人参皂苷Rb<sub>1</sub>、小檗碱及其联合应用对肥胖小鼠肠道菌群的影响

叶紫梦玮; 徐冰蕊; 赵祎; 莫芳芳; 张毅; 方心; 华静; 隋芯; 高思华; 赵丹丹

doi:10.3969/j.issn.1006-2157.2023.11.009

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人参皂苷Rb₁、小檗碱及其联合应用对肥胖小鼠肠道菌群的影响

实验研究 | 更新时间：2023-12-08

- 人参皂苷Rb₁、小檗碱及其联合应用对肥胖小鼠肠道菌群的影响
- Effect of ginsenoside Rb₁, berberine, and their combination on intestinal flora in obese mice
- 北京中医药大学学报 2023年46卷第11期页码：1541-1553
- 作者机构：
  
  1.北京中医药大学中医学院糖尿病研究中心　北京　100029
  2.北京开放大学城市管理学院
  3.北京中医药大学第三附属医院
  4.北京中医药大学信息与教育技术中心
- 作者简介：
  
  叶紫梦玮，女，在读硕士生
  # 赵丹丹，女，博士，副研究员，硕士生导师，主要研究方向：脏腑相关理论防治糖尿病等代谢性疾病的基础与临床研究，E-mail：bucmzhaodandan@163.com
- 基金信息：
  
  国家自然科学基金项目(82174329);中医药传承与创新“百千万”人才工程（岐黄工程）岐黄学者项目(1040063321005)
- DOI：10.3969/j.issn.1006-2157.2023.11.009
  中图分类号： R285.5
- 收稿：2023-05-19，
  
  网络首发：2023-09-12，
  
  纸质出版：2023-11-30
- 稿件说明：
移动端阅览
叶紫梦玮, 徐冰蕊, 赵祎, 等. 人参皂苷Rb₁、小檗碱及其联合应用对肥胖小鼠肠道菌群的影响[J]. 北京中医药大学学报, 2023,46(11):1541-1553. DOI: 10.3969/j.issn.1006-2157.2023.11.009.

YE Zimengwei, XU Bingrui, ZHAO Yi, et al. Effect of ginsenoside Rb₁, berberine, and their combination on intestinal flora in obese mice[J]. Journal of Beijing University of Traditional Chinese Medicine, 2023, 46(11): 1541-1553. DOI: 10.3969/j.issn.1006-2157.2023.11.009.
叶紫梦玮, 徐冰蕊, 赵祎, 等. 人参皂苷Rb₁、小檗碱及其联合应用对肥胖小鼠肠道菌群的影响[J]. 北京中医药大学学报, 2023,46(11):1541-1553. DOI: 10.3969/j.issn.1006-2157.2023.11.009. DOI：

YE Zimengwei, XU Bingrui, ZHAO Yi, et al. Effect of ginsenoside Rb₁, berberine, and their combination on intestinal flora in obese mice[J]. Journal of Beijing University of Traditional Chinese Medicine, 2023, 46(11): 1541-1553. DOI: 10.3969/j.issn.1006-2157.2023.11.009. DOI：

摘要

目的

探讨人参皂苷Rb

、小檗碱及其联合应用对高脂饮食诱导肥胖小鼠肠道菌群的影响。

方法

42只SPF级雄性C57BL/6J小鼠高脂饲料喂养12周建立肥胖小鼠模型。将符合肥胖标准的32只肥胖小鼠任意分为4组：对照组、人参皂苷Rb

组(20 mg/kg)、小檗碱组(50 mg/kg)、人参皂苷Rb

＋小檗碱组(人参皂苷Rb

20 mg/kg ＋小檗碱50 mg/kg)，每组8只。连续灌胃给药8周，给药期间小鼠继续给予高脂饲料喂养。每周记录各组小鼠的体质量，每2周检测小鼠空腹血糖。实验结束后留取粪便，进行16 S rDNA测序，观察各组小鼠肠道菌群变化。

