Effects of Ginkgo leaf tablets on the pharmacokinetics of losartan and its metabolite EXP3174 in rats and its mechanism

Dong, Baiping; Yuan, Suowei; Hu, Junjie; Yan, Yanzhen

doi:10.1080/13880209.2018.1481107

Cited by 8 publications

(7 citation statements)

References 28 publications

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“…Losartan is an antagonist of angiotensin (Ang) II receptor with antihypertensive activity [6]. Previous studies showed that losartan could relieve patients who suffer from hypertension, congestive heart failure, and renal diseases [7].…”

Section: Introductionmentioning

confidence: 99%

Losartan Attenuates Atherosclerosis in Uremic Mice by Regulating Treg/Th17 Balance via Mediating PTEN/PI3K/Akt Pathway

Wei

Sun

et al. 2022

Nephron

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Introduction: Uremia could accelerate atherosclerosis (AS) formation involving Treg/Th17 imbalance. Losartan regulates the imbalance between regulatory T cells (Treg cells) and T helper 17 cells (Th17 cells). However, their interactions in uremia accelerated AS (UAAS) remained poorly understood. Methods: UAAS mice model was established, and after losartan and VO-OHpic (VO, phosphatase and tensin homolog [PTEN] inhibitor) injection, biological indexes, and inflammatory cytokines (transforming growth factor-β1, TGF-β1; interleukin-10 [IL-10]; IL-17 and IL-6) levels were determined using enzyme-linked immunosorbent assay. Pathological changes on aorta were observed using hematoxylin-eosin staining. Percentages of Treg cells (CD4+CD25+Foxp3+) and Th17 cells (CD4+IL-17+) in total CD4+ T cells were determined using flow cytometry. PTEN expressions were measured using Western blot, quantitative real-time polymerase chain reaction, and immunohistochemistry staining as needed. Results: After UAAS mice model construction, biological indexes (urea, cholesterol, and triglycerides) levels were increased, and aortic atherosclerotic plaque was formed. In UAAS mice, in total CD4+ T cells, Treg cells percentage was decreased yet Th17 cells percentage was increased, and TGF-β1 and IL-10 levels were downregulated yet IL-17 and IL-6 levels were upregulated. An opposite effect was found after losartan treatment. PTEN was downregulated in UAAS mice, and suppressing PTEN reversed the alleviating effects of losartan in UAAS mice. Conclusion: Losartan attenuated UAAS in mice by regulating Treg/Th17 cells balance via mediating PTEN/PI3K/Akt pathway, providing possible therapeutic method for UAAS in clinical practice.

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Section: Introductionmentioning

confidence: 99%

Losartan Attenuates Atherosclerosis in Uremic Mice by Regulating Treg/Th17 Balance via Mediating PTEN/PI3K/Akt Pathway

Wei

Sun

et al. 2022

Nephron

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“…Dong et al indicated that Ginkgo leaf tablets could reduce the serum concentration of EXP3174 and increase the serum concentration of LOS. The AUC 0-t of LOS was increased by 70% and this increase was higher than that of SMI ( Dong et al, 2018 ). Choi et al demonstrated that licochalcon A increased the serum concentration of LOS without affecting the serum concentration of EXP3174.…”

Section: Discussionmentioning

confidence: 87%

Evaluation of Potential Herb-Drug Interactions Between Shengmai Injection and Losartan Potassium in Rat and In Vitro

