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Houttuynia cordata Thunb: A Review of Phytochemistry and Pharmacology and Quality Control

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Houttuynia cordata Thunb is an important medicinal plant widely distributed in East Asia. The collected information is an attempt to cover recent developments in the pharmacology, phytochemistry and quality control of this species. During the past several decades, the medicinally important phyto-constituents have been identified including essential oil, flavonoids and other polyphenols, fatty acids and alkaloids. A survey of the literatures shows H. cordata possesses a variety of pharmacological activities including antiviral, antitumor, antimicrobial, anti-inflammatory, and antioxidative effects. Little attempt has been done to review the techniques used for its quality control. Future efforts should concentrate more on in vitro, in vivo studies and clinical trials in order to confirm traditional wisdom in the light of a rational phytotherapy. The information summarized here is intended to serve as a reference tool to practitioners in the fields of ethnopharmacology and natural products chemistry.
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Chinese Medicine, 2013, 4, 101-123
http://dx.doi.org/10.4236/cm.2013.43015 Published Online September 2013 (http://www.scirp.org/journal/cm)
Houttuynia cordata Thunb: A Review of Phytochemistry
and Pharmacology and Quality Control
Jiangang Fu, Ling Dai, Zhang Lin, Hongmei Lu*
College of Chemistry and Chemical Engineering, Central South University, Changsha, China
Email: *hongmeilu@csu.edu.cn
Received July 1, 2013; revised August 6, 2013; accepted August 21, 2013
Copyright © 2013 Jiangang Fu et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Houttuynia cordata Thunb is an important medicinal plant widely distributed in East Asia. The collected information is
an attempt to cover recent developments in the pharmacology, phytochemistry and quality control of this species. Dur-
ing the past several decades, the medicinally important phyto-constituents have been identified including essential oil,
flavonoids and other polyphenols, fatty acids and alkaloids. A survey of the literatures shows H. cordata possesses a
variety of pharmacological activities including antiviral, antitumor, antimicrobial, anti-inflammatory, and antioxidative
effects. Little attempt has been done to review the techniques used for its quality control. Future efforts should concen-
trate more on in vitro, in vivo studies and clinical trials in order to confirm traditional wisdom in the light of a rational
phytotherapy. The information summarized here is intended to serve as a reference tool to practitioners in the fields of
ethnopharmacology and natural products chemistry.
Keywords: Houttuynia cordata Thunb; Phytochemical Constituents; Pharmacological Activity; Quality Control
1. Introduction
There is a long history of herbal medicine in far Eastern
countries; in particular, Chinese people have utilized
herbs and plants to treat various diseases for more than
8000 years [1]. With the advance of modern medicine
and drug research, chemical synthesis has replaced plants
as the primary source of medicinal agents in industrial-
ized countries. However, in 1985, the World Health Or-
ganization estimated that about 80% of the world’s popu-
lation relied on traditional medicines including herb med-
icines for their primary health care needs [2]. Several
aspects: 1) the high cost of chemical synthesis drug dis-
covery, 2) the efficiency of herb medicine on complex
illnesses such as cancer and cardiovascular disease, 3)
the unique activities of herbal medicine aiming at the
system level via interactions with a multitude of targets
in the human body, make people return to the herbal
medicine, a potential reservoir for new drugs [3].
Houttuynia cordata Thunb, the sole species in the ge-
nus Houttuynia that belongs to the Saururaceae family,
is a flowering and perennial herb native to China, Japan,
Korea and Southeast Asia. In China, this plant is distrib-
uted widely, eastwards to Taiwan, southwest to Yunnan
and Tibet, and north to Shaanxi and Gansu. It grows opti-
mally on moist, shady hillside, wayside and ridge of field
with an altitude of 300 - 2600 m.
H. cordata is a well known traditionally used medici-
nal material in the indigenous medicine systems of
Southeast Asia. It is commonly called Yu-Xing-Cao,
Ji-Cai, historically called Cen-Cao (Wuyue Chunqiu), Ji
(Mingyi Bielu), Zi-Bei-Yu-Xing-Cao (Lü Chan Yan Ben
Cao), Zi-Ji (Jiuji Yifang), Zu-Zi (Bencao Gangmu),
Zu-Cao (Xinxiu Bencao), Chou-Zhu-Cao (Yilin zuan-
yao··yaoxing), Ce-Er-Gen (Zunyifu Zhi), Zhu-Bi-Kong
(Tianbao Bencao), Jiu-Jie-Lian (Lingnan Caiyao Lu),
Zhe-Er-Gen or Fei-Xing-Cao (Guizhou Mingjian Fan-
gyao Ji), and Chou-Xing-Cao (Quanzhou Bencao) in
China; dokudame in Japan; E-Sung-Cho in Korea; Khao-
tong or Plu-khao in Thailand; gip cá or diếp cá in Viet-
nam. It has the functions of relieving fever, resolving
toxin, reducing swelling, draining pus and promoting
urination [4]. During the period of the Severe Acute Res-
piratory Syndrome (SARS) outbreak, it was one of the
ingredients in the SARS prevention formulas recognized
by the Health Ministry of China. Recently, several stud-
ies also provided scientific data to support and unveil its
anti-SARS [5], anti-inflammatory [6,7], anti-allergic
[8,9], virucidal [10,11], antileukemic [12], anti-oxidative
*Corresponding author.
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J. G. FU ET AL.
102
[13,14] and anti-cancer [15] activities. It was reported
that H. cordata contains groups of such chemical com-
ponents as flavones, essential oil and alkaloids [16].
Over the last few years, there has been a rapid increase
in the information available on the structures and phar-
macological activities of H. cordata (Figure 1). In this
review, we present recent H. cordata plant research in
three sections: phytochemistry, pharmacological activi-
ties and quality control. The information was mainly
collected from databases (Scifinder, ISIWeb of Knowl-
edge) and several books.
2. Morphological Description
H. cordata is herbaceous perennial plant growing to 20 -
80 cm, the flowers are greenish-yellow, borne on a ter-
minal spike 2 - 3 cm long with 4 - 6 large white basal
bracts; spike terminal yellowish-brown. The odour is
fishy on rubbing and the taste is slightly adstringent (Fig-
ure 2).
3. Traditional Uses of H. cordata
The uses differ from one country to another. In China, H.
cordata has been used to treat anisolobis sores. The
documented folk uses and indications in China were
listed in detail in Table 1. In Korea, it has been used for
the treatment of cough, pneumonia, bronchitis, dysentery,
dropsy, leukorrhea, uteritis, eczema, herpes simplex,
acne, chronic sinusitis and nasal polyps [11,17]. In Thai-
land, it has been used for immune stimulization and as
anticancer agent [18]. In Japan, it has been mainly used
as diuretics [19] and also used for the treatment of stom-
ach ulcers [20], the control of the infection [21], and as
antimicrobial [22,23], antitumor [24], promoting agents
for the production of an antibiotic substance by a strain
of gram-positive, spore-bearing bacilli [25]. In India, the
shoot has been used for the freshness, good sleep, heart
disorders by Apatani who have traditionally settled in
seven villages in the Ziro valley of Lower Subansiri dis-
trict of Arunachal Pradesh in the Eastern Himalayan re-
gion of India [26]. Besides general medicinal uses, H.
cordata is employed as food (Table 2) and cosmetic for-
mulations. In Korea and Japan, H. cordata is frequently
used in combination with other herbal medicines as cos-
metic. Its extraction are used as cosmetic composition for
preventing or treating wrinkle [27], preventing chapped
skin [28], antiaging [29,30], improving the skin condi-
tions [31], removing freckles and skin-whitening [30].
The fermented extract with other herbal medicine are
used for alleviating atopic dermatitis [32] and other skin
troubles [33], owing to the anti-inflammatory and skin-
calming effect, pruritus-alleviating effect, and humidify-
ing effect of this composition. The extraction is also used
for protecting or nourishing hair and preventing dandruff
[34,35]. In addition, H. cordata is used to prepare the
massage pack which is able to treat acne, chloasma,
atopy, and freckle without leaving any scar [36].
4. Phytochemistry
To date, the majority of phytochemical studies on H.
cordata have focused on three types, namely: essential
oil, flavonoid and alkaloids components [16]. Recent
pharmacological studies indicated the essential oil com-
ponents in H. cordata possess anti-inflammatory, anti-
bacterial and antiviral activities [6,10]. The flavonoid
components revealed antineoplastic, antioxidant, anti-
mutagenic and free radical scavenging capacity [14,
37,38]. Similarly, the alkaloid components demonstrated
significant potent antiplatelet and cytotoxic activities
[15].
4.1. Essential Oil
Most of previous studies were mainly focused on the
chemistry of essential oil. The volatile oils of H. cordata
were extracted by various methods, supercritical CO2 ex-
traction [39,40], steam distillation [41-43], petroleum
ether extraction [39,42], solid-phase microextraction [43],
flash evaporation and simultaneous distillation-extrac-
tion [44,45], isolated by preparative HPLC [45,46], and
analyzed qualitatively and quantitatively by GC , GC-
MS, GC-MS with on-column derivatization procedure
[41] TLC [47,48], flash GC [49], combined gas-liquid
chromatography and mass spectroscopy [48]. The con-
siderable differences may depend on the extraction pro-
cedure, the season, the part, the dry process, the stage of
development and the distinct habitat in which the plant
has been collected [47,50-54]. A total of 346 volatile
components were reported. They were composed mainly
of terpenoids (27.0%), hydrocarbons (16.8%), esters
(11.9%), alcohols (11.6%), ketones (7.2%), aldehydes
(4.9%), acids (3.8%), phenols (1.7%), aethers (0.9%) and
mixed compounds (14.2%). Among these, which were
found with higher frequency are: methyl n-nonyl ketone,
-myrcene, houttuynin, decanal, trans-caryophyllene, de-
canoic acid, camphene, β-pinene, lauraldehyde, bornyl
acetate, α-pinene, limonene, 4-terpineol, caryophyllene
oxide, nonanol and linalool so on.
4.2. Flavonoids and Other Polyphenols
As would be expected in biologically active plants, a
number of flavonoids and other polyphenols have been
isolated and identified from H. cordata (Table 3). The
quercitrin is the first flavonoids extracted from the leaves
and stems of H. cordata [55]. Quercetin-3-O-β-D-galac-
toside-7-O-β-D-glucoside, kaempferol 3-O-[α-L-rha-
mnopyranosyl-(16)-β-D-glucopyranoside], quercetin
Copyright © 2013 SciRes. CM
J. G. FU ET AL.
Copyright © 2013 SciRes. CM
103
1920 1930 1940 1950 1960 1970 1980 1990 2000 2010
0
50
100
150
200
250
300
350
Year
Number of reference
Figure 1. The increasing trend of the research work about H. cordata (The data was collected from Scifinder database).