结果

与对照组比较，人参皂苷Rb

组、小檗碱组和人参皂苷Rb

＋小檗碱组第4～6周小鼠体质量降低，第4、6、8周小鼠空腹血糖降低(均

0.05)。人参皂苷Rb

组、小檗碱组和人参皂苷Rb

＋小檗碱组高脂饮食诱导的肠道生态失调均改善，拟杆菌门/厚壁菌门值增加，脱铁杆菌门、小螺菌属、螺杆菌属、多尔菌属、瘤胃球菌属和臭气杆菌属等有害菌群的相对丰度降低。

结论

人参皂苷Rb

、小檗碱及其联合应用可降低高脂饮食诱导的肥胖小鼠体质量，作用机制可能与其调节肠道菌群的结构有关。

Abstract

Objective

To investigate the effect of ginsenoside Rb

berberine

and their combination on the intestinal flora in obese mice induced by a high-fat diet.

Methods

Forty-two male SPF grade C57BL/6J mice were fed on a high-fat diet for 12 consecutive weeks to establish an obese mice model. The 32 up to the standard obese mice were randomly divided into four groups: the control group

ginsenoside Rb

group (20 mg/kg)

berberine group (50 mg/kg)

and ginsenoside Rb

+ berberine group (ginsenoside Rb

20 mg/kg+ berberine 50 mg/kg)

with eight mice in each group. The mice in each group received the corresponding drugs by gavage for 8 consecutive weeks

and the mice were fed with high-fat diet during the administration period. The body weight of the mice in each group was recorded every week

and the fasting blood glucose of mice in each group was detected every 2 weeks. After the experiment

fecal samples were collected for 16 S rDNA sequencing to observe the changes in the intestinal flora in each group of mice.

Results

Compared with the control group

the body weight from 4 to 6 weeks in the ginsenoside Rb

group

the berberine group and the ginsenoside Rb

+ berberine group were reduced

and the fasting blood glucose at 4

6 and 8 weeks were reduced (

0.05). Furthermore

the imbalanced intestinal flora induced by the high-fat diet were improved

manifesting as an increased ratio of Bacteroides/Firmicutes

and the relative abundance of harmful bacteria

such as Deferribacteres

Mucispirillum

Helicobacter

Dorea

Ruminococcus

and

Odoribacter

were reduced.

Conclusion

Ginsenoside Rb

berberine

and their combination could reduce the body weight of mice with diet-induced obesity

and this effect is likely mediated through the modulation of the intestinal flora composition.

关键词

Keywords

references

World Health Organization . Obesity and Overweight [EB/OL] ( 2021-06-09 ) [ 2023-02-20 ]. http://www.who.int/mediacentre/factsheets/fs311/en/ .

KELLY T , YANG W , CHEN CS , et al . Global burden of obesity in 2005 and projections to 2030 [J]. Int J Obes (Lond) , 2008 , 32 ( 9 )： 1431 - 1437 .

SAFAEI M , SUNDARARAJAN EA , DRISS M , et al . A systematic literature review on obesity: Understanding the causes & consequences of obesity and reviewing various machine learning approaches used to predict obesity [J/OL]. Comput Biol Med , 2021 , 136 : 104754 [ 2023-02-20 ]. https://www.sciencedirect.com/science/article/pii/S0010482521005485?via%3Dihub .

GUO P , WU CM . Gut microbiota brings a novel way to illuminate mechanisms of natural products in vivo [J]. Chin Herb Med , 2017 , 9 ( 4 )： 301 - 306 .

GOMES AC , HOFFMANN C , MOTA JF . The human gut microbiota: Metabolism and perspective in obesity [J]. Gut Microbes , 2018 , 9 ( 4 )： 308 - 325 .

