Clitoria ternatea
Learning, Memory-Enhancing, and Anti-Alzheimer’s Effects
In a study by Rai et al. [71] assessed the effects of Clitoria
ternatea (C. ternatea) aqueous root extract on memory and
learning in neonatal rat pups (7 days old) by using PAT, EPM,
and T-maze test or spatial learning tests. Interestingly, it was
found in this study that memory in rats increased considerably
when an extract of C. ternatea roots was used at different doses
as an oral treatment. Conversely, neonatal rat pups were
intubated at the dose of 50 mg/kg and 100 mg/kg of aqueous
root extract of C. ternatea for 30 days during their growth spurt
period. Memory improving properties was observed with
C. ternatea root extract; nonetheless, it did not disturb motor
activity. In addition, in the case of both time points of behavioral
tests, it showed enhanced retention and spatial learning
performance. Henceforth it was evident that permanent change
in the brain mediated by C. ternatea extracts resulted in enhanced
learning and memory. This memory increasing activity
was significantly higher in neonatal rats (i.e., especially during
their growth spurt period) treated for 30 days with C. ternatea
extract (100 mg/kg body weight). So, it seems that treatment
with C. ternatea extract can cause permanent changes in the
rat’s brain and can enhance memory and learning [71].
In rats, in case of the alcoholic extracts of aerial parts and
roots of C. ternatea (i.e., 300 and 500 mg/kg) lessened amnesia
induced by electroshock through conditional avoidance response
paradigm [72]. C. ternatea extract, at the dose of 300 mg/kg,
triggered substantial retention of memory and the root parts
found to be significantly effective; however, the dose of
300 mg/kg appeared very high. The researchers in this study also
assessed the most likely mechanism by which C. ternatea exerts
the anti-amnesic effects on central cholinergic activity. For this
assessment, they evaluated the whole brain’s acetylcholine
(ACh) content and AChE activity at different parts of the rat
brain, specifically midbrain, cerebral cortex, cerebellum, and
medulla oblongata. In this study, in comparison with aerial parts,
C. ternatea extract of roots was found to be more effective in
lessening memory deficits. Alternatively, the pathway via which
C. ternatea generated retention of memory seems to be analogous
to pyritinol (i.e., standard cerebro protective drug). In rat
hippocampus, the effects of aqueous C. ternatea root extract on
the ACh content were discovered [73, 74]. In contrast, when
C. ternatea aqueous root extracts were used at a dose of
100 mg/kg for 30 days in neonatal rat pups (i.e., 7 days old)
and young adult rats (i.e., 60 days old), substantial increase in
the content of ACh was noticed in their hippocampi in comparison
with that of age-matched controls. In 90-day old control
rats, hippocampal ACh content was found to be considerably
less as compared to 37-day old control rats. In the central nervous
system, ACh is considered as one of the key neurotransmitters.
ACh helps to enhance attention and also ease the process
of learning. As a result, in rat hippocampus, increased ACh
content possibly the neurochemical basis for enhanced learning
and memory. Treatment with aqueous C. ternatea root extract
might be effective in strengthening disrupted cholinergic transmission
in specific age-related memory disorders. Furthermore,
in normal individuals, learning and enhanced memory may also
be facilitated by aqueous root extract of C. ternatea. However, it
is yet to be discovered whether this extract exerts similar action
in senile animals or not [75].
Rai et al. [76], in another study, showed that retention in the
PAT memory can also be ominously improved by using
C. ternatea. When young adult rats were orally intubated for
30 days at a dose of 100 mg/kg per day, increased retention
was noticed 48 h after the learning process in the same group
of C. ternatea treated young adult rats in comparison with agematched
saline controls. This further specifies an upsurge in the
capacity to maintain avoidance memories, suggesting possible
effects exerted by C. ternatea on amygdaloid neurons. These
findings collectively specify that treatment by aqueous root extract
of C. ternatea has a specific contribution in the increment of
amygdaloid neuronal dendritic arborization and also hippocampal
CA3 neurons [76]. In a different study Rai et al., [77] further
assessed the effect of C. ternatea aqueous root extract on the
dendritic cytoarchitecture of amygdala neurons [77]. Along with
age-matched saline controls, when Wistar rats (i.e., either sex)
were orally intubated with C. ternatea aqueous root extract (i.e.,
50 and 100 mg/kg) for 30 days and exposed to PAT, a significant
increase was found in retention of passive avoidance and learning.
