Journal of Advanced Research
·
2024
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IF 11.4
Han-Yan Luo,Jing Fang,Wei-Hao Zhang,Kam-Chun Chan,Yui-Man Chan,Cai-Xia Dong,Song-Lin Li,Ai-Ping Lyu,Jun Xu
Introduction Ginseng demonstrates therapeutic potential in treating obesity, with both experimental and clinical studies suggesting its anti-obesity effects are mediated by gut microbiota. Nonetheless, the specific chemical components responsible for this effect remain largely unidentified. Objectives This study aims to investigate the anti-obesity effects and mechanisms of ginseng polysaccharides (GP) and ginsenosides (GS), the primary chemical components of ginseng, with a focus on their impact on gut microbiota. Methods The impact of GP and GS on high-fat diet (HFD)-induced obesity was assessed using a mouse model. Molecular mechanisms were explored through a combination of chemical analysis, metagenomics, RT-qPCR, ELISA, and biochemical assays. Results GP or GS administration effectively prevented adiposity in HFD-fed mice, and both effects were mediated by gut microbiota. Chemical analysis revealed diverse glycosyl groups in GP and GS. Metagenomics data suggested that GP-enriched species, e.g., Bacteroides stercorirosoris and Clostridiales bacterium encoded carbohydrate-active enzymes GH35, GH43 and PL9_1, while GS-enriched Sulfurospirillum halorespirans encoded GH16_5. These enzymes facilitated the utilization of glycosyl groups in GP and GS, selectively stimulating bacterial growth and reshaping the gut microbiota. Furthermore, bacterial species enriched by GP or GS encoded specific functional genes involved in short-chain fatty acid (SCFA) synthesis (K00625 and K00925 for GP; K18118, K00100, and K18122 for GS) and intestinal gluconeogenesis (IGN) (K01678, K00024, and K01596 for GP; K18118 and K00278 for GS). Consequently, the SCFA-GLP-1/PYY signaling and IGN were activated by both GP and GS to ameliorate obesity phenotypes. Conclusion GP and GS, containing diverse glycosyl groups, selectively stimulate specific gut bacteria, triggering mechanisms involved in SCFA-GLP-1/PYY signaling and IGN activation to reduce adiposity in HFD-fed mice. The study enhances understanding of the chemical components crucial for the gut microbiota-mediated anti-obesity effect of ginseng. The mechanistic understanding provides valuable insights for developing ginseng-based drugs or health products to combat obesity.
研究领域:
营养学
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药理学
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微生物学
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分子生物学
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肥胖研究
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2016
·Vol. 37
·期 4
·889-900
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IF 2.348
Jieqiong He,Chao Wang,Yunpeng Sun,Bo Lu,Jinjin Cui,Nana Dong,Maomao Zhang,Youbing Liu,Bo Yu
Exendin-4 (ex-4) is a long-acting glucagon-like peptide-1 receptor (GLP-1R) agonist which exerts beneficial effects on glycemic control and promotes cell viability. In the present study, we investigated the anti-apoptotic effects of ex-4, as well as the potential mechanisms responsible for these effects in rat bone marrow-derived mesenchymal stem cells (BM-MSCs) under conditions of oxygen, glucose and serum deprivation (OGD). The apoptosis of the MSCs was induced by subjecting the cells to OGD conditions for 4 h and was detected by Annexin V/PI and Hoechst 33258 staining. The MSCs were pre-conditioned with ex-4 for 12 h prior to being subjected to OGD conditions, and the expression levels of an apoptotic marker (cleaved caspase-3), endoplasmic reticulum (ER) stress markers [phosphorylated (p-)protein kinase RNA-like endoplasmic reticulum kinase (PERK), PERK, binding immunoglobulin protein (BIP), activating transcription factor 4 (ATF-4) and C/EBP homologous protein (CHOP)], as well as those of a survival marker (Bcl-2) were measured by western blot analysis. Furthermore, the mRNA levels of ATF-4 and CHOP were determined by RT-qPCR. ELISA was used to examine the activity of intracellular cAMP. Moreover, the GLP-1R antagonist, exendin9-39 (ex9-39), the protein kinase A (PKA) inhibitor, H89, and small interfering RNA (siRNA) targeting rat ATF-4 and CHOP were co-incubated with the MSCs. The apoptotic rate was markedly diminished following pre-conditioning with ex-4 in a dose‑dependent manner (P<0.05). The ER stress markers, p-PERK, BIP, ATF-4 and CHOP, were upregulated in the cells subjected to OGD conditions. Ex-4 pre-conditioning significantly decreased the mRNA and protein levels of ATF-4 and CHOP (P<0.05), and increased the activity of intracellular cAMP (P<0.05). Furthermore, the anti-apoptotic effects of ex-4 were almost reversed by treatment with either H89 or ex9-39 (P<0.05); transfection with siRNA-CHOP significantly reduced the apoptotic rate of the MSCs and did not impair the cytoprotective effects of ex-4. Taken together, these findings suggest that ex-4 protects rat BM-MSCs from OGD-induced apoptosis through the activation of the PKA/cAMP pathway and the attenuation of the ER stress signaling pathway. Ex-4 may thus prove to be a therapeutic agent with the potential to improve the viability of MSCs in the ischemic milieu, and consequently, to optimize the therapeutic effects of MSC therapy in acute myocardial infarction.
