Berberine protects against diet-induced obesity through regulating metabolic endotoxemia and gut hormone levels

Xu, Jing; Liu, Xing Zhen; Pan, Wei; Zou, Da Jin

doi:10.3892/mmr.2017.6321

Cited by 65 publications

(50 citation statements)

References 46 publications

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“…As a traditional Chinese medicine, BBR has been used to treat diarrhea in China (Chen et al, 2015). Accumulating evidence suggests that BBR can improve metabolic syndrome by regulating glucose and lipid metabolism and attenuating insulin resistance (Kong et al, 2004;Zhang et al, 2014;Xu et al, 2017). Since BBR has low bioavailability, modulation of gut bacteria might be one possible mechanism for its antidiabetic and antiobesity effects (Han et al, 2011;Xie et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Berberine Directly Affects the Gut Microbiota to Promote Intestinal Farnesoid X Receptor Activation

Tian¹,

Cai²,

Gui³

et al. 2018

Drug Metab Dispos

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Intestinal bacteria play an important role in bile acid metabolism and in the regulation of multiple host metabolic pathways (e.g., lipid and glucose homeostasis) through modulation of intestinal farnesoid X receptor (FXR) activity. Here, we examined the effect of berberine (BBR), a natural plant alkaloid, on intestinal bacteria using in vitro and in vivo models. In vivo, the metabolomic response and changes in mouse intestinal bacterial communities treated with BBR (100 mg/kg) for 5 days were assessed using NMR-and mass spectrometry-based metabolomics coupled with multivariate data analysis. Short-term BBR exposure altered intestinal bacteria by reducing Clostridium cluster XIVa and IV and their bile salt hydrolase (BSH) activity, which resulted in the accumulation of taurocholic acid (TCA). The accumulation of TCA was associated with activation of intestinal FXR, which can mediate bile acid, lipid, and glucose metabolism. In vitro, isolated mouse cecal bacteria were incubated with three doses of BBR (0.1, 1, and 10 mg/ml) for 4 hours in an anaerobic chamber. NMR-based metabolomics combined with flow cytometry was used to evaluate the direct physiologic and metabolic effect of BBR on the bacteria. In vitro, BBR exposure not only altered bacterial physiology but also changed bacterial community composition and function, especially reducing BSHexpressing bacteria like Clostridium spp. These data suggest that BBR directly affects bacteria to alter bile acid metabolism and activate FXR signaling. These data provide new insights into the link between intestinal bacteria, nuclear receptor signaling, and xenobiotics.

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Section: Introductionmentioning

confidence: 99%

Berberine Directly Affects the Gut Microbiota to Promote Intestinal Farnesoid X Receptor Activation

Tian¹,

Cai²,

Gui³

et al. 2018

Drug Metab Dispos

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“…A previous report showed that the BER improves diabetes by an enhanced insulin receptor (IRS) expression [35]. Thus, using by Western blot method, we measured the IRS phosphorylation levels at 30 min and the IRS expression levels at 8 days after the stimulation.…”

Section: Discussionmentioning

confidence: 97%

(-)-O-Methylcubebin from Vitex trifolia Enhanced Adipogenesis in 3T3-L1 Cells via the Inhibition of ERK1/2 and p38MAPK Phosphorylation

et al. 2019

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In this study, for the purpose of elucidation for antidiabetic components, we isolated and identified compounds that could become lead compounds for the development of antidiabetic agents from the herbal medicine Vitex trifolia, which is used for liver protection in Myanmar. Three kinds of lignan, (-)-O-methylcubebin (MC), (-)-hinokinin, and (-)-cubebin, were isolated from the ethyl acetate extract of the leaves of V. trifolia, using various chromatography. Among the three isolated compounds, MC showed the strongest effects to increase intracellular lipid accumulation in 3T3-L1 cells. From the results of the elucidation of the MC’s effects on the adipogenesis of 3T3-L1 cells, the downsizing of adipocytes and the promotion of the expression of adipogenesis-related proteins, as well as adiponectin, were observed. On the other hand, since the activity of MC was inhibited by antagonists of PPARγ and improved by inhibitors of the classical mitogen-activated protein kinase (MAPK) pathway and p38MAPK pathway, MC was considered to be an agonist of PPARγ, and furthermore promoted adipogenesis via the inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38MAPK phosphorylation. Although MC showed similar effects to those of rosiglitazone (RO) used as a positive control, RO promoted the migration of GLUT4 from the cytoplasm to the cell membrane, whereas MC did not show such an effect. From the abovementioned results, it was considered that MC could be a lead compound for the development of antidiabetic drugs that does not show weight gain, which is a side effect of RO.

