Elevating the significance of legume intake: A novel strategy to counter aging-related mitochondrial dysfunction and physical decline.

Mitochondrial dysfunction increasingly becomes a target for promoting healthy aging and longevity. The dysfunction of mitochondria with age ultimately leads to a decline in physical functions. Among them, biogenesis dysfunction and the imbalances in the metabolism of reactive oxygen species and mitochondria as signaling organelles in the aging process have aroused our attention. Dietary intervention in mitochondrial dysfunction and physical decline during aging processes is essential, and greater attention should be directed toward healthful legume intake. Legumes are constantly under investigation for their nutritional and bioactive properties, and their consumption may yield antiaging and mitochondria-protecting benefits. This review summarizes mitochondrial dysfunction with age, discusses the benefits of legumes on mitochondrial function, and introduces the potential role of legumes in managing aging-related physical decline. Additionally, it reveals the benefits of legume intake for the elderly and offers a viable approach to developing legume-based functional food.

Low-Carbohydrate Diet Modulates Glucose-Lipid Utilization in Skeletal Muscle of Diabetic Mice.

Type 2 diabetes is associated with many complications, including skeletal muscle atrophy. Ketogenic diets and low-carbohydrate diets (LCD) have recently been introduced as dietary interventions in patients with diabetes, but their effects on glucose and lipid metabolism in skeletal muscle have not been studied. In the current study, we compared the effects of LCD and ketogenic diet on glucose and lipid metabolism in skeletal muscle of diabetic mice. C57BL/6J mice with type 2 diabetes, constructed by a high-fat diet combined with streptozotocin, were fed a standard diet, a high-fat diet, an LCD, or a ketogenic diet for 14 weeks, respectively. Here, we found that the LCD, rather than the ketogenic diet, retained skeletal muscle weight and suppressed the expression of atrophy-related genes in diabetic mice. In addition, the LCD had more glycolytic/type IIb myofiber content and inhibited forkhead box O1 and pyruvate dehydrogenase kinase 4 expression, leading to improved glucose utilization. However, the ketogenic diet maintained more oxidative/type I myofibers. Moreover, compared with the ketogenic diet, the LCD decreased intramuscular triglycerides content and muscle lipolysis, suggesting improvement in lipid metabolism. Taken together, these data suggested that the LCD improved glucose utilization, and inhibited lipolysis and atrophy in skeletal muscle of diabetic mice, while the ketogenic diet showed metabolic disorders in skeletal muscle.

5-Heptadecylresorcinol Regulates the Metabolism of Thermogenic Fat and Improves the Thermogenic Capacity of Aging Mice via a Sirtuin 3-Adenosine Monophosphate-Activated Protein Kinase Pathway.

5-Heptadecylresorcinol (AR-C17), a well-known biomarker for whole grain rye consumption, is a primary homolog of alkylresorcinols. In this study, the effects of AR-C17 on the thermogenesis of brown adipocytes and 3T3-L1 adipocytes were investigated. The results showed that AR-C17 increased sirtuin 3 (Sirt3) expression, and the expressions of specific thermogenic genes in adipocytes were increased. Furthermore, AR-C17 increased the mitochondrial functions during the thermogenic activation of adipocytes. In in vivo study, AR-C17 increased the cold tolerance and thermogenic capacity of adipose tissues in aging mice. In addition, Sirt3 activity was required for AR-C17-induced thermogenesis. Meanwhile, AR-C17 increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, and AMPK was involved in the regulation of AR-C17 on thermogenic adipocytes. Mechanically, AR-C17 upregulated a Sirt3-AMPK positive-feedback loop in adipocytes and further increased the expression of uncoupling protein 1 to activate thermogenesis. This study indicated that AR-C17 could be a promising thermogenic activator of adipocytes to alleviate obesity and aging-associated metabolic diseases.