研究领域:
干细胞生物学
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药理学
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细胞信号传导
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心血管疾病
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-17
·
IF 12.6
Li Li,Wang Wang,Li Rong,Guo Jiayue,Hu Xulin,Pan Yu,Zhang Taoyuan,Chi Sensen,Gu Zili,Zhu Gaohui,Liu Qi,Tan Shuai
Gut microbiota is increasingly recognized for its profound influence on host metabolism. However, the mechanisms underlying the distinct metabolic phenotype observed in germ-free (GF) mice are not fully understood. Here, the serum levels of metabolic hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) were shown with significant elevation in GF than the conventionally-raised (CONV-R) mice. Single-cell transcriptome analysis revealed that Secretogranin II ( Scg2 ), with a known function in secretion control, was exclusively expressed in enteroendocrine cells (EECs). Scg2 transcript levels were significantly up-regulated in GF mice, positively correlated with enhanced GLP-1 and peptide PYY secretion. To examine the functional significance of Scg2 in hormone regulation, cross-linked nanoparticles capable of long-term adhesion to intestinal epithelium were designed, with AAV adsorbed within the cross-linked structure. This innovative design enhances its stability and retention in vivo, providing a robust platform for continuous and efficient gene delivery. We evidenced that over-expression of Scg2 via AAV-loaded nanocarriers in the colons of mice on high-fat diet or with the ob/ob genotype not only enhanced the secretion of GLP-1 and PYY but also mitigated weight gain in these mice by reducing their appetite. A multi-omics analysis reveals that Scg2 overexpression in the colon decreased hypothalamic inflammation and activated tryptophan metabolic pathways. Collectively, our findings suggest a potential therapeutic approach for treating metabolic disorders by enhancing Scg2 expression in colonic EECs. Graphical
研究领域:
分子生物学
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遗传学
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生物化学
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药理学
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纳米技术
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微生物学
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内分泌学
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代谢组学
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神经科学
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产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2024
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IF 7
Jingyan Shi,Jianing Li,Wentao Su,Chang Xue,Yuan Zhang,Xinghua Gao
Recent advancements in the food industry have rekindled interest in the safety of food additives, such as sugar substitutes and food pigments. Consequently, the main purpose of this study was to develop models that can more accurately predict the effects of these additives on the human body. In response to this demand, we have created an innovative pancreas islet-on-a-chip system featuring a concentration gradient generator and a perfusable 3D cell culture array. This setup facilitates the 3D culture of pseudo-islets under stable biochemical and biophysical conditions. When compared to static culture environments, our dynamic environment maintains islet cell viability at over 95 %, resulting in larger cell clusters that exhibit a higher tendency for aggregation up to 30 μm. Furthermore, the expression levels of key factors integral to islet development, namely INS-1, INS-2, and PDX-1, increased by 4.5-fold, 1.9-fold, and 5.8-fold respectively in the dynamic environment. Utilizing this sophisticated pancreas islet-on-a-chip model, we discovered that the consumption of sugar substitutes like erythritol and sucralose for 1 h does not impact insulin secretion levels. In contrast, the administration of glucagon-like peptide 1 (GLP-1), GLP-1 receptor (GLP-1R) agonist exendin-4, curcumin, and a combination therapy group led to a substantial increase in insulin secretion levels (p < 0.01). Such engineered microenvironments and pancreatic islet-on-chips offer a groundbreaking platform for evaluating sugar substitutes and antidiabetic compounds.
