Protective effects of hepatic diseases by bioactive phytochemicals in Fusarium oxysporum - A review.

Lately, liver diseases were categorized as one of the most prevalent health problems globally as it causes a severe threat to mankind all over the world due to the wide range of occurrence. There are multiple factors causing hepatic disorders, such as alcohol, virus, poisons, adverse effects of drugs, poor diet, inherited conditions and obesity. Liver diseases have various types including alcoholic liver disease, non-alcoholic fatty liver disease, autoimmune hepatitis, liver cancer, hepatocellular carcinoma, liver fibrosis and hepatic inflammation. Therefore, it is imperative to find effective and efficacious agents in managing liver diseases. Fusarium oxysporum, an endophytic fungus and containing many bioactive compounds, could be served as a forked medication for enormous number and types of maladies. It was characterized by producing biochemical compounds which had rare pharmacological properties as it may be found in a limit number of other medicinal plants. The majority of the past researches related to Fusarium oxysporum recited the fungal negative field either on the pathogenic effects of the fungus on economical crops or on the fungal chemical components to know how to resist it. The present review will highlight on the bright side of Fusarium oxysporum and introduce the functional activities of its chemical compounds for treating its target diseases. The key point of illustrated studies in this article is displaying wide range of detected bioactive compounds isolated from Fusarium oxysporum and in other illustrated studies it was elucidated the therapeutical and pharmacological potency of these biologically active compounds (isolated from medicinal plants sources) against different types of liver diseases including non-alcoholic fatty liver disease, alcoholic liver disease, cirrhosis and others. It was demonstrated that F. oxysporum contains unique types of isoflavones, flavonoids, phenols and another active chemical compounds, and these compounds showed recently a fabulous clinical contribution in the therapy of liver injury diseases, which opens new and unprecedented way for evaluating the maintaining efficacy of Fusarium oxysporum bioactive compounds in dealing with hepatic complications and its remedy impacting on liver diseases and injured hepatocytes through recommending implement a practical study.

Metabolites isolated from the mangrove endophytic fungus Didymella sp. CYSK-4 and their cytotoxic activities.

Two new 12- or 13- membered-ring macrocyclic alkaloids ascomylactam D and E (1 & 2), and a pair of new enantiomer (+)- and (-)- didymetone (3) were purified from the mangrove endophytic fungus Didymella sp. CYSK-4. Their structures and absolute configurations were determined by extensive spectroscopic analysis, single-crystal X-ray diffraction, ECD and 13C NMR calculations. Compound 2 exhibited significant cytotoxicity against human A549 and KYSE 150 cancer cell lines with IC50 values of 2.8 µM and 5.9 µM, respectively.

New iridoids from Patrinia scabiosaefolia and their hypoglycemic effects by activating PI3K/Akt signaling pathway.

Growing in regions of Asia and North America, Patrinia scabiosaefolia is a wild vegetable and herb that has demonstrated health-promoting properties. Iridoids are one of the most bioactive phytochemicals in P. scabiosaefolia but the in-depth study is scarce. Herein we reported the separation and characterization of nine iridoids (compounds 1-9) from P. scabiosaefolia, and two compounds (2 and 6) were new. All the structures of the nine iridoids were characterized and confirmed with NMR (1D & 2D), HRMS, IR and UV. Compound 2 is a five-member ring iridoid, reminiscent of a broken C-1 and C-2 bond. Compound 6 has a typical monoene valerian iridoid, but the 5-deoxyglucose moiety at C-11 position is uncommon in this genus. The anti-diabetic evaluation of the isolated compounds revealed that compounds 1, 2, and 9 significantly increased the glucose absorption in 3 T3-L1 cells (P < 0.01). Further mechanism investigations have demonstrated that compound 1 promoted glucose uptake in dexamethasone-treated 3 T3-L1 adipocytes by activating PI3K/Akt signaling pathway. The expression of GLUT4 mRNA and protein was also upregulated. These results provide scientific references for the potential use of P. scabiosaefolia as a functional food to manage hyperglycemia.

Actinidia deliciosa Mitigates Oxidative Stress and Changes in Pancreatic α-, ß-, and δ-Cells and Immunohistochemical and Histological Architecture in Diabetic Rats.

