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https://www.researchgate.net/publication/12244620 ;
https://www.researchgate.net/publication/12244620_Medicinal_plants_in_China_containing_pyrrolizidine_alkaloids
 
Medicinal plants in China containing pyrrolizidine alkaloids.
Article· Literature Review (PDF Available) in Pharmazie 55(10):711-26 · November 2000 with 6,952 Reads ;


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• 
  Erhard Thomas Röder/ Roeder
  
  • 40.92
  • University of Bonn
  
  
  
  
  
  
  
  
  
  
  
  
  

Abstract

Medicinal plants and remedies are widely used for various ailments throughout the world. Many of these plants contain pyrrolizidine alkaloids (PAs) which are hepatotoxic, pneumotoxic, genotoxic, neurotoxic, and cytotoxic. As a result of their use in Traditional Chinese Medicine (TCM), medicinal plants are becoming increasingly important not only in China but also in many other countries. This paper will therefore give, a critical overview of PA-containing plants belonging mainly to the families Boraginaceae, Leguminosae (Tribus Crotalarieae), and Asteraceae (Tribus Senecioneae and Eupatorieae). The PAs contained in the 38 plants described here differ widely in their structure and toxicity. Their metabolism and the resulting toxicity will be discussed, the dehydroalkaloids (DHAlk) produced in the liver playing a key role in cases of intoxications.
**
Medicinalplants
in
China
containing
pyrrolizidine
alkaloids
E.
ROEDER
Dedicated
toDr.C.C.J.
Culvenor
onthe
occasion
ofhis
75
th
birthday,
CSIRO
Animal
Health,
Geelong,
Victoria,
Australia
Medicinal
plants
and
remedies
are
widely
used
for
variousailmentsthroughout
the
world.
Many
of
theseplantscontain
pyrrolizidine
alkaloids(PAs)which
are
hepatotoxic,
pneumotoxic,
genotoxic,neurotoxic,
and
cytotoxic.
Asa
result
of
their
usein
TraditionalChinese
•
Medicine(TCM),medicinalplants
are
becomingincreasingly
important
not
only
in
China
but
also
in
manyother
countries.
This
paperwilltherefore
give,
a
criticaloverview
of
PA-containingplantsbelong-
ing
mainly
tothe
familiesBoraginaceae,
Leguminosae
(Tribus
Crotalarieae),
and
Asteraceae(TribusSenecioneae
and
Eupatorieae).
ThePAs
contained
inthe38
plants
described
here
differ
widely
in
theirstructure
and
toxicity.Theirmeta-
bolism
andthe
resultingtoxicity
will
be
discussed,
the
dehydroalkaloids
(DHAlk)
produced
inthe
liver
playing
akey
role
in
cases
of
intoxications.
1.
Introduction
2.
Chemistry
of
pyrrolizidinealkaloids
2.1.
Necines
2.2.Necicacids
3.
Biosynthesis
of
pyrrolizidinealkaloids
3.1.
Biosynthesis
of
necines
3.2.Biosynthesis
of
necicacids
4.
Occurrence
of
pyrrolizidinealkaloids
in
Chinese
medicinal
plants
4.1.
Medicinalplants
ofthe
familyOrchidaceaecon-
tainingpyrrolizidine
alkaloids
4.1.1.
Liparis
nerv
o
sä
4.2.Medicinalplants
