Journal of Ethnopharmacology 172 (2015) 10–29

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Journal of Ethnopharmacology
journal homepage: www.elsevier.com/locate/jep

Review

Sophora flavescens Ait.: Traditional usage, phytochemistry

and pharmacology of an important traditional Chinese medicine
Xirui He a,b, Jiacheng Fang b, Linhong Huang a,n, Jinhui Wang c, Xiaoqiang Huang a,n
a
Hong-Hui Hospital, Xi’an Jiaotong University College of Medicine, Xi’an 710054, PR China
b
The College of Life Sciences, Northwestern University, Xi’an 710069, PR China
c
Department of Pharmacy, University Hospital of Gansu Traditional Medicine, Lanzhou 730020, PR China

art ic l e i nf o a b s t r a c t

Article history: Ethnopharmacological relevance: Sophora flavescens (Fabaceae), also known as Kushen (Chinese: 苦参),
Received 2 January 2015 has been an important species in Chinese medicine since the Qin and Han dynasties. The root of Sophora
Received in revised form flavescens has a long history in the traditional medicine of many countries, including China, Japan, Korea,
3 June 2015
India and some countries in Europe. In traditional Chinese medicine (TCM), Sophora flavescens has been
Accepted 5 June 2015
used extensively, mainly in combination with other medicinal plants in prescriptions to treat fever,
Available online 16 June 2015
dysentery, hematochezia, jaundice, oliguria, vulvar swelling, asthma, eczema, inflammatory disorders,
Keywords: ulcers and diseases associated with skin burns. The aim of this review is to provide updated and
Sophora flavescens comprehensive information regarding the botany, ethnopharmacology, phytochemistry, biological
Ethnopharmacology activities and toxicology of Sophora flavescens and to discuss possible trends and opportunities for
Flavonoids
further research on Sophora flavescens.
Alkaloids
Materials and methods: We systematically searched major scientific databases (PubMed, Elsevier,
Antitumor activity
Antimicrobial activity
SpringerLink, Google Scholar, Medline Plus, ACS, “Da Yi Yi Xue Sou Suo (http://www.dayi100.com/login.
jsp)”, China Knowledge Resource Integrated (CNKI) and Web of Science) for information published
between 1958 and 2015 on Sophora flavescens. Information was also acquired from local classic herbal
literature, conference papers, government reports, and PhD and MSc dissertations.
Results: The broad spectrum of biological activities associated with Sophora flavescens has been
considered a valuable resource in both traditional and modern medicine. Extracts are taken either orally
or by injection. More than 200 compounds have been isolated from Sophora flavescens, and the major
components have been identified as flavonoids and alkaloids. Recent in vitro and in vivo studies indicate
that at least 50 pure compounds and crude extracts from Sophora flavescens possess wide-ranging
antitumor, antimicrobial, antipyretic, antinociceptive, and anti-inflammatory pharmacological abilities.
The anticancer and anti-infection abilities of these components are especially attractive areas for
research.
Conclusions: Sophora flavescens is a promising traditional medicine, but there is a need for more precise
studies to test the safety and clinical value of its main active crude extracts and pure compounds and to
clarify their mechanisms of action. Moreover, some existing studies have lacked systematic methods and

