Phytochemistry, pharmacology and medicinal properties of Carthamus tinctorius L

Abstract

Carthamus tinctorius L. is commonly known as Safflower. C. tinctorius extracts and oil are important in drug development with numerous pharmacological activities in the world. This plant is cultivated mainly for its seed, which is used as edible oil. For a long time C. tinctorius has been used in traditional medicines as a purgative, analgesic, antipyretic and an antidote to poisoning. It is a useful plant in painful menstrual problems, post-partum hemorrhage and osteoporosis. C. tinctorius has recently been shown to have antioxidant, analgesic, anti-inflammatory and antidiabetic activities. Carthamin, safflower yellow are the main constituents in the flower of C. tinctorius. Carthamidin, isocarthamidin, hydroxysafflor yellow A, safflor yellow A, safflamin C and luteolin are the main constituents which are reported from this plant. Caryophyllene, p-allyltoluene, 1-acetoxytetralin and heneicosane were identified as the major components for C. tinctorius flowers essential oil. Due to the easy collection of the plant and being widespread and also remarkable biological activities, this plant has become both food and medicine in many parts of the world. This review presents comprehensive analyzed information on the botanical, chemical and pharmacological aspects of C. tinctorius.

Full text

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Carthamus tinctorius
L. commonly known
as Safflower or false saffron is a thistle like, self-
compatible, annual, diploid (2
n
=24) herbaceous crop
that thrives in hot and dry climates and is believed to
have been domesticated somewhere in the Fertile
Crescent region over 4,000 years ago.
(1)
It belongs to Asteraceae family in the order of
Asterales that contains about 22,750 genera and more
than 1,620 species.
Carthamus
species probably
originate from Southern Asia and is known to have been
cultivated in China, India, Iran and Egypt almost from
prehistoric times. During middle ages it was cultivated
in Italy, France, and Spain, and was introduced into
United States in 1925 from the Mediterranean region.
C
.
tinctorius
has been known as "Golrang" in Iran. It is
grown for the red/orange pigment in the flower petals
which is used for coloring rice and bread, and for dyeing
cloth. After synthetic aniline dyes took over this market in
the 1800's the crop was grown as an oilseed.
(2)
C
.
tinctorius
is described as a bushy, herbaceous
annual possessing several branches, which are
categorized as primary, secondary, and tertiary,
with each terminating into a globular structure called
capitulum. Stem and branches are encompassed
with leaves having numerous spines. Safflower is
mainly grown under dry land conditions as an oilseed
crop. It produces white, shiny, and smooth seeds
(fruits) called achenes. They may be with or without
pappus (tufts of hair present on the seed) and are four
sided, having thick pericarp. Each branch produces a
globular flower capitulum which is enclosed by tightly
attached bracts. Safflower has a taproot system that
elongates to 2–3 m in soils with adequate depth. The
deep root system in safflower helps to extract the
water and a nutrient from much deeper layers of soil,
compared to other crop plants, and thus makes it an
ideal plant for rain-fed cropping systems.
(3)
This plant is cultivated mainly for its seed, which
is used as edible oil and as birdseed. This crop was
also grown for its flowers, used for coloring and
flavoring foods and making dyes. It has become an
increasingly important crop in some parts of the world
including Turkey and Iran due to the rich content and
high nutritional value of its edible oil.
(4)
It contains a
high amount of polyunsaturated fatty acid linoleic acid
(70%) and monounsaturated oleic acid (10%) with
small amounts of stearic acid.
(5)
REVIEW
Phytochemistry, Pharmacology and Medicinal
Properties of
Carthamus tinctorius
L.
Jinous Asgarpanah
1
and Nastaran Kazemivash
2
©The Chinese Journal of Integrated Traditional and Western
Medicine Press and Springer-Verlag Berlin Heidelberg 2013
1. Department of Pharmacognosy, Pharmaceutical Sciences
Branch, Islamic Azad University, Tehran, Iran; 2. Biology
Department, Faculty of Biosciences, Tehran North Branch,
Islamic Azad University, Tehran, Iran
Correspondence to: Dr. Jinous Asgarpanah, Tel: 0098-22640051,
Fax: 0098-22602059, E-mail: asgarpanah@iaups.ac.ir
DOI: 10.1007/s11655-013-1354-5
ABSTRACT
Carthamus tinctorius
L. is commonly known as Safflower.
C
.
tinctorius
extracts and oil are
important in drug development with numerous pharmacological activities in the world. This plant is cultivated
mainly for its seed, which is used as edible oil. For a long time
C
.
tinctorius
has been used in traditional
medicines as a purgative, analgesic, antipyretic and an antidote to poisoning. It is a useful plant in painful
menstrual problems, post-partum hemorrhage and osteoporosis.