Highland Barley Tea Polyphenols Extract Alleviates Skeletal Muscle Fibrosis in Mice by Reducing Oxidative Stress, Inflammation, and Cell Senescence.

The tea of roasted Highland barley is a cereal-based drink rich in polyphenols. A model of skeletal muscle senescence and fibrosis was constructed using d-galactose-induced C2C12 myotubes, and Highland barley tea Polyphenols (HBP) were extracted for the intervention. We found that HBP effectively alleviated oxidative stress, inflammation, and fibrosis induced by d-galactose-induced skeletal muscle senescence. Also, HBP treatment significantly down-regulated pro-fibrotic genes, inflammation, and oxidative stress levels in a contusion model of senescent mice. Reduced levels of SIRT3 protein was found to be an essential factor in skeletal muscle senescence and fibrosis in both cellular and animal models, while HBP treatment significantly increased SIRT3 protein levels and viability in skeletal muscle. The ability of HBP to mitigate skeletal muscle fibrosis and oxidative stress was significantly reduced after SIRT3 silencing. Together, these results suggest that HBP intervention can significantly alleviate aging-induced oxidative stress, inflammation, and skeletal muscle fibrosis, with the activation of SIRT3 as the underlying mechanism of action.

Effect of boiling and roasting on phenolic components and their bioaccessibilities of highland barley.

This study investigated the effects of two thermal treatments (boiling and roasting) on highland barley (HB) phenolics and their bioaccessibilities (in-vitro). The UPLC Q-TOF-MS system was utilized to identify the individual phenolic compounds in HB. Twenty-one phenolics and two non-phenolic compounds were identified in HB, and the fundamental phenolics in HB were flavanols and phenolic acids. Both boiling and roasting improved free and bound phenolics' extractability and antioxidant activity by loosening the grain matrix. In-vitro simulated digestion showed that thermal-treated HB had higher bioaccessibility of phenolics than raw samples, and the boiled samples had higher bioaccessibility (36.3%) of phenolics than those of roasted samples (22.75%). Therefore, boiling and roasting could be used as non-chemical treatments to improve whole grain's phenolic content and their bioaccessibility.

Polyphenols in Highland Barley Tea Inhibit the Production of Advanced Glycosylation End-Products and Alleviate the Skeletal Muscle Damage.

SCOPE: Highland barley tea is a kind of caffeine-free cereal tea. Previous studies have shown that it is rich in polyphenol flavonoids. Here, the effect of Highland barley tea polyphenols (HBP) on the production of advanced glycosylation end-products and alleviate the skeletal muscle damage is systematically investigated. METHODS AND RESULTS: HBP effectively inhibits the formation of AGEs in vitro, and 12 phenolic compounds are identified. In addition, d-galactose is used to construct a mouse senescence model and intervenes with different doses of HBP. It is found that high doses of HBP effectively inhibit AGEs in serum and flounder muscle species and increased muscle mass in flounder muscle; also, high doses of HBP increase the expression of the mitochondrial functional protein SIRT3 and decrease the expression of myasthenia-related proteins. Furthermore, cellular experiments show that AGEs can significantly increase oxidative stress in skeletal muscle. CONCLUSION: These data indicate that the relationship between the biological activity and HBP properties is relevant since Highland barley can be a potential functional food to prevent AGEs-mediated skeletal muscle damage.

Maternal secretin ameliorates obesity by promoting white adipose tissue browning in offspring.

Our knowledge of the coordination of intergenerational inheritance and offspring metabolic reprogramming by gastrointestinal endocrine factors is largely unknown. Here, we showed that secretin (SCT), a brain-gut peptide, is downregulated by overnutrition in pregnant mice and women. More importantly, genetic loss of SCT in the maternal gut results in undesirable phenotypes developed in offspring including enhanced high-fat diet (HFD)-induced obesity and attenuated browning of inguinal white adipose tissue (iWAT). Mechanistically, loss of maternal SCT represses iWAT browning in offspring by a global change in genome methylation pattern through upregulation of DNMT1. SCT functions to facilitate ubiquitination and degradation of DNMT1 by activating AMPKα, which contributes to the observed alteration of DNMT1 in progeny. Lastly, we showed that SCT treatment during pregnancy can reduce the development of obesity and improve glucose tolerance and insulin resistance in offspring of HFD-fed females, suggesting that SCT may serve as a novel biomarker or a strategy for preventing metabolic diseases.