Table 1. Ethnomedical uses of H. cordata in China.
Traditional uses Document Historial period
Anisolobis sores Mingyi Bielu (Appendant Records of
Famous Physicians) 220-450 AD
Sores, tinea capitis Rihuazi Bencao
(The Herbal Medicine of Rihuazi) 935-965 AD
Heatstroke Lü Chan Yan Ben Cao 1220 AD
Lung carbuncles and refractory hemoptysis, large intestine heat-toxin, hemorrhoids Diannan Bencao 1436 AD
Heat-toxin, carbuncle, hemorrhoids and rectocele, malaria, salammoniac poison Bencao Gangmu (Compendium of CMM) 1592-1596 AD
Lung carbuncles and cough with pyoid blood Shennong Bencao Jingshu 1625
Tonsillitis, chronic phlegm Bencao Fengyuan 1695 AD
Diuresis, resolving mass and swelling, miasma, heatstroke, toxin from the
viper and insect, dermatophytosis, sores and carbuncles with pyogenesis, gore Yilin zuanyao··yaoxing 1758 AD
Swelling, malaria Yaoxing Kao 1772 AD
Scrotal abscess, whitlow Bencao Qiu Yuan 1848 AD
Deobstruant, febrifuge Caomu Bianfang 1870 AD
Hydr opsy, weakn ess , wooden belly Fenlei Caoyaoxing 1906
skin ulcer, diarrhoea, dysentery Lingnan Caiyao Lu 1936
Sores and tinea, eczema, lumbago, coronary heart disease angina Xiandai Shiyong Zhongyao 1956
Syphilis, urethritis, tummy, purulent disease, cellulitis, tympanitis, mastitis,
lung abscess, tuberculosis, hysteritis, first-aid emetic for taking poison Zhongguo…Yaoyong Zhiwu Tujian 1960
Stenocardia Shaanxi Zhongyao Zhi 1962
clearing heat and detoxifying, mastitis, cellulitis, tympanitis, enteritis Changyong Zhongcaoyao Shouce 1969
Lung abscess, lobar pneumonia, malaria, chincough, diarrhoea, dysentery,
appendicitis, urethritis, infantile diarrhea, heatstroke, cold, tonsillitis, cholecystitis,
stubborn dermatitis, boils, wound by the viper
Fujian Yaowu Zhi 1979
3-O-α-L-rhamnopyranosyl-7-O-β-D-glucopyranoside three
flavonoid glycosides [56], chlorogenic acid methyl ester,
4-[(2E)-3-(
-D-glucopyranosyloxy)-2-buten-1-yl]-4-hy-
droxy-3,5,5-trimethyl-2-cyclohexen-1-one, 2-(4-hy-
droxyphenyl)ethyl-β-D-glucopyranoside, 2-(3,4-dihydro-
xyphenyl) ethyl-
-D-glucopyranoside, 4-(
-D-glucopy-
rano-syloxy)-3-hydroxybenzoic acid five polyphenols
[57], catechin, procyanidin B, houttuynamide A, houut-
tuynoside A [18,58] (Figure 3), were isolated from H.
cordata. The structures of new compounds are listed in
J. G. FU ET AL.
104
Figure 2. Houttuynia cordata Thunb.
Figure 3.
The flavonoids and other polyphenols of H. cordata
were extracted by various methods, hot soaking extrac-
tion [59,60], EtOAc extraction [61], ethanol/methanol
refluent extraction [56], Soxhlet extraction [59], ultra-
sonic extraction [62], microwave-assisted extraction [63,
64] and pressurized liquid extraction [60], isolated and
purified by macroreticular resin [65], various column
chromatography [57] and bioactivity-guided fractiona-
tion and isolation [66], and identified and analyzed by
physiochemical properties analysis [67], capillary elec-
trophoresis with wall-jet amperometric detection [68],
TLC [67,69], GC [69], HPLC [69-72], HPLC-MS [73],
HPLC-DAD-ESI-MS [66,74] and spectral analysis in-
cluding UV-VIS [59,67], NMR and MS [56,75]. Among
the above-mentioned extraction methods, microwave-as-
sisted extraction and pressurized liquid extraction are
favorable to the other methods. The microwave-assisted
extraction not only has higher extraction efficiency but
also the advantages of being fast and energy saving.
The amounts of five flavonoid glycosides contained in
H. cordata, quercitrin, hyperin, rutin, isoquercitrin and
afzelin, were determined by HPLC [70,76]. The order of
the flavonoids content in the different parts was as:
flower > leaf > fruit > stem. No flavonoid was found in
rhizome.
A correlation between flavonoid glycoside contents of
H. cordata and light intensity has been reported. The
flavonoid glycoside content was the highest when the
plant was cultivated without shade and decreased as the
shading rate increased [77].
The contents of flavonoids in freeze-dried H. cordata
from different habitats were measured by HPLC-MS. It
was found that flavonoids in Hongkong were higher than
those in Sichuan and Guangdong Province. The relation-
ship between the content of flavonoids in H. cordata and
their biological characteristics such as morphologic and
growth traits or a geographic origin were analyzed. The
result revealed that the levels of three major flavonoids,
hyperin, quercitrin, and quercetin, varied remarkably in
the plants from different provinces, and variation in quer-
citrin was significantly correlated to the biological char-
acteristics of the plant but not correlated to the geo-
graphic region where the plant grows [72].
4.3. Alkaloids
During the past 20 years, many kinds of alkaloid have
been isolated from H. cordata, including aporphine, pyri-
dine and the others. The structures of these compounds
are shown in Table 4. cis-N-(4-Hydroxystyryl) benza-
mide and trans-N-(4-Hydroxystyryl) benzamide were
isolated from the CHCl3 extraction of this herb by a com-
bination of HPLC and other techniques [78]. Probstle and
co-workers isolated aristolactam A, aristolactam B, pi-
perolactam A and norcepharacdione B from H. cordata.
Jong and Wang isolated 7-chloro-6-demethyl-cephara-
dione, long chain substituted pyridine alkaloids 3,5-dide-
canoyl-pyridine,2-nonyl-5-decanoylpyridine which are
rare in nature and N-methyl-5-methoxy-pyr-rolidin-2-
one from this plant [79,80], respectively.
4.4. Organic Acid and Fatty Acid
Palmitic acid, stearic acid, heptanoic acid, nonanoic acid,
undecanoic acid, octanoic acid, hexanoic acid, lauric acid,
capric acid, heptadecanoic acid, tetradecanoic acid, tri-
decanoic acid, pentadecanoic acid, octadecenoic acid,
hexadecenoic acid, octadecadienoic acid, aspartic acid,
glutamic acid capric acid, lauric acid and palmitic acid in
this plant were identified using gas chromatograph [81].
In addition, chlorogenic acid, crypto-chlorogenic acid,
neo-chlorogenic acid, quinic acid and caffeic acid were
identified using mass spectra and fragmentation patterns
[18]. Takagi and coworkers extracted chlorogenic acid,
detected palmitic acid, linoleic acid, oleic acid, and stea-
ric acid in the benzene fraction [82]. Wu and co-workers
seperated and purified the chemical components by sol-
vent extraction, thin-layer chromatograph and silica gel
column chromatograph, and identified the structures by
IR, EI-MS, 1H-NMR and 13C-NMR [83]. Bauer and col-
leagues identified linolenic, linoleic, oleic, palmitic and
stearic acid by phytochemical examination [16]. Wang
and colleagues isolated and purified succinic acid from
dried rhizome of this plant by solvent extraction, silica
gel and Sephadex LH-20 column chromatographs [80].
Copyright © 2013 SciRes. CM
J. G. FU ET AL.
Copyright © 2013 SciRes. CM
105
Table 2. Food applications of H. cordata.
Countries Used part Traditional uses References
China, Vietnam Root, leaves Vegetable [145,146]
Japan Leaves, entire plant Beverage, deodorant [147,148]
Korea Entire plant
Kimchi, soy sauce, knife-cut noodles, syrup,
carbonated drinks [149-151]
Thailand Young leaves vegetable [18]
Table 3. Flavonoids and other polyphenols from H. cordata.
Number Compounds Classes Parts References
1 Quercetin Flavonoids E, A [61,75,150]
2 Rutin Flavonoids A, L, SP, S [68-70,76,82,150]
3 Hyperin Flavonoids A, SP, L, S [69,70,75,76,82,85,149,150]
4 Afzelin Flavonoids E, A, L, SP, S [61,70,75,76,82,85,150]
5 Quercitrin Flavonoids A, E, L, SP, S [24,55,56,61,69,70,75,76,84,85,103,150]
6 Isoquercitrin Flavonoids A, L, SP, S [69,70,76,88,149,150]
7 Apigenin Flavonoids A [75]
8 Quercetin-3-O-β-D-galactoside-7-O
-β-D-glucoside Flavonoids* E, L, R, S [56]
9
Kaempferol
3-O-[α-L-rhamnopyranosyl-(16)-
β-D-glucopyranoside]
Flavonoids* E, L, R, S [56,71]
10
Quercetin
3-O-α-L-rhamnopyranosyl-7-O-β-D
-glucopyranoside
Flavonoids* E, R, S [56]
11 Quercetin hexoside Flavonoids L [18]
12 Kaempferol Flavonoids E [71]
13 Isorhamnetin Flavonoids E [71]
14 Phloridzin Flavonoids L [152]
15 Avicularin Flavonoids L [152]
16 Protocatechuic acid Polyphenols E, A [61,75,85,150]
17 Chlorogenic acid Polyphenols A, E, L, R, S [18,82,150]
18 Vanillic acid Polyphenols NR [85,153]
19 p-Hydroxy-benzoic acid
methyl ester Polyphenols NR [84,153]
20 Chlorogenic acid methyl ester Polyphenols* E [57]
J. G. FU ET AL.
106
Continued
21
4-[(2E)-3-(
-D-glucopyranosyloxy)
-2-buten-1-yl]-4-hydroxy-3,5,
5-trimethyl-2-Cyclohexen-1-one
Polyphenols* E [57]
22 2-(4-Hydroxyphenyl)ethyl-β-
D-Glucopyranoside Polyphenols* E [57]
23 2-(3,4-Dihydroxyphenyl)ethyl-
-D-Glucopyranoside Polyphenols* E [57]
24 4-(
-D-glucopyranosyloxy)-3
-hydroxybenzoic acid Polyphenols* E [57]
25 Cryptochlorogenic acid Polyphenols L [18]
26 Neochlorogenic acid Polyphenols L [18]
27 Procyanidin B Polyphenols* L [18]
28 Catechin Polyphenols* L [18]
29 Quinic acid Polyphenols L [18]
30 Caffeic acid Polyphenols L [18]
31 cis-Methyl ferulate Polyphenols E [85]
32 trans-Methyl ferulate Polyphenols E [85]
33 Methyl vanillate Polyphenols E [85]
34 Vanillin Polyphenols E [85]
35 Houttuynamide A Polyphenols* E [85]
36 Houuttuynoside A Polyphenols* E [85]
*Novel compound; E, entire plants; A, aerial parts; R, roots; S, stems; SP, spikes; B, barks; L, leaves; NR, not reported.
