Table 2.
Plants used in TCM and their constituents with relevance for dementia: cognition
| Plant name*, part and phytochemicals associated with biological activities | Traditional uses | Relevant bioactivities | Clinical effects/observations in humans |
|---|---|---|---|
| Ginkgo/maidenhair tree | TCM use dates back for centuries; Pharmacopoeia of the People's Republic of China includes seeds as a remedy for cough and asthma [55]. In Europe, leaf preparations were used to treat circulatory disorders in the 1960s; now a popular herbal remedy reputed to alleviate memory problems [56]. | EGb 761: Favorable effects on cerebral circulation, neuronal cell metabolism, the cholinergic system; has antioxidant activity, reduces apoptosis, and is neuroprotective against NO‐ and β‐amyloid‐induced toxicity; the latter effect is associated with the flavonoids [16, 56]. Other extracts improve cognition in young and old rats, short‐term memory in mice, and spatial learning and memory in rats with aluminum‐induced brain dysfunction; reduce cognitive impairment and hippocampal damage after ischemia and attenuate scopolamine‐induced amnesia in rats [16, 56]. Cognitive activities may be due to effects on cholinergic function and/or by modulation of the glutamatergic system, and/or possibly via histaminergic mechanisms [19]. | Clinical efficacy of extracts (including EGb 761) has been extensively evaluated in numerous RCTs with both AD and healthy subjects [16, 19, 56, 57]. A meta‐analysis of RCTs demonstrates clinically relevant positive results with G. biloba in AD patients [58]. Many trials indicate G. biloba can modestly improve cognitive ability, but trial outcomes are not consistently based on objective methods of analysis. One RCT in multiple sclerosis patients (120 mg extract twice daily) showed G. biloba to produce no significant improvement in cognition, but it was suggested to influence some cognitive processes (e.g., mental flexibility) [16]. Generally, oral administration is well‐tolerated with no serious adverse effects [16]. The use of G. biloba with antiplatelet or anticoagulant medicines may increase the risk of hemorrhage [59]. |
| Ginkgo biloba L. (Ginkgoaceae) | |||
| Leaves | |||
| Many studies have focused on a standardized extract of G. biloba: EGb 761 (contains flavonoid glycosides and terpenoid lactones amongst other constituents) | |||
| Huperzia serrata (Thunb.) Trevis. (Lycopodiaceae) | Used in TCM as a treatment for memory loss [56]. | Huperzine A: Improves cognitive processes in cognitively impaired and chronically hypoperfused rats, and in gerbils following ischemia [56]. Reversibly inhibits AChE in vitro and in vivo; more potent than huperzine B [14]. Is eight‐fold more potent than donepezil and two‐fold more potent than rivastigmine in increasing cortical ACh levels, with a more prolonged action [19]. Is neuroprotective against β‐amyloid peptide, oxygen‐glucose deprivation, free radical‐induced cytotoxicity, and glutamate; also an NMDA receptor antagonist in the cerebral cortex [56]. Attenuates apoptosis by inhibiting the mitochondria‐capase pathway and has neurotrophic effects [56]. Numerous synthetic analogues of huperzines A and B; include huprines X, Y, and Z which inhibit AChE more potently than huperzine [14]; a dimer derivative of huperzine B potently inhibits AChE, is neuroprotective against β‐amyloid, and improves scopolamine‐induced spatial performance deficits in rodents [4, 14]. | In phase IV clinical trials, huperzine A improved memory in elderly, AD, and VaD patients, with few adverse effects [16]. Clinical efficacy of huperzine A also demonstrated in other RCTs in AD patients with improvements in cognition, behavior, and mood [19]. A pro‐drug of huperzine, Debio 9902 (ZT‐1), was safe and effective when administered once daily to AD patients in a phase IIa clinical trial; further trials are in progress [7]. One small trial (14 VaD participants) showed no significant beneficial effect of huperzine A on improvement of cognitive function [60]. |