Hydroxysafflor yellow A triggered a fast-to-slow muscle fiber-type conversion via regulating FoxO1 in myocytes.

Hydroxysafflor yellow A (HSYA) is the main bioactive component of safflower and has been reported to have significant health-promoting abilities. However, the regulation of HSYA on different types of skeletal myofibers is largely unknown. Here, in vitro experiments found that the water extract of safflower could significantly increase MyHC I, MB and Tnni1 mRNA expression while downregulating MyHC IIb mRNA expression. Furthermore, HSYA triggered fast-to-slow fiber-type switching and increased gene expression related to mitochondrial biosynthesis both in vitro and in vivo. Autodock analyses proved that FoxO1 is a potential target of HSYA, and qRT-PCR and western blotting further showed that HSYA significantly promoted the activation of the FoxO1 signaling pathway. Additionally, the levels of PGC1α, downstream of FoxO1, also significantly increased after HSYA treatment. Together, our findings suggested that HSYA triggered a fast-to-slow myofiber-type shift through the FoxO1 signaling pathway.

Advanced glycation end products in food and their effects on intestinal tract.

With the development of living standards, harmful substances in diet and food safety have seriously endangered people health and life. Advanced glycation end products (AGEs), which formed by Maillard reactions in processed food, have been shown a significantly associated with many chronic diseases, such as nephropathy, atherosclerosis, Alzheimer's disease, and tumors. In recent years, the research about diet advanced glycation end products (dAGEs) have widespread controversy in academia. The main arguments include the production mechanism of dAGEs, metabolic pathways, and relationships with chronic diseases, especially related to the intestines, gut microbiota, and intestinal disorders. So this review attempts to briefly summarize the dAGE in following aspects, including the influencing factors, metabolism, absorption, and so forth. In addition, the effects of dAGEs on intestinal health and gut microbes were discussed, which can offer a goal for boff in to design low dAGEs products and provided some perspectives for further study with AGEs in the future.

A novel regulatory mechanism of geniposide for improving glucose homeostasis mediated by circulating RBP4.

BACKGROUND: Systemic insulin signal transduction is influenced by the inter-tissue crosstalk, which might be the potential therapeutic strategy for T2DM. Although anti-diabetic function of geniposide has been previously reported, the underlying mechanism was not completely clear in light of the complex pathogenesis of T2DM. PURPOSE: The present experiment is devoted to investigate the potential effects of geniposide on systemic insulin sensitivity mediated by hepatokine-RBP4 in high fat diet (HFD)-fed mice. METHODS: The HFD-fed wild type mice were administered with geniposide (25 or 50 mg/kg/d) by intraperitoneal injection, and the normal saline and Metformin were used as negative control group and positive control group, respectively. After administration for 4 weeks, the food intake, body weight, glucose tolerance tests, insulin tolerance tests and serum biochemical indices were examined, along with insulin signaling pathway-associated proteins and hepatic histomorphological analysis. The liver, gastrocnemius and mouse primary hepatocytes were also harvested for molecular mechanism study. RESULTS: After geniposide treatment for 4 weeks, the blood glucose level was reduced in HFD-fed mice. Furthermore, geniposide treatment improved insulin sensitivity both in the liver and gastrocnemius (GAS). In terms of mechanism, geniposide disturbed circulating RBP4 level including its synthesis, secretion and homeostasis. Moreover, geniposide modified fuel selection and promoted glucose uptake in skeletal muscle and reduced glycogen storage, which were closely related to impaired circulating RBP4 homeostasis, leading to ameliorative systemic insulin sensitivity. CONCLUSION: Our current study proposes a novel regulatory mechanism of geniposide for improving glucose homeostasis through regulating circulating RBP4 level, which also provides new strategies for the prevention and treatment of T2DM.