ofthe
familyFabaceaecontain-
ing
pyrrolizidinealkaloids
4.2.1.
Crotalaria
albida
4.2.2.Crotalariaassamica
4.2.3.
Crotalaria
mucronata
4.2.4.
Crotalaria
sesseliflora
4.2.5.
Crotalariatetragona
4.3.Medicinalplants
ofthe
family
Boraginaceaecon-
taining
pyrrolizidinealkaloids
4.3.1.Arnebia
euchroma
4.3.2.
Cordia
myxa
4.3.3.
Cynoglossumamabile
4.3.4.
Cynoglossumlanceolatum
4.3.5.
Cynoglossum
officinale
4.3.6.
Cynoglossum
zeylanicum
4.3.7.
Heliotropium
indicum
4.3.8.
Lappula
intermedia
4.3.9.
Lithospermum
erythrorizon
4.4.
Medicinal
plants
ofthe
family
Asteraceaecontain-
ing
pyrrolizidinealkaloids
4.4.1.
Ageratum
conyzoides
4.4.2.
Chromolaena
odorata
4A3.
Eupatorium
cannabinum
4.4.4.Eupatoriumchinense
4.4.5.
Eupatoriumfortunei
4.4.6.
Eupatorium
japonicum
4.4.7.Cacaliahastata
4.4.8.Cacaliahupehensis
4.4.9.
Crassocephalum
crepidioides
4.4.10.
Emilia
sonchifolia
4.4.11.
Farfugium
japonicum
4.4.12.
Gynurabicolor
4.4.13.
Gynuradivaricata
4.4.14.
Gynurasegetum
4.4.15.
Ligulariadentata
4.4.16.
Petasites
japonicus
4.4.17.
Senecioargunensis
4.4.18.
Senecio
chrysanthemoides
4A.19.
Senecio
integrifolius
var.fauriri
4.4.20.
Senecionemorensis
4A..21.
Senecioscandens
4.4.22.
Syneilesisaconitifolia
4.4.23.
Tussilago
farfara
5.
Metabolism
and
toxicity
of
pyrrolizidinealkaloids
6.
Conclusion
7.
Appendix:Alkaloids
in
Chinesemedicalplants
1.
Introduction
Over
the
past
20
yearsinterest
in
TraditionalChineseMedi-
cine(TCM)
has
increasedconsiderably
not
only
in
Europe
but
also
in
NormAmerica
and
Australia.
In
addition
to
acu-
puncture,acupressure,massage,moxibustion,
and
magne-
totherapy,phytotherapy
plays
a
particularlyimportantrole.
In
Chinamedicinalplants
and
theirpreparationshave
beenused
for
2200
years.
The
fact
thatthey
areso
much
in
vogue
inthe
western
countries
may
be
attributed
not
only
to
anxiety
ofthe
consumers
of
syntheticdrugsabout
undesired
secondary
effects
of
thesedrugs
but
also
tothe
«Green
Movement»
which
has
beenresurgent
in
Europe,
NormAmerica,
and
Australia
forthe
last
20
years.
After
the
political
and
economicalopening
of
Chinanumerous
remedies
and
medicinalplantsbecameavailable
inthe
West
particularlybecause
the
difficulties
in
writing
and
speakingChinesehavebeen
overcome
byuseoftheso-
calledpinyin.
Since
the
landarea
of
Chinaextendspractically
from
the
arctic
tothe
tropicalclimaticzone,
an
unusually
large
number
of
plantsgrow
inthe
country,
a
greatmany
of
which
are
used
äs
medicinalplants.
It
is
thereforeper-
fectly
understandablethatmorethan
5700
plants
and
ani-
mals
used
for
medicinal
purposes
are
described
inthe
well-known
modernwork,
the
«TraditionalMedicinalDic-
tionary»
of
1979
[1].
Many
of
thisränge
of
plantshaveobtained
officinal
sta-
tus,
being
listed
inthe
Chinesepharmacopoeiawherethey
Pharmazie
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711



