Actin turnover protects the cytokinetic contractile ring from structural instability.

In common with other actomyosin contractile cellular machineries, actin turnover is required for normal function of the cytokinetic contractile ring. Cofilin is an actin-binding protein contributing to turnover by severing actin filaments, required for cytokinesis by many organisms. In fission yeast cofilin mutants, contractile rings suffer bridging instabilities in which segments of the ring peel away from the plasma membrane, forming straight bridges whose ends remain attached to the membrane. The origin of bridging instability is unclear. Here, we used molecularly explicit simulations of contractile rings to examine the role of cofilin. Simulations reproduced the experimentally observed cycles of bridging and reassembly during constriction, and the occurrence of bridging in ring segments with low density of the myosin II protein Myo2. The lack of cofilin severing produced ∼2-fold longer filaments and, consequently, ∼2-fold higher ring tensions. Simulations identified bridging as originating in the boosted ring tension, which increased centripetal forces that detached actin from Myo2, which was anchoring actin to the membrane. Thus, cofilin serves a critical role in cytokinesis by providing protection from bridging, the principal structural threat to contractile rings.

Lactobacillus, Bifidobacterium and Lactococcus response to environmental stress: Mechanisms and application of cross-protection to improve resistance against freeze-drying.

The review deals with lactic acid bacteria in characterizing the stress adaptation with cross-protection effects, mainly associated with Lactobacillus, Bifidobacterium and Lactococcus. It focuses on adaptation and cross-protection in Lactobacillus, Bifidobacterium and Lactococcus, including heat shocking, cold stress, acid stress, osmotic stress, starvation effect, etc. Web of Science, Google Scholar, Science Direct, and PubMed databases were used for the systematic search of literature up to the year 2020. The literature suggests that a lower survival rate during freeze-drying is linked to environmental stress. Protective pretreatment under various mild stresses can be applied to lactic acid bacteria which may enhance resistance in a strain-dependent manner. We investigate the mechanism of damage and adaptation under various stresses including heat, cold, acidic, osmotic, starvation, oxidative and bile stress. Adaptive mechanisms include synthesis of stress-induced proteins, adjusting the composition of cell membrane fatty acids, accumulating compatible substances, etc. Next, we reveal the cross-protective effect of specific stress on the other environmental stresses. Freeze-drying is discussed from three perspectives including the regulation of membrane, accumulation of compatible solutes and the production of chaperones and stress-responsive proteases. The resistance of lactic acid bacteria against technological stress can be enhanced via cross-protection, which improves industrial efficiency concerning the survival of probiotics. However, the adaptive responses and cross-protection are strain-dependent and should be optimized case by case.

Urolithin A Ameliorates Athletic Ability and Intestinal Microbiota in Sleep Deprivation from the Perspective of the Gut-Muscle Axis.

SCOPE: Urolithin A (UA), a gut-microbiota-derived metabolite of ellagic acid, presents various benefits to intestinal microecology. The presence of "gut-muscle axis" regulating the onset and progression of exercise-related physical frailty and sarcopenia has been recently hypothesized. This study aims to explore the underlying mechanism of gut-muscle axis by which UA enhances muscle strength and fatigue resistance of sleep-deprived (SD) mice. METHODS AND RESULTS: UA is gavaged to C57BL/6 mice (50 mg kg-1 bw) before 48-h SD. The results indicate that pretreatment of UA significantly enhances motor ability and energy metabolism. The inflammation is suppressed, and intestinal permeability is improved after prophylactic treatment with UA. The decreased level of serum lipopolysaccharide (LPS) is concomitant with augmentation of the intestinal tight junction proteins. 16s rRNA analysis of colonic contents reveals that UA significantly reduces the abundance of Clostridia_UCG-014 and Candidatus_Saccharimonas, and upregulates Lactobacillus and Muribaculaceae. UA probably influences on gut microbial functions via several energy metabolism pathways, such as carbon metabolism, phosphotransferase system (PTS), and ATP binding cassette (ABC) transporters. CONCLUSIONS: The dietary intervention of UA helps to create a systemic protection, a bidirectional communication connecting the gut microbiota with muscle system, able to alleviate SD-induced mobility impairment and gut dysbiosis.

