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Plants traditionally used in age related brain

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Plants traditionally used in age related brain disordersA survey

of ethnobotanical literature
Michael Adams, Francine Gmunder, Matthias Hamburger
Institute of Pharmaceutical Biology, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland

Abstract
In traditional herbal medicine, numerous plants have been used to treat age related cognitive disorders. In this review we compiled available
literature from four Swiss university libraries, scientific journals and online database querys on plants and remedies used in traditional medicinal
systems for such diseases. Over 150 plant species in various preparations and mixtures were found. European herbals from the 16th and 17th
century alongside traditional Chinese and Indian medicinal works were the most prolific sources. The information is organised into geographic
regions and when available the findings are discussed in the light of more recent scientific findings concerning their secondary metabolites and
in vitro and in vivo activities relevant to dementia and Alzheimers disease.
Keywords: Ethnomedicine; Traditional medicine; Herbal remedies; Alzheimers disease; Senile dementia

Contents
1.
2.
3.
4.
5.
6.

7.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Literature search and organisation of information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Europe . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
The Americas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Africa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Asia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.1. Traditional Chinese medicine (TCM) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.2. Korea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.3. Japan . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.4. Ayurveda. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Conclusions and perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Appendix A. Supplementary data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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378

1. Introduction

Abbreviations: ACh, acetylcholine; AChE, acetylcholinesterase; APP,

amyloid precursor protein; BuChE, butyrylcholinesterase; ChAT, choline acetyltransferase; GABA, gamma aminobutyric acid; NMDA, N-methyl-d-aspartate;
PKC, protein kinase C; TCM, traditional Chinese medicine.
Corresponding author. Tel.: +41 61 267 14 25; fax: +41 61 267 14 74.
E-mail address: matthias.hamburger@unibas.ch (M. Hamburger).

The occurrence of dementia and age related brain disorders

is dramatically on the rise as life expectancy likewise increases.
Alzheimers disease (AD), a complex, multifactoral, progressive, neurodegenerative disease primarily affecting the elderly
population is estimated to account for 5060% of dementia
cases in persons over 65 years of age. According to the World

Health Organisation (WHO, 2006), around 35 million people

in industrialized countries will suffer from AD by 2010. The
disease is characterized by loss of memory and impairment of
multiple cognitive and emotional functions (Frank and Gupta,
2005). The pathological features identified in the central nervous system (CNS) in AD are amyloid plaques, neurofibrillary
tangles, inflammatory processes and disturbance of neurotransmitters (Selkoe, 2001; Bossy-Wetzel et al., 2004). Basically
brain cells wither away and die, causing disorientation, dementia and severe changes in personality and social interactions.
There is currently no cure for most forms of dementia including
AD. Pharmacotherapy is focussed on symptomatic benefit and
slowing disease progression (Desai and Grossberg, 2005), but
a number of possible disease modifying and preventive strategies based on current understanding of AD pathophysiology are
under investigation (Citron, 2004; Selkoe, 2005).
Before the development of modern medicine people relied
on a large arsenal of natural remedies for the treatment of CNS
related maladies. In western societies, here has been increasing interest in herbal medicines, which are often perceived as
a more natural and soft treatments compared to synthetic
drugs. Successful treatments for dementia have been developed from herbal drugs. Extracts from Ginkgo biloba (mainly
EGb 761a standardised extract marketed by Wilmar Schwabe
GmbH) have been proven effective in clinical trials as a treatment for Alzheimer type dementia and vascular dementia (Gertz
and Kiefer, 2004). Ginkgo extracts also has a favourable safety
profile (Andrieu et al., 2003; Stromgaard et al., 2005). Galantamine, an alkaloid obtained from the bulbs and flowers of the
Caucasian snowdrop Galanthus woronowii (Amaryllidaceae)
(Heinrich and Teoh, 2004), is a fine example of a plant secondary compound successfully used for the treatment of mild
to moderate AD (Bullock and Dengiz, 2005; Marco-Contelles
et al., 2006). Several milestones in the history of drug therapy
have been discovered from ethnomedical knowledge, such as
atropine, pilocarpine, cardiac glycosides, curare, and reserpine.
Sourcing in ethnomedical information may also be useful as a
starting point for the discovery of new drugs for the treatment of
AD and cognitive disorders. Here we have compiled literature
available from seven libraries and recent literature of scientific
journals from online database searches.
2. Literature search and organisation of information
The four main Swiss university libraries in Berne, Basel,
Zurich, and Geneva were searched for relevant ethnobotanical
literature. Furthermore, the Library of the Museum of Cultures
(Museum der Kulturen), of a third world project, Mission 21
and the Swiss Pharmaceutical Museum, all three in Basel, were
also at our disposal. Suitable books of potential literature sources
were identified in online databases of the particular libraries by
searching for the terms ethno medicine, traditional medicine,
folk medicine, indigenous medicine, herbs, traditional herbs,
plants, indigenous plants, ethno botany and botanical medicine.
The search was further refined by checking the titles of retrieved
books. Finally, a total of 192 books were consulted. Information
was searched for by scanning the indices of books for keywords

related to the topic. For books lacking an index, the tables of

contents and list of plants were scanned through. Of these 192
books, 140 contained no specific listings for certain plants used
in the treatment of age related brain disorders. They are nevertheless listed separately as Supplementary information. The
relevant remainder of this collection was carefully viewed, information extracted and corroborated with data from other sources
to compile this survey.
Two electronic sources, the online databases PubMed and
Scifinder, were used to search for additional information in journals. Linguistic constraints limited us to literature in English,
Italian, French, German and Spanish. The terms ethno medicine,
traditional medicine, folk medicine, indigenous medicine, herbs,
traditional herbs, plants, indigenous plants, ethno botany and
botanical medicine were combined with terms like Alzheimer,
Alzheimers disease, used to treat Alzheimers disease, dementia, senile dementia, and memory loss. Plants and herbal
combinations traditionally used for the treatment of age related
brain diseases are listed according to geographic regions.
3. Europe
Europe is the birthplace of modern western rational medicine.
With the industrialization came the development of modern
synthetic drugs, medicinal equipment and health care institutions such as hospitals or nursing homes. Yet the continent has
long traditions of phytotherapy dating back thousands of years.
Especially in the German speaking world herbal remedies still
play an important role and any pharmacy will provide and produce a large number of plant based medicines (Reuter, 1991).
Today, many traditional medical practices in Europe are summarized by the popular terms alternative or complementary
medicine. In widespread understanding these terms also include
more recent techniques such as homeopathy, spagyrik, dance
or music therapy, acupuncture, etc.
Tabernaemontanus (1687) recommended sage, Salvia sp.,
from various regional provenances for the treatment of a weak
brain. Flowers should be crushed and mixed with sugar. Or
the plant can be extracted in strong wine in the sun for a day
before distilling. The remedies help those who shiver and suffer the effects stroke and strengthen weak minds and memories.
Most pharmacological research on Salvia has been done with
the essential oils of Salvia ofcinalis and Salvia lavendulifolia,
and a number of promising pharmacological results have been
published. Since Perry et al. (2000, 2003) recently provided a
review, summarizing available literature on the use of Salvia
species in dementia therapy, this plant will only be treated briefly.
Savelev et al. (2004) examined the inhibition of the butyrylcholinesterase (BuChE) by essential oils from Salvia fruticosa,
Salvia ofcinalis var. purpurea, Salvia ofcinalis and Salvia
lavendulaefolia. The IC50 values measured after 5 min of incubation were 0.05, 0.4, 0.03, 0.07 and 0.0.3 mg/ml, respectively.
Additionally pure compounds from the oil were tested, none of
which could fully account for the activity of the essential oils.
Salvia lavandulaefolia and Salvia ofcinalis purpurea oils had
apparent dual cholinergic activity, as they were active on both,
AChE and BuChE (Savelev et al., 2004). Besides the choliner-

gic activity, there has already been a wider range of activities

reported for the genus Salvia, which may be relevant for CNS
disorders. These include nicotinic activity (Wake et al., 2000),
anti-inflammatory properties (Moretti et al., 1997), antioxidant
(Zupko et al., 2001), estrogenic (Bartram, 1995) and glutamergic
activities (Kuang and Xiang, 1994). In a double blind, randomized, placebo-controlled trial, with 39 patients, Akhondzadeh et
al. (2003) assessed the efficacy and safety of Salvia ofcinalis
extract in patients with mild to moderate AD. The participants
experienced statistically significant benefits in cognition after 16
weeks of treatment. Despite the limitations of this study, a small
number of patients and a relatively short period of follow-up, this
initial clinical data suggests that Salvia lavandulaefolia essential oil and extracts, may have potential for treatment of AD
and memory related disorders. Salvia spp. leaves contain tannins, tannosetonins and essential oil. The essential oil content of
12% varies within the plant and location. The components of
the essential oil vary in the different Salvia species (Savelev et
al., 2004). The oil of Salvia ofcinalis is rich in -caryophyllene
(23.2%), camphor (11.0%) and borneol (8.7%), while, camphor, 1,8-cineole and 2-carene are abundant in the oil of Salvia
lavendulaefolia (Sfikas, 1980).
Aerial parts of lemon balm, Melissa ofcinalis (Lamiaceae)
are finely cut and covered in good wine over night in a clean dish,
before being distilled. Taken on an empty stomach a spoonful
quickens the senses, brightens the mind and improves memory.
It aides shaking limbs caused by stroke, and helps retrieve the
lost ability to speak (Lonicerus, 1679). The remainder of this
historic citation is a romantic description of clever bees sucking
at the flowers. Essential oil of Melissa ofcinalis, which contains
monoterpenes such as citral and citronellal (Mills, 1993), shows
a dose-dependent inhibitory effect on the enzyme AChE, with
IC50 values of less than 0.1 l/ml (Perry et al., 1996).
Lonicerus (1679) reports that dried parsley roots (Petroselinum crispum, Apiaceae) soaked in good wine can
improve brain function and memory, alongside their then more
widespread uses as an abortifacient, aiding birth labour and
weaning.
Galbanum, a resin from the roots of Ferula gummosa (Apiaceae) and its subspecies and varieties should be crushed, hot
water added and left overnight. Then essential oil is distilled here
from. The oil can be applied to the neck or drunk for improving
memory, hearing and sense of smell (Tabernaemontanus, 1687).
The use of this plant, native to Syria and grown in herb gardens
by European practitioners might have biblical roots, as it was
part of incense in the tabernacle (Exodus 30, 3436).
The flowers of Caryophyllus species (Caryophyllaceae) are
crushed with sugar so create a candy Confecta florum
Caryophyllum which is consumed to treat fever, strengthen
the brain and the memory. Cloves, the highly revered fruits of
Syzygium aromaticum (Myrtaceae) were regarded as a similar
plant and served as a remedy against weakness of the brain,
stroke and loss of memory (Tabernaemontanus, 1687). Another
non-native plant used in a confectum was the fruit of Anacardium
orientale (Anacardiaceae). It was processed to a Confectio
Sapientum a wisdom candy. Flowers of German chamomile,
Matricaria recutita (Asteraceae) are soaked in water. A person