Hydroxysafflor Yellow A Alters Fuel Selection From Glucose to Fat by Activating the PPARδ Pathway in Myocytes.

Modulation of fuel selection is critical in skeletal muscle function. Hydroxysafflor yellow A (HSYA) is the major bioactive component in safflower (Carthamus tinctorius L.) and, in our previous study, has been demonstrated to promote a shift from fast to slow myofiber. However, the effects of HSYA on fuel selection in skeletal muscle and its underlying mechanisms remain unclear. In this study, the in vitro experiments found that water extracts of safflower, rich in HSYA, significantly suppressed the expressions of the genes related to glucose utilization and activated the expressions of the lipolysis genes. Furthermore, HSYA resulted in a shift in substrate utilization toward fat relative to carbohydrates in C2C12 myotubes. Animal tests showed HSYA could significantly reduce the respiratory exchange ratio and prolonge endurance performance in mice and also trigger a switch in intramuscular fuel selection preference from carbohydrates to fat at rest and during exercise. Mechanistic studies revealed that HSYA converted this fuel selection by activating peroxisome proliferator activated receptor δ (PPARδ), and these effects of HSYA could be reversed by specific suppression of PPARδ by PPARδ siRNA. Collectively, our study demonstrated that HSYA can switch substrate utilization from glucose to fat in myocytes by activating PPARδ signaling, resulting in prolonged endurance performance. These findings provided direct evidence for the endurance performance enhancement effect of HSYA and explored new perspectives for the innovation and application of HSYA in the health care industry.

Geniposide suppresses thermogenesis via regulating PKA catalytic subunit in adipocytes.

Geniposide has been widely found to ameliorate many metabolic diseases. The recruitment and activation of brown/beige adipocytes are effective and promising methods for counteracting obesity and related diseases. However, the effect of geniposide on thermogenesis of adipocytes and its underlying mechanism have not yet been investigated. Here, we demonstrate that geniposide (25 mg/kg) reduces body temperature and cold tolerance of mice via suppressing thermogenic genes in interscapular brown adipose tissue (iBAT) and inguinal white adipose tissue (iWAT). Consistently, geniposide (20 mg/mL) suppresses thermogenic capacity of adipocytes (brown adipocytes and 3T3L1 preadipocyte cells) in vitro. Mechanistically, geniposide reduces the level of protein kinase A (PKA) catalytic subunit and further suppresses transcription activity and protein stability of uncoupling protein 1 (UCP1), leading to reduction of thermogenic capacity in adipocytes. Moreover, pharmacological PKA activation reverses geniposide-induced UCP1 inhibition, which indicated that geniposide suppresses thermogenesis of adipocytes via regulating PKA signaling. Together, our findings suggest that geniposide is an inhibitor of fat thermogenesis, establishing a novel function characteristic of geniposide.

Growth hormone receptor disrupts glucose homeostasis via promoting and stabilizing retinol binding protein 4.

