The disorder of intestinal flora leads to the decline of anti-inflammatory reaction ability in the intestinal tract, low levels of SCFAs reduced the activation of GPR41 and GPR43, cause the ...occurrence of intestinal inflammation, insulin resistance, and as a result, lead to the occurrence of T2DM.
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•Intestinal flora disorders, such as the reduction of beneficial bacteria and the increase of harmful bacteria, are prone to occur in patients with type 2 diabetes mellitus.•The mechanisms of type 2 diabetes induced by intestinal flora imbalance include short-chain fatty acid theory, fatty acid theory, and endotoxin theory, etc.•Treatments based on the regulation of intestinal flora, such as fecal bacteria transplantation, regulating probiotics and content of intestinal SCFAs, may have a role in the prevention and treatment of type 2 diabetes.
Type 2 diabetes mellitus (T2DM) is a common clinical chronic disease, while its pathogenesis is still inconclusive. Intestinal flora, the largest micro-ecological system in the human body, is involved in, meanwhile has a major impact on the body's material and energy metabolism. Recent studies have shown that in addition to obesity, genetics, and islet dysfunction, the disturbance of intestinal flora may partly give rise to diabetes. In this paper, we summarized the current research on the correlation between T2DM and intestinal flora, and concluded the pathological mechanisms of intestinal flora involved in T2DM. Moreover, the ideas and methods of prevention and treatment of T2DM based on intestinal flora were proposed, providing theoretical basis and literature reference for the treatment of T2DM and its complications based on the regulation of intestinal flora.
Some biochemical index changes in diabetics with kidney Yin deficiency, which are related to amino acid metabolism, energy metabolism and the changes of intestinal flora.
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•Combining ...the advantages of Chinese and modern medicine may lead to a deeper exploration and diagnosis of diabetes.•Syndromes can reveal the essence of the diabetes in a more comprehensive way, different syndromes have disparate metabolic characteristics, corresponding to disparate biomarkers.•Modern research methods are applied to analyze the main Traditional Chinese Medicine syndromes of diabetes from clinical and basic aspects.•Biomarkers of syndrome classification are intended to be searched according to its symptoms and biochemical indicators.
With the improvement of people's living standard and the changes of environment, the incidence of diabetes mellitus (DM) is on the rise day by day, while clinical treatment mainly aims at lowering blood glucose, instead of fundamental prevention and treatment. What's worse, the measures of prevention and treatment of DM complications remain inadequate. Both Chinese and modern medicine have advantages and disadvantages in treating DM, therefore, it would be a worthy attempt to break through the bottleneck of DM treatment by combining the advantages of both, and explore the new measures to prevent and deal with DM from the perspective of the combination of Traditional Chinese Medicine (TCM) syndrome and modern medicine. In this paper, modern research methods and possible indicators of TCM syndromes of DM were expounded from clinical and basic research aspects, aiming to find specific biomarkers of TCM syndromes, and providing experimental supports for the diagnosis and treatment of DM and the verification of TCM theory.
In this study, LEfSe multilevel species hierarchical tree directly reflects the differences of gut microbiota between control and T1DM rats at the Phylum-to-Family level, the result showed that the ...gut microbiome of T1DM rats changed significantly. The abundance of pathogenic bacteria associated with infection and inflammation in T1DM rats was up-regulated such as Ruminococcaceae, Shigella, Enterococcus, Streptococcus, Rothia and Alistipes, while the abundance of beneficial bacteria and bacteria producing SCFAs were reduced such as Lactobacillus, Faecalitalea, Butyricicoccus and Allobaculum.
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•The incidence of type 1 diabetes is increasing year by year, some studies have pointed out that the development of type 1 diabetes is closely related to intestinal flora.•We investigate the changes of gut microbiome in type 1 diabetic mellitus rats based on high-throughput sequencing.•The result showed that the gut microbiome of type 1 diabetes rats changed significantly.•The abundance of pathogenic bacteria associated with infection and inflammation in type 1 diabetes rats was up-regulated, while beneficial bacteria were reduced.•The results indicate that dysbacteria cause to the intestinal inflammation and others, which plays an important role in the pathogenesis of type 1 diabetes.
