by Taylor Brusca
Wilkes University,
Wilke-Barre,
PA
July 2017
Piper
methysticum G. Forst., also known as Kava, belongs
to the Piperaceae (the pepper family). P. methysticum
is a perennial shrub that produces heart shaped leaves and
can grow to about two meters tall. The species is native
to the South Pacific Islands, where it thrives in areas of
loose soil (Jhoo, 2006). Kava is cultivated for its thick
rhizome that can be harvested as an antianxiety remedy
when added to water (Shimoda, 2012, Savage, 2014).
In the South Pacific Islands, P. methysticum
serves as a recreational beverage, where the ground roots
and stems of the plant are extracted and used to create
the relaxing beverage (Shimoda, 2012). The species has
also been accepted in the West as an anxiolytic and an
insomnia remedy (Rowe, 2011).
The Kava plant produces a class of lactones called
kavalactones. About eighteen kavalactones are present in
the rhizome of P. methysticum. Six major kavalactones are
present including methysticum, dihydromethysticin, kavain,
dihydrokavain, yangonin, and desmethoxyyangonin. These six
major kavalactones are detected in the beverages prepared
from the rhizome of Kava in addition to five solvents
(hexane, acetone, methanol, ethanol, and ethyl acetate).
The beverage with ethanol as the solvent gives the highest
extraction efficiency for the six major kavalactones
(Wang, 2015).
Numerous studies have examined the health effects of P.
methysticum. A study was performed in order to test
the antianxiety properties of kava. A blind trial of a
kava extract versus a placebo group was performed and
anxiety was measured using the Hamilton Anxiety Rating
Scale. The results revealed a significant reduction in
anxiety for the kava extract group versus the placebo
group (Sarris, 2013).
Several studies examined the ability of kava to be an
anticancer remedy. Einbond (2016) used ground kava
that was prepared traditionally from the lateral roots and
then performed an MTT
(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide) assay to determine the growth inhibitory activity
of the preparations on colon and breast cancer cells and
nonmalignant intestinal epithelial cells. The results from
this experiment showed that traditional preparations of
kava inhibit the growth of breast and colon cancer cells.
Additionally, a study was performed to determine the
effects of Kava on prostate cancer (Li 2012). In this
study, prostate myofibroblast cells were treated with
commercial Kava extracts, kavalactones, and flavokawain B.
The results of this experiment showed that the Kava
extracts and flavokawain B were able to effectively
down-regulate the expression of androgen receptors which
in turn is able to downgrade prostate cancer (Li,
2012). Another study completed by Zhongbo (2017)
supports that a particular kavalactone, yangonin,
participates in an anti-bladder cancer mechanism.
An additional study was performed to determine that the
pharmacological effects of kava ingestion appear to be due
to the compounds present in the lipid soluble fraction.
Central nervous activity was measured for mice exposed to
the aqueous and the lipid extract of kava. The aqueous
exposed mice showed a loss of spontaneous activity as did
the lipid exposed mice, however the lipid mice also showed
a reduction in motor control (Jamieson, 1989). Studies
have been completed via behavior assays to determine the
effects of kavalactones at neuromuscular junctions. The
results of this study have shown that kavalactones disrupt
the inhibitory-excitatory balance at the neuromuscular
junction (Kautu, 2017). Fragoulis (2017) tested an in vivo
kavalactone treatment in a mouse model of Alzheimer’s
Disease. The results of this experiment showed that
administration of the kavalactones leads to a decrease in
neuroinflammation, damage and memory loss. Finally, a
study was completed to determine whether Kava extracts can
be used to protect against the ischemic brain damage. In
this experiment, a model of focal cerebral ischemia in
mice and rats. As a result, the Kava extract appeared to
diminish the infarct area in mouse brains and the infarct
volume in rat brains (Backhauss & Krieglstein, 1992).
Within the past few years, kava has been associated with
liver toxicity. Following Kava use, inflammation appears
to be present and results from the activation of liver
macrophages either directly or through kava metabolites
(Rowe, 2011). Behl (2011) tested Kava in relation to
liver toxicity in rats and mice. The rats and mice were
administered kava extracts and the results obtained showed
an increase in liver weights as well as incidences of
hepatocellular hypertrophy. Another test was conducted
following the consumption of kava in relation to driving
behavior. The results of this study showed that the use of
kava is associated with a significant excess of serious
injury-involved road crashes (Wainiqolo, 2016). It is
unknown if the harmful effects of Kava are due to the
total kavalactone content or by one or more of the primary
kavalactone constituents (Feltenstein, 2003).
Overall, P. methysticum is used in the South
Pacific Islands as a recreational beverage and Western
societies have adopted Kava as an anxiolytic. Through
several studies, Kava have shown to have other beneficial
medicinal value such as deterring against prostate cancer
and protecting against ischemic brain damage.
Additionally, recent studies have shown Kava to be
involved in liver toxicity, however the direct cause of
this relationship is still unknown. Even though P.
methysticum can be used in many helpful remedies,
this plant is also associated with detrimental health
effects that could continue to adversely impact the
overall use and popularity of P. methysticum.
