Medicinal Herbs in Iranian Traditional Medicine for Learning and Memory

Abstract

Background:
A few factors such as age, stress, and emotions may lead to impaired learning, memory loss, amnesia, and dementia or threats like schizophrenia and Alzheimer's disease (AD). Iranian traditional medicine (ITM) recommends some herbs and herbal preparations for the treatment or prevention of CNS problems.

Methods:
In this study, scientific evidence related to the effectiveness of ITM herbal medicine on memory, learning and AD is reviewed. The scientific evidence of plant efficacy was searched in electronic databases including PubMed, Scopus, SID, Science Direct, and Google Scholar by keywords such as memory, Alzheimer, amnesia, learning and scientific plant names from 1969 to 2014.

Results:
The findings of this study confirmed the effectiveness of certain ITM medicinal plants on enhancing memory and learning or in the treatment/prevention of amnesia and AD. Some ITM plants like Melissa officinalis, Crocus sativus and Nigella sativa showed improving effects on memory and the treatment of AD in clinical trials. In some cases, active principles responsible for the efficacy of these plants on memory were also determined.

Discussion:
Most of the studies on ITM plants were designed in animal models and a few herbs were evaluated in clinical trials on AD. Furthermore, there are insufficient or no investigations on certain herbal medicines used in ITM to confirm their effectiveness on memory and learning. Therefore, further experimental and clinical studies are necessary to evaluate the effectiveness of these plants on memory and AD as well as determining their active components.

Full text

Shojaii et al., Afr J Tradit Complement Altern Med. (2016) 13(2):199-209
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MEDICINAL HERBS IN IRANIAN TRADITIONAL MEDICINE FOR LEARNING AND MEMORY
Asie Shojaii1*, Roshanak Ghods2, Mehri abdollahi Fard1
1. Department of medicinal plant, Research Institute for Islamic and Complementary Medicine, Iran
University of Medical Sciences, Tehran, Iran. 2. Department of traditional medicine, Research Institute for
Islamic and Complementary Medicine, Iran University of Medical Sciences, Tehran, Iran.
*Corresponding Author E-mail: shojaii.a@iums.ac.ir
Abstract
Background: There are some factors such as age, stress and emotions that may lead to impaired learning, memory loss, amnesia,
and dementia or threats like Schizophrenia and Alzheimer's disease (AD). Traditional Iranian medicine (TIM) recommended some
herbs and herbal preparations for treatment or prevention of CNS problems. In this study, the scientific evidences related to
effectiveness of TIM herbal medicine on memory and learning will be reviewed.
Materials and Methods: The scientific evidences of the plant efficacy were searched in electronic databases including Pub Med,
Scopus, SID, Science Direct, and Google Scholar by keywords like memory, Alzheimer, amnesia, learning and scientific plant
names from 1969 to 2014.
Results: The finding of this study confirmed effectiveness of some of TIM medicinal plants on enhancing memory and learning or in
treatment or prevention of amnesia and AD. Some of TIM plants like Melissa officinalis, Crocus sativus and Nigella sativa showed
improving effect on memory in clinical trials. In some cases, the active principles responsible for efficacy of these plants on memory
were also determined.
Conclusion: Most of the studies on TIM plants were designed in animal models and a few herbs were evaluated in clinical trials on
AD. Also, for some of the herbal medicine used in TIM, there are no or not enough studies to confirm their effectiveness on memory
and learning. Therefore, further experimental and clinical studies are necessary to evaluate the effectiveness of these plants on
memory and AD and also to determine the active components of them.
Key words: Memory, Iranian Traditional Medicine, Medicinal plants, learning
Introduction
Learning is the process of acquiring knowledge about the world, and memory is the retention of the acquired knowledge
which can be retrieved as and when required (Kupfermann, 1993). Memory is an important part of Cognition for which the brain
plays interesting games of neurotransmitter with billion of neurons. Different types of memory are associated with different parts of
the brain. For example, Short term memory is associated with prefrontal cortex, Long term memory occurs in hippocampus and
temporary lobe and skill memory processed in cerebellum (Terry et al., 2011). The disturbance in such area leads to amnesia and
hence memory loss (Soman et al., 2013). Poor learning abilities, impaired memory, lower retention and slow recall are the common
problems in stressful situations. Moreover, age, stress and emotions are conditions that may lead to impaired learning, memory loss,
amnesia, and dementia or to more ominous threats like Schizophrenia and AD (Francis et al., 1999) AD is a neurodegenerative
disease that is characterized by progressive memory loss and cognitive impairment and beta-amyloid (
of neural functions (Long and Dougherty, 2003; Selkoe, 1994).