4.5. Sterols
A number of common sterols have been isolated from H.
cordata. Stigmast-4-en-3-one, 3
-hydroxystigmast-5-en-
7-one, 5α-stigmastane-3,6-dione and stigmast-4-ene-3,6-
dione were isolated from this plant [84]. Stigmast-3,6-
dione, sitoindoside I and daucosterol were isolated and
purified from dried rhizome of H. cordata by solvent
extraction, silica gel and Sephadex LH-20 column chro-
matographs [80].
-Sitosterol [4,82,85],
-sitosterol glu-
coside [85], brassicasterol [4], stigmasterol [4], spinas-
terol [4], and stigmast-4-ene-3,6-dione [16] were also
found in this plant.
4.6. Amino Acid and Microelements
H. cordata contains more than 20 amino acids, including
alanine, valine, glutamic acid, aspartic acid, isoleucine,
proline, leucine, glycine, serine, lysine, cystine, tyrosine,
methionine, phenylalanine, histidine, threonine, trypto-
phane, arginine, hydroxyproline and citrulline [81,86].
The major components were alanine, valine, glutamic
acid, aspartic acid, isoleucine, proline leucine [81]. Among
all amino acids, the glutamic acid content was the highest
followed by leucine and aspartic acid [86]. Many micro-
elements including iron, magnesium, manganese, potas-
sium, copper, zinc and calcium, etc., can be in H. cordata
[86,87]. The involucre of H. cordata containes high lev-
els of zinc, copper, and Zn/Cu ratios at the stages of fruc-
tification [86].
4.7. Other Compounds
N-phenethyl-benzamide, glyceryl linoleate and n-butyl-
α-D-fructopyranoside were isolated and purified from
dried rhizome of H. cordata by solvent extraction, silica
gel and Sephadex LH-20 column chromatographs [80].
Vomifoliol, sesamin and 1,3,5-tridecanoylbenzene were
isolated from the aerial parts of H. cordata. 1,3,5-tride-
canoylbenzene was also isolated [84]. Chou character-
ized N-(1-hydroxymethyl-2-phenylethyl) benzamide, N-
(4-hydroxyphenylthyl) benzamide, 4-hydroxybenzamide,
4-hydroxy-3-methoxybenzamide, 6,7-dimethyl-1-ribitol-
1-yl-1,4-dihydroquinoxaline-2,3-dione, (1H)-quinolinone,
indole-3-carboxylic acid, dihydrovomifoliol, reseoside,
7-(3,5,6-trihydroxy-2,6,6-trimethylcyclohexyl)but-3-en-2-
one, 6-(9-hydroxy-but-7-enyl)-1,1,5-trimethylcyclhexane-
3,5,6-triol, 4-hydroxybenzoic acid, methylpara-ben, p-
hydroxybenzaldehyde, benzyl-
-D-glucopyranoside and
cycloart-25-ene-3
,24-diol from H. cordata using 1D
and 2D NMR and mass spectra [85]. The carotenoids
were observed in H. cordata. The content of
-carotene
and violaxanthin are relatively high in the cotyledonous
stage and decreased in fructification, while the content of
lutein is low in the cotyledonous stage and progressively
increased with the growth [86].
5. Pharmacological Activities
5.1. Diuretic Effects
The components quercitrin extracted from the leaves and
Copyright © 2013 SciRes. CM
J. G. FU ET AL. 107
O
O O
O
O
OH
OH
HO
HO
HO
OH
O
OH
HO
HO
OH
OH
O
O
HO
OH
OH O
O
O O
HO
HO
OH
HO
OH
OH
CH
3
O
O
OH
OH
OH
OH
O
OH
OH
O
O
O
CH
3
OH
OH
OH
HO
(a) (b) (c)
O
OCH
3
OH
OH
OH
HO
OH
OH
O
O
O
HO
HO
HO
CH3
CH3CH3
O
CH3
HO
HO
HO
O
OH
OH
OH
OH
O
(d) (e) (f)
O
O
HO
HO
HO
HO
OH
OH
O
O
HO
HO
HO
HO OH
COOH
O
O
OH
OH
OH
OH
HO
HO
OH
HO
OH
HO
(g) (h) (i)
O
OH
OH
OH
OH
HO
N
OOH
HO
OH
H
OCH
2
OOO
OH
HO
O
OH
HO
OCH
3
HO
(j) (k) (l)
Figure 3. Flavonoids and other polyphenols were isolated or detected from H. cordata for the first time. (a) Quercetin
3-O-α-L-rhamnopyranosyl-7-O-β-D-glucopyranoside; (b) Kaempferol 3-O-[α-L-rhamnopyranosyl-(16)-β-D-glucopyrano-
side]; (c) Quercetin 3-O-α-L-rhamnopyranosyl-7-O-β-D-glucopyranoside; (d) Chlorogenic acid methyl ester; (e) 4-[(2E)-
3-(
-D-glucopyranosyloxy)-2-buten-1-yl]-4-hydroxy-3,5,5-trimethyl-2-cyclohexen-1-one; (f) 2-(4-Hydroxyphenyl)ethyl-β-D-
glucopyranoside; (g) 2-(3,4-Dihydroxyphenyl)ethyl-
-D-glucopyranoside; (h) 4-(
-D-glucopyranosyloxy)-3-hydroxybenzoic-
acid; (i) Procyanidin B; (j) Catechin; (k) Houttuynamide A; (l) Houttuynoside A.
Copyright © 2013 SciRes. CM
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108
Table 4. Alkaloids from H. cordata.
Number Compounds Structures References
1 Aristolactam A
NH
OCH
3
HO
O
[15,85,120,153]
2 Aristolactam B
NH
OCH
3
H
3
CO
O
[15,16,74,79,85,120,153]
3 Piperolactam A
NH
OH
H
3
CO
O
[15,16,74,85,120,153]
4 3,4-Dimethoxy-N-methyl
aristolactam
H3CO
H3CO
N
O
CH3
[85]
5 Lysicamine
N
OCH
3
H
3
CO
O
[85]
6 Noraritolodione
N
H
OH
H
3
CO
O
O
[85]
7 Norcepharadione B
N
H
OCH
3
H
3
CO
O
O
[15,85,120,153]
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J. G. FU ET AL. 109
Contimued
8 Cepharadione B
N
OCH
3
H
3
CO
O
O
CH
3
[15,61,79,85,153]
9 Splendidine
N
OCH
3
H
3
CO
OCH
3
O
[15,85]
10 3,5-Didecanoylpyridine
N
CC
OO
(CH
2
)
8
(CH
2
)
8
OCH
3
H
3
CO
[16,79,154]
11 2-Nonyl-5-decanoylpyridine
N
C(CH
2
)
8
O
CH
3
(CH
2
)
8
H
3
C
[16,79,131,154]
12 3,5-Didecanoyl-4-nonyl-1,
4-dihydropyridine
H
N
C
O
(CH2)8
O
C
(CH2)8(CH2)8CH3
H3C
CH3
[16,154]
13 3-Decanoyl-4-nonyl-5-dodecan
oyl-1,4-dihydropyridine
H
N
C
O
(CH
2
)
8
O
C
(CH
2
)
8
(CH
2
)
10
CH
3
H
3
C
CH
3
[16,154]
14 3,5-Didodecanoyl-4-nonyl-1,
4-dihydropyridine
H
N
C
O
(CH2)8
O
C
(CH2)10 (CH2)10 CH3
H3C
CH3
[16,154]
Copyright © 2013 SciRes. CM
J. G. FU ET AL.
Copyright © 2013 SciRes. CM
110
Contimued
15 7-chloro-6-
demethylcepharadione B
N
H
OCH
3
H
3
CO
O
O
Cl
[79,153]
16 3-Nonylpyrazole
N
HN (CH
2
)
8
CH
3
[96]
17 N-methyl-5-methoxy-
pyrrolidin-2-one
NOCH
3
O
CH
3
[80]
18 cis-N-(4-Hydroxystyryl)
benzamide
N
H
O
HO
Z
[78]
19 trans-N-(4-Hydroxystyryl)
benzamide
HO O
H
N
E
[78]
stems, isoquercitrin from the floral spikes and fruit spikes
of this herb show diuretic action [55,88]. The diuretic
action is attributed to quercitrin, KCl and K2SO4 [89].
The extract of H. cordata showed similar diuretic action
of acetylcholine, lactic acid and aspartic acid [19].
minimal inhibitory concentrations (MICs) against Sta-
phylococcus aureus of water extracts of fresh and dry H.
cordata were 12.5 and 100 mg/mL, and those of ethanol
extracts were 25 and 100 mg/mL respectively. The fresh
extract had better pharma-cological activity than dry one,
and water extract had better pharmacological activity
than ethanol extract. Lu et al reported that oils obtained
by hydrodistillation from the above and the below
ground parts shows antimicrobial activity with MIC val-
ues of 0.0625 × 103 to 4.0 × 103 mL/mL against Sta-
phylococcus aureus and Sarcina ureae [53]. Zhang et al.
found that the MICs of the essential oil against Staphy-
lococcus aureus and Sarcina increased with the storage
time [92]. Moderate antibacterial activities are observed
against Escherichia coli and Staphyloccocus aureus by
[93,94], but not by [95].
5.2. Antimicrobial Effects
Zhang [90] found that oil extract had inhibitory effect on
β-Hemolytic streptococcus, Streptococcus aureus,
Pseudomonas aeruginosa and Escherichia coli. Kwon [44]
noticed that the volatile flavor components showed
strong antibacterial activities against Bacillus cereus, Ba-
cillus subtilis, Vibrio cholerae and Vibrio parahaemo-
lyticus. Meng [91] found that water and ethanol extracts
of fresh and dry H. cordata showed antimicrobial activity
against Staphylococcus aureus and Escherichia coli. The
J. G. FU ET AL. 111
The volatile essential oil isolated from H. cordata was
seperated into 11 fractions by preparative HPLC. In a test
of the antibacterial activity of 11 fractions, the growth of
nine Gram-negative bacteria was inhibited when treated
with Fraction 6 including methyl n-nonyl ketone, β-
myrcene, β-ocimene, 1-decanol and houttuynin, and frac-
tion 5 including decanal, bornyl acetate, fenchene and
decanoic acid, respectively [46]. Houttuynin isolated
from the rhizome of H. cordata suppressed the growth of
yeasts and molds [22] and 3-nonylpyrazole inhibited the
growth of Staphylococcus aureus, Bacillus subtilis, Tri-
chophytons, Zygosaccharomyces salsus, and Asper-
gillus niger [96]. Kim et al. observeed that the anti-
bacterial activity of H. cordata water extract (HCWE)
against Salmonella typhimurium increased in a dose-de-
pendent manner at concentrations from 25 to 100 mg/ml
during 8-h incubation in vitro, without showing cytoto-
xicity in RAW 264.7 cells. Furthermore, HCWE showed
virulence reduction effects in S. typhimurium-infected
BALB/c mice in vivo [97].
