OBJECTIVE: To elucidate the effect of Huanglian-Renshen-Decoction (HRD) on ameliorating type 2 diabetes mellitus by maintaining islet β -cell identity through regulating paracrine and endocrine glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) in both islet and intestine. METHODS: The db/db mice were divided into the model (distilled water), low-dose HRD (LHRD, 3 g/kg), high-dose HRD (HHRD, 6 g/kg), and liraglutide (400 µ g/kg) groups using a random number table, 8 mice in each group. The db/m mice were used as the control group (n=8, distilled water). The entire treatment of mice lasted for 6 weeks. Blood insulin, glucose, and GLP-1 levels were quantified using enzyme-linked immunosorbent assay kits. The proliferation and apoptosis factors of islet cells were determined by immunohistochemistry (IHC) and immunofluorescence (IF) staining. Then, GLP-1, GLP-1R, prohormone convertase 1/3 (PC1/3), PC2, v-maf musculoaponeurotic fibrosarcoma oncogene homologue A (MafA), and pancreatic and duodenal homeobox 1 (PDX1) were detected by Western blot, IHC, IF, and real-time quantitative polymerase chain reaction, respectively. RESULTS: HRD reduced the weight and blood glucose of the db/db mice, and improved insulin sensitivity at the same time (P<0.05 or P<0.01). HRD also promoted mice to secrete more insulin and less glucagon (P<0.05 or P<0.01). Moreover, it also increased the number of islet β cell and decreased islet α cell mass (P<0.01). After HRD treatment, the levels of GLP-1, GLP-1R, PC1/3, PC2, MafA, and PDX1 in the pancreas and intestine significantly increased (P<0.05 or P<0.01). CONCLUSION HRD can maintain the normal function and identity of islet β cell, and the underlying mechanism is related to promoting the paracrine and endocrine activation of GLP-1 in pancreas and intestine.
Animals ; Glucagon-Like Peptide 1/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Glucagon-Like Peptide-1 Receptor/metabolism* ; Insulin-Secreting Cells/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Male ; Blood Glucose/metabolism* ; Insulin/blood* ; Mice ; Intestinal Mucosa/pathology* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Islets of Langerhans/pathology*

OBJECTIVES: To investigate the role of sphingosine-1-phosphate receptor 5 (S1PR5) in modulating barrier function of mouse brain microvascular endothelial cells with oxygen-glucose deprivation and reoxygenation (OGD/R). METHODS: Mouse brain microvascular endothelial cells (bEnd.3) were exposed to OGD/R to induce barrier dysfunction following treatment with S1PR5-specific agonist A971432 or lentivirus-mediated transfection with a S1PR5-specific siRNA, a S1PR5-overexpressing plasmid, or their respective negative control sequences. The changes in viability and endothelial barrier permeability of the treated cells were evaluated with CCK-8 assay and FITC-dextran permeability assay; the levels of intracellular reactive oxygen species (ROS) and localization and expression levels of the proteins related with barrier function and oxidative stress were detected using immunofluorescence staining, DCFH-DA probe and Western blotting. RESULTS: S1PR5 activation obviously enhanced viability of bEnd.3 cells exposed to OGD/R (P<0.0001). Both activation and overexpression of S1PR5 reduced FITC-dextran leakage, while S1PR5 knockdown significantly increased FITC-dextran leakage in the exposed bEnd.3 cells. Activation and overexpression of S1PR5 both increased the cellular expressions of the barrier proteins ZO-1 and occludin, while S1PR5 knockdown produced the opposite effect. In cells exposed to OGD/R, ROS production was significantly reduced by S1PR5 activation and overexpression but increased following S1PR5 knockdown. Overexpression of S1PR5 obviously increased the expressions of the antioxidant proteins Nrf2, HO-1 and SOD2 in the exposed cells. CONCLUSIONS S1PR5 activation and overexpression significantly improve cell viability and reduce permeability of a mouse brain microvascular endothelial cell model of OGD/R, the mechanism of which may involve the reduction in ROS production and upregulation of the antioxidant proteins.