Abbreviations: 5-HT, 5-hydroxytryptamine; 5R-DHT, 5R-dihydrotestosterone; Ach, Acetylcholine; AGE, Advanced glycation end product; AHR, Airway hyperreactivity; ALP,
Alkaline phosphatase; ANP, Atrial natriuretic peptide; ASM, Airway smooth muscle; cGMP-PDE5, Cyclic guanosine monophosphate (cGMP)-phosphodiesterase type 5; CK,
Casein kinase; COX-2, Cyclooxygenase-2; DGAT, Diacylglycerol acyltransferase; DHT, Dihydrotestosterone; DNFB, 1-Fluoro-2,4-dinitrofluorobenzene; EC50, Concentration for
50% of maximal effect; ECA, Ehrlich ascites carcinoma cell lines; Eca-109, Human esophageal squamous carcinoma Eca-109 cell line; ER, Estrogen receptor; ERK, Extracellular
regulated protein kinases; EtOAc, Ethyl acetate; H460, Non-small cell lung cancer H460; HBeAg, Hepatitis B e antigen; HBsAg, Hepatitis B surface antigen; HBV, Viral hepatitis
type B; HDL-C, High-density lipoprotein-cholesterol; HMC-1, Human mast cell-1; HPLC, High performance liquid chromatography; HPLC-DAD-ESI/MS, High performance
liquid chromatography with diode-array detector and electrospray ionization-tandem mass spectrometry; HRAR, Human recombinant aldose reductase; HSV, Herpes
simplex virus; HT29, Colon cancer cell line; IC50, 50% inhibition concentration; IGF-1, Insulin and insulin-like growth factor-1; IL, Interleukin; IFN-γ, Interferon-gamma; iNOS,
Inducible nitric oxide synthase; KGF, Kinetics gain factor; LD50, Median lethal dose; LDL-C, Low-density lipoprotein-cholesterol; LH, Luteinizing hormone; LPS,
Lipopolysaccharide; LVSP, Left ventricular systolic pressure; LVEDP, Left ventricular end-diastolic pressure; MAO, Monoamine oxidase; MC3T3-E1, Murine calvaria-derived
osteoblastic cell line; MCF-7, Human breast adenocarcinoma cell lines; MCP-1, Monocyte chemoattractant protein-1; MDA, Malondialdehyde; MIC, Minimal inhibitory
concentration; MTT, Methylthiazolyldiphenyl-tetrazolium bromide; NF-κB, Nuclear factor kappa B; NO, Nitric oxide; PDE, Phosphodiesterase; PFS, Prenylated flavonoid-
enriched fraction; PGE2, Prostaglandin E2; PMA, Phorbol 12-myristate 13-acetate; PPARs, Peroxisome proliferator-activated receptors; RANKL, Receptor activator for nuclear
factor-κ B ligand; RLAR, Rat lens aldose reductase; ROS, Reactive oxygen species; S180, Sarcoma 180; SFE, Sophora flavescens extract; SFL, Lectin from Sophora flavescens; sGC-
cGMP, Soluble guanylyl cyclase-cyclic guanosine monophosphate; SGLT, Na þ -glucose cotransporter; SOD, Superoxide dismutase; SR, Root of Sophora flavescens; TC, Total
cholesterol; TCM, Traditional Chinese Medicine; TG, Triglycerides; TLC, Thin layer chromatography; TNF-α, Tumor necrosis factor-alpha
n
Corresponding authors. Tel.: þ 86 29 87800002.
E-mail addresses: xiruihe6105194@163.com (X. He), hxrhist@163.com (L. Huang).

http://dx.doi.org/10.1016/j.jep.2015.06.010
0378-8741/& 2015 Published by Elsevier Ireland Ltd.
 X. He et al. / Journal of Ethnopharmacology 172 (2015) 10–29 11

integration with the existing literature, and some of the experiments were isolated, used small sample
sizes and were unreliable. More validated data are therefore required.
& 2015 Published by Elsevier Ireland Ltd.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
2. Botany and ethnopharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
2.1. Botany . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
2.2. Ethnopharmacology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
3. Phytochemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
3.1. Flavonoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
3.2. Alkaloids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
3.3. Triterpenoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
3.4. Other compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
4. Methods of quality control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
5. Effects of crude extract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
5.1. Antitumor activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
5.2. Anti-inflammatory and antinociceptive activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
5.3. Antianaphylaxis and antiasthma activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
5.4. Antimicrobial activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
5.4.1. Antibacterial activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
5.4.2. Antiviral activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
5.4.3. Insecticidal activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
5.4.4. Antifungal activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
5.5. Effect on the cardiovascular system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
5.5.1. Antiarrhythmic activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
5.5.2. Antimyocardial fibrosis activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
5.5.3. Effect on myocardial contractility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
5.5.4. Vascular relaxing and antimyocardial hypoxic activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
5.6. Immunoregulatory activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
5.7. Other activities. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
6. Toxicity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
7. Future perspectives and conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