5.3. Antiviral Effects
Over the past decade, substantial progress has been made
in research on the natural products for the treatment of
AIDS. Several plants and their products including H.
cordata have shown anti-HIV activity [98]. The distillate
and three major compounds from fresh plants of H. cor-
data showed dose-dependent virucidal acitivity against
HIV-1 without showing cytotoxicity in vitro. At 2-fold
dilution, approximately 20% and 40% of HIV-1 were
inactivated by the pretreatment with the distillate for 2 h
and 6 h, respectively. While no significant activity was
observed at the concentrations less than 0.0017% (w/v),
each of three components exerted virucial activity against
HIV-1 at 0.0083% (w/v). Lauryl aldehyde was found to
be the most potent constituent of the three components
[10]. Vpr, an accessory gene product of HIV-1 induced
abnormality in cell cycle leading to the increased HIV
replication, was supposed to be a possible target for anti-
AIDS drugs. Quercetin, a compound from this crude
drug, efficiently inhibited Vpr function without affecting
its expression. Furthermore, the data suggested that Vpr-
induced transcription from HIV-LTR was considerably
abrogated by quercetin. These in vitro data indicated that
quercetin, a flavonoid previously reported inhibited HIV
replication, also targeted Vpr [99].
An in vitro study evaluated the anti-HSV (herpes sim-
plex virus) activity of H. cordata, using XTT-based col-
orimetric assay. BCC-1/KMC cells were infected with
HSV and were cultured in HCWE. The results showed
that HCWE significantly inhibited the replication of HSV
at a concentration of 250 µg/mL, 10.2% for HSV type 1
(HSV-1) (p < 0.05) and 32.9% for HSV type 2 (HSV-2)
(p < 0.005). The ED50 of HSV-1 and HSV-2 were 822.4
µg/mL and 362.5 µg/mL respectively. H. cordata had
better effect against HSV-2 than HSV-1, and had a low
ED50 against HSV-2 [11]. The distillates extracted from
fresh plants of H. cordata and three components, methyl
n-nonyl ketone, lauryl aldehyde, and capryl aldehyde are
also assayed for anti-HSV activity. The distillates, lauryl
aldehyde and capryl aldehyde exhibited moderate antivi-
ral activity against HSV-1 (ED50 = 0.0013%, ED50 =
0.0008%, ED50
= 0.00038%, w/v). Methyl n-nonyl ke-
tone was not so effective against it (ED50 = 0.0091%, w/v)
[10]. In another in vitro study, norcepharadione B iso-
lated from the whole plant of H. cordata significantly
suppresses HSV-1 replication by 46.38% at the concen-
tration of 100 µM [58].
Severe acute respiratory syndrome (SARS) is a life-
threatening form of pneumonia caused by SARS coro-
navirus (SARS-CoV). From late 2002 to mid 2003, it
infected more than 8000 people worldwide, of which
over 7000 cases were found in China (http://www.who.
int/en/). Owing to the high infectious rate and the ab-
sence of definitive therapeutic Western medicines, State
Administration of Traditional Chinese Medicine of the
People’s Republic of China proposed six traditional Chi-
nese medicine formulae to general public as preventive
measures on 24 April 2003 (http://www.satcm.gov.cn/
zhuanti/jbfz/20060901/100052.shtml). H. cordata was
one of the component herbs in a heatremoving and de-
toxifying formula. Recently, immunomodulatory effect H.
cordata was investigated in mouse splenic lymphocytes,
inhibitory activity on SARS coronaviral 3C-like protease
(3CLpro) and RNA-dependent RNA polymerase (RdRp).
The results showed that HCWE stimulated the prolifera-
tion of mouse splenic lymphocytes significantly and
dose-dependently. By flow cytometry, it revealed that H.
cordata increased the proportion of CD4(+) and CD8(+)
T cells. H. cordata exhibited significant dose-dependent
inhibitory effects on SARS-CoV 3C-like protease (3CL
(pro)) and RdRp activity. At concentration of 200 µg/ml
or above, significantly inhibited the activity of 3CLpro (p
< 0.05). At the highest testing dose (1000 µg/ml), the
3CLpro activity was decreased by 50%. The essential oil
could inhibit the growth of influenza virus in cultures
with ED50 = 41% (v/v) [100], and a complete inhibition
at 250 mg/mL [90]. The antiviral assays demonstrated
that quercetin 3-rhamnoside (Q3R) possessed strong an-
tiviral activity of about 86% against influenza A/WS/33
virus at concentration of 100 µg/ml and antiviral activity
of about 66% at the same virus at concentration of 10
µg/ml. The research on antivirus activities was carried
out using amantadine, ribavirin and H. cordata injection
(HCI) in vitro and in vivo. The abilities of treating pneu-
monia of mice when three kinds of drugs were used co-
operatively were far higher than those alone in BALB/c
mice [101]. Therefore, these findings provided important
Copyright © 2013 SciRes. CM
J. G. FU ET AL.
112
information for the utilization of H. cordata for influenza
treatment.
Another one flavonoid compound, quercetin 7-rham-
noside (Q7R), showed antiviral activity against rotavirus
and rhinovirus [102]. Q7R was used to inhibit porcine
epidemic diarrhea virus (PEDV), was the predominant
cause of severe entero-pathogenic diarrhea in swine. It
inhibited PEDV replication by 50% using 0.014 µg/mL.
Several structural analogues of Q7R, quercetin, apigenin,
luteolin and catechin, also showed moderate anti-PEDV
activity. Q7R did not directly interact with or inactivate
PEDV particles and affect the initial stage of PEDV in-
fection by interfering of PEDV replication. The effec-
tiveness of Q7R against transmissible gastroenteritis vi-
rus (TGEV) and porcine respiratory coronavirus (PRCV),
was lower compared to PEDV. Q7R could be considered
as a lead compound for development of anti-PEDV drugs
[103].
The inhibitory effect of H. cordata on epidemic hem-
orrhagic fever virus (EHFV) infection was also reported
[104]. H. cordata extract (HCE) could neutralize EV71-
induced cytopathic effects in Vero cells. The IC50 of
HCE for EV71 was 125.92 ± 27.84 µg/mL. Antiviral
screening of herb extracts was also conducted on 3 geno-
types of EV71, coxsackievirus A16 and echovirus 9.
HCE had the highest activity against genotype A of
EV71. A plaque reduction assay showed that HCE sig-
nificantly reduced plaque formation. Viral protein ex-
pression, viral RNA synthesis and virus-induced caspase
3 activation were inhibited in the presence of HCE, sug-
gesting that it affected apoptotic processes in EV71-in-
fected Vero cells by inhibiting viral replication. The an-
tiviral activity of HCE was greater in cells pretreated
with extract than those treated after infection. Therefore,
it was concluded that HCE had antiviral activity, and it
offered a potential to develop a new anti-EV71 agent
[105].
5.4. Anticancer/Antitumour Effects
Some extracts and compounds from H. cordata and some
traditional Chinese medicine formulae containing H.
cordata were reported to have anticancer effect. A tradi-
tional Chinese medicine formulae containing H. cordata
was used for treating lung cancer and improving human
immunity. It had the advantages of good curative effect,
no obvious toxic or side effect, simple manufacturing
process, and low cost [106,107].
HCE treatment caused lowering of cell viability in
various human cancer cell lines [108], and administered
on the acupuncture point prevented the increase of mass
weight of melanoma BBL16 tumor cells inoculated into
mice [109]. The cellular effects of HCE and the signal
pathways of HCE-induced apoptosis in HL-60 human
promyelocytic leukemia cell line were investigated. HCE
treatment caused apoptosis of cells as evidenced by dis-
continuous fragmentation of DNA, the loss of mitochon-
drial membrane potential, release of mitochondrial cyto-
chrome c into the cytosol, activation of procaspase-9 and
caspase-3, and proteolytic cleavage of poly(ADP-ribose)
polymerase (PARP). Pretreatment of Ac-DEVD-CHO,
caspase-3 specific inhibitor, or cyclosporin A, a mito-
chondrial permeability transition inhibitor, completely
abolished HCE-induced DNA fragmentation. Together,
these results suggested that HCE possibly caused mito-
chondrial damage leading to cytochrome c release into
cytosol and activation of caspases resulting in PARP
cleavage and execution of apoptotic cell death in HL-60
cells [110]. The 100 µg/mL of methanolic extract of H.
cordata root showed significant protective effects (p <
0.01) against hydrogen peroxide-induced DNA damage
in HepG2 cells and increased cell viability against hy-
drogen peroxide. The study indicated that H. cordata
root methanol extract acted as a potential antioxidant,
and exhibited potential anticancer properties [111]. The
investigation examined the anticancer activity of the
methanol extract from H. cordata on ICR mouse with
induced abdominal cancer and L1210 cancer cells. To get
an insight into the reaction mechanism undelying the
anticancer activity, 2
O
ion quantity and antioxidant en-
zyme activities such as superoxide dismiutase (SOD) and
glutathione peroxidase (GPx) of L1210 cells in the pres-
ence of HCE were measured. The increased values of
SOD and GPx enzyme activities in addition to the aug-
mented generation of 2
O
ion in L1210 cells implied
that the reactive oxygen species including 2
O
ion
which were presumably induced by HCE might have
participated in the process of L1210 cells cytotoxicity
[112,113]. In another study, HCWE inhibited five leu-
kemic cell lines, namely L1210, U937, K562, Raji and
P3HR1, with IC50s between 478 µg/mL and 662 µg/mL.
It was proved to be a potential medicinal plant for treat-
ing leukemia [12].
In a study, forty-eight Sprague-Dawley rats were fed
with a diet containing 0%, 2% or 5% H. cordata powder
and 15% fresh soybean oil or 24-h oxidized frying oil
(OFO) for 28 days. The level of microsomal protein, total
cytochrome 450 content (CYP450) and enzyme activities
including NADPH reductase, ethoxyresorufin O-deeth-
hylase (EROD), pentoxyresorufin O-dealkylase (PROD),
aniline hydroxylase (ANH), aminopyrine demethylase
(AMD), and quinone reductase (QR) were determined.
