Regulating Gut Microbiota Research Articles

Berberine and magnolol exert cooperative effects on ulcerative colitis in mice by self-assembling into carrier-free nanostructures

The risk of ulcerative colitis (UC) is increasing worldwide with limited success using classical drugs, which has underscored the development of novel agents. Recently, carrier-free molecular assembly has been proven to be an effective drug delivery system, but it has yet to be examined for UC drug development using phytochemicals. Based on traditional Chinese medicine compatibility and potential medicinal uses, a pair of natural compounds, berberine (BBR) and magnolol (MAG), were found to self-assemble into nanostructures in aqueous solutions. Spectral analysis revealed that the assembly mechanisms of BBR and MAG were mediated through charge interactions and π-π stacking. Pharmacokinetic studies and animal imaging showed that BBR-MAG self-assembly (BM) effectively promoted the oral bioavailability and biodistribution of BBR in the colon. BM exhibited superior effects in regulating inflammatory factors, maintaining colon barrier integrity, and regulating gut microbiota in a dextran sulfate sodium salt-induced colitis mouse model. Additionally, no apparent signs of toxicity were observed, suggesting that BM has a favorable safety profile. This study presents a new strategy for UC management and highlights the cooperative effects of combined phytochemicals.Graphical

Corn Peptides Alleviate Nonalcoholic Fatty Liver Fibrosis in Mice by Inhibiting NLRP3 Inflammasome Activation and Regulating Gut Microbiota.

This study aimed to investigate the effects of corn gluten-derived soluble epoxide hydrolase (sEH) inhibitory peptides on nonalcoholic fatty liver fibrosis induced by a high-fat diet and carbon tetrachloride in mice. Mice treated with corn peptides at doses of 500 or 1000 mg/kg/d for 4 weeks exhibited reduced sEH activity in serum and liver, enhanced lipid metabolism, and decreased lipid accumulation and oxidative stress. Corn peptides effectively downregulated the mRNA levels of Pro-IL-1β, Pro-IL-18, NOD-like receptor protein 3 (NLRP3), ASC, Pro-caspase-1, Caspase-1, and GSDMD in the liver. This hepatoprotective effect of corn peptides by inhibiting NLRP3 inflammasome activation was further validated in H2O2-induced HepG2 cells. Moreover, corn peptides restored the composition of the gut microbiota and promoted short-chain fatty acid production. This study provides evidence that corn-derived sEH inhibitory peptides have hepatoprotective activity against nonalcoholic fatty liver fibrosis by suppressing NLRP3 inflammasome activation and modulating gut microbiota.

EIF6 deficiency regulates gut microbiota, decreases systemic inflammation, and alleviates atherosclerosis.

Altered composition of the gut microbiota affects immunity and metabolism. This study previously found that eIF6 gene knockdown changes the composition of the intestinal flora in the eIF6 gene knockdown mouse model. Lactobacillus acidophilus is significantly increased in the model. This study was designed to investigate the role of L. acidophilus in the pathogenesis of atherosclerosis. Transcriptomic data from 117 patients with coronary artery disease (CAD) and 79 healthy individuals were obtained. ApoE-/- and ApoE-/-/eIF6+/- mice on normal chow diet or a high-fat diet were treated for 16 weeks; eIF6 deficiency was evaluated atherosclerosis. ApoE-/- mice on normal chow diet or a high-fat diet were treated with L. acidophilus by daily oral gavage for 16 weeks. Moreover, one group was treated with lipopolysaccharide at 12 weeks. The levels of eIF6, RNASE3, and RSAD2 were notably higher in the patients with CAD than in the healthy individuals. eIF6 deficiency altered the composition of gut microbiota. eIF6 deficiency reduced the atherosclerotic lesion formation in ApoE-/-/eIF6+/- mice compared with the ApoE-/- mice. The microbial sequencing and metabolomics analysis demonstrated some beneficial bacterial (L. acidophilus, Ileibacterium, and Bifidobacterium) and metabolic levels significantly had deference in ApoE-/-/eIF6+/- mice compared with the ApoE-/- mice. Correlational studies indicated that L. acidophilus had close correlations with low-density lipoprotein cholesterol, lesion area, and necrotic area. L. acidophilus inhibited high-fat diet-induced inflammation and atherosclerotic lesion, increasing the expression of tight junction proteins (ZO-1 and claudin-1) and reducing the gut permeability. However, lipopolysaccharide reversed the protective effect of L. acidophilus against atherosclerosis. eIF6 deficiency protected against atherosclerosis by regulating the composition of gut microbiota and metabolites. L. acidophilus attenuated atherosclerotic lesions by reducing inflammation and increasing gut permeability.IMPORTANCEeIF6 deficiency modulates the gut microbiota and multiple metabolites in atherosclerotic ApoE-/- mice. L. acidophilus was reduced in the gut of atherosclerotic ApoE-/- mice, but administration of Lactobacillus acidophilus reversed intestinal barrier dysfunction and vascular inflammation. Our findings suggest that targeting individual species is a beneficial therapeutic strategy to prevent inflammation and atherosclerosis.