who drinks this at least 23 times a week and washes his feet in
it should retain good memory (Tabernaemontanus, 1687).
There are numerous recipes for various types of aquavit. Aquavits, literally water of life, are strong alcoholic
beverages with very complex modes of preparation. Numerous such drinks, are still widely sold today for medical or
recreational purposes. Only one such comprehensive recipe
will exemplarily be described here, as further listings would
exceed the scale of this review. Tabernaemontanus (1687) lists
an aquavit which was claimed to be particularly useful in
treating forgetful old people. Arial parts of Achillea millefolium (Asteraceae), Adiantum capillus-veneris (Pteridaceae),
Horminum sp. (Lamiaceae), Eryngium caeruleum (Apiaceae),
Foeniculum vulgare (Apiaceae), Petroselinum crispum (Apiaceae) and roots of Asparagus ofcinalis (Asparagaceae) and
Cichorium endivia (Asteraceae) are extracted with good wine.
This concoction is then distilled before cinnamon (Cinnamomum verum, Lauraceae), caraway (Carum carvi, Apiaceae),
either lavender (Lavandula angustifolia, Lamiaceae) or valerian
(Valeriana celtica, Valerianaceae), ginger (Zingiber ofcinale,
Zingiberaceae) and pepper (Piper nigrum, Piperaceae) are added
alongside more good red wine. Then the roots of greater
galangal (Alpinia galanga, Zingiberaceae), lovage seeds (Levisticum ofcinale, Apiaceae), Caryophyllus sp. (Caryophyllaceae)
seeds, nutmeg (Myristica fragrans, Myristicaceae) and finally
Piper cubeba (Piperaceae) are placed in the concoction before
it is left for 8 days and then again distilled. Finally, to complete the aquavit recipe musk and amber are added. This remedy
should be mixed with wine and consumed regularly by old
people to strengthen the head, brain and memory according to
Tabernaemontanus (1687), who made a strong emphasis on the
quality of wine used for its preparation.
Half a spoonful of coriander, Coriandrum sativum (Apiaceae)
seeds covered in a little sugar can be taken to strengthen head,
brain and memory. If so much sugar was used to coat the seeds
that they were as large as peas, then the remedy helped patients
fall asleep (Tabernaemontanus, 1687).
The flowers of the Lilly of the Valley, Convallaria majalis
(Convallariaceae) should be crushed with sugar to make a candy
to treat fever and strengthen the brain, senses and memory
(Tabernaemontanus, 1687). Actually two forms of the herb
are described, of which one fits the description of Convallaria majalis, and the other one is said to be identical but for
the fact that it blooms red. Herba Convalariae contains toxic
cardenolides like convallatoxin, convallatoxol, lokundjosid and
convallosid, as well as flavanoids and saponins (Krenn et al.,
1996). It has been used for heart insufficiency, and was officially
listed in the German pharmacopoeia.
Herb from Euphrasia ofcinalis complex (Orobanchaceae,
formerly included amongst the Scrophulariaceae) is traditionally used in many parts of Europe for ailments of the eyes.
Tabernaemontanus (1687) states that the powdered herb, when
taken in wine may cure a stupid brain and strengthens the
head. It contains various iridoid glycosides, such as aucubin,
catalpol and euphrosid, the lignan dehydrodiconiferylalcohol4-d-glucoside, tannins and flavanoids (Sticher and Salama,
1981).

To sharpen senses and memory wine containing marjoram, Origanum majorana (Lamiaceae) should be consumed. It
strengthens the head and the inner organs (Tabernaemontanus,
1687). Powdered marjoram can be spread on the tongue to return
lost speech and strengthen brain and memory. Snuffed it makes
you sneeze and thereby cleanses the brain. In salt and vinegar it is said to help against scorpion bites and in wine it is
a diuretic (Fuchs, 1543). Origanum majorana contains large
amounts of essential oil consisting mainly of monoterpenes and
some sesquiterpenes (Raghavan et al., 1997). Basil, Ocimum
basilicum (Lamiaceae) strengthens the heart and head and
dispels darkness from the eyes (Fuchs, 1543).
Fuchs (1543) recommended smelling the very aromatic
flowers of Lavandula stoechas (Lamiaceae) in its various
geographic forms to strengthen a stupid and dizzy brain.
Tabernaemontanus (1687) cites Plinius in warning that ivy (Hedera helix, Araliaceae) should not be consumed because it makes
one wrong in ones head and weakens the nerves.
In 1978 Brndegaard reported on the traditional use of plants
in Denmark, from the Middle Ages through to present times.
Based on this, the genus Corydalis (Papaveraceae) was selected
for the isolation of compounds and in vitro examinations, as it
had been used in the treatment of memory dysfunction. Adsersen
et al. (2005) showed that protoberberine and protopine-type
alkaloids, common compounds in Corydalis species, are potent
AChE inhibitors. The inhibition of the enzyme was examined,
with methanolic and aqueous extracts of Corydalis species. Inhibition by methanolic extracts was generally higher than by the
water extracts. Tuber- and herb-extracts were assayed at concentrations of 0.1, 0.05 and 0.025 mg/ml. With 92%, 83% and 77%
for the methanolic tuber extract of Corydalis cava showed the
best results compared to Corydalis intermedia, Corydalis solida and Corydalis solida ssp. slivenensis. Pure protopine had an
IC50 value of 50 M (Adsersen et al., 2005). In a passive avoidance task test mice treated with protopine exhibited diminished
scopolamine-induced dementia (Kim et al., 1999).
Galanthamine is an alkaloid from Galanthus spp. and other
Amaryllidaceae, such as Narcissus and Leucojum species. It is a
selective and competitive AChE inhibitor. It has been approved
and is successfully used as a treatment for AD in numorous
countries. Wether or not galanthamine containing plants were
traditionally used in Europe to treat dementia is not really clear
(Heinrich and Teoh, 2004). It is appellative that a drug for the
treatment of the most severe form of dementia was developed
from the little snowdrop the first sign of spring a symbol of
regeneration in nature (Heinrich, 2005).
Consistent with current aroma therapeutic applications of
rosemary Rosmarinus ofcinalis (Lamiaceae) to improve memory, the ancient Greeks considered this herb a stimulator of the
mind, in particular the memory. Indeed many early European
writings refrain to rosemary to be a memory enhancer (see Perry
et al., 1999, and citations therein).
In a handwritten folk-medicinal document from the Diemtigtal valley in the Berner Oberland in Switzerland Artemisia
absinthium L. (Asteraceae) together and chervil (Anthriscus
cerefolium, Apiaceae) water a distilled beverage is recommended to improve memory (Personal communication M.

Kluge, Swiss Pharmaceutical Museum). Artemisia absinthium

has a record of use against declining cognitive function (see
Wake et al., 2000). An alcohol extract displaced nicotine from
nicotine binding receptors (Perry et al., 1996; Wake et al., 2000).
Hodl et al. (2000) showed -thujon to have GABAA receptor
antagonist activity. These reports should be viewed with caution, considering the toxicity of absinthe, a strong alcoholic
drink, which when abused, leads to hallucinations, sleeplessness,
tremors, and convulsions, a syndrome known as absinthism. The
monoterpene thujon is responsible for these effects (Olsen, 2000;
Lachenmeier et al., 2006) (Table 1).
4. The Americas
The meaning of the term medicine to Native Americans
was quite different from that of Western societies. Illness was
regarded as a disharmony or imbalance that may be directly
related to spiritual causes, which may have natural, human or
supernatural origins. A persons equilibrium can be lost as a
result of grief, sadness, hatred or personal wrongdoing (Kavasch
and Baar, 1999). The concept of healing is to determine what
has to be rectified and to bring the person back into balance.
Practices to draw people back into equilibrium, include rituals,
sweat lodge rites of purification, spirit feasts, fumigation and
smoke therapy, massage, prayers, blessings, incantations and
herbals (Vogel, 1970).
Despite the vast number of books and references on American Indian medicine and related topics, we only found a few
references of plants used in the treatment of AD and related
symptoms affecting the memory.
One remedy, unknown from which tribe it originated,
includes eight different plants: Clematis sp. (Ranunculaceae),
Larrea tridentate (Zygophyllaceae), Oplopanax horridus
(Araliaceae), Capsicum annuum (Solanaceae), Ginkgo biloba
(Ginkgoaceae), Centella asiatica (Apiaceae), Chrysanthemum
sp. (Asteraceae) and Rosmarinus ofcinalis (Lamiaceae). A
blend of these herbs was administered to assist memory as well
as for eczema, emphysema and asthma. It must be remarked
that Centella asiatica and Ginkgo biloba are not native to North
America but to Asia (Kavasch and Baar, 1999).
A tincture of the roots of Lachnanthes tinctoria (Haemodoraceae) was prepared against typhus, pneumonia, various and
severe forms of brain diseases, rheumatic wryneck and laryngeal cough. Unfortunately there was no specification given about
the various and severe forms of brain diseases. Constituents
of Lachnanthes tinctoria are glycosides, chelidonic acid and
naphthalene derivatives, as well as phenylphenalenone pigments
(Millspaugh, 1974). Nowadays, Lachnanthes tinctoria is a remedy known in homeopathy, amongst others, for pains for in the
joints.
Mexico is famous for the pre-Columbian Aztecs, whose
sophisticated empire came to a dire end with the arrival of Spanish invaders. In 1571 King Philipp II of Spain commissioned a
physician to document medicinal remedies used by the Aztecs.
Tagetes lucida (Asteraceae) known to the Aztecs as yauhtli
was a remedy for ailments such as fever, fear, dementia, lightening stroke and was also used as a diuretic (Ortiz de Montellano,

Table 1
Plants used in Europe in the context of age related CNS disorders
Plant

Family

Traditional use

References

Anacardium orientale auct. ex

Steud.
Artemisia absinthium L.
Caryophyllus spp.
Convallaria majalis L.

