Bacopa monniera Wettst

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Bacopa monniera Wettst. (Scrophulariaceae), known by the common name 'brahmi', has been used in Ayurvedic medicine for almost 3000 years as a nerve tonic and to improve intellect and memory [128]. Various investigations have attempted to substantiate and identify a scientific basis for the reputed effects. A number of in vivo studies have shown B. monniera extracts to improve cognitive function [128-130]. The mode of action to explain these effects has yet to be fully elucidated. Some studies suggest that the antioxidant effects of B. monniera may protect the CNS from oxidative damage. Extracts of B. monniera have been reported to induce a dose-related increase in superoxide dismutase, catalase and glutathione peroxidase activities in the rat frontal cortex, striatum and hippocampus [131], to dose-dependently inhibit nitric oxide (NO)-related toxicity (DNA damage) in cultured rat astrocytes [132] and to inhibit aluminium-induced neurotoxicity in the rat brain [133]. The antioxidant effects of B. monniera have also been suggested to alter amyloid plaque formation [134,135]. In addition to antioxidant effects, B. monniera has also shown anti-inflammatory activity in vivo [128, 136]. It is reported to modulate the cholinergic system [128] and has an anxiolytic action [137]. It is therefore possible that B. monniera may exert multiple effects on the CNS.

Although the majority of relevant studies which have investigated the reputed cognitive-enhancing effects of B. monniera have focused on extracts rather than isolated constituents, it is the triterpenoid saponins, reported to occur in the aerial parts of B. monniera [138-142], which have been associated with the activity. The dammarane-type triterpenoid saponins, a mixture known as bacoside A which includes bacoside A3 (15), have been shown to protect rat brains from smoking-induced apoptosis [143] and from structural and functional impairment of mitochondria [144].

Clinical studies have so far only been undertaken on healthy volunteers. In one double-blind, placebo-controlled study with normal healthy subjects treated with B. monniera extract, no acute effects on cognitive function were observed [145]. However, a double-blind, randomised, placebo-controlled study on patients aged 40 to 65 years showed that those given a standardised extract of B. monniera resulted in a significant improvement in retention of new information but no difference in the rate of learning, attention, and verbal and visual short-term memory [146]. Another similar study investigated the speed of visual information processing, learning rate and memory consolidation and concluded that the B. monniera extract improved higher-order cognitive processes such as learning and memory [147].

15.4.3 Centella asiatica (L.) Urb.

An ancient Ayurvedic remedy, Centella asiatica (L.) Urb. (Apiaceae), also known by the synonym Hydrocotyle asiatica L., is reputed to restore youth, memory and longevity [148]. In Sanskrit, and commonly as an herbal product, it is known as 'gotu kola'. An Ayurvedic formulation composed of four herbs including C. asiatica, is used to retard age and prevent dementia, and the herb combined with milk is given to improve memory [149]. In TCM C. asiatica has been used for various disorders, such as traumatic diseases, and for combating physical and mental exhaustion [150, 151]. The essential oil from C. asiatica leaf contains monoterpenoids, including bornyl acetate, a-pinene, (P-pinene and y-terpinene [150, 152], all of which are reported to inhibit AChE [153-155]. However, monoterpenoid AChE inhibitors are weak compared to the anti-ChE alkaloid, physostigmine [154]. In view of the relatively weak anti-ChE activity of monoterpenoids reported to date, it is unlikely that they would be therapeutically effective in cognitive disorders.

The pharmacological basis to explain the reputed antiamnesic effects of C. asiatica has been explored in a number of studies. An alcoholic extract of C. asiatica was tranquillising in rats, an activity that was attributed to a triterpenoid, brahmo-side [148, 156]. Further studies showed the extract of C. asiatica leaf to be sedative, antidepressant and potentially cholinomimetic in vivo [156], and asiaticoside, a triterpenoid saponin from C. asiatica, is a reported anxiolytic [157, 158]. These findings suggest that C. asiatica may be appropriate to treat symptoms of depression and anxiety in AD, and that it may also influence cholinergic activity and, thus, cognitive function. Cognitive enhancing effects have been observed in rats following oral administration of an aqueous extract of C. asiatica; this effect was associated with an antioxidant mechanism in the CNS [159]. Further evidence for the antioxidant benefits of C. asiatica extract were observed when it was administered orally to rats and was shown to protect the rat brain against age-related oxidative damage [160]. Knowledge regarding the compounds responsible for these effects is lacking, although phenolic compounds in C. asiatica have been correlated with antioxidative activity in vitro [161]. An aqueous extract of this plant has also been shown to decrease seizures and prevent cognitive impairment in an animal model for epilepsy [162].

Alterations in other neurotransmitter systems have been associated with AD pathology [163,164]. Interestingly, an aqueous extract of C. asiatica leaf modulated dopamine, 5-hydroxytryptamine (5-HT) and noradrenaline systems in rat brain and improved learning and memory processes in vivo [165]. Glutamate may induce neuronal degeneration by overstimulation of NMDA receptors, and memantine (13), an NMDA receptor antagonist, is therapeutically effective in AD patients [112, 113]. The triterpenoid asiatic acid (16) (found in C. asiatica) and its derivatives have been shown to protect cortical neurons from glutamate-induced excitotoxicity in vitro [166]. A neuroprotective action may contribute to changes in the dendritic morphology of neurons in the CNS. This has been suggested by a study in which stimulation of neuronal dendritic growth in hippocampal neurons was observed following administration of leaf extracts of C. asiatica to neonatal rat pups [167]. Components in C. asiatica including asiatic acid have also been suggested to accelerate repair of damaged neurons [168]. This action, perhaps in conjunction with other observed biological activities relevant to the alleviation of cognitive dysfunction, could explain the basis for the reputed memory-enhancing effects of this plant.

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