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Views & Citations
Phytotherapy
is the most commonly used method in “Traditional and Complementary Medicine”
applications. It is based on scientific studies and clinical studies. It is
known to treat with phytotherapy especially during the preventive medicine
phase.
Phytotherapy
for the treatment of epilepsy is a traditional practical medical form in
various cultures. Herbal medical traditions are reported in China, Iran, Europe
and America. Phytotherapy is the prominent approach to complementary and
alternative drugs that play a significant role in controlling epileptic
seizures or complications caused by anti-epileptic drugs. Patients with
epilepsy have access to herbal remedies in developing countries, their goals
and attitudes are different from those in developed countries. Herbal medicines,
which are the most commonly used and alternative drugs in developed countries;
seizure control and anti-epileptic drugs are used to reduce the complications,
caused by general health care.
For this
reason, a review of the phytotherapeutic agents used for epilepsy on all
continents was prepared.
INTRODUCTION
Phytotherapy, which can be defined as plant
use in the prevention or treatment of diseases; medicinal and aromatic plants,
various parts of the plants secreted by the gums, balsams, resins such as
exudates, extracts, essential oils are defined as the help to the treatment
[1]. Phytotherapy is not an alternative method of treatment but a complementary
treatment. Phytotherapy is a rational, evidence-based, allopathic treatment
method and it is determined which agent group is responsible for the biological
effects [2].
F Recent studies, experimental tests in most
experimental studies, herbal medicines are reported to be used for epilepsy.
However, there is no robust evidence for the efficacy and toxicity of most
plants in epilepsy. Approximately 30% of epileptic patients receiving
anti-epileptic drugs are still reported to have seizures [3].
In summary, phytotherapy studies are thought
to provide a high degree of success to scientists in finding new molecular
mechanisms and anti-epileptic drugs for epilepsy [4]. Therefore, a review of
herbal medicines' efficacy on epilepsy is presented. The literature review is
planned on the classification of phytotherapeutic agents according to use in
all continents.
LITERATURE REVIEW
·
1996-2006
In a 1996 study, the inhibition of neuronal
activity in hippocampal slices of epilepsy rats by Aconitum alkaloids was
investigated. Accordingly, it was concluded that 10 wM lappaconitine, an
extract of aconitum alkaloid, reduces epileptiform activity by maintaining
normal neuronal activity [5].
In a 1997 study, the antiepileptic effect of
nimodipine (NIM) on penicillin-induced seizures in rats was investigated. It
has shown that NIM, a calcium antagonist, can significantly inhibit seizures
and epileptic discharge. This supports NIM as a new type of anti-convulsant in
clinical practice [6].
In 1999, the proconvulsive effect of tea (Camellia sinensis) on mice was
investigated. Tea extract (both black and green) significantly accelerated the
onset of convulsions and increased the duration of convulsions and mortality in
mice. Based on an earlier report that both black and green tea can be effective
in the Ca2+ channels, since both extracts cannot alter the level of
GABA in the brain, it is suggested that the observed proconvulsive effect of
tea is mediated by Ca2+ channels, not through GABA [8].
Lavandula stoechas L. (Lamiaceae) has been used as
anti-convulsant in traditional medicine. In a 2000 study, the anticonvulsant
activity of Lamiaceae was evaluated ethnopharmacologically on mice. Plant
extract shows anti-convulsant activity and it is also thought that calcium
channel blockage may be associated with these activities [9]. In 2000, the
anti-convulsant properties of the root source of Afrormosia laxiotora (Leguminosae) were investigated. Doses of
0-300 mg/kg of this extract significantly reduced the duration of convulsive
symptoms and increased seizure latency in both picrotoxin and
electroshock-induced seizures compared to controls. The results reveal the
potential beneficial effects of plant root for epilepsy [10].
In a study published in 2001, the
anti-convulsant properties of Annona
diversifolia leaves of the palmiton were examined. The pharmacological
profile of palmitone for the pentylene tetrazole (PTZ) model epilepsy suggests
that this compound may be effective on the GABAergic inhibiting system [11].
Streblus asper Lour Moraceae is a small tree
native to tropical countries such as India, Sri Lanka, Malaysia, the
Philippines and Thailand. It was mentioned that S. asper root extract was recommended for use in epilepsy and
cardiac disorders [12].
