Polygala tenuifolia Willd. (Polygalaceae) root is a remedy used in TCM for cardiotonic and cerebrotonic effects and is considered to act as a sedative and tranquilliser and to alleviate amnesia, neuritis and insomnia. According to the Chinese Materia Medica, the root is supposed to produce an effect upon the will and mental powers, improving understanding and strengthening memory, and the Pharmacopoeia of the People’s Republic of China (2005) includes Polygala tenuifolia root as a remedy to anchor the mind and for forgetfulness.
Since in TCM a mixture of herbs, rather than one single herb or other substance, is commonly prescribed, a number of studies have investigated a traditional Chinese prescription, known as DX-9386, for any activities that could have relevance in improving cognitive processes. DX-9386 is composed of Polygala tenuifolia in addition to Panax ginseng C.A. Mey. (Araliaceae), Acorus gramineus [Soland.] (Acoraceae) and Poria cocos (Schwein.) FA. Wolf (Fomitopsidaceae) (in the ratio 1:1:25:50 dry weight). Although this prescription has shown a number of favourable biological activities in relation to treating cognitive dysfunction, the contribution of each of the components in the prescription to the observed effects is unclear. Studies conducted have shown that DX-9386 may slow the ageing process as it ameliorated memory impairment and reduced lipid peroxide levels and prolonged lifespan in senescence-accelerated mice, and it ameliorated ethanol-induced memory impairment in rodents. The enhancement of hippocampal long-term potentiation of synaptic transmission by DX-9386 was attributed to P. ginseng and P. cocos, with Polygala tenuifolia only producing a minor effect.
Other studies have also investigated Polygala tenuifolia amongst a mixture of 12 prescription components in a formula known as kami-utan-to (KUT), a remedy used in traditional Japanese medicine to treat psychoneurological diseases. Studies have shown KUT to dose-dependently upregulate choline acetyltransferase activity and increase NGF secretion in vitro, and to improve passive avoidance behaviour and induce choline acetyltransferase activity in the cerebral cortex of aged rats and in scopolamine-induced memory impaired rats. These activities were mainly attributed to the Polygala tenuifolia content of the prescription, since the effects on choline acetyltransferase activity and NGF secretion were not as pronounced when treated with KUT in the absence of Polygala tenuifolia root, and Polygala tenuifolia root extract alone was shown to upregulate choline acetyltransferase activity and increase NGF secretion in vitro. The clinical potential of KUT in cognitive disorders has shown some promise, as KUT treatment improved memory-related behaviour in Alzheimer’s disease patients.
Some studies on Polygala tenuifolia root extract alone in the absence of other traditional remedies have provided more evidence to explain the use of this plant in TCM for CNS effects. Extracts reversed scopolamine-induced cognitive impairment and, to some extent, improved memory and behavioural disorders induced by CNS lesions in rodents; in addition, they showed a neuroprotective action against glutamate and amyloid precursor protein (amyloid precursor protein) in vitro and dose-dependently inhibited acetylcholinesterase activity in vitro, indicating an effect on cholinergic function in addition to other modes of action. Although extracts of Polygala tenuifolia have been associated with a neuroprotective action and an aqueous extract enhanced axonal length in cortical neurons treated with amyloid in vitro, the aqueous extract was not effective in recovering dendritic atrophy and synaptic loss. Anti-inflammatory activity could also contribute to the favourable CNS effects associated with this plant. An aqueous extract of Polygala tenuifolia root inhibited IL-1 mediated TNF secretion by astrocytes and dose-dependently inhibited ethanol-induced IL-1 secretion in vitro.
The compounds responsible for the effects of Polygala tenuifolia are unknown, although some cinnamic acid derivatives may explain the suggested cholinergic action as sinapic acid, a cinnamic acid derivative from Polygala tenuifolia root, increased choline acetyltransferase activity in the frontal cortex in brain-lesioned rats. Also from Polygala tenuifolia root is the acylated oligosaccharide tenuifoliside B, which has a sinapoyl moiety in its structure. This compound showed a cerebral protective effect on KCN-induced anoxia, and it ameliorated the scopolamine-induced impairment of performance in a passive avoidance task in rodents. It is suggested that sinapic acid, or a sinapoyl moiety, could be an important structural feature for the molecular interactions that modulate cognitve function. To support this theory, a further study was conducted which showed that sinapic acid also inhibited KCN-induced hypoxia and scopolamine-induced memory impairment and it inhibited basal-forebrain-lesion-induced cerebral cholinergic dysfunction in rodents. Tenuigenin, extracted from Polygala tenuifolia, inhibited β-amyloid secretion via β-secretase inhibition in vitro. Other compounds that have been associated with some of the in vitro effects observed with Polygala tenuifolia extracts include saponins with the aglycone pre-senegenin (onjisaponins A, B, E, F and G), which increased NGF levels in astrocyte cultures, with onjisaponin F also inducing the choline acetyltransferase mRNA level in rat basal fore-brain cells.