Chlorogenic acid improves the cognitive deficits of sleep-deprived mice via regulation of immunity function and intestinal flora.

BACKGROUND: Sleep deprivation (SD) has become a global health concern with serious consequences containing memory deficits and gastrointestinal dysfunctions. The gut-brain axis serves as a crucial link between the brain and gut, and the utilization of chlorogenic acid (CGA) presents a compelling strategy for mitigating or potentially resolving various neuroinflammation-associated disorders. However, it is still unknown how CGA may interact with the gut, microbiota and the brain during SD. PURPOSE: This study aims to explore the therapeutic effect and underlying mechanism of microbiota-gut-brain axis by which CGA prevents SD-induced cognitive deficits. STUDY DESIGN AND METHODS: CGA (30, 60 mg/kg.bw.) was gavaged to C57BL/6 mice, and then they were submitted to 48-h SD. The cognitive and spatial learning abilities were investigated through behavioral tests. Furthermore, we explored the action mechanism of this compound with haematological analysis, histopathological examination, Western blot, ELISA and 16S rRNA gene pyrosequencing from colonic contents. RESULTS: The cognitive deficits induced by SD were significantly relieved by administration of CGA in a dose-dependent manner. The hematoxylin and eosin staining of hippocampus and colon tissues indicated that pretreatment of CGA not only protected brain tissue from SD, but also maintained intestinal integrity. In the hippocampus, the increased pro-inflammatory neurometabolites were significantly prevented by CGA, and an immune profile capable of hippocampal-dependent spatial memory was improved via Nrf2/PPAR signaling pathways. The observed immunomodulatory effect was concomitant with augmentation of the intestinal barrier, as evidenced by the heightened expressions of tight junction proteins. 16S rRNA analysis of colonic contents revealed that levels of Clostridia_UCG-014 and lipopolysaccharide were significantly inhibited, and those of Lactobacillus and intestinal tight junction proteins were upregulated in the CGA group. Pathways of ko05322 (immune disease) and ko04610 (immune system) were significantly regulated by CGA. Based on PICRUSt2 algorithm, CGA probably influenced gut microbial functions via several metabolism pathways, such as arginine biosynthesis, pyrimidine metabolism and purine metabolism. CONCLUSION: The present study first proved the efficacy and mechanism of CGA in alleviating SD-induced cognitive impairment and neuroinflammation via creating a systemic protection, a bidirectional communication system connecting the gut with the brain. The intestinal barrier improvement and the reshaped "SD microbiota" profiles restored immunity functions, which were probably the main contributors to Nrf2/PPAR activation and the neuroprotective effect of CGA. Overall, this work provided novel insights of CGA, which might guide the more reasonable clinical use of CGA in the pathogenesis of sleep-related disorders.

A combined effect of fish-originated collagen peptides and caffeine on the cognitive function of sleep-deprived mice.

Refreshing beverages, consumed worldwide, commonly take advantage of caffeine's impacts on attention and motor performance. However, excessive long-term caffeine intake might disturb sleep/wake rhythms and exacerbate daily anxiety. Fish-originated collagen peptides (FCP) are of high nutrient value with stimulating, calming or relaxing effects, which could reduce the excitotoxicity of caffeine. This study aims to investigate two facets: (1) the combined effect of caffeine and FCP (namely C&F) on the cognitive function of sleep-deprived mice by different administration strategies with dose dependence (low and high dose) or time dependence (intervention in a day and prevention for a week); (2) the potential "microbiota-gut-brain" mechanism by which C&F improves sleep deprivation (SD)-induced cognitive impairments. Here, C57BL/6 mice were administered caffeine (10 or 20 mg per kg per bw) combined with FCP (100 or 200 mg per kg per bw) and were then subjected to 48 h SD. The open-field and Morris water maze tests were performed to evaluate the cognitive function and spatial learning capacities of mice. Our results indicated that the cognitive impairments of SD mice were significantly relieved to a different degree by treating C&F in a dose- and time-dependent manner. The pathological observation of the hippocampus indicated both intervention (time of a day) and prevention (time of a week) of the C&F protected brain tissue from SD-induced injuries. The accumulated pro-inflammatory neurometabolites and factors were significantly inhibited by C&F via the hypothalamus-hippocampal circuit. Furthermore, 16S rDNA analysis of colonic contents showed that the level of Lactobacillus murinus was significantly upregulated and that of Clostridia_UCG-014 was suppressed in the C&F group. The receiver operating characteristic (ROC) curve of Lactobacillus murinus indicated a certain diagnostic utility to distinguish C&F intervention (AUC = 0.52) or prevention (AUC = 0.68). Pathways of ko04622 (immune system) and ko00472 (metabolism processes) were significantly regulated by C&F in a time-dependent manner. Based on PICRUSt2 algorithm analysis, C&F might potentially regulate gut microbial functions through several metabolic pathways, including the RIG-I-like receptor signaling pathway and limonene and pinene degradation. In conclusion, C&F plays a key role in brain function and behavior, which could synergistically relieve cognitive impairments via the microbiota-gut-brain axis.