C
.
tinctorius
has recently been shown to
have antioxidant, analgesic, anti-inflammatory and antidiabetic activities. Carthamin, safflower yellow are the
main constituents in the flower of
C
.
tinctorius
. Carthamidin, isocarthamidin, hydroxysafflor yellow A, safflor
yellow A, safflamin C and luteolin are the main constituents which are reported from this plant. Caryophyllene,
p-allyltoluene, 1-acetoxytetralin and heneicosane were identified as the major components for
C
.
tinctorius
flowers essential oil. Due to the easy collection of the plant and being widespread and also remarkable biological
activities, this plant has become both food and medicine in many parts of the world. This review presents
comprehensive analyzed information on the botanical, chemical and pharmacological aspects of
C
.
tinctorius
.
KEYWORDS
Carthamus tinctorius
, Asteraceae, Safflower, phytochemistry, pharmacology

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Chin J Integr Med 2013 Feb;19(2):153-159
Safflower is a very good purgative, analgesic,
antipyretic and an antidote to poisoning.
(6)
It is a useful
plant for painful menstrual problems, post-partum
hemorrhage, whooping cough and chronic bronchitis,
rheumatism and sciatica.
(7)
The flowers of
C
.
tinctorius
are an important medicinal material in prescriptions used
for cardiovascular, cerebrovascular and gynecological
diseases. In China, the water extract of
C
.
tinctorius
has been developed as an intravenous injection, which
is extensively applied to treat cardiovascular diseases
clinically.
(8)
Its dye is mainly used as a coloring agent.
(1)
There are records that it is used for reducing
ailments from the neurotropic, cardiotropic,
hemopoietic, and diaphoretic systems. Many clinical
and laboratory studies support the use of the medicine
properties of safflower for menstrual problems,
cardiovascular disease, pain, and swelling associated
with trauma.
(9)
Modern pharmacological studies
demonstrated that
C
.
tinctorius
extracts had a number
of biological activities, such as anticoagulantion,
vasodilation, antihypertension, antioxidation,
neuroprotection, melanin production inhibition,
immunosuppression and antitumor activity; and most of
the effects are related to its water extract.
(8)
Safflower
may probably be employed as a potent phytoremediator
of mercury (Hg) and selenium (Se) from polluted soils.
Phytoremediation is the biotechnological application of
plants to detoxify pollutants, and is a modern technique
for environmental clean-up.
(10)
A number of chemical constituents such as
flavonoids, phenylethanoid glycosides, coumarins, fatty
acids and steroids have been isolated from different
parts of the plant.
(8)
From current pharmaceutical studies,
additional pharmaceutical applications of
C
.
tinctorius
have revealed antioxidant,
(11)
anti-inflammatory,
(12)
analgesic,
(13)
anticonvulsant,
(14)
increase of peripheral
blood flow, inhibition of platelet aggregation, increase
in the beating amplitude of cultured myocardial cell
sheet, elicited central depressant and inhibition of tumor
promotion in mouse skin carcinogenesis
(15)
effects.
Since review and systemic analysis of chemistry,
pharmacology and clinical properties of
C
.
tinctorius
have not been reported, we prompted to provide the
currently available information on traditional and local
knowledge, ethno biological and ethno medicinal issues,
identification of pharmacologically important molecules
and pharmacological studies on this useful plant.
The aim of this paper is to introduce
C
.
tinctorius
as a potent medicinal plant by highlighting its
traditional applications as well as the recent findings
for novel pharmacological and clinical applications.
Chemical Composition
More than 200 compounds have been isolated
from
C
.
tinctorius
and the commonly known ones are
flavonoids, phenylethanoid glycosides, coumarins,
fatty acids, steroids and polysaccharides.
(8)
Analysis
of safflower seeds showed that crude protein ranged
from 14.9% to 17%, total sugar from 3.2% to 9.2%
and extractable lipids from 25% to 40%.
