Structural Changes of Gut Microbiota during Berberine-Mediated Prevention of Obesity and Insulin Resistance in High-Fat Diet-Fed Rats

Zhang, Xu; Zhao, Yuwu; Zhang, Menghui; Pang, Xiaoyan; Xu, Jin-Quan; Kang, Chaoying; Li, Meng; Zhang, Chenhong; Zhang, Zhiguo; Zhang, Yifei; Li, Xiaoying; Ning, Guang; Zhao, Liping

doi:10.1371/journal.pone.0042529

Cited by 457 publications

(399 citation statements)

References 66 publications

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“…25 In agreement with a previous study, BBR actions were confirmed here in decreasing body weight, fasting blood glucose levels, HOMA-IR, and improving impaired glucose tolerance and insulin tolerance in diabetic mice. 26 BBR-SLNs at 100 mg/kg dosage showed more potent effects than the equivalent dose of BBR in db/db mice, especially in improving glucose tolerance and insulin sensitivity. In addition, BBR-SLNs increased the pancreatic islet numbers.…”

Section: Hypoglycemic Effect Of Bbr-slnmentioning

confidence: 89%

Characterization, pharmacokinetics, and hypoglycemic effect of berberine loaded solid lipid nanoparticles

Xue¹,

Yang²,

Zhang³

et al. 2013

IJN

120

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The high aqueous solubility, poor permeability, and absorption of berberine (BBR) result in its low plasma level after oral administration, which greatly limits its clinical application. BBR solid lipid nanoparticles (SLNs) were prepared to achieve improved bioavailability and prolonged effect. Developed SLNs showed homogeneous spherical shapes, small size (76.8 nm), zeta potential (7.87 mV), encapsulation efficiency (58%), and drug loading (4.2%). The power of X-ray diffraction combined with 1 H nuclear magnetic resonance spectroscopy was employed to analyze chemical functional groups and the microstructure of BBR-SLNs, and indicated that the drug was wrapped in a lipid carrier. Single dose (50 mg/kg) oral pharmacokinetic studies in rats showed significant improvement ( P <0.05) in the peak plasma concentration, area under the curve, and variance of mean residence time of BBR-SLNs when compared to BBR alone ( P <0.05), suggesting improved bioavailability. Furthermore, oral administration of both BBR and BBR-SLNs significantly suppressed body weight gain, fasting blood glucose levels, and homeostasis assessment of insulin resistance, and ameliorated impaired glucose tolerance and insulin tolerance in db/db diabetic mice. BBR-SLNs at high dose (100 mg/kg) showed more potent effects when compared to an equivalent dose of BBR. Morphologic analysis demonstrated that BBR-SLNs potentially promoted islet function and protected the islet from regeneration. In conclusion, our study demonstrates that by entrapping BBR into SLNs the absorption of BBR and its anti-diabetic action were effectively enhanced.

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Section: Hypoglycemic Effect Of Bbr-slnmentioning

confidence: 89%

Characterization, pharmacokinetics, and hypoglycemic effect of berberine loaded solid lipid nanoparticles

Xue¹,

Yang²,

Zhang³

et al. 2013

IJN

120

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show abstract

“…Because Berberine, as a strongly intestinal protector used widely in the treatment of enteritis, is insoluble and rarely absorbed in gastrointestinal tract, it is reasonable to suggest that it may improve diabetes through the modulation of intestinal microbiota and intestinal permeability. Zhang et al (2012) studied the alteration of gut microbiota before and after Berberine treatment, …”

Section: Discussionmentioning

confidence: 99%

Alteration of the intestinal barrier and GLP2 secretion in Berberine-treated type 2 diabetic rats