Anacardiaceae

A Confectio Sapientuma wisdom candy

Tabernaemontanus (1687)

Asteraceae
Caryophyllaceae
Convallariaceae

Howes et al. (2003)

Tabernaemontanus (1687)
Tabernaemontanus (1687)

Coriandrum sativum L.

Apiaceae

Corydalis sp.

Papaveraceae

Euphrasia ofcinalis complex

Hayne
Ferula gummosa Boiss.
Matricaria recutita L.

Orobanchaceae

Melissa ofcinalis L.

Lamiaceae

Lavendula stoechas L.
Ocimum basilicum L.

Lamiaceae
Lamiaceae

Origanum majorana Moench

Lamiaceae

Peroselinum vulgare (Mill.)

Nym. and A.W. Hill
Rosmarinus ofcinalis L.

Apiaceae

Traditionally for lost or declining cognitive function

Strengthen the brain and the memory
A candy to treat fever and strengthen the brain, senses and
memory
Covered in a little sugar can be taken to strengthen head, brain
and memory
Several species used in folk medicine for treatment of memory
dysfunction
Powdered herb when taken in wine may cure a stupid brain
and strengthens the brain
Oil can be applied to the neck or drunk for improving memory
Flowers soaked in water. Drunk and used to wash feet to retain
good memory
To sharpen the senses and improve memory, strenghtens the
brain, clears the head
To strengthen a stupid and dizzy brain.
for abdominal cramps, upset stomach, nervous migraine,
memory, strengthens the heart and head loss and forgetfulness
To return lost speech and strengthen brain and memory,
cleanses the brain
Soaked in good wine can improve brain function and memory

Lamiaceae

Salvia ofcinalis L.

Lamiaceae

As a circulatory stimulant for improving concentration and

memory. To stimulate the mind, in particular the memory. Used
by herbalists and aromatherapists for memory problems
Remedies help those who shiver and suffer the effects stroke
and strengthen weak minds and memories, for a sensitive
stomach, general debility, irregular menstruation and dementia

Chevallier (1996), Perry et al.

(1998) and Price and Price
(1995)
Tabernaemontanus (1687),
Sfikas (1980), Savelev et al.
(2004), Akhondzadeh et al.
(2003) and Perry et al. (2003)

Syzygium aromaticum (L.)

Merrill and Perry
Achillea millefolium L.
Adiantum capillus-veneris L.
Asparagus ofcinalis L.
Carum carvi L.
Caryophyllus sp.
Cichorium endivia L.
Cinnamomum verum J. S. Presl
Eryngium caeruleum M. Bieb.
Foeniculum vulgare Mill.
Horminum sp.
Lavandula angustifolia Mill.
Levisticum ofcinale Koch
Myristica fragrans Houtt.
Petroselinum crispum (Mill.)
Nym. and A.W. Hill
Piper cubeba L.
Valeriana celtica L. musk and
amber are added

Myrtaceae

Remedy against weakness of the brain, stroke and loss of

memory
This complex aqua vit is prepared stepwise by extraction and
distillation of a large number of plants. The remedy should be
mixed with wine and consumed regularly by old people to
strengthen the head, brain and memory

Tabernaemontanus (1687)

Apiaceae
Asteraceae

Asteraceae
Pteridaceae
Asparagaceae
Apiaceae
Caryophyllaceae
Asteraceae
Lauraceae
Apiaceae
Apiaceae
Lamiaceae
Lamiaceae
Apiaceae
Myristicaceae
Apiaceae

Tabernaemontanus (1687)
Adsersen et al. (2005)
Tabernaemontanus (1687)
Tabernaemontanus (1687)
Tabernaemontanus (1687)
Lonicerus (1679), Perry et al.
(1998) and Mills (1993)
Tabernaemontanus (1687)
Fuchs (1543) and Sfikas (1980)
Fuchs (1543)
Lonicerus (1679)

Tabernaemontanus
(1687)

Piperaceae
Valerianaceae

1990). Originally, Tagetes lucida is native to Mexico, but was

soon introduced to Europe as a decorative plant and a substitute for French tarragon. Campherole, tagetiin, tagetone and
quercetagritin, flavonol-gylcosides, quercetagenin, glucopyranoside, phenolic acids, propanoic acids, flavonols, aromatic
acids, methoxycoumarin were found to be present in the plant
(Aquino et al., 2002).
Nowadays cocoa is of great global significance as good deal
of the 3,000,000 tonnes produced each year (WHO, 2007) are

used to meet our craving desire for chocolate. Theobroma cacao

(Sterculiaceae), however, was used by the Aztecs as medicine,
where potions of ground bark and roots were used to treat stupor (Roeder, 1988). The chemical constituents of Theobroma
cacao include sterols, coumarins, catechins, catechol, glycosides, galactosides, tannins, polyphenols, triglycerides, linoleic
acids, and alkaloids including caffeine, theophylline, and theobromine, rutin, vitexin. The stimulating effects are most likely
only due to caffeine, theophylline, and theobromine.

Table 2
Plants used in North America in the context of age related CNS disorders
Plant

Family

Traditional use

References

Erythroxylum catuaba A.J. Silva

Erythroxylaceae

Taylor (1998)

Capsicum annuum L.
Centella asiatica (L.) Urban
Chrysanthemum sp.
Clematis sp.
Ginkgo biloba L.
Larrea tridentata (Sesse et Moc.) Coville
Oplopanax horridus Sm. Mic.
Rosmarinus ofcinalis L.

Solanaceae
Apiaceae
Asteraceae
Ranunculaceae
Ginkoaceae
Zygophyllaceae
Araliaceae
Lamiaceae

It is used as aphrodisiac, stimulant of the CNS, for sexual impotence,

general exhaustion, fatigue, poor memory and insomnia related to
hypertension
Native healers blend these herbs assisting memory, as well as for
eczema, emphysema, asthma and other ailments of aging

Lachnanthes tinctoria Ell.

Haemodoraceae

A tincture of the roots was used against typhus and typhoid fevers,
pneumonia, various and severe forms of brain diseases, rheumatic
wryneck and laryngeal cough

Millspaugh (1974)

Today, in the United States, Medicago sativa (Fabaceae),

alfalfa, is considered an invasive plant. In Mexico, it was believed
to improve the memory, cure skin eruptions, kidney pain,
cough, sore muscles and inflammation. Triterpenes, saponins
and sapogenins were identified in Medicago sativa (Finkler,
1985) (Table 2).
Brugmansia candida (Solanaceae) was used by native El Salvadorian peoples in various cases of memory problems. Five
to ten flowers were used to make a decoction for one bottle.
More than one cup had to be drunk, because the first couple of
cups would not be effective (Gonzalez Ayala, 1994). The genus
Brugmansia is known for toxic tropane alkaloids, so the remedy
should be treated with necessary caution.
A remedy reported from Guadeloupe was Lantana camara
(Verbenaceae), used to medicate memory weakness and enhance
intellect and cognition. Tea brewed from the leaves should be
drunk before going to bed (Muller-Ebeling and Ratsch, 1989).
It is remarkable that this use of a globally spread toxic invasive
plant should have an activity known merely in tiny Guadalupe.
Lantana camara contains triterpenes such as the toxins lantaden
A and B, essential oil, and sesquiterpenes.
Ananas comosus, pineapple (Bromeliaceae) originally cultivated in Central and South America, is used for ailments of
the CNS in South American traditional folk medicine. It was
also administered for neurasthenia, melancholy, sadness and for
weakness of memory (Wolters, 1994). Unfortunately, there was
no detailed description about the exact region or tribes where
it was used for this purpose. The best known bioactive com-

Kavasch and Baar

(1999)

ponent of the Ananas sp. is the proteolytic enzyme bromelaine,

which is responsible for the positive effects on digestion and has
recently been advertised for rapid weight-loss. Highest contents
of bromelaine occur in the stem and in the fruit. Considering
the wide use and popularity of pineapple, astonishingly little is
known about the phytochemistry of pineapple plants (Table 3).
As in Europe, in Ecuadorian traditional medicine rosemary
Rosmarinus ofcinalis is used in connection with AD and
dementia, for general symptoms of old age, debility and fatigue.
It was also applied for neuralgia, indigestion, pain of nervous
origin, circulatory disorders and hypertension (CESA, 1992).
CESA (1993), and De Barradas (1957), listed the leaves of
Chenopodium ambrosioides (Chenopodiaceae) in the context of
dementia symptoms. Its traditional indications include uses for
headache, caries, toothache and memory. Lactuca sativa, lettuce
(Asteraceae) is, according to Ecuadorian natives, supposed to
help with insomnia and weak memory (Schweitzer de Palacios,
1994).
In Brazil catuaba has traditionally been used as a stimulant
of the CNS with aphrodisiac properties. The source of catuaba is said to be the elusive Erythroxylum catuaba, a poorly
defined botanical entity, lacking both proper description and a
type specimen. The botanically correct identity the drug may be
Erythroxylum vacciniifolium (Erythroxylaceae), Anemopaegma
mirandum (Bignoniaceae), Trichilia catigua (Meliaceae) or others (see Kletter et al., 2004). One to three cups of a bark
decoction are to be consumed daily against sexual impotence and
weakness, agitation, nervousness, neurasthenia, poor memory,

Table 3
Plants used in Central America and the Caribbean Islands in the context of age related brain disorders
Plant

Family

Traditional use

References

Brugmansia candida Pers.

Lantana camara L.

Solanaceae
Verbenaceae

Gonzalez Ayala (1994)

Muller-Ebeling and Ratsch (1989)

Medicago sativa L.

Fabaceae

Tagetes lucida Cav.

Theobroma cacao L.

