Modulation of P‐glycoprotein ATPase activity by some phytoconstituents

Najar, Ishtiyaq Ahmad; Sachin, B.S.; Sharma, Sumit; Satti, N. K.; Suri, K. A.; Johri, R.K.

doi:10.1002/ptr.2951

Cited by 72 publications

(40 citation statements)

References 18 publications

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“…Andrographolide, berberin, glycyrrhizin and magniferin are the other natural constituents, which are also classified under this category. The explanation for their characterization as both inducers and inhibitors is given by their "biphasic protein modulation" by which they stimulate the protein efflux at lower concentrations and inhibit the same at their higher concentrations (Najar et al, 2010). Rifampicin is classified as an inducing substrate of P-gp as it is transported by the protein and as well has an up regulating effect on P-gp expression.…”

Section: Characterization Of the Interaction Of Certain Compounds Witmentioning

confidence: 99%

Overview of P-glycoprotein inhibitors: a rational outlook

Srivalli

Lakshmi

2012

Braz. J. Pharm. Sci.

186

119

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P-glycoprotein (P-gp), a transmembrane permeability glycoprotein, is a member of ATP binding cassette (ABC) super family that functions specifically as a carrier mediated primary active efflux transporter. It is widely distributed throughout the body and has a diverse range of substrates. Several vital therapeutic agents are substrates to P-gp and their bioavailability is lowered or a resistance is induced because of the protein efflux. Hence P-gp inhibitors were explored for overcoming multidrug resistance and poor bioavailability problems of the therapeutic P-gp substrates. The sensitivity of drug moieties to P-gp and vice versa can be established by various experimental models in silico, in vitro and in vivo. Ever since the discovery of P-gp, the research plethora identified several chemical structures as P-gp inhibitors. The aim of this review was to emphasize on the discovery and development of newer, inert, non-toxic, and more efficient, specifically targeting P-gp inhibitors, like those among the natural herb extracts, pharmaceutical excipients and formulations, and other rational drug moieties. The applications of cellular and molecular biology knowledge, in silico designed structural databases, molecular modeling studies and quantitative structure-activity relationship (QSAR) analyses in the development of novel rational P-gp inhibitors have also been mentioned. Glicoproteína-p (P-gp), uma glicoproteína de transmembrana permeável, é um membro da superfamília (ABC) de cassete de gene de ligação de ATP que funciona especificamente como um carreador mediado pelo transportador de efluxo ativo primário. É amplamente distribuído por todo o corpo e apresenta uma gama diversificada de substratos. Diversos agentes terapêuticos vitais são substratos para P-gp e sua biodisponibilidade é reduzida ou a resistência é induzida devido ao efluxo de proteínas. Portanto, os inibidores da P-gp foram explorados para a superação da resistência a múltiplas drogas e problemas de biodisponibilidade deficiente dos substratos terapêuticos da P-gp. A sensibilidade das moléculas da droga à P-gp e vice-versa, pode ser estabelecida por vários modelos experimentais in silico, in vitro e in vivo. Desde a descoberta da P-gp, diversas pesquisas identificaram várias estruturas químicas como inibidores da P-gp. O objetivo deste presente estudo foi o de enfatizar a descoberta e desenvolvimento de inibidores mais novos, inertes, atóxicos e mais eficazes, visando especificamente os da P-gp, como aqueles entre os extratos vegetais, excipientes e formulações farmacêuticas, e outras moléculas racionais de droga. As aplicações do conhecimento de biologia celular e molecular, bancos de dados estruturais in silico, estudos de modelagem molecular e análises da relação quantitativa estrutura-atividade (QSAR) no desenvolvimento de novos inibidores racionais da P-gp também foram mencionados.Unitermos: Glicoproteína-p. Resistência a múltiplas drogas. Cluster de diferenciação 243. Esfingolipídeos. Inibidores competitivos.

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Section: Characterization Of the Interaction Of Certain Compounds Witmentioning

confidence: 99%

Overview of P-glycoprotein inhibitors: a rational outlook

Srivalli

Lakshmi

2012

Braz. J. Pharm. Sci.