Nowadays, it seems that pharmacotherapy use of psychoactive drugs which are not effective in all cases and exerts
numerous side effects (especially with long term administration) causes different problems (Vyawahare et al., 2007). On the other
hand, there are some medicinal herbs which recommended through different traditional medicine as memory enhancing agents or
treatment of amnesia. Some of these herbs like Hypericum perforatum, Ginkgo biloba or Ginseng showed significant effect in
experimental or clinical studies on memory and learning (Rai et al., 1991; Wesnes et al., 2000; Hasanein and Shahidi, 2011; Abd-
Elhady et al., 2013).
Traditional Iranian medicine (TIM) includes all the knowledge and practices used in diagnosis, prevention and elimination
in Persia from ancient times to present and its roots go back over 2000 years (Naseri, 2004). TIM has recommended some herbs and
herbal preparations for treatment or prevention of CNS problems like epilepsy, Parkinson and amnesia (called Nesyan in TIM). In
the previous review, we mentioned the most important plants in TIM for treatment of epilepsy (Abdollahi Fard and Shojaii, 2013). In
the present study, the most important herbal medicine mentioned for memory enhancing and treatment of amnesia will be reviewed
and also scientific evidences which confirm their effectiveness will be discussed.
Materials and Methods
In this paper, we reviewed the most important ancient herbal treatments which are effective on learning, memory or treatment
of amnesia and AD. To find these herbal medicines, the most famous TIM books like Makhzan, Tohfeh, Tebe Akbari, and Moalejate

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Aghili were searched and then plant scientific names were identified using combinations of old and new sources. We considered
these medicinal herbs as the key words for the next step of our study (Arzani, 2005; Aghili Khorasani, 2009; Tonkaboni, 2007).
Then electronic databases including Pub Med, Scopus, SID, Science Direct, and Google Scholar were searched from 1966 to 2014
for each of the plants in TIM plus memory, Alzheimer, amnesia and learning as the keywords; the findings summarized as tables.
Results
There are some medicinal plants which were used in TIM for treatment of "Nesyan" (means amnesia) or for enhancing memory
and learning. The results showed that there are some experimental and clinical trials to confirm the effectiveness of these plants on
memory and learning and treatment of amnesia or related disease like Alzheimer (Table 1& 2).
Acorus Calamus
Acorus calamus is recommended for enhancing memory in TIM. Evaluation of the effect of A.calamus on improvement of
learning and memory showed that oral and intraperitoneal administration of the extract in higher dose could have increase spatial
recognition and recalling the data (Naderi et al., 2010). In a study, the effect of a polyherbal formulation (Bramhi Ghrita) containing
A.calamus on learning and memory in rats was evaluated. This preparation caused significant reduction in transfer latency in
Elevated Plus Maze (EPM) and escape latency in Morris Water Maze (MWM) test and so it act as a memory enhancer formulation
(Achliya et al., 2004).
The effect of A.calamus extract and its active principle, a-asarone on memory impairment, revealed that co-administration
of rats with A.calamus and a-asarone could prevent the stress induced alterations significantly. So administration of A. calamus
extract and a-asarone prevent noise; this noise stress induced memory impairment (Sundaramahalingam et al., 2013).
Allium Sativum
Garlic is mentioned to be effective in treatment of amnesia in TIM. Evaluation of the acute and chronic effects of crude
garlic extract on learning and memory showed that long-term administration of crude garlic extract may improve learning and
memory in mice while the underlying mechanism of action may be attributed to the anti-Acetylcholine Esterase (AchE) activity and
anti-oxidant property of garlic (Mukherjee and Banerjee, 2013). Also, it showed that twelve week treatment with shallot or garlic
significantly prevented the learning and memory deficits induced by fructose-feeding (Jalal et al., 2011). Evaluation of the
mechanism of garlic effect on memory showed that garlic administration in rats affects brain serotonin (5- hydroxytryptamine) levels
and memory-enhancing effect of garlic may be due to increase in serotonin metabolism in rat brain (Haider et al., 2008).
Table 1: Traditional medicinal plants for memory and learning
Name of plant
Traditional name
Part used
in TIM
Preparation or compound used in
experimental study
Acorus calamus
(Araceae)
Vaj
Roots
Ethanol extract
Ethylacetate extract
-asarone
poly herbal formulation
Allium sativum
(Alliaceae)
Soom
bulb
Crude garlic Extract
Aged garlic extract
Cooked garlic extract
S-allylcysteine
Z-ajoene
Anacyclus pyrethrum
(compositae)
Aghargharha
Roots
Hydroalcoholic extract
Boswellia sp.