The present study evaluated the antioxidant capacity and antidiabetic effect of Actinidia deliciosa in diabetic rats. Rats were grouped as follows: control, Actinidia deliciosa aqueous extract (ADAE, 1 g/kg, daily and orally), streptozotocin (STZ, 50 mg/kg BW, single intraperitoneal dose), and STZ plus ADAE, respectively. Twenty-eight components were detected by GC-MS analysis with high phenolic contents and high DPPH scavenging activity. In vivo results revealed that rats treated with STZ showed a highly significant elevation in blood glucose and a decrease in insulin hormone levels. Thiobarbituric acid-reactive substances and hydrogen peroxide levels were elevated, while bodyweight, enzymatic, and nonenzymatic antioxidants were significantly decreased. Furthermore, histopathological and immunohistochemical insulin expression, besides ultrastructure microscopic variations (ß-cells, α-cells, and δ-cells), were seen in pancreas sections supporting the obtained biochemical changes. Otherwise, rats supplemented with ADAE alone showed an improved antioxidant status and declined lipid peroxidation. Moreover, diabetic rats augmented with ADAE showed significant modulation in oxidative stress markers and different pancreatic tissue investigations compared to diabetic ones. Conclusively, ADAE has a potent antioxidant and hypoglycemic influence that may be utilized as a health-promoting complementary therapy in diabetes mellitus.

Residues of Culinary-Medicinal Winter Mushroom, Flammulina velutipes (Agaricomycetes), Cultivation as a Potential Source of Functional Skin Substitute with Multiple Bioactivities.

Residues generated during the cultivation of edible mushroom Flammulina velutipes are abundant and utilized with low efficiency. In this study, the composition and bioactivities of a skin substitute named TG05 obtained from residues of the F. velutipes cultivation process were investigated. The main composition of TG05 was considered to be chitin and it inhibited growth of Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa. TG05 also suppressed the inflammatory response through the inducible nitric oxide synthase signaling pathway. Inflammation was attenuated by reducing the expression of tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and prostaglandin E2 at the transcription level. Furthermore, TG05 exhibited antioxidant activities based on hydroxyl, 2,2-diphenyl-1-picryl-hydrazy, 2,2'-azobis-(3-ethylbenzothiazoline-6-sulfonic acid), superoxide anion radical scavenging activity, and reducing power assays. However, the effect of TG05 was independent of hyaluronidase inhibitory activity. Taken together, specific mechanisms related to the notable wound-healing-promoting activity of TG05 were demonstrated, mainly attributable to its antimicrobial, anti-inflammatory, and antioxidant activities. Therefore, TG05 may have potential for use as a functional biomaterial in various applications.

Antrodia cinnamomea exerts an anti-hepatoma effect by targeting PI3K/AKT-mediated cell cycle progression in vitro and in vivo.

Antrodia cinnamomea is extensively used as a traditional medicine to prevention and treatment of liver cancer. However, its comprehensive chemical fingerprint is uncertain, and the mechanisms, especially the potential therapeutic target for anti-hepatocellular carcinoma (HCC) are still unclear. Using UPLC‒Q-TOF/MS, 139 chemical components were identified in A. cinnamomea dropping pills (ACDPs). Based on these chemical components, network pharmacology demonstrated that the targets of active components were significantly enriched in the pathways in cancer, which were closely related with cell proliferation regulation. Next, HCC data was downloaded from Gene Expression Omnibus database (GEO). The Cancer Genome Atlas (TCGA) and DisGeNET were analyzed by bioinformatics, and 79 biomarkers were obtained. Furtherly, nine targets of ACDP active components were revealed, and they were significantly enriched in PI3K/AKT and cell cycle signaling pathways. The affinity between these targets and their corresponding active ingredients was predicted by molecular docking. Finally, in vivo and in vitro experiments showed that ACDPs could reduce the activity of PI3K/AKT signaling pathway and downregulate the expression of cell cycle-related proteins, contributing to the decreased growth of liver cancer. Altogether, PI3K/AKT-cell cycle appears as the significant central node in anti-liver cancer of A. Cinnamomea.

Hepatoprotective Effect of Actinidia deliciosa against Streptozotocin-Induced Oxidative Stress, Apoptosis, and Inflammations in Rats.