Extracellular polysaccharides from Sporidiobolus pararoseus alleviates rheumatoid through ameliorating gut barrier function and gut microbiota.

Rheumatoid arthritis (RA) is becoming a prevalent autoimmune disease affecting people worldwide, necessitating the exploration of novel therapeutic approaches due to the associated adverse effects of conventional therapeutic drugs. Sporidiobolus pararoseus polysaccharide (SPP) has been shown to exhibit significant immune stimulation and antioxidant activities. In this study, we constructed a mouse model of type II collagen-induced arthritis (CIA) to investigate the effects and potential mechanisms of SPP intervention on RA. Results showed that SPP intervention alleviated the degree of ankle swelling, joint histopathologic changes, joint pathological score and the expression of serum-associated inflammatory mediators (such as IL-1ß and IL-6). 16S rRNA sequencing results indicated that SPP intervention significantly remodeled the intestinal microbiota composition. In particular, SPP intervention significantly increased the relative abundance of beneficial bacteria (Parabacteroides, Bacteroides and Rikenellaceae_RC9_gut_group) with the potential to degrade fungal polysaccharides or produce short-chain fatty acids (SCFAs). The production of SCFAs (especially acetic acid, propionic acid and butyric acid) indeed increased significantly. These SCFAs played an important role in maintaining intestinal barrier function and regulating immune homeostasis, which helped reduce inflammatory responses and alleviate the symptoms of RA.

Echinacea purpurea polysaccharide intervene in hepatocellular carcinoma via modulation of gut microbiota to inhibit TLR4/NF-κB pathway.

Echinacea purpurea polysaccharide (EPP) exhibit various pharmacological activities, including immunomodulatory, anti-inflammatory, and anti-tumor effects. In this study, we investigated the potential mechanism of EPP intervention in hepatocellular carcinoma (HCC). The results demonstrated that EPP effectively mitigated liver injury caused by HCC, inhibited the proliferation of HCC, and induced apoptosis. Following EPP intervention, there was a significant increase in propionic acid and butyric acid-producing gut microbiota such as Coprococcus, Clostridium and Roseburia, leading to enhanced expression of intestinal tight junction proteins and the repair of the intestinal barrier. This controls lipopolysaccharide (LPS) leakage, which in turn inhibits the TLR4/NF-κB pathway and reduces the expression of inflammatory factors such as IL-6, as well as migration factors like MMP-2. Metabolomics revealed the downregulation of pyrimidine metabolism and nucleotide metabolism, along with the upregulation of butyrate metabolism in tumor cells. This study demonstrated that EPP effectively regulated LPS leakage by modulating gut microbes, and this modulation influenced the TLR4/NF-κB pathway, ultimately disrupting tumor cell survival induced by HCC in mice.

Actomyosin pulsing rescues embryonic tissue folding from disruption by myosin fluctuations.

During early development, myosin II mechanically reshapes and folds embryo tissue. A much-studied example is ventral furrow formation in Drosophila , marking the onset of gastrulation. Furrowing is driven by contraction of actomyosin networks on apical cell surfaces, but how the myosin patterning encodes tissue shape is unclear, and elastic models failed to reproduce essential features of experimental cell contraction profiles. The myosin patterning exhibits substantial cell-to-cell fluctuations with pulsatile time-dependence, a striking but unexplained feature of morphogenesis in many organisms. Here, using biophysical modeling we find viscous forces offer the principle resistance to actomyosin-driven apical constriction. In consequence, tissue shape is encoded in the direction-dependent curvature of the myosin patterning which orients an anterior-posterior furrow. Tissue contraction is highly sensitive to cell-to-cell myosin fluctuations, explaining furrowing failure in genetically perturbed embryos whose fluctuations are temporally persistent. In wild-type embryos, this catastrophic outcome is averted by pulsatile myosin time-dependence, a time-averaging effect that rescues furrowing. This low pass filter mechanism may underlie the usage of actomyosin pulsing in diverse morphogenetic processes across many organisms.