(16)
Oil content
of the seeds is similar to that of olive and includes
linoleic acid (63%–72%), oleic acid (16%–25%) and
linolenic acid (1%–6%).
(17)
Seven antioxidative serotonin derivatives, N-[2-
(5-hydroxy-1H-indol-3-yl)ethyl]-ferulamide, N-[2-
(5-ydroxy-1H-indol-3-yl)ethyl]-p-coumaramide,
N-,N-[2,2'-(5,5-dihydroxy-4,4'-bi-1H-indol-3,3'-yl)
diethyl]-di-pcomaramide, N-[[3'[2-(p-comaramido)
ethyl]-5, 5'-dihydroxy-4,4'-bi-1H-indol-3-yl]ethyl]
ferulamide, N,N'-[2,2'-(5,5'-dihydroxy-4,4'-1H-indol-
3,3'yl)diferulamide, N-[2[5-(beta-D-glucosyloxy)-1H-
indol-3-ylethyl]-p-comatamide and N-[2-[5-(beta-
D-glucosyloxy)-1H-indol-3-yl]-ethyl] ferumaramide
were isolated from the oil of safflower.
(18)
Serotomide
(trans-N-caffeoylserotonin) and safflomide (trans-N-
caffeoyltryptamine) belonging to serotonin-derived
phenyl propenoid amides have also been found
in
C
.
tinctorius
.
(19)
A new coumaroylspermidine
elucidated as N(1),N(5)-(Z)-N(10)-(E)-tri-p-
coumaroylspermidine also identified in this plant.
(20)
Heliaol, α-amyrin, β-amyrin, lupeol, cycloartenol,
24-methylenecycloartanol, tirucalla-7,24-dienol and
dammaradienol are triterpene alcohol constituents
isolated from the flowers.
(21)
Flavonoid glycosides, carthamin, a flavonoid type
dye and safflower yellow are the main constituents in
the flower of
C
.
tinctorius
.
(1)
The flowers also contains
carthamidin, isocarthamidin, quercetin, kaempferol,
6-hydroxykaempferol and its glycosides, chalcones
including hydroxysafflor yellow A, safflor yellow A,
safflamin C and safflamin A, and safflomin-A.
(22-24)
Some acetylenic glucosides namely carthamoside A1
and Carthamoside A2 are also reported.
(25)
The flavone luteolin and its glucopyranoside

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luteolin 7-O-beta-D-glucopyranoside and luteolin-7-
O-(6''-O-acetyl)-beta-D-glucopyranoside accompany
with lauric acid, myristic acid, palmitic acid, linoleic
acid, arachiidic acid and oleic acid were found in
C
.
tinctorius
flowers.
(26)
Luteolin and its glucopyranosides
have been also found in the leaves.
(27)
A new quinochalcone C-glycosides, tinctormine,
was isolated from the plant together with safflor yellow
B.
(28)
Nicotiflorin is a natural flavonoid extracted from
coronal of C.
tinctorius
.
(29)
Eleven novel secondary
alkane-1,3-diols were isolated from the dried flower
petals of
C
.
tinctorius
.
(30)
Caryophyllene, p-allyltoluene,
1-acetoxytetralin and heneicosane were identified as the
major constituents of
C
.
tinctorius
flowers essential oil.
(31)
Potential of
C
.
Tinctorius
in Phytotherapies
Anti-inflammatory and Analgesic Properties
Although a number of steroidal or non-steroidal
anti-inflammatory drugs have been developed,
researchers are changing their focus to natural
products to develop new anti-inflammatory agents due
to the side-effects of chemical drugs.
(32,33)
As a result,
the search for other alternatives seems necessary and
beneficial.
C
.
tinctorius
are an open door for new and
effective compounds. Many cells and mediators are
involved in proceeding inflammation. For example,
macrophages are representative inflammatory cells
involved in acute or chronic inflammatory responses
by over-production of pro-inflammatory cytokines [for
example, tumor necrosis factor (TNF)-α, interleukin
(IL)-1b and granulocyte/macrophage colony stimulating
factor (GMCSF)] and inflammatory mediators.
