Inhibitory effects of herbal constituents on P-glycoprotein in vitro and in vivo: Herb–drug interactions mediated via P-gp

Li, Xue; Hu, Jiye; Wang, Baolian; Li, Sheng; Liu, Zhihao; Yang, Shuang; Li, Yan

doi:10.1016/j.taap.2013.12.015

Cited by 91 publications

(66 citation statements)

References 63 publications

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“…Some of the ginsenoside constituents within SMI have an inhibitory effect on P-gp. As reported, 20(S)-ginsenoside F1 exhibited significant inhibition on P-gp in MDR1-MDCKII and Caco-2 cells [23] . Three ginsenoside metabolites, CK, Ppd, and Ppt, significantly enhanced rhodamine 123 retention in Caco-2 cells and decreased the efflux ratio of digoxin; these effects were comparable to the effects of the known P-gp inhibitor verapamil [24] .…”

Section: Discussionsupporting

confidence: 69%

Shenmai injection enhances the cytotoxicity of chemotherapeutic drugs against colorectal cancers via improving their subcellular distribution

et al. 2016

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Shenmai injection (SMI) is a Chinese patent-protected injection, which was mainly made of Red Ginseng and Radix Ophiopogonis and widely used for treating coronary heart disease and tumors by boosting Qi and nourishing Yin. In this study we examined whether SMI could produce direct synergetic effects on the cytoxicity of adriamycin (ADR) and paclitaxel (PTX) in colorectal cancers in vivo and in vitro, and explored the underlying pharmacokinetic mechanisms. BALB/c nude mice with LoVo colon cancer xenografts were intraperitoneally injected with ADR (2 mg·kg -1 ·3d -1 ) or PTX (7.5 mg·kg -1 ·3d -1 ) with or without SMI (0.01 mL·g -1 ·d -1 ) for 13 d. Co-administration of SMI significantly enhanced the chemotherapeutic efficacy of ADR and PTX, whereas administration of SMI alone at the given dosage did not produce visible anti-cancer effects, The chemosensitizing action of SMI was associated with increased concentrations of ADR and PTX in the plasma and tumors. In Caco-2 and LoVo cells in vitro, co-treatment with SMI (2 μL/mL) significantly enhanced the cytotoxicity of ADR and PTX, and resulted in some favorable pharmacokinetic changes in the subcellular distribution of ADR and PTX. In addition, SMI-induced intracellular accumulation of ADR was closely correlated with the increased expression levels of P-glycoprotein in 4 colon cancer cell lines (r 2 =+0.8558). SMI enhances the anti-cancer effects of ADR and PTX in colon cancers in vivo and in vitro by improving the subcellular distributions of ADR and PTX.

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Section: Discussionsupporting

confidence: 69%

Shenmai injection enhances the cytotoxicity of chemotherapeutic drugs against colorectal cancers via improving their subcellular distribution

et al. 2016

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“…According to work done by Zhao et al (2012), GA inhibited 1 0 -hydroxylation of midazolam with an IC 50 value of 13.79 mM in HLM. In another study, 18b-GA (10 mM) inhibited CYP3A activity by 44% in RLM (Li et al, 2014c). It should be noted that these two in vitro studies showed that GA inhibited CYP3A activity.…”

Section: Interactions Of Gz and Ga With Cyp450smentioning

confidence: 88%

“…An in vitro study found that daunorubicin, a substrate of P-gp, had increased accumulation in the presence of 50 mM GA in KB-C2 cells (Nabekura et al, 2008). Furthermore, when digoxin was co-administered with 18b-GA to male SD rats, the AUC 0Àt and C max of digoxin increased by approximately 51 and 58%, respectively (Li et al, 2014c). Another study revealed that 18b-GA significantly inhibited (450%) P-gp in MDR1-MDCKII and Caco-2 cells (Li et al, 2014c).…”