Animals ; Mice ; Oxidative Stress ; Endothelial Cells/cytology* ; Brain/blood supply* ; Reactive Oxygen Species/metabolism* ; Receptors, Lysosphingolipid/metabolism* ; Sphingosine-1-Phosphate Receptors ; Blood-Brain Barrier/metabolism* ; Glucose ; Cell Line ; Oxygen/metabolism* ; NF-E2-Related Factor 2/metabolism*

OBJECTIVES: To investigate the effects of live combined Bacillus subtilis and Enterococcus faecium (LCBE) on glucose and lipid metabolism in mice with type 2 diabetes mellitus (T2DM) and circadian rhythm disorder (CRD) and explore the possible mechanisms. METHODS: KM mice were randomized into normal diet (ND) group (n=8), high-fat diet (HFD) group (n=8), and rhythm-intervention with HFD group (n=16). After 8 weeks of feeding, the mice were given an intraperitoneal injection of streptozotocin (100 mg/kg) to induce T2DM. The mice in CRD-T2DM group were further randomized into two equal groups for treatment with LCBE (225 mg/kg) or saline by gavage; the mice in ND and HFD groups also received saline gavage for 8 weeks. Blood glucose level of the mice was measured using a glucometer, and serum levels of Bmal1, PER2, insulin, C-peptide and lipids were determined with ELISA. Colon morphology and hepatic lipid metabolism of the mice were examined using HE staining and Oil Red O staining, respectively, and fecal short-chain fatty acids (SCFAs) was detected using LC-MS; GPR43 and GLP-1 expression levels were analyzed using RT-qPCR and Western blotting. RESULTS: Compared with those in CRD-T2DM group, the LCBE-treated mice exhibited significant body weight loss, lowered levels of PER2, insulin, C-peptide, total cholesterol (TC) and LDL-C, and increased levels of Bmal1 and HDL-C levels. LCBE treatment significantly increased SCFAs, upregulated GPR43 and GLP-1 expressions at both the mRNA and protein levels, and improved hepatic steatosis and colon histology. CONCLUSIONS LCBE ameliorates lipid metabolism disorder in CRD-T2DM mice by reducing body weight and improving lipid profiles and circadian regulators possibly via the SCFAs/GPR43/GLP-1 pathway.
Animals ; Mice ; Lipid Metabolism ; Diabetes Mellitus, Type 2/metabolism* ; Enterococcus faecium ; Glucagon-Like Peptide 1/metabolism* ; Bacillus subtilis ; Diabetes Mellitus, Experimental/metabolism* ; Circadian Rhythm ; Blood Glucose/metabolism* ; Receptors, G-Protein-Coupled/metabolism* ; Fatty Acids, Volatile/metabolism* ; Male ; Chronobiology Disorders/metabolism*

OBJECTIVES: To investigate the effects of Naoluo Xintong Decoction (NLXTD) on proliferation of rat brain microvascular endothelial cells (BMECs) after oxygen-glucose deprivation/reoxygenation (OGD/R) injury and role of the HIF-1α/VEGF pathway in mediating its effect. METHODS: Using a BMEC model of OGD/R, we tested the effects of 10% NLXTD-medicated rat serum, alone or in combination with 2ME2 or 10% NAKL, on cell proliferation, migration, tube-forming ability and permeability using CCK-8 assay, Transwell chamber assay, tube formation assay and permeability assay. Cellular expressions of VEGF and Notch were detected using ELISA and laser confocal immunofluorescence analysis, and the expressions of HIF-1α, VEGFR2, Notch1, ERK and P-ERK1/2 proteins were detected with Western blotting. RESULTS: OGD/R injury significantly decreased viability of BMECs. NLXTD treatment of the cells with OGD/R could significantly promoted cell proliferation, migration and tube formation ability, but these effects were strongly attenuated by application of 2ME2. NLXTD treatment also significantly increased the percentages of VEGF- and Notch-positive cells in the cell models and obviously enhanced the expression levels of HIF-1α, VEGFR2, Notch1 and P-ERK1/2. CONCLUSIONS NLXTD promotes proliferation, migration, and tube formation of rat BMECs after OGD/R injury possibly by activating the HIF-1α/VEGF signaling pathway.