Inflammation-oriented montmorillonite adjuvant enhanced oral delivery of anti-TNF-α nanobody against inflammatory bowel disease

Oral delivery of proteins faces challenges due to the harsh conditions of the gastrointestinal (GI) tract, including gastric acid and intestinal enzyme degradation. Permeation enhancers are limited in their ability to deliver proteins with high molecular weight and can potentially cause toxicity by opening tight junctions. To overcome these challenges, we propose the use of montmorillonite (MMT) as an adjuvant that possesses both inflammation-oriented abilities and the ability to regulate gut microbiota. This adjuvant can be used as a universal protein oral delivery technology by fusing with advantageous binding amino acid sequences. We demonstrated that anti-TNF-α nanobody (VII) can be intercalated into the MMT interlayer space. The carboxylate groups (-COOH) of aspartic acid (D) and glutamic acid (E) interact with the MMT surface through electrostatic interactions with sodium ions (Na+). The amino groups (NH2) of asparagine (N) and glutamine (Q) are primarily attracted to the MMT layers through hydrogen bonding with oxygen atoms on the surface. This binding mechanism protects VII from degradation and ensures its release in the intestinal tract, as well as retaining biological activity, leading to significantly enhanced therapeutic effects on colitis. Furthermore, VII@MMT increases the abundance of short-chain fatty acids (SCFAs)-producing strains, including Clostridia, Prevotellaceae, Alloprevotella, Oscillospiraceae, Clostridia_vadinBB60_group, and Ruminococcaceae, therefore enhance the production of SCFAs and butyrate, inducing regulatory T cells (Tregs) production to modulate local and systemic immune homeostasis. Overall, the MMT adjuvant provides a promising universal strategy for protein oral delivery by rational designed protein.

Carbonic anhydrase 2 mediates anti-obesity effects of black tea as thermogenic activator

Obesity is a metabolic disorder due to over-accumulation of adipose tissue and ultimately becomes a “disease”. Brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning emerge as a potential strategy of anti-obesity by dissipating energy as heat. However, drugs based on adipose tissue thermogenesis have not been successfully approved yet. In current study, we found that black tea extract (BTE) obtained by patent-authorized manufacturing process prevented body weight gain as novel thermogenic activator with reduction of adiposity, improvement of adipose distribution, and glucose metabolism improvement in diet-induced obesity mice. Mechanismly, anti-obesity effect of BTE depends on promoting BAT thermogenesis and WAT browning with upregulation of uncoupling protein 1 (UCP1), especially visceral adipose tissue (VAT) with browning resistance. Specifically, utilizing in silico approach of network pharmacology and molecular docking, we identified carbonic anhydrase 2 (CA2) in nitrogen metabolism as anti-obesity target of BTE and further elucidated that protein kinase B (AKT) signaling pathway linked CA2 and UCP1. Meanwhile gut microbiota regulation may prompt the CA2-dependent thermogenesis activation. Our findings demonstrated anti-obesity effect of BTE as thermogenic activator through CA2-mediated BAT thermogenesis and WAT browning via CA2-AKT-UCP1 signaling pathway, which could be developed as promising anti-obesity agent with good safety and efficacy.

