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Centella asiatica: phytochemistry and mechanisms of neuroprotection and cognitive enhancement

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Abstract

This review describes in detail the phytochemistry and neurological effects of the medicinal herb Centella asiatica (L.) Urban. C. asiatica is a small perennial plant that grows in moist, tropical and sub-tropical regions throughout the world. Phytochemicals identified from C. asiatica to date include isoprenoids (sesquiterpenes, plant sterols, pentacyclic triterpenoids and saponins) and phenylpropanoid derivatives (eugenol derivatives, caffeoylquinic acids, and flavonoids). Contemporary methods for fingerprinting and characterization of compounds in C. asiatica extracts include liquid chromatography and/or ion mobility spectrometry in conjunction with high-resolution mass spectrometry. Multiple studies in rodent models, and a limited number of human studies, support C. asiatica’s traditional reputation as a cognitive enhancer, as well as its anxiolytic and anticonvulsant effects. Neuroprotective effects of C. asiatica are seen in several in vitro models, for example against beta amyloid toxicity, and appear to be associated with increased mitochondrial activity, improved antioxidant status, and/or inhibition of the pro-inflammatory enzyme, phospholipase A2. Neurotropic effects of C. asiatica include increased dendritic arborization and synaptogenesis, and may be due to modulations of signal transduction pathways such as ERK1/2 and Akt. Many of these neurotropic and neuroprotective properties of C. asiatica have been associated with the triterpene compounds asiatic acid, asiaticoside and madecassoside. More recently, caffeoylquinic acids are emerging as a second important group of active compounds in C. asiatica, with the potential of enhancing the Nrf2-antioxidant response pathway. The absorption, distribution, metabolism and excretion of the triterpenes, caffeoylquinic acids and flavonoids found in C. asiatica have been studied in humans and animal models, and the compounds or their metabolites found in the brain. This review highlights the remarkable potential for C. asiatica extracts and derivatives to be used in the treatment of neurological conditions, and considers the further research needed to actualize this possibility.

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Fig. 1
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Adapted from Azerad (2016)

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Adapted from Gray et al. J. Ethnopharmacology (2016)

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Adapted from Soumyanath et al. (2012)

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Acknowledgements

The authors acknowledge the following sources of grant support: NIH-NCCIH K99 AT008831 (NG), NIH-NCCIH R01AT008099 (AS, AA, CSM, JFS, JQ, PL), NIH-NCRR S10RR027878 (JFS), NIH-NCRR S10RR025628 (CSM), NIH-NCCIH T32 AT002688 (KW), Department of Veterans Affairs Merit Review grant (JQ).

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Gray, N.E., Alcazar Magana, A., Lak, P. et al. Centella asiatica: phytochemistry and mechanisms of neuroprotection and cognitive enhancement. Phytochem Rev 17, 161–194 (2018). https://doi.org/10.1007/s11101-017-9528-y

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