The Health and Medicinal Benefits of Ashitaba

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The Health and Medicinal Benefits of
Ashitaba

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without the prior written permission of the author.

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Table of Contents
Botantical History
Similar Plants Speices
Cultural History
Chemcial Constituients of Ashitaba
Chalcones
Medicinal Benefits of Ashitaba
Clinical Trials
Product Resources
Endnotes/References

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Botanical History
Ashitaba, which is the common name used in Japan, is botanically
known as Angelica keiskei or Angelica Keiskei Koidzumi. The
English translation of the Japanese word “Ashitaba” (アシタバ or
明日葉) is “Tomorrow's Leaf". Ashita means ‘tomorrow and ba
means ‘leaf.’ The name stems from the plant’s ability to quickly
regenerate new leaves after taking cuttings. This give an indication
of its potential for longevity of life.
Figure 1.1 Angelica keiskei (Ashitaba)
Ashitaba is from the botanical species of Angelica, which derives
from the Latin for angel. The word keiskei is named for Ito
Keisuke, the 19th century Japanese botanist called the father of
modern Japanese botany.
Angelica keiskei is the only Angelica plant that exudes yellow sap
from the stem.

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Figure 1.2 Location of the Izu Islands of Japan
Ashitaba is indigenous to a small area called the Seven Islands of
Izu. Although traditionally referred to as the "Izu Seven" (伊豆七島
), there are in fact more than a dozen islands and islets. It is
endemic to Hachijō-jima island, which lies off the southern coast of
Japan. Ashitaba is also cultivated in the islands of Izu Ōshima,
Mikura-jima, Nii-jima, To-shima and parts of Honshū. It is also
commercially cultivated and harvested in Indonesia.

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Similar Plants Species
Archangelica keiskei Miq.
Archangelica keiskei Miq. is a plant that is often confused with and
is often considered synonymous with Angelica keiskei. The name
Archangelica keiskei Miq. is unresolved by botanists. [ 1 ]
Figure 2.1 Comparison of Archangelica keiskei (left) and Angelica keiskei (right)
Angelica japonica
"Hama-udo" (Angelica japonica) belongs to the family Apiaceae
(the Carrot family). It is an evergreen perennial herb. Angelica
kiusiana Maxim. is a synonym of Angelica japonica A. Although
similarly in appearance to Ashitaba, Angelica japonica is a different
species within the Angelica family.

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Figure 2.2 Angelica japonica
Sabungai (Gynura procumbens)
Gynura procumbens (Sabuñgai) is a twining vine found in the
Philippines, the Malay Archipelago, Thailand, and Indo-China.
Sabuñgai (Gynura procumbens) is also known as “Longevity
Spinach”.
There is evidence that some Ashitaba powder being sold is actually
Sabuñgai (Gynura procumbens) rather than Ashitaba (Angelica
keiskei).
Comparison of the two plants can be seen in Figures 2.3 and 2.4.

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Figure 2.3 Sabungai (Gynura procumbens) (Notice the similarity to Ashitaba)
Figure 2.4 Angelica Kekeii (Ashitaba) (Looks similar to Sabungai (Gynura procumbens))

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Cultural History
Li Shizhen (Li Shih-chen; simplified Chinese: 李时珍; traditional
Chinese: 李時珍) was a medical doctor, scientist, pharmacologist,
herbalist and acupuncturist of the Ming dynasty. He lived from July
3, 1518 – 1593). His major contribution to clinical medicine was
his 27-year work, which is found in his scientific book Compendium
of Materia Medica (Bencao Gangmu).
The Compendium of Materia Medica is regarded as the most
complete and comprehensive medical and scientific book ever
written in the history of traditional Chinese medicine. It lists all the
plants, animals, minerals, and other items that were believed to
have medicinal properties. It is the first written record of
Ashitaba.
The Compendium of Materia Medica was introduced into Japan
and presented to the Shogun by Razan Hayashi in 1606. Hayashi
Razan, also known as Hayashi Dōshun, was a Japanese
Neo-Confucian philosopher, serving as a tutor and an advisor to the
first four shoguns of the Tokugawa bakufu.
According to Japanese folklore and medicine, the yellow sap from
stems and stalks once used for external treatment of smallpox,
whereas the roots were used as diuretic, laxative, analeptic, and
galactagogue. Other uses for medical purposes would include a
remedy for bowel disturbances, arthritis, and immune diseases.

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According to Chinese folklore and medicine, Ashitaba was believed
to activate Qi and Xue. In China it was used in the treatment of
menstrual problems, and was also believed to increase kidney yin
and yang qi. The Chinese also used it as a lactagogue to increase
mother's milk.
The Japanese Neo-Confucianist philosopher and botanist, Kaibara
Ekken wrote in 1709 the book entitled Yamato honzō (Medicinal
herbs of Japan) which was a seminal study of Japanese plants. In
this book he descried Ashitaba using the name of ashitagusa (鹹草
), as "a powerful tonic drug."
Ashitaba has been consumed as a vegetable and medicine for
many hundreds of years by inhabitants of Seven Islands of Izu . In
Japanese traditions, Ashitaba was used as a culinary staple, as it is
today. It was and is consumed as a vegetable, the leaves, roots
and stems eaten raw or cooked. Sometimes the roots are pickled.
There are many uses of Ashitaba in recipes, including in the
preparation of soba, tempura, socho, tea, and ice cream.

