skin inflammation in trinitrochlorobenzene (TNCB)-treated mouse ear skins. Collectively, these results indicate that rhododendrin is a biologically active compound that exhibits anti-inflammatory activity and is a promising candidate molecule to treat inflammatory skin diseases, such as psoriasis.

Mast cell stabilizing effect of (-)-Elema-1,3,11(13)-trien-12-ol and thujopsene from Thujopsis dolabrata is mediated by down-regulation of interleukin-4 secretion in antigen-induced RBL-2H3 cells.

Several isolated compounds from the wood part of Thujopsis dolabrata were evaluated for their inhibitory effects against antigen-induced mast cell degranulation and interleukin-4 (IL-4) secretion, as well as IL-4 mRNA and protein expression in immunoglobulin E (IgE)-sensitized RBL-2H3 cells. Among the five isolated compounds, (-)-elema-1,3,11(13)-trien-12-ol (1) and thujopsene (2) exhibited the potent inhibitory activity against mast cell degranulation measured by ß-hexosaminidase release with IC values of 27.4 µM and 25.1 µM, respectively. These compounds also inhibited the release of IL-4 (IC values of 7.0, 6.7 µM, respectively), IL-4 mRNA expression (IC values of 16.5, 7.2 µM, respectively) and IL-4 protein expression (IC values of 17.0, 9.6 µM, respectively) in antigen-induced IgE-sensitized RBL-2H3 cells. These results suggested that (-)-elema-1,3,11(13)-trien-12-ol (1) and thujopsene (2) effectively inhibits mast cell degranulation as well as IL-4 production, suggesting that these compounds from Thujopsis dolabrata can be used as candidates for IgE-mediated allergic disorders.

Kurarinone regulates immune responses through regulation of the JAK/STAT and TCR-mediated signaling pathways.

Sophora flavescens is a medicinal herb that contains flavonoids and quinolizidine alkaloids and has a wide range of biological activities due to its anti-inflammatory, anti-bacterial and anti-cancer properties. We isolated a series of flavonoids from the roots of Sophora flavescens and examined their ability to inhibit immune responses. Among the flavonoids, kurarinone exhibited the strongest inhibitory effect on immune responses. Kurarinone suppressed the differentiation of CD4(+) T cells by inhibiting the expression and production of T-cell lineage-specific master regulators and cytokines. Our results also demonstrated that kurarinone directly suppressed the cytokine-induced Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling and T-cell receptor (TCR) pathways. In two established animal models of chronic inflammatory skin disease, one in which psoriasis-like skin disease was induced by an interleukin 23 (IL-23) injection into mouse ears and another in which 2,4,6-trinitrochlorobenzene (TNCB) application on the abdomens of mice was used to induce contact dermatitis, kurarinone repressed disease development by inhibiting the expression of pro-inflammatory mediators, including cytokines, chemokines and enzyme in murine ear skin. This study provides new evidence that kurarinone may ameliorate chronic inflammatory skin diseases through the suppression of pathogenic CD4(+) T-cell differentiation and the overall immune response.

Acylated kaempferol glycosides from Laurus nobilis leaves and their inhibitory effects on Na+/K+-adenosine triphosphatase.

Na(+)/K(+)-adenosine triphosphatase (ATPase) inhibitors have considerable therapeutic potential against some heart diseases like congestive heart failure and cardiac arrhythmias. Through bioassay-guided separation of the leaf extract of Laurus nobilis, six acylated kaempferol glycosides (compounds 1-6) were isolated. Their structures were determined on the basis of spectroscopic analysis and comparison with reported data. All the isolates were subjected to in vitro bioassays to evaluate their inhibitory activities against Na(+)/K(+)-ATPase from porcine cerebral cortex and bacterial growth. These studies led to the identification of compounds 1-6 as potent Na(+)/K(+)-ATPase inhibitors, with IC(50) values in the range of 4.0 ± 0.1-10.4 ± 0.6 µM. These compounds also exhibited a broad spectrum of antibacterial activity. In particular, compounds 4 and 6 showed potent inhibitory activities against several bacterial strains, except Escherichia coli, with minimum inhibitory concentration (MIC) values in the range of 0.65-2.08 µg/mL. Thus, L. nobilis-derived acylated kaempferol glycosides may have a potential to be leads for the development of Na(+)/K(+) ATPase inhibitors (1-6) and antibacterial agents (4, 6).

In vitro sortase A inhibitory and antimicrobial activity of flavonoids isolated from the roots of Sophora flavescens.

A series of flavonoids (1-14) was isolated from the roots of Sophora flavescens. We evaluated their ability to inhibit both microbial growth and sortase A, an enzyme that plays a key role in cell wall protein anchoring and virulence in Staphylococcus aureus. Most prenylated flavonoids (7-13) displayed potent inhibitory activity against gram-positive and gram-negative bacteria except E. coli, with minimum inhibitory concentrations values ranging from 4.40 to 27.7 µM, and weak or no activity against fungal strains tested. Kurarinol (6) was a potent inhibitor of sortase A, with an IC(50) value of 107.7 ± 6.6 µM. A preliminary structure-activity relationship, including essential structural requirements, is described.

In vitro Na+/K+-ATPase inhibitory activity and antimicrobial activity of sesquiterpenes isolated from Thujopsis dolabrata.

A series of sesquiterpenes and hinokitiol-related compounds (1-15) was isolated from the essential oil of Thujopsis dolabrata Sieb. et Zucc. var. hondai Makino, and their structures were determined by combined spectroscopic analyses. The inhibitory effects of these compounds on microbial cell growth and Na(+)/K(+)-ATPase were evaluated in vitro. It was found that (-)-elema-1,3,11(13)-trien-12-ol (5), α,ß,γ-costol (8), and chamigrenol (11) inhibit the activities of Na(+)/K(+)-ATPase, with IC(50) values of 11.2 ± 0.11, 12.2 ± 0.09, and 15.9 ± 0.54 µg/mL, respectively. Thujopsene (1), cedrol (9), γ-cuparenol (10), and chamigrenol (11) showed potent antibacterial activity, with MIC values in the range of 25-50 µg/mL, and ß-thujaplicin (12) exhibited a broad spectrum of antibacterial and antifungal activity. These results indicate that these isolated compounds are promising candidates for the development of potent Na(+)/K(+) ATPase inhibitors and antimicrobial agents.