Insulin-resistant HepG2 Cells Research Articles

Identification of α-glucosidase inhibitors from Mulberry using UF-UPLC-QTOF-MS/MS and molecular docking

As a medicinal and edible plant, Mulberry has shown good hypoglycaemic activity at the animal level, but its active ingredients and hypoglycaemic mechanisms remain unclear. In this study, we used ultrafiltration-ultra performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UF-UPLC-QTOF-MS/MS) and molecular docking to screen for high-affinity α-glucosidase inhibitors in Mulberry. Our innovation was to determine the inhibitory activity of Mulberry extracts in vitro and screen the active small molecules in the extracts using advanced UF-UPLC-QTOF-MS/MS techniques and validate these compounds at the molecular docking and cellular levels, laying the foundation for studying the mechanism of type 2 diabetes in Mulberry. α-Glucosidase incubation experiments showed that the IC50 value of Mulberry crude extracts was 37.58 μg/mL. Six possible α-glucosidase activity inhibitory components were identified using UF-UPLC-QTOF-MS/MS. Molecular docking studies showed that these small molecules were more likely to occupy the active site of α-glucosidase than the positive control acarbose, scoring above the threshold, indicating that Mulberry is a potential source of hypoglycemic agents. Further cellular level studies showed that different extracts and active small molecules of Mulberry improved insulin resistance in HepG2 cells. Through the analysis of glucose-lowering targeting components, the subject clarified that Mulberry exerts therapeutic effects on Diabetes Mellitus (DM) through a multi-component, multi-target, and multi-pathway relationship, which is consistent with Traditional Chinese Medicine (TCM) theory as a potential source of glucose-lowering agents.

Astragaloside IV ameliorates insulin induced insulin resistance in HepG2 cells through reactive oxygen species mediated c-Jun N-terminal kinase pathway.

To investigate the effects and elucidate the mechanism of Astragaloside IV (AS-IV) for insulin resistance (IR) and type 2 diabet es mellitus (T2DM). CCK8 kit was used to detect cell viability, glucose detection kit was used to detect the concentration of glucose in cell supernatant, reactive oxygen species (ROS) detection kit and Western blot were used to explore the mechanism of Astragaloside IV (AS-IV) in improving IR. A diabetic rat model was also established by feeding high sugar and fat diet and streptozotocin (STZ) injection. After treatment with AS-IV, rosiglitazone (ROZ), or normal saline, the fasting blood glucose (FBG), C peptide (C-P), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and the glucose tolerance were assessed. AS-IV could effectively reduce the content of ROS and increase the glucose uptake in high insulin-treated IR-type HepG2 cells. The results of molecular mechanisms indicated that AS-IV could improve insulin resistance by reducing JNK phosphorylation and regulating c-Jun N-terminal kinase (JNK) downstream protein expression. Additionally, AS-IV could significantly reduce the levels of FBG, TNF-α, IL-6 and the glucose tolerance in diabetic rats ( < 0.05 or < 0.01). The high and medium dose groups of AS-IV could significantly increase the C-P levels in diabetic rats ( < 0.05 or < 0.01). Our results indicated that AS-IV improve liver IR through the JNK pathway and ROS, which meant a new molecular target for the treatment of diabetes. The AS-IV also helped to prevent and improved the insulin resistance of rats.

Polyphenol-Rich Extract of Fermented Chili Pepper Alleviates Insulin Resistance in HepG2 Cells via Regulating INSR, PTP1B, PPAR-γ, and AMPK Pathways

Fermented Capsicum frutescens L. is a well-known traditional food ingredient in China with a variety of potential nutritional functions due to the increased content of polyphenolic compounds during the fermentation process. This study aimed to investigate the ameliorative effect of fermented chili peppers (FCP) on insulin resistance and the potential mechanism of action. HepG2 cells were treated with 5 × 10−6 mol/L insulin for 12 h to establish the insulin resistance model. The results showed that the ethanol extract of FCP (1 mg/mL), rather than non-FCP extract, significantly increased glucose consumption in insulin-resistant HepG2 cells, which was at least partly attributed to an increase in polyphenolic compounds after fermentation, including kaempferol-3-O-rutinoside, caffeic acid, kaempferol-3-O-glucoside, luteolin, and apigenin. Molecular docking analysis suggested that these five significantly increased polyphenolic compounds in FCP could partially and effectively interact with the key amino acid residues of four key insulin resistance-related receptors (INSR, PTP1B, PPAR-γ, and AMPK). In conclusion, the fermentation process enhanced or even conferred a pronounced anti-insulin resistance effect on chili peppers, and the increased polyphenolic compounds in chili pepper had synergistic effects in modulating the INSR, PTP1B, PPAR-γ, and AMPK pathways to regulate the destruction of glucose consumption.