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Chemical Constituents
There have been numerous studies conducted to determine the
chemical compounds of Ashitaba. The results of the studies and
findings are illustrated in Table 4.1.
Table 4.1 Active Chemical Compounds of Angelica keiskei
Koidzumi (Ashitaba)
Ashitaba
Compound Sub-Compound Notes/Reference(s)
Chalcones
Ashitaba-chalcone [2]
Xanthoangelol [3]
Xanthoangelol-B
2′,4,4′-trihydroxy-3′
-[(E)-6-hydroxy-3,7-dimethyl-2,7-o
ctadienyl]chalcone [4
]
Xanthoangelol-C
2′,4,4′-trihydroxy-3′
-[(E)-3-methy]-6-oxo-2-hexenyl]ch
alcone [5
]
Xanthoangelol-D
2′,4-dihydroxy-4′-methoxy-3′
-(2-hydroxy-3-methyl-3-butenyl)ch
alcone [6
]
Xanthoangelol-E
2′,4-dihydroxy-4′-methoxy-3′
-(2-hydroperoxy-3-methyl-3-buten
yl)chalcone [7
]
Xanthoangelol H [8
]
Xanthoangelol I [9]

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Xanthoangelol F
Xanthoangelol J [10]
Isobavachalcone [11
]
Deoxydihydroxantho
angelol H
[12]
4-Hydroxyderricin
Xanthohumol
Xanthokeismin A [13]
Coumarins
Psoralen Found in roots [14
]
Imperatorin
Columbianagin
Isorhazelpitin
Rhazelpiton
Selenidin
xanthotoxin Found in roots [15
]
angelicin Found in roots [16
]
archangelicin furo-coumarin
8(S),9(S)-angeloylox
yl-8,9-dihydrooroselo
l
furo-coumarin
Chroman
The benzopyrylium cation is the
parent of a large number of natural

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products. Chroman, or
3,4-dihydro-2 H-1-benzopyran, is
itself not found in nature, but the
chroman unit is present in many
natural products. Chroman
contained in Ashitaba can induce
nerve growth factor (NGF) [17]
Luteolin-7-glucosi
de
[18
]
Cynaroside
[19
] Cynaroside is a flavone, a
flavonoid-like chemical compound.
luteolin-7-O-α
-D-glucpyranosid
e
[20
]
1-cerotol [21
]
daucosterol [22
]
stigmasterol [23
]
quercetin-3-O-β
-D-glucopyransid
e
[24
]
steviol-l3-O-β
-glucopyranoside
19-β
-glucopyranosyl
ester octaacetate
[25
]
isoquercitrin

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Ruteorin
Angelic acid
Bergapten Found in roots [26
]
Beta-carotene
Vitamin C
Vitamin B12 normally produced in animals and
not plants
Vitamin B2
Vitamin A
Vitamin K
Potassium
Calcium
Iron
Chlorophyll
The Japan Science and Technology Agency published a table
comparing Ashitaba with other vegetables in Table 4.2.
Table 4.2 Comparitive nutrients of Ashitaba
Source: The Japan Science and Technology Agency (JST)

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Ashitaba, compared to other vegetables, indicate a very high level
of vital nutrients, especially vitamin K and potassium. In Table 4.3,
the protein content of Ashitaba is second only to broccoli.
Table 4.3 Nutrients in Ashitaba
Source: Food Composition Database in Sugiyama Univ. Standard Tables of Food
Composition in Japan
Table 4.4 illustrates the general composition of minerals, amino
acids and other substances of Ashitaba. These substances were
discovered and evaluated in a study written in 2012 indicating the
potent antioxidants capability of Ashitaba, and its ability to induce
an enhanced antioxidant enzymes in the body.

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Table 4.4 General Composition of Ashitaba
The general composition, minerals, and high luteolin content of Ashitaba
Source: Kim E, Choi J, Yeo I. The effects of Angelica keiskei Koidz on the expression of antioxidant
enzymes related to lipid profiles in rats fed a high fat diet. Nutrition Research and Practice.
2012;6(1):9-15. doi:10.4162/nrp.2012.6.1.9.

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Table 4.5 illustrates the comparison between raw Ashitaba leaves
and dried Ashitaba powder. Apparently, the dried Ashitaba
powder contains more nutrients than the raw Ashitaba leaves.
Table 4.5 Ashitaba Nutrition Data Comparison with Ashitaba
Powder
Source: Japan Food Research Laboratories

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Chalcones
There are two separate substances (products) that are derived
from the Ashitaba plant.
The first is the hot-air dried powder of Ashitaba from the leaves
and stems. The color of this powder is bright green. The leaves of
the Ashitaba plant contain approximately 0.25% to 0.35%
chalcones.
The second is the powder made from the unique yellow sap which
is collected from the Ashitaba's stem. It is commonly called
Ashitaba Chalcone Powder which consists up to 8% chalcones.
The color of Ashitaba Chalcone Powder is bright yellow and is a
fat-soluble substance.
Although the green Ashitaba powder from the leaves and stems
provide nutritional and health benefits, it is the Ashitaba Chalcone
Powder (bright yellow powder from the sap of the stem) that is the
Figure 5.1 Young bud emerging from stem with sap

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Chalconoids are natural phenols related to chalcone. They form the
central core for a variety of important biological compounds.
Chalcones are the active factors in Angelica Keiskei Koidzumi.
At least 20 chalcones have been identified in Angelica Keiskei.
Ashitaba contains a thick, sticky yellow sap, which is not found in
other celery plants, and are unique to this strain of angelica. This
yellowish element in Ashitaba contain the chalconoids.
Figure 5.2 Yellow sap from stem contains Chalcones
The two most active chalconoids found in Angelica Keiskei are
named "Xanthoangelol" and "4-Hydroxyderricin". They are the
two chalconoids that are the subject of most of the studies,
although others have been studied.

