Effect of dendrobium mixture in alleviating diabetic cognitive impairment associated with regulating gut microbiota

Zheng, Yanfang; Zhou, Xian; Wang, Chenxiang; Zhang, Jialin; Chang, Dennis Hsu-Tung; Zhuang, Shuting; Xu, Wen; Chen, Yong; Wang, Xiaoning; Nan, Lihong; Sun, Yibin; Lin, Xiaohui; Lin, Wei; He, Caigu; Lian, Dai; Zhang, Jieping; Chen, Jianyu; Shi, Hong; Huang, Mingqing

doi:10.1016/j.biopha.2022.112891

Cited by 25 publications

(18 citation statements)

References 44 publications

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“…This difference may be due to variation in the geographical background, dietary habits, and age of subjects. The latest study found for the first time that Dendrobium mixture could regulate phyla of Firmicutes and Bacteroidetes to restore cognitive and memory function in DCI mice (27). Consistent with the present study, previous studies indicated that Actinobacteria was elevated at the class level in T2DM patients with cognitive impairment (15).…”

Section: Discussionsupporting

confidence: 91%

“…In addition, T2DM could cause microglial activation and subsequent production of pro-inflammatory cytokines in db/db mice (14). Dendrobium mixture has been shown to improve the cognitive and memory function by restoring the homoeostasis of gut microbiota in DCI mice attributed to its anti-inflammatory activities (27). However, anti-inflammatory medicines failed to be used in clinical studies, and the underlying mechanism remained unclear (28).…”

Section: Introductionmentioning

confidence: 99%

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Association of gut microbiota with sort-chain fatty acids and inflammatory cytokines in diabetic patients with cognitive impairment: A cross-sectional, non-controlled study

et al. 2022

Front. Nutr.

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Emerging evidence suggests that gut microbiota, short-chain fatty acids (SCFAs), and inflammatory cytokines play important roles in the pathogenesis of diabetic cognitive impairment (DCI). However, little is known about alterations of gut microbiota and SCFA levels as well as the relationships between inflammatory cytokines and cognitive function in Chinese DCI patients. Herein, the differences in the gut microbiota, plasma SCFAs, and inflammatory cytokines in DCI patients and type 2 diabetes mellitus (T2DM) patients were explored. A cross-sectional study of 30 DCI patients and 30 T2DM patients without mild cognitive impairment (MCI) was conducted in Tianjin city, China. The gut microbiota, plasma SCFAs, and inflammatory cytokines were determined using 16S ribosomal RNA (rRNA) gene sequencing, gas chromatography-mass spectrometry (GC-MS), and Luminex immunofluorescence assays, respectively. In addition, the correlation between gut microbiota and DCI clinical characteristics, SCFAs, and inflammatory cytokines was investigated. According to the results, at the genus level, DCI patients presented a greater abundance of Gemmiger, Bacteroides, Roseburia, Prevotella, and Bifidobacterium and a poorer abundance of Escherichia and Akkermansia than T2DM patients. The plasma concentrations of acetic acid, propionic acid, isobutyric acid, and butyric acid plummeted in DCI patients compared to those in T2DM patients. TNF-α and IL-8 concentrations in plasma were significantly higher in DCI patients than in T2DM patients. Moreover, the concentrations of acetic acid, propionic acid, butyric acid, and isovaleric acid in plasma were negatively correlated with TNF-α, while those of acetic acid and butyric acid were negatively correlated with IL-8. Furthermore, the abundance of the genus Alloprevotella was negatively correlated with butyric acid, while that of Holdemanella was negatively correlated with propanoic acid and isobutyric acid. Fusobacterium abundance was negatively correlated with propanoic acid. Clostridium XlVb abundance was negatively correlated with TNF-α, while Shuttleworthia abundance was positively correlated with TNF-α. It was demonstrated that the gut microbiota alterations were accompanied by a change in SCFAs and inflammatory cytokines in DCI in Chinese patients, potentially causing DCI development. These findings might help to identify more effective microbiota-based therapies for DCI in the future.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Association of gut microbiota with sort-chain fatty acids and inflammatory cytokines in diabetic patients with cognitive impairment: A cross-sectional, non-controlled study

et al. 2022

Front. Nutr.

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“…Apart from the upregulated steroids, 5,6-epoxy-8,11,14-eicosatrienoic acids (5, 6-EET) are tightly related to arachidonic acid metabolism and isovaleric acid, which is associated with cognitive impairment and systemic inflammation ( Zheng et al, 2022 ), and were decreased in the SAE-grouped hippocampus ( Table 1 and Figure 3C ). This result indicated that their anti-inflammatory effects were blocked, which might cause further cognitive impairment in the hippocampus during the progression of SAE ( Dalli et al, 2017 ; Wang et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Integrated transcriptomics and metabolomics analysis of the hippocampus reveals altered neuroinflammation, downregulated metabolism and synapse in sepsis-associated encephalopathy

Zhang

et al. 2022

Front. Pharmacol.