Effect of goat milk protein hydrolysates on antidiabetic activity and its insulin resistance in HepG2 cells

Effect of goat milk protein hydrolysates on antidiabetic activity and its insulin resistance in HepG2 cells

Arctigenin mitigates insulin resistance by modulating the IRS2/GLUT4 pathway via TLR4 in type 2 diabetes mellitus mice.

Arctigenin (AR), extracted from Arctium lappa L. (Burdock), is a folk herbal medicine used to treat diabetes. However, its mechanism of action has remained elusive. In this study, type 2 diabetes mellitus (T2DM) mice received AR orally for 10weeks to evaluate its therapeutic effect based on changes in glucose and lipid metabolism, histological examination of target tissues, and liver immunohistochemistry. Furthermore, HepG2 insulin-resistant cells were established to verify the mechanism of AR against diabetes. The results showed that AR treatment reduced blood glucose and lipid levels, reversing liver as well as pancreas tissue damage in T2DM mice. AR reduced the levels of pro-inflammatory cytokines in the serum of T2DM mice, as well as those in insulin-resistant HepG2 cell supernatants, while increasing interleukin-10 (IL-10) levels. The levels of p-p65, phospho-c-Jun N-terminal kinase (p-JNK), induced nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were reduced in the liver tissue of T2DM mice, accompanied by an upregulation of glucose transporter 4 (GLUT4) and insulin receptor substrate 2 (IRS-2). In vitro studies further showed that AR downregulated toll-like receptor 4-mediated inflammation, while upregulating insulin pathway-related proteins and ultimately improving glucose uptake in insulin-resistant HepG2 cells. In conclusion, AR protected mice from insulin resistance, and its therapeutic effect was likely associated with inhibition of toll-like receptor 4 inflammatory signaling to reactivate IRS-2/GLUT4.

A polysaccharide from mycelia of Metarhizium taii: Structural characterization, inhibition on α-glucosidase and improvement of insulin resistance in HepG2 cells

Polysaccharide is one of the important bioactive components of Metarhizium taii. A homogeneous polysaccharide named as HLP-S was first purified from the mycelium of M. taii. HLP-S had a molecular weight of 2.81 × 103 kDa and consisted mainly of mannose, glucose, and galactose in a ratio of 2.31:2.89:3.59. The structure of HLP-S was determined by various chemical structure analysis methods, which showed that the sugar linkage units of HLP-S consist of T-Manp, T-Glcp, →4,6)-Glcp-(1→, →2)-Manp-(1→, →4)-Glcp-(1→, →4)-Galp-(1→, →4,6)-Manp-(1→, →3,4)-Glcp-(1→). The Hypoglycemic activity of HLP-S was investigated by enzyme inhibition assay in vitro and a model of insulin resistance in HepG2 cells. The results of α-glucosidase activity inhibition assay in vitro showed that different concentrations of HLP-S inhibited α-glucosidase activity with a mixture of competitive and non-competitive inhibition types. Various concentrations of HLP-S were applied to HepG2-IR cells. The results of the experiments suggested that HLP-S might effectively improve the glucose consumption of HepG2-IR cells and promote the synthesis of glycogen, hence reducing insulin resistance.

Four undescribed iridoid glycosides with antidiabetic activity from fruits of Cornus officinalis Sieb. Et Zucc.

Four novel iridoid glycosides neocornuside E–H (1–4), together with nine known ones (5–13), were isolated from fruits of Cornus officinalis. Their chemical structures were determined on the basis of spectroscopic analyses and comparing of the literature data. All of the isolated compounds were evaluated for their antidiabetic activity in insulin resistant HepG2 cells. Compounds 2, 4, 5, 8, and 12 exhibited antidiabetic activities with EC50 values of 40.12, 2.54, 70.43, 15.31, and 4.86 μM, respectively. Flow Sight cytometry analysis indicated that compounds 2, 4, 5, 8, and 12 improved the ability of 2-NBDG uptake of insulin-induced HepG2 cells.

