Interaction between lactic acid bacteria and Polygonatum sibiricum saponins and its application to microencapsulated co-delivery.

This study aimed to investigate the interaction between L.casei and L.bulgaricus with Polygonatum sibiricum saponins (PSS) and to explore the co-microencapsulation to reduce their loss rate during storage and consumption. 1% PSS was added to the culture broth, and it was found that the growth and metabolism of the strains were accelerated, especially in the compound probiotic group, indicating that PSS has potential for prebiotics. LC-MS observed significant differences in the composition and content of saponins in PSS. The metabolomics results suggest that the addition of PSS resulted in significant changes in the metabolites of probiotics. In addition, it was found that the combination of probiotics and PSS may have stronger hypoglycemic ability (ɑ-glucosidase, HepG2). Finally, a co-microencapsulated delivery system was constructed using zein and isomaltooligosaccharide. This system can achieve more excellent resistance of probiotics and PSS in gastrointestinal fluids, effectively transporting both to the small intestine.

Effect of Polygonatum sibiricum saponins on gut microbiota of mice with ulcerative colitis.

Polygonatum sibiricum is a plant with medicinal and nutritional properties. Saponins are the important biologically active components of Polygonatum sibiricum. In this study, the specific components of Polygonatum sibiricum saponins (PSS) were analyzed, and the regulation effect of PSS on intestinal flora in patients with ulcerative colitis (UC) was investigated by inducing male Kunming mice with dextran sulfate sodium (DSS). PSS could ameliorate the symptoms of weight loss, high DAI score and colon length reduction compared to DSS-induced treatment. Colonic fragments were taken for H&E staining and histopathological scoring. PSS could significantly improve the pathological abnormality of colitis mice. 16S rRNA analysis showed that the intestinal microbial community of mice treated with DSS was significantly damaged. PSS could restore the richness and diversity of intestinal microbial flora, reduce the number of pathogenic bacteria, and increase the abundance of Lactobacillus spp. and Muribaculaceae, and improve the intestinal microbial flora disorder. Generally, PSS had an obvious effect in relieving colitis in mice. This study confirmed that Polygonatum sibiricum saponins play a therapeutic and palliative role in ulcerative colitis by regulating the microbiome balance.

Effect of Pleurotus eryngii on the Characteristics of Pork Patties during Freezing and Thawing Cycles.

Temperature fluctuations severely damage the quality, oxidation stability, and structure of pork patties. This study investigated the potential reasons for Pleurotus eryngii (Pe) to protect frozen pork patties from quality degradation caused by temperature fluctuations and promoted the application of a natural ingredient. In this experiment, the pH, the water holding capacity (WHC), the properties of color and texture, the appearance, the degree of protein and lipid oxidation, and the microstructure of patties with different additions of Pe (0%, 0.25%, 0.50%, 1.00%, and 2.00%) were intensified during freezing and thawing (F-T) cycles. The results showed that patties with 0.50% Pe exhibited a distinguishable improvement in the changes of pH, WHC, color, and texture during F-T cycles (p < 0.05). With the times of F-T cycles increasing, 0.50% Pe was able to inhibit lipid oxidation of patties by decreasing the peroxide value (POV) and the thiobarbituric acid reactive substances (TBARS) value to 0.87 and 0.66-fold, respectively, compared to those in the control group. It was also able to suppress the protein oxidation of the patties with a protein sulfhydryl content increasing to 1.13-fold and a carbonyl content decreasing to 0.49-fold compared to the patties in the control group (p < 0.05) after 5 F-T cycles. In addition, the figures of appearance and microstructure of samples indicated that 0.50% Pe effectively restrained the deterioration of structure features from patties after 5 F-T cycles. Thus, the addition of Pe effectively maintained the characteristics of pork patties under F-T cycles.

EFHD2 suppresses intestinal inflammation by blocking intestinal epithelial cell TNFR1 internalization and cell death.