研究领域:
生物医学工程
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药理学
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内分泌学
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细胞生物学
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药物发现
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
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2021
·Vol. 11
·期 60
·37952-37965
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IF 3.361
Jin-Bo Bai,Ji-Chun Ge,Wang-Juan Zhang,Wang Liu,Jian-Ping Luo,Feng-Qing Xu,De-Ling Wu,Song-Zi Xie
Polygonatum species, including P. cyrtonema, P. kingianum, and P. sibiricum, are edible plants with medicinal purposes, which have long been consumed as food due to their high nutritional value. In this study, polysaccharides from P. cyrtonema (PCP), P. kingianum (PKP) and P. sibiricum (PSP) were obtained, and their physicochemical properties and in vitro biological activities were investigated. Our results demonstrated that PCP, PKP, and PSP consist of major fructose and minor glucose, galacturonic acid, and galactose in different molar ratios with the molecular weights of 8.5 × 103 Da, 8.7 × 103 Da, and 1.0 × 104 Da, respectively. The three polysaccharides had triple-helical structures with β-D-Fruf, α-D-Glcp, α-D-Galp sugar residues, and an O-acetyl group, and displayed peak-shaped structures in different sizes. They also exhibited thermal, shear-thinning behavior and viscoelastic properties, and PCP presented the highest viscoelasticity. Moreover, they exerted strong free radical-scavenging abilities, and significant reducing capacity. PCP was the strongest, followed by PSP and then PKP. They significantly promoted the polarization of the M1 macrophage, with the effect of PCP ranking first. All three had similar effects on GLP-1 secretion. It is, therefore, necessary to identify the various roles of these three Polygonatum polysaccharides as functional agents based on their bioactivities and physicochemical properties.
研究领域:
药理学
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生物化学
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食品科学
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植物科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2024
·
IF 5.1
Sijia Zhu,Jiyu Yang,Pengkui Xia,Sha Li,Qi Wang,Kaikai Li,Bin Li,Jing Li
Konjac glucomannan (KGM) is a dietary fiber supplement that exhibits multiple biological activities, including weight control and regulation of glucose and lipid metabolism. Currently, KGM intake patterns in practical applications include KGM sol, thermal irreversible gel, and frozen thermal irreversible gel. In this study, four intake patterns of KGM, namely KGM sol (KS), deacetylated KGM (DK), KGM gel (KG) and frozen KGM gel (FKG), were used as materials to explore the effects of KGM intake patterns on glucose and lipid metabolism and intestinal flora of obese mice induced by high fat diet under the same dose. Results showed that any type of KGM intake could reduce body weight, fat mass, lipid levels, and insulin resistance in obese mice, as well as partially alleviating liver damage and inflammation caused by obesity. However, KS has the most significant effect on controlling blood glucose and blood lipid in obese mice. Additionally, it was found that KS, DK, KG and FKG can increase the α-diversity of intestinal microflora in high-fat mice, and improve the microflora disorder in high-fat mice. Finally, KS may increase the levels of fasting appetite hormones GLP-1 and PYY in mice, up-regulate the expression of LDLR, GCK and G-6-pase mRNA, and increase the production of short-chain fatty acids (SCFAs) in the intestinal flora of mice, thus regulating glucose and lipid metabolism . This study systematically investigated the effects of different intake forms of KGM on metabolism and intestinal flora in obese mice, which is of great significance for further understanding the role of KGM in the prevention and treatment of obesity metabolic diseases, and for developing targeted dietary interventions.
研究领域:
营养学
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代谢研究
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肥胖研究
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肠道微生物
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）