Ying Yang, Wentao Shao, Huiyun Shu, Ping Wang, Yi Tao
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High-fat diet (HFD)–induced obese C57BL/6J mice were established and then administered with the nine combinations of CAVA-G extracts for 6 weeks. The trajectory of mice's body weights was analyzed. Besides, hematoxylin and eosin (HE) staining of the liver and oil red O staining of adipose tissue were performed. ELISA assay was employed to measure serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Moreover, serum metabolic profiling was conducted through UPLC-Q-TOF/MS analysis. Gut microbiota analysis was performed via 16S rRNA gene sequencing. Pattern recognition and Pearson correlation analysis were used to pinpoint the key endogenous metabolites and microbiota. Two groups of CAVA-G combination treatment (C3 and A1) significantly prevented the increase of weight in mice. According to our analysis, the best anti-obesity effect was achieved when the ratio between CAVA and ginger was 37:63. The levels of TC and LDL-C were dramatically decreased in the C3 group, whereas the level of TG was significantly reduced in the A1 group. Interestingly, HDL-C level was increased dramatically in the C3 group. Compared with the model group, a total of 16 and 25 biomarkers were identified for groups C3 and A1, respectively. These biomarkers are mainly implicated in lipid metabolism and primary bile acid biosynthesis. Interestingly, the abnormal diversity of gut microbiota was induced by HFD feeding. Treatment with C3 or A1 significantly increased the relative abundance of <i>Akkermansia</i> and <i>Novosphingobium</i>, while reducing the relative abundance of <i>Dorea</i>, <i>Bacteroides</i> and <i>Roseburia</i>. Of note, this is the first report that <i>Novosphingobium</i> is involved in preventing obesity. 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However, the combinatorial use of the two plants on obesity remains elusive. Our endeavor aimed to identify the optimal synergistic ratio between CAVA and ginger and to explore the underlying mechanism of their anti-obesity effects. Aqueous CAVA and ginger extracts were prepared separately and then combined into nine different ratios. The constituents of CAVA and ginger were unambiguously characterized by employing LC–MS. High-fat diet (HFD)–induced obese C57BL/6J mice were established and then administered with the nine combinations of CAVA-G extracts for 6 weeks. The trajectory of mice's body weights was analyzed. Besides, hematoxylin and eosin (HE) staining of the liver and oil red O staining of adipose tissue were performed. ELISA assay was employed to measure serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Moreover, serum metabolic profiling was conducted through UPLC-Q-TOF/MS analysis. Gut microbiota analysis was performed via 16S rRNA gene sequencing. Pattern recognition and Pearson correlation analysis were used to pinpoint the key endogenous metabolites and microbiota. Two groups of CAVA-G combination treatment (C3 and A1) significantly prevented the increase of weight in mice. According to our analysis, the best anti-obesity effect was achieved when the ratio between CAVA and ginger was 37:63. The levels of TC and LDL-C were dramatically decreased in the C3 group, whereas the level of TG was significantly reduced in the A1 group. Interestingly, HDL-C level was increased dramatically in the C3 group. Compared with the model group, a total of 16 and 25 biomarkers were identified for groups C3 and A1, respectively. These biomarkers are mainly implicated in lipid metabolism and primary bile acid biosynthesis. 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引用次数: 0
摘要