TNF acts as one pathogenic driver for inducing intestinal epithelial cell (IEC) death and substantial intestinal inflammation. How the IEC death is regulated to physiologically prevent intestinal inflammation needs further investigation. Here, we report that EF-hand domain-containing protein D2 (EFHD2), highly expressed in normal intestine tissues but decreased in intestinal biopsy samples of ulcerative colitis patients, protects intestinal epithelium from TNF-induced IEC apoptosis. EFHD2 inhibits TNF-induced apoptosis in primary IECs and intestinal organoids (enteroids). Mice deficient of Efhd2 in IECs exhibit excessive IEC death and exacerbated experimental colitis. Mechanistically, EFHD2 interacts with Cofilin and suppresses Cofilin phosphorylation, thus blocking TNF receptor I (TNFR1) internalization to inhibit IEC apoptosis and consequently protecting intestine from inflammation. Our findings deepen the understanding of EFHD2 as the key regulator of membrane receptor trafficking, providing insight into death receptor signals and autoinflammatory diseases.

Virus-induced lncRNA-BTX allows viral replication by regulating intracellular translocation of DHX9 and ILF3 to induce innate escape.

The roles of long noncoding RNA (lncRNA) and RNA-binding proteins (RBPs) in antiviral innate response warrant further investigation. Here, we identify an lncRNA, termed lncRNA-BTX (between Tbk1 and Xpot), which is upregulated upon viral infection via an IRF3-type I interferon-independent pathway, promoting viral innate immune escape. Deletion of lncRNA-BTX in cells or mice significantly reduces viral load in vitro or in vivo, respectively. Mechanistically, lncRNA-BTX strengthens the interactions between DHX9 or ILF3 (two RBPs that have opposite functions in regulating the replication of RNA virus) and their respective partner, JMJD6 or ILF2, which regulates intracellular translocations of DHX9 and ILF3 from the nucleus to the cytoplasm. Put simply, lncRNA-BTX facilitates DHX9's return to the cytoplasm and retains ILF3 within the nucleus, promoting viral replication. This work unveils a strategy developed by the virus to bypass host innate immunity, thus providing a potential target for antiviral therapeutics.

Lysine methyltransferase SMYD2 inhibits antiviral innate immunity by promoting IRF3 dephosphorylation.

Phosphorylation of IRF3 is critical to induce type I interferon (IFN-I) production in antiviral innate response. Here we report that lysine methyltransferase SMYD2 inhibits the expressions of IFN-I and proinflammatory cytokines in macrophages upon viral infections. The Smyd2-deficient mice are more resistant to viral infection by producing more IFN-I and proinflammatory cytokines. Mechanistically, SMYD2 inhibits IRF3 phosphorylation in macrophages in response to viral infection independent of its methyltransferase activity. We found that SMYD2 interacts with the DNA-binding domain (DBD) and IRF association domain (IAD) domains of IRF3 by its insertion SET domain (SETi) and could recruit phosphatase PP1α to enhance its interaction with IRF3, which leads to decreased phosphorylation of IRF3 in the antiviral innate response. Our study identifies SMYD2 as a negative regulator of IFN-I production against virus infection. The new way of regulating IRF3 phosphorylation will provide insight into the understanding of IFN-I production in the innate response and possible intervention of the related immune disorders.

MFSD2A potentiates gastric cancer response to anti-PD-1 immunotherapy by reprogramming the tumor microenvironment to activate T cell response.

BACKGROUND: The efficacy of anti-programmed cell death protein 1 (PD-1) immunotherapy in various cancers, including gastric cancer (GC), needs to be potentiated by more effective targeting to enhance therapeutic efficacy or identifying accurate biomarkers to predict clinical responses. Here, we attempted to identify molecules predicting or/and promoting anti-PD-1 therapeutic response in advanced GC (AGC). METHODS: The transcriptome of AGC tissues from patients with different clinical responses to anti-PD-1 immunotherapy and GC cells was analyzed by RNA sequencing. The protein and mRNA levels of the major facilitator superfamily domain containing 2A (MFSD2A) in GC cells were assessed via quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry. Additionally, the regulation of anti-PD-1 response by MFSD2A was studied in tumor-bearing mice. Cytometry by Time-of-Flight, multiple immunohistochemistry, and flow cytometry assays were used to explore immunological responses. The effects of MFSD2A on lipid metabolism in mice cancer tissue and GC cells was detected by metabolomics. RESULTS: Higher expression of MFSD2A in tumor tissues of AGC patients was associated with better response to anti-PD-1 immunotherapy. Moreover, MFSD2A expression was lower in GC tissues compared to adjacent normal tissues, and its expression was inversely correlated with GC stage. The overexpression of MFSD2A in GC cells enhanced the efficacy of anti-PD-1 immunotherapy in vivo by reprogramming the tumor microenvironment (TME), characterized by increased CD8+ T cell activation and reduced its exhaustion. MFSD2A inhibited transforming growth factor ß1 (TGFß1) release from GC cells by suppressing cyclooxygenase 2 (COX2)-prostaglandin synthesis, which consequently reprogrammed TME to promote anti-tumor T cell activation. CONCLUSIONS: MFSD2A potentially serves as a predictive biomarker for anti-PD-1 immunotherapy response in AGC patients. MFSD2A may be a promising therapeutic target to potentiate the efficacy of anti-PD-1 immunotherapy by reprogramming the TME to promote T cells activation.