These rats were sacrificed by decapitation after the PAT. The
amygdala was treated for Golgi staining and following staining
neuronswere traced by using a camera lucida and examined. The
findings of the study revealed a substantial increase in branching
points, dendritic processes, and dendritic intersections that arise
from the soma of amygdaloid neurons in aqueous root extract
treated rats when compared to age-matched saline controls.
Besides that, in the aqueous C. ternatea root extract, treated rats
enhanced dendritic arborization of amygdaloid neurons links
with the improved passive avoidance learning and memory.
The results of the study showed that aqueous root extract of
C. ternatea improves memory by triggering the functional
growth of amygdala neurons. Alternatively, an aqueous root extract
of C. ternatea also influences the structures of the brain
which governs learning and memory specifically amygdala and
hippocampus. These changes related to behavior are considered
comparatively permanent and denotes that C. ternatea can affect
neurotransmitter biosynthesis namely ACh, which plays a significant
role in the learning process and also in memory. In addition,
these changes can also cause permanent changes in the brain.
Moreover, C. ternatea perhaps also facilitates long-term potentiation
[71]. The aqueous root extract of C. ternatea was not only
found to support neurogenesis in the amygdala; nevertheless, it
also triggers the release of neuromodulators or hormones that
control the neurotransmitters and neuromodulators activity specifically
which play vital roles in memory and learning, thus
playing roles in improving memory and learning. Following
comprehensive clinical trials in adults, it was detected that treatment
by aqueous root extract of C. ternatea possibly be foreseen
as an enhancer of memory and also might be beneficial in the
treatment of amygdala-related neurodegenerative disorders [77].
Neuroprotective, Cognition-Enhancing, and Anti-Alzheimer’s
Effects
Talpate et al. [78] analyzed the nootropic and neuroprotective
activity of ethanol extract of C. ternatea extract on diabetesassociated
cognitive impairment in a rat model. The ethanol
extract of C. ternatea (200 and 400 mg/kg) caused a substantial
upsurge in spatial reference memory (P< 0.001), spatial
working memory (P < 0.05) and spatial working-reference (P
< 0.001) in retention trials on Morris water maze, Y-maze and
radial armmaze accordingly. Instead, marked decrease in lipid
peroxide (P < 0.001), AChE activity (P< 0.05), total nitric
oxide (P< 0.001) and significant increase in CAT, SOD,
and GSH levels were detected in animals treated with ethanol
extract of C. ternatea (200 and 400 mg/kg) in comparison
with diabetic control group [78].
Recently, in a study, Rajashree et al., [79] in the streptozocininduced
young diabetic rats, examined the effects of the alcoholic
roots extracts of the C. ternatea on the behavioral and
cognitive changes. A substantial improvement was observed
only in the memory and learning among the diabetic group
and C. ternatea groups of rats [79]. In another study by
Ravishankar et al., [80] examined the neuroprotective effect
of ethanolic C. ternatea root extracts against amnesia triggered
by stress. In this study, conditioned avoidance response by
employing Cook’s pole climbing apparatus and transfer latency
using EPM were used in stress-induced and normal rats to
evaluate cognitive-improving activities. When C. ternatea
was orally administered daily at doses of 150 and 300 mg/kg,
it improves cognition in a dose-dependent way in normal rats.
In extract treated stress-induced rats, fast retrieval was observed
as compared to the stress control group [80]. The neuroprotective
anticholinergic, cognitive, and memory-enhancing, as well
as antioxidant, effects of the C. asiatica extracts and its bioactive
metabolites are specified in Table 3 and Table 4.