(34-36)
The intraperitoneal injection of safflow yellow A
at doses of 50–100 mg/kg in mice showed sustained
analgesic action. This compound also inhibited
formaldehyde-induced foot swelling, histamine-
stimulated capillary permeability, and formation of
cotton ball granuloma in rats. The central inhibition
induced by barbital of chloralin mice was markedly
enhanced by safflor yellow A. The coramine-induced
convulsions and death were markedly reduced.
(37)
Anti-inflammatory action of methanol extract of
C
.
tinctorius
(MEC) involves in heme oxygenase-1
(H0-1) induction. The results show that MEC induces
HO-1 expression via Nrf2 translocation and inhibits
nuclear factor kappa B (NF-κB) activity, which may
be responsible for anti-inflammatory action.
(12)
The flavone luteolin and its glucopyranoside
such as luteolin 7-O-beta-D-glucopyranoside and
luteolin-7-O-(6''-O-acetyl)-beta-D-glucopyranoside
have been reported to exert anti-inflammatory effects
in vitro
and
in vivo
(38)
and several works have shown
that these compounds which are rich in
C
.
tinctorius
flowers inhibited NF-κB activity at concentrations in
the low micromolar range.
(39)
Flowers of
C
.
tinctorius
possess central analgesic
activity (500 mg/kg) and potentially may lead to the
development of morphine-like substances devoid of the
side effects of morphine and related drugs.
(13,40)
Anticoagulant Effects
The brain is susceptible to ischemia-induced
damage followed by thrombotic block. Generally,
cerebral ischemia is characterized by the state of
hypercoagulability and hyperviscosity in circulation,
which is prone to form thrombosis.
(41)
Studies have
demonstrated that Hydroxysafflor yellow A (HSYA)
contained in
C
.
tinctorius
flowers markedly extended
coagulation time in mice, which raises the possibility
that it might exert therapeutic actives on cerebral
ischemia induced by thrombosis. Followed researches
have shown that HSYA dose dependently improved
the neurological deficit scores and reduced the cerebral
infarct area and it bore a similarity in potency of the
therapeutic effects on focal cerebral ischemia to
nimodipine as the standard drug. The inhibition rates of
thrombosis formation by HSYA at the doses of 1.5, 3.0
and 6.0 mg/kg, at 30 min after the onset of ischemia
were 20.3%, 43.6% and 54.2%, respectively. Inhibitory
activities of HSYA were observed on adenosine
diphosphate (ADP)-induced platelets aggregation
in a dose-dependent manner, and the maximum
inhibitory aggregation rate of HSYA was 41.8%. Blood
rheological parameters were markedly improved by
HSYA, such as whole blood viscosity, plasma viscosity,
deformability and aggregation of erythrocyte, but no
significant effect of HSYA on hematocrit was found.
The underlying mechanisms exerted by HSYA might be
involved in its inhibitory effects on thrombosis formation
and platelet aggregation as well as its beneficial action
on regulation of prostacyclin/thromboxane (PGI2/TXA2)
and blood rheological changes in rats.
(41)
C
.
tinctorius
is commonly used in Chinese medicine
to promote blood circulation and remove blood stasis.
Blood stasis, i.e. the decrease of blood flow velocity,

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indicates hemorheological abnormalities. Studies
have been shown the effects of carthamins yellow
contained in safflower flowers on blood stasis. Results
have demonstrated that this compound significantly
decreased the whole blood viscosity, plasma viscosity
and erythrocyte aggregation index which were increased
in blood stasis. Hematocrit and platelet aggregation were
reduced while the prothrombin time was delayed. So
this natural food coloring agent could be a great value in
the prevention of hemorheological disorders-associated
diseases in at risk patients.
(42)
Antioxidant Activity
An antioxidant is defined as any substance
that, when present at low concentrations compared
to those of an oxidizable substrate, significantly
delays or prevents oxidation of that substrate.
(34,43-45)
Antioxidants are of interest to biologists and clinicians
because they help to protect the human body against
damages induced by reactive free radicals generated
in atherosclerosis, ischemic heart disease, cancer,
Alzheimer's disease, Parkinson's disease and even
in aging process.
(46,47)
There are many evidences that
natural products and their derivatives have efficient
antioxidative characteristics, consequently linked
to anticancer, hypolipidemic, antiaging and anti-
inflammatory activities.
(34,43-46,48,49)
Antioxidative capacities of
C
.
tinctorius
were
evaluated by determining its effect on 2,2-diphenyl-1-
picrylhydrazyl (DPPH) radical scavenging and ferric
reduction.