(Burseraceae)
B.serrata
B.papyrifera
B.carterii
Condor
Gum resin
Gum resin
aqueous extract
Ethanolic extract
-boswellic acid
aqueous extract
Boswellic acid fraction
aqueous Extract
Ethylacetate fraction
N-butanol fraction
Cocos nucifera
Arecaceae
Narjil
Water
Coconut water
Crocus sativus
Za'faran
Alcoholic extract

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(Iridaceae)
Methanol/water extract
Herbal formulation
Crocin
safranal
Cyperus rotundus
Cyperaceae
So'de Kofi
Roots
Ethanolic extract
Ferula asa-foetida
(Apiaceae)
Anghoseh
Gum resin
Aqueous extract
Lavandula sp. (Lamiaceae)
L. officinalis
L.angustifolia
L.hybrida
Ostokhoddos
Aerial
parts
Ethanolic extract
Aqueous extract
Essential oil
Odor(Part of aromatherapy)
Melissa officinalis
(Lamiaceae)
Badrangboyeh
Aerial
parts
Hydroalcoholic extract
Ethanolic extract
Nigella sativa
(Ranunculaceae)
Shoneez
Seeds
oil
Phyllantus embelica
(Phyllanthaceae)
Amlaj
Fruits
Methanolic extract
Hydroalcoholic extract
Ruta graveolens
(Rutaceae)
Sudab
Aerial
parts
Methanolic extract
Santalum album
(Santalaceae)
Sandal
Wood
Alcoholic extract
Aqueous extract
Terminallia chebula
(Combretaceae)
Halile-kaboli
Fruits
Seed powder
Teucrium polium
(Lamiacea)
Ja'deh
Aerial
parts
Hydroalcoholic extract
Aqueous extract
Vitis vinifera
(Vitaceae)
Maveez*
Fruits
Methanolic extract
Methanolic fraction
Viniferin glucoside
Seed polyphenolic extract
skin extract of black grape
Zingiber officinalis
(Zingiberaceae)
Zangebil
Rhizoms
Alcoholic extract
Hydroalcoholic extract
Essential oil
Zingicomb(ginger+ginkgo)
*Maveez is a dried fruit of some kinds of grape
There are lots of studies about the effect of aged garlic on memory and it's mechanism of action. Investigation of the
beneficial effects of fresh, aged, and cooked garlic extracts on memory in diabetic rats showed that fresh and cooked but not aged
garlic extract (AGE) increased memory in diabetic rats significantly (Sarkaki et al., 2013). Another studies showed that chronic
ingestion of this extract markedly improved the learning deficits of Senescence-accelerated mouse (SAM) and also prevented brain
atrophy and kept the brain size at the control level (Nishiyama et al., 1997; Moriguchi et al., 1996). AGE also improved learning and
memory deficits of SAM and showed an antiaging effect on the SAM (Moriguchi et al., 1997). Chauhan and Sandoval showed that
feeding of AGE prevented deterioration of hippocampal based memory tasks in mice and suggesting that AGE has a potential for
preventing AD progression (Chauhan and Sandoval, 2007). It was suggested that consumption of garlic may lead to i
aggregation and AGE may improve cognitive impairment against Aβ-induced neuronal deficit, and has a beneficial effects on AD
(Gupta et al., 2009; Jeong et al., 2013).
S-allylcysteine is a major thioallyl compound found in garlic extract. Investigations revealed that diet supplementation
with S-allylcysteine may reduce age-related learning disabilities and cognitive disorders in senescence-accelerated mice (Nishiyama
et al., 2001). Furthermore AGE and its active ingredients, S-allyl-L-cysteine can restrict several pathological cascades related to the
synaptic degeneration and neuroinflammatory pathways associated with AD (Ray et al., 2011) and AGE protects neuronal PC12
cells against Aβ (25-35) toxicity in a dose dependent manner (Griffin et al., 2000).
The inhibitory effects of Z-ajoene, major compound containing sulfur in oil-macerated garlic products, showed against
scopolamine-induced memory impairment in mice. This study suggested that Z-ajoene may act on the cholinergic system and on
memory impairment caused by excess activity of AChE (Yamada et al., 2004).
Anacyclus Pyrethrum
Anacyclus pyrethrum, called "Aghergherha" in TIM, has been recommended for improving memory in traditional medicine.
Pre-treatment with the extract of A. pyrethrum roots (250 and 500 mg/kg) showed antiepileptic effect and also showed protection

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against cognitive impairment by decreasing oxidative stress and rho kinase ROCK II expression in pentylenetetrazol kindled mice
(Pahuja et al., 2013).
Boswellia Sp.