Neuropharmacological Effects
In rats and mice, C. ternatea root’s ethanol extract was assessed
for various neuropharmacological actions including exploratory
behavior, general behavior, sleeping time induced by phenobarbitone
and muscle relaxant activity. At the doses of 100 and
150 mg/kg, the extract caused a decrease in spontaneous activity,
reduction in the exploratory behavioral pattern by Y-maze and the
head dip test, decrease in the muscle relaxant activity by rotarod,
traction tests, and 300 inclined screens [94]. Furthermore,
C. ternatea extract considerably increased the phenobarbitone-
mediated sleeping time [94]. In rats, Kulkarni et al. [81] observed
the effect exerted by an alcoholic extract of aerial part of
C. ternatea on special discrimination. When alcoholic extract
was given orally at a dose of 460 mg/kg, a significant increase
in the time taken to traverse the maze was noticed, which was
alike to that generated by chlorpromazine; nonetheless, at a lower
dose (i.e., 230 mg/kg), chlorpromazine was not effective.
Nootropic and Anxiolytic Effects
EPM and object recognition tests were used to evaluate the
nootropic activity of C. ternatea aerial parts extract [82]. On
the 9th day, a marked increase in inflection ratio was noticed in
the case of the animals, which were treated with C. ternatea
(100 mg/kg). It was noticed in the object recognition test that
mice which were treated with C. ternatea took considerably
less amount of time to find out the familiar object as compared
to the new object and markedly decreased the discrimination
index. So, the increased discrimination index and inflection
ratio clearly indicate the nootropic activity of the species. In
addition, C. ternatea also met a key condition for nootropic
activity, which is specifically the memory improvement in cognitive
deficit’s absence. In association with the nootropic drug’s
assumption, a decrease in transfer latency was observed by
C. ternatea in the EPMtest.However, improved inflection ratio
on the 9th day denoted C. ternatea’s less significant effect on
long-term memory. Conversely, Jain et al. [82] conducted a
study by employing the light or dark exploration and EPM test
to evaluate the anxiolytic potential of a methanolic extract of
aerial part of C. ternatea. It was observed that when C. ternatea
(100–400 mg/kg) was administered orally, it augmented the
time spent in the light-box and the time spent in the open
arm. In contrast, in the same study, it was noticed that there is
a reduction in time spent in the dark box. Failure to exert any
substantial effect in both animal models of anxiety was noticed
with the oral administration of C. ternatea at a dose of
30 mg/kg; however, a weaker effect was detected in case of
both the animal models.Malik et al. [95] stated that C. ternatea
aqueous methanol extract showed supremememory-improving
and anxiolytic effect at the doses of 100 and 200 mg/kg.
Anti-Alzheimer’s Effects in Human Studies
In a randomized, crossover study, Chusak et al. [96], in 15
healthy men, estimated the effects of C. ternatea flower extract
on antioxidant status and postprandial plasma glycemia
response. Surprisingly, after 30 min of ingestion, the insulin
and postprandial plasma glucose levels were inhibited when
consuming sucrose and 2 g and 1 g C. ternatea flower extract.
Furthermore, insulin concentration in the fasting state and
glucose level in plasma was not altered due to this extract
consumption. Instead, in the individuals who received 2 g
and 1 g C. ternatea flower extract, a decrease in the level of
MDA and a marked rise in plasma antioxidant capacity (i.e.,
oxygen radical absorbance capacity, trolox equivalent antioxidant
capacity, ferric reducing ability of plasma, and protein
thiol) were detected. In addition, sucrose-stimulated reduction
in trolox equivalent antioxidant capacity and oxygen radical
absorbance capacity and also the increase in plasma MDA
were protected due to the C. ternatea flower extract consumption.
These results suggested that, without hypoglycemia in
the fasting state, plasma antioxidant capacity is increased due
to an acute ingestion of C. ternatea flower extract. It has been
summarized, in adults, following detailed clinical trials, that
treatment with aqueous root extract of C. ternatea may be
beneficial in the treatment of neurodegenerative diseases relating
the amygdala and might also be foreseen as an enhancer
of memory [77]. The possible mechanism of action for anti-
Alzheimer’s potential of C. ternatea is illustrated in Fig. 2.
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