(11)
In both assays, aqueous extract of the flowers
exhibited high antioxidant activity. DPPH scavenging
effect was 96.65%. The 50% inhibitory concentration
(IC
50
) value for Ferric reduction assay was determined
as 1,140.5 μmol/g.
(11)
Total phenolic content from
the flowers was determined as 2.12 and 1.32 g/100 g
for methanolic and aqueous extracts respectively.
(50)
As the flowers contained high phenolic compounds
including it confirmed that they have an important role
in antioxidant activities.
(51)
Ethanol extract of safflower seeds inhibited low
density lipoprotein (LDL) oxidation induced
in vitro
by an
azo-containing free-radical initiator V70 or copper ions.
Two serotonin derivatives, N-(p-coumaroyl) serotonin,
and N-feruloylserotonin and their glucoside derivatives
were identified as the major phenolic and active
constituents of the extract. It was demonstrate that these
serotonin derivatives were absorbed into circulation and
attenuate atherosclerotic lesion development possibly
because of the inhibition of oxidized LDL formation
through their strong antioxidative activity.
(52)
Effects on Osteoporosis
Osteoporosis can result from such conditions
as senility, post menopause, calcium deficiency and
immobilization as well as endocrinological and nutritional
changes. Increased bone loss in postmenopausal
osteoporosis is suggested to result from estrogen
deficiency. Estrogen deficiency and calcium deficiency
are reported to be additive factors in the genesis of
osteoporosis.
(2)
Safflower seed oil has high linoleic acid level,
which possesses anti-inflammatory activity in bone by
moderating prostanoid formation, correcting bone loss
due to ovariectomy and increasing intestinal calcium
absorption.
(2)
Safflower seed powder contains many minerals
especially calcium, magnesium and potassium, and is
effective in preventing the osteoporotic process caused
by bilateral ovariectomy in rat model.
(2)
Safflower seed
powder effectively prevented reduction of cortical bone
width and bone loss in the established osteoporotic rat
resulting from estrogen deficiency. It was demonstrated
that the safflower seed powder effectively inhibited
bone loss associated with estrogen deficiency in rats.
(2)
Also, oral administration of safflower seed oil at
a dose of 1 mL/kg to ovariectomized rats for 30 days
showed positive changes compared to the vehicle
treated ovariectomized control rats. Safflower seeds
have shown a possible role in the improvement of
ovariectomy induced osteoporosis in rats.
(53)
The aqueous extract of safflower seed significantly
accelerated rates of osteoblast differentiation in the
experimental group as compared to the control group in
murine osteoblastic cells of the MC3T3-E1 line cultured
on modified Eagle's minimum essential medium.
(54)
Phytoestrogen rich safflower seeds demonstrated a
protective effect on bone loss caused by estrogen
deficiency, without substantial effect on the uterus. The
beneficial effect of safflower seeds may be mediated,
at least in part, by the stimulating effect of polyphenolic
compounds on proliferation of osteoblasts.
(55)

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On processing bone metabolism, PGE2
accelerated production of IL-1b in fetal mouse
osteoblast and stimulated physiological activation
substance, IL-1b. The novel class of Src tyrosine
kinase inhibitors, Herbimycin A (HERB) and HHI
reduced cyclooxygenase (COX-2) mRNA levels as
well as prostaglandin E (PGE2) production induced
by IL-1b, TNF-α and IL-6. HHI inhibited
in vitro
and
in
vivo
bone resorption by inhibition of phosphorylation
of peptide substrates. HHI dose-dependently reduced
the hypercalcemia induced in mice by IL-1b and partly
prevented bone loss and microarchitectural changes in
young ovariectomized rats, showing that the protective
effect on bone was exerted via the inhibition of bone
resorption. These results indicate that the synergy
between IL-b, TNF-α, IL-6 on PGE2 production is
due to an enhanced gene expression of COX-2 and
that tyrosine kinase (s) are involved in the signal
transduction of COX-2 in mouse calvarial osteoblasts.