Fig. 1. Sophora flavescens Ait. (A) the aerial parts, (B) roots, and (C) traditional Chinese medicine decoction pieces.
12 X. He et al. / Journal of Ethnopharmacology 172 (2015) 10–29
1. Introduction
Sophora is a widespread genus in the Fabaceae family that
consists of approximately 52 species, nineteen varieties, and seven
forms that grow throughout Asia, Oceania, and the Pacific Islands.
Approximately fifteen species in this genus have been the focus of
the most attention since antiquity (Panthati et al., 2012). The root
of Sophora flavescens, also known as Kushen (Chinese: 苦参), has a
strong, bitter taste and cold properties and has been widely used
in traditional and popular medicine as a functional food ingredient
for the treatment of conditions including fevers, dysentery, jaun-
dice, vaginal itching with leukorrhagia, abscesses, carbuncles,
enteritis, leukorrhea, pyogenic infections of the skin, scabies,
swelling, and pain (State Administration of Traditional Chinese
Medicine, 1999; Chinese Pharmacopoeia Commission, 2010). In
China, Sophora flavescens is documented in editions of the Phar-
macopoeia of the People’s Republic of China from 1977 to 2010.
Extracts of Sophora flavescens were, in the past, mainly used in
compound formulas or as decoctions for other herbal drug
products and was always taken orally. More recently, with the
emergence and development of new dosage forms (e.g., tablets,
capsules and injections) and the characterization of a pharmaco-
logical profile for Sophora flavescens, injection administration has
become gradually more accepted and used in clinics for the
treatment of cancer and infectious diseases (Chen et al., 2012;
Yanju et al., 2014).
The chemical profile of Sophora flavescens is extensive and is
known to contain molecules with therapeutic importance. Exten-
sive studies have led to a rapid increase in the amount of
information available regarding the pharmacological activities of
Sophora flavescens components. Several authors have published
reviews about the chemistry and biological activity of Sophora
flavescens components. However, no comprehensive review has
yet been published. Here, we systematically review the ethno-
pharmacology, phytochemistry, pharmacological activity and toxi-
city of Sophora flavescens based on a survey of the scientific
literature between 1958 and 2015. This current and comprehen-
sive information is provided to support the development of better
therapeutic agents and good clinical practices related to Sophora
flavescens.
2. Botany and ethnopharmacology
2.1. Botany
Sophora flavescens Ait. (Fabaceae) is a deciduous shrub that is
0.5 1.5 m tall and is distributed throughout East Asia (especially
China, Korea and Japan) and some European countries. The root of
Sophora flavescens is cylindrical in shape, 10–30 cm in length,
1–6.5 cm in diameter, and externally gray-brown. The leaves are
pinnately compound (odd) and up to 12–25 cm long. The raceme
is 10–20 cm long and has numerous mitriform calyces and a
yellowish white corolla that is slightly longer than the other
petals. The linear pod is 5–12 cm long, has an apex with a long
beak, is slightly beaded, and does not crack after maturity. Sophora
flavescens flowers between May and July and its fruit ripens
during August and September into a brown, spherical pod with
1–5 seeds (Fig. 1).
2.2. Ethnopharmacology
Current available resources show that Sophora flavescens plants
have been pharmacologically used by ethnic groups as a popular
herbal medicine in various regions of the world, especially in Asian
countries. Two thousand years ago, the dried root of Sophora
flavescens was listed in the first Chinese medical classic,
“Shen-Nung’s Pen-Ts’ao”, in 200 A. D., where it was ranked as a
“Middle grade” medicine. According to the “Compendium of Materia
Medica”, another authoritative monograph of TCM, the root of
Sophora flavescens is bitter in taste, cold in nature and described as
having activities related to such processes as clearing away the heat-
evil, expelling superficial evils, dispelling wind, relieving rheuma-
tism, improving eyesight, and nourishing the liver and gall. In
ancient times, more than fifteen classical pharmaceutical books
created by distinguished medical experts in China contained records
of this medicinal plant. It was described as the main component in
some noted prescriptions and recipes. Briefly, according to “Tang
materia medica”, the dried root of Sophora flavescens was used to
improve leg numbness and as an insecticide in the Tang dynasty. In
the Ming dynasty, according to two famous classical books from the
Chinese materia medica called “Ben Cao Jing Bai Zhong Lu” and “Dian
Nan Ben Cao”, the root of Sophora flavescens was considered to be
cold in nature, was thought to act on the heart meridian, and was
used as a treatment for itching skin, hematochezia, solid tumors,
purulent phlegm, inflammation and other diseases. In the Qing
dynasty, it was described in the Chinese book “Ben Cao Cun Xin” as
being used to eliminate dampness, to clear away the heat-evil and to
treat spermatorrhea. Some of the abovementioned uses have been
supported by evidence from an increasing number of studies and
clinical reports.
In China, Sophora flavescens is currently distributed mainly in
the Shanxi, Hubei, Henan and Hebei provinces. The powder from
the dried root of Sophora flavescens has been listed in the
Pharmacopoeia of the People0 s Republic of China for the treatment
of dysentery, hematochezia, jaundice, oliguria, vulvar swelling,
eczema, ulcers, scabies, and leprosy (Chiang Su New Medical
College, 1977; Zhu, 1998; Chinese Pharmacopoeia Commission,
2010). The 2010 edition of the Chinese Pharmacopoeia officially
listed nine Chinese patented medicines that contained mainly
Sophora flavescens, including Kushen tablets, Danggui Kushen
tablets, Kushen capsules, and compound Kushen injections.
Kushen tablets, for example, are a common traditional Chinese
medicine that has been used for the treatment of infectious
diseases in China for over 40 years. Reported effects of Kushen
tablets include clearing heat, eliminating dampness and killing
insects, and it is very effective for treating dysentery, intestinal
catarrh and eczema in clinics. A multitude of classic prescriptions
(e.g., Kushen decoction, Kushen powder, Kushen Shierwei pills)
created by ancient doctors and pharmacists continue to be
frequently used in clinics (State Administration of Traditional
Chinese Medicine, 1999).
The root of this herb is also used as an effective agent and is
available in other countries. In Korea, Sophora flavescens is com-
mercially available as the generic “Kosam”, and it has long been
used in popular medicine as an antipyretic, analgesic, antihelmin-
tic and stomachic, as well as for the treatment of fever, inflam-
matory disorders, ulcers and skin burns (Hur, 1994; Bae, 2000). In
Japan, the dried root of Sophora flavescens, known as “Kujinn”, was
documented in the 16th edition of the Japanese Pharmacopoeia for
its use as a stomachic, antifebrile, analgesic and anthelmintic. (Wu
et al., 1985a). In Hawaiian popular medicine, “Kushen” (Sophora
flavescens Ait.) has been used for treating asthma by practitioners
of Hawaiian herbal medicine.
3. Phytochemistry
Sophora flavescens produces a wide range of secondary metabo-
lites, some of which have received considerable attention due to
their wide-reaching biological activities and novel structures. Prior
to early 2015, more than 200 compounds had been isolated and
 X. He et al. / Journal of Ethnopharmacology 172 (2015) 10–29 13