The oxidized frying oil feeding produced a significant
increase in the content of CYP450, microsomal protein,
activities of NADPH reductase, EROD, PROD, ANH,
AMD and QR in rats (P < 0.05). In addition, the active-
ties of EROD, ANH and AMD decreased and QR in-
creased after feeding with H. cordata in OFO-fed group
(P < 0.05). The feeding with 2% H. cordata diet showed
Copyright © 2013 SciRes. CM
J. G. FU ET AL. 113
the most significant effect. The findings suggested that
polyphenol in H. cordata could be an important and nec-
essary factor in the defense against CYP450-mediated
cancers and other chronic diseases [114].
The anticancer activity of flavonoid extracts from H.
cordata was studied on Sarcoma-180. They exhibited
cytotoxic activity on S-180. The total flavonoid extract of
H. cordata gave highest rate of death and showed good
inhibitory effect on the growth of ascites tumor by S-180
in mice [37]. The inhibiting rate of flavonoids was de-
tected by MTT assay. The apoptosis of HL60 and B16-
BL6 was detected by FCM. Flavonoid from H. cordata
also inhibited HL60 and B16BL6 and induced cell apop-
tosis. The IC50 in HL60 and B16BL6 was 0.410 and
0.122 g/L respectively [115].
Furthermore, six alkaloids exhibited cytotoxicity against
five human tumor cell lines (A-549, SK-OV-3, SK-
MEL-2, XF-498 and HCT-15) in vitro, including aristo-
lactam B, piperolactam A, aristolactam A, norcepha-
radione B, cepharadione B and splendidine isolated by
bioactivity-guided fractionation of a methanolic extract.
Among them, splendidine exhibited the strongest cyto-
toxicity and aristolactam B selectively suppressed XF-
498 (ED50 = 0.84 μg/ml) [15].
5.5. Anti-Inflammatory Effects
Many kinds of extracts from H. cordata showed anti-
inflammatory activity. The inflammation induced by xy-
lene in the mice ear edema model was adopted to study
the anti-inflammatory activity of chloroform extract, wa-
ter extract, ethanol extract and n-butanol extract. All
forms showed good anti-inflammatory activity, and the
water extract had better pharmacological activity than
ethanol extract, while the extract of fresh H. cordata had
better pharmacological activity than that of dry one
[91,116].
Shuang-Qing-Cao (SQC), a folk Chinese medicinal
formula composed of Lonicera japonica Thunb (Caprifo-
liaceae), Isatis indigotica Fort (Cruciferae) and H. cor-
data, was used for treating diseases related with inflame-
mation in the folk of China. The results indicated that
SQC extract in β-cyclodextrin was greatly effective on an
experimental model of acute lung inflammation induced
by the intratracheal instillation of lipopolysaccharide
(LPS) in vivo [117]. 40 - 400 mg·kg1 of fresh HCE re-
duced the increase of LPS-induced leucocytes in bro-
choalveolar lavage fluid (BALF) in ICR mice, and alle-
viated the infiltration of inflammatory cells in pathologi-
cal lung tissue, which showed that fresh HCE inhibited
the LPS-induced lung inflammation [118].
A study investigated the effect of HCE on the migra-
tion of the human mast cell line, HMC-1, in response to
stem cell factor (SCF). Treatment with HCE at a concen-
tration of 10 µg/mL for 24 h showed no significant de-
crease in the survival rate of the HMC-1 cells. SCF
showed the typical bell-shape curve for the HMC-1 cell
chemoattraction with the peak of the curve at the SCF
concentration of 100 ng/mL. HC-1, which was the whole
plant extracted with 80% EtOH, and HC-3, which was
the residue successively partitioned with EtOAc, both
had inhibitory effects on HMC-1 cell movement. After
the treatment with 10 µg/mL HC-1 extract for 6 and 24 h,
the chemotactic index (CI) of HMC-1 cells decreased to
74% and 63%, respectively. HC-3 extract treatment for 6
and 24 h lowered the CI to 72% and 44%, respectively.
The HC-1 and HC-3 extracts had no inhibitory effect on
the mRNA and surface protein expressions of c-kit, SCF
receptor. SCF mediated the chemotaxis signaling via nu-
clear factor
B (NF-
B) activation, and both extracts
inhibited the activation. Therefore, the results indicated
that HC-1 and HC-3 extracts decreased the chemotactic
ability of HMC-1 cells in response to SCF by inhibiting
NF-
B activation, and these substances may be useful for
treating mast cell-induced inflammatory diseases [8].
Ethanol fraction was obtained from dried and powdered
whole plants of H. cordata. The residue was diluted with
water and was successively partitioned with n-hexane,
EtOAc and BuOH. H. cordata fractions (HcFs) inhibited
the expression of IL-4 and IL-5 in response to phorbol
12-myristate 13-acetate (PMA) and calcium ionophore
(CaI) in Jurkat T cells and the human mast cell line,
HMC-1. IL-4 and tumor necrosis factor-alpha (TNF-α)-
induced thymus and activationregulated chemokine
(TARC) production was blocked by HcFs in skin fibro-
blast CCD-986sk cells, particularly by the ethanol extract
of Hc. Stimulants included in PMA, phytohemagglutinin
(PHA) and CaI, increase the mRNA level of CC che-
mokine receptor 4 (CCR4), a receptor of TARC, in Jur-
kat T cells, and the ethanol extract of HcF weakly blocks
the increased mRNA level. The ethanol extract inhibited
TARC-induced migration, as well as basal migration of
Jurkat T cells. Recent studies showed the usefulness of
HcFs in the ethnopharmacological treatment of Th2-me-
diated or allergic inflammation, through the down-regu-
lation of the production of Th2 cytokines, TARCand cell
migration [119].
The effects of aqueous extract of H. cordata on the
production of the pro-inflammatory mediators, nitric ox-
ide (NO) and TNF-α were examined in an activated
macrophage-cell line; RAW 264.7. The aqueous extract
from H. cordata inhibited NO production in a dose-de-
pendent manner, but minimally (~30%) TNF-α secretion
at 0.0625 and 0.125 mg/mL [7]. Another study investi-
gated the effects of aqueous extract on passive cutaneous
anaphylaxis (PCA) in mice and on IgE-mediated allergic
response in rat mast RBL-2H3 cells. Oral administration
of aqueous extract inhibited IgE-mediated systemic PCA
in mice. It also reduced antigen (DNP-BSA)-induced re-
Copyright © 2013 SciRes. CM
J. G. FU ET AL.
114
lease of β-hexosaminidase, histamine, and reactive oxy-
gen species in IgE-sensitized RBL-2H3 cells. In addition,
it inhibited antigen-induced IL-4 and TNF-α production
and expression in IgE-sensitized RBL-2H3 cells. It in-
hibited antigen-induced activation of NF-
B and degra-
dation of IKB-α, and suppressed antigen-induced phos-
phorylation of Syk, Lyn, LAT, Gab2, and PLCγ2 and
phosphorylation of Akt and MAP kinases (ERK1/2 and
JNK1/2 but not p38 MAP kinase).
HCE showed remarkable COX inhibitory activity.
Phytochemical investigation of HCE has led to the isola-
tion of three aristolactams, two 4,5-dioxoaporphine de-
rivatives, and several pyridine and dihydropyridine de-
rived alkaloids. Finally it was found that unsaturaed fatty
acids, like oleic and linoleic acid, were responsible for
the high acitivity of the extract (IC50: 13, 4 and 0, 25 µM
respectively; indomethacin: 1, 15 µM) [120]. The anti-
inflammatory activities of quercitrin isolated from H.
cordata were evaluated in mice, rats, and guinea pigs.
Quercitrin (50, 100, and 200 mg/kg orally) inhibited the
rat hind paw edema induced by carrageenin, dextran,
histamine, serotonin, and bradykinin in a dose-dependent
manner; at 200 mg/kg this compound also inhibited the
scald edema induced by 54˚C hot water. Quercitrin did
not show any inhibition of the UV light-induced erythe-
ma in guinea-pigs and of the increase of vascular perme-
ability induced by acetic acid in mice. Quercitrin did not
affect the granuloma formation in a cotton pellet implant
and the development of adjuvant arthritis in rats. Quer-
citrin had an inhibitory effect on acute inflammation
[121].
HCI, an aqueous solution of the steam distillate from
plants of H. cordata, was used to treat ulcerative colitis
(UC). Forty-two first episode type UC patients were
randomly divided into HCI treatment group (n = 21) and
Sulfasalazine group (n = 21). Clinical effects were ob-
served in the 2 groups while ultrastructure of colonic
mucosa, ICAM-1 and the pressure of distant colon were
studied in HCI group. The clinical effect of HCI group
(complete remission in 20, 95.2%; improvement in 1,
4.8%) was better than that of Sulfasalazine group (com-
plete remission in 15, 72.4%, improvement in 5, 23.8%;
inefficiency in 1, 3.8%, P < 0.01). The time of stool fre-
quency recovering to normal (5.6 ± 3.3 d), and blood
stool disappearance (6.7 ± 3.8 d) and abdominal pain
disappearance (6.1 ± 3.5 d) in HCI group compared with
Sulfasalazine group (9.5 ± 4.9 d, 11.7 ± 6.1 d, 10.6 ± 5.3
d, P < 0.01). HCI inhibited the epithelial cell apoptosis of
colonic mucous membrane and the expression of ICAM-
1 (45.8 ± 5.7% vs 30.7 ± 4.1%, P < 0.05). Compared
with normal, the mean promotive speed of contraction
wave steped up (4.6 ± 1.6 cm/min vs 3.2 ± 1.8 cm/min, P
< 0.05) and the mean amplitude of the wave decreased
(14.2 ± 9.3 kPa vs 18.4 ± 8.0 kPa, P < 0.05) in active UC
patients. After treatment with HCI, these 2 indexes im-
proved significantly (17.3 ± 8.3 kPa, 3.7 ± 1.7 cm/min, P
< 0.05). In normal persons, the postprandial pressure of
sigmoid (2.9 ± 0.9 kPa) was higher than that of descend-
ing colon (2.0 ± 0.7 kPa) and splenic flexure (1.7 ± 0.6
kPa), while the colonic pressure (1.5 ± 0.5 kPa, 1.4 ± 0.6
kPa, 1.3 ± 0.6 kPa) decreased significantly (P<0.05) in
active UC patients. The pain threshold of distant colon
(67.3 ± 18.9 mL) in active UC patients decreased sig-
nificantly compared with normal persons (216.2 ± 40.8
mL, P < 0.05) and recovered to normal after treatment
with HCI (187.4 ± 27.2 mL, P < 0.05) [122]. Injection of
carrageenan into the pleural cavity elicited an acute in-
flammatory response characterized by protein rich fluid
accumulation and leukocyte infiltration in the pleural
cavity. The inflammatory responses including fluid vol-
ume, protein concentration, C-reactive protein and cell
infiltration reached peak after 24 h. The results showed
that these parameters were attenuated by HCI and touch-
ed bottom at dose of 0.54 mL/100g. The results clearly
indicated that HCI had anti-inflammatory activity [6].