The present research intended to assess the possible protective and hypoglycemic effect of Actinidia deliciosa fruit aqueous extract (ADAE) in diabetic rats. The scavenging antioxidant capabilities of ADAE were evaluated using GC-MS analysis. In addition, rats were divided into four groups: control, ADAE, streptozotocin-induced DM (STZ), and STZ-treated rats + ADAE in an in vivo investigation. GC-MS analysis of ADAE was shown to include major components with high total phenolic contents and high DPPH scavenging activity. In diabetic rats, significant elevation in blood glucose level, lipid peroxidation, bilirubin, and lactate dehydrogenase activity as well as a change in lipid profile was observed, while insulin, body and liver weights, enzymatic and nonenzymatic antioxidants, liver function biomarkers, and protein content were significantly decreased. Furthermore, changes in the expression of the peroxisome proliferator-activated receptor (PPAR-γ), apoptotic, and inflammation-related genes were found. In addition, histological differences in rat liver tissue architecture were discovered, corroborating the biochemical modifications. However, consuming ADAE alone reduced lipid peroxidation and improved antioxidant status. Furthermore, diabetic rats given ADAE showed significant reductions in oxidative stress indicators and biochemical parameters, as well as improved tissue structure, when compared to the diabetic rats' group. Also, ADAE supplementation protects diabetic rats' hepatic tissue by upregulating PPAR-γ and downregulating apoptotic and inflammatory-related gene expression. In conclusion, A. deliciosa has beneficial protective effects so, it might be used as a complementary therapy in diabetes mellitus.

Inflammatory Response and Oxidative Stress as Mechanism of Reducing Hyperuricemia of Gardenia jasminoides-Poria cocos with Network Pharmacology.

Hyperuricemia (HUA) is a metabolic disease, closely related to oxidative stress and inflammatory responses, caused by reduced excretion or increased production of uric acid. However, the existing therapeutic drugs have many side effects. It is imperative to find a drug or an alternative medicine to effectively control HUA. It was reported that Gardenia jasminoides and Poria cocos could reduce the level of uric acid in hyperuricemic rats through the inhibition of xanthine oxidase (XOD) activity. But there were few studies on its mechanism. Therefore, the effective ingredients in G. jasminoides and P. cocoa extracts (GPE), the active target sites, and the further potential mechanisms were studied by LC-/MS/MS, molecular docking, and network pharmacology, combined with the validation of animal experiments. These results proved that GPE could significantly improve HUA induced by potassium oxazine with the characteristics of multicomponent, multitarget, and multichannel overall regulation. In general, GPE could reduce the level of uric acid and alleviate liver and kidney injury caused by inflammatory response and oxidative stress. The mechanism might be related to the TNF-α and IL-7 signaling pathway.

Origanum majorana L.: A Nutritional Supplement With Immunomodulatory Effects.

Origanum majorana L. is an aromatic herb that has been grown in several Mediterranean countries since ancient times, but became popular during the Middle Ages as a medicinal plant and seasoning ingredient. O. majorana has many pharmacological effects, but its immunoreactive components and mechanisms are still unclear. In this study, four compounds were isolated and identified from O. majorana by a spectral analysis, including 1H and 13C-NMR. They were 1H-indole-2-carboxylic acid (1), (+)-laricresol (2), (+)-isolaricresol (3), and procumboside B (4, pB), which were isolated for the first time in O. majorana. The immunomodulatory effects of the four compounds were screened, and pB had good immunomodulatory activity on RAW 264.7 cells. The immunomodulatory mechanism of pB was proved, in which pB could increase the secretion of nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and reactive oxygen species (ROS) and simultaneously upregulate the expression of CD80 and CD86 on the cell surface. These results suggested that the mechanism of pB may be related to the activation of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinases (MAPKs)-signaling pathways. O. majorana is rich in nutrients and is commonly used in diets, so it can be used as a nutritional supplement with immunomodulatory effects.

Immunomodulatory effects of Nigella sativa seed polysaccharides by gut microbial and proteomic technologies.