Rationale: The molecular mechanisms underlying the pathogenesis of systemic insulin resistance in type 2 diabetes remain elusive. Growth hormone receptor (GHR) deficiency has long been known to improved insulin sensitivity. However, whether hepatic GHR overexpression or activation is a cause of insulin resistance is still unknown. The aim of this study was to identify the new role of GHR in systemic insulin resistance and explore the underlying mechanism. Method: Different samples obtained from obese humans, ob/ob mice, db/db mice, high-fat diet (HFD)-fed mice and primary mouse hepatocytes were used to evaluate the correlations between GHR and metabolic disorders. Recombinant adeno-associated viruses encoding GHR and STAT5 and GHR knockout mice were used to investigate the roles of hepatic GHR in glucose homeostasis. Tissue H&E, Oil Red O and PAS staining were performed for histomorphological analysis. Gel filtration chromatography was employed for the separation of serum RBP4-TTR complexes. Plasmids (related to GHR, STAT5 and HIF1α), siRNA oligos (siGHR and siSTAT5), luciferase activity and ChIP assays were used to explore the potential mechanism of hepatic GHR. Results: Here, we found that hepatic GHR expression was elevated during metabolic disorder. Accordingly, hepatic GHR overexpression disrupted systemic glucose homeostasis by promoting gluconeogenesis and disturbing insulin responsiveness in the liver. Meanwhile, hepatic GHR overexpression promoted lipolysis in white adipose tissue and repressed glucose utilization in skeletal muscle by promoting the circulating level of RBP4, which contributed to impaired systemic insulin action. A mechanistic study revealed that hepatic GHR disrupted systemic insulin sensitivity by increasing RBP4 transcription by activating STAT5. Additionally, overexpression of hepatic GHR promoted TTR transcriptional levels by enhancing the expression of HIF1α, which not only increased the protein stability of RBP4 but also inhibited renal clearance of RBP4 in serum. Conclusions: Hepatic GHR overexpression and activation accelerated systemic insulin resistance by increasing hepatic RBP4 production and maintaining circulating RBP4 homeostasis. Our current study provides novel insights into the pathogenesis of type 2 diabetes and its associated metabolic complications.

Novel Metabolic Regulation of Bile Acid Responses to Low Cholesterol in Whole-Grain-Diet-Fed Mice.

Hypercholesterolemia is a major risk factor for chronic metabolic diseases. Nevertheless, a whole-grain diet could ameliorate this issue in a number of ways, including by regulating bile acid metabolism. However, the potential mechanism is unclear. The aim of the current study is to explore the effects of whole-grain diets (brown rice diet and whole wheat diet) on bile acid homeostasis. After intervention for 8 weeks in mouse model, whole-grain diets showed reduced feed conversion ratio, and the lipid levels (total cholesterol (TC) and triglycerides (TG)) were also meliorated in the serum and liver of mice. Moreover, whole-grain diets reduced the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) (cholesterol synthesis) in the liver of mice. Interestingly, whole-grain diets not only promoted the mRNA expressions of low-density lipoprotein receptor (LDLR), ATP binding cassette transporter G1 (ABCG1), and scavenger receptor class B type I (SR-BI) (reverse cholesterol transport) but also facilitated the expressions of cytochrome P450, family 7, subfamily a, polypeptide 1 (CYP7a1) and cytochrome P450, family 27, subfamily a, polypeptide 1 (CYP27a1) (bile acid synthesis). Further study found that whole-grain diets promoted intestinal bile acid reabsorption and reduced bile acid excretion. Our study provided a novel metabolic regulation of bile acids in response to reduced cholesterol levels induced by whole-grain diets.

l-Arabinose Attenuates Gliadin-Induced Food Allergy via Regulation of Th1/Th2 Balance and Upregulation of Regulatory T Cells in Mice.