Actomyosin pulsing rescues embryonic tissue folding from disruption by myosin fluctuations.

During early development, myosin II mechanically reshapes and folds embryo tissue. A muchstudied example is ventral furrow formation in Drosophila, marking the onset of gastrulation. Furrowing is driven by contraction of actomyosin networks on apical cell surfaces, but how the myosin patterning encodes tissue shape is unclear, and elastic models failed to reproduce essential features of experimental cell contraction profiles. The myosin patterning exhibits substantial cell-to-cell fluctuations with pulsatile time-dependence, a striking but unexplained feature of morphogenesis in many organisms. Here, using biophysical modeling we find viscous forces offer the principal resistance to actomyosin-driven apical constriction. In consequence, tissue shape is encoded in the direction-dependent curvature of the myosin patterning which orients an anterior-posterior furrow. Tissue contraction is highly sensitive to cell-to-cell myosin fluctuations, explaining furrowing failure in genetically perturbed embryos whose fluctuations are temporally persistent. In wild-type embryos this disastrous outcome is averted by pulsatile myosin time-dependence, which rescues furrowing by eliminating high frequencies in the fluctuation power spectrum. This low pass filter mechanism may underlie the usage of actomyosin pulsing in diverse morphogenetic processes across many organisms.

Immunosenescence and macrophages: From basics to therapeutics.

Ageing decreases the function of the immune system and increases susceptibility to some chronic, infectious, and autoimmune diseases. Senescence cells, which produce senescence-associated secretory phenotypes (SASPs), can activate the innate and adaptive immune responses. Macrophages are among the most abundant innate immune cell types in senescent microenvironments. Senescence-associated macrophages, recruited by SASPs, play a vital role in establishing the essential microenvironments for maintaining tissue homeostasis. However, it's important to note that these senescence-associated macrophages can also influence senescent processes, either by enhancing or impeding the functions of tissue-resident senescent cells. In this discussion, we describe the potential targets of immunosenescence and shed light on the probable mechanisms by which macrophages influence cellular senescence. Furthermore, we analyze their dual function in both clearing senescent cells and modulating age-related diseases. This multifaceted influence operates through processes including heightened inflammation, phagocytosis, efferocytosis, and autophagy. Given the potential off-target effects and immune evasion mechanisms associated with traditional anti-ageing strategies (senolytics and senomorphics), 'resetting' immune system tolerance or targeting senescence-related macrophage functions (i.e., phagocytotic capacity and immunosurveillance) will inform treatment of age-related diseases. Therefore, we review recent advances in the use of macrophage therapeutics to treat ageing and age-associated disorders, and outline the key gaps in this field.

Aqueous Extract of Brassica rapa L.'s Impact on Modulating Exercise-Induced Fatigue via Gut-Muscle Axis.

Exercise-induced fatigue is a common physiological response to prolonged physical activity, often associated with changes in gut microbiota and metabolic responses. This study investigates the potential role of Brassica rapa L. in modulating these responses. Using an animal model subjected to chronic exercise-induced stress, we explored the effects of Brassica rapa L. on fatigue-related biomarkers, energy metabolism genes, inflammatory responses, intestinal integrity, and gut microbiota composition. Our findings revealed that Brassica rapa L. exhibits significant antioxidant activity and effectively modulates physiological responses to fatigue. It influences gene expression related to the tricarboxylic acid (TCA) cycle in muscle tissue through the AMPK/PGC-1α/TFAM signaling pathway. Furthermore, Brassica rapa L. has been found to alleviate inflammation by inhibiting lipopolysaccharide (LPS) infection and suppressing the activation of the NF-κB pathway. It also maintains intestinal integrity and controls Gram-negative bacterial growth. A correlation analysis identified several pathogenic bacteria linked with inflammation and energy metabolism, as well as beneficial probiotic bacteria associated with improved energy metabolism and reduced inflammation. These findings underscore Brassica rapa L.'s potential for managing prolonged exercise-induced fatigue, paving the way for future therapeutic applications. The results highlight its impact on gut microbiota modulation and its role in nutrition science and sports medicine.