Section: Interactions Of Gz and Ga With Ugtsmentioning

confidence: 99%

Potential drug interactions associated with glycyrrhizin and glycyrrhetinic acid

Feng

Ding

Qiu

2015

Drug Metabolism Reviews

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Glycyrrhizin (GZ), the main active component of licorice, is a widely used therapeutic in the clinic. Depending on the disease, the treatment may involve a long course of high dose GZ. Another component of licorice, glycyrrhetinic acid (GA), is the main active metabolite of GZ and is thought to be responsible for the majority of the pharmacological properties of GZ. Therefore, GZ and GA are both used for therapeutic purposes. In addition, GZ and GA are also widely used to sweeten and flavor foods. Due to this widespread, multifaceted use of these substances, potential drug interactions with GZ and GA have recently gained attention. Along these lines, this review covers the known effects of GZ and GA on drug-metabolizing enzymes and efflux transporters. We conclude that both GZ and GA may have an effect on the activity of CYPs. For example, GZ may induce CYP3A activity through activation of PXR. Also, GZ and GA may affect glucuronidation in rats and humans. Furthermore, 18β-GA is a potent inhibitor of P-gp, while GZ and GA are inhibitors of MRP1, MRP2 and BCRP. The pharmacokinetics and pharmacodynamics of many medications may be altered when used concurrently with GZ or GA, which is also covered in this review. Overall, GZ, GA or related products should be taken with caution when taken with additional medications due to the possible drug interactions.

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“…At the concentration of 10 µM, G-Rh1 suppressed midazolam 1-hydroxylase activity by 54 % and increased P-glycoprotein ATPase activity to 17.2 nmol P i / mg protein/min, but it exerted negligible effects on these at the low concentration of 1 µM. In contrast, Li et al [66] found weak inhibitory activity of G-Rh1 on P-glycoprotein by 8.94 % at 75 µM using a transport assay on Caco-2 cells. In agreement with the two abovementioned works, G-Rh1 was confirmed as a CYP3A4 inhibitor owing to 15 % suppression of midazolam metabolism at 10 µM.…”

Section: Other Pharmacological Effectsmentioning

confidence: 89%

Untitled

2018

Planta Med

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Supporting information available online at http://www.thieme-connect.de/products ABSTR AC TGinsenoside Rh1 is one of major bioactive compounds extracted from red ginseng, which has been increasingly used for enhancing cognition and physical health worldwide. The objective of this study was to review the pharmacological effects of ginsenoside Rh1 in a systematic manner. We performed searches on eight electronic databases including MEDLINE (Pubmed), Scopus, Google Scholar, POPLINE, Global Health Library, Virtual Health Library, the System for Information on Grey Literature in Europe, and the New York Academy of Medicine Grey Literature Report to select the original research publications reporting the biological and pharmacological effects of ginsenoside Rh1 from in vitro and in vivo studies regardless of publication language and study design. Upon applying the inclusion and exclusion criteria, we included a total of 57 studies for our systemic review. Ginsenoside Rh1 exhibited the potent characteristics of anti-inflammatory, antioxidant, immunomodulatory effects, and positive effects on the nervous system. The cytotoxic effects of ginsenoside Rh1 were dependent on different types of cell lines. Other pharmacological effects including estrogenic, enzymatic, anti-microorganism activities, and cardiovascular effects have been mentioned, but the results were considerably diverged. A higher quality of evidence on clinical trial studies is highly recommended to confirm the consistent efficacy of ginsenoside Rh1.

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Inhibitory effects of herbal constituents on P-glycoprotein in vitro and in vivo: Herb–drug interactions mediated via P-gp

Cited by 91 publications

References 63 publications

Shenmai injection enhances the cytotoxicity of chemotherapeutic drugs against colorectal cancers via improving their subcellular distribution

Shenmai injection enhances the cytotoxicity of chemotherapeutic drugs against colorectal cancers via improving their subcellular distribution

Potential drug interactions associated with glycyrrhizin and glycyrrhetinic acid

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