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

January 2013
Chinese Medicine 04(03):101-123

January 2013
04(03):101-123

DOI:10.4236/cm.2013.43015

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CC BY 4.0

Authors:

Hongmei Lu

Central South University

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.

The increasing trend of the research work about H. cordata (The data was collected from Scifinder database).

…

Houttuynia cordata Thunb.

…

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Available via license: CC BY 4.0

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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

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; giấp 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.

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-(1→6)-β-D-glucopyranoside], quercetin

J. G. FU ET AL.

103

1920 1930 1940 1950 1960 1970 1980 1990 2000 2010

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].

J. G. FU ET AL.

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]

Kaempferol

3-O-[α-L-rhamnopyranosyl-(1→6)-

β-D-glucopyranoside]

Flavonoids* E, L, R, S [56,71]

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

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

J. G. FU ET AL. 107

O O

OH O

O O

(a) (b) (c)

OCH

CH3

CH3CH3

CH3

(d) (e) (f)

HO OH

COOH

(g) (h) (i)

OOH

OCH

OOO

OCH

(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-(1→6)-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.

J. G. FU ET AL.

108

Table 4. Alkaloids from H. cordata.

Number Compounds Structures References

1 Aristolactam A

OCH

[15,85,120,153]

2 Aristolactam B

OCH

[15,16,74,79,85,120,153]

3 Piperolactam A

[15,16,74,85,120,153]

4 3,4-Dimethoxy-N-methyl

aristolactam

H3CO

CH3

[85]

5 Lysicamine

OCH

[85]

6 Noraritolodione

[85]

7 Norcepharadione B

OCH

[15,85,120,153]

J. G. FU ET AL. 109

Contimued

8 Cepharadione B

OCH

[15,61,79,85,153]

9 Splendidine

OCH

[15,85]

10 3,5-Didecanoylpyridine

(CH

)

(CH

)

OCH

[16,79,154]

11 2-Nonyl-5-decanoylpyridine

C(CH

)

(CH

)

[16,79,131,154]

12 3,5-Didecanoyl-4-nonyl-1,

4-dihydropyridine

(CH2)8

(CH2)8(CH2)8CH3

H3C

CH3

[16,154]

13 3-Decanoyl-4-nonyl-5-dodecan

oyl-1,4-dihydropyridine

(CH

)

(CH

)

(CH

)

[16,154]

14 3,5-Didodecanoyl-4-nonyl-1,

4-dihydropyridine

(CH2)8

(CH2)10 (CH2)10 CH3

H3C

CH3

[16,154]

J. G. FU ET AL.

110

Contimued

15 7-chloro-6-

demethylcepharadione B

OCH

[79,153]

16 3-Nonylpyrazole

HN (CH

)

[96]

17 N-methyl-5-methoxy-

pyrrolidin-2-one

NOCH

[80]

18 cis-N-(4-Hydroxystyryl)

benzamide

[78]

19 trans-N-(4-Hydroxystyryl)

benzamide

HO O

[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 × 10−3 to 4.0 × 10−3 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

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



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



ion in L1210 cells implied

that the reactive oxygen species including 2



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

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·kg−1 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-

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-

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

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

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-

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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Quality evaluation and identification of Houttuynia cordata bleached with sodium metabisulfite based on whole spectrum metabolomics

Article

Full-text available

May 2024

Houttuynia Cordata (HC) is a widely distributed plant in Asia and is used extensively for both food and medicinal purposes. A preliminary investigation found that HC is often bleached with sodium metabisulfite solution during its field processing, leading to health risks. In this study, the effects of sodium metabisulfite on the quality of HC were comprehensively evaluated using volatile and non-volatile targeted metabolomic methods. The results revealed a positive correlation between the extent of chemical composition changes and the bleaching time. These notable changes mainly occurred at the initial stage of bleaching. Subsequently, an untargeted UPLC/Q-TOF MS method was used to explore the potential chemical bleaching markers in bleached HC. The marker 1-hydroxy-3-oxodecane-1-sulfonic acid was subsequently prepared, isolated, and identified. Market sample verification further validated the accuracy and effectiveness of this marker.

