Comparison of the Pharmacokinetic Profiles of a Standardized Extract of Centella asiatica and A Mixture of Madecassoside and Asiaticoside in Rats

Abstract

Centella asiatica is a tropical plant commonly used as an herbal remedy in traditional medicines in many countries. In an attempt to establish an herbal extract with well-defined characteristics, a standardized extract of C. Asiatica, ECa 233, was developed. This extract contains at least 80% triterpenoid glycosides with the major constituents madecassoside and asiaticoside at a ratio of 1.5±0.5:1. In the present study, comparative pharmacokinetics of ECa 233 with its mixture of madecassoside and asiaticoside were conducted in rats. Following intravenous or oral administration of the test compounds, blood, tissues, urine, and feces were collected for the determination of madecassoside, asiaticoside, and their metabolite levels using liquid chromatography tandem mass spectrometry. Plasma levels of madecassoside and asiaticoside in the ECa 233-treated group were found to be higher than their respective counterparts in the mixture. Madecassoside and asiaticoside in both test formulae appeared to be widely distributed in several organs, and more than 50% of the administered doses were recovered as madecassic acid and asiatic acid in the feces within 24 to 48 h. The results clearly demonstrated the pharmacokinetic advantage of a standardized extract of C. Asiatica, ECa 233, compared with a mixture of madecassoside and asiaticoside at an equivalent amount. Other minor constituents that naturally exist in ECa 233 appeared to positively modulate the pharmacokinetics of its major constituents, resulting in relatively better pharmacokinetic profiles than those from a mixture of pure compounds.

Inverted U-shaped response of a standardized extract of Centella asiatica (ECa 233) on memory enhancement

“…ECa 233 is an off-white extracted powder of Centella asiatica . The compounds of the ECa 233 extract were analyzed by using HPLC ESI-QTOF-MS/MS technique compared with analytical standards, and the quantitative analysis was performed with a triple quadrupole LC-MS/MS system 40 . Two major components corresponding to the two major peaks in the analysis were madecassoside and asiaticoside.…”

Acute enhancing effect of a standardized extract of Centella asiatica (ECa 233) on synaptic plasticity: an investigation via hippocampal long-term potentiation

“…The effects of ECa 233 could possibly be related to some absorption-influencing factors, such as intestinal metabolism and efflux transporters (Anukunwithaya et al 2017a). As observed, the oral administration of ECa 233 demonstrated a slow onset of action, possibly because of its poor oral bioavailability and the large molecular weight of its parent compounds (Anukunwithaya et al 2017b;Khemawoot et al 2018); hence, the distribution of the compounds to various organs might be time dependent. According to a pharmacokinetic study, 4 h after ECa 233 administration, the distribution of the parent compounds in the brain tissues by the oral route was slightly lower than that by the IV route (Anukunwithaya et al 2017b).…”

“…However, the mechanisms of C. asiatica extract, especially the exact active compounds of the extract that produce the memoryenhancing effect, remain unclear. Although C. asiatica extract mainly contains triterpenoid glycosides with very few triterpenic acid metabolites, namely, madecassic acid and asiatic acid (<1% in ECa 233), b-glycosidases from gut microbiota metabolize the triterpenoid glycosides to triterpenic acid metabolites after the oral administration of the extract (Anukunwithaya et al 2017b;Khemawoot et al 2018). In rats, triterpenic acid metabolites were largely found in faeces (approx.…”

“…Other studies have demonstrated that the duration of oral administration ranged from 2 weeks to 2 months (Soumyanath et al 2012;Tabassum et al 2013;Puttarak et al 2017;Gray et al 2018;Ar Rochmah et al 2019). In contrast, intravenous ECa 233 shows 100% bioavailability, and it can cross the blood-brain barrier, as observed in brain tissue accumulation (Anukunwithaya et al 2017b;Khemawoot et al 2018;Boondam et al 2019). Thus, ECa 233 perfusion into the acute hippocampal slices will show the direct action of ECa 233 on the hippocampal neurons in which their synaptic plasticity is crucial for learning and memory.…”

Untitled

“…CA builds up large quantities of pentacyclic triterpenoid saponins that include asiaticoside, centelloside, madecassoside, brahmoside, brahminoside, thankuniside, sceffoleoside, centellose, asiatic, brahmic-, centellicand madecassic acids 30,68 . Asiaticoside and madecassoside and the sapogenin -asiatic acid are generally employed as the bioactive markers for standardization of the plant 31,69 .…”