The gum resin of Boswellia species (commonly named oilbanum) recommended for enhancing memory and treatment of
amnesia in traditional texts. The effect of olibanum gum resin on memory and learning of rat newborns was investigated in
numerous studies. In a study by Rasoli et al., aqueous extract of B. carterri gum resin (especially in dose 0.05 g/kg) showed
significant effect on learning ability and especially in the strengthening and maintaining of memory in rat's newborns comparing to
control groups (Tavakkolifar et al., 2009; Rasoli et al., 2001). Also, consumption of oilbanum in lactation period (8 weeks) in female
rats has a good effect on learning and short-term memory of newborns which their mothers use of this gum during lactation (Vahidi
et al., 2003). Hosseini et al. showed that olibanum could prevent impaired learning and memory caused by methimazole-induced
hypothyroidism in adult rats (Hosseini et al., 2010).
Ethyl acetate and N-butanol fractions of B. carterii gum resin showed significant effects on enhancing the memory ability in
rats which was much significant with ethyl acetate fraction (Hosseinzadeh et al., 2010). Consumption of the aqueous extract of B.
serrata gum resin in rat mothers during lactation in two-month old rats showed significant increase in short-term memory and long-
term memory in experimental group as compared to control group (Hosseini SharisAbad et al., 2003). Evaluation of the effect of the
aqueous extract of B. papyrifera on learning and memory revealed that it can be an agent for facilitation of learning and memory
(Farshchi et al., 2010). Another study on B. papyrifera revealed that it can affect spatial memory retention irrespective of the
treatment period and also systemic administration of the boswellic acids fraction obtained from B. papyrifera, enhanced spatial
memory retention in a dose-dependent manner (Mahmoudi et al., 2011).
The dendritic systems are the functional core of neuronal collections as they signify most of the receptive surface of neurons
and their organization is essential for integration and transfer of information at the synaptic level (Sharifabad and Esfandiari 2007).
In a study using Boswellia-treated young rats prenatally, it was concluded that better learning and memory performance in the
offspring of the mothers who consumed olibanum during their pregnancy is related to an increase in the somal volume of
hippocampal neurons in cornu ammonis and also these rats showed more dendritic branches in CA3 (cornu ammonis) pyramidal
neurons (Sharifabad and Esfandiari 2007). Beta boswellic acid, the major component of Boswellia serrata gum resin, could enhance
neurite outgrowth and branching in hippocampal neurons. Also long-term administration of Boswellia resin can attenuate age-related
dendritic regression in the superior region of cornu ammonis pyramidal cells in rat hippocampus (Hosseini-Sharifabad and
Esfandiari, 2015).
Cocos Nucifera
Cocos nucifera (coconut) is recommended for improving and enhancing memory in TIM. It was reported that young
coconut water has a high concentration of a hormone – estrogen - which helps to delay the onset of AD. This experiment on
removing both ovaries of white mice, as a model of women with menopause that are deficient in estrogen, revealed that the mice that
received the coconut water have less pathological symptoms than the ones that did not receive it. It is stated in her recent study that
young coconut water could significantly reverse some pathologies associated with AD (Chomchalow, 2013).
Crocus Sativus
Crocus sativus (Saffron) is an important TIM herb which is mentioned to enhance memory. There are numerous studies
about the effect of saffron and its active constituent's crocin, crocetin and safranal on learning, memory and AD. Investigation of the
effects of an alcohol extract of C. sativus on learning and memory suggested that saffron extract ameliorates the impairment effects
of ethanol on learning and memory processes, and possesses a sedative effect (Zhang et al., 1994). In another study showed that pre-
training treatment with C. sativus extract could significantly antagonized the scopolamine-induced performance deficits in the step-
through passive avoidance test (Pitsikas and Sakellaridis, 2006). It has been shown that C. sativus extract antagonized ethanol-
induced memory impairment in the passive avoidance task in the mouse (Sugiura et al., 1995a).
Evaluation of the effect of saffron in aged mice showed significant improvement in learning and memory in saffron-treated
mice, accompanied by reduced lipid peroxidation products, higher total brain antioxidant activity and reduced caspase-3 activity in
age groups of mice (Papandreou et al., 2011). Investigation of the cognitive enhancement effect of an herbal extract containing C.
sativus showed that this preparation can reduce the decline in spatial cognition, which might be due to its effects on reducing Aβ
plaque formation and ameliorating histopathology and ultra structure in hippocampus of mouse brain (Cong et al., 2012).
Crocin is one of the active constituents of saffron which has been reported to enhance memory (Pitsikas et al., 2007).
Saffron extract and crocin improved ethanol-induced impairments of learning behaviors in mice, and prevented inhibition of
hippocampal long-term potentiation induced by ethanol (Abe and Saito, 2000). Also, it reported that crocin (50 to 200 mg/kg) had
beneficial effect on improving of ethanol-induced memory retrieval deficit of mice in passive avoidance task (Sugiura et al.,
1995b). Saito showed that crocin improved learning deficits by attenuating the inhibitory effect of ethanol on long-term potentiating
generation, and it can be considered as a candidate for treatment of ethanol-induced central nervous system disorders (Saito, 2004).