Reshaped Gut Microbial Composition and Functions Associated with the Antifatigue Effect of Salidroside in Exercise Mice.

SCOPE: Salidroside (SA) is an active compound derived from Rhodiola rosea and is widely used in healthcare foods. However, the underlying mechanism and its specific role in regulating the gut microbial community during exercise (Ex) remains unknown. METHODS AND RESULTS: Mice are subjected to a weight-loaded swimming test (WST) Ex to determine how gut microbiota affects the antifatigue activity of SA. The SA-treated group mice (100 mg kg-1 .bw.) display a significant increase in swimming time compared to the control group (26.2 versus 10.5 min, p < 0.01), as well as an increase in respiratory enzymatic activities after swimming. The respiratory enzymatic activities are significantly higher in the SA-treated group than in the RS (regular rest) group after swimming. The bacteria profiles in the Ex + SA group change significantly with higher species diversity and abundance. Receiver operating characteristic (ROC) curves of Alistipes, Rikenellaceae, Parabacteroides, Candidatus Arthromitus, and Lactobacillus indicate a high diagnostic utility to distinguish SA treatment. Microbial function analysis shows that SA may improve Ex-induced fatigue by modulating energy metabolism-related processes. CONCLUSIONS: SA demonstrates antifatigue effects on various levels of regulating energy metabolism and microbial composition, providing insights into the underlying mechanisms of SA as a natural prebiotic.

Pharmacological Effects of Urolithin A and Its Role in Muscle Health and Performance: Current Knowledge and Prospects.

Urolithin A (UA) is a naturally occurring compound derived from the metabolism of gut microbiota, which has attracted considerable research attention due to its pharmacological effects and potential implications in muscle health and performance. Recent studies have demonstrated that Urolithin A exhibits diverse biological activities, encompassing anti-inflammatory, antioxidant, anti-tumor, and anti-aging properties. In terms of muscle health, accumulating evidence suggests that Urolithin A may promote muscle protein synthesis and muscle growth through various pathways, offering promise in mitigating muscle atrophy. Moreover, Urolithin A exhibits the potential to enhance muscle health and performance by improving mitochondrial function and regulating autophagy. Nonetheless, further comprehensive investigations are still warranted to elucidate the underlying mechanisms of Urolithin A and to assess its feasibility and safety in human subjects, thereby advancing its potential applications in the realms of muscle health and performance.

Pharmaceutical Potential of High-Altitude Plants for Fatigue-Related Disorders: A Review.

Natural plants from plateaus have been the richest source of secondary metabolites extensively used in traditional and modern health care systems. They were submitted to years of natural selection, co-evolved within that habitat, and show significant anti-fatigue-related pharmacological effects. However, currently, no review on high-altitude plants with anti-fatigue related properties has been published yet. This study summarized several Chinese traditional high-altitude plants, including Rhodiola rosea L., Crocus sativus L., Lepidium meyenii W., Hippophaerhamnoides L., which are widely used in the Qinghai-Tibet Plateau and surrounding mountains, as well as herbal markets in the plains. Based on phytopharmacology studies, deeper questions can be further revealed regarding how these plants regulate fatigue and related mental or physical disease conditions. Many active derivatives in high-altitude medical plants show therapeutic potential for the management of fatigue and related disorders. Therefore, high-altitude plants significantly relieve central or peripheral fatigue by acting as neuroprotective agents, energy supplements, metabolism regulators, antioxidant, and inflammatory response inhibitors. Their applications on the highland or flatland and prospects in natural medicine are further forecast, which may open treatments to reduce or prevent fatigue-related disorders in populations with sub-optimal health.

An integrated network pharmacology and metabolomics approach to reveal the immunomodulatory mechanism of Brassica rapa L. (Tibetan Turnip) in fatigue mice.