Dietary inositol supplementation improves meat quality by modulating amino acid metabolism and gut microbiota composition of finishing pigs

Intramuscular fat (IMF) content influences various meat quality traits, including tenderness, flavor, juiciness and nutritional value. This study aimed to investigate the effects of dietary inositol supplementation on meat quality, metabolic profiles, and gut microbiota composition of finishing pigs. A total of 144 finishing pigs (initial body weight 70.41 ± 0.78 kg) were randomly divided into control, 0.075%, 0.15%, and 0.3% inositol groups. The data showed that inositol increased backfat thickness at the 6th to 7th rib and 10th rib, IMF content, and improved tenderness (P ≤ 0.05, n = 8). Paralleling an increase in fat deposition, 0.3% inositol also increased the protein level of PPARγ in the subcutaneous fat (P ≤ 0.05) and longissimus thoracis (LT) muscle (P = 0.062). Inositol elevated the content of amino acids in LT muscle and enhanced amino acid metabolism of finishing pigs, including lysine degradation, tyrosine metabolism, and arginine and proline metabolism. The 16S ribosomal RNA (rRNA) sequencing showed that 0.3% inositol supplementation altered the profiles of microbes in the colon, particularly decreasing the abundance of Firmicutes (P < 0.01) and increasing the abundance of Bacteroidota (P ≤ 0.05). Correlation analysis showed that differential microbes had strong correlation with differential metabolites in serum, including amino acids. In conclusion, this study demonstrated that dietary inositol supplementation could effectively improve IMF content and tenderness of pork, enhance amino acid metabolism, and regulate gut microbiota composition of finishing pigs.

Role of Gut Microbiota in Immune System Regulation

Role of Gut Microbiota in Immune System Regulation

Characterization of gut microbiota in the Uyghur osteopenia population

The objectives of this study were to investigate the composition of gut microbiota and its relationship with bone loss in the Uyghur osteopenia population, identify potential disease-related taxa and collect information for the prevention and treatment of osteopenia in different people by regulating gut microbiota. We selected Uyghur residents, measured their heel BMD, collected faeces and general information, grouped them by BMD level, obtained faecal 16S rRNA sequences, and compared and analysed the differences between the groups. This study showed that the numbers of OTUs and species in the gut microbiota in the osteopenia group were higher than those in the control. At the phylum level, Erysipelotrichia was more abundant in the osteopenia group. At the genus level, Phascolarctobacterium was less abundant, and Ruminiclostridium_5 was more abundant in the osteopenia group compared to the control. Phascolarctobacterium and Z-score were positively correlated, and Ruminiclostridium_5 was negatively correlated with T and Z score. The different composition of the gut microbiota in Uyghur osteopenia patients and controls found in this study fills a knowledge gap in this ethnic group. The relationship between Uyghur osteopenia and BMD-associated bacterial genera deserves further exploration.

Ulva lactuca polysaccharides combined with fecal microbiota transplantation ameliorated dextran sodium sulfate-induced colitis in C57BL/6J mice.

Fecal microbiota transplantation (FMT) of healthy donors improves ulcerative colitis (UC) patients by restoring the balance of the gut microbiota. However, donors vary in microbial diversity and composition, often resulting in weak or even ineffective FMT. Improving the efficacy of FMT through combination treatment has become a promising strategy. Ulva lactuca polysaccharides (ULP) have been found to benefit host health by regulating gut microbiota. The effect of the combination of ULP and FMT in ameliorating UC has not yet been evaluated. The present study found that supplementation with ULP combined with FMT showed better effects in ameliorating UC than supplementation with FMT alone. Results suggested that FMT or ULP combined with FMT alleviated the symptoms of UC in mice, as evidenced by prevention of body weight loss, improvement of disease activity index and protection of the intestinal mucus. Notably, ULP in combination with FMT was more effective than FMT in reducing levels of cytokines and related inflammatory enzymes. In addition, ULP combined with FMT effectively restored the dysbiosis induced by dextran sulfate sodium (DSS) and further enriched probiotics (such as Bifidobacterium). The production of short-chain fatty acids, especially acetic acid, was also significantly enriched by ULP combined with FMT. Supplementation of ULP combined with FMT could significantly ameliorate DSS-induced colitis in mice by inhibiting inflammation and restoring dysbiosis of gut microbiota. These results suggested that ULP combined with FMT has potential application in ameliorating UC. © 2024 Society of Chemical Industry.

Untargeted Metabolomics Analysis of Lactic Acid Bacteria Fermented Acanthopanax senticosus with Regard to Regulated Gut Microbiota in Mice.

