UPLC-Q-TOF/MS-based metabonomics reveals mechanisms for Holothuria leucospilota polysaccharides (HLP)-regulated serum metabolic changes in diabetic rats.

This study aimed to use metabolomic methods to explore how Holothuria leucospilota polysaccharides (HLP) improved metabolism disorders in the liver of Goto-Kakizaki (GK) rats with spontaneous type 2 diabetes. The results showed that HLP effectively improved the metabolic disorder. Based on KEGG functional analysis, five key biomarkers associated with bile acid metabolism were detected and screened (P < 0.05). The results of serum total bile acid levels and liver damage in diabetic rats further showed the regulatory effects of HLP on bile acid metabolism. The results of bile acid-related gene expression in the liver showed that HLP inhibited liver farnesoid X Receptor - small heterodimer partner (FXR-SHP) signalling and increased the expression of bile acid synthesis genes (P < 0.05). Our results explored the underlying mechanisms by which HLP accelerated cholesterol consumption to anti-hypercholesterolemia and anti-diabetic by inhibiting liver FXR-SHP signaling. HLP's effect on bile acid regulation provides insights into treating T2DM.

Microbiome-Metabolomics Analysis Reveals the Mechanism of Holothuria leucospilota Polysaccharides (HLP) in Ulcerative Colitis.

SCOPE: Holothuria leucospilota polysaccharides (HLP) are bioactive polysaccharides with immunomodulatory effects. This study aims to investigate the impact of HLP on dextran sodium sulfate (DSS)-induced colitis in rats and further investigate the complex interactions between changes in intestinal microbiota, cometabolites, and intestinal inflammation under HLP intervention. METHODS AND RESULTS: The ulcerative colitis (UC) model of Sprague Dawley (SD) rats is established by a normal diet with 3%DSS. The effects of HLP on UC are studied by gavage of different doses of HLP for 2 weeks. The results show that HLP alleviate the inflammation of UC and reduce histological damage and secretion of tumor necrosis factor-α (TNF-α), IL-6, IL-1ß, and IL-10. After HLP treatment, the intestinal flora of UC rats is regulated, and the flora diversity is restored. Fecal metabolomics analysis reveal the modulatory effects of HLP on amino acid metabolism, antimicrobial peptide anabolism, and energy metabolism in rats with colitis. Correlation analysis of microbial and intestinal metabolites reveals the potential mechanism of HLP affecting colitis. CONCLUSION: HLP repair the intestinal compartment's metabolic disorder by regulating intestinal flora's structure and alleviating colonic mucosal injury and inflammation in colitis rats.

Polysaccharides from Holothuria leucospilota Relieve Loperamide-Induced Constipation Symptoms in Mice.

A vital bioactive component of marine resources is Holothuria leucospilota polysaccharides (HLP). This study examined whether HLP could regulate intestinal flora to treat loperamide-induced constipation. Constipated mice showed signs of prolonged defecation (up by 60.79 min) and a reduced number of bowel movements and pellet water content (decreased by 12.375 and 11.77%, respectively). The results showed that HLP treatment reduced these symptoms, reversed the changes in related protein expression levels in the colon, and regulated the levels of active peptides associated with the gastrointestinal tract in constipated mice, which significantly improved water-electrolyte metabolism and enhanced gastrointestinal motility. Meanwhile, it was found that intestinal barrier damage was reduced and the inflammatory response was inhibited through histopathology and immunohistochemistry. As a means to further relieve constipation symptoms, treatment with low, medium, and high HLP concentrations increased the total short-chain fatty acid (SCFA) content in the intestine of constipated mice by 62.60 µg/g, 138.91 µg/g, and 126.51 µg/g, respectively. Moreover, an analysis of the intestinal flora's gene for 16S rRNA suggested that the intestinal microbiota was improved through HLP treatment, which is relevant to the motivation for the production of SCFAs. In summary, it was demonstrated that HLP reduced loperamide-induced constipation in mice.

Holothuria Leucospilota polysaccharides alleviate hyperlipidemia via alteration of lipid metabolism and inflammation-related gene expression.

Hyperlipemia is becoming a chronic disease that threatens human health. At the same time, people pay more and more attention to hyperlipemia. Holothuria Leucospilota polysaccharide (HLP) has been reported to ameliorate hyperlipidemia in high-fat diet-induced rats. Therefore, this study aimed to explore further metabolomics' role in improving liver function and reveal its mechanism. After oral administration of HLP for 4 weeks, total cholesterol (TC) and triglycerides (TG) levels of the liver in 100 and 200 mg/kg HLP groups were both decreased significantly (p < .05). The results showed that serum AST and ALT activity decreased by professing to be convinced of HLP. HLP also exerted antioxidant activities and up-regulated the expression of ACC, CD36, TNF-α and NF-κB in the liver of diabetic rats. Six potential biomarkers were recognized by UPLC-Q-TOF/MS and OPLS-DA. HLP alleviated liver injury by regulating the contents of metabolic end products in the serum of hyperlipidemic rats, such as nadolol and glycodeoxycholic acid. The results indicated that HLP effectively relieved HFD-induced hyperlipidemia by regulating metabolic disorders. PRACTICAL APPLICATIONS: As a chronic disease, hyperlipidemia has attracted more and more attention. Studies have shown that HLP regulates dyslipidemia, oxidative damage and inflammation to relieve hyperlipidemia. It mainly improved the liver damage caused by hyperlipidemia by inhibiting the expression of hepatic lipogenesis, oxidative stress and inflammatory factors. At the same time, we also detected six metabolites, among which high GDCA content indicated serious liver damage. Therefore, in the future, it can be suggested that HLP may be used as a functional, active substance in health products to assist in relieving hyperlipidemia, and GDCA may be used as an essential metabolic marker for the degree of liver injury.