Also, crocin can inhibit scopolamine-induced impairments of spatial learning and memory in rats (Ghadami and Pourmotabbed,
2009). It has been shown that Intracerebroventricular streptozotocin (STZ) can cause cognitive impairment in rats. Evaluation of the
effects of crocin on cognitive performance of these rats showed that crocin treatment improved cognitive performance and resulted
in a significant reduction in malondialdehyde levels and elevation in total thiol content and glutathione peroxidase activity
(Naghizadeh et al., 2013). Further studies revealed that crocin specifically antagonizes the inhibitory effect of ethanol on N-methyl-
d-aspartate (NMDA) receptor-mediated responses in hippocampal neurons (Abe et al., 1998). C. sativus extract and crocin have
potential effect in the treatment of neurodegenerative diseases such as AD (Khalili et al., 2009; Khalili and Hamzeh, 2010).

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Also, saffron extract and crocin, improve spatial cognitive abilities following chronic cerebral hypo-perfusion and these
effects may be related to the antioxidant effects of these compounds (Hosseinzadeh et al., 2012). Evaluation of the effect of C.
sativus stigma extract and its constituents, crocin and safranal, on memory and learning showed that saffron aqueous extract, crocin
and safranal did not have effect on intact memory but the saffron extract and crocin inhibited the hyoscine unpaired
acquisition/performance activity (Hosseinzadeh and Ziaei, 2006). A similar study supported previous findings and suggested crocin
involvement in the modulating storage and/or retrieval of information. Crocin also showed positive effects in preventing the
impairment of learning and oxidative stress damage induced by chronic stress (Ghadrdoost et al., 2011).
The effect of saffron on AD was studied in several studies. It was shown that the water: methanolic extract of C. sativus stigmas
inhibited Ab-peptide fibrillogenesis possibly due to the presence of trans-crocin-4 and its digentibiosyl moiety (Papandreou et al.,
2011).
Two clinical trials by Akhondzadeh et al. revealed the effectiveness of saffron in mild to moderate AD (AD). In one study, 46
patients with probable AD received saffron capsules (15 mg) twice daily. Results suggest that using saffron capsules can be
associated with a better outcome on cognitive functions compared to the placebo group in a 16-week study (Akhondzadeh et al.,
2010a). Another study on 54 adults with similar doses of saffron evaluated the efficacy of saffron compared with donepezil (10
mg/day) in treating mild to moderate AD in a 22-week trial. Results demonstrate similarity in cases with adverse effects except
vomiting, which occurred more frequently in the donepezil treated group (Akhondzadeh et al., 2010b). In a randomized double-blind
clinical trial, treatment of electroconvulsive therapy-induced memory impairment with a preparation including saffron in patients
with mood disorders caused improvement in impaired memory, especially one or two months after the last electroconvulsive
therapy session. However, it had no significant effects during and immediately after the electroconvulsive therapy period
(Akuchekian et al., 2012). (Table 2)
Cyperus Rotundus
Cyperus rotundus is used for improving of memory in TIM. Evaluation of the effect of ethanolic extract of Cyperus
rotundus root (100, 200 mg/kg) on midazolam induced acute memory loss revealed that this extract significantly decreases the
transfer latency in EPM which measures the increase in memory at the time of retrieval and therefore cyperus rotundus shows
significant nootropic activity on retrieval and non significant on consolidation (Soman. et al., 2013).
Also, investigation of the effect of C. rotundus tubers on learning and memory in the rat model of AD suggest that C.
rotundus tubers has some repairing effects on the memory and behavioral disorders produced by lesioning of the nucleus basalis of
Meynert in rats (Rabiei et al., 2013).
Ferula Asafoetida
Ferula species are endemic plants of Iran and recommended for nervous problems like epilepsy and amnesia in TIM. Oral
administration of Ferula asafoetida aqueous gum extract showed significant improvement in memory score at 400 mg/kg dose in
passive avoidance model and dose-dependent improvement of transfer latency in EPM model. Also, dose-dependent inhibition of
brain cholinesterase and significant improvement in antioxidant levels were also observed. So, Memory enhancing potential of F.
asafoetida can be attributed to AchE inhibiting and antioxidant properties (Vijayalakshmi et al., 2012).
Lavandula Sp.
Lavender is used is some CNS disease like epilepsy, seizure and amnesia in TIM. Investigation of the effect of Lanvandula
officinalis extract on memory, learning and nociception in rats showed lavender extract at doses 100, 200 and 400 mg/kg improved
learning and memory compared to the control group (Rabiei et al., 2014).