The subsequent GC-MS analysis result indicated that
main effect compounds in HCIs were methyl n-nonyl
ketone, houttuynin, lauryl aldehyde, capryl aldehyde,
-
pinene,
-linalool, 1-nonanol, 4-terpineol, α-terpineol,
bornyl acetate, n-decanoic acid and acetic acid, geraniol
ester etc [123,124].
5.6. Antioxidative Effects
Chen [14] showed that both aqueous and methanolic ex-
tracts of H. cordata had antioxidant properties under
OFO feeding-induced oxidative stress on Sprague-Daw-
ley rats. The rats were fed diets containing 0%, 2%, or
5% H. cordata and 15% fresh or OFO for 28 days. The
levels of polyphenols in feces, blood plasma, and liver
were determined. The low-density lipoprotein (LDL) oxi-
dation lag time, plasma total antioxidant status (TAS),
and levels of thiobarbituric acid-reactive substances
(TBARS) were used as antioxidant indexes and the pro-
tein carbonyl groups were used as oxidative index. The
polyphenol levels decreased in blood plasma and in-
creased in feces when feeding OFO; the apparent absorp-
tion of polyphenols also decreased. The polyphenol lev-
els in plasma increased when feeding H. cordata. The
OFO-fed rats had higher plasma TBARS and hepatic
protein carbonyl group concentrations and shorter LDL
lag times than controls. The total TAS was elevated and
the LDL lag time was prolonged with H. cordata feed-
ing.
Ng [13] examined the antioxidant properties of H.
cordata and its protective effect on bleomycin-induced
pulmonary fibrosis in rats. Results showed that aqueous
extract of H. cordata exhibited a different magnitude of
antioxidant activities in all model systems tested. Al-
Copyright © 2013 SciRes. CM
J. G. FU ET AL. 115
though H. cordata showed weaker free radical scaveng-
ing and xanthine oxidase inhibitory activity than vitamin
E, its anti-lipid peroxidation activity in rat liver homo-
genate was close to that of vitamin E. In animal studies,
H. cordata significantly decreased the levels of superox-
ide dismutase, malondialdehyde, hydroxyproline, inter-
feron-γ, and TNF-α. However, an increase in the concen-
tration of catalase was noted in the bronchoalveolar lav-
age fluid. H. cordata also remarkably improved the mor-
phological appearance of the lung of bleomycin-treated
rats. This protective effect was more pronounced than
that of vitamin E. In Korea, the reactive oxygen radical
species (ROS) scavenging effects of 50 kinds of Korean
medicinal plant leaves were examined. H. cordata exhib-
ited over a 95% scavenging effect of superoxide anion in
1 ppm concentration of test solution. The correlation co-
efficient of total phenolic content with superoxide anion,
hydrogen peroxide, hydroxyl radical and DPPH radical
scavenging effects were 0.8111, 0.8057, 0.8809 and
0.9810, respectively [125]. Furthermore, the polyphenols
isolated from H. cordata, quercetin, quercetin-3-O-
-
D-galactoside, quercetin-3-O-α-L-rhamnoside and kaemp-
ferol-3-O-α-L-rhamnoside, exerted strong DPPH radical-
scavenging activity [126]. In addition, the antioxidative
activities of those medicinal plants and the compounds
were investigated using the thiocyanate method to evalu-
ate inhibitory effects on lipid peroxidation in the linoleic
acid system. The peroxide levels gradually increased
during incubation in the presence of linoleic acid over 3
days, and most of the plants inhibited lipid peroxidation.
The aerial part of H. cordata reduced lipid peroxidation
more effectively as lipid peroxidation progressed, result-
ing in inhibition of about 80% relative to the control
value by the 3rd day of incubation. The polyphenols iso-
lated from H. cordata, quercetin, quercetin-3-O-
-D-ga-
lactoside and quercetin-3-O-α-L-rhamnoside, also show-
ed marked and dose-dependent inhibitory effects on lipid
peroxidation. Moreover, quercetin glycosides showed
stronger activity than quercetin, suggesting that glycosy-
lation increased the antioxidative activity of quercetin
[127]. The antioxidative and anti-lipid peroxidative effi-
cacies of the fractions (H2O, 20% MeOH, 40% MeOH,
60% MeOH, 100% MeOH) from H. cordata were meas-
ured by DPPH method and TBARS assay on rat liver
homogenate. It was revealed that 60% MeOH fractions
had potential antioxidative activity and inhibited lipid
peroxidation significantly. The DNA damage was ana-
lyzed by tail moment (TM) and tail length (TL), which
used markers of DNA strand breaks in SCGE. The 100
µg/mL of methanolic extract of H. cordata root showed
significant protective effects (P < 0.01) against H2O2-in-
duced DNA damage in HepG2 cells and increased cell
viability against H2O2. The results of this study indicated
that H. cordata root methanol extract acted as a potential
antioxidant, and exhibited potential anticancer properties,
which might provide a clue to find applications in new
pharmaceuticals for oxidative stability. The free radical
scavenging capacities and antioxidant activities of H.
cordata were evaluated using commonly accepted as-
says, including xanthine-xanthine oxidase assay, linoleic
acid peroxidation and DPPH spectrophotometric assays,
rapid screening of antioxidant by dot-blot and DPPH
staining, TLC analysis with DPPH staining and DNA
strand scission by hydroxyl radicals. H. cordata was ex-
tracted with dichloromethane, methanol or ethanol, re-
spectively and selected for the best antioxidant results.
Each sample under assay condition showed a dose-de-
pendent free radical scavenging effect of DPPH and a
dose-dependent inhibitory effect of xanthine oxidase and
lipid peroxidation. They also showed a protective effect
on DNA damage caused by hydroxyl radicals generated
from UV-induced photolysis of hydrogen peroxide. A
rapid evaluation for antioxidants using TLC screening
and DPPH staining methods demonstrated each extract
having various free radical scavenging capacity. Stained
silica layer revealed a purple background with yellow
spots at the location of drops, which showed radical sca-
venging capacity [138].
5.7. Antidiabetic Effects
The essential oils from H. cordata has been shown to
have an effect on improving fat metabolism, the urinary
albumin and insulin resistance of diabetes mellitus rats
[128,129]. The rat model of diabetes mellitus was in-
duced with streptozotocin (STZ) and high glucose-li-
poids animal feeds, treated with H. cordata for 8 weeks.
After treatment, fasting insulin level was lower in H.
cordata group than in control, rosiglitazone and losartan
group (P < 0.05). Insulin sensitivity index increased in H.
cordata group and rosiglitazone group (P < 0.05 com-
pared with the losartan group). The urinary albumin and
24 h urine volume were the lowest in H. cordata group
(P < 0.05). The concentration of triglyceride in serum
was lower in H. cordata and rosiglitazone group than
that in control group (P < 0.05). H. cordata had a protec-
tive effect on the renal tissues in diabetic rats, which was
probably correlated with the decrease of the expression
of transforming growth factor-
1 and collagen I and with
the increase of the expression of bone morphogenetic
protein-7 in the renal tissues [130,131].
5.8. Anti-Allergic Effects
Human basophilic KU812F cells express a high-affinity
immunoglobulin (Ig) E receptor, FcεRI, which plays an
important role in IgE-mediated allergic reactions. Flow
cytometric analysis showed that the FcεRI expression
and the IgE binding activity were suppressed when the
Copyright © 2013 SciRes. CM
J. G. FU ET AL.
116
cells were cultured with HCE. Reverse transcription-
polymerase chain reaction analysis showed that levels of
the mRNAs for FcεRIα- and γ-chains were decreased by
the treatment of HCE. Addition of HCE to culture me-
dium also resulted in a reduction in the release of hista-
mine from the cells. These results suggested that HCE
may exert its anti-allergic activity through down-regula-
tion of FcεRI expression and a subsequent decrease in
histamine release [17]. Oral administration of HCWE
inhibited compound 48/80-induced systemic anaphylaxis
in mice. HCWE also inhibited the local allergic reaction,
PCA, activated by anti-dinitrophenyl (DNP) IgE anti-
body in rats. HCWE reduced the compound 48/80-in-
duced mast cell degranulation and colchicine-induced de-
formation of rat peritoneal mast cells (RPMC). More-
over, HCWE dose-dependently inhibited histamine re-
lease and calcium uptake of RPMC induced by com-
pound 48/80 or anti-DNP IgE. Another study investi-
gated the effects of HCWE on PCA in mice and on IgE-
mediated allergic response in rat mast RBL-2H3 cells.
Oral administration of HCWE inhibited IgE-mediated
systemic PCA in mice, and reduced antigen (DNP-BSA)-
induced release of
-hexosaminidase, histamine, and re-
active oxygen species in IgE-sensitized RBL-2H3 cells.
In addition, HCWE inhibited antigen-induced IL-4 and
TNF-α production and expression in IgE-sensitized RBL-
2H3 cells. HCWE inhibited antigen-induced activation of
NF-
B and degradation of I
B-α. To investigate the in-
hibitory mechanism of HCWE on degranulation and cy-
tokine production, the activation of intracellular FcεRI
signaling molecules were examined. HCWE suppressed
antigen-induced phosphorylation of Syk, Lyn, LAT,
Gab2, and PLC γ2, further downstream, inhibited anti-
gen-induced phosphorylation of Akt and MAP kinases
(ERK1/2 and JNK1/2 but not p38 MAP kinase).
5.9. Antimutagenic Effects
The antimutagenic effects of both aqueous and methano-
lic extracts of H. cordata were examined using the Ames
test. They had dose-dependent antimutagenic effects on
benzo(a)pyrene, aflatoxin B1, and OFO, and the anti-
mutagenic ability of aqueous extracts was higher than of
methanolic extracts [14]. The inhibitory actions of chlo-
roform extracts from H. cardata on the mutagenicity of
Trp-P-2 and 1-NP was examined [132]. Inhibitory action
was clarified on the following three points: 1) extract had
the repressive effect on the two kinds of mutagenic sub-
stances which were composed of the indirect mutagen
(Trp-P-2) requiring metabolic activation with S-9mix and
of the direct mutagen (1-NP), 2) extract had the repres-
sive effect on Trp-P-2 (NHOH), an activated form of
Trp-P-2, and 3) extract had the represssive effect on
metabolic process of Trp-P-2 with S-9mix. These results
suggested that the antimutagens in chloroform extracts
had wide mechanism of repression.