REVIEW
are
described
exactly
in
monographs
[2]
which
in
most
caseshavebeentranslatedinto
German
[3].
Meanwhile,
there
area
number
of
books
of
both
official
[4,5]and
populär
nature[6-8]devoted
tothe
most
important
med-
icinal
plants.
There
are
alsobooksdealinguncriticallywithChinese
medicinal
plants
and
suggestingmiraclecures,such
äs
in
particular
a
book
by
Hoehnewith
the
title
«Healing
Teas
Work
Miracles»
[9].
In
thisbook
a
greatnumber
of
asia-
tic,
especiallyChineseplants,unknown
in
western
coun-
tries
are
cited.
These
plants
may
causeintoxication
byim-
proper
use.
In
addition,
in
various
regions
of
China
different
plants
are
marketedunder
the
same
drug
nameleading
to
confu-
sionwith
fatal
consequences
äs
illustrated
by
several
ex-
amples
reported
inthe
medicinalliterature[10,
11].
After
pyrrolizidine
alkaloid-containingplantsbecamediscredited
worldwide
[12-20],
Chinesemedicinalplantswereinves-
tigated
from
thispoint
of
view.Thesestudiesrevealedthat
38
plants
of
TraditionalChineseMedicine(TCM)belong-
ing
to
particularplantfamiliescontainpyrrolizidine
alka-
loids
(PAs)
of
varying
toxicity
äs
confirmed
by
scientific
studies.
Inthe
following
sections
only
thoseplantswill
be
discussedwhosecomponentshavebeendetermined
un-
equivocally.
2.
Chemistry
of
pyrrolizidinealkaloids
2.1.
Necines
The
ester-typepyrrolizidinealkaloids(PAs)usuallycon-
tain
a
necinebase,callednecine,which
isa
fused
5/5ring
System
with
a
nitrogenatom
äs
bridgeheadrepresenting
a
tertiary
base.
In
almost
all
cases
the
necine
hasa
hydroxy-
methyl
group
at
C-l
and
generallyalso
a
hydroxylgroup
at
C-7.Thesehydroxylgroups
are
usuallyesterifiedwith
a
necicacidgiving
monoester,
open-chaindiester,
and
macrocyclicdiesteralkaloids.
Figure
l
shows
the
necines
ofthe
alkaloids
sofar
found
in
Chineseplants.
In
addition
tothe
hydroxylgroup
atC-7
they
may
also
have
a
hydroxylgroup
atC-2orC-6
resulting
inthe
for-
mation
of
stereoisomers.
The
necine
can
either
be
satu-
rated
or
possess
a
doublebond
inthe
1,2-position
(ring
B,
Fig.
1).All
known
PAs
found
inthe
plantsstudied
can
form
N-oxidederivativesexcept
the
otonecinealkaloids.
The
corresponding
esterification
of
necinescontaining
a
double
bond
inthe
1,2-positionyieldstoxicalkaloids.
Otonecine
plays
a
special
role
because
itisnota
true
bi-
cyclic
ring
System,
buta
N-methylated
azacyclooctan-4-
onering
System.
Itmayact
äs
a
pyrrolizidinering
System
due
to
transannular
interactions.
The
bindingbetween
the
N
atom
andtheCO
group
is
widened
to
such
an
extent
that
the
resonance
structures
indicatedresult.
ThePAsde-
rived
from
thesestructuresconstitute
the
subgroup
ofthe
otonecine
alkaloids
(OPAs)
1
.
2.2.Necicacids
The
necicacids
found
in
PAs,excludingaceticacid,pos-
sess
5,7,8and10
carbonatoms.
They
canbe
mono-
or
dicarboxylicacidswithbranchedcar-
bon
chains,bearing
äs
substituentshydroxy,epoxy,carboxy,
acetoxy,
methoxy
or
otheralkoxygroups.
Thus,
numerous
structural,
stereo-
and
diastereoisomers
maybe
formed.
Ta-
bles
land2
H
stthe
mostimportantmono-
and
dicarboxylic
acids
thathavebeen
found
in
alkaloids
so
far.
necic
acid(s)
necine
R1
R2
R1
R2
HH
isoretronecanole
OH
H
platynecine
OH
H
hastanecine
OH
OH
rosmarinecine
H
H
supinidine
OH
H
retronecine
HOH
heliotridine
dehydrootonecine
Fig.
l:
Structure
of
basic
alkaloids
and
necines
occurring
in
Chinesemed-
icinal
plants
The
possibilities
of
esterification