Efficacy of Lavender also studied in AD. Soheili et al. showed that aqueous extract of L. angustifolia improves the spatial
performance of AD in rat. In the next study, they concluded that the lavender extract at the doses of 100 and 200 mg/kg markedly
decreased the extent of Ab aggregates which is a major cause of cognitive dysfunction in AD (Soheili et al., 2012). Also,
investigating the protein profile of the effects of aqueous extract of L. angustifolia on spatial performance of AD in rats showed 80
new proteins that expressed and 104 protein that suppressed in control group which receive 200 mg/kg of lavender (Videira et al.,
2013). Chronic exposure to L. angustifolia and L. hybrida essential oils in rats subjected to scopolamine-induced dementia, showed
positive effect on memory formation and reverse spatial memory deficits induced by dysfunction (Hritcu et al., 2012).
Use of lavender essential oil as a part of an aromatherapy in 28 elderly people (17 of whom had AD), showed significant
improvement in personal orientation related to cognitive function after therapy. So, this aromatherapy was efficacious therapy for
dementia (Jimbo et al., 2009). In a cross-over experiment, lavender or lemon odor improved performance four weeks later in both
free recall and recognition of a word list. In the other experimental group of this study to evaluate the effect of these two odor cues in
three learning and memory tests it showed that no significant main effect was observed on recall performance as a result of having
lemon or lavender at either learning or test. Although lavender had some effect on problem solving, context-dependent retrieval was
seen only in free recall and spatial learning (Parker et al., 2001).
Mellisa Officinalis
Melissa officinalis (Lemon balm) is mentioned to improve memory and consciousness in TIM. Hydro-alcoholic extract of
M. officinalis showed no significant effect on learning in MWM task but increases short-term memory in lower dose (25 mg/kg),
although, it may have prevention effect on making short-term memory in higher dose (100 mg/kg) (Yosofi et al., 2011) Soodi et al.
reported that M. officinalis (200 mg/kg) could significantly enhance learning and memory of rats and significantly ameliorate

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scopolamine-induced learning deficit. It is suggested that inhibition of AChE activity by M. officinalis extract is the at least one of
the mechanisms contributed in memory (Soodi et al., 2014).
There are some clinical trials for evaluating the effect of M. officinalis on memory. In a controlled trial, the effect of M.
officinalis extract on patients with mild to moderate AD was investigated. The results showed that patients who received M.
officinalis extract experienced significant benefits in cognition after 16 weeks of treatment. The findings was emphasized by the
improvements seen in both the cognitive subscale of AD assessment scale and clinical dementia rating–sum of the boxes measures in
the Melissa group (Akhondzadeh et al., 2003). In another study the acute effects of M. officinalis extract was studied on cognition
and mood of healthy, young participants at 7-day intervals. The results showed improvement in accuracy of attention with dose 600
mg of M. officinalis and time- and dose-specific reductions in both Secondary memory and working memory factors. This study
suggests that the ingestion of single doses of M. officinalis can modulate both the mood and the cognitive performance of healthy
volunteers in a dose- and time-dependent manner (Kennedy et al., 2003; Kennedy et al., 2002).
Nigella Sativa
The seeds of Nigella sativa used for enhancing learning and memory in TIM. Evaluation of the effect of Nigella sativa oil
on the spatial memory performance of rats revealed that there was a significant decrease in the overall mean number of working
memory error in the Nigella oil-treated group and therefore N. sativa oil could enhance the learning and memory abilities of the rats
(Sahak et al., 2013).
In a clinical study, the effect of N. sativa on memory, attention and cognition in elderly volunteers was evaluated in two
groups of volunteers during 9 weeks. The results showed significant difference in the score of logical memory test-I and II, total
score of digit span, 30 min delayed-recall, percent score in Rey-Osterrieth complex figure test, time taken to complete letter
cancellation test, time taken in trail making test-A and test-B, score in part C of stroop test due to ingestion of N. sativa and there
were not statistically significant changes in any of the biochemical markers during the study period. So, it can be a good candidate
food for preventing alzheimer's disease (Bin Sayeed et al., 2013) (Table. 2)
Phyllanthus Emblica
Phyllanthus emblica or Embellica officinalis is recommended for enhancing learning and memory in TIM. Evaluation of
the memory enhancing effect of the methanolic extract of P. emblica fruits showed that it could significantly improve learning and
memory, prevented scopolamine and sodium nitrite induced experimental amnesia and may be a great potential in memory deficits
(Ashwlayan and Singh, 2011). In another study it revealed that embelica extract possesses memory enhancing, antioxidant and anti-
cholinesterase activity (Golechha et al., 2012). Vasudevan et al. showed that Anwala churna (Emblica officinalis Gaertn) caused a
dose-dependent improvement in memory scores of mice and also it reversed the amnesia induced by scopolamine and diazepam. So
it may prove to be a useful remedy for the management of AD (Vasudevan and Parle, 2007).