GONG X , LI X , BO A , et al . The interactions between gut microbiota and bioactive ingredients of traditional Chinese medicines: A review [J/OL]. Pharmacol Res , 2020 , 157 : 104824 [ 2023-02-20 ]. https://www.sciencedirect.com/science/article/pii/S1043661820311324?via%3Dihub .

SCHEITHAUER TPM , RAMPANELLI E , NIEUWDORP M , et al . Gut Microbiota as a Trigger for Metabolic Inflammation in Obesity and Type 2 Diabetes [J/OL]. Front Immunol , 2020 , 11 : 571731 [ 2023-02-20 ]. https://www.frontiersin.org/articles/10.3389/fimmu.2020.571731/full .

ORTEGA MA , FRAILE-MARTÍNEZ O , NAYA I , et al . Type 2 Diabetes Mellitus Associated with Obesity (Diabesity). The Central Role of Gut Microbiota and Its Translational Applications [J/OL]. Nutrients , 2020 , 12 ( 9 )： 2749 [ 2023-02-26 ]. https://www.mdpi.com/2072-6643/12/9/2749 .

ZHANG ZW , TIAN T , CHEN Z , et al . Characteristics of the gut microbiome in patients with prediabetes and type 2 diabetes [J/OL]. PeerJ , 2021 , 9 : e10952 [ 2023-03-06 ]. https://peerj.com/articles/10952/ .

VALLIANOU N , CHRISTODOULATOS GS , KARAMPELA I , et al . Understanding the Role of the Gut Microbiome and Microbial Metabolites in Non-Alcoholic Fatty Liver Disease: Current Evidence and Perspectives [J/OL]. Biomolecules , 2021 , 12 ( 1 )： 56 [ 2023-03-08 ]. https://www.mdpi.com/2218-273X/12/1/56 .

ZHU WH , WINTER MG , BYNDLOSS MX , et al . Precision editing of the gut microbiota ameliorates colitis [J]. Nature , 2018 , 553 ( 7687 )： 208 - 211 .

MARQUES FZ , MACKAY CR , KAYE DM . Beyond gut feelings: how the gut microbiota regulates blood pressure [J]. Nat Rev Cardiol , 2018 , 15 ( 1 )： 20 - 32 .

CHANG CJ , LIN CS , LU CC , et al . Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota [J/OL]. Nat Commun , 2015 , 6 : 7489 [ 2023-03-10 ]. https://www.nature.com/articles/ncomms8489 .

WANG K , BAO L , ZHOU N , et al . Structural Modification of Natural Product Ganomycin I Leading to Discovery of a α-Glucosidase and HMG-CoA Reductase Dual Inhibitor Improving Obesity and Metabolic Dysfunction in Vivo [J]. J Med Chem , 2018 , 61 ( 8 )： 3609 - 3625 .

HE K , HU YR , MA H , et al . Rhizoma Coptidis alkaloids alleviate hyperlipidemia in B6 mice by modulating gut microbiota and bile acid pathways [J]. Biochim Biophys Acta , 2016 , 1862 ( 9 )： 1696 - 1709 .

WANG P , GAO JP , KE WX , et al . Resveratrol reduces obesity in high-fat diet-fed mice via modulating the composition and metabolic function of the gut microbiota [J]. Free Radic Biol Med , 2020 , 156 : 83 - 98 .

LIU MT , HUANG YJ , ZHANG TY , et al . Lingguizhugan decoction attenuates diet-induced obesity and hepatosteatosis via gut microbiota [J]. World J Gastroenterol , 2019 , 25 ( 27 )： 3590 - 3606 .

YANG XY , DONG BJ , AN LJ , et al . Ginsenoside Rb1 ameliorates glycemic disorder in mice with high fat diet-induced obesity via regulating gut microbiota and amino acid metabolism [J/OL]. Front Pharmacol , 2021 , 12 : 756491 [ 2023-03-15 ]. https://www.frontiersin.org/articles/10.3389/fphar.2021.756491/full .