Effects of saponins isolated from Polygonatum sibiricum on H2O2-induced oxidative damage in RIN-m5F cells and its protective effect on pancreas.

The damage of islet cells caused by oxidative stress is closely related to diabetes. The aim of this study is to investigate the protective effect of saponins isolated from polygonatum sibiricum (PSS) on pancreas injury by using in vitro and in vivo models. The oxidative stress model of RIN-m5F cells induced by H2O2 was established. We found that PSS could decrease the apoptosis of RIN-m5F cells under oxidative stress. After PSS treatment, ROS and MDA levels in cells significantly decreased. Moreover, the levels of SOD and GSH were significantly increased. PSS could increase the insulin secretion level of cells under oxidative stress. The expression level of intracellular Bcl-2 increased, and the expression levels of Bax, caspase-3, caspase-8, and caspase-9 decreased significantly. In addition, the type 2 diabetes mouse model was established. The results showed that PSS had a protective effect on the injury of the pancreas in T2DM mice. PSS can relieve oxidative stress and high glucose-mediated pancreas cytotoxicity. PSS may be a promising candidate for diabetes intervention and functional foods.

Comprehensive in silico analysis of the probiotics, and preparation of compound probiotics-Polygonatum sibiricum saponin with hypoglycemic properties.

In this study, a combined application of Polygonatum sibiricum saponin (PSS) with probiotics was developed as a new formulation that could be a candidate for a dietary supplement. The properties of nine probiotics were evaluated by principal component and heatmap analysis. And the hypoglycemic properties of compound probiotics were compared with single strains. The results showed the inhibition (%) of α-amylase was higher when L. casei ATCC393 was used synergistically with L. Bulgaricus 1.1480 compared with single strains as well as other strain combinations. And it was also found that the inhibition (%) of α-amylase was higher as 70.35 % after PSS and the compound probiotic were compounded as a ratio of 2:1. Furturemore, PSS-compound probiotics could regulate the composition of the gut microbiome of T2DM mice and enhance the metabolic capacity. In conclusion, the combination of PSS and compound probiotics has shown massive potential as management nutraceuticals of T2DM.

Polygonatum sibiricum saponin Exerts Beneficial Hypoglycemic Effects in Type 2 Diabetes Mice by Improving Hepatic Insulin Resistance and Glycogen Synthesis-Related Proteins.

Type 2 diabetes mellitus (T2DM) is a systemic metabolic disorder characterized by insulin deficiency and insulin resistance. Recently, it has become a significant threat to public health. Polygonatum sibiricum saponin (PSS) has potential hypoglycemic effects, but its specific mechanism needs further study. In this study, PSS significantly decreased the level of blood glucose, water intake, and the organ index in diabetic mice. Meanwhile, PSS effectively reduced the content of total triglyceride (TG), total cholesterol (TCHO), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in the blood, and increased the content of high-density lipoprotein cholesterol (HDL-C). This suggests that PSS could reduce the content of blood lipids and initially improve the damage of hepatocytes. We found that PSS alleviated hepatic insulin resistance, repaired islet beta cells, and enabled insulin to play its biological role normally. It also improved oral glucose tolerance and abated serum lipopolysaccharide (LPS) and glycosylated hemoglobin (HbA1c) levels in T2DM mice. Furthermore, studies have found that PSS increased the content of phosphorylated protein kinase B (AKT), thereby promoting the effect of glucose transporter 4 (GLUT-4), and activating glycogen synthase kinase 3beta (GSK-3ß) and glycogen synthase (GS) proteins to promote hepatic glycogen synthesis. Finally, we found that PSS could promote the growth of beneficial bacteria such as Bifidobacterium and Lactobacillus, reduce the growth of harmful bacteria such as Enterococcus and Enterobacter, and preliminarily improve the composition of important bacteria in the intestine. These studies indicate that PSS has an excellent hypoglycemic effect, which provides a potential new treatment for T2DM and guidance for more in-depth research.