are
exemplified
by
sev-
eralalkaloids.Necinescontaining
one
hydroxylgroup
can
be
esterifiedwith
one
monocarboxylicacid
only
äs
shown
in
Figure
2for
amabiline.Necinesbearing
two
hydroxyl
groupssuch
äs
7,9-necinediols
canbe
esterified
with
a
monocarboxylicacideither
inthe7-or
9-position
äs
de-
monstrated
by
7-angeloyl-
and
9-angeloylretronecine.
Echimidine
isan
example
ofa
twofoldesterification.With
dicarboxylicacids
a
doubleesterificationtakes
place
lead-
ing
exclusively
tothe
formation
of
alkaloids
with
11
-to
14-membered
ringSystems.
The
mostwidelyknown
PAs
arethe
11
-membered
monocrotaline,
the
12-membered
al-
Table
1:The
most
important
monocarboxylic
necic
acids
oc-
curring
inPAs
CarbonatomsAcidname
Aceticacid
Tiglicacid
Angelic
acid
Senecioic
acid
Sarracinic
acid
2-Methylbutyric
acid
(+,
—)
Viridifloric
acid
(+,
—)
Trachelanthicacid
and
derivative
Echimidinic
acid
Lasiocarpic
acid
712
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55
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REVIEW
Table2:
The
most
important
dicarboxylic
necic
acids
occur-
ring
inPAs
CarbonAtomsAcid
name
10
Monocrotalicacid
Crotaleschenicacid
Incanicacid
Globiferic
acid
Trichodesmic
acid
Senecinicacid
Integerrinecic
acid
Senecivernic
acid
Isatinecic
acid
Seneciphyllicacid
Spartioidinic
acid
Ridelliic
acid
Erucifolinecic
acid
Petasinecicacid
kaloids
senecionine
and
senkirkine,
the
13-membered
dor-
onenine,
andthe
14-membered
parsonsine.
Through
combination
of
necineswithnecicacids
anex-
ceedingly
large
number
of
alkaloids
may
theoretically
be
obtained.
In
naturemorethan
350
alkaloidshavebeen
found
sofarand
theirstructureselucidated.Apart
from
about
33
knownotonecinealkaloids,whichcannotform
N-oxides,including
the
N-oxides
ofthe
otheralkaloids
morethan
660
alkaloids
are
known
[13-20].
3.
Biosynthesis
of
pyrrolizidinealkaloids
Significant
progress
has
beenmade
inthe
past
few
years
in
the
understanding
ofthe
biosynthesis
ofthe
necines
and
necic
acids
chiefly
byuseof
precursorscontaining
the
stableisotopes
2
H,
13
C,
and
I5
N.
During
amino
acid
metabolism
the
unstableisotopes
3
H
and
14
C
of
both
the
necinebases
and
necicacids
are
produced
[21,
22].
Root
cultures
of
Senecio
and
Eupatorium
specieshavebeen
found
tobe
excellentin-vitroSystems
for
studying
PA
bio-
chemistry(23).
3.1.Biosynthesis
of
necines
Biochemicalstudieshaverevealedthatnecinebasebio-
synthesis
is
linked
to
primarymetabolism
via
putrescine
and
spermidineboth
of
which
are
exclusivelyderived
from
arginine.
Ornithine
is
incorporated
via
arginine.Homospermidine
has
been
identified
äs
thefirst
intermediate
ofthe
specific
alkaloidpathway.
It
is
formed
by
homospermidine
synthase
(HSS),
an
enzymethatcatalyzes
thefirst
reaction
inthe
biosynthesis.
Fora
long
time
itwas
assumedthat
HSS
cat-
alyzes
the
transfer
ofthe
aminobutylgroup
of
eitherputres-
cine
or
spermidine
toa
secondputrescinemolecule
yield-
ing
homospermidine.
A
reinvestigationrevealed,however,
that
HSS
usesonlyspermidine
äs
an
aminobutanoldonor.
The
carbonskeleton
ofthe
necinebasemoiety
is
derived
half
and
half
from
spermidine
and
putrescine.
Me
amabiline
O
7-angeloy
Iretronec
i
ne
OMe
Me
O
Me
O9-angeloylretronecine
HQ
"9
,Me
Me
HO*
N—Me
\
Me
7
OH
HO
Me
HO
Me
parsonsine
Fig.
2:
Examples
of
toxic
pyrrolizidine
alkaloids
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55
(2000)
10
713