Brassica rapa L. has been widely used as an edible, feeding and medicinal plant in the Qinghai-Tibet Plateau due to its several pharmacological effects of alleviating deficiency or weakness, anti-inflammation, and relieving acute mountain sickness. However, its therapeutic efficacy and the underlying mechanism against fatigue have not been elucidated. The aim of this study is to investigate the action mechanisms of Brassica rapa L. extract (BE) in treating fatigue, with emphasis on the fatigue-related biomarkers, targets and pathways, via network pharmacology and widely targeted metabolomics. Based on the UHPLC-MS results, a total of 33 components were identified and the energy metabolic homeostasis and inflammation related signaling pathways were considered crucial for BE against fatigue by gene functional enrichment analysis. Western blotting (WB) showed that BE significantly up-regulated Nrf2/HO-1, phosphorylation of AMPK, and expression of the downstream signaling pathway, which was further verified by quantitative real-time PCR (q Rt-PCR). The metabolic pathway analysis of BE showed that linoleic acid metabolism was mainly involved, as well as the generation and degradation of ketone bodies, and taurine and hypotaurine metabolism, which are closely related to the regulation of energy metabolism and immunoregulation. Furthermore, the drug-containing serum of BE attenuated intracellular ROS levels in macrophage Raw264.7 cells and reversed the M1 polarization by enhancing the level of IL-10 and Arg-1 and inhibiting that of IL-12 and iNOS in vitro. Hence, Brassica rapa L. has the potential to become a functional food or alternative therapy for fatigue management among immune-compromised people.

Deciphering the potential role of Maca compounds prescription influencing gut microbiota in the management of exercise-induced fatigue by integrative genomic analysis.

A growing number of nutraceuticals and cosmeceuticals have been utilized for millennia as anti-fatigue supplements in folk medicine. However, the anti-fatigue mechanism underlying is still far from being clearly explained. The aim of the study is to explore the underlying mechanism of the Maca compound preparation (MCP), a prescription for management of exercise-induced fatigue. In this study, mice weight-loaded swimming test was used to evaluate the anti-fatigue effect of MCP. MCP significantly improved the forelimb grip strength and Rota-rod test in behavioral tests via regulating energy metabolism. 16S rDNA sequencing results showed MCP can regulate the intestinal flora at the genus level by increasing several beneficial bacteria (i.e., Lactobacillus, Akkermansia and etc.), and decreasing the harmful bacteria (i.e., Candidatus_Planktophila and Candidatus_Arthromitus), where notable high relevance was observed between the fatigue-related biomarkers and fecal microbiota. The results of microbial function analysis suggested that MCP might improve exercise-induced fatigue by enhancing energy metabolism, carbohydrate and lipid metabolism and metabolism of terpenoids and polyketides and breakdown of amino acid metabolism. In addition, and H2O2-induced oxidative stress model on C2C12 cells was employed to further validate the regulation of MCP on energy metabolisms. MCP pre-treatment significantly reduced intracellular ROS accumulation, and increased glycogen content, ATP generation capacity and mitochondrial membrane potential of skeletal muscle cells, as well as conferred anti-cell necrosis ability. In conclusion, MCP plays a key role in regulating fatigue occurrence in exercising and gut microbiota balance, which may be of particular importance in the case of manual workers or sub-healthy populations.

Ameliorative effects of chlorogenic acid on alcoholic liver injury in mice via gut microbiota informatics.

Chlorogenic acid (CGA) is a functional phenolic acid widely used in food and medicine-related fields. It has been proved to be effective in the treatment of alcoholic liver disease (ALD). However, the exact mechanism by which CGA prevents ALD, especially from the crosstalk between gut and liver, has not been previously reported. This work was aimed to explore the protective effects of CGA against ALD and its relationships to gut-liver axis abnormalities. Experimental results showed the increased (p < 0.05) serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), low density lipoprotein (LDL), total cholesterol (TC) and triglyceride (TG) levels of mice fed with ethanol were ameliorated by supplementing with CGA. Moreover, CGA promoted the production of n-butyric acid by nearly 3 times (1.78 vs 0.62 nM, p < 0.01), a short-chain fatty acid that helps maintain the integrity of the intestinal barrier. Furthermore, CGA alleviated microbial dysbiosis, evidenced by the increased relative abundances of beneficial bacteria Muribaculaceae, Bacteroides, Alloprevotella, and Parabacteroides, and decreased that of opportunistic pathogens Eubacterium_nodatum, Eubacterium_ruminantium, and Anaerotruncus. Correlation analysis further elucidated the microbiota altered after CGA intervention was positively correlated with short-chain fatty acids and antioxidant indexes, while negatively correlated with inflammatory cytokines. In summary, these findings suggested the hepatoprotective effect of CGA was ascribed to the modulation of gut-liver axis homeostasis.