Shan¹,

Yang²,

Yang³

et al. 2013

Journal of Endocrinology

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For centuries, Berberine has been used in the treatment of enteritis in China, and it is also known to have anti-hyperglycemic effects in type 2 diabetic patients. However, as Berberine is insoluble and rarely absorbed in gastrointestinal tract, the mechanism by which it works is unclear. We hypothesized that it may act locally by ameliorating intestinal barrier abnormalities and endotoxemia. A high-fat diet combined with low-dose streptozotocin was used to induce type 2 diabetes in male Sprague Dawley rats. Berberine (100 mg/kg) was administered by lavage to diabetic rats for 2 weeks and saline was given to controls. Hyperinsulinemia and insulin resistance improved in the Berberine group, although there was no significant decrease in blood glucose. Berberine treatment also led to a notable restoration of intestinal villi/mucosa structure and less infiltration of inflammatory cells, along with a decrease in plasma lipopolysaccharide (LPS) level. Tight junction protein zonula occludens 1 (ZO1) was also decreased in diabetic rats but was restored by Berberine treatment. Glutamine-induced glucagon-like peptide 2 (GLP2) secretion from ileal tissue decreased dramatically in the diabetic group but was restored by Berberine treatment. Fasting insulin, insulin resistance index, plasma LPS level, and ZO1 expression were significantly correlated with GLP2 level. In type 2 diabetic rats, Berberine treatment not only augments GLP2 secretion and improves diabetes but is also effective in repairing the damaged intestinal mucosa, restoring intestinal permeability, and improving endotoxemia. Whether these effects are mechanistically related will require further studies, but they certainly support the hypothesis that Berberine acts via modulation of intestinal function.

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“…Therefore, the leptin levels of rats fed a high-fructose diet should be higher, as compared with those in the control group. The present study demonstrated that high-fructose foods may lead to excessive insulin secretion, thereby stimulating the production of leptin (29,31). All L. rotatum flavonoids were able to downregulate leptin and, owing to their potential hypolipidemic effects, further studies investigating the flavonoids of various Mongolian medicines are recommended in the future.…”

Section: Discussionmentioning

confidence: 60%

Hypolipidemic effects of flavonoids extracted from Lomatogonium rotatum

Zhang

Wang

2016

Experimental and Therapeutic Medicine

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Abstract. Contained in the Mongolian volumes of Chinese Materia Medica, Lomatogonium rotatum Fries ex Nym. may reduce blood lipid levels and prevent obesity; however, its exact mechanism of action remains unclear. The present study investigated the hypolipidemic and obesity-inhibiting effects of four similarly structured flavonoids extracted from L. rotatum. According to a well-established method, flavonoids such as decussatin were extracted from the whole herb of L. rotatum, and male Wistar rats were subsequently fed a high-fructose diet supplemented with flavonoids (20 mg/kg) for 12 weeks. The levels of total cholesterol, triglyceride (TG), low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol (HDL-C) were detected. In addition, hepatic and epididymal adipose tissues were weighed, and levels of blood glucose, alanine aminotransferase, aspartate aminotransferase, non-esterified fatty acid, insulin and leptin were determined. The mRNA expression levels of fatty acid synthase (FAS) were analyzed using a reverse transcription polymerase chain reaction; whereas FAS, adenosine monophosphate-activated protein kinase (AMPK) and threonine-172 phosphorylated AMPK protein levels were detected by western blotting. The epididymal adipose tissues of rats fed with flavonoids were lighter, as compared with those fed with fructose in the model group. Following a 12-week administration of flavonoids, the serum levels of fasting blood glucose, feeding blood glucose and leptin were decreased. Furthermore, flavonoid treatment reduced TG and cholesterol levels in the blood and increased serum HDL-C levels, as compared with the model group. High-fructose diet administration significantly increased FAS mRNA and protein expression levels, whereas the FAS protein levels of flavonoid-treated rats were markedly reduced.The flavonoid compounds also enhanced threonine-172 phosphorylation of AMPK in the liver lysate, and all flavonoids successfully downregulated leptin levels and the majority decreased the relative weights of epididymal adipose tissue. Therefore, flavonoids may function in a similar way to epigallocatechin gallate, which has previously been shown to inhibit FAS activity by stimulating AMPK in hepatocyte cells via the liver kinase B1 pathway.

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Structural Changes of Gut Microbiota during Berberine-Mediated Prevention of Obesity and Insulin Resistance in High-Fat Diet-Fed Rats

Cited by 457 publications

References 66 publications

Characterization, pharmacokinetics, and hypoglycemic effect of berberine loaded solid lipid nanoparticles

Characterization, pharmacokinetics, and hypoglycemic effect of berberine loaded solid lipid nanoparticles

Alteration of the intestinal barrier and GLP2 secretion in Berberine-treated type 2 diabetic rats

Hypolipidemic effects of flavonoids extracted from Lomatogonium rotatum

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