LITERATURE
CITED:
Backhauss, C., & J.
Krieglstein. 1992. Extract of Kava (Piper methysticum)
and its methysticin constituents protect brain tissue
against ischemic damage in rodents. European Journal
of Pharmacology 15: 265-269.
Behl, M., A. Nyska, R. Chhabra, G. Travlos, L. Fomby, B.
Sparrow, M. Hejtmancik, & P. Chan. 2011. Liver
toxicity and carcinogenicity in F344/N Rats and B6C3F1
mice exposed to Kava Kava. Food and Chemical
Toxicology 49: 2820-2829.
Einbond, LS., A. Negrin, DM. Kulakowski, HA. Wu, V.
Antonetti, F. Jalees, W. Law, M. Roller, S., Redenti, EJ.
Kennelly, & MJ. Balick. 2016. Traditional preparations
of kava (Piper methysticum) inhibit the growth of
human colon cancer cells in vitro. Phytomedicine 24:
1-13.
Feltenstein, M., L. Lambdin, M. Ganzera, H. Ranjith, W.
Dharmaratne, N. Nanayakkara, I. Khan, & K. Sufka.
2003. Anxiolytic properties of Piper methysticum
extract samples and fractions in the chick
social-separation-stress procedure. Psychopharmacology
(Berl). 155(1):86-90.
Fragoulis, A., S. Siegl, M. Fendt, S. Jansen, U. Soppa,
LO. Brandenburg, T. Pufe, J. Weis, & CJ. Wruck. 2017.
Oral administration of methysticin improves cognitive
deficits in a mouse model of Alzheimer’s disease. Redox
Biology 12: 843-853.
Jamieson, DD., PH. Duffield, D. Cheng, AM. Duffield. 1989.
Comparison of the central nervous system activity of the
aqueous and lipid extract of kava (Piper methysticum).
301: 66-80.
Jhoo, J., J. Freeman, T. Heinze, J. Moody, L.
Schnackenberg, R. Beger, K. Dragull, C. Tang, & C.
Ang. 2006. In vitro cytotoxicity of nonpolar
constituents from different parts of Kava plant (Piper
methysticum). Food Chemistry 19: 3157-3162.
Kautu, BB., J. Phillips, K. Steele, MS. Mengarelli, &
EA. Nord. 2017. A behavioral survey of the effects of
kavalactones on Caenorhabditis elegans
neuromuscular transmission. J Exp Neurosci.
11:1179069517705384.
Li, X., Z. Liu, X. Xu, C. Blair, Z. Sun, J. Xie, M. Lilly,
& X. Zi. 2012. Kava components down-regulate
expression of AR and AR splice variants and reduce growth
in patient-derived prostate cancer xenografts in mice. PLoS
One. 7(2):e3121.
Rowe, A., L. Zhang, & I. Ramzan, 2011. Toxicokinetics
of Kava. Advanced Pharmacological Sciences 2011:326724.
Sarris, J., C. Stough, CA. Bousman, ZT. Wahid, G. Murray,
R. Teschke, KM. Savage, A. Dowell, C. Ng, & I.
Schweitzer. 2013. Kava in the treatment of generalized
anxiety disorder: a double-blind, randomized,
placebo-controlled study. J Clin Psychopharmacol.
33: 643-648.
Savage, K., C. Stough, G. Byrne, A. Scholey, C. Bousman,
J. Murphy, P. Macdonald, C. Suo, M. Hughes, S. Thomas, R.
Teschke, C. Xing, & J. Sarris. 2014. Kava for the
treatment of generalized anxiety disorder (K-GAD): study
protocol for randomized controlled trial. Trials
16: 493.
Shimoda, L., C. Park, A. Stokes, H. Gomes, & H.
Turner. 2012. Pacific Island ‘Awa (Kava) extracts, but not
isolated kavalactones, promote proinflammatory responses
in model mast cells. Phytother Res.
26(12):1934-41.
Wainiqolo, I., B. Kafoa, B. Kool, E. Robinson, J. Herman,
E. McCaig, & S. Ameratunga. 2016. Driving following
Kava use and road traffic injuries: A population- based
case – control study in Fiji (TRIP 14). PLoS One.
11(3):e0149719.
Wang, J., W. Qu, H. Bittenbender, & Q. Li. 2015.
Kavalactone content and chemotype of kava beverages
prepared from roots and rhizomes of Isa and Mahakea
varieties and extraction efficiency of kavalactones using
different solvents. Journal of Food Science and
Technology 52: 1164-1169.
Zhongbo, L., H. U-Syn, Y. Ke, W. Chunli, Y. Noriko, &
Z. Xialon. 2017. Kavalactone yangonin induces autophagy
and sensitizes bladder cancer cells to flavokawain A and
docetaxel via inhibition of the mTOR pathway. J Biomed
Res. doi: 10.7555/JBR.31.20160160.