Previous studies have shown that Acanthopanax senticosus (AS) has a beneficial preventive and therapeutic effect on colitis. The fermentation of lactic acid bacteria (LAB) can alter the efficacy of AS by modifying or producing new compounds with potential bioactive properties. However, the specific components and mechanisms that enhance the efficacy are still unclear. In the present experiment, untargeted metabolomics was used to analyze the changes in active components before and after LAB fermentation of AS. The aim was to explain the mechanism of AS fermentation in treating colitis using a colitis model in mice. The results indicated that the fermentation of LAB could enhance the levels of total flavonoids and total polyphenols in FAS. Additionally, the beneficial components such as Delphinidin chloride, Diosmetin, Psoralidin, and Catechol significantly increased (p < 0.05). The colitis treatment experiment demonstrated that fermented AS could alleviate symptoms and improve the morphology of colitis in mice by enhancing antioxidant enzymes like CAT, T-SOD, and T-AOC. It also regulated the composition and abundance of intestinal flora species, such as Lactobacillus and Pseudogracilibacillus. The effectiveness of fermented AS was significantly superior to that of unfermented AS (p < 0.05). In conclusion, this study contributes to the application of lactic acid bacteria in AS fermentation and reveals the mechanism of fermentation AS for colitis.

Screening and Characterization of Probiotics Isolated from Traditional Fermented Products of Ethnic-Minorities in Northwest China and Evaluation Replacing Antibiotics Breeding Effect in Broiler.

In this study, Lactobacillus fermentum DM7-6 (DM7-6), Lactobacillus plantarum DM9-7 (DM9-7), and Bacillus subtilis YF9-4 (YF9-4) were isolated from traditional fermented products. The survival rate of DM7-6, DM9-7, and YF9-4 in simulated intestinal gastric fluid reached 61.29%, 44.82%, and 55.26%, respectively. These strains had inhibition ability against common pathogens, and the inhibition zone diameters were more than 7 mm. Antioxidant tests showed these strains had good scavenging capacity for superoxide anion, hydroxyl radical and DPPH, and the total reduction capacity reached 65%. Then DM7-6, DM9-7 and YF9-4 were fed to broilers to study the effects on antioxidant capacity, immune response, biochemical indices, tissue morphology, and gut microbiota. 180 healthy broilers were allocated randomly into six experimental groups. SOD, GSH-Px, and T-AOC in broilers serum were detected, and the results showed probiotics significantly improve antioxidant capacity compared to CK group, while antibiotics showed the opposite result. Besides, IgA, IgM, IgG, TNF-α, and IL-2 indicated it could significantly improve immunity by adding probiotics in broilers diets. However, antibiotics reduced immunoglobulin levels and enhanced inflammation index. Biochemical indicators and tissue morphology showed probiotics had a protective effect on metabolic organs. Gut microbiota analysis proved antibiotics could significantly decrease microbial community diversity and increase the proportion of opportunistic pathogens, while probiotics could improve the diversity of gut microbiota and promote the colonization of beneficial microorganisms. In summary, probiotics DM7-6, DM9-7, and YF9-4 can improve the broiler's health by improving antioxidant capacity and immune function, regulating gut microbiota, and can be used as alternative probiotics for antibiotics-free breeding of broilers.

Neuroprotective effects of mesenchymal stromal cells in mouse models of Alzheimer’s Disease: The Mediating role of gut microbes and their metabolites via the Microbiome-Gut-Brain axis

