Centella asiatica: phytochemistry and mechanisms of neuroprotection and cognitive enhancement

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.

Centella Asiatica Improves Memory and Promotes Antioxidative Signaling in 5XFAD Mice

“…Numerous active CAW compounds are currently being examined in our laboratory to elucidate their effects on cognitive function, oxidative stress, and mitochondrial biogenesis and function. Previously, in vitro studies have shown that both CAW whole extract and isolated compounds (detailed in a review [32]) facilitate neurite outgrowth [6,28,106], and elicit neuroprotection [107][108][109][110][111]. The neurological effects of certain CAW active compounds are also observed in vivo, increasing learning and memory while providing neuroprotection in rodents [2,13,112].…”

“…Also, CA extracts have demonstrated positive effects on neurite elongation [6], neurodegeneration [29], antioxidant activity [30], and mitochondrial dysfunction [31]. These observations are the subject of a recent review [32].…”

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

“…Moreover, it is able to affect the brain; indeed, it is employed for its cognitive properties as a brain tonic and for its ability to improve learning performance and memory [5,6]. The terpenes of C. asiatica have been shown to have neuroactive and neuroprotective effects in different experimental models [7].…”

Kleeb Bua Daeng, a Thai Traditional Herbal Formula, Ameliorated Unpredictable Chronic Mild Stress-Induced Cognitive Impairment in ICR Mice

“…The methanolic extract of P. nigrum fruits was reported to enhance the cognitive function in the β-amyloid (1-42)-induced spatial memory impairment rat model by increasing the catalase, superoxide dismutase, glutathione peroxidase activities, as well as to reduce the level of malondialdehyde (MDA) [11]. On the other hand, C. asiatica was described to have cognitive enhancing properties by improving the antioxidant status, enhancing the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response pathway, decreasing the oxidative stress and inhibiting the proinflammatory enzyme, phospholipase A2 [12,13]. N. nucifera was found to exhibit antidepressant, anti-anxiety, and cognitive enhancement activities.…”