5.10. Others
Two compounds, cis- and trans-N-(4-hydroxystyryl)
benzamide, were isolated from the CHCl3 extract of H.
cordata, and proved to be potent inhibitors of platelet
aggregation [78]. The injection and aqueous extract of H.
cordata were illustrated to enhance immune function by
modulating ex vivo pro-inflammatory cytokine and NO
production as well as the expression of iNOS and COX-2
[133,134]. Effects of H. cordata extracts on the level of
lipid peroxide and the enzyme activities of the liver were
investigated in bromobenzene-induced rats. Lipid perox-
ide content in liver was increased by bromobenzene. It
was decreased when the methanol extract of H. cordata
was given to the rat. The methanol extract reduced the
activities of aminopyrine N-demethylase and aniline hy-
droxylase that increased by bromobenzene, however did
not affect glutathione S-transferase activity. The metha-
nol extract recovered the activity of epoxide hydrolase
activity that decreased significantly by bromobenzene. It
was suggest that the extract might play an important play
in the prevention of hepatotoxicity by reduction of ami-
nopyrine N-demethylase and aniline hydroxylase activi-
ties as well as enhancement of epoxide hydrolase activity
[75].
6. Quality Control
During our market surveillance, H. cordata has been sold
in medicinal materials, tablet, injection, formula, grain,
capsule and oral liquid, either presenting as single herb
or as collections of herbs. However, like most of tradi-
tional herbal medicines and their preparations, despite its
existence and continued use over many centuries, and its
popularity and extensive use during the last decade, the
quantity and quality of the safety and efficacy data are
far from sufficient to meet the criteria needed to support
its use world-wide. During the past several decades, with
the extensive herbal treatment, adverse drug reactions
accompany. HCI, the extract of sterile volatile oils from
distillation of fresh H. cordata with a milliliter equivalent
to 2 g of herbal materials, was reported a substantial in-
cidence of life threatening anaphylaxis. The Chinese Na-
tional Adverse Reaction Monitoring Center reports over
5000 adverse reactions to HCI from January 1988 to
April 2006 including 222 serious cases [135]. The State
Food and Drug Administration of China (SFDA) halted
the use of HCI in hospitals in June 2006. Later, Lei and
co-worker found that polysorbate-80, one of supplemen-
tary material in the injection caused serious adverse reac-
tions in dogs with intravenous drip of HCI, when the
concentration of polysorbate-80 was greater than 0.01
mg/ml. The distillate without polysorbate-80 showed no
Copyright © 2013 SciRes. CM
J. G. FU ET AL. 117
adverse reaction. This revealed that the adverse reactions
of this injection may cause by supplementary material,
not by the raw material herb [136,137]. Then, after re-
examining HCI manufacturing conditions and quality
control, the SFDA gave permission to few manufacturers
to recommence HCI production. An allergen-warning
label was requested to be added to the product.
As metioned above, H. cordata herb contains dozens
of components. However, only one or two markers or
pharmacologically active components is currently em-
ployed for evaluating the quality and authenticity, iden-
tifying the single herb or herb medicine preparations. The
quality of HCI is assured based on the content of methyl
n-nonyl ketone, whose content is set to the least 1.0
µg/ml injection. The quality of “fufang yuxingcao” tablet
is assured based on the content of baicalin, whose con-
tent is set to the least 2.7 mg per tablet [138]. This stan-
dard is neither sufficient to determine the identity of an
extracted plant material nor to ensure the quality of pro-
ducts. The chemical constituents in H. cordata vary de-
pending on harvest seasons, plant origins, drying proc-
esses and other factors. Thus, it is necessary to develop
accepted guideline for evaluating traditional medicine
[139] and for determining most of the phytochemical
constituents of herbal products in order to ensure the re-
liability and repeatability of pharmacological and clini-
cal research, to understand their bioactivities and possi-
ble side effects of active compounds and to enhance pro-
duct quality control [140].
The concept of phytoequivalence is developed in
Germany in order to ensure consistency of herbal prod-
ucts [141]. According to this concept, a chemical profile
concept, such as a fingerprint, is developed and proposed
for standardizing medicinal products manufactured from
herb medicines and their raw materials. In 2004, the Chi-
nese State Food and Drug Administration (SFDA) regu-
lated the compositions of liquid injection with herb
medicine ingredients, using stringent quality procedures
such as chemical assay and standardization. Fingerprints
of herb medicine liquid injections are compulsorily car-
ried out for this purpose. Comparing with conventional
method focusing mainly on the determination of a certain
active compound, fingerprinting can offer integral char-
acterization of a complex system with a quantitative de-
gree of reliability. The method for authentication and
quality assessment of herb medicine has recently been
accepted by the World Health Organization (WHO) as a
strategy for the assessment of herbal medicines [142].
Under such circumstances, China Pharmacopoeia Com-
mittee organizes several scientific research institutions
including our group, Research center for modernization
of Chinese herbal medicine, college of chemistry and
chemical engineering, Central south university, to estab-
lish the fingerprint of 70 traditional Chinese medicine
injections and the technology platforms.
7. Conclusions
Throughout our literature review, many modern chemi-
cal, physical and biological methods are applied for the
investigation of H. cordata. Despite the great progress,
there are still some key tasks to do:
1) Find actual bioactive components. As mentioned
above, the chemical composition of this herb is complex
and diverse. Essential oil, alkaloids, flavonoids and other
polyphenols are studied frequently in this species. The
remaining chemical compounds are not well studied.
Most of the mentioned studies focus on crude prepara-
tions of H. cordata, and the chemical profiles are not
well detailed or standardized. There is a scarcity of de-
tailed isolation studies works published. We believe that
the isolation of new active principles for drug discovery
from individual perspective, and establishment of detail
chemical profiles for standardized extracts from holistic
perspective would be of great scientific merit.
2) Understand the mechanism. Despite the extensive
past and present traditional uses, and recent progress in
pharmacological studies, biological data to correlate the
ethnobotany to the chemistry are still lacking. In addition
to recognized antibacterial ingredients such as decanoyl
acetaldehyde and undecanone, some non-volatile com-
ponents such as flavonoids, alkaloids and water-soluble
polysaccharide have been found to have strong pharma-
cological activities gradually. Many studies on the phar-
macological effects of H. cordata are reported, but the
anti-inflammatory effects and immune mechanism are
not clear, which are more important. The quantification
of individual phytoconstituents and pharmacological pro-
file of extracts based on in vitro, in vivo studies and on
clinical trials are urgently needed in order to confirm
traditional wisdom in the light of rational phytotherapy.
3) Find new ways. It is very difficult to find how the
mixtures of ingredients act in concert, partly due to the
complexity of H. cordata but also due to the lack of ap-
propriate approaches within research of complex herbal
mixtures. Recent arisen technologies, such as proteomics
and metabolomics, offer additional complementary ap-
proaches and provide a deeper and holistic insight in
systems biology. They are addressed as promising tools
to investigate herb medicines [143].
4) Establish effective quality control methods. Allergic
compounds in the product HCI are not entirely clear.
And the current Chinese Pharmacopoeia only provides
TLC distinction of undecanone for this herb [144]. The
comprehensive and effective quality control methods for
complex active ingredients of this herb are lack.
Although HCI has been halted, there is no doubt about
the efficacy of this herb. This herb, particularly its oral
formulations, has high value and broad application pros-
Copyright © 2013 SciRes. CM
J. G. FU ET AL.
118
pects. Therefore, in order to better development and uti-
lization of this herb, it is urgent to use modern technol-
ogy to clarify the material basis of its efficacy and me-
chanism, improve the quality control standards, and ex-
pand the clinical use for traditional efficacy and phar-
macological effect. The collected information reviewed
here provides a resource for future ethnopharmacological
and phytochemical studies of the genus. The scientific
validation for the popular use of H. cordata deserves
more investigations.
8. Acknowledgements
The authors would like to thank National Natural Science
Foundation of China for support of the projects (No.
20975115, 21175157 and 21375151), China Hunan Pro-
vincial science and technology department for support of
the project (No. 2012FJ4139), Central South University
for special support of the basic scientific research project
(No. 2010QZZD007), China Postdoctoral Science Foun-
dation for support of the project (No. 201104511).
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... Houttuynia cordata Thunb., belonging to Saururaceae, is a medicinal and edible perennial herb native to China, Japan, and Taiwan [1]. H. cordata is rich in nutrients and contains a variety of vitamins, amino acids, and trace elements, such as zinc, potassium, and copper [2]. ...
... Essential oils were utilized in pharmaceutical and other related medical, and the amount of published evidence on aromatherapy and essential oils has gradually increased [10,11]. The essential oil components of H. cordata include decanoyl acetaldehyde, 2-undecanone, β-myrcene, decanal, and trans-caryophyllene [1]. Because the essential oil compounds of H. cordata will affect its pharmacological effects, analyses of the volatile components are also used to determine plant quality [12]. ...
... 2-undecanone, β-myrcene, decanal, and trans-caryophyllene [1]. Because the essential oil compounds of H. cordata will affect its pharmacological effects, analyses of the volatile components are also used to determine plant quality [12]. ...
Article
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Houttuynia cordata Thunb. is a medicinal and edible plant that has been commonly used in traditional Chinese medicine since ancient times. This study used headspace solid-phase microextraction (HS-SPME) and direct injection, combined with gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS), to identify the volatile compounds in H. cordata. Extraction from different parts of the plant using different extraction techniques for the identification of volatile compounds were determined. A total of 93 volatile components were analyzed in the leaves, stems, rhizomes, and whole plant samples of H. cordata. The leaves contained more (Z)-3-hexenal, β-myrcene, (Z)-β-ocimene, and (4E,6E)-allo-ocimene; the stems contained more geranyl acetate and nerolidol; and rhizomes contained more α-pinene, β-pinene, limonene, 2-undecanone, and decanoyl acetaldehyde. Among them, the essential oil extracted by HS-SPME could produce more monoterpenes, while direct injection could obtain higher contents of aliphatic ketones, terpene esters, sesquiterpenes, and was more conducive to the extraction of 2-undecanone and decanoyl acetaldehyde.
... In India, it is harvested as a medicine and daily food [8]. A significant amount of scientific evidence shows that H. cordata, as a whole plant or in the form of its extracts, has important medicinal effects [9]. Recently, several studies showed and unveiled its anti-allergic [10,11], anti-inflammatory [12,13], anti-viral [14], anti-oxidative [15], anti-leukemic [16], anti-cancer [17], and anti-SARS [18] activities. ...