The intricacy and multifaceted nature of Alzheimer’s disease (AD) necessitate therapies that target multiple aspects of the disease. Mesenchymal stromal cells (MSCs) emerge as potential agents to mitigate AD symptoms; however, whether their therapeutic efficacy involves modulation of gut microbiota and the microbiome-gut-brain axis (MGBA) remains unexplored. In this study, we evaluated the effects of three distinct MSCs types—derived from the umbilical cord (UCMSC), dental pulp (SHED), and adipose tissue (ADSC)—in an APP/PS1 mouse model of AD. In comparison to saline control, MSCs administration resulted in a significant reduction of behavioral disturbances, amyloid plaques, and phosphorylated tau in the hippocampus and frontal cortex, accompanied by an increase in neuronal count and Nissl body density across AD-afflicted brain regions. Through 16S rRNA gene sequencing, we identified partial restoration of gut microbial balance in AD mice post-MSCs treatment, evidenced by the elevation of neuroprotective Akkermansia and reduction of the AD-associated Sphingomonas. To examine whether gut microbiota involved in MSCs efficacy in treating AD, SHED with better anti-inflammatory and gut microbiota recovery effects among three MSCs, and another AD model 5 × FAD mice with earlier and more pathological proteins in brain than APP/PS1, were selected for further studies. Antibiotic-mediated gut microbial inactivation attenuated MSCs efficacy in 5 × FAD mice, implicating the involvement of gut microbiota in the therapeutic mechanism. Functional analysis of altered gut microbiota and targeted bile acid metabolism profiling revealed a significant enhancement in bile acid variety following MSCs therapy. A chief bile acid constituent, taurocholic acid (TCA), was orally administered to AD mice and similarly abated AD symptoms. Nonetheless, the disruption of intestinal neuronal integrity with enterotoxin abrogated the ameliorative impact of both MSCs and TCA treatments. Collectively, our findings substantiate that MSCs confer therapeutic benefits in AD within a paradigm that primarily involves regulation of gut microbiota and their metabolites through the MGBA.

Unveiling gut microbiota's role: Bidirectional regulation of drug transport for improved safety.

Drug safety is a paramount concern in the field of drug development, with researchers increasingly focusing on the bidirectional regulation of gut microbiota in this context. The gut microbiota plays a crucial role in maintaining drug safety. It can influence drug transport processes in the body through various mechanisms, thereby modulating their efficacy and toxicity. The main mechanisms include: (1) The gut microbiota directly interacts with drugs, altering their chemical structure to reduce toxicity and enhance efficacy, thereby impacting drug transport mechanisms, drugs can also change the structure and abundance of gut bacteria; (2) bidirectional regulation of intestinal barrier permeability by gut microbiota, promoting the absorption of nontoxic drugs and inhibiting the absorption of toxic components; (3) bidirectional regulation of the expression and activity of transport proteins by gut microbiota, selectively promoting the absorption of effective components or inhibiting the absorption of toxic components. This bidirectional regulatory role enables the gut microbiota to play a key role in maintaining drug balance in the body and reducing adverse reactions. Understanding these regulatory mechanisms sheds light on novel approaches to minimize toxic side effects, enhance drug efficacy, and ultimately improve drug safety. This review systematically examines the bidirectional regulation of gut microbiota in drug transportation from the aforementioned aspects, emphasizing their significance in ensuring drug safety. Furthermore, it offers a prospective outlook from the standpoint of enhancing therapeutic efficacy and reducing drug toxicity, underscoring the importance of further exploration in this research domain. It aims to provide more effective strategies for drug development and treatment.

The protective effect of S-adenosylmethionine on chronic adolescent stress-induced depression-like behaviors by regulating gut microbiota

The efficacy and tolerability of current antidepressants for adolescent depression are inadequate. S-adenosylmethionine (SAMe), known for its effectiveness and minimal side effects in adult depression, remains unstudied in adolescents. This study explored the potential of SAMe to address depression-like behaviors in juvenile rats induced by chronic unpredictable mild stress (CUMS), with a focus on gut microbiome interactions. Adolescent male Wistar rats were subjected to a 4-week CUMS regimen and received daily intraperitoneal injections of 300 mg/kg SAMe. Behavioral assessments included the sucrose preference test, elevated plus maze test, open field test, and Y-maze test. Histopathological changes of the hippocampus and colon were observed by Nissl staining and hematoxylin and eosin staining, respectively. Gut microbiome composition was analyzed using Accurate 16S absolute quantification sequencing. The results showed that SAMe significantly improved behavioral outcomes, reduced histopathological damages in hippocampal neurons and colon tissues, and modulated the gut microbiota of depressed rats. It favorably altered the ratio of Bacteroidetes to Firmicutes, decreased the absolute abundance of Deferribacteres, and adjusted levels of key microbial genera associated with depression-like behaviors. These results suggested that SAMe could effectively counter depression-like behaviors in CUMS-exposed adolescent rats by mitigating hippocampal neuronal and colon damage and modulating the gut microbiota. This supports SAMe as a viable and tolerable treatment option for adolescent depression, highlighting the importance of the gut-brain axis in therapeutic strategies.

Oral Yak Whey Protein Can Alleviate UV-Induced Skin Photoaging and Modulate Gut Microbiota Composition.