Table 1
The compounds and activities of some flavonoids isolated from the roots of Sophora flavescens.

No. Compounds Biological activity Results References

1 Quercetin Li et al. (2004)

2 Rutin Li et al. (2004)
3 Kushenol C Antibacterial activity Inhibited the growth of Staphylococcus aureus and Streptococcus mutans Wu et al. (1985a); Yamaki
with MIC of 12.5 and 12.5 μg/mL, respectively. et al. (1990)
Aldose reductase Showed marked inhibitory activity on HRAR with IC50 values of Jung et al. (2008)
inhibitory activity 0.85 μM, and also possessed good inhibitory activity toward AGE
formation with IC50 values of 84.6 μg/mL.
4 5-methylkushenol C Yagi et al. (1989)
5 Kushenol G Wu et al. (1985b)
6 Noranhydroicaritin Inhibited the growth of S. aureus and S. mutans with MIC of 25 and Komatsu et al. (1970);
50 mg/mL, respectively. Yamaki et al.(1990)
7 Isoanhydroicaritin Komatsu et al. (1970)
8 Sophoflavescenol PDEs inhibitory Showed the most potent inhibitory activity (IC50 ¼ 13 nM) against Shin et al. (2002)
activity cGMP-PDE5 with 31.5- and 196.2-fold selectivity over PDE3 and PDE4.
9 Resokaempferol Ding and Chen, 2005
10 8-lavandulylkaempferol Aldose reductase Showed inhibitory activity on RLAR and HRAR with IC50 values of Shen et al. (2006); Jung
inhibitory activity 3.8 and 0.79 μM, respectively. It also possessed good inhibitory activity et al. (2008)
toward AGE formation with IC50 values of 132.1 μg/mL.
11 8-prenylkaempferol Estrogenic activity Exhibited estrogenic activity by binding to rat uterine ER with EC50 of Hillerns and Wink (2005)
(Desmethylanhydroicaritin) 3.71 70.62 mg/mL.
Aldose reductase Showed marked inhibitory activity on RLAR and HRAR with IC50 values Jung et al. (2008)
inhibitory activity of 0.95 and 0.45 μM, respectively. And it also possessed good inhibitory
activity toward AGE formation with IC50 values of 104.3 μg/mL.
Osteogenesis Significantly promoted ALP activity, up-regulated mRNA expressions of Chiou et al. (2011)
promising osteocalcin and osteopontin in MC3T3-E1 cells.
0
12 8-lavandulvl-5,7,4 -trihydroxy- Cao (2007)
flavonol
13 Citrusinol Lin (2006)
14 Flavenochromane B Antitumor activity Active against A549 (human lung cancer line), 1A9 (ovarian carcinoma), Ding et al. (2004)
MCF-7 (breast adenocarcinoma), KB (epidermoid carcinoma of the
nasopharynx), and KB-Vin (drug-resistant variant KB) with IC50 values
1.0, 1.2, 3.6, 1.7 and 1.3 mM, respectively.
15 Flavenochromane C Antitumor activity Against A549, 1A9, KB, and KB-Vin with IC50 values r 1.7 mM, and Ding et al. (2004)
against the MCF-7 with IC50 value of 3.6 mM.
Flavanones
16 Kushenol A Antibacterial activity Against the bacteria S. aureus, B. subtilis, S. epidermidis and P. acnes with Wu et al. (1985a);
the MIC of 5.0, 2.5, 5.0 and 10.0 mg/mL, respectively. Kuroyanagi et al. (1999)
Antiandrogen activity 100 mg/mL showed antiandrogen activity on 5α- reductase and 5α-DHT- Kuroyanagi et al. (1999)