REVIEW
The
further
course
ofthe
biosynthesis
isthe
same
not
only
amongrepresentatives
ofthe
generaSeneciossp.,
and
Eupatorium
ssp.
but
alsoamongthose
ofthe
genera
Crotalaria
ssp.,
Heliotropium
ssp.
and
Cynoglossumssp.
It
is
described
in
Scheme
l
whichrepresents
the
present
state
of
research.
The
resultsobtained
are
documented
for
the
necinestrachelanthamidine,isoretronecanole,rosmari-
necine,
retronecine,
and
heliotridine
[23-28].
Formally,
rosmarinecine
isa
ß-hydroxyderivative.ß-Hy-
droxy
compounds
are
known
tobe
very
unstable,yielding
a,
ß-unsaturatedcompoundswithelimination
of
water.
In
the
casestudiedretronecine
would
be
formed
from
ros-
marinecine
withelimination
of
waterunderphysiological
conditions
also.
Otonecine
is
produced
from
retronecine
from
its
alkaloids
by
hydroxylation
of
retrocineesteralkaloids
atC-8
[21,
29].
A
methyl
group
is
assumed
tobe
transferred
from
S-adeno-
sylmethionine
äs
donor
tothe
nitrogenatom
[30].
3.2.Biosynthesis
of
necicacids
Due
tothe
enormous
variability
of
necicacids,biosyn-
thesisproceedsnotably
less
homogeneouslythan
inthe
case
of
necines,
and
only
afew
syntheticpathwayshave
beenelucidated
sofar
[21].
The
aminoacids
L-isoleu-
cine,
L-leucine,
L-threonine,
and
L-valine
are
known
tobe
precursors,
the
decarboxylation
and
deamination
of
which
Scheme
1:
Biosynthesis
of
necines
NH
2
homospermidine
imimum
Ion
CHO
/
\
H
CH
2
OH
.?
isoretronecanole
CD
trachelanthamidine
givee.g.
C5
acidssuch
äs
angelic
or
tiglic
acid
or
CIQ
acids
such
äs
senecic
acid.
The
biosyntheticpathway
of
the
latterprocess
was
recentlycompletelyelucidated.Stir-
ling
et
al.
demonstratedthatbiosynthesisproceeds
viatwo
L-isoleucine
molecules
and
does
not
involveketonicinter-
mediates
[31].
The
corresponding
studieswereperformed
on
representa-
tives
ofthe
generaSenecio
ssp.,
Cynoglossum
ssp.,
and
Crotalariassp.Studies
of
Weber
etal.on
rootcultures
of
Eupatorium
clematideum
recentlyshowedthattrache-
lanthic
acid
is
biosynthesized
bythe
addition
ofa
two-
carbonmoiety
from
hydroxyethyl-TPP
[«activated
acetal-
dehyde»]
to
2-oxoisovaleric
acidfollowed
bya
reduction
step
[32].
4.
Occurrence
of
pyrrolizidine
alkaloids
in
Chinese
medicinal
plants
In
flora
PAsare
widelydistributed
äs
products
of
second-
ary
metabolism.
However,
they
mainlyoccuronly
in
cer-
tainfamilies
and
here,
in
turn,generallyonly
in
some
tribes
or
genera.
Table3:
Occurrence
of
pyrrolizidinealkaloids
in
different
Chinese
medicinal
plants
Family
TribusGenus
Orchidaceae
Fabaceae
(Leguminosae)
Boraginaceae
Epidendreae
Crotalarieae
Cordioideae
Lithospermeae
Cynoglosseae
Heliotropieae
Eritrichieae
Asteraceae(Compositae)Eupatorieae
Senecioneae
Liparis
Crotalaria
Cordia
Lithospermum
Arnebia
Cynoglossum
Heliotropium
Lappula
Ageratum
Chromolaena
Eupatorium
Cacalia
Crassocephalum
Emiüa
Farfugium
Gynura
Ligularia
Petasites
Senecio
Syneilesis
Tussilago
HO
,
CH
2
OH
H
,
UM
2^
«OH
rosmarinecine
HO
H
CH
2
OH
1
+Me+
(methionine
)
CH
2
OH
heliotridine
HO
o
CH
2
OH
N-
Me
4.1.Medicinalplants
ofthe
familyOrchidaceaecontain-
ing
pyrrolizidinealkaloids
4.1.1.Liparis
nervosa
(Thunb.)
Lindl.
(syn.
Ophrys
nervo-
sa
Thunb.)
[Chin.:
Jian
xue
qing,
Japn.:
Kokuran,
EngL:
Twayblade]
Liparis
nervosagrows
in
CentralChina.
Itisa
traditional
medicinal
plantcollectedthroughout
the
year.
The
decoc-
tion
prepared
from
10-20
gofthe
plant
is
used
in
cases
of
hemoptysis,
hematemesis,bleeding,woundssurgical
bleeding,snakebites,
andleg
ulcers.
All
parts
ofthe
plant
contain
the
alkaloidnervosine(42)composed
ofthene-
cine
lindelofidine
(d-isoretronecanole)
andthe
necicacid
nervisinic
acid.Since
no
toxic
effects
of
these
two
compo-
nentshave
yet
been
reported
[33,
34]
there
areno
objec-
tions
tothe
aforementioneduses
ofthe
plant.
714
Pharmazie
55
(2000)
10