Excessive UV exposure can lead to skin roughness, wrinkles, pigmentation, and reduced elasticity, with severe cases potentially causing skin cancer. Nowadays, various anti-photoaging strategies have been developed to maintain skin health. Among them, dietary supplements with anti-photoaging properties are gaining increasing attention. Yak whey protein (YWP) possesses multiple benefits, including anti-inflammatory, antioxidant, and immune-boosting properties, effectively protecting the skin. This study used a mixed UVA and UVB light source to irradiate a nude mouse model, exploring the advantages of YWP in anti-photoaging and regulating gut microbiota. The results indicated that YWP alleviated UV-induced skin damage, wrinkles, dryness, and reduced elasticity by inhibiting oxidative stress, inflammatory factors (IL-1α, IL-6, and TNF-α), and matrix metalloproteinases (MMP-1, MMP-3, and MMP-12), thereby increasing the levels of elastin, type I collagen, and type III collagen in the extracellular matrix (ECM). Additionally, YWP significantly improved the abundance of Firmicutes and Bacteroidota in the gut microbiota of mice, promoting the growth of beneficial bacteria such as Lachnospiraceae_NK4A136_group, Ruminococcus_torques_group, and Clostridia_UCG_014, mitigating the dysbiosis caused by photoaging. These findings underscore the potential of YWP in anti-photoaging and gut microbiota improvement, highlighting it as a promising functional food for enhancing skin and gut health.

Astragaloside IV Ameliorates Colonic Adenomatous Polyps Development by Orchestrating Gut Bifidobacterium and Serum Metabolome.

Astragaloside IV (AS-IV), a natural triterpenoid isolated from Astragalus membranaceus, has been used traditionally in Chinese medicine. Previous studies have highlighted its benefits against carcinoma, but its interaction with the gut microbiota and effects on adenomatous polyps are not well understood. This present study investigates the effects of AS-IV on colonic adenomatous polyp (CAP) development in high-fat-diet (HFD) fed [Formula: see text] mice. [Formula: see text] mice were fed an HFD with or without AS-IV or Naringin for 8 weeks. The study assessed CAP proliferation and employed 16S DNA-sequencing and untargeted metabolomics to explore correlations between microbiome and metabolome in CAP development. AS-IV was more effective than Naringin in reducing CAP development, inhibiting colonic proinflammatory cytokines (IL-1β, IL-6, and TNF-α), tumor associated biomarkers (c-Myc, Cyclin D1), and Wnt/β-catenin pathway proteins (Wnt3a, β-catenin). AS-IV also inhibited the proliferative capabilities of human colon cancer cells (HT29, HCT116, and SW620). Multiomics analysis revealed AS-IV increased the abundance of beneficial genera such as Bifidobacterium pseudolongum and significantly modulated serum levels of certain metabolites including linoleate and 2-trans,6-trans-farnesal, which were significantly correlated with the number of CAP. Finally, the anti-adenoma efficacy of AS-IV alone was significantly suppressed post pseudoaseptic intervention in HFD-fed [Formula: see text] mice but could be reinstated following a combined with Bifidobacterium pseudolongum transplant. AS-IV attenuates CAP development in HFD-fed [Formula: see text] mice by regulating gut microbiota and metabolomics, impacting the Wnt3a/β-catenin signaling pathway. This suggests a potential new strategy for the prevention of colorectal cancer, emphasizing the role of gut microbiota in AS-IV's antitumor effects.

A preliminary examination of gut microbiota and emotion regulation in 2- to 6-year-old children

A preliminary examination of gut microbiota and emotion regulation in 2- to 6-year-old children

Polysaccharides from bile Arisaema exert an antipyretic effect on yeast-induced fever rats through regulating gut microbiota and metabolic profiling