Cyclophosphamide (CTX) was used to establish the immunosuppressive mice model. The immune organ viscera index, phagocytes vitality, the levels of cytokines in serum, the oxidative stress resistance, proteomics and intestinal flora in mice were investigated to evaluate the effect of immune regulation of Nigella sativa seed polysaccharide (NSSP). The results showed that the high-dose NSSP group could significantly increase the thymus and spleen index. The levels of ACP, LDH, T-AOC, SOD, IL-2, IL-4 and IL-6 were significantly increased and the levels of TNF-α and MDA were reduced. All evidences indicated that NSSP could improve the immune effects of the immunosuppressed mice. Proteomics investigation showed that NSSP could improve the immune by regulating the differential proteins of PI3K and PTEN, and regulating the metabolism-related pathways such as autoimmune diseases and PI3K-Akt signaling pathway. of Gut microbes analysis showed that NSSP could exert immunomodulatory effects by improving the structure of the intestinal flora, increasing the diversity of the flora, and regulating metabolic pathways such as lipid metabolism, polysaccharide synthesis and signal transduction by the prediction of flora metabolic functions. In addition, NSSP could regulate intestinal environment by regulating the content of short chain fatty acids.

A rapid method and mechanism to identify the active compounds in Malus micromalus Makino fruit with spectrum-effect relationship, components knock-out and molecular docking technology.

Fingerprints of 20 batches of Malus micromalus Makino fruit were established by HPLC coupled with hierarchical cluster analysis (HCA) and principal component analysis (PCA) to estimate the common peaks on the basis of traditional similarity evaluation methods. Chromatographic peaks were identified as p-coumaric acid (P2), ferulic acid glycoside (P6), 4-O-ß-Glucopyranosyl-cis-coumaric acid (P8), phloretin-2'-xyloglucoside (P10), phloridzin (P11) and quercetin-3-O-α-rhamnoside (P12) by UPLC-MS/MS method. The results of tyrosinase kinetics experiments showed that: P2 and the concentration of P11 was greater than 0.50 mmol/L mainly had a competitive inhibitory effect on tyrosinase, and the concentration of phlorizin was less than at 0.25 mmol/L, it has a mixed inhibitory effect. P8 was mainly a non-competitive activation type in the concentration range, while P12 was a mixed activation type. The results of tyrosinase molecular docking showed that: P2, P8, P11, P12 was located in the active center of the hydrophobic pocket of the enzyme. They bound to tyrosinase residues by hydrogen bonds and interacted with many hydrophobic residues around them to maintain the structure of the complex. This research provides a rapid method to determine the active compounds in edible plants with the technology of spectrum-effect relationship, component knock-out and molecular docking.

Metabolites with Anti-Inflammatory Activity from the Mangrove Endophytic Fungus Diaporthe sp. QYM12.

One new diterpenoid, diaporpenoid A (1), two new sesquiterpenoids, diaporpenoids B-C (2,3) and three new α-pyrone derivatives, diaporpyrones A-C (4-6) were isolated from an MeOH extract obtained from cultures of the mangrove endophytic fungus Diaporthe sp. QYM12. Their structures were elucidated by extensive analysis of spectroscopic data. The absolute configurations were determined by electronic circular dichroism (ECD) calculations and a comparison of the specific rotation. Compound 1 had an unusual 5/10/5-fused tricyclic ring system. Compounds 1 and 4 showed potent anti-inflammatory activities by inhibiting the production of nitric oxide (NO) in lipopolysaccharide (LPS)-induced RAW264.7 cells with IC50 values of 21.5 and 12.5 µM, respectively.

Natural Products: Review for Their Effects of Anti-HBV.

Hepatitis B is a global infectious disease, seriously endangering human health. Currently, there are mainly interferons and nucleoside analogues treatment of hepatitis B in the clinic, which have certain therapeutic effects on hepatitis B, but their side effects and drug resistance are increasingly prominent. Therefore, it is urgently needed to discover and develop new anti-HBV drugs, especially natural products, which have novel, high efficiency, and low toxicity anti-HBV compounds with novel antiviral mechanisms. In this manuscript, the natural products (polysaccharides and 165 compounds) with the activity of antihepatitis B virus are discussed according to their chemical classes, including 14 phenylpropanoids, 8 flavonoids,12 xanthones, 13 anthroquinones, 47 terpenoids, 6 alkaloids, 15 enediynes, 11 aromatics, 18 phenylalanine dipeptides compounds, and 13 others. In addition, the anti-HBV mechanism and targets of natural product were also discussed. The aim of this review is to report new discoveries about anti-HBV natural products and to provide reference for researchers.

Anticancer Effects and Mechanisms of Action of Plumbagin: Review of Research Advances.