REVIEW
4.2.Medicinal
plants
ofthe
familyFabaceaecontaining
pyrrolizidinealkaloids
4.2.1.
Crotalariaalbida
Heyne
ex
Roth
(syn.
C.
formosa-
na
Matsum.
ex
Ito
&
Matsum,,
syn.
C.
montanaRoxb.)
[Chin.:
Huang
huadi
ding,
EngL:
Rattlebox]
Crotalaria
albida
isa
semi-perennial
plantgrowing
in
In-
dia
and
China
at
altitudes
of200to
2800
m.
The
whole
plant
is
collected
in
summer
and
fall
and
dried,
and
25-50
gofitare
prepared
äs
a
decoction
and
used
in
cases
of
urinary
tractinfections,
boils,
pyodermas,
and
cough.
Thisplantcontains
the
nontoxicalkaloidcroalbidine
(64)
[35,
36].
There
areno
objections
to
therapeutic
use.
4.2.2.CrotalariaassamicaBenth.
(syn.
C.
burmannii
DC.,
syn.
C.
sericea
Burm.
F.)
[Chin.:
Zi
xiao
rong]
This
isa
plantgrowing
in
India
and
China,
atan
altitude
of
upto
3000
m.Itisa
subshrub
thatreaches
a
height
of
l
-2mand
grows
on
slopes,margins
of
forests
or
banks
of
watercourses.
The
plant
flowers
from
Jury
to
October
and
is
used
äs
a
folk
remedy.
The
stems
and
leaves
are
collected
in
summer,
theripe
seeds
inthe
fall.
The
stems
and
leaves
are
used
in
cases
of
boils
and
pyodermas,
cough,
and
toothache,
andthe
seeds
are
used
äs
an
antitu-
morigenic
agent.
The
antitumorigenic
activity
was
studied
extensively
bythe
»Crotolaria
Plant
Research
Group"
in
the
case
of
skincancer;
however,
the
secondary
effects
on
the
liver
turned
outtobe
very
harmful
[37].
The
plant
contains
a
highconcentration
ofthe
alkaloid
monocrota-
line
(62)
anda
minor
amount
of
assamicadine
(29);
the
seeds
alone
contain
upto
2.9%
of
monocrotaline
[38-41].
It
should
not
longer
be
used
äs
a
traditionalmedicinal
plant
because
ofits
highalkaloidcontent
andthe
hepato-
toxic
effect
ofthe
monocrotaline.
4.2.3.CrotalariamucronataDesv.
(syn.
C.
pallida
Alton)
[Chin.:
Xiang
ling
cao,
EngL:Rattlebox]
Crotalaria
mucronata
isa
perennial
subshrub-like
herb
with
a
height
oflm
whichgrows
in
villages
and
among
roadside
thickets
and
flowers
from
June
to
October.
For
medicinal
purposes
the
wholeplant
and
seeds
are
col-
lected.Pods
are
collected
in
fall,
and
dried
inthe
sun,
and
the
seeds
are
collected.They
are
used
for
dizziness,
neu-
rasthenia,
nocturnal
emission,prematureejaculation,leucor-
rhea,enuresis,
and
polyurea.Stems
and
leaves
are
used
for
dysentery
and
abdominalpain,
andthe
roots
for
lymphade-
nopathy,
mastitis,dysentery,
infantile
malabsorption,
and
malnutrition.
The
followingquantities
are
used:
-seeds
6-
16
g,
stems
6-18
g,
roots
15-30
g
äs
decoctions.
The
plant,
particularly
the
seeds,containshighamounts
of
usamarine
(syn.
mucronatinine)
(52)
and
nilgirine
(59)
[42-48].
As
alreadystated
in
Chineseregulations
the
seeds
are
poi-
sonous
and
should
be
usedwithcaution(contraindicated
in
pregnancy).
Pigs
fed
withherbshowsigns
of
intoxication
resembling
those
of
atropine
[48].
Alcoholic
and
aqueous
extracts
obtained
from
leaves
and
dried
fruit
showed
no
clastogenic
effects
on
mousebone
marrow
cells
[49].
4.2.4.Crotalaria
sessiliflora
L.
(syn.
C.
brevipesChamp.
ex
Benth.,
C.
eriantha
Sieb,
et
Zucc.)
[Chin.:
Yebaihe;
Nong
ji
U]
It
isan
annual
erectherb,growing
in
Japan,Korea
and
China;
inthe
latter
country
uptoan