TABANDEH MR , JAFARI H , HOSSEINI SA , et al . Ginsenoside Rb1 stimulates adiponectin signaling in C2C12 muscle cells through up-regulation of AdipoR1 and AdipoR2 proteins [J]. Pharm Biol , 2015 , 53 ( 1 )： 125 - 132 .

赵丹丹，白颖，吴瑞，等 . 人参皂苷Rb1对肥胖小鼠骨骼肌胰岛素抵抗及AMPK信号通路的影响 [J]. 世界中医药， 2019 , 14 ( 4 )： 852 - 858 .

WU YZ , YU YH , SZABO A , et al . Central inflammation and leptin resistance are attenuated by ginsenoside Rb1 treatment in obese mice fed a high-fat diet [J/OL]. PLoS One , 2014 , 9 ( 3 )： e92618 [ 2023-03-16 ]. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0092618 .

张明发，沈雅琴．非处方药小檗碱抗腹泻作用的再评价 [J]. 中国医院用药评价与分析， 2003 ， 3 ( 3 )： 148 - 153 .

WANG Y , LIU HY , ZHENG MY , et al . Berberine Slows the Progression of Prediabetes to Diabetes in Zucker Diabetic Fatty Rats by Enhancing Intestinal Secretion of Glucagon-Like Peptide-2 and Improving the Gut Microbiota [J/OL]. Front Endocrinol (Lausanne) , 2021 , 12 : 609134 [ 2023-03-18 ]. https://www.frontiersin.org/articles/10.3389/fendo.2021.609134/full .

XIE WD , GU DY , LI JN , et al . Effects and action mechanisms of berberine and Rhizoma coptidis on gut microbes and obesity in high-fat diet-fed C57BL/6J mice [J/OL]. PLoS One , 2011 , 6 ( 9 )： e24520 [ 2023-03-20 ]. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0024520 .

ZHANG X , ZHAO YF , XU J , et al . Modulation of gut microbiota by berberine and metformin during the treatment of high-fat diet-induced obesity in rats [J/OL]. Sci Rep , 2015 , 5 : 14405 [ 2023-03-20 ]. https://www.nature.com/articles/srep14405 .

ZHANG LC , WU XY , YANG RB , et al . Effects of Berberine on the Gastrointestinal Microbiota [J/OL]. Front Cell Infect Microbiol , 2020 , 10 : 588517 [ 2023-03-22 ]. https://www.frontiersin.org/articles/10.3389/fcimb.2020.588517/full .

CAI ZX , CHEN Y . Synergetic protective effect of berberine and ginsenoside Rb1 against tumor necrosis factor alpha-induced inflammation in adipocytes [J]. Bioengineered , 2021 , 12 ( 2 )： 11784 - 11796 .

BAI Y , BAO XL , MU QQ , et al . Ginsenoside Rb1, salvianolic acid B and their combination modulate gut microbiota and improve glucolipid metabolism in high-fat diet induced obese mice [J/OL]. PeerJ , 2021 , 9 : e10598 [ 2023-03-23 ]. https://peerj.com/articles/10598/ .

LUO CB , LI YQ , CHEN Y , et al . Bamboo lignocellulose degradation by gut symbiotic microbiota of the bamboo snout beetle Cyrtotrachelus buqueti [J/OL]. Biotechnol Biofuels , 2019 , 12 : 70 [ 2023-03-24 ]. https://biotechnologyforbiofuels.biomedcentral.com/articles/10.1186/s13068-019-1411-1 .

GUO XL , TANG RY , YANG SY , et al . Rutin and its combination with inulin attenuate gut dysbiosis, the inflammatory status and endoplasmic reticulum stress in paneth cells of obese mice induced by high-fat diet [J/OL]. Front Microbiol , 2018 , 9 : 2651 [ 2023-03-28 ]. https://www.frontiersin.org/articles/10.3389/fmicb.2018.02651/full .

