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Kava Kava
Kava Kava
Keywords: Abstract
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Neuroprotective profile of Piper Methysticum (Kava Kava) and its effects on the Central Nervous System: a
systematic review
56
Neuroprotective profile of Piper Methysticum (Kava Kava) and its effects on the Central Nervous System:
a systematic review
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Neuroprotective profile of Piper Methysticum (Kava Kava) and its effects on the Central Nervous System: a
systematic review
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Neuroprotective profile of Piper Methysticum (Kava Kava) and its effects on the Central Nervous System:
a systematic review
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Neuroprotective profile of Piper Methysticum (Kava Kava) and its effects on the Central Nervous System: a
systematic review
Figure 1: Flowchart showing the selection process of the articles used in this review.
The number of articles shown in this flowchart refers to studies that investigated the
neuroprotective effect of Piper Methysticum on the central nervous system found in
PubMed, Science direct, Web of Science, Capes Journals, Scopos, Medline (Pros-
quest) and Cochrane.
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Neuroprotective profile of Piper Methysticum (Kava Kava) and its effects on the Central Nervous System:
a systematic review
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Neuroprotective profile of Piper Methysticum (Kava Kava) and its effects on the Central Nervous System: a
systematic review
/ dose regimen, tests performed and main fluid; DMSO, dimethyl sulfoxide; SLE´s,
findings. ARE, element responsive to an- series of events similar to seizures; 5-HT,
tioxidants; APP, amyloid precursor pro- 5-Hydroxytryptamine; COPD, dihydro-
tein; PSEN1, presenilin-1; Nrf2, Nuclear xyphenylacetic acid; HVA, 4-hydroxy-
Factor derived from Erythroid 2; μM, mi- -3-methoxy-phenylacetic acid; 5-HIAA,
crometer; μG, microgram; iNOS, induci- 5-hydroxyindolacetic acid; HPCL-ECD,
ble nitric oxide synthase enzyme; NO, electrochemical detection coupled to
nitric oxide; LPS, Lipopolysaccharide; HPLC; mV, millivolts; Hz, hertz.
HO-1, Heme oxygenase-1; NAC, N-ace-
tylcysteine; HPLC, high performance li-
quid chromatography; GABA-A, type A
gamma-aminobutyric acid receptor; V.O,
orally; SD, standard deviation; MCA,
middle cerebral artery; via I.P.,
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Neuroprotective profile of Piper Methysticum (Kava Kava) and its effects on the Central Nervous System:
a systematic review
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Neuroprotective profile of Piper Methysticum (Kava Kava) and its effects on the Central Nervous System: a
systematic review
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Neuroprotective profile of Piper Methysticum (Kava Kava) and its effects on the Central Nervous System:
a systematic review
65
Neuroprotective profile of Piper Methysticum (Kava Kava) and its effects on the Central Nervous System: a
systematic review
66
Neuroprotective profile of Piper Methysticum (Kava Kava) and its effects on the Central Nervous System:
a systematic review
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Neuroprotective profile of Piper Methysticum (Kava Kava) and its effects on the Central Nervous System: a
systematic review
xidant defense systems and reac- dants, since they inhibit or delay
tive oxygen species (ROS), occur- oxidative degradation (WUL et al.,
ring when excess oxygen radicals 2002), researched six biologically
are produced in cells, generating active compounds from the roots
the accumulation of these ROS of Piper methysticum (kava kava),
and, consequently, overloading to evaluate the inhibitory potential
the normal antioxidant capacity of cyclooxygenase and antioxi-
(GAGNÉ, 2006; EMERIT; EDE- dant effects. The results indicated
AS; BICAIRE, 2004). Most ROS that Dihydrokawain and yangonin
are produced by living organis- showed higher concentrations of
ms as a result of the usual cellu- COX-I and inhibitory activities
lar metabolism, generated during of COX-II. In addition, yangonin
respiration in the mitochondria. In and methysticim showed modera-
low to moderate concentrations, te antioxidant activity in the free
they play physiological roles, radical scavenging test.
however, in high concentrations, On the other hand, the
they produce adverse changes in work conducted by Tananka et al.
cellular components (STADT- (2010) shows that chemically mo-
MAN, 2004). Hydrogen Peroxide dified kavalactones also have the
(H2O2) is one of the main ROS potential to increase cellular an-
and an inducer of cellular oxida- tioxidant capacity and improve di-
tive stress (HALLIWELL, 2012; seases related to oxidative stress.