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Figure 5.3 Chemical structure of Xanthoangelol and 4-Hydroxyderricin
Research has shown that the unique healing properties of Ashitaba
are largely due to the chalconoids as illustrated in Table 5.1.
Table 5.1 Medical Properties of Chalcones
Medical Properties
of Chalcones
Condition Properties Reference
Antibacterial Some heterocyclic chalcone
derivatives presented good
anti-microbial activities against
Gram-positive bacteria
[ 27 ]
Antifungal Sixteen chalcones were
prepared and their antifungal
activities against four common
pathogenic fungi in vitro were
examined. Some of them
[ 28 ]

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exhibited antifungal activities to
a certain extent.
Antitumor Based on the current studies,
chalcones are highly
multifunctional and their targets
cover almost all of the actions of
tumor cells, including growth,
proliferation, invasion, and
metastasis. Moreover,
researchers have discovered
several chalcones with
significant antitumor activity
both in vitro and in vivo, such as
xanthohumol, isoliquiritigenin,
and butein.
[ 29 ]
Anti-inflammatory Chalcones showed an
anti-inflammatory protective
effect when administered orally
or by the intraperitoneal route.
[ 30 ]
Aromatase inhibitor Chalcones are potent inhibitors
of aromatase
[ 31 ]
Hypertension 4-hydroxyderricin, one of the
major chalcones exerted
hypotensive and lipid regulatory
[ 32 ]

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actions in stroke-prone
spontaneously hypertensive rats

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Medicinal Benefits of Ashitaba
The medicinal benefits of Ashitaba has only recently been
discovered by science, particulary due to the discover of the many
chalcones in Ashitaba. From this discovery, a number of medical
benefits have been discussed in the medical literature. Table 6.1
is a summary of the numerous medical benefits of Ashitaba.
Table 6.1 Medical Benefits of Ashitaba
Medical Benefits
of Ashitaba
Condition Properties Reference
Alzheimer’s Memory
Impairment
One study found that Ashitaba
might be a useful agent in
preventing deficit of learning
and memory caused by
Alzheimer’s and aging.
1 study
Anti-Bacterial
Two studies show evidence of
strong antibacterial action.
3 studies
Anti-Depressant
One study in 2013 points to
Ashitaba as a potent candidate
for development of combined
antidepressant drugs.
1 study
Anti-Diabetic Five studies show strong 5 studies

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evidence for the ability of
Ashitaba to decrease blood
glucose levels and to improve
insulin resistance conditions.
Anti-Inflammatory
The data demonstrates that
Angelica keiskei can suppress
inflammation and taken
together, may have efficacy as
anti-inflammatory agents.
5 studies
Antioxidant
Ashitaba can increase the
expression of antioxidant
enzymes and protect DNA from
oxidative stress
4 studies
Anti-thrombotic
Ashitaba is thought to have
anti-thrombotic properties
through the inhibition of
inflammatory-induced
plasminogen activator inhibitor
1 (PAI-1) production
1 study
Anti-tumor Agent
Angelica keiskei roots exhibited
cytotoxic activity against many
tumor cells
7 studies
Cancer Treatment Isobavachalcone induces 2 studies

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and Preventative apoptotic cell death in
neuroblastoma via the
mitochondrial pathway and has
no cytotoxicity against normal
cells.
HDL Cholesterol
(Increases)
Dietary Angelica keiskei
produces elevation of serum
HDL levels
1 study
Hypertension
4-hydroxyderricin, one of the
major chalcones in Angelica
keiskei extract, exerted
hypotensive regulatory actions
2 studies
LDL Cholesterol
(Decreases)
Dietary xanthoangelol results in
a reduction of serum LDL levels
1 study
Liver Protector
Angelica keiskei extract
demonstrates hepatoprotection
3 studies
Metabolic
Syndrome
Angelica keiskei suggest
potential benefit in preventing
the metabolic syndrome.
2 studies
Neurogenesis
Angelica keiskei has an
enhancing action for NGF
production
2 studies

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Quinone Reductase
Ashitaba is considered to have
contained certain substances
that could induce Quinone
Reductase activity
1 study
Skin Cancer
An external application of the
Ashitaba extract controlled ski
cancer
1 study
Visceral Fat
(Reduces)
Clinical study showing
compelling weight loss effects
of Ashitaba Chalcone Powder
2 studies
Alzheimer’s Memory Impairment
A study was conducted in 2012 which evaluated the effects of
Ashitaba on scopolamine-induced memory impairments in mice.
The findings showed that Ashitaba significantly attenuated
scopolamine-induced cognitive impairment in mice.
Taken together, these results provide experimental evidence that
Ashitaba might be a useful agent in preventing deficit of learning
and memory caused by Alzheimer’s and aging. [ 33 ]
Antibacterial
Ashitaba shows evidence of strong antiacterial action.

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A study connducted by The Pharmaceutical Society of Japan in
1999 indicated that two chalcones, xanthoangelol (I) and
4-hydroxyderricin (II), isolated from the root of Angelica keiskei
koidzumi (Umbelliferae) showed antibacterial activity against
gram-positive pathogenic bacteria. [ 34 ]
The Kangweon National University in Korea evaluated the
pharmacological activities of nine Umbelliferae plants. Angelica
keiskei was selected and its restoring activity against
antimicrobial activity were tested and compared. [ 35 ]
Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterium
that causes infections in humans. It is also called oxacillin-resistant
Staphylococcus aureus (ORSA). In a study published in 2008 in
the International Journal of Medicinal Mushrooms, the authors
discovered 2 known chalcones, xanthoangelol and
4-hydroxyderricin, in the extract of S. crispa, which have been
previously isolated from the plant Angelica keiskei. The purpose
of the study was to screen for compounds that inhibit MRSA
growth. These compounds showed anti-MRSA activity.
The result study indicates the possibility that S. crispa might be a
promising source for the production of chalcones, in addition to the
plant Angelica keiskei. [ 36 ]

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Anti-Depressant
The Journal of Applied Pharmacology published a study in May
2013 suggest that the two prenylated chalcones, xanthoangelol and
4-hydroxyderricin isolated from A. keiskei K., are expected for
potent candidates for development of combined antidepressant
drugs.
These two isolated compounds are the major active ingredients of
A. keiskei K. to inhibit MAOs activities.
A. keiskei K. will be an excellent new bio-functional food material
that has combined antidepressant effect. [ 37 ]
Anti-Diabetic
There is strong evidence for the ability of Ashitaba to decrease
blood glucose levels and to improve insulin resistance conditions.
One Chinese study from 2013 showed that Angelica keiskei
chalcones may increase the expression levels of Glut1 and Glut4 in
skeletal muscle cells, decrease fasting blood glucose and insulin of
type 2 diabetic rats and improve their insulin resistance condition. [
38 ]
A study published in 2007 in the Journal of Agricultural and Food
Chemistry found that the ethanol extract from a Japanese herb
"Ashitaba", Angelica keiskei, contained two major chalcones of
4-hydroxyderricin (4-HD) and xanthoangelol that showed strong