In-depth investigation of the mechanisms of Echinacea purpurea polysaccharide mitigating alcoholic liver injury in mice via gut microbiota informatics and liver metabolomics.

Accumulating evidence suggests that the pathogenesis of alcoholic liver disease (ALD) is strongly correlated with abnormalities of the gut-liver axis. Echinacea purpurea polysaccharide (EPP) is a homogeneous polysaccharide, which has been shown to mitigate ALD. However, the effects of EPP on gut microbiome and consequently on hepatic metabolism have yet to be explored. In this study, the microbiome and metabolomics were combined to explore the effects of EPP on gut microbiota and hepatic metabolism, and the relationship between both was further revealed by Spearman correlation analysis. Results exhibited EPP reversed alcohol-induced disturbances in gut microbiota, evidenced by increased abundance of Muribaculaceae, Lactobacillus, and Bacteroides and decreased abundance of Escherichia_Shigella and Enterococcus. Besides, EPP promoted the production of n-butyric acid, a short-chain fatty acid that maintains the integrity of the intestinal barrier. Moreover, EPP improved alterations in hepatic metabolites, and characteristic metabolites such as Berberine and Ponasterone as well as key metabolic pathways, particularly Nitrogen metabolism, were identified. Furthermore, correlation analysis suggested significant associations between gut microbes and hepatic metabolites, which in turn confirmed EPP alleviated ALD via the gut-liver axis. Therefore, these findings elucidated in-depth mechanisms of EPP against ALD and provided a new target for intervention in alcohol-related diseases.

Network Pharmacology Exploration Reveals Gut Microbiota Modulation as a Common Therapeutic Mechanism for Anti-Fatigue Effect Treated with Maca Compounds Prescription.

Maca compounds prescription (MCP) is a common botanical used in dietary supplements, primarily to treat exercise-induced fatigue. The aim of this study is to elucidate the multi-target mechanism of MCP on fatigue management via network pharmacology and gut microbiota analysis. Databases and literature were used to screen the chemical compounds and targets of MCP. Subsequently, 120 active ingredients and 116 fatigue-related targets played a cooperative role in managing fatigue, where several intestine-specific targets indicated the anti-fatigue mechanism of MCP might be closely related to its prebiotics of intestinal bacteria. Thus, forced swimming tests (FSTs) were carried and mice fecal samples were collected and analyzed by 16S rRNA sequencing. Gut microbiota were beneficially regulated in the MCP-treated group in phylum, genus and OTU levels, respectively, and that with a critical correlation included Lactobacillus and Candidatus Planktophila. The results systematically reveal that MCP acts against fatigue on multi-targets with different ingredients and reshapes the gut microbial ecosystem.

Effect of polysaccharides from Tibetan turnip (Brassica rapa L.) on the gut microbiome after in vitro fermentation and in vivo metabolism.

Tibetan turnip (Brassica rapa L.) polysaccharide (TTP) is an active ingredient and has been studied for many years due to its biological effect. There are a few studies on its digestion properties and the regulation of the intestinal microbiota. In this study, the regulation of intestinal health by TTP was investigated in vitro and in vivo. The results showed that TTP was not degraded after simulated gastrointestinal digestion. When TTP was fermented by the gut microbiota, the content of short-chain fatty acids (SCFAs) and the relative abundance of Bifidobacterium, Catenibacterium increased; the relative abundance of Prevotella, Phascolarctobacterium decreased. The in vivo experiments showed that TTP could reduce the abundances of Muribaculaceae and enrich Lactobacillus. The results of KEGG indicated that TTP could promote arginine and ornithine metabolism, fructose and mannose metabolism, and lipopolysaccharide biosynthesis. These data showed that TTP exerted its prebiotic effect by regulating the intestinal flora and could be used for preventing disease and improving health by maintaining intestinal health.