The incidence of type 1 diabetes mellitus (T1DM) is increasing year by year, gut microbiota is considered to be closely related to the occurrence and development of T1DM in recent years. In this study, Sprague Dawley (SD) rats were intraperitoneally injected with 75mg/kg streptozotocin to establish T1DM model, fecal samples were collected and DNA were extracted, 16S rRNA microbial gene clone library were constructed, and lastly high-throughput sequencing and bioinformatics analysis were performed. The results showed that the abundances of pathogenic bacteria such as Ruminococcaceae, Shigella, Enterococcus, Streptococcus, Rothia and Alistipes associated with infection and inflammation in T1DM rats were up-regulated, while the abundances of beneficial bacteria such as Lactobacillus, Faecalitalea, Butyricicoccus and Allobaculum were reduced. Among them, Butyricicoccus and Allobaculum protect intestinal barrier function by producing short-chain fatty acids. This study suggests that intestinal inflammation and reduction of short chain fatty acids (SCFAs) caused by the imbalance of gut microbiota are crucial to the pathogenesis of T1DM.
Mammalian adipose tissue can be divided into two major types, namely, white adipose tissue (WAT) and brown adipose tissue (BAT). According to classical view, the main function of WAT is to store ...excess energy in the form of triglycerides, while BAT is a thermogenic tissue that acts a pivotal part in maintaining the core body temperature. White adipocytes display high plasticity and can transdifferentiate into beige adipocytes which have many similar morphological and functional properties with brown adipocytes under the stimulations of exercise, cold exposure and other factors. This phenomenon is also known as 'browning of WAT'. In addition to transdifferentiation, beige adipocytes can also come from de novo differentiation from tissue-resident progenitors. Activating BAT and inducing browning of WAT can accelerate the intake of glycolipids and reduce the insulin secretion requirement, which may be a new strategy to improve glycolipids metabolism and insulin resistance of obese and type 2 diabetes mellitus (T2DM) patients. This review mainly discusses the significance of brown and beige adipose tissues in the treatment of obesity and T2DM, and focuses on the effect of the browning agent on obesity and T2DM, which provides a brand-new theoretical reference for the prevention and treatment of obesity and T2DM.
Acute lung injury (ALI) is characterized by dysfunction of the alveolar epithelial membrane caused by acute inflammation and tissue injury. Qingwenzhike (QWZK) prescription has been demonstrated to ...be effective against respiratory viral infections in clinical practices, including coronavirus disease 2019 (COVID-19) infection. So far, the chemical compositions, protective effects on ALI, and possible anti-inflammatory mechanisms remain unknown.
In this study, the compositions of QWZK were determined
the linear ion trap/electrostatic field orbital trap tandem high-resolution mass spectrometry (UHPLC-LTQ-Orbitrap MS). To test the protective effects of QWZK on ALI, an ALI model induced by lipopolysaccharide (LPS) in rats was used. The effects of QWZK on the LPS-induced ALI were evaluated by pathological changes and the number and classification of white blood cell (WBC) in bronchoalveolar lavage fluid (BALF). To investigate the possible underlying mechanisms, the contents of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein (MCP-1), interleukin-1β (IL-1β), interleukin-18 (IL-18), and immunoregulatory-related factors interferon-γ (IFN-γ) were detected by ELISA. Furthermore, the expression of Toll-like receptor 4 (TLR4), p-IKKα/β, IKKα, IKKβ, p-IκBα, IκBα, p-NF-κB, nuclear factor-κB (NF-κB), NOD-like receptor family pyrin domain containing 3 (NLRP3), cleaved caspase-1, pro-caspase-1, apoptosis-associated speck-like protein containing CARD (ASC), and β-actin were tested by Western blot.