Asteraceae
Sterculiaceae

Tea or decoction is used for memory problems

Tea of the leaves is believed to prevent weakness of memory
and enhances intellect and cognition
To improve the memory, cure skin eruptions, kidney pain,
cough, sore muscles and inflammation
To treat fever, fear, dementia, lightning stroke and as a diuretic
In a potion for stupor

Finkler (1985)
Ortiz de Montellano (1990)
Roeder (1988)

forgetfulness and insomnia. Erythroxylum vaciniifolium bark

contains a number of tropane alkaloids (Zanolari et al., 2005).
Paullinia cupana (Sapindaceae), guarana, has been used for
centuries as an effective tonic, heart tonic, to thin the blood
and for mental acuity and to benefit long-term memory. Today
guarana is used word-wide as a tonifying drink against fatigue
(Taylor, 1998). Due to its caffeine content guarana is a substitute for coffee. Other phytochemicals are adenine, catechutannic
acid, choline, d-catechin, guanine, guaranine, hypoxanthine,
mucilage, saponin, tannins, theobromine, theophylline, timbonin and xanthine. An in vivo study with an interesting outcome
on mental insufficiency was conducted in 1997. Guarana was
administered in single and chronic doses to rats. Physical activity, physical endurance under stress and memory effort increased
in both of the doses administered. It is interesting that the whole
seed extract of guarana showed better results than a comparable
dose of caffeine (Espinola et al., 1997).
Colombia hosts a vast diversity of plants and numerous
indigenous tribes. The Colombian Indians reputably treat aged
members of the clan with care, patience and honour. Over twenty
remedies for afflictions of old age were described by Richard
Evans Schultes (1993a,b), the father of ethnobotany, a most
outstanding botanist who spent many years in the North Western
Amazone.
The Puinave Indians living along the Rio Vaupe mixed the
dried leaves of Unonopsis veneciorum (Annonaceae) into the
food of elderly patients suffering from not knowing how to talk
(Wolters, 1994). Pulverised leaves of Unonopsis stipitata, are
added to the food of elderly people who have difficulty speaking. The genus Unonopsis has interesting azafluorenones and
bisaporphinoids (Laprevote et al., 1987, 1988). Warm decoctions of the whole plant of Justicia ideogenes (Acanthaceae)
are poured over the lower limbs to treat trembling. Latex from
Galactophora crassifolia (Apocynaceae) is used for children
with uncontrollable shaking of the head. A root decoction
of Mandevilla steyermarkii (Apocynaceae) is administered to
the aged and the weak. The latex of Parahamcornia amapa
(Apocynaceae) is used against general debility in the Brasilian
Amazonas. Vismia tomentosa (Clusiaceae) provides a remedy
for the aged who have difficulty in understanding instructions,
talking and suffering of physical degeneration. Tukano medicine
men prepared tea of the leaves of Tabernaemontana heterophylla
(Apocynaceae) to give to elderly who were slow and forgetful.
The tree contains a number of indole alkaloids (Wolter et al.,
1983). Leaves of Lundia erionema (Bignoniaceae) or Memora
schomburgkii (Bignoniaceae) are crushed by Vaupes medicine
men and mixed with a palm oil to treat elderly who speak
crazily without making sense. Tikuna Indians make a tea from
Schlegelia macrophylla (Bignoniaceae) leaves for those who
refuse to eat and lose appetite. The Muinane Indians, who live
in the area of the Ro Caqueta, knew about the properties of the
rather unknown plant called Pagaea recurva (Gentianaceae). A
very bitter decoction, made of the whole plant, was prepared
and indicated in cases of debilitating forgetfulness among the
elderly (Schultes, 1993a,b). Practically nothing is known about
the chemistry of this plant. For patients with mental problems,
a recipe of the seeds of Barbieria pinnata (Fabaceae) was used.

The seeds are soaked in a fermented drink made of manioc

or maize before being administered. Cassia lucens (Fabaceae)
represents another remedy with a rather vague indication. This
plants most known use is as an insect repellent. Some Kubeo
people administer a drink from the dried and powdered leaves to
people with poor memory (Schultes, 1993a,b). The gymnosperm
Gnetum nodiorum (Gnetaceae) is used by the Wyana tribe in
Suriname for cases of physical and mental weakness (Schultes,
1993a,b) (Table 4).
5. Africa
The relative numbers of traditional practitioners and doctors
in proportion to the population in most African countries demonstrate the importance of traditional medicine. In the Venda area of
South Africa, for example, there is one traditional practitioner for
every 7001200 people, compared to one university-trained doctor for almost 18,000 people. Drugs used are considered a divine
gift, valued as much for its symbolic and spiritual significance as
for its medicinal effect. In addition to plants, healers may employ
charms, incantations and casting of spells in their healing methods (Tella, 1979; Helwig, 2006; Kale, 1995). African healing is
an inextricable part of African religion (Kale, 1995). This needs
to be considered when cures for mental diseases involve practices such as wrapping plants around a persons head or similar
pharmacologically less plausible forms of administration.
In East Africa, the roots of water lettuce, Pistia stratiotes
(Araceae), a perennial floating plant, are wrapped in a rag and
tied around a demented persons head. At the same time an
infusion of the leaves is poured over the head (Kokwaro, 1976).
In South Africa leaves, stems and roots of Asparagus
africanus (Asparagaceae) are pounded and soaked in water to
make an infusion. Drunken two to three times a day, it should
relieve problems of mental disturbance (Kokwaro, 1976). The
plant contains steroidal saponins and lignans (Debella et al.,
2000).
The following three recipes refer to the Yoruba speaking
part of West Africa. They are a large linguistic group of 40
million individuals mostly in Nigeria, Benin and Togo. One
recipe consists of the leaves of Hydrolea glabra (Hydrophilaceae), the leaves of Digitaria species (Poaceae) and a guinea
pig. The ingredients are eaten together with Indian cornmeal
and are believed to enhance memory (Fatumbi, 1995). A blend
of leaves of Pleiocarpa pycnantha (Apocynaceae), leaves of
Spondias mombin (Anacardiaceae) and a fruit of Aframomum
melegueta (Zingiberaceae) are administered to gain and retain
good memory (Fatumbi, 1995). According to traditional healers a formula consisting of Symphonia globulifera (Clusiaceae),
Hydrolea glabra (Hydrophilaceae), and Glyphaea brevis (Tiliaceae) was also given to aid memory. A snake was also added
to the concoction (Fatumbi, 1995).
In Senegal a maceration of the roots of Ximenia americana
(Olacaceae) native to Africa not the Americas, as the name
suggests is used to cure leprosy and is applied externally for
mental sickness (Sofowora, 1982).
Crinum glaucum and Crinum jagus (Amaryllidaceae) have
been used in Southwest Nigeria by traditional healers for mem-

Table 4
Plants used in South America in the context of age related CNS disorders
Plant

Family

Traditional use

References

Ananas comosus (L.) Merill

Bromeliaceae

Wolters (1994)

Barbieria pinnata (Pers.) Baill.

Fabaceae

Cassia lucens Vog.

Fabaceae

Chenopodium ambrosioides L.

Chenopodiaceae

Erythroxylum catuaba A.J.Silva

Juniperus brasiliensis

Erythroxylaceae;
Cupressaceae

Gnetum nodiorum Brongn.

Gnetaceae

Justicia ideogenes Leonard

Acanthaceae

Lactuca sativa L.

Asteraceae

Against neurasthenia, melancholy, sadness, weakness of memory

and stupidity
The Kubeos prepared a tea of the seeds for elderly men with
various mental problems
A drink prepared from powdered leaves for people with bad
memory
For headache, memory, caries and toothache
Preparations of the leaves are used to ameliorate the memory
The Indios believe that the plant has potential to increase the
memory
In Brazil, a decoction is used for sexual impotency, agitation,
nervousness, neurasthenia, poor memory, forgetfulness and sexual
weakness
Wyana Indians administered the plant in the treatment of physical
and mental weakness
Kofan Indians pour warm decoction over lower limbs for palsy-like
trembling
Lactuca is used for insomnia and believed to help a weak memory

Lundia erionema De Candolle

Aristolochiaceae

Mandevilla steyermarkii Woodson

Pagaea recurva Benth. Bentham et
Hooker fil
Parahamcornia amapa (Hub.) Ducke
Paullinia cupana KUNTH ex. H. B. K

Apocynaceae
Gentianaceae
Apocynaceae
Sapindaceae

Rosmarinus ofcinalis L.

Lamiaceae

Schlegia macrophylla Ducke

Tabernaemontana heterophylla Vahl.

Bignoniaceae
Apocynaceae

Unonopsis veneciorum (Mart.) R.E.

Fries
Unonopsis stipitata Diels
Vismia tomentosa Ruiz and Pav.

Annonaceae
Annonaceae
Clusiaceae

Crushed leaves mixed with Jessenis oil are given to elderly who
speak crazily without making sense
Given to the aged and the sick
Amongst the Muinane Indians a decoction of the whole plant was
prepared for debiliating forgetfulness in the elderly
Is used against general debility in the Brasilian Amazonas
Indians used guarana as a heart tonic, energy tonic, to thin the
blood, for mental acuity and long-term memory
For circulatory disorders, hypertension, pain of nervous origin,
indigestion, neuralgia, general debility and fatigue, and for general
symptoms of old age
Leaves given to people who refuse to eat and lose appetite
Tukano Indians prepared a tea of the leaves for the old folks who
are slow and forgetful
Puinave Indians at Rio Vaupe mixed dried leaves in the food of
elderly people who forgot how to talk
Added to the food of elderly people who have difficulty speaking
Yukuna and Makuna Indians prepared the plant for the elderly who
suffer difficulty in understanding instructions and have physical
degeneration and difficulty in talking

ory loss and other mental ailments associated with aging.

Houghton et al. (2004) isolated alkaloids from the plants
and tested their AChE inhibitory properties. Hamayne (IC50
250 M) and lycorine (IC50 450 M) showed only slight activities compared to the positive control physostigmine (IC50 of
0.25 M). A preparation of macerated roots of Opilia celtidifolia
(Opiliaceae) is believed to help with mental illness when taken
as a beverage for about 1 week (Assi and Guinko, 1991). Triterpenoid saponins were found to be present in the plant (Crespin
et al., 1993). The mark of Canthium glabriorum (Rubiaceae)
is used for cough and mental diseases (Bep, 1960) (Table 5).
6. Asia
Asia is the largest and, with 60% of the worlds population
also the most populous continent of the world. It is home to the
worlds oldest documented medical systems, traditional Chinese
medicine (TCM) and Ayurveda.