| Moss | |||
| Alkaloids: huperzines A and B | |||
| Ginseng | Used in TCM as a general tonic and reputed to invigorate the body and to prolong life [61]. | Numerous in vivo studies show individual ginsenosides to reduce or prevent memory deficits associated with cholinergic function; activation of estrogen receptors also suggested to explain effects on learning processes [61, 62]. Ginsenosides, Rg1 and Rb1 in particular, improve learning and memory in various memory‐impairment models [63] and enhance ACh levels in the CNS, by increasing choline acetyltransferase (ChAT) activity or by inhibiting AChE activity [19]. Extracts and ginsenosides are neuroprotective; ginsenoside Rg3 inhibits NMDA receptors [18, 19, 64]. | Studies in healthy volunteers show improved abstract thinking, attention, information processing, cognitive performance, auditory reaction time, social functioning, and mental health with a standardized ginseng extract (> 4% ginsenosides per oral dose); other studies in healthy volunteers show no quantifiable effects on memory; conflicting trial data are considered to be due to compositional differences in ginsenosides [62]. A review of RCTs using any type of P. ginseng to treat patients with AD focused on two trials assessing the effectiveness of ginseng as an adjunct to drug therapy on cognitive function compared with conventional drug therapy; results (MMSE and Alzheimer's Disease Assessment Scale) were significantly in favor of ginseng; due to methodological limitations, evidence for efficacy of ginseng in AD is inconclusive [65]. |
| Panax ginseng C.A.Mey. (Araliaceae) | |||
| Other species of Panax are used for similar indications | |||
| Root | |||
| Triterpenoid saponins: ginsenosides | |||
| Polygala tenuifolia Willd. (Polygalaceae) | Used in TCM for cardiotonic and cerebrotonic effects [16]; Pharmacopoeia of the People's Republic of China: a remedy to anchor the mind and for forgetfulness [55]. Used in traditional Japanese medicine as a mixture with 12 other prescription components (kami‐utan‐to (KUT)), to treat psycho neurological diseases. | Extracts reverse scopolamine‐induced cognitive impairment, are neuroprotective against glutamate, and APP in vitro and dose‐dependently inhibit AChE activity in vitro[16, 66]. Numerous studies on a TCM prescription (DX‐9386**), which ameliorates memory impairment in vivo[24, 56]. KUT increases nerve growth factor secretion in vitro, improves passive avoidance behavior, and induces ChAT activity in the cerebral cortex of aged rats and in scopolamine‐induced memory impaired rats; activities are mainly attributed to the P. tenuifolia content of the prescription [16]. | An extract (BT‐11) enhanced some cognitive functions including memory in elderly humans in a RCT [66]. In a 12‐month RCT (seven AD patients treated with KUT) the rate of cognitive decline was significantly slower than patients receiving no medication for AD, with efficacy most obvious at 3 months [67]. In a 12‐week trial, KUT combined with donepezil produced benefits on cognition and brain perfusion in AD patients, compared to donepezil monotherapy [68]. |
| Root | |||
| Only some cinnamic acid derivatives and onjisaponins have shown some relevant activities in vitro[16] | |||
| Saffron | Used in TCM to treat disorders of the nervous system [24]. | An extract and crocin improve learning behavior in vivo; crocin suppresses TNF‐α‐induced apoptosis of neuronally differentiated PC12 cells in vitro[24]. Extract and carotenoids inhibit β‐amyloid aggregation and are antioxidant [69]. | In a 22‐week double‐blind trial, AD patients treated with saffron showed comparable improvements in cognition compared to donepezil [70]. |
| Crocus sativus L. (Iridaceae) | |||
| Stigmas | |||
| Carotenoids: crocin |
*Common and Latin names (plant family).
**Composition: Polygala tenuifolia, Panax ginseng, Acorus gramineus[Soland.] (Acoraceae), Poria cocos (Schwein.) F.A. Wolf (Fomitopsidaceae) (ratio 1:1:25:50).