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Sepsis-associated encephalopathy (SAE) is an intricated complication of sepsis that brings abnormal emotional and memory dysfunction and increases patients’ mortality. Patients’ alterations and abnormal function seen in SAE occur in the hippocampus, the primary brain region responsible for memory and emotional control, but the underlying pathophysiological mechanisms remain unclear. In the current study, we employed an integrative analysis combining the RNA-seq-based transcriptomics and liquid chromatography/mass spectrometry (LC-MS)-based metabolomics to comprehensively obtain the enriched genes and metabolites and their core network pathways in the endotoxin (LPS)-injected SAE mice model. As a result, SAE mice exhibited behavioral changes, and their hippocampus showed upregulated inflammatory cytokines and morphological alterations. The omics analysis identified 81 differentially expressed metabolites (variable importance in projection [VIP] > 1 and p < 0.05) and 1747 differentially expressed genes (Foldchange >2 and p < 0.05) were detected in SAE-grouped hippocampus. Moreover, 31 compounds and 100 potential target genes were employed for the Kyoto Encyclopedia of Genes and Genomes (KEGG) Markup Language (KGML) network analysis to explore the core signaling pathways for the progression of SAE. The integrative pathway analysis showed that various dysregulated metabolism pathways, including lipids metabolism, amino acids, glucose and nucleotides, inflammation-related pathways, and deregulated synapses, were tightly associated with hippocampus dysfunction at early SAE. These findings provide a landscape for understanding the pathophysiological mechanisms of the hippocampus in the progression of SAE and pave the way to identify therapeutic targets in future studies.

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“…), etc. ( Chen et al, 2021 ; Wang et al, 2022 ; Zheng et al, 2022 ). Our works here already showed that DM can be advantageous in reducing IR, improving disorders of glucolipid metabolism, anti-oxidation damage, reducing inflammation, and gradually improving diabetic liver and kidney function ( Lin et al, 2018 ; Chen et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Dendrobium mixture ameliorates type 2 diabetes mellitus with non-alcoholic fatty liver disease through PPAR gamma: An integrated study of bioinformatics analysis and experimental verification

et al. 2023

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Dendrobium mixture (DM) is a patented Chinese herbal medicine indicated which has anti-inflammatory and improved glycolipid metabolism. However, its active ingredients, targets of action, and potential mechanisms are still uncertain. Here, we investigate the role of DM as a prospective modulator of protection against non-alcoholic fatty liver disease (NAFLD) induced by type 2 diabetes mellitus (T2DM) and illustrate the molecular mechanisms potentially involved. The network pharmacology and TMT-based quantitative protomics analysis were conducted to identify potential gene targets of the active ingredients in DM against NAFLD and T2DM. DM was administered to the mice of DM group for 4 weeks, and db/m mice (control group) and db/db mice (model group) were gavaged by normal saline. DM was also given to Sprague-Dawley (SD) rats, and the serum was subjected to the palmitic acid-induced HepG2 cells with abnormal lipid metabolism. The mechanism of DM protection against T2DM-NAFLD is to improve liver function and pathological morphology by promoting peroxisome proliferator-activated receptor γ (PPARγ) activation, lowering blood glucose, improving insulin resistance (IR), and reducing inflammatory factors. In db/db mice, DM reduced RBG, body weight, and serum lipids levels, and significantly alleviated histological damage of liver steatosis and inflammation. It upregulated the PPARγ corresponding to the prediction from the bioinformatics analysis. DM significantly reduced inflammation by activating PPARγ in both db/db mice and palmitic acid-induced HepG2 cells.

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Effect of dendrobium mixture in alleviating diabetic cognitive impairment associated with regulating gut microbiota

Cited by 25 publications

References 44 publications

Association of gut microbiota with sort-chain fatty acids and inflammatory cytokines in diabetic patients with cognitive impairment: A cross-sectional, non-controlled study

Association of gut microbiota with sort-chain fatty acids and inflammatory cytokines in diabetic patients with cognitive impairment: A cross-sectional, non-controlled study

Integrated transcriptomics and metabolomics analysis of the hippocampus reveals altered neuroinflammation, downregulated metabolism and synapse in sepsis-associated encephalopathy

Dendrobium mixture ameliorates type 2 diabetes mellitus with non-alcoholic fatty liver disease through PPAR gamma: An integrated study of bioinformatics analysis and experimental verification

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