Antibacterial Activity Of Clay Mask From Houttuynia Cordata Leaves Extract Against Staphylococcus Aureus

Article

Apr 2024

Muhammad Ryan Radix Rahardhian

Facial skin that often looks dull and not glowing can be caused by the accumulation of dead skin cells. The solution to this problem is to exfoliate using a scrub. The content of secondary metabolites in Amis-amisan leaves (Houttuynia cordata Thunb) has antibacterial activity. This study aimed to determine the antibacterial activity of the face scrub ethanol extract of amis-amisan leaves against Staphylococcus aureus. The extract was obtained using the remaceration method using 96% ethanol. Concentrations of face scrub are 10%, 20%, and 30%. Antibacterial activity using the pour plate method. The results antibacterial activity of face scrub with concentrations of 10%, 20%, and 30% are 1.127 cm, 1.282 cm and 1.460 cm, respectively. The best antibacterial activity is a 30% concentration face scrub. The physical characteristics of the organoleptic, homogeneity, pH, spreadability, adhesion, and irritation tests of the face scrub meet the specified requirements.

Quality and production enhancement of fish mint, Houttuynia cordata Thunb., cultivated in a hydroponic planting system with designed plant growth-promoting additives

Article

Full-text available

Mar 2024

Fish mint, Houttuynia cordata Thunb. (HCT) is an edible vegetable that has also been used in traditional folk medicines. As both a medicinal herb and a dietary source, HCT has been clinically proven to be a pivotal ingredient in formulas administered to alleviate COVID-19 symptoms. With the increasing market demand for imported materials, ensuring the quality consistency of HCT becomes a significant concern. In this study, the growing time for hydroponically-cultivated HCT with seaweed extract and amino acids added (HCTW) reduced by half compared to conventional soil-cultivated HCT (HCTS). Key quantified components in HCTW, flavonoid glycosides and caffeoylquinic acid derivatives, exhibited a 143% increase over HCTS. These crucial constituents were responsible for possessing antioxidant activity (IC50 < 25 μg/mL) and anti-nitrite oxide production (IC50 < 20 μg/mL). An economically-designed hydroponic system with appropriate additives is proposed to replace HCTS with improvements of growth time, overall production yields, and bioactive qualities.

Endophytic Pseudomonas fluorescens promotes changes in the phenotype and secondary metabolite profile of Houttuynia cordata Thunb

Article

Full-text available

Jan 2024

The interactions between microbes and plants are governed by complex chemical signals, which can forcefully affect plant growth and development. Here, to understand how microbes influence Houttuynia cordata Thunb. plant growth and its secondary metabolite through chemical signals, we established the interaction between single bacteria and a plant. We inoculated H. cordata seedlings with bacteria isolated from their roots. The results showed that the total fresh weight, the total dry weight, and the number of lateral roots per seedling in the P. fluorescens-inoculated seedlings were 174%, 172% and 227% higher than in the control seedlings. Pseudomonas fluorescens had a significant promotional effect of the volatile contents compared to control, with β-myrcene increasing by 192%, 2-undecanone by 203%, decanol by 304%, β-caryophyllene by 197%, α-pinene by 281%, bornyl acetate by 157%, γ-terpinene by 239% and 3-tetradecane by 328% in P. fluorescens-inoculated H. cordata seedlings. the contents of chlorogenic acid, rutin, quercitin, and afzelin were 284%, 154%, 137%, and 213% higher than in control seedlings, respectively. Our study provided basic data to assess the linkages between endophytic bacteria, plant phenotype and metabolites of H. cordata to provide an insight into P. fluorescens use as biological fertilizer, promoting the synthesis of medicinal plant compounds.

Study on medicinal food plants in the Gaoligongshan Biosphere Reserve, the richest biocultural diversity center in China