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insulin-like activities via a pathway independent of the peroxisome
proliferator-activated receptor-gamma activation. [ 39 ]
Ashitaba also appears to protect the endothial cells in those with
type 2 diabetes. The study that concluded these findings was
published by the Institute of Nutrition,Qingdao University Medical
College in China. Their conclusion was that Ashitaba may reduce
the levels of serum ET-1 and VE-ca and protect the endothelial
cells of rats with type 2 diabetes. [ 40 ]
A 2004 study found that ethanol extract of Angelica keiskei has
insulin mimic compounds. Their investigation revealed that there
are two insulin mimic activities of Ashitaba: (a) adipocyte
differentiation activity and (b) enhancement activity of glucose
uptake, using pre-adipocyte cell line 3T3-L1.
The two major chalcons peculiar to Angelica keiskei, xanthoangelol
(XA) and 4-hydroxyderricin (4HD) have both activities (a) and (b).
These results demonstrate that chronic ingestion of "Ashitaba"
Powder containing Chalcone (4HD) moderately reduces the blood
glucose and improved blood glucose control through increase of
adiponectin in subjects with borderline or mild hyperglycemia and
that it is also very safe. [ 41 ]
The Japan Society for Bioscience, Biotechnology, and
Agrochemistry pulished an article in 2012 investigating the effect of
A. keiskei on insulin resistance and hypertriglyceridemia in
fructose-drinking rats as a model for the metabolic syndrome. The

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results suggest that AE improved the insulin resistance and
hypertriglyceridemia of the fructose-drinking rats. [ 42 ]
Anti-Inflammatory
A new study from 2013 pulished by The Journal of Agricultural and
Food Chemistry investigated the effects and underlying molecular
mechanisms of 4-hydroxyderricin and xanthoangelol on
lipopolysaccharide (LPS)-induced inflammatory responses in
RAW264 mouse macrophages. 4-Hydroxyderricin and
xanthoangelol reduced the phosphorylation (at serine 536) level of
the p65 sub unit of NF-κB. 4-Hydroxyderricin and xanthoangelol
may be promising for the prevention of inflammatory diseases. [ 43 ]
Figure 6.1 4-hydroxyderricin and xanthoangelol suppresses only AP-1 and had no effect on NF-κB in
The Journal of Agricultural and Food Chemistry study of 2013
Source: J. Agric. Food Chem., 2014, 62 (2), pp 462–467 DOI: 10.1021/jf404175t Publication Date (Web): December 26, 2013

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The March 2011 edition of the Archives of Pharmacal Research
published a study that identified six chalcone compounds isolated
from the leaves of Angelica keiskei K (Umbelliferae). (See Table
4.1) Among the isolates, some compounds appeared to have
potent inhibitory activity of IL-6 production in TNF-α-stimulated
MG-63 cells, while some compounds did not. [ 44 ]
A research study published in the Journal of Medicinal Food in June
2010 found that the n-hexane fraction of A. keiskei (HAK)
significantly inhibited LPS-induced NO and prostaglandin E2
production and tumor necrosis factor-α secretion. A. Keiskei also
inhibited the expression of LPS-induced iNOS and COX-2 proteins
and their mRNA levels. The data suggest that the anti-inflammatory
effect of HAK is mediated through down-modulation of iNOS and
COX-2 gene products by blocking the signaling pathways of MAPKs
and NF-κB. [ 45 ]
Another later study also published in the Journal of Medicinal Food
in December 2014 indicated that the seven chalcones identified
from Ashitaba inhibited the production of NO and the expression of
pro-inflammatory cytokines, interleukin (IL)-1β and IL-6, in
LPS-activated macrophages.
The data demonstrates that four chalcones (1, 2, 4, and 5) from A.
keiskei can suppress inflammation and taken together, four
chalcones from A. keiskei may have efficacy as anti-inflammatory
agents. [ 46 ]

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A 2005 study published in the Biological & Pharmaceutical Bulletin
Journal showed the effects of xanthoangelol, xanthoangelol D, E,
and F, which isolated from the root of Angelica keiskei KOIDZUMI
(Umbelliferae), on NF-kappaB activation and ET-1 gene expression
in cultured porcine aortic endothelial cells (PAECs). The results
suggest that xanthoangelol D may be useful for the treatment of
various vascular diseases involved NF-kappaB activation. [ 47 ]
Antioxidant
Scientists in China discovered that the antioxidant activities of
Ashitaba leaves ethanol extracts were significantly higher than
stem ethanol extracts. Results showed that leaf ethanol extracts
from Angelica keiskei Koidzmi can be used as a natural antioxidant
for development and utilization in the future. [ 48 ]
It appears that Ashitaba can increase the expression of antioxidant
enzymes, including Hepatic catalase, superoxide dismutase (SOD),
glutathione reductase (GsR), glutathione peroxidase (GPx), and
glutathione transferase (GT) amRNA. [ 49 ]
Ashitaba also can protect DNA damage from oxidative stress. A
study from 2004 published in BioFactors supported the hypothesis
that Ashitaba in the form of a green vegetable drink exerts a
cancer-protective effect via a decrease in oxidative damage to DNA
in humans. [ 50 ]

33
Ashitaba chalcone appears to enhance the antioxidant capacity
and inhibit the proliferative activity of tumor cell in H22
hepatoma-bearing mice. [ 51 ]
Anti-thrombotic
Ashitaba is thought to have anti-thrombotic properties through the
inhibition of inflammatory-induced plasminogen activator inhibitor
1 (PAI-1) production. [ 52 ]
Anti-tumor Agent
A study from 2011 published in the Journal of Oleo Science found
that an extract of Angelica keiskei roots exhibited cytotoxic activity
against 4 human tumor cell lines, HL60 (leukemia), CRL1579
(melanoma), A549 (lung), and AZ521 (stomach).
4-Hydroxyderricin may therefore hold promise as an effective
antitumor agent. [ 53 ]
Study evaluated the antitumor and antimetastatic effects of various
fractions from a 50% ethanol extract of roots. Study isolated
xanthoangelol which showed inhibition of tumor growth in
LLC-bearing mice as well as lung metastases, and prolonged
survival time in carcinectomized mice. These results indicate that
the antitumor and/or antimetastatic activities of xanthoangelol may