... [12,33] Alcohols Anti-viral activities and anti-inflammatory activities. [12,30,33] Flavonoids Quercetin Inflammatory mediator, anti-viral [9,35] Quercitrin Anti-inflamatory [36] Hyperin Anti-viral, anti-inflamatory [9,37] Rutin Inhibition of cholestasis [9,38] Afzelin Lower inflamatory cytokines [28,39] Kaempferol Anti-inflamatory [9] Isoquercitrin Anti-inflamatory [9] Alkaloids (Alkaloids) ...
... [12,33] Alcohols Anti-viral activities and anti-inflammatory activities. [12,30,33] Flavonoids Quercetin Inflammatory mediator, anti-viral [9,35] Quercitrin Anti-inflamatory [36] Hyperin Anti-viral, anti-inflamatory [9,37] Rutin Inhibition of cholestasis [9,38] Afzelin Lower inflamatory cytokines [28,39] Kaempferol Anti-inflamatory [9] Isoquercitrin Anti-inflamatory [9] Alkaloids (Alkaloids) ...
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Houttuynia cordata Thunb (H. cordata) is a rhizomatous, herbaceous, and perennial plant widely distributed in Asia. It has multiple chemical constituents, such as alkaloids, essential oils, phenolic acids, and flavonoids used against various health problems. The essential oils and flavonoids are the main components of H. cordata that play an essential role in disease treatment and traditional health care. Moreover, the leaves and stems of H. cordata have a long medicinal history in China. In addition, H. cordata is used against several health issues, such as cold, cough, fever, pneumonia, mumps, and tumors, due to its anti-inflammatory, anti-bacterial, anti-viral, anti-oxidant, and anti-tumor effects. It protects organs due to its anti-inflammatory activity. H. cordata regulates immunity by enhancing immune barriers of the oral cavity, vagina, and gastrointestinal tract, and shows broad-spectrum activity against liver, lung, breast, and colon tumors. However, there are some gaps to be filled to understand its pathways and mechanisms. Mechanisms such as its interaction with cells, cell membranes, and various drugs are important. Studies in relation to the blood–brain barrier, lipophilicity, cAMP signaling, and skin permeability, including pharmaceutical effects, will be very useful. This review includes the biological and pharmacological activities of H. cordata based on up-to-date research.
... Houttuynia cordata Thunb (HCT) is a well-known traditional Chinese medicinal and edible herb, which possesses a variety of pharmacological activities including diuretic, anti-microbial, anti-viral, anti-diabetic, anti-inflammatory, anti-oxidative, anti-mutagenic and anti-cancer properties [1,2]. It has shown therapeutic effect on many diseases including inflammation, pneumonia, severe acute respiratory syndrome (SARS), covid-19/SARS-CoV-2 [3,4], muscular sprain, cancer, obesity, stomach ulcer and cancer [1][2]5]. ...
... Houttuynia cordata Thunb (HCT) is a well-known traditional Chinese medicinal and edible herb, which possesses a variety of pharmacological activities including diuretic, anti-microbial, anti-viral, anti-diabetic, anti-inflammatory, anti-oxidative, anti-mutagenic and anti-cancer properties [1,2]. It has shown therapeutic effect on many diseases including inflammation, pneumonia, severe acute respiratory syndrome (SARS), covid-19/SARS-CoV-2 [3,4], muscular sprain, cancer, obesity, stomach ulcer and cancer [1][2]5]. HCT has inhibitory effects on cell growth of colon cancer [6], gastric cancer [7], melanoma [8], hepatocellular carcinoma [9], breast cancer [10], colorectal cancer [11], lung cancer [12] and leukemia in vitro [13]. ...
... HCT possesses anti-inflammatory activity [1,2], and it can reduce inflammatory cell infiltration in different animal inflammation models [33,34]. HCT treatment reverses oxaliplatin-induced neuropathic pain in the rat by regulating Th17/Treg balance [43]. ...
... It has been traditionally used as a therapeutic plant in folk medicine during the last century, and its phytochemical ingredients (such as essential oils, alkaloids, organic acids, fatty acids, sterols, amino acids, and microelements) are used in some pharmaceutical formulas. It has been applied to treat various diseases because of its pharmacological functions, such as diuretic, anti-microbial, anti-viral, anti-cancer/anti-tumor, anti-inflammatory, anti-oxidative, anti-diabetic, anti-allergic, and anti-mutagenic effects [16][17][18][19][20][21]. ...
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Houttuynia cordata Thunb., called Yuxingcao in Chinese, is an important medicinal plant and vegetable consumed in the southern regions of China. This review aims to summarize studies on the phyto-physiological chemistry, cytology, molecular biology, and genomics of H. cordata. Studies on the physiology and biochemistry of H. cordata have grown over the past few decades. Phenotypic and agronomic traits, tissue culture, elemental analysis, photosynthetic studies, bioactive compound identification, and antioxidant research have been reported. Molecular biological studies, such as those of molecular markers, microRNAs, DNA variations, protein variations, and transcriptomes have also advanced. Recent studies have focused on the rDNA and chloroplast genome of this plant. This review could serve as a basis to perform the genetic breeding, genomic advance, and cultivation of this valuable diversified plant resource for medicinal applications and vegetable production.
... Most of these genes are associated with inflammation, hypoxia, and angiogenesis [50]. This result aligned with the findings of previous studies of HC extract and confirmed that HC can down-regulate specific inflammatory mediators, such as TNF-α, IL6, prostaglandin E2 (PGE2), and nitric oxide (NO) production in the cells, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) expression [7]. ...
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Used in Asian countries, including China, Japan, and Thailand, Houttuynia cordata Thumb (H. cordata; Saururaceae, HC) is a traditional herbal medicine that possesses favorable antiviral properties. As a potent folk therapy used to treat pulmonary infections, further research is required to fully elucidate the mechanisms of its pharmacological activities and explore its therapeutic potential for treating pneumonia caused by SARS-CoV-2. This study explores the pharmacological mechanism of HC on pneumonia using a network pharmacological approach combined with reprocessing expression profiling by high-throughput sequencing to demonstrate the therapeutic mechanisms of HC for treating pneumonia at a systemic level. The integration of these analyses suggested that target factors are involved in four signaling pathways, including PI3K-Akt, Jak-STAT, MAPK, and NF-kB. Molecular docking and molecular dynamics simulation were applied to verify these results, indicating a stable combination between four metabolites (Afzelin, Apigenin, Kaempferol, Quercetin) and six targets (DPP4, ELANE, HSP90AA1, IL6, MAPK1, SERPINE1). These natural metabolites have also been reported to bind with ACE2 and 3CLpro of SARS-CoV-2, respectively. The data suggest that HC exerts collective therapeutic effects against pneumonia caused by SARS-CoV-2 and provides a theoretical basis for further study of the active drug-like ingredients and mechanism of HC in treating pneumonia.
... 37 Some reports have revealed that HC contains sundry active constituents such as EOs, avonoids, alkaloids, organic and fatty acids, sterols and microelements, which possess diverse pharmacological activities including diuretic, antibacterial, antiviral, antitumor, anti-inammatory, antioxidative, anti-diabetic, anti-allergic, and anti-mutagenic effects. 38,39 A large number of reports have conrmed that the antimicrobial effect of HC primarily comes from EOs which show a signicant inhibitory effect on SARS coronavirus, HSV, Bacillus cereus, Bacillus subtilis (B. subtilis), Staphylococcus aureus, Vibrio parahaemolyticus, Penicillium, Aspergillus niger, and so on. ...
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This study aims to develop an antibacterial agent that can be used for food packaging. Essential oils of Houttuynia cordata Thunb., a well-known medical herb, were extracted by two methods: multi-solvent consecutive extraction method and single ethanol extraction with a pre-heating method. Consequently, the extract obtained by the single ethanol extraction with a pre-heating method was more satisfactory from the operational and economic aspects. Afterwards, one of the encapsulation techniques: co-precipitation method using β-cyclodextrins as wall materials, was applied to form capsules for the protection of the obtained extract. After the capsule synthesis, the results of scanning electron micrographs and X-ray diffraction showed β-cyclodextrin crystallites in the form of thinner plates became oriented upon co-precipitation. Combining the results of Fourier transform-infrared spectra and an antibacterial assay using Bacillus subtilis as an object microorganism, the extract was confirmed to be successfully encapsulated within hollow cavities of β-cyclodextrins. A significant inhibitory activity on the growth and breeding of Bacillus subtilis was observed after the addition of fabricated capsules, which suggests the capsules containing the Houttuynia cordata Thunb. extract can be used as eco-friendly antibacterial agents for food packaging.
Article
The purpose of this study was to reveal the antibacterial components of Houttuynia cordata Thunb. crude extract (HCCE), analyze the antibacterial activity and mechanism of HCCE against Cronobacter sakazakii, and evaluate the bactericidal effect of HCCE as a natural disinfectant. Using an ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-QE-MS) non-target metabolomics technology, 15 kinds oforganic acids (18.65%), 14 kinds of phenols (16.17%), 10 kinds of flavonoids (12.32%), 5 kinds of terpenoids (5.87%), 3 kinds of alkaloids (1.62%), and 3 kinds of aldehydes (1.28%) were detected from HCCE. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of HCCE against C. sakazakii were 7.5 mg/mL and 15 mg/mL, respectively, and when the concentration was 2 MIC, C. sakazakii stagnated in sluggish phase. C. sakazakii exposed to HCCE showed hyperpolarization of cell membrane, increased intracellular ROS content, decreased protein and DNA content, impaired cell membrane integrity, improved cell membrane permeability, cell fluid leakage, and partial cell fragmentation. After treatments with 1 MIC and 2 MIC of HCCE for 5 min, C. sakazakii strains on 8 contact surfaces including stainless steel, tinplate, glass, polystyrene, bamboo, plank, ceramic, and tin foil paper were significantly inhibited (P < 0.05), and the reduction amounts ranged from 3.00 to 3.68 log CFU/100 cm2 and 3.97 to 4.53 log CFU/100 cm2, respectively. These findings demonstrate the potential of HCCE as a natural disinfectant and provide a new idea to reduce the C. sakazakii contamination caused by surface contact.
Article
Houttuynia, a widely used crude drug, is the dried stems and leaves of Houttuynia cordata Thunb. (family Saururaceae) collected during the flowering season. The crude drug has been used from olden times as diuretic and the leaves have been found to contain quercitrin. Studies were carried out to determine the suitability of the collecting season. The floral spike and fruit spike were collected separately from both of which isoquercitrin, and not quercitrin, was confirmed. The leaves contained quercitrin but not isoquercitrin. Both quercitrin and isoquercitrin are 3′, 4′-dihydroxyflavonol and possess mild laxative and diuretic action. According to Ozawa, this compound also possesses rutin-like action. It follows, therefore, that if the terrestrial plant is collected during the flowering season, the additive pharmacological action of the two chemicals could be expected.