Plumbagin (PLB), a natural naphthoquinone constituent isolated from the roots of the medicinal plant Plumbago zeylanica L., exhibited anticancer activity against a variety of cancer cell lines including breast cancer, hepatoma, leukemia, melanoma, prostate cancer, brain tumor, tongue squamous cell carcinoma, esophageal cancer, oral squamous cell carcinoma, lung cancer, kidney adenocarcinoma, cholangiocarcinoma, gastric cancer, lymphocyte carcinoma, osteosarcoma, and canine cancer. PLB played anticancer activity via many molecular mechanisms, such as targeting apoptosis, autophagy pathway, cell cycle arrest, antiangiogenesis pathway, anti-invasion, and antimetastasis pathway. Among these signaling pathways, the key regulatory genes regulated by PLB were NF-kß, STAT3, and AKT. PLB also acted as a potent inducer of reactive oxygen species (ROS), suppressor of cellular glutathione, and novel proteasome inhibitor, causing DNA double-strand break by oxidative DNA base damage. This review comprehensively summarizes the anticancer activity and mechanism of PLB.

Anti-Hepatoma Compound Determination by the Method of Spectrum Effect Relationship, Component Knock-Out, and UPLC-MS2 in Scheflera heptaphylla (L.)Frodin Harms and Its Mechanism.

Scheflera heptaphylla (L.)Frodin, a kind of Traditional Chinese Medicine, is commonly used in anti-inflammatory, analgesic, anti-viral, anti-tumor, and hemostasis. This study aimed to determine the anti-hepatoma components and its mechanism from the leaves of S. heptaphylla. The spectrum-effect relationships were analyzed by the method of Partial least squares, indicating that P1, P2, and P10 were positively correlated to inhibitory activity of Huh7 cells. Whereas others were negatively correlated. The technologies of component knock-out and UPLC-MS2 were used to determine compounds as 3,4-Dicaffeoylquinic acid (P6), 3,5-Dicaffeoylquinic acid (P7), 3α-Hydroxy-lup-20(29)-ene-23,28-dioic acid (P10, named Compound A). The results forecasted that Compound A had the best correlation with inhibitory activity. The effects of Compound A on the activities of human hepatoma cells (Huh7, SMMC-7721, HepG 2) and normal hepatocytes (L0-2, Chang liver) were evaluated. Cell apoptosis was observed with inverted microscope and flow cytometer. In addition, the proteins, related to apoptosis, were detected by Western blot. The results showed that Compound A (400 nM) could significantly inhibit the activity of three hepatoma cells (P < 0.001) with slight toxicity to normal hepatocytes, and the IC50 values were 285.3 and 315.1 nM, respectively, which were consistent with the prediction of spectrum-effect relationships. After treatment with Compound A, the number of hepatoma cells decreased significantly. And the apoptosis rate of Huh7 cells increased significantly (P < 0.001) in Compound A (200, 400 nM) groups, SMMC-7721 and HepG 2 were directly necrotic. Compound A groups could significantly improve the level of intracellular reactive oxygen species (ROS) (P < 0.05, P < 0.001) in Huh7 with no effect on normal hepatocytes. The content of apoptotic protein (Bax and Bim) in mitochondria was significantly increased in Compound A groups (P < 0.001). On the contrary, the content of anti-apoptotic protein (Bcl-xL and Mcl-1) decreased significantly (P < 0.001). These results demonstrated that Compound A was the main anti-hepatoma active component in the S. heptaphylla leaves. It achieved the effect of promoting apoptosis of Huh7 cells by regulating the levels of ROS and Bcl-2 family protein in mitochondrial apoptosis pathway.

Bromelain from Ananas comosus stem attenuates oxidative toxicity and testicular dysfunction caused by aluminum in rats.