DASURI; ZHANG; KELLER, Among the 81 compounds tested,
2013). a kavalactone derivative, named
Given the pathogenic impact compound, exhibited stronger
of oxidative stress and neuroin- ARE enhancing activity and the
flammation, therapeutic strategies induction of the HO-1 protein was
in order to mitigate these proces- superior to that of natural kavalac-
ses are considered an effective tones.
way of providing neuroprotection One of the mechanisms that
(VAN MUISWINKEL; KUIPE- elucidate this finding is the action
RIJ, 2005). Many plants are con- of compound¹ in potentiating the
sidered a rich source of antioxi- cellular defense system, activa-
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Neuroprotective profile of Piper Methysticum (Kava Kava) and its effects on the Central Nervous System:
a systematic review
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Neuroprotective profile of Piper Methysticum (Kava Kava) and its effects on the Central Nervous System: a
systematic review
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Neuroprotective profile of Piper Methysticum (Kava Kava) and its effects on the Central Nervous System:
a systematic review
mol daily for 8 weeks. The results that support the anxiolytic effects
showed that in 127 patients, no of Kava extract and kavapyrones
significant differences were ob- are not so clear yet and need more
served in relation to medications information to be elucidated (SA-
and, therefore, Kava-Kava LI150 VAGE et al., 2015; CAIRNEY;
is well tolerated and as effective as MARUFF; CLOUGH, 2002 ;
Buspirone and Opipramol. DINH et al., 2001; SAVAGE et
The therapeutic properties al., 2018).
of kava are supported by the six Baum, Hill and Rommels-
main kavalactones (dihydrome- pacher (1998) developed a study
thysticin, kavain, dihydrokavain, with the purpose of knowing the
methysticin, yangonin and deme- effects of kava extract and indivi-
thoxiangonin), of which kawain dual kavapironas on the mesolim-
and dihydrokawain have more in- bic reward system, specifically, on
tense anxiolytic activity (WUL et the levels of neurotransmitters in
al., 2002). Current evidence indi- the nucleus accumbens, through
cates that kavalactones play their in vivo microdialysis. After intra-
role. peritoneal (ip) administration of
The from specific actions kava extract and kavapyronas in
postulated on the gamma-amino- male rats, the levels of dopamine,
butyric acid (GABA) pathway, 5-hydroxytryptamine (5-HT) and
including blocking voltage-ga- some of its metabolites changed,
ted sodium ion channels, greater causing feelings of relaxation,
ligand binding to type A GABA drowsiness and euphoria (depen-
receptors, decreased release of ding on the dosage ). The authors
excitatory neurotransmitters due proved that a small dose of kava
to calcium channel, reduced neu- extract (20 mg / kg ip) caused
ronal reuptake of norepinephrine changes in the behavior of the rat
(norepinephrine), reversible inhi- (relaxation), activated dopaminer-
bition of monoamine oxidase B gic neurons and the mesolimbic
and cyclooxygenase. However, dopaminergic reward system, the
the pathophysiology of anxiety effects remaining for several hou-
and the neurobiological actions rs due to the lipophilic properties
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Neuroprotective profile of Piper Methysticum (Kava Kava) and its effects on the Central Nervous System: a
systematic review
of the active compound of the ex- tive behavioral tests in mice and
tract (OOI et al., 2018). compared behavioral changes
In this study, it can also be induced by kava and diazepam.
shown that the minor components The research findings demonstra-
of kava extract cause pharmaco- te that the increase in kava dose
logical effects. Kavalactones D, caused a reduction in locomotor
O L-kawain induced a decrease activity, revealing that kava has
in dopamine levels (low doses) dose-dependent anxiolytic proper-
and an increase or no change in ties in both behavioral tests, ano-
dopamine concentrations (larger ther factor to be considered in the
doses). Yangonin caused a de- study is that flumazenil blocked
crease in dopamine levels, redu- the anxiolytic effects. and diaze-
cing the activity of dopaminergic pam sedatives, but had no effect
neurons. Desmethoxyyangonin on kava’s behavioral actions. In
an increased levels of dopamine. addition, it has been shown that
Dihydrokawain, methysticin and Kava extracts produce significant
dihydromethysticin did not show behavioral changes similar to an-
significant effects. Other findings xiolytics and significant sedation
of the present study were changes that are not mediated through the
in the concentrations of 5HT af- benzodiazepine binding site in the
ter administration of kava extract GABAA receptor complex. The
or individual kavapyronas. About mechanisms proposed for the afo-
half of the rats had increased le- rementioned study, referring to the
vels of 5-HT after the action of anxiolytic and sedative action of
kava extract and, this effect, can these constituents, are represented
explain the sleep-inducing action in Figure 2.
(BAUM; HILL; ROMMELSPA-
CHER, 1998).
In their analysis Garrett et
al. (2003) systematically evalua-
ted the anxiolytic and sedative
effects dependent on the acute
dose of kava extract in quantita-
Figure 2: Proposed mechanisms of Kava
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Neuroprotective profile of Piper Methysticum (Kava Kava) and its effects on the Central Nervous System:
a systematic review
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Neuroprotective profile of Piper Methysticum (Kava Kava) and its effects on the Central Nervous System: a
systematic review
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Neuroprotective profile of Piper Methysticum (Kava Kava) and its effects on the Central Nervous System:
a systematic review
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Neuroprotective profile of Piper Methysticum (Kava Kava) and its effects on the Central Nervous System: a
systematic review
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Neuroprotective profile of Piper Methysticum (Kava Kava) and its effects on the Central Nervous System:
a systematic review
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Neuroprotective profile of Piper Methysticum (Kava Kava) and its effects on the Central Nervous System: a
systematic review
Nil.
Conflicts of interest
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Neuroprotective profile of Piper Methysticum (Kava Kava) and its effects on the Central Nervous System:
a systematic review
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