Animals ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Vascular Endothelial Growth Factor A/metabolism* ; Endothelial Cells/metabolism* ; Rats ; Cell Proliferation/drug effects* ; Signal Transduction/drug effects* ; Glucose ; Brain/blood supply* ; Cells, Cultured ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor Receptor-2/metabolism* ; Oxygen/metabolism* ; Cell Hypoxia

OBJECTIVE: To explore the association between blood glucose trajectories within 7 days of intensive care unit (ICU) admission and mortality in patients with sepsis-associated acute respiratory distress syndrome (ARDS). METHODS: Based on the MIMIC-IV database, sepsis-associated ARDS patients with daily blood glucose monitoring data within 7 days of ICU admission were selected. Blood glucose trajectories were analyzed using group-based trajectory modeling (GBTM), and the optimal number of groups was determined based on the minimum Akaike information criterion (AIC), Bayesian information criterion (BIC), average posterior probability (AvePP), odds of correct classification (OCC), and proportion of group membership (Prop). Baseline characteristics including demographics, comorbidities, severity scores, vital signs, laboratory indicators within the first 24 hours of ICU admission, and treatments were collected. Kaplan-Meier survival curves were used to compare 28-day and 1-year survival across trajectory groups. Multivariate Logistic regression was performed to evaluate the associations between glucose trajectory groups and in-hospital mortality, ICU mortality. The incidence of hypoglycemia within 7 days in the ICU was analyzed among different groups. RESULTS: A total of 3 869 patients with sepsis-associated ARDS were included, with a median age of 63.52 (52.13, 73.54) years; 59.6% (2 304/3 869) were male. Based on glucose levels within 7 days, patients were categorized into three groups: persistent hyperglycemia group (glucose maintained at 10.6-13.1 mmol/L, n = 894), moderate glucose group (7.8-8.9 mmol/L, n = 1 452), and low-normal glucose group (6.1-7.0 mmol/L, n = 1 523). There were statistically significant differences in 28-day mortality and 1-year mortality among low-normal glucose group, moderate glucose group, and persistent hyperglycemia group [28-day mortality: 11.42% (174/1 523), 19.83% (288/1 452), 25.50% (228/894), χ ² = 82.545, P < 0.001; 1-year mortality: 23.31% (355/1 523), 33.75% (490/1 452), 39.49% (353/894), χ ² = 77.376, P < 0.001]. Kaplan-Meier analysis showed that higher glucose trajectories were associated with significantly lower 28-day and 1-year cumulative survival rates (Log-rank test: χ ² were 83.221 and 85.022, both P < 0.001). There were statistically significant differences in in-hospital mortality and ICU mortality among the low-normal glucose group, moderate glucose group, and persistent hyperglycemia group [in-hospital mortality: 9.65% (147/1 523), 19.70% (286/1 452), 24.50% (219/894), χ ² = 102.020, P < 0.001; ICU mortality: 7.22% (110/1 523), 16.05% (233/1 452), 20.13% (180/894), χ ² = 93.050, P < 0.001]. Logistic regression confirmed that, using the persistent hyperglycemia group as the reference, the low-normal glucose group had significantly lower risks of in-hospital mortality and ICU mortality after multiple factor adjustment. Although the moderate glucose group showed a trend toward lower mortality, the differences were not statistically significant. Using the moderate glucose group as a reference, the low-normal glucose group had 43.1% lower in-hospital mortality [odds ratio (OR) = 0.569, 95% confidence interval (95%CI) was 0.445-0.726, P < 0.001] and 42.0% lower ICU mortality (OR = 0.580, 95%CI was 0.439-0.762, P < 0.001). There was no statistically significant difference in the incidence of hypoglycemia within 7 days of ICU admission among low-normal glucose group, moderate glucose group, and persistent hyperglycemia group [2.82% (43/1 523), 2.69% (39/1 452), 3.02% (27/894), χ ² = 0.226, P = 0.893]. CONCLUSIONS Blood glucose trajectories during ICU stay are closely associated with prognosis in patients with sepsis-associated ARDS. Persistent hyperglycemia (10.6-13.1 mmol/L) is linked to significantly higher short- and long-term mortality.