receptor binding with the inhibitory rate 51.4 % and 89.3 %, respectively.
Neuraminidase Dose-dependently inhibited the neuraminidase activity with IC50 of Ryu et al. (2008)
inhibitory activity 14.8 mM.
Glycosidase inhibitory Showed strong α-glucosidase inhibitory activity with IC50 values of Kim et al. (2006)
activity 45 μM, and was shown to be noncompetitive inhibitor.
17 Kushenol B Antitumor activity Inhibited the proliferation of A549, SK-OV-3, SK-MEL-2, XF498 and Wu et al. (1985a); Ryu
HCT-15 with the ED50 of 3.8, 4.3, 3.4, 2.7 and 3.0 mg/mL. et al. (1997)
PLCγ1 inhibitory Showed potent PLCγ1 inhibitory activity with IC50 values of 7.5 mM. Lee et al. (1997)
activity
18 Kushenol E Antitumor activity Inhibited the proliferation of A549, SK-OV-3, SK-MEL-2, XF498 and Wu et al. (1985b); Ryu
HCT-15 with the ED50 of 6.4, 6.4, 5.3, 5.0 and 4.6 mg/mL. et al. (1997)
PLCγ1 inhibitory Showed PLCγ1 inhibitory activity with IC50 values of 11.8 mM. Lee et al. (1997)
activity
19 Kushenol F Monoamine oxidase Dose-dependenly inhibited the activity of MAO-A and MAO-B with IC50 Wu et al. (1985b); Hwang
inhibitory activity values of 103.7 and 63.1 mM, respectively. et al. (2005)
20 Kushenol P Antiandrogen activity 100 mg/mL showed antiandrogen activity on 5α- reductase and 5α-DHT- Kuroyanagi et al. (1999)
receptor binding with the inhibitory rate 76.1 % and 77.0 %, respectively.
21 Kushenol Q Antibacterial activity Against the bacteria S. aureus and Bacillus subtilis with the MIC of Kuroyanagi et al. (1999)
5.0 and 5.0 mg/mL.
Antiandrogen activity 100 mg/mL showed antiandrogen activity on 5α- reductase and 5α-DHT- Kuroyanagi et al. (1999)
receptor binding with the inhibitory rate 34.8 % and 82.4 %,
respectively.
22 Kushenol R Antibacterial activity Against the bacteria S. aureus, B. subtilis, S. epidermidis and Kuroyanagi et al. (1999)
Propionibacterium acnes with the MIC of 5.0, 2.5, 5.0 and 10.0 mg/mL.
Antiandrogen activity 100 mg/mL showed antiandrogen activity on 5α- reductase and 5α-DHT- Kuroyanagi et al. (1999)
receptor binding with the inhibitory rate 23.6 % and 67.5 %, respectively.
23 Kushenol S Antibacterial activity Against the bacteria S. aureus and B. subtilis with the MIC of 5.0 and Kuroyanagi et al. (1999)
5.0 mg/mL.
Antiandrogen activity 100 mg/mL showed antiandrogen activity on 5α- reductase and 5α-DHT- Kuroyanagi et al. (1999)
receptor binding with the inhibitory rate 22.9 % and 47.7 %, respectively.
24 Kushenol T PPARs Significantly activated the transcription of PPARα and PPARγ with EC50 Kuroyanagi et al. (1999);
transactivational values of 16.0 73.4 and 25.5 7 3.1 mM, respectively. Quang et al. (2013)
properties
Antiandrogen activity 100 mg/mL showed antiandrogen activity on 5α- reductase and 5α-DHT- Kuroyanagi et al. (1999)
receptor binding with the inhibitory rate 54.8 % and 84.9 %,
respectively.
25 Kushenol U Antibacterial activity Kuroyanagi et al. (1999)
14 X. He et al. / Journal of Ethnopharmacology 172 (2015) 10–29

Table 1 (continued )