altitude
of
1500
m.
The
plant,
flowering
until
September,
is
hairy,
20-200
cm
high
andis
widespread
on
roadsides,
and
riverbanks
and
in
thickets.
It
plays
an
important
role
in
folk
medicine
and
is
alsolisted
inthe
PharmacopoeiaSinica
of
1985.
The
wholeplant
is
used;
the
seeds
are
used
in
cases
of
boils
and
pyodermas,tinnitus,deafness,dizzines,
vertigo,
and
for
skincancer,esophagealcancer,
and
cervicalcancer.
15-60
gare
taken
internally
äs
a
decoction
while
crushed
fresh
herb
or
ground
and
driedherb
is
used
for
topical
application.
In
cancertherapy,
the
duration
of
treatment
variesbetween
3and4
months.
Aqueousextractsshowedinhibitoryactivity
to
several
ro-
denttumorssuch
äs
sarcoma
180,
leukemia
615,
and
Walkercarcinoma
256
(50).
Plant
and
seeds
containmonocrotaline
(62)
in
high
con-
centration,
and
trichodesmine
(63)
and
integerrimine
(53)
[51-53]
in
low
concentration.According
to
present
knowledge
Crotalaria
sesseliflora
should
notbe
usedthera-
peutically
even
for
external
purposes.
4.2.5.
CrotalariatetragonaRoxb.
ex
Andrews
(syn.
C.
esquirolii
H.
Lev.,
syn.
C.
grandiflora
Zoll.)
[Chin.:
Hua
jin
dan]
Thisplantgrows
in
India,Nepal,Bhutan,Myanmar,Viet-
nam,
and
China
at
altitudes
of
500-1600
m,
mainly
inthe
provinces
of
Guangdong,Guanxi,Sichuan,
and
Yunnan.
It
is
a
perennialherb
and
blooms
in
September.
For
medi-
cinalpurposes
the
wholeplanttogetherwith
the
root
is
used.
Itis
also
used
äs
a
folk
remedy
in
cases
of
indiges-
tion
and
stomachache.
All
parts
ofthe
plant,especially
its
seeds,
containhighamounts
of
trichodesmine
(63)
andin-
tegerrimine
(53)
[54].
Thisplantshould
no
longer
be
used
therapeutically.
4.3.Medicinal
plants
ofthe
familyBoraginaceae
con-
tainingpyrrolizidinealkaloids
4.3.1.Arnebiaeuchroma
(Royle)
Johnst.
(syn.
Macroto-
mia
euchroma
(Royle)
Pauls)
[Chin.:
Zi
cao,
*Ruan
zi
cao,Juan
tsu
tsao,
Japn.:
Nanshikon,
EngL:Arnebia]
It
isan
annual
to
semi-perennialplantwith
a
height
of
25-
50cm
that
flowers
from
August
to
September
andis
then
collected.
Itisan
officinal
medicinalplantlisted
inthe
Phar-
macopoeia
Sinica
1985/1990.
The
roots
are
usedinternally
for
improving
the
blood
circulation,
äs
an
antiviralagent,
andfor
liverdiseases.
Thered
dystuff
ofthe
roots,
shiko-
ninederivates,
is
used
for
stainingfoods
and
cosmetics.
The
rootscontain
O
7
-angeloylretronecine
(1)und
O
9
-angeloyl-
retronecine
(2)ina
totalamount
of
only
lOppm
[55].
Intoxication
has
therefore
not
been
reported.
4.3.2.Cordiamyxa
L.
(syn.
C.
dichotomaForst.)
[Chin.:
Qin
tong
cuimu,
EngL:Sebesten
Plum]
Cordia
myxa
L.isa
shrub
or
treewhich
may
reach
a
height
of5to
10m
andis
native
to
regions
of
Chinawith
a
warmclimate.
The
roots
are
collectedthroughout
the
year.Decoctions
of
25-50
g
obtained
from
driedroots
are
used
for
gastricpain.
The
plantcontains
the
nontoxicalka-
loidmacrophylline
(37)
[56].
There
areno
objections
to
its
use.
4.3.3.Cynoglossum
amabile
Stapf.
&J.R.
Drumm.
[Chin.:
Goushi
hua]
This
plant
is
native
to
Tibet,Bhutan,
and
China.
In
China
it
grows
äs
a
perennialherb
at
heights
of
2600
to
3700
m
in
the
provinces
of
Gansu,Guizou,Sichuan,Xizang,
and
Pharmazie
55
(2000)
10
715