Gliadins are the main cause of wheat allergies, and the prevalence of gliadin allergy has increased in many countries. l-Arabinose, a kind of plant-specific five-carbon aldose, possesses beneficial effects on food allergy to gliadins. This study investigated the antiallergic activities and underlying mechanisms of l-arabinose in a wheat gliadin-sensitized mouse model. BALB/c mice were sensitized to gliadin by intraperitoneal injections with gliadin followed by being given a gliadin challenge. l-arabinose-treated mice exhibited a marked reduction in the productions of total immunoglobulin E (IgE), gliadin-specific IgE, gliadin-specific IgG1, and histamine, with an increase in IgG2a level as compared with gliadin-sensitized mice. Beside that, a significant decrease in Th2-related cytokine level, IL-4, and an increase in Th1-related cytokine level, IFN-γ, in the serum and splenocytes were observed after treatment with l-arabinose. l-Arabinose treatment also improved the imbalance of Th1/Th2 immune response on the basis of the expression levels of related cytokines and key transcription factors in the small intestine and spleen of sensitized mice. In addition, gliadin-induced intestinal barrier impairment was blocked by l-arabinose treatment via regulation of TJ proteins and suppression of p38 MAPK and p65 NF-κB inflammation signaling pathways. Notably, the results confirmed that l-arabinose treatment increased CD4+ Foxp3+ T cell populations and Treg-related factors associated with increased expression of IL-2 and activation of STAT5 in gliadin-sensitized mice. In conclusion, l-arabinose attenuated the gliadin-induced allergic symptoms via maintenance of Th1/Th2 immune balance and regulation of Treg cells in a gliadin-induced mouse model, suggesting l-arabinose could be used as a promising agent to alleviate gliadin allergy.

L-Arabinose suppresses gluconeogenesis through modulating AMP-activated protein kinase in metabolic disorder mice.

l-Arabinose is a kind of plant-specific five-carbon aldose with benefits in type 2 diabetes mellitus. It has been shown to have good properties in improving glucose homeostasis, but the underlying molecular mechanisms are still not clear. Hepatic gluconeogenesis is critical for regulating glucose homeostasis. Here, this study aimed to investigate whether l-arabinose could improve glucose metabolism via suppressing hepatic gluconeogenesis. High-fat-high-sucrose diet (HFHSD) or high-sucrose diet (HSD)-fed mice were supplemented with or without l-arabinose for 12 weeks. Fasting blood glucose levels were measured and glucose tolerance test and the histological analysis were performed after l-arabinose administration. AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), peroxisome proliferator activated receptor-γ coactivator-1α (PGC1α), Forkhead box O1 (FoxO1), phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) expression levels were determined by RT-PCR and western blotting. As expected, l-arabinose apparently decreased body weight and attenuated hyperglycemia and glucose intolerance caused by HFHSD or HSD. l-Arabinose also had beneficial effects on glycogen synthesis by inactivating GSK3ß. The expression levels of gluconeogenic genes were all decreased by l-arabinose administration in vivo and in vitro. In addition, our work revealed that AMPK is required for the inhibitory effects of l-arabinose on hepatic gluconeogenesis. l-Arabinose significantly up-regulated the phosphorylated levels of AMPK and its downstream protein ACC. Furthermore, blocking AMPK signaling through an inhibitor (compound C) or siAMPK significantly attenuated the inhibition of hepatic gluconeogenesis and the promotion of glycogen synthesis with l-arabinose, indicating that the inhibitory effect of l-arabinose on hepatic gluconeogenesis was AMPK dependent. Our work revealed that l-arabinose is a promising natural product for the regulation of hyperglycemia through inhibition of hepatic gluconeogenesis by activating AMPK.

Circulating miR-27a-3p as a candidate for a biomarker of whole grain diets for lipid metabolism.