No. Compounds Biological activity Results References

Against the bacteria S. aureus and B. subtilis with the MIC of 10.0 and
10.0 mg/mL.
Antiandrogen activity 100 mg/mL showed antiandrogen activity on 5α- reductase and 5α-DHT- Kuroyanagi et al. (1999)
receptor binding with the inhibitory rate 50.3 % and 85.1 %,
respectively.
26 Kushenol V Antibacterial activity Against the bacteria S. aureus and B. subtilis with the MIC of 10.0 and Kuroyanagi et al. (1999)
10.0 mg/mL.
27 Kushenol W Antibacterial activity Against the bacteria S. aureus and B. subtilis with the MIC of 10.0 and Kuroyanagi et al. (1999)
10.0 mg/mL.
28 Kurarinone Antitumor activity Inhibited proliferation of HL-60 and HepG2 cells with an IC50 of 18.5 Hatayama and Komatsu
and 36.2 mM, respectively; inhibited the proliferation of A549, SK-OV-3, (1971); Ko et al. (2000);
SK-MEL-2, XF498 and HCT-15 with the ED50 of 9.0, 9.4, 6.4, 5.9 and Ryu et al. (1997)
8.6 mg/mL.
Anti-inflammatory Dose-dependently inhibited TNFα-induced NF-κB transcriptional Quang et al. (2013); Kim
activity activity in HepG2 cells with IC50 values of 4.0 μM. and Kim, 2013
Antibacterial activity Against the bacteria S. aureus and B. subtilis with the MIC of 2.5 and Kuroyanagi et al. (1999);
2.5 mg/mL, respectively. Besides, it also exhibited potent antibacterial Ryu et al. (2008)
activity with 10.0 mg/disk against Gram-positive bacteria (B. cereus and
Escherichia coli).
Antifungal activity Against P. vanterpooli and P. Graminicola at a concentration of 12.5 mg/ Yagi et al. (1989)
mL, and weakly inhibited the growth of P. aphanidermatum
(MIC ¼ 25.0 mg/mL).
Insecticidal activity 50 and 25 mg/mL showed insecticidal activity on Mosquito larvae. Zheng et al. (1999)
PLCγ1 inhibitory Showed inhibitory activity against PLCγ1 with IC50 values of 14.1 mM. Lee et al. (1997)
activity
β-secretase inhibitory It was shown to be a noncompetitive inhibitor toward β-secretase with Hwang et al.(2008)
activity IC50 of 3.3 mM.
Neuraminidase Dose-dependently inhibited the neuraminidase activity with IC50 of Ryu et al. (2008)
inhibitory activity 15.1 mM.
Tyrosinase inhibitory Exhibited extremely tyrosinase inhibitory activity (noncompetitive Ryu et al. (2008); Sasaki
activity inhibitors, IC50 of 2.2 mM), and also demonstrated to be noncompetitive et al. (2014)
inhibitors of protein tyrosine phosphatase 1B based on a kinetic
analysis with IC50 o30.0 mM.
Antiandrogen activity 100 mg/mL showed antiandrogen activity on 5α- reductase and 5α-DHT- Kuroyanagi et al. (1999)
receptor binding with the inhibitory rate 40.5 % and 89.2 %,
respectively.
Glycosidase inhibitory Showed strong α-glucosidase and β-amylase inhibitory activities with Kim et al. (2006)
activity IC50 values of 68 and 85 μM, respectively, and were shown to be
noncompetitive inhibitor.
Aldose reductase Showed marked inhibitory activity on RLAR with IC50 values of 2.99 μM. Jung et al. (2008)
inhibitory activity
DGAT inhibitory Dose-dependently inhibited DGAT activity with IC50 values of 10.9 μM. Chung et al. (2004)
activity
SGLT inhibitory Showed strong inhibitory activity against SGLT1 and SGLT2 at 50 μM Sato et al. (2007)
activity with inhibition rate of 98.8 % and 99.7 %, respectively.
MCP-1 inhibitors Inhibited the migration of THP-1 cells induced by MCP-1 with IC50 Lee et al. (2005)
value of 19.2 μg/mL.
0
29 2 -methoxykurarinone Antitumor activity Inhibited proliferation of HL-60 and HepG2 cells with an IC50 of 13.7 Kang et al. (2000a); Ko
and 21.1 mM, respectively. et al. (2000)
PPARs Dose-dependently activated the transcription of PPARα and PPARβ(δ) Quang et al. (2013)
transactivational with EC50 values of 11.17 2.2 and 21.4 72.5 mM, respectively.
properties
β-secretase inhibitory It was shown to be a noncompetitive inhibitor toward β-secretase with Hwang et al. (2008)
activity IC50 of 6.7 mM.
Tyrosinase inhibitory Demonstrated to be noncompetitive inhibitors of protein tyrosine Sasaki et al. (2014)
activity phosphatase 1B based on a kinetic analysis with IC50 o 30 mM.
Glycosidase inhibitory Showed strong α-glucosidase and β-amylase inhibitory activities with Kim et al. (2006)
activity IC50 values of 155 and 45 μM, respectively.
Aldose reductase Showed inhibitory activity on RLAR with IC50 values of 3.77 μM. Jung et al. (2008)
inhibitory activity
Osteoclast Dose-dependently inhibited osteoclast differentiation in bone marrow Kim et al. (2014)
differentiation cell-osteoblast cocultures and RANKL-induced osteoclast
inhibition differentiation from bone marrow macrophages.
30 Isokurarinone Antibacterial activity Against the bacteria S. aureus, B. subtilis, S. epidermidis and P. acnes with Kyogoku et al. (1973);
the MIC of 2.5, 2.5, 5.0 and 10.0 mg/mL, respectively. Kuroyanagi et al. (1999)
Antiandrogen activity 100 mg/mL showed antiandrogen activity on 5α- reductase and 5α-DHT- Kuroyanagi et al. (1999)
receptor binding with the inhibitory rate 87.1 % and 99.8 %, respectively.
31 (þ ) -norkurarinone PPARs Activated the transcription of PPARα, PPARβ(δ) and PPARγ with EC50 Hatayama and Komatsu
transactivational values of 5.6 7 0.2, 20.7 71.5 and 6.6 7 1.1 mM, respectively. (1971); Quang et al. (2013)
properties
Antibacterial activity Against the bacteria S. aureus, B. subtilis, S. epidermidis and P. acnes with Kuroyanagi et al. (1999)
the MIC of 2.5, 2.5, 10.0 and 10.0 mg/mL, respectively.
Antiandrogen activity 100 mg/mL showed antiandrogen activity on 5α- reductase and 5α-DHT- Kuroyanagi et al. (1999)
receptor binding with the inhibitory rate 86.4 % and 85.8 %,
respectively.
Estrogenic activity Hillerns and Wink (2005)
 X. He et al. / Journal of Ethnopharmacology 172 (2015) 10–29 15