186

119

View full text Add to dashboard Cite

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“…Pip inhibits P-gp-mediated efflux in Caco-2 cells and CYP3A4-mediated drug metabolism (16). Pip reduces the ATPase activity of P-gp at high concentrations, while stimulates it at low concentrations (17). Pip can reverse MDR in short-and long-term treatments, and may improve the outcome of chemotherapy by inhibiting P-gp, MRP1 and breast cancer resistance protein effectively by downregulating the expression of these transporter genes (18).…”

Section: Introductionmentioning

confidence: 99%

Solid lipid nanoparticles with TPGS and Brij 78: A co-delivery vehicle of curcumin and piperine for reversing P-glycoprotein-mediated multidrug resistance in vitro

Tang

Ren

et al. 2016

Oncology Letters

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Abstract. Multidrug resistance (MDR) is a main clinical hurdle for chemotherapy of cancer, and overexpression of P-glycoprotein (P-gp) is a key factor. In the present study, a new co-delivery system for reversing MDR was designed and developed. The system was composed of curcumin (Cur) and piperine (Pip) encapsulated in solid lipid nanoparticles (SLNs) with tocopheryl polyethylene glycol succinate (TPGS) and Brij 78 [(Cur+Pip)-SLNs]. TPGS and Brij 78 could sensitize MDR tumors by inhibiting the P-gp drug efflux system. The combination of Cur and Pip, when administered in SLNs formulations, resulted in a significant enhancement in cytotoxicity and allowed efficient intracellular delivery of the drugs in drug-resistant A2780/Taxol cells. This dual inhibitory strategy may have significant potential in the clinical management of MDR in cancer.

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“…However, oral administration of BBH exhibited low bioavailability and poor stability (Tan et al, 2011;Liu et al, 2014) mainly due to its hydrophobic properties resulted from the chemical structure, which contains two methoxy groups and a quaternary ammonium cation. Besides, the cationic group in the structure shows high affinity to the multidrug efflux pump P-glycoprotein (P-gp) in gastrointestinal tract (Zhang & Cui, 2008;Qiu et al, 2009;Najar et al, 2010). In addition, the apparent oil-water partition coefficient of BBH determined in our preliminary study (lgP app ¼ À1.08) indicated low membrane permeability (Lu et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Nanoemulsion-based delivery system for enhanced oral bioavailability and Caco-2 cell monolayers permeability of berberine hydrochloride

Lü

et al. 2017

Drug Delivery

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Berberine hydrochloride (BBH) has a variety of pharmacological activities such as antitumor, antimicrobial, anti-inflammation, and reduce irritable bowel syndrome. However, poor stability and low oral bioavailability limited its usage. Herein, an oil-in-water nanoemulsion system of BBH was developed to improve its stability and oral bioavailability. The pseudoternary phase diagrams were constructed for the determination of composition of various nanoemulsions. The nanoemulsions of BBH composed of Labrafil M 1944 CS (oil phase), RH-40 (surfactant), glycerin (co-surfactant), and water (aqueous phase). The O/W nanoemulsion of BBH showed a relative bioavailability of 440.40% compared with unencapsulated BBH and was stable in our 6-month stability study. Further, there was a significant increase in intestinal permeability of BBH as assessed by Caco-2 cell monolayers and a significant reduction in efflux of BBH by the multidrug efflux pump P-glycoprotein. This study confirmed that the nanoemulsion formulation could be used as an alternative oral formulation of BBH to improve its stability, oral bioavailability and permeability.ARTICLE HISTORY

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Modulation of P‐glycoprotein ATPase activity by some phytoconstituents

Cited by 72 publications

References 18 publications

Overview of P-glycoprotein inhibitors: a rational outlook

Overview of P-glycoprotein inhibitors: a rational outlook

Solid lipid nanoparticles with TPGS and Brij 78: A co-delivery vehicle of curcumin and piperine for reversing P-glycoprotein-mediated multidrug resistance in vitro

Nanoemulsion-based delivery system for enhanced oral bioavailability and Caco-2 cell monolayers permeability of berberine hydrochloride

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