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

Abstract

The herb Centella asiatica has long been considered a memory tonic. A recent review found no strong evidence for improvement of cognitive function, suggesting negative results were due to limitations in dose, standardization and product variation. We used a standardized extract of C. asiatica (ECa 233) to study behavioral, cellular and molecular effects on learning and memory enhancement. ECa 233 (10, 30, and 100 mg/kg) was given orally to normal rats twice a day for 30 days. We used the Morris water maze to test spatial learning and performed acute brain slice recording to measure changes of synaptic plasticity in the hippocampus, a core brain region for memory formation. Plasticity-related protein expressions (NR2A, NR2B, PSD-95, BDNF and TrkB) in hippocampus was also measured. Rats receiving 10 and 30 mg/kg doses showed significantly enhanced memory retention, and hippocampal long-term potentiation; however, only the 30 mg/kg dose showed increased plasticity-related proteins. There was an inverted U-shaped response of ECa 233 on memory enhancement; 30 mg/kg maximally enhanced memory retention with an increase of synaptic plasticity and plasticity-related proteins in hippocampus. Our data clearly support the beneficial effect on memory retention of a standardized extract of Centella asiatica within a specific therapeutic range.

Centella asiatica L. Phytosome Improves Cognitive Performance by Promoting Bdnf Expression in Rat Prefrontal Cortex

“…Our results suggest that triterpenes may be mostly responsible for the effects observed on cognitive performance; however, a quantitative analysis by LC-MS/MS performed on the whole brain only detected very low amount of madecassic and asiatic acids, very close to the limit of detection, whereas the corresponding glycosides were absent. Our findings are in accordance with a previous study [42], whereas contrasting results have been reported by other authors who have demonstrated the presence of asiaticoside and madecassoside in the hippocampi of rats that were treated with a standardized extract of C. asiatica [37]. Discrepancies could be due to several conditions, such as the dose, length of treatment, formulation, and composition of the phytocomplex.…”

“…Interestingly, we demonstrated that chronic treatment with the higher dose of C. asiatica L. improved cognitive performance. On the contrary, it has been demonstrated that C. asiatica L. induces memory enhancement at the doses of 10 and 30 mg/kg, but it does not do so at 100 mg/kg [37]. This discrepancy could be due to the different extracts or the lengths of treatment.…”

Therapeutic Potential of Centella asiatica and Its Triterpenes: A Review

“…The concentration of this factor is reduced in the brain of patients with neurodegenerative diseases (Lima Giacobbo et al, 2019). C. asiatica extract, asiatic acid, and (Gopi and Arambakkam Janardhanam, 2017;Nataraj et al, 2017b;Chintapanti et al, 2018;Boondam et al, 2019). C. asiatica and its triterpenoids affect neurological diseases possibly through the mitogen-activated protein kinase (MAPK) signaling pathway, phosphotidylinositol 3 kinase/protein kinase B/ mammalian target of rapamycin (PI3K/Akt/mTOR)signaling pathway, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling pathway ( Table 2).…”

Simultaneous analysis of five triterpenes in Centella asiatica by high performance liquid chromatography with cyclodextrins as the mobile phase additives

“…In China, it has been a long history of therapeutic uses, e.g., dampness-heat jaundice, heat stroke diarrhea, wound healing 1 – 4 . In recent years, its extracts and bioactive components have been reported to have anti-inflammatory 5 , anti-tumor 6 , 7 , anti-oxidant 8 , wound healing 9 , cardioprotective 10 and improving-memory effect 11 , 12 . Triterpenes are considered to be the major active components in C. asiatica , such as asiatic acid, madecassic acid, asiaticoside, madecassoside and asiaticoside B 13 , 14 .…”