Schultes (1993a,b)
Schultes (1993a,b)
CESA (1993)
CESA (1992)
De Barradas (1957)
Taylor (1998)

Schultes, 1993a,b
Schultes (1993a,b)
Schweitzer de Palacios
(1994)
Schultes (1993a,b)

Schultes, 1993a,b
Schultes (1993a,b)
Taylor (1998)
CESA (1993)

Schultes (1993a,b)
Schultes (1993a,b)
Schultes (1993a,b)
Schultes (1993a,b)
Schultes (1993a,b)

6.1. Traditional Chinese medicine (TCM)

Chinese herbal medicine is an interesting subject for medicinal plant research. According to But et al. (1980), from 26,092
species listed in Flora Sinica, 4941 (19%) are used medicinally.
TCM concepts such as yin, yang and qi are used to describe
specific medical states but are difficult to translate into western medical terms. Despite the entirely different underlying
philosophical frameworks, there has been a great amount of
cooperation between TCM and western medicine in recent years.
Using western methods and techniques traditional remedies
have been pharmacologically and clinically validated, and many
have been shown to have therapeutic value in terms of western medical understanding. Besides herbal therapy acupuncture,
moxibustion, massage, hydrotherapy, dietetics and exercise are
therapeutic forms in TCM treatment. For detailed information
on the spiritual and philosophical aspects of TCM please refer
to specialised literature (such as Jiang, 2005).

Sofowora (1982)

Zingiberaceae

Apocynaceae
Anacardiaceae

Tiliaceae
Hydrophilaceae
Clusiaceae

Olacaceae

Aframomum melegueta (Roskoe) K.

Schum.
Pleiocarpa pycnantha (K. Schum.)
Spondias mombin L.

Glyphaea brevis (Spreng.) Mon.

Hydrolea glabra Schum. and Thonn.
Symphonia globulifera L. A snake

Ximenia americana L.

This recipe is for a good memory, to recall

memory and to organise the own memory

Rubiaceae
Amaryllidaceae;
Amaryllidaceae
Hydrophilaceae;
Poaceae
Opiliaceae
Araceae
Canthium glabriorum Hiern.
Crinum glaucum A. Chevalier
Crinum jagus C.
Hydrolea glabra Schum. and Thonn.
Digitaria sp.
Opilia celtidifolia Guill. and Perr.
Pistia stratiotes L.

A maceration of roots is used in treating leprosy and is applied internally and

externally for mental sickness

Fatumbi (1995)

Fatumbi (1995)

Assi and Guinko (1991) and Langeland and Craddock Burks (2005)
Kokwaro (1976)

Fatumbi (1995)

Administered for good memory. The two herbs are mixed together with the
guinea pig and eaten with Indian cornmeal
Roots macerated in water are taken to treat mental illness
The roots are wrapped in a rag and tied around the head of a demented person,
and at the same time, an infusion of the leaves is poured over the head
Extracts of the plants are taken to have a
good memory and to keep a good memory

Bep (1960)
Hostettmann et al. (2006)

Kokwaro (1976) and Debella et al. (2000)

Liliaceae
Asparagus africanus Lam.

Infusions of Leaves, stems and roots are drunk 23 times a day for the
treatment of mental disturbance
The mark of this plant is used for coughs and mental diseases
For memory loss and other mental symptoms associated with aging

References
Traditional use
Family
Plant

Table 5
Plants used in Africa in the context of age related CNS disorders

The club moss Huperzia serrata (Lycopodiaceae) is used in

TCM to alleviate problems of memory loss, promote circulation,
for fever and inflammation (Houghton and Howes, 2005). Qian
Ceng Ta is a formula prepared from Huperzia serrata, used in
TCM to treat memory loss (Howes et al., 2003). It is reported
to be a cognition enhancer that facilitates memory and motor
activity in aged persons and was recommended in the treatment
of senile dementia, including AD and multi-infarct dementia
(Kee, 1999).
Huperzine A, an alkaloid from Huperzia serrata, was found
to be a reversible AChE inhibitor and is neuroprotective
(Skolnick, 1997; Chiu and Zhang, 2000; Yaniv and Bachrach,
2005). It was shown that huperzine A has a neuroprotective
effect against -amyloid peptide fragment 2553, oxygen glucose deprivation and against free radical-induced cytotoxicity. It
also attenuates apoptosis by inhibiting the mitochondria-caspase
pathway. In cortex or synaptic plasma membranes it counteracted N-methyl-d-aspartate-induced toxicity (NMDA) This may
be due to the fact that huperzine A facilitates cholinergic neurotransmission by increasing the concentration of acetylcholine in
the CNS about 100 times more effectively than tacrine, a drug
used for AD (Anekonda and Reddy, 2005). In cell culture studies huperzine A decreased neuronal cell death caused by toxic
levels of glutamate (Bores et al., 1996).
In rats huperzine A reversed -amyloid-(140) induced
deficit in learning in a water maze task, and reduced the loss
of choline acetyltransferase activity in cerebral cortex, and the
neuronal degeneration induced by -amyloid protein-(140). It
reversed the down-regulation of anti-apoptotic Bcl-2 and the
up-regulation of pro-apoptotic Bax and P53 proteins as well
as reducing apoptosis caused by -amyloid injection. The beneficial effects are not confined to the cholinergic system, but
also include favourable changes in the expression of apoptosisrelated proteins and in the extent of apoptosis in other regions
of the brain (Wang et al., 2001).
Huperzine A (400 g) was given daily to 100 patients for
12 weeks. It was reported to be more selective for AChE than
BuChE and was less toxic than the synthetic AChE inhibitors
donepezil and tacrine (Frank and Gupta, 2005). Possible side
effects are nausea, vomiting, diarrhoea and muscle cramps have
been observed. Cholinergic effects may also worsen pulmonary
and peptic ulcer disease and cardiac arrhythmia (Ott and Owens,
1998).
Qingkailing, a traditional Chinese formulation, does not
have a direct indication in traditional medicine for dementia
or AD therapy. Some recent data, however, indicates a certain potential to be used as such. The herbs Scutellaria spp.
(Lamiaceae), Lonicera spp. (Caprifoliaceae), Pittosporum spp.
(Pittosporaceae) and Isatis tinctoria (Brassicaceae) are combined with cow-bezoar (Jinzhoun, 1998). It is a remedy used
for re-establishing the energy balance and to remove the causes
of heat and phlegm, which in TCM are symptoms, associated with dementia. Clinical studies report beneficial effects
of qingkailing: Patients with dementia following a stroke,
received qingkailing intravenous daily, for 30 days. At the same
time, a tea was given twice daily. It contained Pinellia ternata (Araceae) tubers, Acorus gramineus (Acoraceae), Angelica

dahurica (Apiaceae) roots, Atractylodes macrocephala (Asteraceae), and Pseudostellaria heterophylla (Caryophyllaceae)
root. An improvement of intellect by increasing the score 10
points on Hasegawa Dementia Scale was stated by five patients.
Three patients improved 5 or less points, while two patients
remained without benefit. In a randomized double blind study,
with 15 participants with syndromes of vascular dementia,
qingkailing was administered i.v. to 10 patients daily for 14 days.
The control group (n = 5), received an infusion of chuanxiong
piperazine (Ligusticum chuanxiong, Apiacae). The qingkailing
group improved their score by 10.4, whereas the score of the
control group increased only by 4.9. These studies have, at
best, a pilot character and need to be followed up by larger
trials.
Polygala tenuifolia (Polygalaceae) is used in TCM and
Japanese formulas for the treatment of psychoneurological diseases. It is thought to have an effect on the will and mental
powers, improving understanding and strengthening the memory. It is also indicated as a cerebrotonic, cardiotonic, sedative
and tranquillizer (Howes and Houghton, 2003).
6.2. Korea
Oh et al. (2004) lists seven plants in Koreas history of traditional medicine, including Acorus calamus rhizome, Acorus
gramineus rhizome, Bupleurum falcatum root, Dioscorea
batatas rhizome, Epimedium koreanum herb, Poria cocos sclerotium and Zizyphus jujuba fruit, which are used for the general
indication for improvement of cognition and memory function in
old age. They were all tested for cholin esterase inhibitory properties using the Ellman colorimetric method. The data revealed
that extracts of Acorus gramineus, Dioscorea batatas and Zizyphus jujuba did not show any inhibitory effects on AChE.
Significant dose-dependent inhibition of the enzyme at the high
dose of 200 g/ml was observed for methanolic extracts from
Acorus calamus and Epimedium koreanum.
Paeng-Jo-Yeon-Nyeon-Baek-Ja-In-Hwan (PJBH) is a decoct
of 18 dried herbs including the whole plant of Dendrobium
moniliforme, seeds of Thuja orientalis (Cupressacae), fruits
of Torilis japonica (Apiaceae), Rubus coreanus (Rosaceae),
Cornus ofcinalis (Cornaceae) and Schizandra chinensis
(Schisandraceae), roots of Morinda ofcinalis (Rubiaceae),
Asparagus cochinchinensis (Asparagaceae), Polygala tenuifolia
(Polygalaceae), Phlomis umbrosa (Lamiaceae), Panax ginseng
(Araliaceae) and Rehmannia glutinosa (Gesneriaceae), stems of
Cinnamomum cassia (Lauraceae), rhizome of Acorus calamus
(Araceae), Alisma canaliculatum (Alismataceae) and Dioscorea
japonica (Dioscuraceae) and leaves of Cistanche salsa (Orobanchaceae). PJBH has an extensive history in Korea, and is
also used in TCM to activate brain function, promote memory and lengthen life span. The herbal medicine has shown
various activities including immune modulation, anti-infarct,
anti-inflammatory and anti-allergic effects (Koo et al., 2004).
The effects of PJBH on H2 O2 induced injury in PC12 cells was
examined and revealed an elevating effect on catalase and glutathione peroxidase activities as well as on cell survival (Koo et
al., 2004).

