Chinese Journal of Integrative Medicine最新文献

Objective: To investigate the impact of puerarin on gut microbiota and epithelial integrity and glucose metabolism on a type 2 diabetes mellitus (T2DM) rat model.

Methods: A total of 20 male Sprague-Dawley rats were randomly divided into 4 groups, including the normal control (NC), high-fat diet (HFD), diabetes mellitus (DM), and puerarin-treated (Pue) groups (n=5). Except for the NC group, the rats in the other groups were fed a HFD. Additionally, rats in the DM group were injected with streptozotocin (STZ) to induce diabetes. Rats in the Pue group were fed an HFD, injected with STZ and treated with puerarin via intraperitoneal injection at a dosage of 100 mg/kg daily for 4 weeks. Glucose metabolism indicators, including glycated hemoglobin (HbA1c) and area under the curve (AUC) of glucose tolerance test (GTT) were measured through blood sampling. Gut microbiota was analyzed using 16S ribosomal ribonucleic acid (rRNA) gene sequencing, and the expression of free fatty acid receptors 2 and 3 (FFAR2/FFAR3) was detected by quantitative polymerase chain reaction. Paneth cell function and epithelial integrity were evaluated by analyzing antimicrobial peptide gene expression and tight-junction proteins (zonula occludens-1 and occludin).

Results: Puerarin treatment significantly reduced prolonged glucose exposure, as evidenced by decreased HbA1c and AUC of GTT (P<0.05). Insulin level was increased after puerarin treatment. The gut microbiota composition was significantly altered, with a decrease in Firmicutes/Bacteroidetes ratio. At the class level, puerarin significantly decreased abundance of Desulfovibrionia and Firmibacteria compared to the DM group (P<0.05). At the order level, puerarin reduced abundance of Desulfovibrionales and Negativicutes within Firmibacteria, while increasing abundance of Bifidobacteriales, Enterobacterales, Clostridiales, and Peptococcales (P<0.05). The production of FFAR2 and FFAR3, which was diminished in the DM and HFD groups, was restored after puerarin treatment (P<0.05 or P<0.01). Additionally, puerarin reversed diabetes-associated loss of Paneth cell antimicrobial peptides and restored epithelial tight-junction protein expressions, thus enhanced barrier integrity.

Conclusions: Puerarin administration significantly ameliorates glucose metabolism, modulates gut microbiota toward a beneficial profile, and improves Paneth cell function and epithelial integrity in T2DM rats. These findings highlight puerarin's potential as a multi-target therapeutic agent for T2DM by modulating the gut-pancreas-immune axis.

Objective: To explore whether polysaccharide of Danggui Buxue Decoction (formula polysaccharide, FP) could attenuate colorectal cancer (CRC) via modulating intestinal microflora and metabolites.

Methods: A total of 30 male C57BL/6 mice were randomly assigned to 3 groups according to body weight, including normal control, CRC model and FP groups (n=10). Dextran sulfate sodium and azoxymethane were used to induce CRC model. The mice in FP group were treated with FP [0.9 g/(kg·d)] for 8 weeks. Then the coloretal length, weight and tumors number of colorectal tissues were observed. Colonic tissues were stained with hematoxylin and eosin to evaluate the histological changes. Tight junction proteins including claudin 1 and zonula occludens-1 (ZO-1) were detected using immunohistochemistry. Serum concentrations of endothelial cell specific molecule-1 and carcino embryonic antigen were determined using enzyme-linked immunosorbent assays. Toll-like receptor 4 (TLR4)/nuclear transcription factor-κB (NF-κB) p65 signal-related mRNA and proteins expressions were detected using real-time polymerase chain reaction and Western blot, respectively. Feces samples were detected with 16S rRNA and liquid chromatography-mass spectrometry and non-targeted metabolomics sequencing was used to analyze the composition of intestinal microbiota and metabolic changes.

Results: FP significantly inhibited colorectal tumor growth, attenuated body weight loss, repaired colonic structure, improved intestinal barrier dysfunction, reduced colonic inflammatory cytokine levels and inhibited TLR4/NF-κB pathway related mRNA and protein expressions (all P<0.01). Moreover, FP altered the gut microbiota composition of CRC mice dramatically, characterized by a reduction of Firmicutes-Bacteroidetes ratio at the phylum level. FP suppressed Lachnospiraceae_NK4A136_group, Odoribacter and Romboutsia (P<0.05 or P<0.01), and elevated the abundance of Dubosiella, Candidatus_Saccharimonas and Alloprevotella at the genus level (P<0.01). Non-targeted metabolomics sequencing detected significant differences in metabolites, and the functions of differential metabolites were focused on regulating amino acid metabolism, lipid metabolism and metabolism of cofactors and vitamins.

Conclusions: FP attenuates colonic injury and intestinal inflammatory response in CRC mice, repairs disrupted-intestinal microbiota, and improves metabolites. This research provides experimental basis for application of FP as a potential therapeutic agent for CRC.

