Interactions between Oroxylin A with the solute carrier transporters and ATP-binding cassette transporters: Drug transporters profile for this flavonoid

Ren, Guanghui; Qin, Zhiying; Yang, Nan; Chen, Huili; Fu, Kejia; Lu, Chengcan; Lu, Yang; Li, Ning; Zhang, Yongjie; Chen, Xijing; Zhao, Di

doi:10.1016/j.cbi.2020.109097

Cited by 9 publications

(5 citation statements)

References 33 publications

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“…This suggests that structural modifications may impact the interaction of chlorogenic acid with OATPs/Oatps. In a previous study, the accumulation of oroxylin A was estimated to be 2.41- and 2.19-fold higher in HEK-OATP1B1 and HEK-OATP1B3, respectively, compared to HEK-EV cells 33 . Our current study also found that the accumulation of oroxylin A in CHO-OATP1B1 and HEK-OATP1B3 cells was 2.1- and 2.3-fold higher, respectively, than that in corresponding control cells.…”

Section: Resultsmentioning

confidence: 86%

“…Oroxylin A is a bioactive flavone that possesses a broad spectrum of pharmacological functions, including anti-inflammation, anti-cancer, and neuroprotective properties 32 . Oroxylin A was previously reported to inhibit OAT1 (IC 50 ~ 1.0 µM), OAT3 (IC 50 ~ 0.1 µM), and OATP1B1 (IC 50 ~ 7.0 µM) using p -aminohippuric acid, estrone sulfate, and β -estradiol 17-( β -D-glucuronide) as respective probes in transporter-overexpressing HEK-293 cells 33 . Notably, our current study showed that oroxylin A inhibited the OAT3-mediated uptake of 6-CF, with an estimated IC 50 value of ~ 2 µM, exhibiting 5-fold selectivity over OAT1 ( Fig.…”

Section: Resultsmentioning

confidence: 99%

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Potential Involvement of Organic Anion Transporters in Drug Interactions with Shuganning Injection, a Traditional Chinese Patent Medicine

Xing

Gui

et al. 2023

Planta Med

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Traditional Chinese medicine injections have been widely used in China for the treatment of various diseases. Transporter-mediated drug-drug interactions are a major contributor to adverse drug reactions. However, the research on transporter-mediated Traditional Chinese medicine injection-drug interactions is limited. Shuganning injection is a widely used Traditional Chinese medicine injection for treating various liver diseases. In this study, we investigated the inhibitory effect of Shuganning injection and its four main ingredients (baicalin, geniposide, chlorogenic acid, and oroxylin A) on 9 drug transporters. Shuganning injection strongly inhibited organic anion transporter 1 and organic anion transporter 3 with IC50 values < 0.1% (v/v), and moderately inhibited organic anion transporter 2, organic anion transporting-polypeptide 1B1, and organic anion transporting-polypeptide 1B3 with IC50 values < 1.0%. Baicalin, the most abundant bioactive ingredient in the Shuganning injection, was identified as both an inhibitor and substrate of organic anion transporter 1, organic anion transporter 3, and organic anion transporting-polypeptide 1B3. Oroxylin A had the potential to act as both an inhibitor and substrate of organic anion transporting-polypeptide 1B1 and organic anion transporting-polypeptide 1B3. In contrast, geniposide and chlorogenic acid had no significant inhibitory effect on drug transporters. Notably, Shuganning injection markedly altered the pharmacokinetics of furosemide and atorvastatin in rats. Using Shuganning injection as an example, our findings support the implementation of transporter-mediated Traditional Chinese medicine injection-drug interactions in the development of Traditional Chinese medicine injection standards.

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Section: Resultsmentioning

confidence: 86%

Section: Resultsmentioning

confidence: 99%

Potential Involvement of Organic Anion Transporters in Drug Interactions with Shuganning Injection, a Traditional Chinese Patent Medicine

Xing

Gui

et al. 2023

Planta Med

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“…The extract of Scutellariae Radix could inhibit OCT1 and MATE1 activity in vitro 180 . Oroxylin A might be a substrate of OATP1B1 and OATP1B3, and it can also inhibit OATP1B1, OAT1, OAT3 and BCRP activity 181 . The extract of Scutellariae Radix, salvigenin, could downregulate the activity of UGT1A8 and UGT1A10 182 .…”

Section: Tcms For the Treatment Of Covid-19 Infectionsmentioning

confidence: 99%

Potential herb–drug interactions between anti-COVID-19 drugs and traditional Chinese medicine

Ye¹,

Fan²,

Zhao³

et al. 2023

Acta Pharmaceutica Sinica B

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“…Inside-out vesicles are produced from plasma membranes with their cytoplasmic face oriented outward. When expressing human MDR1 transporters, inside-out vesicles can be used to study drug excretion by P-gp [ 84 ]. The transport direction is from outside-to-inside of the vesicles, instead of across the cell monolayers, as in Caco-2 and MDCK-MDR1 cell models [ 85 ].…”

Section: Mechanism Of P-gp Efflux and Functions Of P-gpmentioning

confidence: 99%

Pharmaceutical Formulations with P-Glycoprotein Inhibitory Effect as Promising Approaches for Enhancing Oral Drug Absorption and Bioavailability

2021

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P-glycoprotein (P-gp) is crucial in the active transport of various substrates with diverse structures out of cells, resulting in poor intestinal permeation and limited bioavailability following oral administration. P-gp inhibitors, including small molecule drugs, natural constituents, and pharmaceutically inert excipients, have been exploited to overcome P-gp efflux and enhance the oral absorption and bioavailability of many P-gp substrates. The co-administration of small molecule P-gp inhibitors with P-gp substrates can result in drug–drug interactions and increased side effects due to the pharmacological activity of these molecules. On the other hand, pharmaceutically inert excipients, including polymers, surfactants, and lipid-based excipients, are safe, pharmaceutically acceptable, and are not absorbed from the gut. Notably, they can be incorporated in pharmaceutical formulations to enhance drug solubility, absorption, and bioavailability due to the formulation itself and the P-gp inhibitory effects of the excipients. Different formulations with inherent P-gp inhibitory activity have been developed. These include micelles, emulsions, liposomes, solid lipid nanoparticles, polymeric nanoparticles, microspheres, dendrimers, and solid dispersions. They can bypass P-gp by different mechanisms related to their properties. In this review, we briefly introduce P-gp and P-gp inhibitors, and we extensively summarize the current development of oral drug delivery systems that can bypass and inhibit P-gp to improve the oral absorption and bioavailability of P-gp substrates. Since many drugs are limited by P-gp-mediated efflux, this review is helpful for designing suitable formulations of P-gp substrates to enhance their oral absorption and bioavailability.

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Interactions between Oroxylin A with the solute carrier transporters and ATP-binding cassette transporters: Drug transporters profile for this flavonoid

Cited by 9 publications

References 33 publications

Potential Involvement of Organic Anion Transporters in Drug Interactions with Shuganning Injection, a Traditional Chinese Patent Medicine

Potential Involvement of Organic Anion Transporters in Drug Interactions with Shuganning Injection, a Traditional Chinese Patent Medicine

Potential herb–drug interactions between anti-COVID-19 drugs and traditional Chinese medicine

Pharmaceutical Formulations with P-Glycoprotein Inhibitory Effect as Promising Approaches for Enhancing Oral Drug Absorption and Bioavailability

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