Article

Full-text available

Jan 2024

Background Traditional knowledge associated with medicinal food plants (MFPs) plays a vital role in fighting hidden hunger and safeguarding the health of local people. MFPs resources are abundant in the Gaoligongshan area, a biosphere reserve with the richest biocultural diversity in China. Local people of different linguistic groups also have rich traditional botanical knowledge. However, there are still few comprehensive and systematic studies on MFPs there. Methods Ethnobotanical investigation including market survey, semi-structured interviews, free listing and key informant interviews was conducted in the Gaoligongshan area, Western Yunnan, Southwest China. A total of 13 local farmers’ markets were selected and information about medicinal food plants, including food categories, medicinal and edible parts, modes of consumption, medicinal effects, and distribution were collected. The relative occurrence frequency (RFO) and cultural food significance index (CFSI) were calculated to identify the culturally significant MFPs. Results A total of 184 species of MFPs, belonging to 83 families, were collected in the Gaoligongshan area, including vegetables (77), medicinal diets (26), fruits (25), spices (18), herbal tea (13), tea substitutes (11), substitutes for staple food (8), nuts (5), oils and fats (4), and dye material (1). The most frequently used families were Fabaceae, Asteraceae and Apiaceae, with 11, 10, and 9 species, respectively. The most frequently used plant parts were the stems, followed by fruits and leaves. Based on the evaluation results of the CFSI and RFO indices, 18 species of MFPs with magnificent local cultural importance have been screened out, such as Houttuynia cordata, Eryngium foetidum, Sechium edule, Centella asiatica and Pseudocydonia sinensis. Conclusion These findings have guiding significance for conservation of traditional knowledge associated with MFPs and facilitation of scientific utilization of MFPs to meet local people’s needs for a healthy life.

Điều chế và tiêu chuẩn hóa cao đặc Diếp cá Houttuynia cordata Thunb

Article

Nov 2023

Đặt vấn đề: Việc bào chế sản phẩm trung gian từ dược liệu như cao đặc, cao khô hoặc bột đang dần được quan tâm nhiều hơn. Mục tiêu: nhóm nghiên cứu tiến hành điều chế và tiêu chuẩn hóa cao đặc Diếp cá (Houttuynia cordata Thunb.). Đối tượng và phương pháp: Dược liệu Diếp cá toàn thân trên mặt đất, thăm dò điều kiện chiết xuất và điều chế cao đặc Diếp cá đạt hiệu suất tối ưu. Kết quả: xây dựng và thẩm định được quy trình định lượng flavonoid toàn phần (theo quercetin) bằng phương pháp quang phổ UV-Vis. Xây dựng được quy trình điều chế và một số tiêu chuẩn cơ sở cao đặc Diếp cá. Kết luận: xây dựng tiêu chuẩn chất lượng cao đặc Diếp cá, góp phần kiểm soát tốt chất lượng nguồn nguyên liệu đưa vào sản xuất các dạng bào chế.

Beyond The Present: Future Research Directions On The Extraction And Fractionation Of Bioactives, With The Focus On Phytochemicals

Article

Full-text available

Nov 2023

Farshad Khademi

Bioactives are naturally occurring compounds that may have various beneficial effects on human health and well-being. These compounds, including phytochemicals, can be extracted and purified from a variety of sources using various methods and utilized as medicines or health-promoting products. This review article explores the promising avenues for future research in the realm of bioactive compound extraction and fractionation. By undertaking a comprehensive study of the extraction and purification techniques, analytical methods, and related pharmaceutical affairs, this review discerns the intricacies of each method and underscores the gaps in knowledge that warrant further investigation. By shedding light on these gaps, we emphasize the need for an approach that combines engineering, chemistry, and biology. We will explore the challenges faced in this field and highlight research directions. These challenges include optimizing process parameters, scaling up extraction systems, fractionating and purifying extracts, identifying and characterizing compounds, evaluating their activities, developing applications, investigating hybrid approaches, integrating analytical methods, advancing technology for bioactive production more efficiently and sustainably, and devising innovative strategies to reduce waste and utilize agricultural byproducts. Overall, this article is a reference for researchers in the field, as it provides insights into the key challenges and changing dynamics of extracting and fractionating bioactive compounds.

Cadmium phytoremediation potential of Houttuynia cordata: Insights from growth, uptake, and rhizosphere mechanisms

Article

May 2024
ECOTOX ENVIRON SAFE

Novel partially reversible NDM-1 inhibitors based on the naturally occurring houttuynin

Article

Apr 2024
BIOORG CHEM

Response surface methodology for aqueous two-phase system extraction: An unprecedented approach for the specific flavonoid-rich extraction of Houttuynia cordata Thunb. leaves towards acne treatment