Objective: To determine risk factors associated with the severity of Xuebijing Injection (XBJ)-related adverse events (AEs).

Methods: Totally 16,031 cases reported XBJ-related AEs were retrospectively analyzed from China national spontaneous reporting system (SRS) from its inception to 2022. Factors including age, gender, weight, ethnicity, family history, and allergic history were examined. Univariate and multivariate logistic regression analyses were performed, followed by propensity score matching (PSM) to control for confounding factors.

Results: A total of 11,131 XBJ-related AE cases were identified after excluding duplicates and incomplete reports, including 9,771 general and 1,360 serious AEs. Serious AEs were mainly distributed among respiratory, thoracic and mediastinal disorders (27.00%). Univariate analysis identified gender, age, history of allergies, and previous AE history, XBJ-other β-lactam antimicrobials combination and XBJ-aminoglycoside antimicrobials combination were potential risk factors of serious AEs (P<0.05 or P<0.01). Multivariate analysis identified age, gender, history of allergies, and XBJ-other β-lactam antimicrobials combination as significant risk factors of AE severity (P<0.05 or P<0.01). PSM further confirmed that patients receiving XBJ combined with β-lactam antibiotics had a significantly higher risk of severe AEs (odds ratio=1.913, P=0.019).

Conclusions: The risk factors influencing the severity of XBJ include age, gender, history of allergies, and its combination with other β-lactam antimicrobials. Among them, PSM further proved that the XBJ-other β-lactam antimicrobials combination needs to be given attention in clinical practice.

Objective: To explore the molecular mechanism by which protein tyrosine phosphatase 1B (PTP1B) enzyme regulates insulin resistance (IR) in diabetes mellitus, and the regulation of isoquercitrin (IS) on PTP1B in vitro and in vivo.

Methods: In vitro, PTP1B overexpression plasmid was constructed and transiently transfected into human hepatocellular liver carcinoma (HepG2) cells. A co-inducer was prepared by mixing a 0.125 mmol/L palmitic acid solution with a 1.0 × 10^-7 mol/L insulin solution to induce IR cell mode. Glucose oxidase assay, quantitative real-time-polymerase chain reaction (qRT-PCR), and Western blot were used to detect the effects of 40 µmol/L IS on glucose uptake and mRNA and protein expressions of related factors on the insulin receptor substrate (IRS)/phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signal pathway in the PTP1B overexpressed IR cell model, respectively. In vivo, PTP1B overexpression adeno-associated virus (Aav-PTP1B) was constructed and injected into the tail vein of mice (200 µ L/piece). The metabolic indicators of mice were measured after 14-d intragastric administration of IS (40 mg/kg). The pancreas tissue was excised to observe the morphology via hematoxylin-eosin staining. Additionally, qRT-PCR and Western blot assays were performed on the liver tissue of mice to determine the expressions of related factors on the IRS/PI3K/AKT signal pathway of db/db and wild type mice after the intervention of IS on Aav-PTP1B.

Results: In both in vivo and in vitro experiments, IS significantly improved IR, reduced levels of blood glucose, total cholesterol, triglycerides, and other metabolic indicators in mice, effectively controlled body weight, and restored pancreatic cell morphology (P<0.05 or P<0.01). At the genomic level, IS improved the expressions of related factors in the IRS/PI3K/AKT signaling pathway by regulating the expression of PTP1B (P<0.05 or P<0.01), thereby maintaining the homeostasis of the pathway.

Conclusion: IS can improve IR by inhibiting the IRS/PI3K/AKT signaling pathway through PTP1B intervention.

Objective: To investigate the effect and safety of phytosomal curcumin supplementation on patients with migraine.

Methods: In this randomized, double-blind and placebo-controlled trial, 70 patients suffered from migraine without aura were randomized into 2 groups to receive 250 mg/d of phytosomal curcumin (intervention group) or maltodextrin (placebo group) for 8 weeks, 35 cases per group. All patients in both groups received their standard treatment and common medications. The severity, duration, frequency of headaches, quality of life (QoL), mental status, headache impact, and sleep quality of patients were assessed before and after treatment. Adverse effects were also assessed.

Results: Sixty-five patients completed the trial (33 in the intervention group and 32 in the placebo group). Phytosomal curcumin supplementation significantly reduced severity, duration and frequency of migraine attacks, stress score, and headache impact, and improved QoL and sleep quality of patients in the intervention group, compared with the placebo group (P<0.05 or P<0.01). However, it had no significant effect on depression and anxiety scores in the intervention group, compared with the placebo group (P>0.05). No adverse effects had been reported in response to the intervention.

Conclusion: Phytosomal curcumin as a safe supplement had a beneficial effect on migraine symptoms, stress level, as well as the sleep quality and QoL in patients with migraine. (Trial registration No. IRCT20201129049534N2).