Pharmacokinetic Herb‐Drug Interaction between Hibiscus sabdariffa Calyces Aqueous Extract and Captopril in Rats

Abstract

Hibiscus sabdariffa L. (Malvaceae) is a traditional medicinal herb widely consumed as a beverage (“hibiscus tea”), and its global popularity is expanding due to health benefits such as blood pressure and cholesterol control. Previous studies showed that Hibiscus sabdariffa is coadministered with antihypertensives and antihyperlipidemics, thus predisposing herb-drug interactions. We investigated the pharmacokinetic interaction between H. sabdariffa L. aqueous extract and captopril, a frequently prescribed antihypertensive. In this study, chemical profile of H. sabdariffa L. aqueous extract was identified using HPLC system equipped with a DAD detector at 360 nm and 520 nm. The male Sprague Dawley rats were divided into two groups of six rats. Group I received a single dose of captopril suspension (4.5 mg/200 g body weight (BW) orally (p.o.)) while group II received H. sabdariffa L. aqueous extract (60 mg/200 g BW; p.o.) daily for two weeks prior to the same captopril dose. Multiple blood samples were collected at predetermined times after captopril administration and the plasma concentration was analyzed using ultrahigh-pressure liquid chromatography-tandem mass spectrometry. Chemical profiling of the H. sabdariffa L. aqueous extract showed that the extract contains chlorogenic acid, myricetin 3-arabinogalactoside, 5-O-caffeoylshikimic acid, quercetin 3-rutinoside, delphinidin 3-sambubioside, and cyanidin 3-sambubioside. Ingestion of the extract significantly reduced the captopril area under the curve (AUC)0−t (0.1745 (0.1254–0.2429)), AUC0−∞ (0.1734 (0.1232–0.2442))], and peak plasma concentration (0.2119 (0.1337–0.3359)) (geometric mean ratio of the coadministration group to the captopril group (90% CI)). The geometric mean ratios were falling outside the 90% CI of 0.8–1.25 bioequivalent range. Conversely, H. sabdariffa L. extract increased the apparent total body clearance (Cl/F, 0.0257 ± 0.0115 vs. 0.1418 ± 0.0338 mL/h·kg) and the apparent volume of distribution (Vd/F, 0.0541 ± 0.0226 vs. 0.3205 ± 0.0790 mL/kg). This study indicated that coadministration of H. sabdariffa L. aqueous extract could change the pharmacokinetic profile of captopril; therefore, its coadministration should be avoided.

Mekanisme Anti-Hipertensi dari Bunga Rosela (Hibiscus sabdariffa L.) dalam Pengobatan Berbasis Bahan Alam: A Systematic Review

“…Aldosteron akan menyebabkan terjadinya vasokontriksi berupa peningkatan penyerapan kembali natrium dan peningkaran cairan ekstraseluler sehingga hal tersebut dapat menyebabkan retensi cairan dimana terjadi peningkatan volume cairan ekstraseluler dan peningkatan tekanan darah di dalam arteri yang menyebabkan tingginya tekanan darah pada penderita hipertensi [27]. Antosianin, asam organik (hibiscus acid dan asam hidroksisitrat), asam fenolik, asam linoleat serta flavonoid (gossypetin, hibiscetin, kaempferol dan kuersetin) merupakan senyawa kimia yang terbuki terkandung dalam bunga rosela dan dapat menghambat perubahan angiotensin I menjadi angiotensin II [4,6,10,11,12,14,16,23,24]. Berdasarkan penelitian Salem dkk.…”

Pharmaceutical properties of sour tea (Hibiscus sabdariffa), Toward an ideal treatment for Hypertension

“…46,47 It has been shown that co-administration of HS aqueous extract can change the Pharmaceutical Sciences (Indexed in ISI and Scopus) https://ps.tbzmed.ac.ir pharmacokinetic profile of captopril; for that reason, its co-administration should be avoided. 48 Several studies have indicated that HS extracts can reduce the levels of TG, Tc, LDLc, and LDLc/HDLc in humans and animal models. 49 The aqueous extract of HS lowered Tc better than simvastatin and improved antihyperlipidemic activity when co-administered at low doses in an animal model.…”