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“…Previous study analyzed nine marker compounds—baicalin, wogonoside, baicalein, wogonin, glycyrrhizin, liquiritin, berberine, coptisine, and palmatine—in the BHSST extract using HPLC-PDA [ 9 ]. Baicalin [ 19 ], baicalein [ 20 ], glycyrrhizin [ 21 ], berberine [ 22 , 23 ], coptisine [ 24 ], and palmatine [ 24 ] have inhibitory effect of obesity in in vitro or in vivo study. In particular, Baicalin, the most abundant component in BHSST, was well known for having antiobesity effects.…”

Section: Discussionmentioning

confidence: 99%

Single Oral Acute Toxicity of Banhasasim‐Tang and Its Antiobesity Effect on Diet‐Induced Obese Mice and 3T3‐L1 Adipocytes

Yoo

Jeong

Lee

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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We had tested antiobesity effect of 52 traditional herbal formulas in 3T3-L1 adipocyte, and Banhasasim-tang (BHSST) was chosen as one of the effective medications to inhibit triglyceride accumulation. We investigated the antiobesity effect of BHSST on 3T3-L1 adipocytes and high-fat diet- (HFD-) induced obese mice. In addition, we evaluated the acute toxicity of BHSST in Sprague Dawley (SD) rats. Differentiated 3T3-L1 cells were treated with various concentrations of BHSST for 8 days. Accumulated triglyceride level and the expressions of adipogenesis-related genes and proteins were subsequently investigated. To evaluate the single oral toxicity of BHSST, the SD rats of each sex were administered a single dose (5000 mg/kg) of BHSST via oral gavage; the control group received vehicle only. After a single administration, the mortality, clinical signs, gross findings, and body weight were monitored for 15 days. Male C57BL/6J mice were fed HFD for 4 weeks to induce obesity and randomly received 50 mg/kg of Orlistat (n=12, OR), 200 mg/kg of BHSST (n=12, B200), and 1000 mg/kg of BHSST (n=12, B1000) for another 8 weeks. BHSST suppressed the triglyceride contents and lipid accumulation in a dose-dependent manner in 3T3-L1 adipocytes. BHSST also downregulated the adipogenesis-related gene levels and protein expression compared with those in undifferentiated adipocytes. In a single oral dose toxicity study, there was no adverse effect on mortality, clinical signs, body weight changes, and gross findings in the treatment group. HFD-fed mice treated with BHSST showed significantly reduced body weight gain, food efficiency ratio, and white adipose tissue weight. The medial lethal dose (LD50) of BHSST was 5000 mg/kg/day body weight for each sex in the rats. BHSST decreased the body weight gain in HFD-fed obese mice and inhibited triglyceride accumulation via a cascade of multiple factors at the mRNA and protein levels in 3T3-L1 adipocytes.

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Berberine protects against diet-induced obesity through regulating metabolic endotoxemia and gut hormone levels

Cited by 65 publications

References 46 publications

Berberine Directly Affects the Gut Microbiota to Promote Intestinal Farnesoid X Receptor Activation

Berberine Directly Affects the Gut Microbiota to Promote Intestinal Farnesoid X Receptor Activation

(-)-O-Methylcubebin from Vitex trifolia Enhanced Adipogenesis in 3T3-L1 Cells via the Inhibition of ERK1/2 and p38MAPK Phosphorylation

Single Oral Acute Toxicity of Banhasasim‐Tang and Its Antiobesity Effect on Diet‐Induced Obese Mice and 3T3‐L1 Adipocytes

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