6.3. Japan
Choto-San, a remedy from Kampo Japanese traditional
medicine adapted from TCM consists of 10 herbs and a
sulphate mineral. The formula is composed of the fruit shell
of Citrus aurantium (Rutaceae), the tubers of Ophiopogon
japonicus (Convallariaceae) and Pinellia ternate (Araceae),
the stem including the hooks of Uncaria tomentosa (Rubiaceae), the roots of Panax ginseng (Araliaceae), Ledebouriella
seseloides (Apiaceae) and Glyzyrrhiza glabra (Fabaceae), the
rhizome of Zingiber ofcinalis (Zingiberaceae), the flowers of
the Chrysanthemum species and parts of Poria cocos. The traditional indication does not relate to age related brain disorders in
particular, but recent data reveals the possible use of Choto-San
in the therapy of cognitive disorders (Murakami et al., 2005).
Murakami et al. (2005) tried to clarify the mechanisms of
action of the Choto-san formula in mice with induced hypoperfusion by permanent occlusion of both the common carotid arteries
which induces spatial memory deficits and neuronal damage in
rodents. Choto-san extract was given orally to mice for 5 days
an hour prior to the start of each experiment. Tacrine was used as
reference. Choto-san and Choto-san Uncaria-free extract were
administered. Choto-san raised the level of ACh, compared
to that in the control group, whereas Choto-san Uncaria-free
extract had no effect. Choto-san also improved 2VO-induced
spatial learning deficits, via the stimulation of muscarinic M1
receptor, while Choto-san Uncaria-free extract did not show
any improvement. Choto-san extract ameliorated the effect of
2VO in the Morris water maze task whereas the Uncaria-free
extract showed no effect. The results suggest that Uncaria plays
a key role in the beneficial effect of Choto-san on learning and
memory impairment caused by chronic hypoperfusion.
6.4. Ayurveda
The history of medicine in India can be traced to the remote
past. The earliest mention of medicinal use of plants is found in
the Rigveda, probably the oldest repositories of human knowledge written between 4500 and 1600 b.c. (Kapoor, 1990).
Ayurveda encompasses philosophy, science and religion and
is a very complex system of knowledge applied to daily life.
Rasayana tantra geriatrics including rejuvenation therapy
is one of eight major disciplines in Ayurveda. Caraka Samhita
defined rasayana as a treatment to attain longevity, intelligence, freedom from age related disorders, youthful appearance,
optimum strength of physique and sense organs, maintain language ability and improve memory (Bala and Manyam, 1999).
Rasayana is not merely a drug therapy but a regimen covering
the general mode of life, social conduct, behaviour, diet and the
use of specific restorative remedies. This process should begin in
late adult life or midlife, and may not be effective when started
too late as many of the approaches are preventive rather than
curative. Some rasayana recipes directly refer to dementia. It is
quite remarkable that an ancient medical system includes such
a well-elaborated medical theory and treatment for age related
problems like dementia, whilst contemporary systems attributed
inexplicable phenomena to the spiritual realm.

One preparation is called Aindrarasayana (Bala and Manyam,

1999). Aindri or Brahmi are names for Bacopa monniera, one of
six plants in the formula. The other five are Alternanthera sessilis (Amaranthaceae), Acorus calamus (Araceae), Piper longum
(Piperaceae), Convolvulus pluricaulis (Convolvulaceae) and one
plant with the Sanskrit name Brahmasuvarcala, which was not
identified. Three parts of Aindrarasayana including the salt and
two parts of gold oxide are mixed with Aconitum chasmanthum
(Ranunculaceae). The mixture is consumed on an empty stomach. Several hours later, when the preparation is digested, honey
and a generous amount of butterfat (ghee) should be consumed.
Another Ayurvedic formula consists of the juice of Centella asiatica (Apiaceae), the powder of Glycyrrhiza glabra
(Fabaceae) mixed with milk, the juice of the stem of Tinospora
cordifolia (Menispermaceae) and a paste made of the roots
and flowers of Convolvulus pluricaulis (Convolvulaceae) mixed
together and taken to prevent dementia, retard age and to improve
complexion and digestion (Bala and Manyam, 1999).
Emblica ofcinalis (Euphorbiaceae) is a native plant with
rasayana properties and the main ingredient in this preparation
for a disease-free life with long lasting youth, great vigour and
no dementia. Terminalia ofcinalis, Acorus calamus, Embelia
ribes, Sida spinosa, Semecarpus anacardium, Bacopa monnieri,
Aternanthera sessilis, Coelogyne evalis, Boerhaavia diffusa,
Desmodium gangeticum, Baliospermum montanum and Polygonatum verticillatum are also added to the mixture. Six plants
with Sanskrit names are not identified but also part of the formula
(Bala and Manyam, 1999).
Another traditional recipe made is prepared with 1000 fruits
of Emblica ofcinalis (Euphorbiaceae) and 1000 fruits of Piper
longum (Piperaceae). They are dipped in alkaline water prepared
from a Butea monosperma (Fabaceae) tree, and then powdered.
The powder is mixed four times its weight with honey and ghee,
and one-fourth of sugar and stored underground for 6 months.
The preparation should be taken life-long from new moon to
full moon starting later in youth or middle age. The dose is
based on the persons individual digestive ability. This remedy
is optimistically recommended for a lifespan of 100 years with
full vigour, cognitive function and to preserve youth (Bala and
Manyam, 1999).
Withania somnifera (Solanaceae) roots are one of the most
highly regarded herbs in Ayurvedic medicine and of similar status of ginseng in TCM. They are classed among the Rasayanas
rejuvenating tonics used for treating age associated decline in
cognitive function (Parrotta, 2001).
Steroid lactones such as withanolides A-Y, glycowithanolides, dehydrowithanolide-R, withasomniferin-A, withasomidienone, withasomniferols A-C, withaferin A, withanone
have been isolated from the root and leaf (Williamson,
2002). The phytosterols, sitoindosides VIIX and perpetual sitosterol were found, alongside the alkaloids ashwagandhine,
ashwaghandhinine, cuscohygrine, anahygrine, tropine, pseudotropine, anaferine, isopelletierine, withasomine, visamine,
somniferine, somniferinine, withanine, withaninine, pseudowithaninine and solasodine.
There have been numerous studies regarding the cognitive
enhancing activities of Withania somnifera. Withanoside IV or

VI produced dendritic outgrowth in normal cortical neurons of

isolated rat cells, whereas axonal outgrowth was observed in
the treatment with withanolide A in normal cortical neurons
(Tohda et al., 2005). Neuritic regeneration or synaptic reconstruction was induced by withanolide A, withanoside IV and
VI in amyloid- (2535)-induced damaged cortical neurons. In
addition, these components also facilitated the reconstruction of
post-synaptic and pre-synaptic regions in neurons, where severe
synaptic loss had already occurred.
Withania somnifera extract, containing the steroidal substances sitoinodosides VIIX and withaferin A augmented
learning acquisition and memory in both young and old rats
(Ghosal et al., 1989). It enhanced AChE activity in the lateral
septum and globus pallidus and decreased it in the vertical diagonal band. Receptor binding on the muscarinic M1 receptor was
enhanced in the lateral and medium septum and in the frontal cortices. M2 receptor binding increased in cortical regions but did
neither affect -aminobutyric acid (GABAA ), benzodiazepine,
nor NMDA receptor binding. The extract reversed ibotenic acid
induced cognitive deficit and reversed the reduction in cholinergic markers, such as acetylcholine (Schliebs et al., 1997).
Acorus calamus is originally native to Europe, but has been
cultivated and naturalized throughout India and Sri Lanka.
Sala et al. (1993) list the plant with traditional uses as an
intellect-promoting agent against depression, mental disorders
and general debility. Acorus calamus is also combined with
Polygala root to help maintain mental and intellectual health
of the elderly (Hou and Jin, 2005). When powdered, it can be of
avail for depressed psychosis and dementia. Further indications
include the loss of consciousness, confusion of the mind, forgetfulness, anorexia and epilepsy and as a traditional Ayurvedic
medicine to treat memory loss (Howes and Houghton, 2003).
Acorus calamus contains essential oil with the main components -asarone and -asarone. Other components found in
the plant are caryophyllene, -humulene and sekishone (Hou
and Jin, 2005). Methanolic extracts of the roots, which contain
essential oil which the toxin -asarone showed inhibitory effect
on AChE with an IC50 value of 188 g/ml (Oh et al., 2004).
In vitro and in vivo studies have shown Acorus calamus oil to
induce malignant tumours, due to -asarone. In view of toxicity,
products should contain no or a negligible amount of -asarone,
such as that from the Acorus calamus var. americanus (Singh
et al., 2001). In mice, the root extract of Acorus calamus protected against acrylamide-induced neurotoxicity and reduced
the incidence of paralysis (Shukla et al., 2002). Acorus calamus is registered in the Pakistani Materia Medica where both
the roots and rhizomes are used for nervous diseases and disorders, whereas the rhizome is especially indicated in cases of
neurological symptoms of the brain (Said and Ahmad, 1986).
The seeds of Celastrus paniculatus (Celastraceae) are credited with emetic, diaphoretic, febrifugal and nerve benefiting
properties and are used in traditional Indian medicine to sharpen
the memory, to cure ulcers, gout, sores and rheumatism. The
seeds and the seed oil are used as a brain tonic, for diseases of
the CNS, epilepsy, oedema, stomach disorders and psychosis.
The leaves, roots and bark do not have indications related to AD
or dementia, so most in vivo and in vitro pharmacological stud-

