Oral epigallocatechin gallate reduces intestinal nadolol absorption via modulation of Oatp1a5 and Oct1 transcriptional levels in spontaneously hypertensive rats

Tan, Hong Jie; Ling, W.C.; Chua, Ang Lim; Lee, Siew-Keah

doi:10.1016/j.phymed.2021.153623

Cited by 7 publications

(5 citation statements)

References 26 publications

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“…The mechanism of interaction is not yet fully elucidated and may involve inhibition of organic anion-transporting polypeptides (OATP)1A2-mediated uptake of nadolol in the bowel by green tea catechins. It has already been shown by in vitro studies that green tea catechins inhibit the activity of OATP1A2 and OATP2B1 expressed in the apical side of the intestinal epithelium in humans [ 21 ]. The effects of green tea extract and epigallocatechin-3-gallate (EGCG) on the pharmacokinetics of nadolol, markedly reducing its bioavailability, were also studied in rats [ 22 ].…”

Section: Resultsmentioning

confidence: 99%

Cardiovascular Effects of Herbal Products and Their Interaction with Antihypertensive Drugs—Comprehensive Review

Nyulas,

Simon-Szabó,

Pál

et al. 2024

IJMS

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Hypertension is a highly prevalent population-level disease that represents an important risk factor for several cardiovascular complications and occupies a leading position in mortality statistics. Antihypertensive therapy includes a wide variety of drugs. Additionally, the potential antihypertensive and cardioprotective effects of several phytotherapy products have been evaluated, as these could also be a valuable therapeutic option for the prevention, improvement or treatment of hypertension and its complications. The present review includes an evaluation of the cardioprotective and antihypertensive effects of garlic, Aloe vera, green tea, Ginkgo biloba, berberine, ginseng, Nigella sativa, Apium graveolens, thyme, cinnamon and ginger, and their possible interactions with antihypertensive drugs. A literature search was undertaken via the PubMed, Google Scholar, Embase and Cochrane databases. Research articles, systematic reviews and meta-analyses published between 2010 and 2023, in the English, Hungarian, and Romanian languages were selected.

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Section: Resultsmentioning

confidence: 99%

Cardiovascular Effects of Herbal Products and Their Interaction with Antihypertensive Drugs—Comprehensive Review

Nyulas,

Simon-Szabó,

Pál

et al. 2024

IJMS

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“…Blood pressure of the SHR were measured on day 0 (one day prior to commencement of EGCG administration), 7, 14, 21, and 28 of the supplementation period using the indirect tail-cuff volume pressure recording method (CODA, Kent Scientific, Torrington, CT, USA) as stated in our previous study [ 16 ].…”

Section: Methodsmentioning

confidence: 99%

“…Uses of green tea or green tea extract in relation to its blood pressure-lowering effect have been demonstrated [ 14 ]. In in vivo studies, it has been demonstrated that the blood pressure-lowering effect of EGCG is in a time and dose-dependent manner [ 15 , 16 ]. Exploratory research has showed that EGCG is a potential blockage agent in inhibiting ACE and renin activities in in silico and in vitro studies [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Safety and Efficacy of Dietary Epigallocatechin Gallate Supplementation in Attenuating Hypertension via Its Modulatory Activities on the Intrarenal Renin–Angiotensin System in Spontaneously Hypertensive Rats

et al. 2022

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This study aimed to identify the no-observed-adverse-effect level (NOAEL) of dietary epigallocatechin gallate (EGCG) supplementation and its possible antihypertensive and nutrigenomics effects in modulating intrarenal renin-angiotensin system (RAS) gene expression in spontaneously hypertensive rats (SHR). EGCG (50, 250, 500 or 1000 mg/kg b.w. i.g., once daily) was administered to SHR for 28 days. All the SHR survived with no signs of systemic toxicity. Increased alanine aminotransferase (ALT), aspartate aminotransferase (AST) and thiobarbituric acid reactive substances (TBARS) were evident in SHR supplemented with 500 and 1000 mg/kg b.w. but not in those supplemented with lower doses of EGCG. Subsequently, the NOAEL of EGCG was established at 250 mg/kg b.w., and the same protocol was replicated to assess its effects on blood pressure and renal RAS-related genes in SHR. The systolic blood pressure (SBP) of the EGCG group was consistently lower than the control group. The mRNA levels of cortical Agtr2 and Ace2 and medullary Agtr2 and Ace were upregulated while medullary Ren was downregulated in EGCG group. Statistical analysis showed that SBP reduction was associated with the changes in medullary Agtr2, Ace, and Ren. Dietary EGCG supplementation exhibits antihypertensive and nutrigenomics effects through activation of intrarenal Ace and Agtr2 and suppression of Ren mediators, while a high dose of EGCG induced liver damage in SHR. In future clinical studies, liver damage biomarkers should be closely monitored to further establish the safety of the long-term use of EGCG.