In a 2001 study, the protective role of Bacopa monniera in morphine-induced
hepatotoxicity on rats was investigated. Bacopa
monniera; is a small creeping plant that grows frequently in marshlands in
India, known as brahmi in the ayurvedic medical system. It is used as a strong
nerve tonic in the treatment of epilepsy [13].
In 2001, anticonvulsant activity of the
ethanolic extract isolated from Delphinium
denudatum, a popular folk medicine for the treatment of epilepsy in the
traditional Unani medical system, was investigated. The results showed the
presence of strong anti-convulsant compounds of D. denudatum [14].
Delphinium denudatum Wall. (Ranunculaceae) is a
medicinal plant used in the treatment of epilepsy. In 2001, the anti-convulsant
activity of the FS-1 subfraction isolated from the roots of ranunculaceae was
studied. According to the results, the compounds of ranunculaceae in FS-1 show
broad and strong anti-convulsant activity [15].
In a study conducted in 2001, the
anti-convulsant properties of Cyperus
articulatus (Cyperaceae) methanolic extract were investigated and results
were found to have anti-convulsant properties for Cyperaceae rhizome used for
epilepsy in Africa [16].
Considering the anti-convulsive benefits of
plants carrying linalool by researchers of various conventional medical
systems, the effects of linalool binding on cortical membranes in 2001 were
studied. It is stated that the anti-convulsant mode of action of linalool
involves a direct interaction with the NMDA receptor complex [17].
In a 2001 study, it was reported that Indigofera tinctoria Linn. plant was
used for the treatment of epilepsy in the Indian medical system [18].
In 2002, the protective effect of Acorus calamus Linn (Araceae) plant
against neurotoxicity due to acrylamide was investigated. According to the
results, this plant shows the effect of seizure delay and decreasing mortality
[19].
In a 2002 study, Goodyerin's anti-convulsant
activity, a flavonol glycoside from Goodyerin
schlechtendalii, was investigated. According to the results, Goodyerin
showed a dose-dependent sedative and anti-convulsant effect [20].
In a 2002 study, four traditional Zulu
medicinal plants (Rhoicissus digitata,
R. rhomboidea, R. tomentosa and R.
tridentata) were tested for anti-oxidant activity from their roots and
leaves. All of these plants known under the name Zulu can be used in the
treatment of epilepsy [21].
In 2002, the effect of St. John Wort (Hypericum perforatum L.) on rabbits was
studied with kindling epilepsy model. The substances present in the butanol
fraction of the yellow centaury suppress epileptic symptoms in 40% of epileptic
animals, while lipid soluble components in the ether fraction increased
epileptic activity [22].
Ferula gummosa Boiss (Apiaceae) is used as an
anti-epileptic drug in traditional Iranian medicine. According to a study,
Apiaceae's seed acetone extract was evaluated for anticonvulsant activity
against seizures caused by PTZ and electroconvulsive shock in mice. The results
showed that it had a protective effect against experimental seizures [23].
In a 1998 study, the effect of Coriaria
Lactone (CL) on calcium homeostasis in the pyramidal neurons of the rat hippocampus
was investigated. Since the opening of L-calcium channels plays an important
role in epileptogenesis, it is thought that CL may play a role in activating
calcium channels as one of the mechanisms of seizure triggering [24].
In 2002, anti-convulsant activity of Sesbania grandi leaves ora leaves in
experimental animals was investigated. According to the results, it protected
against pentylenetetrazole (PTZ) induced seizures. The benzene-ethyl acetate
fraction also showed anti-convulsive activity against PTZ-induced seizures
[25].
Mistletoe is a semi-parasitic plant grown in
dicotyledon trees. In a 2003 study, it was mentioned that for mistletoe
(Loranthaceae), it has been used as a traditional herb for centuries in the
treatment of epilepsy [26].
In 2003, the effect of caffeinated beverages
on seizure control was investigated. The case report showed an increased
seizure frequency due to excessive tea intake. In this context, the authors
suggest that patients with epilepsy should not take excessive caffeine [27].
Gastrodin is one of the natural compounds
isolated from Gastrodia elata and has
anti-convulsant effect. In a 2003 study, a study of the immuno-activity of
aminobutyric acid shunt enzymes in the hippocampus of seizure-sensitive gerbils
was performed and suggested that this might cause elevation of GABA
concentration [28].