et al. 2022

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Aim: The present study aimed to explore the potential herb-drug interactions (HDI) between Shengmai injection (SMI) and losartan potassium (LOS) based on the expression profiles of cytochromes P450 (CYP450) and drug transporters in rat and in vitro.Methods: Different concentrations of SMI were used to explore the influence of SMI on the antihypertensive efficacy of LOS in the hypertension rat model established by N (omega)-nitro-L-arginine methyl ester (L-NAME) for 4 weeks. Subsequently, the serum concentration levels of LOS and losartan carboxylic acid (EXP3174) were determined by Liquid Chromatography Mass Spectrometry (LC-MS) and pharmacokinetic analysis. Human liver microsomes, human multidrug resistance protein 1 (MDR1/P-gp), and breast cancer resistance protein (BCRP) vesicles, human embryonic kidney 293 cell line with stable expression of the organic anion transporting polypeptide 1B1 (HEK293-OATP1B1 cells) and mock-transfected HEK293 (HEK293-MOCK) cells were used to verify the effects of SMI on CYP450 enzymes and drug transporters in vitro.Results: Low, medium, and high concentrations of SMI increased the antihypertensive efficacy of LOS to varying degrees. The high dose SMI increased the half-life (t1/2), the maximum plasma concentration (Cmax), the area under the plasma concentration-time curve (AUC) from time zero to the time of the last measurable plasma concentration (AUC0-t), AUC from time zero to infinity (AUC0-∞), and mean residence time (MRT) values of LOS and decreased its apparent volume of distribution (Vd) and clearance (CL) values. The AUC0-t, AUC0-∞, and MRT of LOS were increased, whereas the CL was decreased by the medium concentration of SMI. In addition, the high, medium, and low doses of SMI increased the relative bioavailability (Frel) of LOS. SMI exhibited no significant effects on the pharmacokinetics of EXP3174. In vitro, SMI exhibited different suppressive effects on the enzyme activity levels of CYP1A2 (6.12%), CYP2B6 (2.72%), CYP2C9 (14.31%), CYP2C19 (12.96%), CYP2D6 (12.26%), CYP3A4 (3.72%), CYP2C8 (10.00–30.00%), MDR1 (0.75%), OATP1B1(2.03%), and BCRP (0.15%).Conclusion: In conclusion, SMI improved the antihypertensive efficacy of LOS in the L-NAME-induced hypertension rat model by increasing the concentration of LOS, while leaving the concentration of EXP3174 intact. SMI affected the pharmacokinetic properties of LOS by decreasing the elimination of LOS. These effects might partly be attributed to the inhibition of the activities of CYP3A4, CYP2C9, and of the drug transporters (P-gp, BCRP, and OATP1B1) by SMI, which need further scrutiny.

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“…For example, Ginkgo leaf tablets increased the plasma concentration of losartan and decreased the concentration of its metabolite via inhibiting the activity of CYP3A4 (Dong et al. 2018 ). Similarly, in the co-administration of berberine and losartan, berberine inhibited the activity of CYP3A4 or CYP2C9, which resulted in the inhibition in the pharmacokinetics of losartan (Li et al.…”

Section: Discussionmentioning

confidence: 99%

“…Previous reported drug-drug interaction indicated that the activity of cytochrome P450 enzymes is an important factor that mediated pharmacokinetic interaction between different drugs. For example, Ginkgo leaf tablets increased the plasma concentration of losartan and decreased the concentration of its metabolite via inhibiting the activity of CYP3A4 (Dong et al 2018). Similarly, in the co-administration of berberine and losartan, berberine inhibited the activity of CYP3A4 or CYP2C9, which resulted in the inhibition in the pharmacokinetics of losartan (Li et al 2016).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic study on the interaction between pachymic acid and bavachin and its potential mechanism

Zhang

Liu

et al. 2021

Pharmaceutical Biology

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Context Pachymic acid and bavachin are commonly used drugs in the therapy of lung cancer. Objective The co-administration of pachymic acid and bavachin was investigated to evaluate their potential drug-drug interaction. Materials and methods The pharmacokinetics of bavachin (10 mg/kg) was studied in male Sprague-Dawley (SD) rats in the presence of pachymic acid (5 mg/kg) ( n = 6). The rats without pre-treatment of pachymic acid were set as the control and the pre-treatment of pachymic acid was conducted for 7 days before the administration of bavachin. The effect of pachymic acid on the activity of CYP2C9 was also estimated in rat liver microsomes with corresponding probe substrates. Results Pachymic acid influenced the pharmacokinetic profile of bavachin with the increased AUC (32.82 ± 4.61 vs. 19.43 ± 3.26 μg/L/h), the prolonged t 1/2 (3.21 ± 0.65 vs. 2.32 ± 0.28 h), and the decreased CLz / F (307.25 ± 44.35 vs. 523.81 ± 88.67 L/h/kg) in vivo . The metabolic stability of bavachin was enhanced by pachymic acid and the transport of bavachin was inhibited by pachymic acid. Pachymic acid was found to inhibit the activity of CYP2C9 with the IC 50 of 21.25 µM as well as the activity of P-gp . Discussion and conclusion The interaction between pachymic acid and bavachin results from the inhibition of CYP2C9 and P-gp . The dose of bavachin should be adjusted when combining with pachymic acid. The study design can be generalized to a broader study population with adjustment in the dose.

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Effects of Ginkgo leaf tablets on the pharmacokinetics of losartan and its metabolite EXP3174 in rats and its mechanism

Cited by 8 publications

References 28 publications

Losartan Attenuates Atherosclerosis in Uremic Mice by Regulating Treg/Th17 Balance via Mediating PTEN/PI3K/Akt Pathway

Losartan Attenuates Atherosclerosis in Uremic Mice by Regulating Treg/Th17 Balance via Mediating PTEN/PI3K/Akt Pathway

Evaluation of Potential Herb-Drug Interactions Between Shengmai Injection and Losartan Potassium in Rat and In Vitro

Pharmacokinetic study on the interaction between pachymic acid and bavachin and its potential mechanism

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