34
be due to inhibition of DNA synthesis in LLC cells and of
tumor-induced neovascularization through inhibition of the
formation of capillary-like tubes by vascular endothelial cells and
inhibition of the binding of VEGF to vascular endothelial cells. [ 54 ]
Two chalcones, 4-hydroxyderricin and xanthoangelol were proved
to have anti-tumor-promoting activity in mouse skin carcinogenesis
induced by 7,12-dimethylbenz[a]anthracene (DMBA) plus TPA.
Both chalcones may reveal anti-tumor-promoting activity via the
modulation of calmodulin involved systems and may be useful to
develop the effective method for cancer prevention. [ 55 ]
Six chalcones from Angelica keiskei KOIDZUMI were examined for
their cytotoxicity in two human neuroblastoma cell lines (IMR-32
and NB-39) and normal cells (primary culture of rat cerebellar
granule cells). All chalcones exhibited cytotoxicity against
neuroblastoma cells, and two of them (isobavachalcone and
xanthoangelol H) had no effect on normal cells even at high
concentration (10(-4) M) exposure. [ 56 ]
A study published in the joural In Vivo in 2005 found that two
chalcone derivatives from Angelica keiskei roots also inhibited
tumor growth and metastasis in tumor-bearing mice through the
inhibition of tumor-induced neovascularization and/or the
inhibition of immune suppression caused by tumors. [ 57 ]

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A recently study reported that the 50 % ethanol extract, the ethyl
acetate-soluble fraction and the isolated xanthoangelol, inhibited
tumor growth and metastasis to the lung in Lewis lung carcinoma
(LLC)-bearing mice. The present study examined the effects of
4-hydroxyderricin on tumor growth and metastasis to the lung or
liver in subcutaneous or intrasplenic LLC-implanted C57BL/6J
female mice. These results suggest that the antitumor and
antimetastatic activities of 4-hydroxyderricin may be modulated by
the immune system and the inhibition of angiogenesis. [ 58 ]
A 2003 study in Cancer Letters of an ethyl acetate fraction of stem
exudates yielded 17 compounds, viz., five chalcones, seven
coumarins, and three flavanones. All compounds, except for 10, 16,
ad 17, exhibited potent inhibitory effects on EBV-EA (Epstein-Barr
virus early antigen) induction in Raji cells, known to be a primary
screening test for antitumor-promoters. [ 59 ]
Cancer Treatment and Preventative
Isobavachalcone is a chalcone isolated from Angelica keiskei. A
study from 2011 published in BioFactors suggest that
isobavachalcone induces apoptotic cell death in neuroblastoma via
the mitochondrial pathway and has no cytotoxicity against normal
cells. Therefore, isobavachalcone may be applicable as an
efficacious and safe drug for the treatment of neuroblastoma. [ 60 ]

36
A study pulished in Cancer Letter in 2002 showed that Ashitaba is
considered to contain certain substances that could induce
quinone reductase (QR) activity, and such induction may play a role
in the anti-carcinogenic action of vegetables. Among 45 different
vegetable samples of the study, an extract of Ashitaba clearly
induced QR activity in Hep G2 cells. Ashitaba is therefore
considered to have contained certain substances that could induce
QR activity, and such induction may play a role in the
anti-carcinogenic action of vegetables. [ 61 ]
HDL Cholesterol (Increases)
The Journal Clinical and Experimental Pharmacology and
Physiology published an article in April 2003 that showed that
Angelica keiskei extract has a effect on serum levels of HDL.
These changes in the serum were due to increases in high-density
lipoprotein (HDL) containing ApoA-I and ApoE. 5.
In conclusion, dietary A. keiskei produces elevation of serum HDL
levels and a reduction of liver triglyceride levels in SHRSP. [ 62 ]

37
Hypertension
The inhibitory activity of angiotensin I-converting enzyme (ACE)
was extracted with 80% ethanol from the leaves of Ashitaba
(Angelica keiskei). The ACE inhibitor from Ashitaba contained in
the anti-hypertensive fraction was speculated to be very similar to
authentic nicotianamine based on a comparative study of inhibitory
activity. [ 63 ]
There is interest in using Ashitaba for hypertension. The isolated
constituent 4-hydroxyderricin, one of the major chalcones in
Angelica keiskei extract (ethyl acetate extract from the yellow
liquid of stems), exerted hypotensive regulatory actions and does
seem to lower blood pressure. [ 64 ]
LDL Cholesterol (Decreases)
In a study from 2007, the authors isolated xanthoangelol, another
major chalcone in A. keiskei extract, and examined the effect of
dietary xanthoangelol on lipid metabolism in SHRSP. In
conclusion, dietary xanthoangelol results in a reduction of serum
LDL levels and decreases in total cholesterol and triglyceride
contents in the liver of SHRSP. These beneficial effects are more
effective following consumption of a diet containing 0.10%
xanthoangelol. [ 65 ]

38
Liver Protector
Previous studies reported that the extracts of Angelica keiskei
Koidzumi (AKE) have antioxidant and anti-inflammatory properties,
suggesting that AKE could improve abnormalities associated with
alcoholic liver disease. These results suggest that AKE
supplementation might improve liver function in heavy drinkers. [ 66
]
A study evaluated the hepatoprotective effects of a methanol
extract of AK in rats with D-galactosamine and carbon tetrachloride
hepatotoxicity. Results showed AK exerted protective effects on
D-galactosamine induced hepatotoxicity. However, it exacerbated
toxicity induced by CCl4, possibly through increase in activity of
aniline hydroxylase, a cytochrome P450 isoenzyme responsible for
the metabolic activation of CCl4. [ 67 ]
The June 2011 of the Chinese-German Journal of Clinical Oncology
investigated the effect of Angelica keiskei chalcone (AC) on the
expression of Caspase-3 and Bax in mice hepatocarcinoma cells.
Study showed Angelica keiskei chalcone can increase the
expression of Caspase-3 and Bax protein in mice, and inhibit the
proliferative activity of mice hepatocarcinoma cells. [ 68 ]
Metabolic Syndrome
A study from 2012 published in the Japanese Journal of
Complementary and Alternative Medicine evaluated the efficacy