Gastrodia elata (GE), a medicinal plant, has
traditionally been used in the treatment of convulsive diseases such as
epilepsy in South Korea and has an essential place in traditional medicine. In
2003, the effect of GE on epilepsy was investigated and the low dose of GE did
not alleviate the hippocampal neuronal damage in the CA1 region, but the high
dose reduced the hippocampal neuronal damage in the same region [29].
In 2003, plants used in traditional medicine
in South Africa were screened for genotoxic effects. In the results, the use of
Gardenia volkensi and Catunaregam spinosa extracts in the
Rubiaceae plant family were discussed in the treatment of epilepsy [30].
In a 2004 study, the acute effect of Ambrosia paniculata was investigated in
epilepsy animal models. Findings show that A.
paniculata acts by enhancing GABAergic neurotransmission, such as a few
conventional anti-epileptic drugs [31].
In 2004, pilocarpine epilepsy model was
induced in rats for herbal treatment after seizures. According to the data, no
seizures developed in rats that received a solution of three herbal liquid
extracts of Scutellaria lat
(Skullcap), Gelsemium sempervirens
(Gelsemium) and Datura stramonium
(Jimson Weed). As a result, it is strongly suggested that the proper
combination of herbal compounds may be helpful as additional interventions,
although there is no evidence that herbal remedies can control limbic or
temporal lobe epilepsy [32].
In a 2005 study, the effect of
intracerebroventricular administration of thymoquinone, the main founder of the
Nigella sativa seeds, on the epileptic seizures in rats was investigated. The
results have shown that thymoquinone may have anti-convulsant activity,
possibly mediated by an opioid receptor in the GABAergic tone [33].
In a 2005 review, plants used by the
traditional researchers of Tanzania to treat epilepsy were investigated. It has
demonstrated competence in the treatment of the disease and 60 commonly used
plants are mentioned. Abrus precatorius
L. (Leguminosae), Clausena anisata
(Willd.) Oliv. (Rutaceae) and Hoslundia
opposita Vahl (Lamiaceae) are among the mentioned plants and these plants
have proven anti-convulsant activity. Several other species in the list have
also been reported to be useful in the treatment of epilepsy [34].
In a study on the seed of Heracleum persicum in 2005,
anti-convulsant activity was investigated in mice by PTZ and
electroshock-induced seizures. According to the results of the experiment, a
dose-dependent protective effect was shown for both seizure models [35].
In 2005, anti-convulsant properties of Tetrapleura tetraptera (fabaceae) fruit
aqueous extract in mice were investigated. The findings provide pharmacological
support for the use of the plant in painful, arthritic inflammatory conditions
or in epilepsy and childhood convulsions in several tropical African countries
[36].
In the study titled “Traditional Chinese
Medicine Treatment of Epilepsy” published in 2006, three adult patients with
epilepsy showing resistance to standard anti-epileptic drugs were studied. The
frequency of seizures was reduced after all three were added to the traditional
treatment (Bu-yanghuan-wu-tang treatment) [37].
In 2006, the reviewing of plants used in
Danish folk medicine to treat epilepsy and convulsions was performed. The
aqueous and ethanolic extracts of 42 plants were tested for affinity to the
GABAA-benzodiazepine receptor [38].
In 2006, the use of medicinal plants in South
Africa was investigated. In the study, Crassulaceae Cotyledon orbiculata L. (kouterie, plakkie), Euphorbiaceae Ricinus communis L. (olieblare,
castorolie boom), Leonotis leonurus
(L.) R. Br. (klipdagga, wilde dagga) and Ruta
graveolens L. (wynruit, rue) plants for the treatment of epilepsy
traditional use is mentioned [39].
According to a study conducted in 2006, the
anticonvulsant effect of Annona
diversifolia saff. and palmitone on penicillin-induced convulsive activity
was investigated. The results showed that A.
diversifolia and palmitone plants were effective in reducing the severity
of penicillin-induced seizures in rats [40].
The various morphological sections of Persea americana Mill (Lauraceae), i.e.,
avocadone, are widely used for the treatment, management and/or control of a
variety of human diseases, including childhood convulsions and epilepsy, in
African traditional drugs. In a 2006 study, anti-convulsant effect of avocado
leaf aqueous extract was investigated in mice. Accordingly, it appears to produce
anti-convulsant effect by increasing GABAergic neurotransmission and/or action
in the brain [41].