Article

Full-text available

Feb 2024

Background Houttuynia cordata Thunb. has long been widely used as a daily vegetable and traditional medicine. The flavonoid component of H. cordata has plenty of pharmacological effects, such as antibacterial, anti-inflammatory, and antioxidant. In this study, we applied the aqueous two-phase system (ATPS) combined with ultrasonic extraction for extracting H. cordata leaves. Methods We optimized the extraction process to improve the extraction efficiency of the two flavonoids, hyperin and quercitrin, by Surface Method Response - Central Composite Design (RSM-CCD). Next, we investigated the antibacterial ability of H. cordata ATPS extract from optimal conditions against two bacterial strains, Cutibacterium acnes and Staphylococcus epidermidis. Results The results showed that using 10% (NH4)2SO4 and 35% ethanol for ATPS extraction resulted in the highest hyperin and quercitrin contents. From the RSM-CCD results, the optimal extraction conditions were determined to be ultrasonic extraction at 50 °C for 30 min, giving results consistent with the predicted model and obtaining hyperin and quercitrin contents at 1.5681 ± 0.0114 and 4.6225 ± 0.0327 mg/g, respectively. Furthermore, ATPS extract has excellent antibacterial activity with a minimum inhibitory concentration (MIC) value of 250 μg/mL on both C. acnes and S. epidermidis. This MIC is significantly lower than the H. cordata ultrasound-assisted (UA) extract, with MICs of 1500.00 and 156.25 μg/mL on C. acnes and S. epidermidis, respectively. In addition, the results from the disk diffusion assay also showed that ATPS extraction has superior internal antibacterial activity with a zone of inhibition diameter at 250 μg/mL of 8.67 ± 1.15 and 5.00 ± 2.00 mm. Meanwhile, those of UA extract on C. acnes is 5.67 ± 1.53 mm (at 1500 μg/mL), and on S. epidermidis is 1.34 ± 0.58 mm (at 156.25 μg/mL). Conclusion To sum up, our research highlights the potential of H. cordata ATPS extracts as the starting material for topical preparations for effectively treating acne.

Studies on the Standardization of Crude Drugs. III: On the Production Conditions and Component of Crude Drugs. (2). On the Component of Houttuynia cordata</i

Article

Feb 1953

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.

Herba houttuyniae extract induces apoptotic death of human promyelocytic leukemia cells via caspase activation accompanied by dissipation of mitochondrial membrane potential and cytochrome c release

Article

Apr 2003

Herba houttuyniae has been used as a constituent of herval medicine prescriptions for the treatment of inflammation, cancer, and other diseases. In the present study, we investigated the cellular effects of herba houttuyniae extract (HHE) and the signal pathways of HHE-induced apoptosis in HL-60 human promyelocytic leukemia cell line. HHE treatment caused apoptosis of cells as evidenced by discontinuous fragmentation of DNA, the loss of mitochondrial membrane potential, release of mitochondrial cytochrome c into the cytosol, activation of procaspase-9 and caspase-3, and proteolytic cleavage of poly(ADP-ribose) polymerase. Pretreatment of Ac-DEVD-CHO, caspase-3 specific inhibitor, or cyclosporin A, a mitochondrial permeability transition inhibitor, completely abolished HHE-induced DNA fragmentation. Together, these results suggest that HHE possibly causes mitochondrial 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.

Extraction and separation of flavonoids from Houttuynia cordata Thunb. Leaves

Article

Oct 2008

The microwave-assisted extraction technique for flavonoids from Houttuynia cordata Thunb. leaves was studied, and the optimization of technological parameters were obtained by orthogonal experiments. At the same time, seven types of macroporous resin were selected to compare their performances in absorbing and desorbing flavonoids from Houttuynia cordata Thunb. leaves. The optimal macroporous resin was decided at last and its dynamic absorbing and desorbing behavior was studied. Results show that the optimum conditions are as follows: Ethanol concentration is 50%, the ratio of solid to liquid is 1:50 (w/v), dipping 30 min, microwave action time is 30 s and microwave power is 540 W. Compared with traditional ethanol extraction, microwave-assisted extraction is able to reduce the extraction time from 3 h to 30.5 min and increases extraction rate from 92.14% to 95.93%. And NKA-9 type macroporous resin possesses higher absorption and desorption capacity. The optimum technological parameters of adsorption and separation are pH 3.00-3.50, velocity of flow 1 mL/min and sample solution concentration 2.21-3.10 mg/mL. When 70% ethanol is used as eluant, the desorption capacity is 97.8%, and 3BV eluant can desorb flavonoids from Houttuynia cordata Thunb. leaves basically.

Pharmacognostical studies of Houttuyniae Herba (1). Flavonoid glycosides contents of Houttuynia cordata Thunb.