In our previous study, bile Arisaema was elucidated to have a significant anti-febrile effect, but the pharmacodynamic material basis of this effect remains uncertain. Herein, we found that the soluble polysaccharide fraction from bile Arisaema presents a remarkable antipyretic effect through balancing the gut microbiota and regulating metabolic profiling. Bile Arisaema polysaccharide (BAP) was characterized for its monosaccharide composition with arabinose, galactose, glucose, mannose and xylose (0.028:0.072:0.821:0.05:0.029, molar ratios) and amino acid composition with arginine, threonine, alanine, glycine, serine, proline and tyrosine (109.33, 135.78, 7.22, 8.86, 21.07, 4.96, 12.31 μg/mg). A total of 50 peptides were identified from BAP using Ltq-Orbitrap MS/MS. The oral administration of 100 mg/kg BAP significantly increased the antipyretic effect in yeast-induced fever rats by comparing the rectal temperature. Mechanistically, the inflammation and disorders of neurotransmitters caused by fever were improved by treatment with BAP. The western blotting results suggested that BAP could suppress fever-induced inflammation by down-regulating the NF-κB/TLR4/MyD88 signaling pathway. We also demonstrated that BAP affects lipid metabolism, amino acid metabolism and carbohydrate metabolism and balances the gut microbiota. In summary, the present study provides a crucial foundation for determining polysaccharide activity in bile Arisaema and further investigating the underlying mechanism of action.

Huperzine a ameliorates sepsis-induced acute lung injury by suppressing inflammation and oxidative stress via α7 nicotinic acetylcholine receptor

Sepsis, characterized by high mortality rates, causes over 50 % of acute lung injury (ALI) cases, primarily due to the heightened susceptibility of the lungs during this condition. Suppression of the excessive inflammatory response is critical for improving the survival of patients with sepsis; nevertheless, no specific anti-sepsis drugs exist. Huperzine A (HupA) exhibits neuroprotective and anti-inflammatory properties; however, its underlying mechanisms and effects on sepsis-induced ALI have yet to be elucidated. In this study, we demonstrated the potential of HupA for treating sepsis and explored its mechanism of action. To investigate the in vivo impacts of HupA, a murine model of sepsis was induced through cecal ligation and puncture (CLP) in both wild-type (WT) and α7 nicotinic acetylcholine receptor (α7nAChR) knockout mice. Our results showed that HupA ameliorates sepsis-induced acute lung injury by activating the α7nAChR. We used the CLP sepsis model in wild-type and α7nAChR −/− mice and found that HupA significantly increased the survival rate through α7nAChR, reduced the pro-inflammatory cytokine levels and oxidative stress, ameliorated histopathological lung injury, altered the circulating immune cell composition, regulated gut microbiota, and promoted short-chain fatty acid production through α7nAChR in vivo. Additionally, HupA inhibited Toll-like receptor NF-κB signaling by upregulating the α7nAChR/protein kinase B/glycogen synthase kinase-3 pathways. Our data elucidate HupA’s mechanism of action and support a “new use for an old drug” in treating sepsis. Our findings serve as a basis for further in vivo studies of this drug, followed by application to humans. Therefore, the findings have the potential to benefit patients with sepsis.

Shenling Baizhu powder attenuates lard diet in a fatigued state-induced diarrhea via targeting microbial metabolites short chain fatty acids-mediated lipid metabolism.

Shenling Baizhu Powder (SLBZP), a traditional Chinese medicine (TCM) prescription renowned for its efficacy, is specifically recognized for its therapeutic effects in managing diarrhea associated with spleen qi deficiency. Our previous research has demonstrated that a lard diet in a fatigued state induced diarrhea belonging to spleen qi deficiency in TCM. Through a comprehensive investigation, we aimed to provide insights into the intricate relationship between SLBZP and the modulation of gut microbiota in alleviating symptoms associated with spleen qi deficiency-induced diarrhea. We induced diarrhea in mice by subjecting them to continuous standing on a multiple-platform apparatus while administering lard through intragastric administration for 14days. Subsequently, we conducted gavage administration of SLBZP at a concentration of 0.637g/ml for seven days. We observed a therapeutic effect of SLBZP on diarrhea induced by a lard diet in a fatigued state. SLBZP mitigated disorders in lipid metabolism and diminished hepatic oxidative responses. Additionally, SLBZP reversed gut microbiota dysbiosis of diarrheic mice and notably increased the production of short-chain fatty acids (SCFAs), primarily acetic acid, butyric acid, and valeric acid. Through correlation analysis, we additionally identified Lactobacillus reuteri and Lactobacillus intestinalisas potentially pivotal species associated with the therapeutic effects of SLBZP. We demonstrated that SLBZP exerts therapeutic effects on diarrhea caused by a lard diet in a fatigued state by repairing the intestinal mucosal barrier, improving lipid metabolism disorders, and regulating gut microbiota and metabolites SCFAs.