A total of 99 compounds were identified in QWZK, including 33 flavonoids, 23 phenolic acids, 3 alkaloids, 3 coumarins, 20 triterpenoids, 5 anthraquinones, and 12 others. ALI rats induced by LPS exhibited significant increase in neutrophile, significant decrease in lymphocyte, and evidently thicker alveolar wall than control animals. QWZK reversed the changes in WBC count and alveolar wall to normal level on the model of ALI induced by LPS. ELISA results revealed that QWZK significantly reduced the overexpression of proinflammatory factors IL-6, TNF-α, MCP-1, IL-1β, IL-18, and IFN-γ induced by LPS. Western blot results demonstrated that QWZK significantly downregulated the overexpression of TLR4, p-IKKα/β, p-IκBα, p-NF-κB, NLRP3, cleaved caspase-1, and ASC induced by LPS, which suggested that QWZK inhibited TLR4/NF-κB signaling pathway and NLRP3 inflammasomes.
The chemical compositions of QWZK were first identified. It was demonstrated that QWZK showed protective effects on ALI induced by LPS. The possible underlying mechanisms of QWZK on ALI induced by LPS was
inhibiting TLR4/NF-kB signaling pathway and NLRP3 inflammasome activation. This work suggested that QWZK is a potential therapeutic candidate for the treatments of ALI and pulmonary inflammation.
With the improvement of living standards and a change in lifestyle, the incidence of type 2 diabetes mellitus (T2DM) is increasing. Its etiology is too complex to be completely understand yet. ...Metabonomics techniques are used to study the changes of metabolites and metabolic pathways before and after the onset of diabetes and make it more possible to further understand the pathogenesis of T2DM and improve its prediction, early diagnosis, and treatment. In this review, we summarized the metabonomics study of T2DM in recent years and provided a theoretical basis for the study of pathogenesis and the effective prevention and treatment of T2DM.
The objective of this study is to analyze the differential protein expression profile in cerebral cortex of rats with middle cerebral ischemia/reperfusion (MCAO/R), explore the brain damage mechanism ...of MCAO/R at protein level, and provide experimental foundation for searching specific marker proteins of MCAO/R. Rat model of MCAO/R was established by modified suture-occluded method, and the model was evaluated by the results of brain 2,3,5-triphenyltetrazolium chloride (TTC) and hematoxylin–eosin (HE) staining. Cerebral cortex of rats from sham-operated group (Sham) and MCAO/R groups was used for FASP enzymatic hydrolysis, i-TRAQ quantitative labeling, and reverse-phase liquid chromatography purification and separation. Orbitrap Q Exactive mass spectrometry was used for qualitative and quantitative analyses of total differential protein expression profiles. MCAO/R rats had obvious cerebral infarction lesions, and the relative surface area of cerebral infarction was significantly different compared with sham rats, suggesting that MCAO/R rat model was successfully prepared. There were 199 significant difference proteins (MCAO/R vs Sham,
p
< 0.05, |fold change|> 1.2), including 104 up-regulated proteins and 95 down-regulated proteins. Gene ontology (GO) enrichment analysis showed that the up-regulated proteins were mainly concentrated in the biological processes of positive regulation of NF-κB transcription and I-κB kinase-NF-κB, etc. Down-regulated proteins were mainly concentrated in long-term synaptic potentiation, cellular response to DNA damage stimulus, etc. KEGG pathway analysis showed that the pathway involved in differential proteins includes oxidative phosphorylation, metabolic pathway, and Ras signaling pathway. Network analysis of differential proteins showed that Alb, ndufb5, ndufs7, ApoB, Cdc42, Ndufa3, Igf1r, P4hb, Mbp, Gc, Nme1, Akt2, and other proteins may play an important role in regulating oxidative stress, apoptosis, and inflammatory response in MCAO/R. Quantitative proteomics based on i-TRAQ labeling reveals the effect of inflammation and apoptosis in brain damage mechanism of MCAO/R. Besides, this research provide some experimental foundation for search and determination of potential therapeutic targets of MCAO/R.