Chinese bayberry (Myrica rubra Sieb. et Zucc.) leaves proanthocyanidins alleviate insulin-resistance via activating PI3K/AKT pathway in HepG2 cells

Chinese bayberry (Myrica rubra Sieb. et Zucc.) leaves proanthocyanidins (BLPs) were natural bioactive compounds in the treatment of obesity and diabetes with a unique structural characteristic. This study aimed to investigate the effect of BLPs on hepatic glucose metabolism in insulin-resistant HepG2 cells and elucidate the underlying mechanism. With the supplementation of BLPs, the glucose consumption and glucose uptake in IR-HepG2 cells were increased. BLPs promoted glycogen synthesis via up-regulating p-GSK3β and GYS2 expression, and attenuated gluconeogenesis by down-regulating PEPCK and G6Pase expression. It was attributed to the activation of PI3K/AKT signal pathway by BLPs, which was confirmed using the PI3K inhibitor LY294002. Moreover, BLPs remarkably reduced the expression of miR-29a, miR-423 and miR-122, which involved in hepatic glucose metabolism. Our results provide an insight of the hypoglycemic potential of BLPs on the hepatic glucose metabolism, suggesting that BLPs can be further used as a novel ingredient in functional food.

Minor iridoid glycosides from the fruits of Cornus officinalis Sieb. et Zucc. and their anti-diabetic bioactivities

Fifteen previously undescribed minor iridoid glycosides, including four monomers and eleven dimers, were isolated from the fruits of Cornus officinalis Sieb. et Zucc. Their chemical structures were determined on the basis of spectroscopic data and chemical evidence. All of the isolated compounds were evaluated for their effects of the glucose consumption on the insulin resistant HepG2 cells, and four compounds, named cornuofficinalisides F, H, L, and O, increased the glucose consumption significantly at 10 μM, the EC50 values of them were determined to be 0.898, 1.625, 0.923, and 8.589 μM, respectively. Moreover, the four compounds could improve the ability of glucose uptake significantly in insulin resistant HepG2 cells.

Isolation of Gingerols and Its Preventive Effect on Insulin Resistance of HepG2 Cells

Isolation of Gingerols and Its Preventive Effect on Insulin Resistance of HepG2 Cells

Anti-diabetic effect of hesperidin on palmitate (PA)-treated HepG2 cells and high fat diet-induced obese mice

The present study examined the relationship between the anti-diabetic effect of hesperidin (HES) and the differential gene expression in HES treated high fat diet (HFD)-induced obese mice. Based on the glucose uptake assay, the treatment of HES restored the glucose uptake to control level in an insulin-independent manner in PA-treated HepG2 cells. Western blot analysis confirmed that the treatment of HES increased the insulin-stimulated phosphorylation of Akt and GSK3β in insulin-resistant PA-treated HepG2 cells. HFD-induced obese mice treated with HES significantly reduced serum insulin, blood glucose, and homeostatic model assessment for insulin resistance (HOMA-IR) values. In addition, both glucose tolerance and insulin tolerance were significantly improved to normal level by HES in HFD-induced obese mice. RNA sequencing analysis disclosed that the expression levels of up-regulated 12 genes and down-regulated 6 genes related to insulin signaling and glucose metabolism were restored to normal level by HES in the liver of HFD-induced obese mice. A protein–protein interaction (PPI) network was constructed via search tool for the retrieval of interacting genes/proteins (STRING) analysis, and Eno1, Pik3cd, Hk2, Trib3, Myc, Nos3, Ppargc1a, and Igf2 were located in the functional hubs of the PPI network of glucose metabolism. Furthermore, Western blot analysis confirmed that HES improved insulin sensitivity and glucose homeostasis by normalizing the expression levels of hexokinase-II, enolase-1, and PI3 kinase p110δ to normal level. The overall results suggest that HES possess a potential anti-diabetic effect by normalizing the expression levels of the insulin signaling and glucose metabolism related genes which were perturbed in the liver of HFD-induced obese mice.

Ultrasonic-Cellulase Synergistic Extraction of Crude Polysaccharides from Moringa oleifera Leaves and Alleviation of Insulin Resistance in HepG2 Cells.

