Intermittent hypoxia is involved in gut microbial dysbiosis in type 2 diabetes mellitus and obstructive sleep apnea-hypopnea syndrome

BACKGROUND Obstructive sleep apnea(OSA)-hypopnea syndrome(OSAHS)has been recognized as a comorbidity of type 2 diabetes mellitus(T2DM);more than half of T2DM patients suffer from OSAHS.Intermittent hypoxia(IH)plays an important role in metabolic diseases,such as obesity and OSAHS,through various mechanisms,including altering the gut microecological composition and function.Therefore,it is important to study the role of gut microbiota in T2DM patients with OSAHS,which has a high incidence and is prone to several complications.AIM To assess whether IH is involved in altering the fecal microbiome in T2DM patients with OSAHS.METHODS Seventy-eight participants were enrolled from Henan Province People’s Hospital and divided into healthy control(HC,n=26),T2DM(n=25),and T2DM+OSA(n=27)groups based on their conditions.The fecal bacterial DNA of the research participants was extracted and subjected to 16S ribosomal RNA sequencing.The clinical indices,such as insulin resistance index,homocysteine(HCY)concentration,and the concentrations of inflammatory factors in the peripheral blood,were assessed and recorded.RESULTS Group T2DM+OSA had the highest apnea-hypopnea index(AHI)(2.3 vs 3.7 vs 13.7),oxygen desaturation index(0.65 vs 2.2 vs 9.1),HCY concentration(9.6μmol/L vs 10.3μmol/L vs 13.81μmol/L)and C-reactive protein(CRP)concentrations(0.3 mg/L vs 1.43 mg/L vs 2.11 mg/L),and lowest mean oxygen saturation(97.05%vs 96.6%vs 94.7%)among the three groups.Twelve and fifteen key differences in amplicon sequence variants were identified when comparing group T2DM+OSA with groups T2DM and HC,respectively.We found progressively decreased levels of Faecalibacterium,Eubacterium,and Lachnospiraceae,and an increase in the level of Actinomyces,which strongly correlated with the HCY,CRP,fasting plasma glucose,and hemoglobin A1c concentrations,AHI,mean oxygen saturation,and insulin resistance index in group T2DM+OSA(P<0.05).CONCLUSION For T2DM patients with OSAHS,IH may be involved in selective alterations of the gut microbiota,which may affect the pathophysiological development of T2DM and DM-related complications.

Therapeutic effects of herbal formula Huangqisan on metabolic disorders via SREBF1,SCD1 and AMPK signaling pathway

Objective:Metabolic syndrome is a complex medical condition that has become an alarming epidemic,but an effective therapy for this disease is still lacking.The use of the herbal formula Huangqisan(HQS)to treat diabetes is documented in the Chinese medical literature as early as 1117 A.D.;however,its therapeutic effects and underlying mechanisms remain elusive.Methods:To investigate the beneficial effects of HQS on metabolic disorders,high-fat diet-induced obesity(DIO),leptin receptor dysfunction(db/db)and low-density lipoprotein receptor-knockout(LDLR^(-/-))mice were used.Obese mice were treated with either HQS or vehicle.Blood,liver tissue,white fat tissue and brown adipose tissue were harvested at the end of the treatment.Metabolic disease-related parameters were evaluated to test effects of HQS against diabetes,obesity and hyperlipidemia.Aortic arches from LDLR^(-/-)mice were analyzed to investigate the effects of HQS on atherosclerosis.RNA-sequence,quantitative real-time polymerase chain reaction and Western blot were performed to investigate the mechanisms of HQS against metabolic disorder.Results:HQS lowered body weight,fasting blood glucose and serum lipid levels and improved glucose tolerance and insulin sensitivity in DIO mice and db/db mice(P<0.05).HQS also blocked atherosclerotic plaque formation in LDLR^(^(-/-)) mice.HQS suppressed de novo lipid synthesis by reducing the expression of messenger RNA for sterol regulatory element-binding factor 1,stearyl coenzyme A desaturase 1 and fatty acid synthase,and enhancing adenosine 5’-monophosphate-activated protein kinase signaling in both in vivo and in vitro experiments,indicating potential mechanisms for HQS’s activity against diabetes.Conclusion:HQS is effective for reversing metabolic disorder and has the potential to be used as therapy for metabolic syndrome.

Rapid Detection of Acetylbritannilactone from Inula britannica in Plasma of Rats by Online Sweeping-Micellar Electrokinetic Chromatography

Objective To establish a rapid method for detecting acetylbritannilactone （ABL） by online sweeping-micellar electrokinetic chromatography （MEKC） and to elevate the sensitivity of the detection. Methods The combination of online sweeping technique with MEKC was used to determine the content of ABL in the extract of Inula britannica in plasma of rats. Results ABL was completely separated within 15 min in running buffer and sample buffer. The optimal conditions were as follows： on uncoated fused quartz silica capillary, with separation voltage of 23 kV, capillary temperature of 25 oC, and detection wavelength of 195 nm. The regression equations revealed good linear relationships between the peak area and concentration of ABL （r = 0.998）, with the detection limits of 0.005-0.15 mg/mL. The relative standard deviations of migration time and peak areas for intra- and inter-batch were 〈 2.45% and 〈 2.26%, respectively. The recovery rate of this method was 96.3~97.2%. Conclusion This method provides some advantages in separation speed, testing sensitivity, and operating convenience, with low sample and reagent consumption. The online sweeping-MEKC is an effective method for pharmacokinetic study and analysis on tracing biological samples.

Spectrum-Toxicity Correlation Study Revealed the Influence of the Nine-Time Steaming and Sun Drying Method on Hepatotoxic Components of Polygoni Multiflori Radix

Objective:Polygoni Multiflori Radix(PM)is a traditional herbal medicine with repeated reports of liver injury events in recent years.We wondered whether the classical processing method,namely,nine-time steaming and sun drying(NSSD),had toxicity-attenuating effects on PM and the relationships between toxicity and times of processing,as well as with the alteration trends of its compounds.Materials and Methods:The chemical fingerprints of different PM extracts were developed using ultra-high-performance liquid chromatography.The spectrum-toxicity correlation between the chemical fingerprints and hepatocellular toxicity was analyzed with multiple correlation analysis.Results:The results suggested that the hepatotoxicity of NSSD processing products markedly decreased with the repeated steaming and sun drying,which was obviously superior to the product processed by the modern method.Comprehensive analysis revealed that the contents of cis-stilbene glycoside and emodin-8-O-β-D-glucoside related to liver injury susceptibility were reduced with the times of NSSD processing,which was consistent with the decreased trend of hepatocellular toxicity.After the five times of NSSD,the contents of them as well as the hepatotoxicity of PM were steady.Moreover,we found that the contents of catechin and physcion declined rapidly after the one time of NSSD and then remained stable until the nine times of NSSD.Based on the fact,they could be utilized to indicate whether PM products were processed by steaming and sun drying.Conclusions:This paper confirmed that the NSSD had a good influence on the toxicity attenuating to PM and found four compounds which could apply for the quality control of PM.