Ruta Graveolens
Ruta graveolens is mentioned to increase nous in TIM. Evaluation of the efficiency of R. graveolens and Peganum
harmala extract in management of neuroinflammatory insults and neuronal apoptosis characterizing AD showed that treatment of
AD-induced rats with these methanolic extract, significantly ameliorates the cholinergic dysfunction and inflammation-induced
neurodegeneration characterizing AD. These effects were achieved through the powerful anti-inflammatory activity and anti-
apoptotic effects of these extract (Salem et al., 2013).
Santalum Album
Santalum album wood has been suggested for enhancing memory in TIM. In a study by Azmathulla et al., aqueous extract
of S. album increase the level of acetyl cholinesterase helpful in the brain for storing the memory and so it has a memory enhancing
property in mice (Azmathulla et al., 2010). Memory enhancing effect of the alcoholic extract of S. album was studied in mice induce
with Aβ protein for memory loss. The results show that the S. album has the property of increased enzyme levels. So, S. album L.
has the memory enhancing property (Papaiah et al., 2010).
Terminallia Chebula
Terminallia chebula has been used for different illnesses in TIM. It is recommended for improving memory and mind and
also treatment of amnesia. The ripe fruit of T. chebula is regarded as a promoter of intellect and memory, and is believed to prolong
life (Manyam, 1999; Misra, 1998). The ripe fruit is reputed to retard the ageing process and to improve cognitive processes and so,
has benefits in AD (Manyam, 1999).
In a study by Park et al., oral administration of T.chebula seeds ( 100mg/Kg) for 7 days caused neuroprotective effect
against ischemic damage in hipocampal C1 regions of the gerbil (Park et al., 2011).
Teucrium Polium
Teucrium polium was mentioned to exhibit positive effects on memory in Iranian traditional texts. The cognitive
impairment which occurs in diabetes mellitus, in a study by Hasanein and Shahidi, showed that administration of T.polium for 30
days from the onset of diabetes improved passive avoidance learning and memory of control rats and alleviated the negative
influence of diabetes on learning and memory (Hasanein and Shahidi, 2012). The findings of another study to evaluate antiamnesic

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activity of lamiacea plants including T. polium L., salvia officinalis and Melissa officinalis revealed that T. polium was active dose-
dependently, in antiamnesic experiment and it had the highest inhibition in the anticholinesterase assay among other plants (Orhan
and Aslan, 2009).
Vitis Vinifera
"Maveez" is a type of dried grape fruits which is mentioned for improving learning in TIM. The effect of methanolic
extract of Vitis vinifera and methanolic fraction of the extract on memory and behavior mediated by monoamines was studied and
the results suggest that V. vinifera possess nootropic activity in view of its facilitator effect on retention of learned task (Kakad et al.,
2008) peptides have an important role in AD. In a study by Riviere et al., viniferin glycoside, which was extracted from stem of
V. vinifera, exhibited the strongest inhibitory activity of Aβ (25-35) aggregation in vitro. Also, viniferin glycoside inhibited Aβ
cytotoxicity and the non-covalent complex between viniferin glycoside and Aβ (Rivière et al., 2010; Richard et al., 2011).
In another study, administration of grape seed polyphenolic extract for five months in in vitro
and attenuates cognitive impairment and AD-related neuropathology in the brains of transgenic mice (Liu et al., 2011). The black
grape skin extract reduces the reactive oxygen species production, protects the cellular membrane from oxidative damage, and
consequently prevents DNA fragmentation and so; it may be used to ameliorate the progression of pathology in AD disease therapy
(Russo et al., 2003).
Zingiber Officinalis
The rhizomes of Zingiber officinalis (ginger) were used for improving memory in TIM. Evaluation of the effects of
alcoholic extract of ginger in rats showed that cognitive function and neurons density in hippocampus of rats receiving ginger extract
were improved while the brain infarct volume was decreased. Indeed, it reduced cognitive deficits induced by focal cerebral
ischemia (Wattanathorn et al., 2011).
3, 4-methylenedioxymethamphetamine (MDMA) is known to produce brain damage and spatial memory impairment.