39
and safety of Ashitaba on patients and candidates with Metabolic
Syndrome (MetS).
Nine adult subjects defined as patients and candidates with MetS
ingested Ashitaba green juice (6.2 g/day of granulated powder
containing 12.3 mg chalcones) for 8 weeks. For evaluation of
efficacy, abdominal fat area, body weight, body fat and blood
parameters were measured. For evaluation of safety, blood
chemistry analysis, hematological analysis and urinalysis were
conducted.
Ingestion of Ashitaba green juice for 8 weeks significantly
decreased visceral fat area, body weight, BMI and body fat,
respectively. There were no adverse clinical changes in blood
analysis and urinary analysis, and no serious symptom was
observed.
These results indicate that it is possible that Ashitaba is a useful
and safe foodstuff for the prevention of MetS. [ 69 ]
A 2012 study pulished in the Journal of Bioscience Biotechnology
and Biochemestry investigated an ethanol extract yielding
xanthoangelol, 4-hydroxyderricin and six chalcones. The chalcones
markedly increased the expression of the adiponectin gene and
production of adiponectin in 3T3-L1 adipocytes. Results suggest
potential benefit in preventing the metabolic syndrome. [ 70 ]

40
Neurogenesis
Scientists at the Biomedical Group of TAKARA Shuzo Co Ltd have
discovered that in vivo production of Nerve Growth Factor (NGF) is
enhanced by several compounds which are contained in edible,
perennial plants such as Ashitaba (Angelica keiskei Koidzumi),
hops (Humulus luplus), edible flowers of chrysanthemum, and
Gajutsu (Curcuma zedoaria Roscoe, one strain of turmeric). Four
coumarin compounds including two novel ones and one chroman
compound were identified in the extract from Ashitaba. Rats were
fed by diet containing 1% Ashitaba dry powders (estimated dose:
750 mg/kg/day) for four days. The rats showed as high as about
20% increase of NGF concentration in the gastrocnemial muscle
compared to animals given a normal diet. [ 71 ]
Takara Bio Inc. in Japan were the assignee of a U.S. Patent on
October 10, 2003 for an “Enhancing agent for nerve growth factor
production comprising a compound having a coumarin backbone or
a compound having a 2-dimethyl chroman backbone”.
The present invention relates to a medicament, a food, a beverage
or a feed, each comprising as an effective ingredient a compound
having an enhancing action for NGF production, which is effective
for a treatment, an amelioration of symptom, prevention or the like
of a disease requiring enhancement of NGF production, wherein
the compound has a coumarin and/or chroman backbone.

41
One of the components to the enhancing agent is a root portion of
Angelica keiskei koidz, which contains chalcones.
7-β-D-glucopyranosyloxy-6-prenyl coumarin,
4′-O-angeloyl-3′-O-[6-O-(β-D-glucopyranosyl)-β-D-glucopyra
nosyl]-khellactone and
8-carboxyl-3-hydroxy-5-methoxy-2-dimethyl chroman are
compounds which are isolated from Angelica keiskei koidz. The
present invention also encompasses these compounds, of which
enhancing actions for NGF production have been also confirmed for
the first time. [ 72 ]
Quinone Reductase (Increases)
Quinone Reductase facilitates the removal of quinones from the
body.
Quinone Reductase may help to prevent many forms of cancer (by
detoxifying carcinogenic quinones) - the body naturally produces
additional Quinone Reductase in areas of the body that are afflicted
with cancer in an endogenous attempt to “fight” Cancer.
A Japanese study from 2002 idicated that Ashitaba is therefore
considered to have contained certain substances that could induce
Quinone Reductase activity, and such induction may play a role in
the anticarcinogenic action of vegetables. Among 45 different

42
vegetable samples, an extract of Ashitaba clearly induced Quinone
Reductase activity in Hep G2 cells. [ 73 ]
Skin Cancer
Dr. Toru Okuyama at Meiji University, College of Pharmacy tested
Ashitaba on mice with tobacco- induced lung cancer and skin
melanomas. In this six month study the skin cancer mice were
given an external application of the Ashitaba extract. The article
stated that the cancer was controlled-with this therapy. In the
tobacco- induced lung cancer the mice were given the extract of
Ashitaba in fluid and food form.
The article stated that the lung cancer progression stopped with
the oral Ashitaba therapy. From the active fraction of "Ashita-Ba",
Angelica keiskei, edible in Japan, five angular pyranocoumarins and
three chalcones, 4-hydroxyderricin, xanthoangelol and were
isolated.
Among these compounds, 4-hydroxyderricin and xanthoangelol
were proved to have anti-tumor-promoting activity in mouse skin
carcinogenesis [ 74 ]

43
Visceral Fat (Reduces)
In April 2010, Japan Bio Science Laboratory announced the results
of their clinical study showing compelling weight loss effects of its
Ashitaba Chalcone Powder.
Figure 6.2 Illustration from Japan Bio Science Laboratory of their randomized, double-blind, parallel
group study
In the randomized, double-blind, parallel group study, 26 slightly
obese male and female patients with BMI between 25 and 30 took
200 mg day of Ashitaba Chalcone as an active ingredient after
dinner for eight weeks. The patients were measured by CT Scan
(total, visceral and subcutaneous fat areas), weight, waist and hip.
After the eight weeks, the researchers observed a marked
reduction in the visceral and subcutaneous fat, as well as in weight,
and waist and hip ratio. The noted that the rate of change in
visceral fat was greater than that of the subcutaneous fat, and