As a worldwide epidemic, overweight and obesity have long been an issue of great interest in a wide range of health areas, and the whole grain diet has been proven to be an effective and healthy manner to prevent them. Recent developments in the field of microRNAs (miRNAs) have led to a renewed interest in lipid metabolism, however, whether a whole grain diet regulates lipid metabolism through miRNAs is still unknown. Hence, our current study was carried out to explore the changes of miRNAs in mice with the treatment of whole grain diets (the brown rice group, BR and whole wheat group, WW) and to screen out miRNAs that can serve as a biomarker to evaluate and regulate lipid metabolism. After whole grain diet treatment for 8 weeks, the lipids both in serum and liver were reduced, as well as the body weight. Moreover, there were 136 miRNAs with significant differences among our three dietary patterns (the CS diet, BR diet and WW diet) analyzed by serum miRNAs sequencing, and only 16 miRNAs showed simultaneous differences in the BR or WW groups compared to the CS group, showing a consistent trend of change. The serum miRNA sequencing and qRT-PCR analysis revealed that miR-27a-3p was decreased in serum and WAT, while it was elevated both in the liver and ileum. We propose that circulating miR-27a-3p could be a novel candidate for a biomarker of whole grain diets for lipid metabolism through the assessment of the KEGG pathway, GO enrichment and the conservative analysis of miRNAs. The potential mechanisms of action could be through binding the 3'UTR of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and fatty acid synthase (FASN), which were key enzymes for lipid synthesis, achieving regulation of lipid metabolism. A luciferase assay was also performed to verify the above mechanism, which shows that miR-27a-3p mimics transfection, repressing the luciferase activity of the two reporters carrying miR-27a-3p regulatory elements found in the 3'-UTR of HMGCR and FASN, respectively. Our study has provided new molecular mechanisms of whole grain diets for lipid metabolism, as well as a new therapeutic target for the treatment of obesity.

Geniposide reduces cholesterol accumulation and increases its excretion by regulating the FXR-mediated liver-gut crosstalk of bile acids.

Hypercholesterolemia is the main risk factor to threaten human health and geniposide has been found to have hypolipidemic functions. However, its underlying mechanism is not clear. In this study, we firstly confirmed the hypolipidemic functions of geniposide in C57BL/6 and ApoE-/- mice (i.p, 50 mg/kg/d). Then hepatic or arterial lipid accumulation was analyzed through histomorphology. Moreover, the effects of geniposide on the bile acid metabolism were analyzed by the hepatic RNA-seq and biological molecular analysis. Mechanistically, GW4064, an FXR agonist, was carried out to verify the mechanisms of geniposide in human HepG2 and Caco2 cells. As expected, geniposide decreased the lipid accumulations both in plasma and liver. Morever, the atherosclerotic plaque shrank in HCD-fed ApoE-/- mice with geniposide treatment. The molecular analysis revealed that geniposide accelerated the hepatic synthesis of bile acids through inactivating the negative feedback regulation of bile acids mediated by FXR, led to the enhancive reverse cholesterol transport and cholesterol catabolism. What's more, geniposide reduced ileal FXR-mediated reabsorption of bile acids, resulting in the increasing excretion of bile acids. Our study pointed out the regulatory functions of geniposide on FXR-mediated liver-gut crosstalk of bile acids and geniposide might be a novel strategy for maintaining cholesterol homeostasis.

l-Arabinose Inhibits Colitis by Modulating Gut Microbiota in Mice.

l-Arabinose is a monosaccharide extracted from plants or fibers, which is known to have a variety of functional properties. In this study, we aim to investigate whether l-arabinose could inhibit colitis by modulating gut microbiota. l-Arabinose was administered in mice daily in a dextran sodium sulfate (DSS)-induced colitis model. The histological analysis, disease index, and the expression of inflammatory genes were measured. 16S-rRNA sequence analysis was performed to investigate gut microbiota. Intriguingly, we found that l-arabinose could repress DSS-induced colitis and inhibit p38-/p65-dependent inflammation activation. Besides that, our data revealed that l-arabinose-modulated DSS-induced gut microbiota were disturbed. Additionally, the perturbed gut microbiota was responsible for the suppressive effects of l-arabinose on DSS-induced colitis treated with antibiotics. Lastly, Caco-2 cells were used to confirm the protective effects of l-arabinose in colitis or inflammatory bowel disease. As expected, the protein expression levels in Caco-2 cells of pro-inflammatory genes, which were treated with l-arabinose and incubated with or without tumor necrosis factor alpha. Our work suggested that l-arabinose exerts anti-inflammation effects in DSS-induced colitis. These beneficial effects have correlations with the composition, diversity, and abundance of the gut microbiota regulated by l-arabinose. l-Arabinose could be a remarkable candidate as a functional food or novel therapeutic strategy for intestinal health.