Epimedii Folium is widely used worldwide as an herbal supplement, and the risk of its induced liver damage has emerged in recent years. Our preliminary study has found that, among several Epimedii ...Folium species specified in the Chinese Pharmacopoeia,
Epimedium koreanum
Nakai has a more severe propensity for hepatotoxicity. However, the mechanism of hepatotoxicity of
Epimedium koreanum
Nakai is still unclear. In this study, untargeted metabolomics was performed to analyze the serum and liver tissue to explore the mechanism of hepatotoxicity of
Epimedium koreanum
Nakai. The results of experiments
in vivo
showed that, after 28 days of exposure to
Epimedium koreanum
Nakai ethanol extract (EEE), the liver weight, levels of AST, ALP, TBIL, etc. in serum of rats in the EEE group were significantly increased, as well as severe cytoplasmic vacuolation appeared in the liver tissue, which suggested that EEE has significant hepatotoxicity. Subsequently, the results of metabolomics revealed significant changes in the metabolic profile in the liver and serum of rats after EEE exposure, in which metabolites in serum such as flavin mononucleotide, phenylacetylglycine, glutathione,
l
-tryptophan, and sphingomyelin were able to accurately identify liver injury caused by EEE and could be used as serum markers to reflect EEE-induced liver injury. The KEGG pathway enrichment analysis revealed that EEE caused extensive effects on rats' metabolic pathways. Some of the most affected pathways included glutathione metabolism, glutamate metabolism pathway, primary bile acid biosynthesis pathway, and sphingolipid metabolism pathway, which were all directed to the biological process of ferroptosis. Then, the main markers related to ferroptosis in the liver were examined, and the results demonstrated that the content of malondialdehyde was significantly increased, the activity of superoxide dismutase was significantly reduced, the ferroptosis inhibitory proteins GPX4 and System x
c
−
were significantly downregulated, and the ferroptosis-promoting protein ACSL4 was significantly up-regulated. Judging from these results, we concluded that the mechanism of hepatotoxicity of
Epimedium koreanum
Nakai was probably related to the induction of ferroptosis in hepatocytes.
Background:
Type 2 diabetes (T2D) is considered as one of the most significant metabolic syndromes worldwide, and the long-term use of the drugs already on the market for T2D often gives rise to some ...side effects. The mulberry leaf (ML),
Morus alba L.
, has advantages in terms of its comprehensive therapeutic efficacy, which are characterized as multicomponent, multitarget, multipathway, and matching with the complex pathological mechanisms of diabetes.
Methods:
T2D rats were established by a high-fat diet combined with an intraperitoneal injection of streptozotocin; an evaluation of the hypoglycemic effects of the ML in combination with fasting blood glucose and other indicators, in addition to the utilization of metabolomics technology, was performed to analysis the metabolite changes in serum of rats.
Results:
MLs significantly reduced the fasting blood glucose of T2D rats, while improving the symptoms of polyphagia and polyuria. ML treatment altered the levels of various metabolites in the serum of T2D rats, which are involved in multiple metabolic pathways (amino acid metabolism, carbohydrate metabolism, and lipid metabolism), played a role in antioxidative stress and anti-inflammation, modulated immune and gluconeogenesis processes, and improved obesity as well as insulin resistance (IR).
Conclusion:
The ML contains a variety of chemical components, and metabolomic results have shown that MLs regulate multiple metabolic pathways to exert hypoglycemic effects, suggesting that MLs may have great promise in the development of new hypoglycemic drugs.
Kudiezi injection (KDZI), also known as Diemailing injection, is a traditional Chinese medicine injection of the composite plant
Hance (also known as Kudiezi), and has been widely used to treat ...coronary heart disease, angina pectoris, and cerebral infarction, but its pharmacological mechanisms remain unclear. This study is designed to explore the effects of KDZI on middle cerebral artery occlusion and reperfusion (MCAO/R) rats, and to identify metabolic features of cerebral ischemia reperfusion by using a nontargeted metabolic profiling method based on ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). In this process, 32 potential biomarkers were found in plasma. KDZI significantly upregulated the levels of taurochenodesoxycholic acid, leucine, l-phenylalanine, l-tryptophan, arachidonic acid (ARA), and phosphatidyl ethanolamines (PE), phosphatidyl cholines (PC) and downregulated the levels of l-valine and 5-hydroxyindole-3-acetic acid (5-HIAA) in plasma. The results indicated that the mechanisms of KDZI on MCAO/R were related to the mechanisms of amino acid and lipid metabolism.
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