(56)
Hepatoprotective Activity
It has been shown that both methanolic extract
at 300 mg/kg and the constituent dehydroabietylamine
isolated from C.
tinctorius
leaves, significantly reduced
the toxic effect of CCl
4
, similar to the standard silymarin
in the levels of liver function serum markers, aspartate
aminotransferase (AST), alanine aminotransferase
(ALT) and alkaline phosphatase (ALP), total bilirubin
and increase in the protein synthesis. The percentage
of protection was greater in dehydroabietylamine at
50 mg/kg which is comparable to the reference drug
silymarin (100 mg/kg).
The protection against the injurious effects of
carbon tetrachloride may be due to the inhibitory
effects on cytochrome P450 resulting in the hindrance
of the formation of hepatotoxic free radicals.
(57)
The rats treated with methanolic extract and
dehydroabietylamine along with toxicant showed signs
of protection against the toxicants.
(57)
Powdered safflower seed lowered the plasma
cholesterol concentration in high-fat and high-
cholesterol fed rats. Safflower seed preparations
including seed powder, ethanol extract and aqueous
extracts of the seeds significantly lowered the plasma
cholesterol and triglyceride concentrations. The
hepatic total cholesterol and hepatic triglyceride
contents were significantly lowered. The hepatic
3-hydroxy-3-methylglutaryl-coenzyme A (HMG-
CoA) reductase activities were significantly high. The
hepatic acylcoenzyme A cholesterol acyltransferase
(ACAT) activities were significantly low. Therefore,
supplementation of safflower seeds is effective
in improving the atherogenic risk factors in high-
cholesterolemia.
(58)
Animals treated with 2%-cholesterol diet and
dichloromethane extracts of the seeds for a week
exhibited decreased body weight. After treatment
for 14 and 30 days, a significant reduction in total
cholesterol and total cholesterol/high density lipoprotein
(HDL)-cholesterol and a significant induction in HDL-
cholesterol were observed in the hypercholesterolemic
rats treated with the dichloromethane extract.
The dichloromethane extract can reduce the total
cholesterol/HDL-cholesterol of hyperlipidemic rats.
(59)
Antidiabetic Effects
Safflower is useful for treatment of diabetes and
its complications. The flower aqueous extract can
reverse the metabolic disorders occurring in alloxan
induced diabetes. Considering these effects on these
lipid components, it can be assumed as a potential
hypolipidemic agent, which will be a great advantage
both in diabetic condition as well as the associated
atherosclerosis or hyperlipidemic conditions.
(60)
C
.
tinctorius
flowers regenerates and restorates
of Langerhan islets, thus the insulin level would be
elevated. Safflower enhances the secretion of insulin
from the beta cells of the islets of Langerhans. Further,
it has an ability to restore the protein breakdown and
enhance the glycogenesis process in the liver of
diabetic rats.
(60)
Serotonin derivatives such as N-p-coumaroyl
serotonin and N-feruloyl serotonin isolated from
C
.
tinctorius
seeds were active as α-glucosidase
inhibitors. These compounds showed a potent
inhibitory activity, IC
50
values were calculated as
47.2 μmol/L and 99.8 μmol/L while that of the
reference drugs acarbose and 1-deoxynojirimycin
were evaluated as 907.5 μmol/L and 278.0 μmol/L,
respectively. These results are helpful for the proper
use of safflower seed as a traditional medicine for
the treatment of diabetes; moreover, it could serve to
develop medicinal preparations as supplements and
functional foods for diabetes.
(61)

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Conclusion
The objective of this review has been to show
the recent advances in the exploration of
C
.
tinctorius
as phytotherapy and to illustrate its potential as a
therapeutic agent. With the current information, it is
evident that
C
.
tinctorius
has pharmacological functions
including antioxidant, anti-inflammation, analgesic,
antidiabetic, hepatoprotective and antihperlipidemic
activities, among others. As the current information
shows, it is also possible that furanocoumarins might
be useful in the development of new drugs to treat
various diseases. However, the present results suggest
a possibility that serotonin derivatives and flavonoids
can be further developed as a potential disease-
curing remedy. It must be kept in mind that clinicians
should remain cautious until more definitive studies
demonstrate the quality and efficacy of
C
.
tinctorius
.
For these reasons, extensive pharmacological and
chemical experiments, together with human metabolism
will be a focus for future studies. Last but not the least,
this review emphasizes the potential of
C
.
tinctorius
to be employed in new therapeutic drugs and provide
the basis for future research on the application of
transitional medicinal plants.
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(Received June 11, 2012)
Edited by ZHANG Wen