Innate immune imprints in SARS-CoV-2 Omicron variant infection convalescents.

SARS-CoV-2 Omicron variant infection generally gives rise to asymptomatic to moderate COVID-19 in vaccinated people. The immune cells can be reprogrammed or "imprinted" by vaccination and infections to generate protective immunity against subsequent challenges. Considering the immune imprint in Omicron infection is unclear, here we delineate the innate immune landscape of human Omicron infection via single-cell RNA sequencing, surface proteome profiling, and plasma cytokine quantification. We found that monocyte responses predominated in immune imprints of Omicron convalescents, with IL-1ß-associated and interferon (IFN)-responsive signatures with mild and moderate symptoms, respectively. Low-density neutrophils increased and exhibited IL-1ß-associated and IFN-responsive signatures similarly. Mild convalescents had increased blood IL-1ß, CCL4, IL-9 levels and PI3+ neutrophils, indicating a bias to IL-1ß responsiveness, while moderate convalescents had increased blood CXCL10 and IFN-responsive monocytes, suggesting durative IFN responses. Therefore, IL-1ß- or IFN-responsiveness of myeloid cells may indicate the disease severity of Omicron infection and mediate post-COVID conditions.

Increased glucose metabolism in TAMs fuels O-GlcNAcylation of lysosomal Cathepsin B to promote cancer metastasis and chemoresistance.

How glucose metabolism remodels pro-tumor functions of tumor-associated macrophages (TAMs) needs further investigation. Here we show that M2-like TAMs bear the highest individual capacity to take up intratumoral glucose. Their increased glucose uptake fuels hexosamine biosynthetic pathway-dependent O-GlcNAcylation to promote cancer metastasis and chemoresistance. Glucose metabolism promotes O-GlcNAcylation of the lysosome-encapsulated protease Cathepsin B at serine 210, mediated by lysosome-localized O-GlcNAc transferase (OGT), elevating mature Cathepsin B in macrophages and its secretion in the tumor microenvironment (TME). Loss of OGT in macrophages reduces O-GlcNAcylation and mature Cathepsin B in the TME and disrupts cancer metastasis and chemoresistance. Human TAMs with high OGT are positively correlated with Cathepsin B expression, and both levels predict chemotherapy response and prognosis of individuals with cancer. Our study reports the biological and potential clinical significance of glucose metabolism in tumor-promoting TAMs and reveals insights into the underlying mechanisms.

Structural analysis and in vitro antitumor effect of polysaccharides from Pholiota adiposa.

Pholiota adiposa is an edible chestnut mushroom with many health benefits, such as antioxidant and anticancer activity. In this paper, polysaccharides were extracted from Pholidota adiposa using an acid extraction process. The crude polysaccharide was purified using DEAE-cellulose chromatography, and two polysaccharide fractions of SPAP2-1 and SPAP2-2 were obtained. The structure was characterized using UV, GPC, GC, FT-IR, methylation, and NMR analysis. Monosaccharide component analysis indicated that SPAP2-1 (19 kDa) and SPAP2-2 (20 kDa) contained mannose, glucose, and galactose with different molecular ratios. Their antitumor effects were investigated using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium (MTT) assay, Annexin V-fluorescein isothiocyanate (FITC), propidium iodide (PI) staining, and flow cytometry. By analyzing the changes in the cells, SPAP2-1 caused damage and changed the proliferation rate of HeLa cells. SPAP2-1 showed strong interference to the cell cycle of HeLa cells and induced cell apoptosis. Overall, these results suggested that polysaccharides from Pholiota adiposa, especially SPAP2-1, may have the potential to be used as a tumor cell inhibitor, which needs further study.

BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility than the BA.2 lineage1. The receptor binding and immune-evasion capability of these recently emerged variants require immediate investigation. Here, coupled with structural comparisons of the spike proteins, we show that BA.2.12.1, BA.4 and BA.5 (BA.4 and BA.5 are hereafter referred collectively to as BA.4/BA.5) exhibit similar binding affinities to BA.2 for the angiotensin-converting enzyme 2 (ACE2) receptor. Of note, BA.2.12.1 and BA.4/BA.5 display increased evasion of neutralizing antibodies compared with BA.2 against plasma from triple-vaccinated individuals or from individuals who developed a BA.1 infection after vaccination. To delineate the underlying antibody-evasion mechanism, we determined the escape mutation profiles2, epitope distribution3 and Omicron-neutralization efficiency of 1,640 neutralizing antibodies directed against the receptor-binding domain of the viral spike protein, including 614 antibodies isolated from people who had recovered from BA.1 infection. BA.1 infection after vaccination predominantly recalls humoral immune memory directed against ancestral (hereafter referred to as wild-type (WT)) SARS-CoV-2 spike protein. The resulting elicited antibodies could neutralize both WT SARS-CoV-2 and BA.1 and are enriched on epitopes on spike that do not bind ACE2. However, most of these cross-reactive neutralizing antibodies are evaded by spike mutants L452Q, L452R and F486V. BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1. Nevertheless, these neutralizing antibodies are largely evaded by BA.2 and BA.4/BA.5 owing to D405N and F486V mutations, and react weakly to pre-Omicron variants, exhibiting narrow neutralization breadths. The therapeutic neutralizing antibodies bebtelovimab4 and cilgavimab5 can effectively neutralize BA.2.12.1 and BA.4/BA.5, whereas the S371F, D405N and R408S mutations undermine most broadly sarbecovirus-neutralizing antibodies. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants.

Effects of Polygonatum sibiricum saponin on hyperglycemia, gut microbiota composition and metabolic profiles in type 2 diabetes mice.

Diabetes is a global disease that endangers human health. As reported, saponins are effective bioactive compounds for treating type 2 diabetes mellitus (T2DM) and have nontoxic side effects. This study aimed to examine the hypoglycemic effects of Polygonatum sibiricum saponin (PSS) on T2DM mice. We found that PSS could significantly decrease the levels of insulin secretion and fasting blood glucose (FBG) in T2DM mice. And the level of triacylglycerol (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the blood was decreased. In contrast, the content of high-density lipoprotein cholesterol (HDL-C) was increased. 16S rDNA sequencing was used to evaluate the changes in the gut microbiota of T2DM mice, and metabolites were analyzed by metabolomic profiling. The results showed that PSS could decrease the abundance of Firmicutes in T2DM mice, increase the abundance of Bacteroidetes. It also increased the abundance of some bacterial genera (Lactobacillus, Lachnospiraceae_NK4A136_group and Intestinimonas). The phenotypes of the gut microbiome also changed accordingly. Metabolomics analysis showed that carbohydrate metabolism and amino acid metabolisms, such as L-alanine and L-glutamic acid, were greatly affected by PSS. In addition, the levels of inositol and chlorogenic acid in metabolites also increased significantly under PSS intervention. In general, PSS could exert its hypoglycemic effect, regulate the gut microbiota and affect the metabolism of T2DM mice.

Chromatin remodeler ARID1A binds IRF3 to selectively induce antiviral interferon production in macrophages.

Transcription factor IRF3 is critical for the induction of antiviral type I interferon (IFN-I). The epigenetic regulation of IFN-I production in antiviral innate immunity needs to be further identified. Here, we reported that epigenetic remodeler ARID1A, a critical component of the mSWI/SNF complex, could bind IRF3 and then was recruited to the Ifn-I promoter by IRF3, thus selectively promoting IFN-I but not TNF-α, IL-6 production in macrophages upon viral infection. Myeloid cell-specific deficiency of Arid1a rendered mice more susceptible to viral infection, accompanied with less IFN-I production. Mechanistically, ARID1A facilitates chromatin accessibility of IRF3 at the Ifn-I promoters by interacting with histone methyltransferase NSD2, which methylates H3K4 and H3K36 of the promoter regions. Our findings demonstrated the new roles of ARID1A and NSD2 in innate immunity, providing insight into the crosstalks of chromatin remodeling, histone modification, and transcription factors in the epigenetic regulation of antiviral innate immunity.