Article

Jan 1994

The amounts of five flavonoid glycosides contained in Houttuynia cordata Thunb., quercitrin, hyperin, rutin, isoquercitrin and afzelin were determined by HPLC. Leaves had a high quarcitrin content and the spikes had high quercitrin and hyperin contents, but the stems contained only a little and the rhizomes scarcely any of these flavonoid glycosides. The flavonoid glycoside contents and the glycoside profiles in the leaves remained constant as the plant grew. The total flavonoid glycoside contents (the sum of five constituent contents) in the leaves of a hundred wild materials collected in 84 locations were all between 2 and 4%, and their flavonoid glycoside profiles were all alike. The commercial crude drugs of Chinese origin tended to have higher hyperin contents than Japanese samples.

Pharmacognostical studies of houttuyniae herba (2): Growth and flavonoid glycoside contents of Houttuynia cordata thunb. Cultivated under shade condition

Article

Jan 1996

A correlation between flavonoid glycoside contents of leaves of wild Houttuynia cordata and the amount of light in the natural habitat has been reported. In this study, the effects of light conditions on the growth and yield of the plant and on the flavonoid glycoside contents of the leaves was studied in a field in Tsukuba. The flavonoid glycoside contents of the leaves of the wild plants growing in bright and shaded places were also studied. The yield of the aerial part of plants cultivated under a shaded condition (shading rate ca. 43%) was the highest. However, the flavonoid glycoside content of leaves was the highest when the plant was cultivated without a shade (open) and decreased as the shading rate increased. In the case of wild plants, too, those growing in brighter places had higher leaf flavonoid glycoside contents and this result agreed well with the result of our present cultivation experiment in the field.

Studies on flavonol glycosides in Houttuynia cordata

Article

Jan 1994

Five flavonol glycosides, quercitrin (I), isoquercitrin (II), afzerin (III), hyperin (IV) and rutin (V) were isolated from the terrestrial part of Houttuynia cordata collected during the flowering season. The quantitative analysis of the five flavonol glycosides in Houttuynia cordata by high-performance liquid chromatography (HPLC) revealed the following results. (1) All the leaves, spikes and stems contained these five flavonol glycosides, and the content was the highest in leaves. (2) The main flavonol glycosides in spikes were I and IV. (3) The flavonol glycoside contents in leaves before and during the flowering season were about the same.

Chemical constituents of Houttuynia cordata

Article

Dec 2007

The effects of Houttuynia cordata on the hepatic bromobenzene metabolizing enzyme system in rats and isolation of phenolic compounds

Article

Jan 2000

Effects of Houttuynia cordata on the level of lipid peroxide and the enzyme activities of the liver were investigated in bromobenzene-induced rats. Lipid peroxide content in liver was increased by bromobenzene. It was decreased when the methanol extract from the aerial parts of H. cordata was treated to the rat. The methanol extract reduced the activities of aminopyrine N-demethylase and aniline hydroxylase that increased by bromobenzene, however did not affect glutathione S-transferase activity. The methanol extract recovered the activity of epoxide hydrolase activity that decreased significantly by bromobenzene. We suggest that under our experimental conditions the extract might play an important play in the prevention of hepatotoxicity by reduction of aminopyrine N-demethylase and aniline hydroxylase activities as well as enhancement of epoxide hydrolase activity. Six phenolic compounds have been isolated from H. cordata and identified by means of spectral analysis as protocatechuic acid, quercetin, apigenin, afzelin, hyperoside and quercitrin.

Reactive oxygen radical species scavenging effects of Korean medicinal plant leaves

Article

Jan 2002

Flavonols from Houttuynia cordata with protein glycation and aldose reductase inhibitory activity

Article

Dec 2006

A 4,5-dioxoaporphine type alkaloid, cepharadione B (1), a phenolic acid, protocatechuic acid (2), and flavonols, quercetin (3), afzelin (4), and quercitrin (5), were isolated from the EtOAc-soluble extract of the whole plants of Houttuynia cordata. All the isolates (1-5) were subjected to in vitro bioassays to evaluate advanced glycation end products (AGEs) formation and rat lens aldose reductase (RLAR) inhibitory activity. The three flavonols 3-5 exhibited a significant inhibitory activity on AGEs formation with IC 50 values of 66.9, 58.9, and 32.3 μM, respectively. While the two flavonol rhamnosides 4 and 5 showed a remarkable inhibitory activity against RLAR with IC50 values of 0.81 and 0.16 μM, respectively.

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

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