Moringa oleifera leaves (MOL) are a new food resource, rich in functional factors. MOL polysaccharides are important active macromolecules within MOL. However, there are problems, such as low extraction rates and lack of evidence for functional activity. Therefore, in this experiment, single-factor experiments were carried out using MOL powder as the raw material, and the Plackett–Burman test was used to screen the significantly influential test factors. The extraction process of MOL polysaccharide was optimized by response surface methodology. The insulin resistance alleviating activity of MOLP polysaccharides was initially explored. The results showed that the extraction of Moringa oleifera leaves crude polysaccharides (MOLP) by ultrasonic assisted cellulase enzymatic digestion was (17.03 ± 1.03)%, and the obtained MOLP was a crude polysaccharide with an average molecular weight (Mw) of 279.48 kDa, consisting of fucose, rhamnose, arabinose, galactose, glucose, xylose, mannose, galacturonic acid, and glucuronic acid. MOLP had an IC50 value of 8.02 mg/mL for α-glucosidase and scavenging activity against free radicals such as ABTS, DPPH, hydroxyl radicals, and superoxide anion with an IC50 value of 0.21 mg/mL 0.31 mg/mL 0.97 mg/mL 0.49 mg/mL. At the same time, MOLP significantly enhanced the glucose consumption, glycogen synthesis, CAT, SOD, GSH-Px activity, and reduced the MDA and ROS content in high glucose-induced insulin-resistant HepG2 (IR-HepG2) cells. This experiment improved the extraction rate of MOLP and demonstrated that MOLP has antioxidant activity and α-glucosidase inhibitory activity, which can alleviate the insulin resistance of high glucose-induced HepG2 cells. It provides partial data support for the possible hypoglycemic effect of MOLP by alleviating oxidative stress, and also provides new ideas for the in-depth study of basic research and industrial application of MOLP.

Hypoglycemic activity of phenols from Pleioblastus amarus (Keng) shells and its main chemical constituents identificatied using UHPLC-Q-TOF-MS

• Pleioblastus amarus (Keng) shells was used as raw material to extract and separate polyphenols (PASP). • The effects of PASP on glucose consumption, intracellular glycogen content, hexokinase and pyruvate kinase activities in insulin-resistant HepG2 cells were measured. • Main chemical constituents of PASP was identified by UHPLC-Q-TOF, and 12 kinds of compounds were identified. • Four kinds of potential α-glucosidase inhibitors were screened by ultrafiltration affinity mass spectrometry. The aim of this study was to investigate the hypoglycemic activity of phenols extracted from Pleioblastus amarus (Keng) shells (PASs), and to isolate and identify the possible components.of which o-coumaric acid, ferulic acid, quercetin-3-0-rhamnoside, and apigenin-7-0-glucoside exhibited a strong affinity with α-glucosidase and were identified as potential The results revealed that, Pleioblastus amarus (Keng) shell phenols (PASP) displayed hypoglycemic activity in vitro, inhibiting α-glucosidase (IC50 = 0.158 ± 0.002 mg/mL) while improving glucose consumption in insulin-resistant (IR) HepG2 cells, as well as the intracellular glycogen content and hexokinase (HK) and pyruvate kinase (PK) activity. Twelve phenolic compounds were detected by UHPLC-Q-TOF-MS, α-glucosidase inhibitors (AGIs). This study suggests that PASs, as a by-product, has the potential to become a new raw material source for hypoglycemic functional food, providing an application prospect for commonly considered waste product.

Effects of PPARD gene variants on the therapeutic responses to exenatide in chinese patients with type 2 diabetes mellitus.