Humans ; Respiratory Distress Syndrome/etiology* ; Sepsis/blood* ; Intensive Care Units ; Male ; Female ; Middle Aged ; Blood Glucose/metabolism* ; Hospital Mortality ; Aged

Objective To investigate the effect and mechanism of baicalin on blood lipid metabolism and immune function in rats with gestational diabetes mellitus (GDM). Methods Female rats fed with high-fat and high-sugar diet and male rats fed with ordinary diet were caged together to prepare pregnant rats, and the GDM rat model was established by intraperitoneal injection of streptozotocin (35 mg/kg). GDM rats were randomly divided into a model group, a fasudil (FA) (RhoA/RocK inhibitor) group (10 mg/kg), low-dose (100 mg/kg) and high-dose (200 mg/kg) baicalin groups, and a high-dose baicalin combined with LPA (RhoA/RocK activator) group (200 mg/kg baicalin+1 mg/kg LPA ), with 12 rats in each group. Another 12 pregnant rats fed with high-fat and high-sugar diet were selected as the control group. After 2 weeks of corresponding drug intervention in each group, the level of fasting blood glucose (FBG) was detected by blood glucose meter. The level of fasting insulin (FINS) in serum was detected by ELISA, and the insulin resistance index (HOMA-IR) was calculated. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) in serum, and the levels of immunomodulator tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and IL-10 in peripheral blood were detected by the kit. The histopathological changes of liver were observed by HE staining. The proportion of T lymphocyte subsets in peripheral blood was detected by flow cytometry. The mRNA and protein expressions of Ras homolog gene family member A (RhoA), Rho associated coiled-coil forming protein kinase 1 (ROCK1), and ROCK2 in liver tissue were detected by real-time quantitative PCR and Western blot. Results Compared with the control group, the levels of FBG, FINS, HOMA-IR, ALT, AST, TG, TC, and LDL-C in serum, the levels of TNF-α, IL-6, the percentage of CD8⁺T cell in peripheral blood, and the mRNA and protein expression of RhoA, ROCK1, and ROCK2 in liver tissue in the model group were higher; the level of HDL-C in serum, the percentage of IL-10 levels, CD3⁺T cells, CD4⁺T cell, and CD4⁺T/CD8⁺T ratio in peripheral blood were lower. Compared with the model group, the levels of FBG, FINS, HOMA-IR, ALT, AST, TG, TC, and LDL-C in serum, the levels of TNF-α, IL-6, the percentage of CD8⁺T cell in peripheral blood, and the mRNA and protein expression of RhoA, ROCK1, and ROCK2 in liver tissue in the the FA group and low-dose and high-dose baicalin groups were lower; the level of HDL-C in serum, IL-10 level, the percentage of CD3⁺T cells, CD4⁺T cell, and CD4⁺T/CD8⁺T ratio in peripheral blood were higher. LPA could obviously weaken the improvement effects of baicalin on blood lipid metabolism and immune function in GDM rats. Conclusion Baicalin may improve blood lipid metabolism and immune function in GDM rats by inhibiting the RhoA/ROCK pathway.
Animals ; Female ; Diabetes, Gestational/metabolism* ; Pregnancy ; rho-Associated Kinases/genetics* ; Flavonoids/pharmacology* ; Rats ; rhoA GTP-Binding Protein/genetics* ; Lipid Metabolism/drug effects* ; Male ; Signal Transduction/drug effects* ; Rats, Sprague-Dawley ; Blood Glucose/metabolism* ; Lipids/blood* ; Tumor Necrosis Factor-alpha/blood* ; rho GTP-Binding Proteins

The relationship between hyperuricemia (HUA) and erectile dysfunction (ED) remains inadequately understood. Given that HUA is often associated with various metabolic disorders, this study aims to explore the multivariate linear impacts of metabolic parameters on erectile function in ED patients with HUA. A cross-sectional analysis was conducted involving 514 ED patients with HUA in the Department of Andrology, Jiangsu Province Hospital of Chinese Medicine (Nanjing, China), aged 18 to 60 years. General demographic information, medical history, and laboratory results were collected to assess metabolic disturbances. Sexual function was evaluated using the 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire. Based on univariate analysis, variables associated with IIEF-5 scores were identified, and the correlations between them were evaluated. The effects of these variables on IIEF-5 scores were further explored by multiple linear regression models. Fasting plasma glucose ( β = -0.628, P < 0.001), uric acid ( β = -0.552, P < 0.001), triglycerides ( β = -0.088, P = 0.047), low-density lipoprotein cholesterol ( β = -0.164, P = 0.027), glycated hemoglobin (HbA1c; β = -0.562, P = 0.012), and smoking history ( β = -0.074, P = 0.037) exhibited significant negative impacts on erectile function. The coefficient of determination ( R ²) for the model was 0.239, and the adjusted R ² was 0.230, indicating overall statistical significance ( F -statistic = 26.52, P < 0.001). Metabolic parameters play a crucial role in the development of ED. Maintaining normal metabolic indices may aid in the prevention and improvement of erectile function in ED patients with HUA.
