Pharmacokinetics of a Standardized Extract of Centella asiatica ECa 233 in Rats

Abstract

ECa 233, a standardized extract of , has been found to exhibit various positive neurological effects and to have a good safety profile. The present study aimed to explore the disposition kinetics of ECa 233, containing madecassoside (53.1 %) and asiaticoside (32.3 %), in rats. The extract was intravenously or orally administered at doses from 50 to 200 mg/kg. Plasma, tissues, urine, and feces were collected at time points from 0 to 48 h after dosing. The levels of madecassoside and asiaticoside, as well as their postulated triterpenic metabolites, madecassic acid and asiatic acid, in biological samples, were simultaneously measured by liquid chromatography-tandem mass spectrometry. The results showed that all animals had a good tolerability for ECa 233, whereas madecassic and asiatic acids were found in negligible amounts after pharmacokinetic assessment. Madecassoside and asiaticoside demonstrated rather similar absorption and tissue distribution profiles. They were rapidly absorbed, reaching maximum levels within 5-15 min after oral administration, but they had poor oral bioavailability, less than 1 %. Both triterpenoids were extensively distributed in the brain, stomach, and skin within 1 h and remained there for at least 4 h after dosing. Madecassoside and asiaticoside in ECa 233 were mainly excreted as an unchanged form after being injected, and exclusively as triterpenic acid metabolites in feces after oral administration. The pharmacokinetic results obtained could provide some guidance for an appropriate dosing regimen of ECa 233 in future studies. This study also provided the first evidence demonstrating the presence of madecassoside and asiaticoside in their target tissues.

GABA‐modulating phytomedicines for anxiety: A systematic review of preclinical and clinical evidence

“…3.2 | Anxiolytic phytomedicines with preclinical and human evidence 3.2.1 | Centella asiatica (Gotu cola/kola, pennywort) Centella asiatica is a native Asian herbaceous species used commonly as a whole plant extract in Indian Ayurvedic and Chinese Traditional Medicine (Diwan, Karwande, & Singh, 1991;Gohil, Patel, & Gajjar, 2010). Modern indications are for dermatotic, antimicrobial, nociceptive, cognition-enhancing, anxiolytic, and anti-depressive purposes (Anukunwithaya, Tantisira, Tantisira, & Khemawoot, 2016;Lokanathan, Omar, Ahmad Puzi, Saim, & Hj Idrus, 2016). The chief constituents are triterpenoid glycogens (saponins), sterols, flavonoids, tannins, and stearic acids.…”

Multiple Oral Dosing Pharmacokinetics of Standardized Extract of Centella asiatica ECa 233 and Its Inductive Effect on Efflux Transporters in Rats

“…Recently, a single-dose pharmacokinetic study of orally given ECa 233 was conducted in rats [20]. It was found that, after a single oral doses of ECa 233 at 50, 100, and 200 mg/kg, madecassoside and asiaticoside were rapidly absorbed, reaching their respective C max (madecassoside 1 654 ± 884, 5 664 ± 3 947, and 9 020 ± 5 744 µg/L; asiaticoside 318 ± 192, 1 283 ± 1 089, and 4 028 ± 3 157 µg/L) within 5-15 min.…”

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“…In agreement with traditional uses, ECa 233 exerts numerous pharmacological activities with minimal toxicity [6][7][8][9]16]. Some pharmacokinetic studies of ECa 233 at its effective dose range have been conducted in recent years [12]. In the present study, comparative pharmacokinetics between ECa 233 and a mixture of madecassoside and asiaticoside at equivalent amounts were conducted in male Wistar rats.…”

“…LC-MS/MS analysis was conducted under conditions and methods previously described in a pharmacokinetic study of ECa 233 [12]. In brief, an LC-MS/MS system was conducted with an Eksigent UPLC 100 and a QTRAP 6500 mass spectrometer and Analyst software version 1.6 (AB Sciex Pte., Ltd.).…”

“…Recently, our laboratory reported pharmacokinetic profiles following single and multiple oral dosings of ECa 233 in rodents [11,12]. This standardized extract showed dose linearity within a pharmacologically effective dose range of 50-200 mg/kg PO in male Wistar rats.…”