Table 1 (continued )

No. Compounds Biological activity Results References

Exhibited estrogenic activity by binding to rat uterine ER with EC50 of

8.22 7 4.14 mg/mL.
32 Kurarinol Antitumor activity Inhibited the proliferation of A549, SK-OV-3, SK-MEL-2, XF498 and Kyogoku et al. (1973); Ryu
HCT-15 with the ED50 of 30.3,25.8, 21.8, 25.9 and 28.7 mg/mL. et al. (1997)
Antiviral activity Against Herpes simplex virus types I and II with the EC50 of 60 73.4 Woo et al. (1998)
and 447 2.9 mg/mL.
Neuraminidase Dose-dependently inhibited the neuraminidase activity with IC50 of Ryu et al. (2008)
inhibitory activity 12.1 mM.
Tyrosinase inhibitory It was shown to be a noncompetitive inhibitor toward tyrosinase with Ryu et al. (2008)
activity IC50 of 1.0 mM.
Antiandrogen activity 200 mg/mL showed antiandrogen activity on 5α- reductase and 5α-DHT- Kuroyanagi et al. (1999)
receptor binding with the inhibitory rate 11.9 % and 65.8 %, respectively.
Aldose reductase Showed marked inhibitory activity on RLAR with IC50 values of 2.13 μM. Jung et al. (2008)
inhibitory activity
DGAT inhibitory Dose-dependently inhibited DGAT activity with IC50 values of 8.6 μM. Chung et al. (2004)
activity
cGMP-PDE5 Showed inhibitory activity against cGMP-PDE5 with an IC50 values of Shin et al. (2002)
inhibitory activity 6.1 μM.
33 Neokurarinol Antibacterial activity Against the bacteria S. aureus, B. subtilis, S. epidermidis and P. acnes with Kyogoku et al. (1973);
the MIC of 2.5, 2.5, 10.0 and 25.0 mg/mL, respectively. Kuroyanagi et al. (1999)
Antiandrogen activity 100 mg/mL showed antiandrogen activity on 5α- reductase and 5α-DHT- Kuroyanagi et al. (1999)
receptor binding with the inhibitory rate 79.3 % and 58.9 %,
respectively.
34 Norkurarinol Antitumor activity Inhibited the proliferation of A549, SK-OV-3, SK-MEL-2, XF498 and Kyogoku et al. (1973); Ryu
HCT-15 with the ED50 of 15.4, 14.8, 12.9, 10.7 and 16.5 mg/mL. et al. (1997)
Tyrosinase inhibitory Showed inhibitory activity on mushroom tyrosinase with IC50 values of Son et al. (2003)
activity 2.1 mM.
Antiandrogen activity 100 mg/mL showed antiandrogen activity on 5α- reductase and 5α-DHT- Kuroyanagi et al. (1999)
receptor binding with the inhibitory rate 41.3 % and 75.4 %, respectively.
35 Isoxanthohumol Glycosidase inhibitory Showed α-glucosidase inhibitory activity. Komatsu et al. (1970);
activity Quang et al. (2012b)
36 Leachianone A Antitumor activity Inhibited proliferation of HL-60 and HepG2 cells with an IC50 of 11.3 Kang et al. (2000a)
and 13.3 mM, respectively.
β-secretase inhibitory It was shown to be a noncompetitive inhibitor toward β-secretase with Hwang et al.(2008)
activity IC50 of 2.6 mM.
Estrogenic activity Exhibited estrogenic activity by binding to rat uterine ER with EC50 of Hillerns and Wink (2005)
8.95 7 3.41 mg/mL.
37 Leachianone G Antibacterial activity Against the bacteria S. aureus and Bacillus subtilis with the MIC of Kuroyanagi et al. (1999)