REVIEW
Yunnan.
The
whole
plant
i
s
collectedduring
theflowering
period
from
June
to
August.
It
is
used
for
medicinal
pur-
poses
in
cases
of
colds,
fever,
cough,hemoptysis,hema-
temesis
und
beriberi,
25-50
gofthe
dried
drug
being
used
äs
a
decoction.
The
plantcontainsamabiline
(11)
and
echinatine
(18)
äs
major
alkaloidsbesides
S'-acetylechinatine
(19),
rinderine
(22),
and
supinine
(12).
The
totalalkaloidcontent
isca.
0.4%
[57-59].
Although
thesealkaloidsshow
only
moderatetoxicity,
they
should
notbe
used
äs
a
remedy.
4.3.4.
Cynoglossum
lanceolatum
Forsk.
(syn.
C.mi-
cranthum
Des/.,
syn.
C.
canescens
Willd.,
syn.
C.
hirsutum
Thunb.)
[Chin.:
Ya
yong
cao]
Thisplant
isa
biennialherb
in
Cambodia,
India,
Laos,
Myanmar,
Nepal,Pakistan,Phillipines,
Sri
Lanka,
and
Thailand.
It
grows
in
China
at
altitudes
of300to
2800
m.
The
plant
is
collectedduring
the
floweringperiod
from
June
to
August.
Decoctions
of
15-25
g
containing
the
nontoxic
alkaloidcynaustraline
(44)
andthe
slightlytoxic
alkaloid
cynaustine
(30)[60]
are
used
for
internal
indica-
tions,
e.g.
for
nephritic
edema,acute
nephritis,
and
tooth-
ache.
There
areno
objections
to
medicinaluses.
4.3.5.Cynoglossum
officinale
L.
[Chin.:
Yao
yong
daoti
hu,
EngL:
Hounds
tongue]
Cynoglossum
officinale
isa
perennialherbwidespread
in
China.
Decoctionsprepared
from
15-25
gof
driedroots
are
used
in
traditionalmedicine.
The
roots
are
collected
in
spring
and/or
fall
andare
used
forthe
treatment
of
pul-
monary
tuberculosis
and
cough,hoarseness,
and
hematem-
esis.
The
plantcontains
the
following
alkaloids:
main
alkaloids:
trachelanthamine
(31),
heliosupine
(27),
andits
N-oxide,
3'-acetylheliosupine
(28),
viridiflorine
(32)
orthe
stereo-
isomer
ofthe
latter;secondaryalkaloids:echinatine
(18)
and
its
N-oxide,
S'-acetylechinatine
(19),
7-angeloylechi-
natine
(21),
7-angeloylheliotridine
(7),
7-tigloylheliotridine
(10);
in
addition
to
traces
of
amabiline
(11),
supinine
(12),
rinderine
(22),
and
7-angeloylrinderine
(24).
With
the
exception
of
viridiflorine
(32)
andits
stereo-
isomer
all
thesealkaloids
are
toxic
[61-71].
The
proportion
ofthe
alkaloids
inthe
plant
is
1.5-2.0%
and
thus
very
high.
Itis
therefore
not
surprising
that
in-
toxication
has
been
reported
withgrazinglivestocksuch
äs
calves
[72,
73]and
horses
[74,
75].
S.
officinale
should
thus
inno
case
be
used
for
medicinal
purposes.
4.3.6.Cynoglossum
zeylanicum
(Vahl)
Thunb.
(syn.
C.furcatum
Wall.)
[Chin.:
TieGu
San]
This
biennial
herb
is
widespread
in
China.From
the
roots
and
leavescollected
in
spring
and
summer,
the
peels
are
used.
15-20
gare
used
äs
a
decoction
in
cases
of
trau-
matic
injuries,
fractures,
snakebites,
boils,
pyodermas,
and
regulär
menses.
The
plantcontains
the
nontoxicalka-
loid
cynaustraline
(44)
[76].
There
areno
objections
toits
use
äs
a
medicinal
plant.
4.3.7.
Heliotropium
indicum
L.
(syn.
H.
anisophyllum
R
de
B.,
H.
parviflorum