·
2007-To
date
Passion flower (Passiflora incarnata) is used in the treatment of epilepsy in the
traditional medicine of Europe and South America. In 2007, the anti-convulsant
effects of Passiflora incarnata
extract were investigated in mice. The results were obtained that may be
beneficial for the treatment of seizures and the effects on GABAergic and
opioid systems [42].
In a 2007 study, the anti-convulsant activity
of Hypoxis hemerocallidea and
hypoxidacea aqueous extracts was investigated in mice. It has been shown that
the aqueous extract of “African potato” has an anti-convulsive effect by
increasing GABAergic neurotransmission and/or movement in the brain. The
results provide a pharmacological assurance for the use of the plant [43].
In traditional medicine, Nigella sativa L. (black seed) has long been widely used as a
natural medicine because of its anti-convulsant effects. In a study published
in 2007, the effect of black seed on refractory pediatric seizures was
investigated. The mean frequency of seizures in the children participating in
the study decreased significantly during the extractive treatment. As a result,
it was concluded that the extract of Nigella
sativa L. has anti-epileptic effects in children with refractory seizures
[44].
In 2007, a study on the binding activity of
anti-plasmodial and GABAA benzodiazepine receptor of a plant used in
traditional medicine in Mali from West African countries was called the use of
traditional treatment in epilepsy for medicinal plant “Trichilia emetica Vahl” [45].
In 2008, the effects of Ginkgo biloba (EGb 761) on the epileptic activity developed in
rabbits were studied. The results show that the epileptogenesis process is
affected by EGb 761 [46].
In a 2008 study, Vitex agnus castus extract was investigated for anti-epileptic
activity in male rats over the kindling seizures in the amygdala. According to
the results of the study, the appropriate dose of Vitex may help to prevent,
prevent or reduce the epileptic activity [47].
The antioxidant activity of Pimpinella anisum L. (Anise) has been
proven to have many biological effects. Probably, the candidate cellular
mechanisms underlying hyperactivity produced by anise oil include increasing Ca2+
channel activity. This finding indicates that a certain attention is required
as anise is used in the treatment of patients suffering from epilepsy [48].
In a study conducted in 2008, the
anti-convulsant effect of Rhus
chirindensis (Baker F.) (Anacardiaceae) root crust aqueous extract was
investigated in mice. It has shown that childhood convulsions and epilepsy may
be used as a natural supplement in the management, control and/or treatment
[49].
In 2009, the effects of Q'eqchi yeast
antiepileptic plants on ethnopharmacology and GABAergic system were
investigated. Q'eqchi yeast has a wide range of plants used to treat
neurological disorders such as epilepsy. Within the results, information about
the anti-epileptic activity of Q'eqchi is pharmacologically related [50].
In 2009, the anti-convulsant effect of
flavonoid, linalool and α-tocopherol structures on the leaf extract of Cissus sicyoides L. was investigated.
The results show that it has an anti-convulsant-like effect in mice, probably
due to the effect of structures found in Vitaceae leaves [51]. In a 2009 study,
the therapeutic role of cerebellar 5-HT2C receptors and Bacopa monnieri extract in pilocarpine-induced epilepsy was investigated
in rats. In the results, B. monnieri
has been shown to have a neuroprotective effect by regulating the 5-HT2C
receptor in epileptic rats. This is of clinical importance for the treatment of
epilepsy [52]. In a 2009 study, anti-convulsant properties of the extracts of Randia nilotica stapf were evaluated in
mice. The results show the potential anti-convulsant activity of the root bark
extract of Randia nilotica Stapf
[53].
In a 2009 study, anti-convulsant activity of Myristica fragrans (small coconut oil)
was investigated. It was shown that coconut oil prevented the spread of
seizures in animal models. In this regard, it has been shown to be effective
against large and partial seizures [54].
Excoecaria agallocha L (Euphorbiaceae) is an essential
mangrove species, mostly distributed in China, India, Philippines and Oceania.
In a study conducted in 2009, Euphorbiaceae obtained from the bark of mangrove
plants were studied. According to the information in this study, euphorbiaceae
is traditionally used in the treatment of epilepsy [55].