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“…The importance of EGCG in altering epigenetics by binding with DNA methyltransferase and histone deacetylases has been emphasized [45]. As a result, Tan et al (2021) suggest that EGCG may affect the transcriptional levels of ileal Oatp1a5 and Oct1 through epigenetic modification [44]. This group of researchers also hypothesize that EGCG suppresses the expression of ileal Oatp1a5 and Oct1 by inhibiting the transactivation of the hepatocyte nuclear factor 4 alpha promoter [46] which ultimately leads to poor nadolol transportation across the enterocytes.…”

Section: Manuscriptmentioning

confidence: 99%

“…Another research team has expanded this research question and shown that 28 days of oral EGCG pretreatment as low as 10 mg/kg body weight significantly reduces the bioavailability of nadolol, C max , and AUC with no changes in nadolol t 1/2 , T max , and renal clearance in spontaneously hypertensive rats (SHRs), while reduced plasma nadolol is significantly associated with losses of the nadolol antihypertensive effect in EGCG-supplemented SHRs [44]. The team has revealed that (1) EGCG downregulates the gene expression of the drug transporters (Oatp1a5 and Oct1) lining the intestinal membrane and subsequently leads to poor nadolol absorption, low bioavailability of nadolol, and eventually lower antihypertensive effect in SHRs; (2) metabolism and elimination are less likely to contribute to the reduced bioavailability of nadolol, as it is a nonmetabolizing drug and renal clearance in EGCG-treated and non-treated groups are comparable [44]. The importance of EGCG in altering epigenetics by binding with DNA methyltransferase and histone deacetylases has been emphasized [45].…”

Section: Epigallocatechin Gallate Reduces Plasma Concentrations Of Be...mentioning

confidence: 99%

An Update on Impacts of Epigallocatechin Gallate Co-administration in Modulating Pharmacokinetics of Statins, Calcium Channel Blockers, and Beta-blockers

et al. 2023

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Brewed green tea, green tea extract (GTE), and its primary active compound, epigallocatechin gallate (EGCG) may interact with drugs and alter the drug’s therapeutic effectiveness ultimately leading to therapeutic failure or drug overdose. Several isolated reports have claimed that EGCG is the main active ingredient that causes these effects. Several isolated reports have claimed that EGCG is the main active ingredient that causes these effects. While a few studies aimed to uncover evidence of EGCG-drug interactions, no study has thoroughly and collectively reviewed them. EGCG is a potential cardio-protective agent used by many patients with cardiovascular diseases as a complementary medicine alongside conventional modern medications, either with or without the knowledge of their physicians. Therefore, this review focuses on the impact of concurrent EGCG supplementation on pharmacokinetics and pharmacodynamics of several commonly used cardiovascular drugs (statins, beta-blockers, and calcium channel blockers). Pubmed index was searched for keywords related to this review, without year limit and the results analysed for interactions of cardiovascular drugs with EGCG. This review concludes that EGCG increases systemic circulation of several statins (simvastatin, fluvastatin, rosuvastatin,) and calcium channel blockers (verapamil), but decreases the bioavailability of beta-blockers (nadolol, atenolol, bisoprolol). Further studies on its clinical significance in affecting drug efficacy are required.

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Oral epigallocatechin gallate reduces intestinal nadolol absorption via modulation of Oatp1a5 and Oct1 transcriptional levels in spontaneously hypertensive rats

Cited by 7 publications

References 26 publications

Cardiovascular Effects of Herbal Products and Their Interaction with Antihypertensive Drugs—Comprehensive Review

Cardiovascular Effects of Herbal Products and Their Interaction with Antihypertensive Drugs—Comprehensive Review

Safety and Efficacy of Dietary Epigallocatechin Gallate Supplementation in Attenuating Hypertension via Its Modulatory Activities on the Intrarenal Renin–Angiotensin System in Spontaneously Hypertensive Rats

An Update on Impacts of Epigallocatechin Gallate Co-administration in Modulating Pharmacokinetics of Statins, Calcium Channel Blockers, and Beta-blockers

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