BackgroundExenatide is a GLP-1R agonist that often exhibits considerable interindividual variability in therapeutic efficacy. However, there is no evidence about the impact of genetic variants in the PPARD on the therapeutic efficacy of exenatide. This research was aimed to explore the influence of PPARD gene polymorphism on the therapeutic effect of exenatide, and to identify the potential mechanism futher.MethodsA total of 300 patients with T2DM and 200 control subjects were enrolled to identify PPARD rs2016520 and rs3777744 genotypes. A prospective clinical study was used to collect clinical indicators and peripheral blood of T2DM patients treated with exenatide monotherapy for 6 months. The SNaPshot method was used to identify PPARD rs2016520 and rs3777744 genotypes, and then we performed correlation analysis between PPARD gene variants and the efficacy of exenatide, and conducted multiple linear regression analysis of factors affecting the therapeutic effect of exenatide. HepG2 cells were incubated with exenatide in the absence or presence of a PPARδ agonist or the siPPARδ plasmid, after which the levels of GLP-1R and the ratio of glucose uptake were determined.ResultsAfter 6 months exenatide monotherapy, we observed that homeostasis model assessment for insulin resistance (HOMA-IR) levels of the subjects with at least one C allele of the PPARD rs2016520 were significantly lower than those with the TT genotype, which suggested that the PPARD rs2016520 TT genotype conferred the poor exenatide response through a reduction of insulin resistance, as measured by HOMA-IR. The carriers of G alleles at rs3777744 exhibited higher levels of in waist to hip ratio (WHR), fasting plasma glucose (FPG), hemoglobin A1c (HbA1c) and HOMA-IR compared to individuals with the AA genotype following 6 months of exenatide treatment, potentially accounting for the lower failure rate of exenatide therapy among the AA homozygotes. In an insulin resistant HepG2 cell model, the PPARδ agonists enhanced exenatide efficacy on insulin resistance, with the expression of GLP-1R being up-regulated markedly.ConclusionThese data suggest that the PPARD rs2016520 and rs3777744 polymorphisms are associated with exenatide monotherapy efficacy, due to the pivotal role of PPARδ in regulating insulin resistance through affecting the expression of GLP-1R. This study was registered in the Chinese Clinical Trial Register (No. ChiCTR-CCC13003536).

Neocornuside A-D, Four Novel Iridoid Glycosides from Fruits of Cornus officinalis and Their Antidiabetic Activity.

Four previously undescribed iridoid glycosides neocornuside A–D (1–4), along with six known ones (5–10), were isolated from Cornus officinalis fruit. Their structures were elucidated by extensive spectroscopic (NMR, UV, IR, and MS) analysis and comparison with data reported in the literature. All isolates were assessed for their antidiabetic activity on the relative glucose consumption in insulin-induced insulin-resistant HepG2 cells. The results showed that compounds 1, 3, and 7 exhibited significant antidiabetic activities with EC50 values of 0.582, 1.275, and 0.742 μM, respectively. Moreover, compounds 1, 3, and 7 could improve the ability of 2-NBDG uptake of insulin-induced HepG2 cells.

The Hypoglycemic Effect of JinQi Jiangtang Tablets Is Partially Dependent on the Palmatine-Induced Activation of the Fibroblast Growth Factor Receptor 1 Signaling Pathway.

JinQi Jiangtang tablet (JQJTT) is a Chinese patent medicine that has been shown to be beneficial for patients with diabetes both preclinically and clinically; however, the molecular mechanism underlying the effects of JQJTT remains unclear. In this study, surface plasmon resonance fishing was employed to identify JQJTT constituent molecules that can specifically bind to fibroblast growth factor receptor 1 (FGFR1), leading to the retrieval of palmatine (PAL), a key active ingredient of JQJTT. In vivo and in vitro experiments demonstrated that PAL can significantly stimulate FGFR1 phosphorylation and upregulate glucose transporter type 1 (GLUT-1) expression, thereby facilitating glucose uptake in insulin resistance (IR) HepG2 cells as well as alleviating hyperglycemia in diabetic mice. Our results revealed that PAL functions as an FGFR1 activator and that the hypoglycemic effect of JQJTT is partially dependent on the PAL-induced activation of the FGFR1 pathway. In addition, this study contributed to the understanding the pharmacodynamic basis and mechanism of action of JQJTT and provided a novel concept for future research on PAL.

Sturgeon protein-derived peptide KIWHHTF prevents insulin resistance via modulation of IRS-1/PI3K/AKT signaling pathways in HepG2 cells

• KIWHHTF improved IR through stimulating IRS-1/PI3K/AKT signaling pathways. • Several key differential metabolites were identified. • Two key pathways were the most enriched. KIWHHTF, a sturgeon protein-derived peptide, has been demonstrated to have potent anti-inflammatory capacity in RAW264.7 macrophages. However, the influence of KIWHHTF on IR remains unclear. The aim of current study was therefore to investigate the effects of KIWHHTF on Insulin resistance (IR) and its underlying molecular mechanisms in HepG2 cells. Our results suggested that KIWHHTF increased the phosphorylation of IRS-1, PI3K, AKT, and the expression level of GLUT4, while down-regulated the phosphorylation of GS and the expression of PEPCK. In addition, metabolomics results suggested that differential metabolites include UDP-GlcNAc, DGA and 1-methyladenosine were increased after glucosamine treatment, but were reserved by KIWHHTF in IR HepG2 cells. Amino sugar and nucleotide metabolism and biosynthesis of unsaturated fatty acids were suggested as the most enriched pathways. Collectively, these results suggested that KIWHHTF improves the IR partly though IRS-1/PI3K/AKT signaling pathway. Moreover, UDP-GlcNAc, DGA and 1-methyladenosine were potential IR biomarker in HepG2 cells.