SWIFT DL , MCGEE JE , EARNEST CP , et al . The Effects of Exercise and Physical Activity on Weight Loss and Maintenance [J]. Prog Cardiovasc Dis , 2018 , 61 ( 2 )： 206 - 213 .

CHAO AM , QUIGLEY KM , WADDEN TA . Dietary interventions for obesity: clinical and mechanistic findings [J/OL]. J Clin Invest , 2021 , 131 ( 1 )： e140065 [ 2023-03-29 ]. https://www.jci.org/articles/view/140065 .

SCHULMAN AR , THOMPSON CC . Complications of Bariatric Surgery: What You Can Expect to See in Your GI Practice [J]. Am J Gastroenterol , 2017 , 112 ( 11 )： 1640 - 1655 .

NARAYANASWAMI V , DWOSKIN LP . Obesity: Current and potential pharmacotherapeutics and targets [J]. Pharmacol Ther , 2017 , 170 : 116 - 147 .

FAN QJ , XU FR , LIANG B , et al . The Anti-Obesity Effect of Traditional Chinese Medicine on Lipid Metabolism [J/OL]. Front Pharmacol , 2021 , 12 : 696603 [ 2023-03-31 ]. https://www.frontiersin.org/articles/10.3389/fphar.2021.696603/full .

SHAO JL , LI C , BAI LT , et al . Recent evidence in support of traditional Chinese medicine to restore normal leptin function in simple obesity [J/OL]. Heliyon , 2022 , 8 ( 5 )： e09482 [ 2023-03-31 ]. https://www.sciencedirect.com/science/article/pii/S2405844022007708?via%3Dihub .

ZHOU W , CHEN ZY , WANG YH , et al . Systems Pharmacology-Based Method to Assess the Mechanism of Action of Weight-Loss Herbal Intervention Therapy for Obesity [J/OL]. Front Pharmacol , 2019 , 10 : 1165 [ 2023-04-02 ]. https://www.frontiersin.org/articles/10.3389/fphar.2019.01165/full .

GURUNG M , LI ZP , YOU H , et al . Role of gut microbiota in type 2 diabetes pathophysiology [J/OL]. EBioMedicine , 2020 , 51 : 102590 [ 2023-04-03 ]. https://www.sciencedirect.com/science/article/pii/S235239641930800X?via%3Dihub .

FORTE N , FERNÁNDEZ-RILO AC , PALOMBA L , et al . Obesity Affects the Microbiota-Gut-Brain Axis and the Regulation Thereof by Endocannabinoids and Related Mediators [J/OL]. Int J Mol Sci , 2020 , 21 ( 5 )： 1554 [ 2023-04-04 ]. https://www.mdpi.com/1422-0067/21/5/1554 .

CHEN XP , DEVARAJ S . Gut Microbiome in Obesity, Metabolic Syndrome, and Diabetes [J/OL]. Curr Diab Rep , 2018 , 18 ( 12 )： 129 [ 2023-04-05 ]. https://link.springer.com/article/10.1007/s11892-018-1104-3 .

ZHU L , ZHANG DY , ZHU H , et al . Berberine treatment increases Akkermansia in the gut and improves high-fat diet-induced atherosclerosis in Apoe -/- mice [J]. Atherosclerosis , 2018 , 268 : 117 - 126 .

BAOTHMAN OA , ZAMZAMI MA , TAHER I , et al . The role of gut microbiota in the development of obesity and Diabetes [J/OL]. Lipids Health Dis , 2016 , 15 : 108 [ 2023-04-07 ]. https://lipidworld.biomedcentral.com/articles/10.1186/s12944-016-0278-4 .

RIDAURA VK , FAITH JJ , REY FE , et al . Gut microbiota from twins discordant for obesity modulate metabolism in mice [J/OL]. Science , 2013 , 341 ( 6150 )： 1241214 [ 2023-04-10 ]. https://www.science.org/doi/10.1126/science.1241214 .