ies have focused on seeds and the seed oil (Parrotta, 2001). In
rats the oil helped improve learning and memory, and decreased
noradrenalin, dopamine and serotonin in the brain (Nalini et al.,
1995). It reversed scopolamine induced task deficit but this was
not associated with an AChE inhibition (Gattu et al., 1997). For
more pharmacological information see Howes and Houghton
(2003).
Traditional indications were found for Convolvulus pluricaulis (Convolvulaceae), a plant common in southern India,
where the whole plant is used in various formulae as a nervine
tonic for improvement of memory and intellect. The leaves and
flowers possess hypotensive properties used for treating anxiety
neurosis. Furthermore, it is also recommended as a brain tonic
to promote intellect and memory, eliminate nervous disorders
and to treat hypertension (Bala and Manyam, 1999).
The bark, leaves, flowers, fruits and pods of Sesbania grandiora (Fabaceae) are used in Ayurvedic medicine. The pods
are considered useful for promoting memory power and for
resolving glandular tumours or enlargements (Parrotta, 2001).
Canscora decusata (Gentianaceae) is a notable Ayurvedic drug
for improving memory and intellect. A paste is made of the
whole plant, including the flowers, to be taken with milk as
a nervine tonic and to alleviate memory problems (Parrotta,
2001). Gmelina arborea (Verbenaceae) is used in Ayurvedic
medicine to improve digestion, strengthen memory, to overcome
giddiness and to treat fever, thirst, emaciation, heart diseases
and nervous disorders (Parrotta, 2001). The ripe fruit of Terminalia chebula (Combretaceae) is considered to possess the
ability to promote memory, intellect and to prolong life. It
is also believed to improve eyesight and has the ability to
delay aging. It is suggested that one ripe fruit should be eaten
every morning to achieve the listed effects (Vohra and Gupta,
2005).
Nardostachys jatamansi (Valerianaceae) is a reputed medhya,
an intellect-promoting herb, with various medicinal properties,
especially on the nervous system (Joshi and Parle, 2006). A
recent study was undertaken to determine the effect of Nardostachys jatamansi as a memory enhancer in mice. An elevated
plus maze and a passive avoidance task were employed to evaluate learning and memory parameters. An ethanolic extract of
the plant was administered orally for at doses of 50, 100 and
200 mg/kg. Furthermore, diazepam and scopolamine induced
amnesia as well as aging induced amnesia was examined. The
high dose of 200 mg/kg dose significantly improved learning and
memory in young mice and also reversed amnesia induced by
scopolamine and diazepam. It was also claimed to have reversed
amnesia due to natural aging of mice (Joshi and Parle, 2006).
Bacopa monnieri L. (syn.: B. monniera) (Scrophulariaceae)
occupies a predominant position in ayurvedic medicine and
is recommended for the management of a range of mental
conditions including anxiety, poor cognition and a lack of concentration (Russo and Borelli, 2005), as a nerve tonic, for
memory and intelligence improvement (Parrotta, 2001) for an
intellect promoting effect and helpful in cases of general debility
(Sala et al., 1993). Russo and Borelli (2005) recently provided
an update of current knowledge of nootropic effects of Bacopa
monnieri.

The effects Bacopa monnieri (40 mg/kg) on learning performance in rats were studied in shock-motivated brightness
discrimination reaction and in conditioned fight reaction. In
both schedules the treated groups showed a shorter reaction time
than the control group. In addition, the rats improved learning
capability confirmed by a maze-learning experimental method
(Williamson, 2002).
Major chemical constituents found in Bacopa monnieri are
saponins, triterpenes and dammaranes, such as bacosides A,
B, C, bacosaponines D, E and F (Williamson, 2002; Russo
and Borelli, 2005). The alkaloids brahmine and herpestine,
flavonoids such as glucuronyl-7-apigenin and glucuronyl7-luteolin, luteolin-7-glucoside and luteolin, phenylethanoid
glycosides, monnierasides IIII and plantainoside B have been
isolated.
The saponins bacoside A and B have been claimed to be
the active principles regarding enhancement of cognitive function (Singh and Dhawan, 1992; Russo and Borelli, 2005). They,
apart from facilitating learning and memory in normal rats,
inhibited the amnesic effects of scopolamine, electroshock and
immobilization stress. Furthermore, Bacopa monnieri has been
shown to enhance protein kinase activity in the hippocampus, which could also contribute to its nootropic action. When
Bacopa monnieri was administered along with phenytoin for 2
weeks, it significantly reversed phenytoin-induced impairment
in rats (Williamson, 2002). Bacopa monnieri, administered for
2 weeks, reversed the depletion of acetylcholine. Further, it
reduced the choline acetylase activity and decreased muscarinic,
cholinergic receptor binding in the frontal cortex and hippocampus, induced by neurotoxins, such as colchicine (Russo and
Borelli, 2005).
In a double blind placebo-controlled trial 76 participants,
aged 4065, received capsules of Bacopa monnieri extract
equivalent to 69 g of dried rhizome. Effects on anxiety and
memory functions were tested. The results did not show any
significant effect on measures of short-term memory, working
memory, attention, or the retrieval of information from long-term
memory acquired pre-experimentally. No effects on subjective measures of psychological state as depression, anxiety and
stress, or everyday memory were observed. There was, however, an activity measured in a task requiring the retention of
new information, recalling unrelated word pairs after a short
delay (Roodenrys et al., 2002).
The medicinal value of Centella asiatica (Apiaceae) is
thought to be similar to that of Bacopa monnieri. The whole
plant is used as a nervine tonic in various brain diseases and
given to children as syrup to increase the memory. It is thought
to be effective for memory disorders, impaired intelligence and
as a rejuvenator and blood purifier. It is used in various skin
diseases. In parts of India it is given with milk to improve
memory against dementia and aging (Ahuja, 1965). Constituents in Centella asiatica include essential oil, triterpenoid
saponins, such as asiaticocide, brahmoside and thankuniside,
alkaloids (hydrocotyline) and some bitter principles (Chevallier,
1996).
Mook-Jung et al. (1999) tested articoside and 28 derivatives for protective effects against A -induced cell death in

Table 6
Plants used in Asia in the context of age related CNS disorders
Origin

Plant

Family

Traditional use

References

China

Qingkailing (QKL)
Isatis tinctoria L.
Lonicera sp.
Pittosporum sp.
Scutellaria sp. cow-bezoar
Coptis chinensis Franch.

Brassicaceae
Caprifoliaceae
Pittosporaceae
Lamiaceae
Ranunculaceae

Jinzhoun (1998)

Huperzia serrata Thunb.

Lycopodiaceae

QKL is not mentioned as traditional: Studies suggest that the most

frequent causes of dementia associated with stroke are heat, phlegm and
blood stasis syndromes. Treatment should re-establish the energy
balance and remove the causes. QKL resolves phlegm and clears the heat
For several conditions including age related
cognitive and memory decline
Huperzine A is found to be an active cognition
enhancer that faciliates memory and motor
activity in aged persons
Qian Ceng Ta is a traditional Chinese formula
to alleviate problems of memory loss. The
formula is prepared from Huperzia serrata
Huperzia serrata has been used and is still a
component of various formulae in traditional
Chinese medicine to alleviate problems of
memory loss, fever, inflammation and for
symtomps of aging

Polygala tenuifolia Willd.

Korea

Paeng-Jo-Yeon-Nyeon- Baek-Ja-In-Hwa (PJBH)

Acorus calamus L.
Alisma canaliculatum A.Br. and Bouche
Asparagus cochinchinensis (Lour.) Merr.
Cinnamomum cassia Blum.
Cornus ofcinalis L.
Cistanche salsa C. A. Mey.
Dioscorea japonica Thunb.
Dendrobium moniliforme (L.) Sw.
Eucommia ulmoides Oliv.
Morinda ofcinalis How.
Panax ginseng C. A. Mey.
Phlomis umbrosa Turc. Bull
Polygala tenuifolia Willd.
Rehmannia glutinosa Gaertn.
Rubus coreanus Miq.
Schizandra chinensis L.
Thuja orientalis (L.) Franco
Torilis japonica (Houtt.)

Polygalaceae

Effect upon the will and mental powers,

improving understanding and strengthening the
memory

Acoraceae
Alismataceae
Asparagaceae
Lauraceae
Cornaceae
Orobanchaceae
Dioscoraceae
Orchidaceae
Eucommiaceae
Rubiaceae
Araliaceae
Lamiaceae
Polygalaceae
Gesneriaceae
Rosaceae
Schisandraceae
Cupressaceae;
Apiaceae

According to ancient Chinese medicinal

literature PJBH supplies and nourishes the
kidney and consolidates essence, thus
activating brain function, promoting memory
and lengthening life span. PJBH has an
extensive history as a medicinal herb in
Korea, and it is possible that widespread
PJBH use may contribute to the reduced
age-adjusted prevalence of AD in Korea

Houghton and Howes (2005)

Kee (1999)

Howes et al. (2003)

Ott and Owens (1998),

Chiu and Zhang (2000),
Anekonda and Reddy (2005),
Houghton and Howes (2005),
Frank and Gupta (2005) and
Houghton et al. (2006)
Howes and Houghton (2003)

Koo et al. (2004)

Table 6 ( Continued )
Origin

Plant

Family

Traditional use

References

Japan (Kampo)

Choto-san
Gypsum brosum
Chrysanthmum sp.
Citrus aurantium L.
Glycyrrhiza glabbra L.
Ledebouriella seseloides (Hoffm.) Wolff.
Ophiopogon japonicus Thunb.
Panax ginseng C. A. Mey.
Pinellia ternata Thunb.
Poria cocos (Schw.) Wolff
Uncaria tomentosa Willd.
Zingiberis ofcinalis L.

Sulphate mineral
Asteraceae
Rutaceae
Fabacea
Apiaceae
Convallariaceae
Araliaceae
Araceae
Polyporaceae
Rubiaceae
Zingiberaceae

The Choto-san formula is usually prescribed

to middle-age patients of considerable build
with a weak physical constitution as well as
for chronic headache, painful tension of the
shoulders and cervical muscle, vertigo,
morning headaches, a heavy feeling of the
head, feelings of uprising heat, tinnitus and
insomnia

Murakami et al. (2005)

Araceae
Amaranthaceae
Scrophulariaceae
Convolvulaceae
Piperaceae
Apiaceae
Convolvulaceae
Fabaceae;
Menispermaceae

This preparation is considered to alleviate

dementia

Bala and Manyam, 1999

This recipe is believed to prevent dementia,

improve digestion and complexion

Bala and Manyam (1999)

The fruits of Embilica ofcinalis are

steamend to remove the seeds, dried and
powdered. The powder is mixed with the
juice of fresh Embilica fruit and mixed with
the other 17 plants. It is then mixed with the
juice of the fruits of Sida spinosa, dried, and
ghee and honey are added. It is stored in
boluses in a vessel underground surrounded
by hemp ashes for 2 weeks. Before
administration, oxide of gold, silver, copper
and iron are added. Brahmarasayana is
thought to create a disease-free, youthful
state and significant vigor and no dementia
The formula is recommended for a life span
of 100 years, to preserve youth, full vigor
and cognitive function
The plant is said to be capable of improving
memory and intellect, treats various diseases
including epilepsy and mental ailments
Withania somnifera is used in cases of debility
from old age

Bala and Manyam (1999)

India (ayurveda)

Aindrarasayana
Acorus calamus L.
Alternanthera sessilis (L.) R. Br.
Bacopa monnieri (L). Pennell
Convolvulus pluricaulis Choisy
Piper longum L.
Centella asiatica (L.) Urban
Convolvulus pluricaulis Choisy
Glycyrrhiza glabra L.
Tinospora cordifolia Miers
Brahmarasayana
Acorus calamus L.
Alternanthera sessilis (L.) R. Br.
Bacopa monnieri (L.) Pennell
Baliospermum montanum (Willd.)
Boerhavia diffusa L.
Coelogyne evalis Lindl.
Emblica ofcinalis Gaertn.
Desmodium gangeticum (L.) DC.
Embelia ribes (Roxb. ex. Willd.) DC.
Polygonatum verticillatum (L.) All.
Terminalia chebula Retz.
Sida spinosa L.
Semecarpus anacardium L. fil.
Butea monosperma (Lam.) Taub
Emblica ofcinalis Gaertn.
Piper longum L.
Acorus calamus L.