In a 2009
study, Searsia species were reported to be used in the treatment of epilepsy in
South Africa. Searsia chirindensis (Baker
F.) Moffett, Searsia dentata (Thunb)
F.A Barkley, Searsia natalensis
(Bernh Ex Krauss) F.A. Barkley and Searsia
pyroides (A. Rich) T.S. Yi, A.J. Mill and J. Wen (bazionym, Rhus pyroides)
are given as examples. As a result, the ethanolic extract of S. dentata showed anticonvulsive
properties in various epilepsy models [56].
In 2013, Musa sp., Sapindus mukorossi Gaertn. and Trema
orientalis (L.) Blume plants have been used in the treatment of epilepsy
[57].
In a 2011
study, A. nilagarica (Cl.) Pamp., Cannabis sativa L., Iris kemaonensis D.
Don ex Royle and Thymus linearis
Benth. Plants are reported to be involved in the treatment of epilepsy [58].
In a study
conducted in 2004, Passiflora incarnata
is considered anti-spasmodic, sedative and narcotic and it is reported to be
beneficial in epilepsy [59].
In a study
conducted in 2012, it draws attention to the use of Passiflora incarnata L. in the treatment of epilepsy. It is used
for epilepsy in Turkey and among 500 species of the genus Passiflora, P. incarnata is the only species with a
broad clinical practice worldwide [60].
In 2012, Viscum album L. is claimed to be useful
in the treatment of epilepsy. The results of the study showed that Viscum album L. exhibited anti-epilectic
activity in mice and rats [61].
In a 2012
study, turmeric obtained from Curcuma
longa rhizomes is known to be used as a traditional medicine in the
treatment of epilepsy in South Asia. To date, in vivo studies on anticonvulsant activity of turmericity have
focused on curcuminoid curcumin [62].
In 2013, in
some cases of epilepsy, the ineffectiveness of drugs and the serious side
effects of antiepileptic drugs and chronic toxicity have led to the use of
herbal treatment. The black fruit of Terminalia
chebula, Halile siah, known as
Agher Gherha, is used in the herbal treatment of epilepsy of Anacyclus
pyrethrum, Anisun, Origanum majorana,
Ferula assafoetida (Anghose), Ruta graveolens (Sodab) and Lavandula stoechas (Ostokhoddos) [57].
Experimental
and clinical studies have shown that changes in brain serotonin may play an
essential role in the pathophysiological changes of epilepsy. Accordingly,
change of Piperin in serotonin levels indicate that it is related to the
treatment of epilepsy [63].
In a study
conducted in 2015, Aloe vera
(Liliaceae) has been reported to be used for the treatment of epilepsy due to
its antioxidant properties [64].
In this study
conducted in 2015, the root stem of Acorus
tatrinowii was investigated and plant-derived agents against epilepsy were
discovered. The anticonvulsant and sedative effects of eudesmin isolated from A. tatarinowii were investigated and
significant results were obtained [65].
In 2011, it
was concluded that the use of Passiflora
incarnata L. species in the treatment of epilepsy was determined [66].
In a 2017
study, it was described that the anti-microbial plant Moringa olifera is widely used for the treatment of epilepsy. The
leaves, shell and seed of it have some anti-inflammatory and therapeutic
properties. M. olifera's success in
using extracts to control pathogens has been reported [67].
In 2017, the
leaves of the Laurus nobilis plant
were reported to be used for the treatment of epilepsy [68].
In a 2017
study, the role of Caryocar coriaceum
Wittm in the treatment of epilepsy was investigated by evaluating the
anticonvulsant effects [69].
It is known
that Moriferin in mango shell and Morinin in Maclura pomace are natural antioxidants. In a study conducted in
2017, they might be used as herbal treatment in pathological conditions such as
epilepsy with the characteristics of these plants [70].
In a study conducted in 2018, a detailed
analysis of herbal medicine used for neurological conditions related to
epilepsy in Asia, Africa and Latin America was conducted. As a result, Acorus calamus L. rhizomes and leaves of
Bacopa monnieri (L.) Wettst, Leonotis leonurus (L.) R. leaves, Uncaria rhynchophylla (Miq.) Miq. ex
Havil., Calotropis gigantea (L.)
Dryand., Ricinus communis L., Asparagus racemosus Willd. and Rauvolfia serpentina (L.) Benth. It has
been reported that ex Kurz may be used for treatment in epilepsy [71].
CONCLUSION
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