Structure and hypoglycemic effect of a neutral polysaccharide isolated from sea cucumber Stichopus japonicus

In addition to its high nutritious value, sea cucumber has been recognized by folk medicine for a long time. This study investigated the structure and hyperglycemic activity of a neutral polysaccharide (NPsj) from sea cucumber Stichopus japonicus, whose molecular weight was determined as 301.75 kDa by HPGPC method. Monosaccharide composition analysis indicated that NPsj is a glucan. The structure of NPsj was obtained by combining the analysis of methylation analysis, FTIR, NMR, periodate oxidation, Smith degradation and ESI-MS, which is mainly composed of (1 → 4)-α-d-glucoses with β-d-glucose(1→) branches substituted at O-6 every 7–9 of 1,4 linked glucoses. An in vitro insulin resistance Hep G2 cells model and a 3 T3-L1 cells model were established, and the NPsj has significant effect to increase glucose consumption with no toxicity at 10–100 μg/mL. Furthermore, NPsj upregulates the phosphorylation of Akt1 and down-regulated GSK3β, and then reduces the phosphorylation of GS, indicating its mechanism of ameliorating insulin resistance via Akt/GSK3β/GS signaling pathway.

The impact of the methyl esters of homogalacturonan on cellular uptake dependent hypoglycemic activity in IR-HepG2 cells

A homogalacturonan (HG) FPLP obtained from Ficus pumila L. was reported to have anti-diabetic activity but how this is influenced by degree of methyl-esterification (DM) of HG is unknown. To comprehensively analyze the role of DM in hypoglycemic activity in insulin-resistant HepG2 cells, HG derivatives (0 < DM < 100) were prepared from FPLP (DM25) by alkali or methanol acidified with acetyl chloride. Interestingly, a quadratic curve relationship revealed that hypoglycemic effect increased and then decreased with DM, and which was the most pronounced with DM54. DM might regulate activity by altering the intracellular drug concentration through cellular uptake. Furthermore, HG-DMn (0 < n < 100) were dependent on macropinocytosis, while HG-DMn (30 < n < 100) were also dependent on caveolae-mediated endocytosis. For HG, higher lipophilicity, smaller particle size, and more endocytosis mechanisms involved were favorable for cellular uptake, thereby increasing the intracellular drug concentration and enhancing the hypoglycemic activity. This work provides ideas for future investigations on structure-activity relationships.

Gut Microbiota Modulation, Anti-Diabetic and Anti-Inflammatory Properties of Polyphenol Extract from Mung Bean Seed Coat (Vigna radiata L.).

The present study investigated the gut health, anti-diabetic, and anti-inflammatory activities of mung bean seed coat extract (MSE). MSE was obtained by pressurized liquid extraction (PLE) using 50% ethanol as the extracting solvent. After 24 h of in vitro human fecal fermentation, MSE exhibited higher productions of total short-chain fatty acids (SCFA) than those of the control group (CON) and other polyphenol-rich substrates, including gallic acid (GA) and vitexin (VIT) (p > 0.05), but still lower than the fructo-oligosaccharide (FOS). In 16S-rRNA next-generation sequencing, MSE regulated the composition of gut microbiota by stimulating the growth of the beneficial bacteria Enterococcus, Ruminococcus, Blautia, and Bacteroides and decreasing the growth of the potential pathogenic bacteria Escherichia-Shigella. Similarly, qPCR showed increased numbers of Bifidobacterium, Lactobacillus, Faecalibacterium prausnitzii, and Prevotella, compared with those of CON (p < 0.05). MSE also reduced reactive oxygen species and increased glucose uptake in insulin-resistant HepG2 cells dose-dependently. The anti-inflammatory activity of MSE was observed in LPS-stimulated THP-1 monocytes with the reduction of TNFα, IL-1β, IL-6, and IL-8 genes. The data demonstrated the potential applications of MSE as a dietary supplement with gut health benefits and its ability to mitigate diabetes and inflammatory-related diseases.