CANI PD , DEPOMMIER C , DERRIEN M , et al . Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms [J]. Nat Rev Gastroenterol Hepatol , 2022 , 19 ( 10 )： 625 - 637 .

LI J , LIN SQ , VANHOUTTE PM , et al . Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/- Mice [J]. Circulation , 2016 , 133 ( 24 )： 2434 - 2446 .

ANHÊ FF , ROY D , PILON G , et al . A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice [J]. Gut , 2015 , 64 ( 6 )： 872 - 883 .

GREER RL , DONG XX , MORAES AC , et al . Akkermansia muciniphila mediates negative effects of IFNγ on glucose metabolism [J/OL]. Nat Commun , 2016 , 7 : 13329 [ 2023-04-13 ]. https://www.nature.com/articles/ncomms13329 .

ANHÊ FF , VARIN TV , LE BARZ M , et al . Arctic berry extracts target the gut-liver axis to alleviate metabolic endotoxaemia, insulin resistance and hepatic steatosis in diet-induced obese mice [J]. Diabetologia , 2018 , 61 ( 4 )： 919 - 931 .

LI K , ZHANG L , XUE J , et al . Dietary inulin alleviates diverse stages of type 2 diabetes mellitus via anti-inflammation and modulating gut microbiota in db/db mice [J]. Food Funct , 2019 , 10 ( 4 )： 1915 - 1927 .

TUNG YC , LIANG ZR , YANG MJ , et al . Oolong tea extract alleviates weight gain in high-fat diet-induced obese rats by regulating lipid metabolism and modulating gut microbiota [J]. Food Funct , 2022 , 13 ( 5 )： 2846 - 2856 .

BARADARAN A , DEHGHANBANADAKI H , NADERPOUR S , et al . The association between Helicobacter pylori and obesity: a systematic review and meta-analysis of case-control studies [J/OL]. Clin Diabetes Endocrinol , 2021 , 7 ( 1 )： 15 [ 2023-04-15 ]. https://clindiabetesendo.biomedcentral.com/articles/10.1186/s40842-021-00131-w .

OH JK , VASQUEZ R , HWANG IC , et al . Cudrania tricuspidata Combined with Lacticaseibacillus rhamnosus Modulate Gut Microbiota and Alleviate Obesity-Associated Metabolic Parameters in Obese Mice [J/OL]. Microorganisms , 2021 , 9 ( 9 )： 1908 [ 2023-04-15 ]. https://www.mdpi.com/2076-2607/9/9/1908 .

MARTIN-GALLAUSIAUX C , MARINELLI L , BLOTTIÈRE HM , et al . SCFA: mechanisms and functional importance in the gut [J]. Proc Nutr Soc , 2021 , 80 ( 1 )： 37 - 49 .

MORRISON DJ , PRESTON T . Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism [J]. Gut Microbes , 2016 , 7 ( 3 )： 189 - 200 .

ZHAO QY , FU YX , ZHANG F , et al . Heat-Treated Adzuki Bean Protein Hydrolysates Reduce Obesity in Mice Fed a High-Fat Diet via Remodeling Gut Microbiota and Improving Metabolic Function [J/OL]. Mol Nutr Food Res , 2022 , 66 ( 8 )： e2100907 [ 2023-04-20 ]. https://onlinelibrary.wiley.com/doi/10.1002/mnfr.202100907 .

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人参皂苷Rb1、小檗碱及其联合应用对肥胖小鼠肠道菌群的影响

Effect of ginsenoside Rb1, berberine, and their combination on intestinal flora in obese mice

DOI：10.3969/j.issn.1006-2157.2023.11.009

摘要

Abstract

关键词

Keywords

references

人参皂苷Rb₁、小檗碱及其联合应用对肥胖小鼠肠道菌群的影响

Effect of ginsenoside Rb₁, berberine, and their combination on intestinal flora in obese mice