Intestinal absorption mechanisms of berberine, palmatine, jateorhizine, and coptisine: involvement of P-glycoprotein

Zhang, Xinfeng; Qiu, Furong; Jiang, Jian; Gao, Chenglu; Tan, Yingzi

doi:10.3109/00498254.2010.529180

Cited by 87 publications

(61 citation statements)

References 28 publications

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“…It has been historically used as an anti-diarrheal, anti-protozoal, and antimicrobial agent in Ayurvedic and Chinese medicine. It also possesses multitude of biological effects, including antiinflammatory, antidiabetic, lipid peroxidation, and neuroprotective activity (Liu et al, 2009;Lee et al, 2010;Wu et al, 2010;Zhou et al, 2010;Zhao et al, 2011). However, quaternary amine cation of BER causes poor water solubility, resulting in low bioavailability.…”

Section: Introductionmentioning

confidence: 99%

“…However, quaternary amine cation of BER causes poor water solubility, resulting in low bioavailability. In addition, BER also induce the activity of multidrug efflux transporter P-glycoprotein (P-gp) in the intestine, responsible for active efflux of drug from cells, cause its own ejection resulting in 90% reduction in BER transport (Zhang et al, 2011;Di Pierro et al, 2012;Shan et al, 2013). Moreover, intramuscular and intravenous administration may leads to risk of adverse reactions, such as drug rash and anaphylactic shock.…”

Section: Introductionmentioning

confidence: 99%

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Formulation and in vitro evaluation of berberine containing liposome optimized by 32 full factorial designs

Sailor¹,

Seth²,

Parmar³

et al. 2015

J App Pharm Sci

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The present study demonstrates the application of 3 2 full factorial design for optimization of berberine loaded liposome for oral administration. Thin film hydration method was used to prepare liposome and optimization was done by 3 2 full factorial designs combined with desirability function. Nine formulations were prepared by using different drug : lipid and soyphosphatidylcholine : cholesterol (SPC:CHOL) ratios and evaluated for entrapment efficiency and vesicle size. The statistical validity of model was done by analysis of variance (ANOVA). Response surface graph and contour plots were used to understand the effect of variables on responses. The optimized formulation with 0.782 desirability value was prepared and evaluated for responses. The results of entrapment efficiency and vesicle size were found to be very close with the predicted values. In addition, an optimized formulation was also characterized for zeta potential, in vitro drug release and morphology. The formulation was found to be spherical shape with an average diameter of 0.823 nm and -1.93 mV zeta potential and also shows sustained release pattern. These results support the fact that 3 2 full factorial designs with desirability function could be effectively used in optimization of berberine loaded liposome.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Formulation and in vitro evaluation of berberine containing liposome optimized by 32 full factorial designs

Sailor¹,

Seth²,

Parmar³

et al. 2015

J App Pharm Sci

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show abstract

“…Given that the rhizoma coptidis alkaloids are substrates of P-gp (Zhang et al, 2011), the reduced intestinal efflux of berberine indicated that the function of intestinal P-gp was decreased with LPS pretreatment. This assumption was confirmed by the reduced intestinal efflux of vinblastine and Rh-123, substrates of P-gp (Ogihara et al, 2006;Tomita et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Likewise, berberine exhibits extremely low plasma concentrations after oral administration (Zuo et al, 2006;Liu et al, 2009). Researchers have proposed the following mechanisms for the low plasma concentrations of these alkaloids: 1) the alkaloids are metabolized in the intestine ; 2) absorbed alkaloids are pumped out by intestinal (Zhang et al, 2011) or hepatic (Tsai and Tsai, 2004) P-glycoprotein (P-gp); 3) absorbed alkaloids are metabolized quickly and extensively after absorption (Tsai and Tsai, 2004;Zuo et al, 2006;Yang et al, 2010); and 4) absorbed alkaloids are distributed widely in tissues Ma et al, 2010). The low plasma concentrations of the alkaloids are insufficient indicators of their in vivo bioactivities.…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, both drug-metabolizing enzymes and transporters, which determine the fate of drugs in vivo, are regulated in these diseases (Morgan et al, 2008). Given that the rhizoma coptidis alkaloids are substrates of P-gp (Zhang et al, 2011) and are eliminated mainly through metabolism , we assume that the pharmacokinetic characteristics of the alkaloids change during inflammation, compared with normal conditions. We hypothesize that this change may be critical to elucidating why rhizoma coptidis cures the aforementioned inflammation-related diseases despite the low plasma concentrations of the alkaloids measured for normal subjects and experimental animals.…”