44
attributed this to the fat-burning promotion and fat accumulation
inhibition effects of the ingredient. [ 75 ]
In another study, ingestion of Ashitaba green juice for 8 weeks
significantly decreased visceral fat area, body weight, BMI and
body fat, respectively. This was the conclusion of a 2012 study
published in the Japanese Journal of Complementary and
Alternative Medicine.
Abdominal fat area, body weight, body fat and blood parameters
were measured and Ashitaba green juice (6.2 g/day of granulated
powder containing 12.3 mg chalcones) was consumed for 8 weeks.
[ 76 ]

45
Clinical Trials
There have been two U.S. Clinical trials on Angelica Keiskei.
The first was filed on July 22, 2008 and the estimated Study
completion date was December 2010. The title of the clicial trial
was “Absorption Kinetics of Polyphenols in Angel's Plant (Angelica
Keiskei)”.
The summary of the clinical trial was “The absorption kinetics of
polyphenols in angel's plant (Angelica keiskei), which is a dark
green leafy vegetable rich in antioxidant nutrients, will be
determined in older adults in this pilot study.”
The USDA-Human Nutrition Research Center on Aging at Tufts
University was the filing and responsible party.
Unfortunately, no study results are posted on ClinicalTrials.gov for
this study. [ 77 ]
The second clinical trial was filed on August 20, 2009 and the
estimated Study completion date was July 2010. The title of the
clicial trial was “Bioactive Plant Foods: Effects on Functional
Bioavailability and Genomic Stability”.
The summary of the clinical trial was “To achieve optimal health
and to reduce the risk of age-related chronic diseases through an
easily achievable dietary modification not achievable by the limited
mixture of antioxidant supplements in older subjects, the
investigators will focus their attention on the biological functions of

46
bioactive plant food (Angelica keiskei and/or Glycine max) and its
effect on genomic stability using noble assays.
The investigators propose to study the ability of bioactive
plant-based food (Nutrition bar made from Angelica keiskei and/or
Glycine max) to 1) exert biological functions: increase total
antioxidant performance, decrease oxidative stress in vivo, and 2)
affect genomic stability: decrease DNA damage and modify DNA
methylation. The investigators hypothesize that bioactive plant
food (green leafy vegetable power, and/or black bean power) will
exert biological functions and affect genomic stability far more
efficiently than the limited mixture of purified antioxidant
supplements in the vulnerable population, older subjects (> 50
years, men and postmenopausal women) with and without
metabolic syndrome.”
Tufts University was the filing and responsible party.
Unfortunately, no study results are posted on ClinicalTrials.gov for
this study. [ 78 ]

47
Product Resources
The following resources are the existing Ashitaba products that can
be found in the United States. It is important to note that all four of
these products contain the green Ashitaba powder from the stems
and leaves of the Ashitaba plant, and not the yellow chalcone
powder from the sap of the stems.
The yellow chalcone powder does not exist at the time of this
publication (March 2015) as a finished product that can be bought
at retail. It does exist however in its raw and bulk form from Japan
Bio Science Laboratory in Japan. The name of the chalcone product
from Japan Bio Science Laboratory is called ChalCurb(TM)
.
Updates will be made to this e-book when the yellow chalcone
powder is made into a finished product by a nutrition company or
formulator.
Swanson's Full Spectrum Japanese Ashitaba
Sun Potion Transformational Foods Ashitaba (Organic) - 80g Jar
Percent Ashitaba
This product comes in three forms: tea, tablets and powder.
Midori Greens (Madre Labs)
This product contains a SuperGreens Blend with a core of three
traditional Japanese ingredients: Ashitaba, Japanese Matcha Green
Tea & Wildcrafted Wasabi.

48
Endnotes/References
1
http://www.ars-grin.gov/cgi-bin/npgs/html/taxon.pl?405623
2
https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&cad=rja&uact=8&ved=0CB
4QFjAA&url=http%3A%2F%2Fkitaplar.ankara.edu.tr%2Fdosyalar%2Fpdf%2F285.pdf&ei=CVD1VOiOO4i2
ogTSu4JQ&usg=AFQjCNFENmIs2qW7vsMil_fRq56ds-CD1Q&sig2=_S_MAsgeivGpkE9rBMk7KQ
3
http://www.pubfacts.com/detail/16079483/Xanthoangelol-a-major-chalcone-constituent-of-Angelica-k
eiskei-induces-apoptosis-in-neuroblastoma-an
4
Chalcones from Angelica keiskei
5
6
7
8
http://www.ncbi.nlm.nih.gov/pubmed/17917255
9
Chalcones and Other Compounds from the Exudates of Angelica keiskeiand Their Cancer
Chemopreventive Effects
10
11
12
13
http://online.liebertpub.com/doi/abs/10.1089/jmf.2013.3037
14
http://en.cnki.com.cn/Article_en/CJFDTOTAL-ZSFX201203034.htm
15
16
17
http://www.dbpia.co.kr/Journal/ArticleDetail/477351
18
19
20

49
21
22
23
24
25
26
27
http://onlinelibrary.wiley.com/doi/10.1002/ardp.201100005/abstract?systemMessage=Wiley+Online+L
ibrary+will+be+disrupted+on+7th+March+from+10%3A00-13%3A00+GMT+%2806%3A00-09%3A00+E
ST%29+for+essential+maintenance.++Apologies+for+the+inconvenience.
28
http://118.145.16.238/Jwk_zgyxen/EN/abstract/abstract248.shtml
29
http://www.hindawi.com/journals/ecam/2013/815621/
30
http://www.sciencedirect.com/science/article/pii/S0960894X13010019
31
32
33
34
Chemical Components of Angelica keiskei Koidzumi, Part VI. Antibacterial Activity of Two Chalcones,
Xanthoangelol and 4-Hydroxyderricin, Isolated from the Root of Angelica keiskei Koidumi. CHEMICAL &
PHARMACEUTICAL BULLETIN 39(6), 1604-1605, 1991 The Pharmaceutical Society of Japan, BABA
KIMIE
35
Pharmacological Activities Of Water Extracts Of Umbelliferae Plants. Kim CM, Heo MY, Kim HP, Sin
KS, Pachaly P. College of Pharmacy, Kangweon National Univ., Chuncheon, Korea. Pharm Res 1991
Mar;14(1):87-92
36
http://www.dl.begellhouse.com/journals/708ae68d64b17c52,74677e1376d0a2ef,2c29695069ad0f3c.htm
l
37