BACKGROUND: Aluminum (Al) has been reported to induce testicular injury via oxidative stress. Ananas comosus stem extract is an inexpensive byproduct waste rich in bromelain which is a group of sulfur-containing enzymes known for its biological activities and medicinal applications. So, the current investigation aims to evaluate the efficacy of bromelain in counteracting oxidative injury and testicular dysfunction stimulated by aluminum in rats. METHODS: Male adult Wistar rats were divided into four groups. The first group used as control, however, the second and third groups were received bromelain (250 mg/kg) and AlCl3 (34 mg/Kg, 1/25 LD50), and the fourth group supplemented with bromelain one hour before AlCl3 intoxication, respectively. Bromelain was administered daily while AlCl3 was given every other day by oral gavages for one month. RESULTS: Al intoxicated animals revealed an elevation in lipid peroxidation (TBARS and H2O2) level and lactate dehydrogenase (LDH) activity. However, reduced glutathione (GSH) and protein contents, antioxidant enzymes (SOD, CAT, GPx, GR, GST), phosphatases (ALP, AcP) and aminotransferases (AST, ALT) activities were significantly reduced. Additionally, considerable amendments in hormonal levels (testosterone, luteinizing and follicle-stimulating hormone) and sperm characteristics were spotted. Further, histological variations in the testes section were detected and this supports the biochemical observations. Otherwise, rats supplemented with bromelain alone diminished TBARS and H2O2 and augmented mostly other parameters. Furthermore, supplementation with bromelain before Al intoxication in rats exhibited worthy betterment in oxidative stress markers, hormones, and sperm quality compared to Al treated group. CONCLUSION: In conclusion, bromelain had a powerful protective role against Al-induced testicular dysfunction so, it represents a novel approach in metal toxicity processing.

Effect of Durio zibethinus rind polysaccharide on functional constipation and intestinal microbiota in rats.

The prevalence of constipation increases rapidly with the increased pressure of some people's life, which seriously affects the quality of life in related patients. In this study, the improvement of functional constipation by Durio zibethinus Murr rind polysaccharide (DZMP) and the effects of DZMP on intestinal microbiota were investigated in a constipation model of Sprague-Dawley (SD) rats established by loperamide hydrochloride. Results showed that DZMP at 200 mg/kg could significantly (P < 0.05) increase the intestinal transit rate, motilin, gastrin, substance P levels and concentration of short-chain fatty acids (SCFAs), reduce the somatostatin levels and improve the gastrointestinal peristalsis of rats. Sequencing showed that the Lachnospiraceae-NK4A136-group in the rats given 200 mg/kg DZMP (16.07%) was significantly higher than that of the model group (10.13%), while the Desulfovibrio was lower (2.99%) than that of the model group (4.19%). Principal co-ordinates analysis (PcoA) revealed a significant difference in intestinal microbiota composition between the model group and the high-dose DZMP group (200 mg/kg). The results demonstrated that DZMP has a regulatory effect of treating functional constipation and regulating intestinal flora in rats.

Recent Progress on Chemical Constituents and Pharmacological Effects of the Genus Nigella.

Seeds of the genus Nigella plants as folk medicine are often used to prevent and treat asthma, diarrhea, dyslipidemia, and other diseases around the world. Pharmacological researches showed that seed extract and seed oil have antibacterial, antioxidant, hypoglycemic, and hepatoprotective effects which attributed to their bioactive constituents such as alkaloids, saponins, flavones, and phenols. This paper has covered recent progresses on chemical and pharmacological researches on these plants, including their compounds and pharmacological effects. It was found that the chemical component researches were focused on the seed oil. Therefore, more attention should be paid to the profile of the whole constituents in the seeds.

Effects of Nigella sativa seed polysaccharides on type 2 diabetic mice and gut microbiota.

Effect of Nigella sativa seed polysaccharides (NSSP) on type 2 diabetic mice and its gut microbiota was investigated on the type 2 diabetic mice model feed by high-fat diet. Fasting blood glucose (FBG), biochemical parameters, expression levels of cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and phosphor-AKT (p-AKT) protein, membrane glucose transporter 4 (GLUT4) in skeletal muscles, as well as the change of gut microbiota profile in mice model were measured. Results showed that the high-dose NSSP could significantly lower the levels of FBG, glycosylated serum protein (GSP), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), malondialdehyde (MDA), TNF-α, IL-6 and IL-1ß, and significantly increased insulin (INS), high-density lipoprotein cholesterol (HDLC), total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT) and the expression levels of p-AKT and GLUT4 in mice. Besides, the high-dose NSSP has significantly increased the abundance of f_Muribaculaceae_Unclassified and Bacteroides, which were significantly suppressed in the mice gut after the treatment of streptozotocin (STZ). These results indicated that NSSP could improve the abnormal state of diabetic mice by regulating the PI3K/AKT signaling pathway with simultaneous changes of the gut microbiota profile.