Hypoglycemic effect of Taraxacum officinale root extract and its synergism with Radix Astragali extract.

Taraxacum officinale (dandelion) and Radix Astragali are traditional medicinal and edible plants with high nutritional value. In this study, the synergistic hypoglycemic effect of DRE and Radix Astragali extract (RAE) was evaluated. Our results showed that water extract of dandelion (DRE-w), mainly containing polysaccharides (63.92 ± 1.82 mg/g), total flavonoid (2.57 ± 0.06 mg/g), total phenolic compounds (8.93 ± 0.34 mg/g), and saponins (0.54 ± 0.05 mg/g), exhibited significantly inhibitory effect on α-glucosidase and α-amylase. DRE-w and RAE had synergistic hypoglycemic effect; we found that DRE-w and its combination with RAE could relieve the state of insulin resistance in IR-HepG2 cells. The combination could more significantly increase the glucose consumption and intracellular glycogen content, and improve the activity of hexokinase and pyruvate kinase in IR-HepG2 cells. In summary, DRE and its combination with RAE can be developed as the drugs or functional foods for diabetes prevention and treatment.

TMT-based quantitative proteomic analysis of antitumor mechanism of Sporisorium reilianum polysaccharide WM-NP-60 against HCT116 cells.

Sporisorium reilianum is an active edible and medicinal phytopathogenic fungus. Our study indicated that the S. reilianum polysaccharide WM-NP-60 could inhibit the growth of HCT116 cells in a dose-dependent manner. In addition, WM-NP-60 could trigger the cell cycle of HCT116 arrest at the G1 phase and induce its apoptosis. In order to explore the anti-tumor mechanism of WM-NP-60, TMT-based quantitative proteomic analysis was used. Results indicated that 369 differentially expressed proteins including 240 up-regulated and 129 down-regulated proteins in WM-NP-60 treated HCT116 cells compared with normal HCT116 cells. Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that 192 pathways were enriched containing 15 metabolic pathways with significant difference (P < 0.05). The levels of mRNA and protein up-regulated TGFßR1, P107, DP1 and down-regulated THBS1 related to TGF-ß signaling pathway were verified with qRT-PCR and Western Blot (WB). These findings will provide theoretical basis for the important role of fungal polysaccharides in the field of tumor treatment.

Hypoglycemic effects and modulation of gut microbiota of diabetic mice by saponin from Polygonatum sibiricum.

Polygonatum sibiricum is a medicinal and homologous plant grown in China, which is commercially available without the provision of medical prescription. Saponin is one of the biologically active components of Polygonatum sibiricum. This study aimed to extract saponin from Polygonatum sibiricum (PSS) and to investigate its hypoglycemic effect and effect on gut micorbiota in diabetic mice. Through single factor and orthogonal experiments, the extraction conditions of saponin were optimized, and the content of saponin in the extract was 3.07 ± 0.02 mg g-1. During the experiment evaluating the hypoglycemic ability, it was found that PSS could inhibit the activity of α-amylase and α-glucosidase at first. Then, HepG2 was used to observe the effect of the saponin on insulin resistance. The results showed that PSS could significantly improve the state of insulin resistance in IR-HepG2 cells, increase the glucose consumption and intracellular glycogen content of cells, and the activity of hexokinase (0.455 ± 0.007 µmol min-1 g-1) and pyruvate kinase (0.174 ± 0.038 U per g prot). Finally, it was found that PSS could alleviate the symptoms of polyphagia and polydipsia in diabetic mice, regulate the gut microbiota of diabetic mice, increase the number of probiotics, and reduce the number of harmful bacteria. In summary, PSS may play an important role in regulating diabetes and can be developed as a promising natural material for diabetes prevention and treatment.