Withania somnifera (L.) Dun.

Araceae
Amaranthaceae
Schrophulariaceae
Euphorbiaceae
Nyctaginaceae
Orchidaceae
Euphorbiaceae
Fabaceae
Myrsinaceae
Liliaceae
Combretaceae
Malvaceae
Anacardiaceae
Fabaceae
Euphorbiaceae
Piperaceae
Araceae

Solanaceae

Bala and Manyam (1999)

Parrotta (2001)

Ahuja (1965)

Dash (1994)

Dash (1994)
Apiaceae

Iridaceae

Centella asiatica (L.) Urban

Iris germanica L.

Tibet

It is a promotor of memory and voice and

believed to be a rejuvenating agent
It is a promotor of intellect and kapha. It is used
in the treatment of insanity, epilepsy and evil
spirits

Woodley (1991)
It is used as a sedative for demented people
Casuarinaceae
Casuarina equisitifolia L.

Sapindaceae
Dimocarpus longan Lour.

Malaysia

Araliaceae
Acanthopanax trifoliatus (L.) Merr.
Vietnam

Magnoliaceae
Michelia champaca L.
Thailand

It is a tonic remedy used in the treatment for

neurasthenia, insomnia, amnesia and mental
deficiency

Agence de Cooperation
Culturelle et Technique
(1990a,b), Du and Gao
(1992) and Kiem et al. (2004)
Agence de Cooperation
Culturelle et Technique
(1990a,b)

Clayton et al. (1994)

Said and Ahmad (1986)

Roots and rhizomes are for nervous diseases

and disorders. The rhizome is used for curing
neurological symptoms of the brain
The leaves are used in the treatment of brain
disorders
It has been used as a stimulant as well as a tonic
and believed to ameliorate the memory
Araceae
Acorus calamus L.
Pakistan

Parrotta (2001), Williamson

(2002), Tohda et al. (2005),
Howes et al. (2003) and
Williamson (2002)
The roots are used in the therapy against senile
debility and to restore memory loss

B103 cells. Hereby asiatic acid showed the strongest protective effect reducing H2 O2 -induced cell death and lowering
intracellular free radical concentration. The triterpene asiatic acid and its derivatives have been also been shown to
protect cortical neurons from glutamate-induced excitotoxicity in vitro. Glutamate can induce neuronal degeneration by
over-stimulation of NMDA receptors. Some NMDA receptor
antagonists like memantine (NamendaTM ), have been approved
by the U.S. Food and Drug Administration (FDA) for the treatment of moderate to severe AD (Farlow, 2004). Rao et al.
(2005) showed that treatment of mice during postnatal development with Centella asiatica extracts influences the neuronal
morphology and promotes higher brain function later on in
life.
Centella asiatica extract (100, 200 and 300 mg/kg) showed a
dose-dependent protective effect against cognitive deficits and
oxidative stress in rats. The results indicated improved acquisition and retention of memory. No significant changes were
observed in the locomotive activity. The rats were sacrificed on
day 21 for estimation of oxidative stress parameters as malondialdehyde (MDA), a marker of lipid peroxidation, SOD, GSH-Px
and CAT. A decrease in MDA and an increase in GSH-Px levels
were observed in rats treated with the rather high doses of 200
or 300 mg/kg extract (Kumar and Gupta, 2003).
In Thailand the leaves of Michelia champaca (Magnoliaceae), a tree valued for its strongly fragrant yellow or
white flowers, are used in the treatment of brain disorders
(Clayton et al., 1994). Michelia champaca contains essential oil,
parthenolide and other sesquiterpene lactones (Jacobsson et al.,
1995).
Two plants were mentioned in the viewed literature on Vietnamese medicine for treating age related dementia (Agence de
Cooperation Culturelle et Technique, 1990a,b). Acanthopanax
trifoliatus (Araliaceae) is used as a stimulant and tonic and
is believed to ameliorate the memory. Some of the chemical constituents of the leaves of Acanthopanax trifoliatus have
are kaur-16-en-19-oic acid, taraxerol, taraxerol acetate (Du and
Gao, 1992), lupane-triterpene carboxylic acids, called acantrifoic acid and acantrifoside (Kiem et al., 2004). Dimocarpus
longan (Sapindaceae), the source of the delicious longan fruits,
is used as a tonic and administered in the treatment for mental deficiency, neurasthenia, insomnia and amnesia (Agence de
Cooperation Culturelle et Technique, 1990a,b). It could not be
determined what part of this widespread plant is used.
In Malaysia Casuarina equisetifolia (Casuarinaceae) a
widespread shrub or tree which somewhat resembles pine trees,
is used as a sedative for the demented and to treat memory
problems (Woodley, 1991).
In Tibet Iris germanica (Iridaceae) is believed to be a promoter of intellect and also useful in the treatment of insanity,
epilepsy and against evil spirits (Dash, 1994). Centella asiatica
already listed in the part on India is also used in Tibet as a promoter of memory and voice and is believed to be rejuvenating
in general. Another remedy, believed to prevent aging is ghee, a
form of melted butterfat which is said to promote complexion,
beauty, voice, intellect, memory and give strength, virility and
longevity (Dash, 1994) (Table 6).

7. Conclusions and perspectives

Despite the access to a large ethnobotanic florilegium in
libraries and databases, the yield in numbers of herbs used for
age related dementia turned out to be rather limited for most geographic regions. Various reasons may be responsible for that: On
the one side, it can be due to cultural reasons. Both Ayurveda and
TCM have clear millennia-old concepts of age related cognitive
disorders and corresponding treatments with specific remedies
(Yan et al., 2000), whereas folk medicines mostly lack this kind
of foundation. Memory loss, confusion and forgetfulness in old
age are fatalistically accepted as inevitable part of life, or oftentimes dementia is attributed to madness caused by spiritual and
supernatural causes. Also, dementias are diseases which occur
at an advanced age which was rarely reached in countries with
a low life expectancy. On the other hand, there may also be
the difficulty of gathering and reporting data, i.e. in translating traditional concepts into scientific terminology. Also, data
recording may not have been optimal from todays perspective. Indeed, the interest of Western medicine in Alzheimers
disease is a relatively recent phenomenon. Our awareness has
substantially increased over the past 20 years, due to significant
scientific progress in the understanding of the disease and the
growing socioeconomic issue for our ageing societies. Before,
age-related loss of cognitive function was largely considered as
a natural phenomenon. Thus, the literature may possibly be negatively biased in the sense that many of the ethnobotanical books
originate from a period where ethnobotanists probably paid less
attention to information concerning treatments for cognitive disorders.
Quite a number of traditionally used medicines were found in
European herbals from the 16th and 17th Century, despite the relatively small number of available references. These herbals were
sometimes printed in a number of languages, many of which
are even available as reprints nowadays (Fuchs, 1543; Pomet,
1717). They formed the basis for what evolved into modern day
pharmacopoeias. However, a major part of what was known to
the antique and medieval world probably was lost in the early
middle ages or has not yet been analyzed by modern science.
This can be concluded from some documents long thought lost,
which have only recently resurfaced. For example, a medieval
account of 412 plants from the late 14th Century was rediscovered in the university library in Basel, Switzerland (Pfister,
1961). Unfortunately, these treasures still await their translation and scientific analysis due to lack of funding and qualified
philologists.
Quite a number remedies for the treatment of age related
cognitive disorders were recorded for the Amazonian region
by the father of modern ethnobotany, Richard Evans Schultes
(Schultes, 1993a,b), who spent many years living with natives
and studying their medicinal herbs.
A small selection of herbs traditionally used for CNS disorders have been evaluated pharmacologically and regarding
their active constituents in terms our modern understanding of
brain functions, but so far very little clinical data is available.
Many prescriptions that claim to prevent or restore cognitive and
memory deficits have not shown any actions in established test

systems. Research for new potential drugs, however, is restricted

to the pathways known or assumed to be included in the progression of AD, which are frequently based on AChE inhibition.
Several traditional remedies have demonstrated interesting in
vitro and in vivo activities and provided promising components
with potential as therapeutics for neurodegenerative disorders.
Most in vitro studies have focussed on inhibition of AChE
(Houghton et al., 2006; Mukherjee et al., 2007), because this has
so far been the most promising clinical approach for the treatment of AD. For some compounds, clinical data is very limited
while others such as galanthamine and huperzine A have already
reached widespread clinical use and contribute a great effort in
the combat of AD.
To date the pathophysiology of AD is not yet nearly clarified.
Further research will provide better understanding of the
molecular pathways involved and hereby lead to the development of additional pharmacological test systems, in which
activities may yet be observed. Also, some traditional medical
systems such as Ayurveda emphasize health maintenance and
disease prevention over curative treatments. Hence, preclinical
and clinical research into protective and preventive effects of
herbals drugs should be carried out in the future. Interestingly,
a large study conducted with Ginkgo extract EGb761 in France
over 7 years suggested a preventive effect in an aged population
cohort (Andrieu et al., 2003). On the basis of this study, two
large interventional studies have been initiated in the USA and
in France (Christen, 2004). The outcome of these long-term
trials will be important in defining a possible role of natural
product based preventive therapy in AD.
Acknowledgements
Thanks are due to Prof. K. Hostettmann, University of
Geneva, for providing access to ethnobotanical literature, and to
Dr. M. Kessler and M. Kluge, Swiss Pharmaceutical Museum,
Basel, for assistance, valuable information and access to herbals.
Appendix A. Supplementary data
Supplementary data associated with this article can be found,
in the online version, at doi:10.1016/j.jep.2007.07.016.
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