Humans ; Male ; Erectile Dysfunction/metabolism* ; Hyperuricemia/metabolism* ; Adult ; Middle Aged ; Cross-Sectional Studies ; Glycated Hemoglobin/metabolism* ; Blood Glucose/metabolism* ; Uric Acid/blood* ; Young Adult ; Triglycerides/blood* ; Adolescent ; Cholesterol, LDL/blood* ; Penile Erection/physiology* ; Surveys and Questionnaires

Coptis chinensis Franch. and Panax ginseng C. A. Mey. are traditional herbal medicines with millennia of documented use and broad therapeutic applications, including anti-diabetic properties. However, the synergistic effect of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng on type 2 diabetes mellitus (T2DM) and its underlying mechanism remain unclear. The research demonstrated that the optimal ratio of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng was 4∶1, exhibiting maximal efficacy in improving insulin resistance and gluconeogenesis in primary mouse hepatocytes. This combination demonstrated significant synergistic effects in improving glucose tolerance, reducing fasting blood glucose (FBG), the weight ratio of epididymal white adipose tissue (eWAT), and the homeostasis model assessment of insulin resistance (HOMA-IR) in leptin receptor-deficient (db/db) mice. Subsequently, a T2DM liver-specific network was constructed based on RNA sequencing (RNA-seq) experiments and public databases by integrating transcriptional properties of disease-associated proteins and protein-protein interactions (PPIs). The network recovery index (NRI) score of the combined treatment group with a 4∶1 ratio exceeded that of groups treated with individual components. The research identified that activated adenosine 5'-monophosphate-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling in the liver played a crucial role in the synergistic treatment of T2DM, as verified by western blot experiment in db/db mice. These findings demonstrate that the 4∶1 combination of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng significantly improves insulin resistance and glucose and lipid metabolism disorders in db/db mice, surpassing the efficacy of individual treatments. The synergistic mechanism correlates with enhanced AMPK/ACC signaling pathway activity.
Animals ; Panax/chemistry* ; Ginsenosides/administration & dosage* ; Diabetes Mellitus, Type 2/metabolism* ; Mice ; Male ; Alkaloids/pharmacology* ; Coptis/chemistry* ; Drug Synergism ; Insulin Resistance ; Mice, Inbred C57BL ; Humans ; Transcriptome/drug effects* ; Blood Glucose/metabolism* ; Hypoglycemic Agents/administration & dosage* ; Drugs, Chinese Herbal/administration & dosage* ; Hepatocytes/metabolism*

Wumei Pills, a classic traditional Chinese medicine(TCM) formula, are widely used in the treatment of biliary ascariasis and diarrhea. In recent years, studies have shown that Wumei Pills have advantages in the treatment of type 2 diabetes mellitus(T2DM), while there are no relevant reports that systematically evaluate the efficacy of Wumei Pills in the treatment of T2DM. This study addresses this issue by systematically evaluating the efficacy and safety of Wumei Pills, aiming to provide an evidence-based basis for clinical practice. PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang, and VIP were researched for the randomized controlled trial(RCT) involving Wumei Pills for the treatment of T2DM that were published from inception to September 2024. RevMan 5.3 was used for the Meta-analysis of the data. A total of 18 RCTs were included, with a total of 1 437 patients. Meta-analysis produced the following results.(1)Treatment group outperformed control group in terms of overall response rate(RR=1.28, 95%CI[1.14, 1.43], P<0.000 1), fasting blood glucose(FPG)(WMD=-0.69, 95%CI[-0.93,-0.46], P<0.000 01), two-hour postprandial plasma glucose(2hPG)(WMD=-0.74, 95%CI[-1.17,-0.31], P<0.000 7), glycated hemoglobin(HbA1c)(WMD=-0.39, 95%CI[-0.60,-0.18], P=0.000 3), high-density lipoprotein(HDL)(WMD=0.38, 95%CI[0.28, 0.48], P<0.000 01), and body mass index(BMI)(WMD=-1.41, 95%CI[-2.40,-0.42], P=0.005).