Section: Introductionmentioning

confidence: 99%

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Increased Systemic Exposure to Rhizoma Coptidis Alkaloids in Lipopolysaccharide-Pretreated Rats Attributable to Enhanced Intestinal Absorption

Ma¹,

Yao²,

Zhong³

et al. 2011

Drug Metab Dispos

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ABSTRACT:Rhizoma coptidis is a rhizome commonly used in traditional Chinese medicine. After oral administration of rhizoma coptidis extract, the plasma concentrations of its effective alkaloid constituents are so low that their systemic therapeutic actions cannot be explained. This study aimed to investigate the influence of lipopolysaccharide (LPS) on the pharmacokinetics of the rhizoma coptidis alkaloids. Pharmacokinetic experiments were performed with rats; both in vitro absorption and efflux experiments were carried out with everted rat gut sacs, whereas in vitro metabolism experiments were conducted with rat liver microsomes and intestinal S9 fractions. Mucosal changes were evaluated with light microscopy and transmission electron microscopy. The results showed that, in rat plasma, LPS pretreatment increased systemic alkaloid exposure. LPS pretreatment increased the in vitro absorption of the alkaloids and decreased their efflux. The efflux of vinblastine and rhodamine 123, P-glycoprotein substrates, also was decreased. The absorption of fluorescein isothiocyanate-labeled dextran (average molecular mass, 4 kDa), a gut paracellular permeability probe, was not influenced. Obvious damage was observed in the mucosa, but the tight junctions between epithelial cells remained intact. Intestinal, rather than hepatic, alkaloid metabolism was decreased. These findings indicated that LPS pretreatment increased systemic exposure to the alkaloids through enhancement of their absorption, which was related to decreased intestinal efflux and metabolism. The results add to the understanding of why rhizoma coptidis is active despite the low plasma concentrations of the rhizoma coptidis alkaloids measured in normal subjects and experimental animals.

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The absorption enhancement of norisoboldine in the duodenum of adjuvant‐induced arthritis rats involves the impairment of P‐glycoprotein

Duan

Guo

Dai

et al. 2017

Biopharm & Drug Disp

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Lindera aggregata (Sims) Kosterm root has been used in traditional Chinese medicine for the treatment of rheumatism palsy, dyspepsia and frequent urination for a long time. Norisoboldine, the main active constituent of this herb drug, possesses outstanding anti-arthritis activity. However, the in vivo disposition of norisoboldine is known to a limited extent, especially under the pathological condition of rheumatoid arthritis (RA). The aim of this study is to investigate whether and how the absorption of norisoboldine is altered in adjuvant-induced arthritis (AIA) rats. Comparative studies of the intestinal absorption of norisoboldine in normal and AIA rats at different pathological stages of the arthritis were performed using in situ single-pass intestinal perfusion, and the effects of an inhibitor of efflux proteins were also investigated. Norisoboldine was shown to be a substrate of P-glycoprotein (P-gp), as P-gp inhibitor verapamil markedly increased the permeability coefficient (P ) of norisoboldine by 88% in the intestine of normal rats. Compared with normal rats, AIA rats displayed increased P values of norisoboldine by 84% and 86% on day 5 and day 10 after the appearance of the secondary response of arthritis, respectively. Verapamil could eliminate the difference of intestinal absorption of norisoboldine between normal and AIA rats. Further studies showed that impaired expression and activity of P-gp in AIA rats play a decisive role in the absorption enhancement of norisoboldine. Notably, the impairment of P-gp function positively correlated with the severity of arthritis. Copyright © 2016 John Wiley & Sons, Ltd.

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Intestinal absorption mechanisms of berberine, palmatine, jateorhizine, and coptisine: involvement of P-glycoprotein

Cited by 87 publications

References 28 publications

Formulation and in vitro evaluation of berberine containing liposome optimized by 32 full factorial designs

Formulation and in vitro evaluation of berberine containing liposome optimized by 32 full factorial designs

Increased Systemic Exposure to Rhizoma Coptidis Alkaloids in Lipopolysaccharide-Pretreated Rats Attributable to Enhanced Intestinal Absorption

The absorption enhancement of norisoboldine in the duodenum of adjuvant‐induced arthritis rats involves the impairment of P‐glycoprotein

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