50
38
Effects of Angelica Keiskei Chalcone on Insulin Resistance of Skeletal Muscle Cells of Type 2 Diabetic
Rats
39
Anti-diabetic activities of chalcones isolated from a Japanese her, Angelica keiskei. Enoki T, Ohnogi H,
et all, J Agric Food Chem. 2007 July 25; 55 (15): 6013-7. Epub 2007 June 21.
40
THE EFFECT OF CHALCONES EXTRACTED FROM ANGELICA KEISKEI ON SERUM ET-1 AND VE-ca
IN RATS WITH TYPE 2 DIABETES
41
Anti - diabetic Activities of Ashitaba (Angelica keiskei) : Induction of Adipocyte Differentiation and
Enhancement of Glucose Uptake in Adipocyte
42
43
http://pubs.acs.org/doi/abs/10.1021/jf404175t
44
http://link.springer.com/article/10.1007%2Fs12272-011-0311-0
45
46
47
Sugii M., Ohkita M., Taniguchi M., Baba K., Kawai Y., Tahara C., Takaoka M. & Matsumura Y. (2005)
Xanthoangelol D isolated from the roots of Angelica keiskei inhibits endothelin-1 production through
thesuppression of nuclear factor-kappaB. Biol Pharm Bull.
48
Comparison of antioxidant content and oxidation resistance of stems and leaves from Angelica keiskei
Koidzmi
49
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3296928/#B3
50
Kang M.H., Park Y.K., Kim H.Y. & Kim T.S. (2004) Green vegetable drink consumption protects
peripheral lymphocytes DNA damage in Korean smokers. Biofactors, 22(1-4): 245-247.
51
Research of Ashitaba Chalcone on the Antioxidant Effect in Tumor-Bearing Mice HOU
Fang-lin,ZHONG Jin-yi,ZHANG Yan(Haici Hospital Affiliated to Medical College of Qingdao
University,Qingdao Shandong 266033)
52
Xanthoangelols isolated from Angelica keiskei inhibit inflammatory-induced plasminogen activator
inhibitor 1 (PAI-1) production.
53
54
Antitumor and antimetastatic activities of Angelica keiskei roots, part 1: Isolation of an active
substance, xanthoangelol

51
55
56
57
Kimura Y. (2005) New anticancer agents: in vitro and in vivo evaluation of the antitumor and
antimetastatic actions of various compounds isolated from medicinal plants. In Vivo, 19(1): 37-60.
58
Antitumor and antimetastatic activities of 4-hydroxyderricin isolated from Angelica keiskei roots.
Kimura Y, Taniguchi M, Baba K.
59
Chalcones, coumarins, and flavanones from the exudate of Angelica keiskei and their chemopreventive
effects
60
Isobavachalcone, a chalcone constituent of Angelica keiskei, induces apoptosis in neuroblastoma. Biol
Pharm Bull. 2007. Biofactors. 2011.
61
62
63
64
65
Ogawa H., Ohno M. & Baba K. (2005) Hypotensive and lipid regulatory actions of 4-hydroxyderricin, a
chalcone from Angelica keiskei, in stroke-prone spontaneously hypertensive rats. Clin Exp Pharmacol
Physiol., 32(1-2): 19-23.
66
67
Protective Effects of Angelica keiskei Extracts Against D-Galactosamine (GalN)-induced
Hepatotoxicity in Rats
68
Effect of Angelica keiskei chalcone on the expression of apoptosis-regulating proteins of mice
hepatocarcinoma cells
69
http://astp.jst.go.jp/modules/search/index.php?page=DocumentDetail&journalId=1348-7922_9_1_Effic
acy+and+Safety+ofi+Ashitaba%2Fi+%28iAngelica+keiskei%2Fi%29+on+the+Patients+and+Candidate
s+with+Metabolic+Syndrome%3A+A+Pilot+Study_N%2FA
70
https://www.jstage.jst.go.jp/article/bbb/76/5/76_110976/_pdf
71
Takara's Scientists Discover Compounds Enhancing in Vivo Production of Nerve Growth Factor

52
72
https://www.google.com/patents/US7078386
73
Hashimoto, K., et al. In vitro induction of the anticarcinogenic marker enzyme, quinone reductase, in
human hepatoma cells by food extracts. Cancer Lett. 180(1):1-5, 2002. Department of Bioproductive
Sciences, Utsunomiya University, Utsunomiya, Japan.
74
https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&cad=rja&uact=8&ved=0CB
4QFjAA&url=http%3A%2F%2Fkitaplar.ankara.edu.tr%2Fdosyalar%2Fpdf%2F285.pdf&ei=CVD1VOiOO4i2
ogTSu4JQ&usg=AFQjCNFENmIs2qW7vsMil_fRq56ds-CD1Q&sig2=_S_MAsgeivGpkE9rBMk7KQ
75
Ashitaba Chalcones Show Efficacy in Battling Visceral Fat, Published April 6, 2010 Nutraceuticals
World
76
http://astp.jst.go.jp/modules/search/index.php?page=DocumentDetail&journalId=1348-7922_9_1_Effic
acy+and+Safety+ofi+Ashitaba%2Fi+%28iAngelica+keiskei%2Fi%29+on+the+Patients+and+Candidate
s+with+Metabolic+Syndrome%3A+A+Pilot+Study_N%2FA
77
https://clinicaltrials.gov/ct2/show/NCT00721643?term=Angelica+keiskei&rank=1
78
https://clinicaltrials.gov/ct2/show/NCT00963118?term=Angelica+keiskei&rank=2

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