(2)The two groups had comparable effects regarding total cholesterol(TC)(WMD=-0.53, 95%CI[-1.13, 0.08], P=0.09) and low-density lipoprotein(LDL)(WMD=-0.25, 95%CI[-0.56, 0.06], P=0.12).(3)Triglycerides(TG)(WMD=-0.28,95%CI [-0.59,0.03],P=0.08), sensitivity analysis showed potential reduction effect(WMD=-0.20,95%CI[-0.36,-0.04],P=0.01). Occurrence of adverse drug reaction(RR=0.43,95%CI [0.23,0.80],P=0.007), sensitivity analysis showed significant disappearance(RR=0.56,95%CI[0.26,1.22],P=0.14), suggesting that the efficacy of treatment group was not better than that of control group. The results indicate that the treatment of T2DM with Wumei Pills is greatly related to the improvement of glucose metabolism, lipid metabolism, and clinical efficacy. The findings provide a basis for clinical application of Wumei Pills in treating T2DM, while the conclusion remains to be verified by clinical studies with higher quality.
Humans ; Diabetes Mellitus, Type 2/blood* ; Drugs, Chinese Herbal/administration & dosage* ; Randomized Controlled Trials as Topic ; Blood Glucose/metabolism* ; Hypoglycemic Agents/therapeutic use* ; Treatment Outcome ; Glycated Hemoglobin/metabolism* ; Female

Ultra performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry/mass spectrometry(UPLC-Q-TOF-MS/MS), network pharmacology, and animal experiments were integrated o explore the blood glucose-lowering effects and mechanisms of Poria aqueous extract. Firstly, the active components of Poria aqueous extract were identified by UPLC-Q-TOF-MS/MS. Subsequently, network pharmacology was employed to predict the blood glucose-lowering components and mechanisms of Poria aqueous extract. Finally, a rat model of diabetes mellitus, 16S rDNA sequencing, and Western blot were employed to investigate the blood glucose-lowering effect and mechanism of Poria aqueous extract. A total of 39 triterpenoids were identified in the Poria aqueous extract, among them, 25-hydroxypachymic acid, 25α-hydroxytumulosic acid, 16α-hydroxytrametenolic acid, polyporenic acid C, and tumulosic acid may be the main active ingredients for treating diabetes. The Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis revealed that Poria might exert its therapeutic effects through multiple pathways such as NOD-like receptor signaling pathway, nuclear factor-kappa B(NF-κB) signaling pathway, and tumor necrosis factor(TNF) signaling pathway. The results of animal experiments demonstrated that Poria aqueous extract significantly reduced the levels of blood glucose and lipids and regulated the intestinal flora in diabetic rats. The main affected taxa included g＿Escherichia-Shigella, g＿Corynebacterium, g＿Prevotella＿9, g＿Prevotellaceae＿UCG-001, and g＿Bacteroidota＿unclassified. In addition, Poria aqueous extract lowered the levels of D-lactic acid and lipopolysaccharide, alleviated colonic mucosal damage, significantly down-regulated the protein levels of NOD-like receptor pyrin domain-containing protein 3(NLRP3), NF-κB, and TNF-α, and significantly up-regulated the protein levels of zonula occludens 1 and occludin in diabetic rates. Poria aqueous extract may play a role in treating diabetes mellitus by repairing the intestinal flora disturbance, protecting the intestinal barrier function, and inhibiting the NF-κB/NLRP3 signaling pathway. The results provide a scientific basis for clinical application and expansion of indications of Poria.
Animals ; Rats ; Network Pharmacology ; Tandem Mass Spectrometry ; Male ; Drugs, Chinese Herbal/pharmacology* ; Chromatography, High Pressure Liquid ; Blood Glucose/drug effects* ; Rats, Sprague-Dawley ; Hypoglycemic Agents/administration & dosage* ; Poria/chemistry* ; Diabetes Mellitus, Experimental/metabolism* ; NF-kappa B/genetics* ; Gastrointestinal Microbiome/drug effects* ; Humans