柑橘aurantium L. var. amara (CAVA)的花和生姜(Zingiber officinale Roscoe)的根茎都是食品和药用同源植物,在中国被用于辅助胃消化和预防肥胖。然而,联合使用这两种植物治疗肥胖仍然难以捉摸。我们的目的是确定CAVA与生姜的最佳协同比例,并探讨其抗肥胖作用的潜在机制。分别制备CAVA和姜提取物,并将其按9种不同的比例组合。采用LC-MS对CAVA和姜的成分进行了明确的表征。建立高脂饮食(HFD)诱导的肥胖小鼠C57BL/6J,然后给予9种CAVA-G提取物组合6周。分析小鼠的体重变化轨迹。肝脏苏木精和伊红(HE)染色,脂肪组织油红O染色。采用ELISA法测定血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平。通过UPLC-Q-TOF/MS分析进行血清代谢谱分析。通过16S rRNA基因测序进行肠道菌群分析。使用模式识别和Pearson相关分析来确定关键的内源性代谢物和微生物群。两组CAVA-G联合治疗(C3和A1)均能显著抑制小鼠体重增加。根据我们的分析,当CAVA与生姜的比例为37:63时,抗肥胖效果最好。C3组TC和LDL-C水平显著降低,而A1组TG水平显著降低。有趣的是,C3组的HDL-C水平显著升高。与模型组比较,C3组和A1组分别鉴定出16种和25种生物标志物。这些生物标志物主要与脂质代谢和初级胆汁酸生物合成有关。有趣的是,HFD喂养引起了肠道微生物群多样性的异常。C3或A1处理显著提高了Akkermansia和Novosphingobium的相对丰度,降低了Dorea、Bacteroides和Roseburia的相对丰度。值得注意的是,这是Novosphingobium参与预防肥胖的第一份报告。这些发现将为使用CAVA-G预防肥胖奠定基础。
Multiomics Analyses of Citrus aurantium L. Var. Amara and Ginger Reveals Lipid Metabolism, Bile Acid Biosynthesis, and Gut Microbiome Rebalance Supporting Their Anti-Obesity Effects
Both the flower of Citrus aurantium L. var. amara (CAVA) and rhizome of Zingiber officinale Roscoe (ginger) are food and medicinal homologous plants that have been used in China for aiding gastric digestion and preventing obesity. However, the combinatorial use of the two plants on obesity remains elusive. Our endeavor aimed to identify the optimal synergistic ratio between CAVA and ginger and to explore the underlying mechanism of their anti-obesity effects. Aqueous CAVA and ginger extracts were prepared separately and then combined into nine different ratios. The constituents of CAVA and ginger were unambiguously characterized by employing LC–MS. High-fat diet (HFD)–induced obese C57BL/6J mice were established and then administered with the nine combinations of CAVA-G extracts for 6 weeks. The trajectory of mice's body weights was analyzed. Besides, hematoxylin and eosin (HE) staining of the liver and oil red O staining of adipose tissue were performed. ELISA assay was employed to measure serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Moreover, serum metabolic profiling was conducted through UPLC-Q-TOF/MS analysis. Gut microbiota analysis was performed via 16S rRNA gene sequencing. Pattern recognition and Pearson correlation analysis were used to pinpoint the key endogenous metabolites and microbiota. Two groups of CAVA-G combination treatment (C3 and A1) significantly prevented the increase of weight in mice. According to our analysis, the best anti-obesity effect was achieved when the ratio between CAVA and ginger was 37:63. The levels of TC and LDL-C were dramatically decreased in the C3 group, whereas the level of TG was significantly reduced in the A1 group. Interestingly, HDL-C level was increased dramatically in the C3 group. Compared with the model group, a total of 16 and 25 biomarkers were identified for groups C3 and A1, respectively. These biomarkers are mainly implicated in lipid metabolism and primary bile acid biosynthesis. Interestingly, the abnormal diversity of gut microbiota was induced by HFD feeding. Treatment with C3 or A1 significantly increased the relative abundance of Akkermansia and Novosphingobium, while reducing the relative abundance of Dorea, Bacteroides and Roseburia. Of note, this is the first report that Novosphingobium is involved in preventing obesity. These findings will layer a foundation for the usage of CAVA-G for preventing obesity.
期刊介绍:
Biomedical Chromatography is devoted to the publication of original papers on the applications of chromatography and allied techniques in the biological and medical sciences. Research papers and review articles cover the methods and techniques relevant to the separation, identification and determination of substances in biochemistry, biotechnology, molecular biology, cell biology, clinical chemistry, pharmacology and related disciplines. These include the analysis of body fluids, cells and tissues, purification of biologically important compounds, pharmaco-kinetics and sequencing methods using HPLC, GC, HPLC-MS, TLC, paper chromatography, affinity chromatography, gel filtration, electrophoresis and related techniques.