Findings of a study by Mehdizadeh et al. revealed that Z. officinalis could protect brain damage in MDMD treated rats and reduced
learning memory deficits that were induced by MDMA (Mehdizadeh et al., 2012). In another study, the essential oil of ginger
produced a cognitive impairment, in the passive avoidance test. The effects of ginger essential oil may be dependent on an
antagonist action on the central muscarinic cholinergic system (Bezerra Felipe et al., 2008). Evaluation of the effectiveness of Z.
officinale in combination with ginkgo biloba extracts revealed that 1 mg/kg of this mixture improved escape learning in the water
maze test (Topic et al., 2002).
Discussion
Poor learning abilities, impaired memory, lower retention and slow recall are the common problems in stressful situations.
In addition, age, stress and emotions are conditions that may lead to impaired learning, memory loss, amnesia, and dementia or AD.
AD is a neurodegenerative disease and characterized by loss of learning ability with ageing (Francis et al., 1999, Terry et al., 2011).
Herbal medicine has been used for improving learning ability and enhancing memory in different traditional medicines.
TIM suggests some plants as single herb or in form of preparations for improving memory and for amnesia (Aghili Khorasani, 2009;
Tonkaboni, 2007). In this article, the most important TIM herbal treatments which are effective on learning, memory or treatment of
AD and amnesia and also scientific evidences for their efficacy were reviewed.
For Some of these plants, such as saffron, Olibanum gum, Garlic, Lavender and lemon balm, there are several studies
which confirmed the memory enhancing ability and effectiveness of them on learning and memory. The efficacy of saffron, lemon
balm, lavender and Nigella sativa was confirmed in clinical studies too. For some herbs such as saffron, garlic or ginger, the major
chemical constituents which may responsible for their memory enhancing effect was also studied.
There are some other herbal medicines in TIM which have still not been investigated for their pharmacological effect on
memory, such as Pistacia vera (Fostogh), Pistacia lentiscus (Mastaki) and Urginea maritime (Esghil).
Medicinal herbs which reviewed in this article would be good candidates for future studies on memory or treatment of AD
and amnesia. Some of TIM herbs such as Ruta graveolens or Cocos nucifera need further studies to confirm their effectiveness on
memory. It is suggested that more experimental and clinical studies were designed to confirm effectiveness of TIM plants on
memory, learning and AD as well as determining their active principles and mechanisms of action.
Acknowledgment
This study was supported by the Research Institute for Islamic and Complementary Medicine (Iran University of Medical
Sciences). The authors express their thanks to the library staff that helped them with the study’s data collection.

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Table 2: Clinical studies of TIM medicinal plants effective on memory
Plant
name
Design
Intervention
participants
Out come
reference
Crocus
sativus
Multi-center,
,double blind
RCT*(22-week)
15 mg cap saffron(twice
daily) or Donpezil(5mg
twice daily)
54 adults with mild
to moderate AD**
Saffron at this
dose was effective
similar to
donepezil
) Akhondzade et
al., 2010b(
Crocus
sativus
RCT (16week)
15 mg cap saffron(twice
daily) or placebo
46 patients with
mild to moderate
AD
Saffron has
significantly
better outcome
than placebo
(Akhondzadeh et
al., 2010a)
Crocus
sativus
double blind RCT
Herbal combination(9gr
twice daily) or placebo
Mood disorders
which candidate for
electroconvulsive
therapy
Improvement in
impaired memory
(Akuchekian et
al., 2012)
Lavender
crossover
method with
washout period 28
days
Part of aromatherapy***
28 elderly
people(17 of whom
had AD)
significant
improvement in
personal
orientation related
to cognitive
function
(Jimbo et al.,
2009)
Lavender
Cross-over study
Lavender or lemon odor
1****.Ninety first
year psychology
undergraduates
participated
2. Forty-eight
undergraduate
subjects
Context-
dependent
retrieval in free
recall and spatial
learning
( Parker et al.,
2001)
Mellia
officinalis
Double blind RCT
(4 months)
Mellia extract 60 drops/day
or placebo
42 patients with
mild to moderate
AD
significant
improvement in
cognition in
mellisa group
(Akhondzadeh et
al., 2003)
Mellia
officinalis
Double-blind
RCT, balanced
cross over
Single dose of 300, 600,
900 mg of mellisa or
placebo
Healthy participants
modulate the
mood and the
cognitive
performance
( Kennedy et al.,
2003; Kennedy et
al., 2002)
Nigella
sativa
RCT
(9 weeks)
500 mg cap or placebo
40 Healthy elderly
volunteers
significant
difference in the
score of logical
memory test
(Bin Sayeed et al.,
2013)
*RCT= Randomized, placebo controlled trial
**AD= Alzhiemer's disease
*** aromatherapy contitunts: aroma of 0.04 mL lemon and 0.08 mL rosemary essential oil in the morning and to 0.08 mL lavender
and 0.04 mL orange essential oils in the evening
**** Two different experimental groups
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