5.0 and 2.5 mg/mL.
Antiandrogen activity 100 mg/mL showed antiandrogen activity on 5α- reductase and 5α-DHT- Kuroyanagi et al. (1999)
receptor binding with the inhibitory rate 80.5 % and 84.8 %,
respectively.
38 Sophoraflavanone B Zhao et al. (1993)
39 5-methylsophoraflavanone B Antibacterial activity Against Candida albicans, E. coli, Salmonella typhimurium, S. epidermis Kang et al. (2000b); Sohn
and S. aureus. with MIC of 25, 20, 20, 20, 20 mg/mL. et al. (2004)
40 (  ) -sophoraflavanone G Antitumor activity Inhibited proliferation of HL-60 and HepG2 cells with an IC50 of 12.5 Wang and Han (1996); Ko
and 13.3 mM, respectively; inhibited the proliferation of A549, SK-OV-3 et al. (2000); Ryu et al.
(ovary), SK-MEL-2 (skin), XF498 (central nerve system) and HCT-15 (1997)
(colon) with the ED50 of 6.4, 7.9, 3.9, 5.8 and 5.7 mg/mL.
Anti-Inflammatory 2.5–20 μM inhibited the levels of NO and PGE2 and decreased the Wun et al. (2013)
activity production of IL-1b, IL-6 and TNFα.
Antibacterial activity 10 mg/disk against Gram-positive bacteria (B. subtilis, B. cereus and E. Ryu et al. (2008); Kim
coli). Besides, it showed strong antibacterial activity on E.coli, S. et al. (2013); Sohn et al.
epidermis and S. aureus with MIC of 20, 20 and 20 mg/mL. (2004)
Insecticidal activity 50 and 25 mg/mL showed insecticidal activity on Mosquito larvae. Zheng et al. (1999)
PLCγ1 inhibitory Showed potent PLCγ1 inhibitory activity with IC50 values of 8.2 mM. Lee et al. (1997)
activity
β-secretase inhibitory It was shown to be a noncompetitive inhibitor toward β-secretase with Hwang et al. (2008)
activity IC50 of 5.2 mM.
Neuraminidase Dose-dependently inhibited the neuraminidase activity with IC50 of Ryu et al. (2008)
inhibitory activity 13.5 mM.
Tyrosinase inhibitory It was shown to be a noncompetitive inhibitor toward tyrosinase with Ryu et al. (2008)
activity IC50 of 4.7 mM.
Glycosidase inhibitory Showed strong α-glucosidase and β-amylase inhibitory activities with Kim et al. (2006)
activity IC50 values of 37 and 55 μM, respectively.
Naþ -Glucose Showed strong inhibitory activity against SGLT1 and SGLT2 at 50 μM Sato et al. (2007)
cotransporter (SGLT) with inhibition rate of 99.2 % and 100 %, respectively.
inhibitory activity
41 Sophoraflavanone K Shen et al. (2006)
42 Sophoraflavanone L Shen et al. (2006)
43 Naringenin Yagi et al. (1989)
44 Naringenin-7-O-β-D-glucosyl-40 -O-β- Shen and Zhang(2012)
D-glucose
45 5-methoxy-7,20 ,40 -trihydroxy-8- Li et al. (2008)
prenylflavanone
46 Cao (2007)
16 X. He et al. / Journal of Ethnopharmacology 172 (2015) 10–29

Table 1 (continued )

No. Compounds Biological activity Results References

(2S)-6-lavandulyl-isopentenyl-5-
methoxy-7,20 ,40 ,- trihydroxy-
flavonone
47 (2S)-8-isopentenyl-7,20 ,40 ,-5- Cao (2007)
methoxyflavonone
48 (2S)-6[2(3-hydroxyisopropyl)-5- Ma et al. (2008)
methyl-4-hexenyl]-5-methoxy-
7,20 ,40 -trihydroxyflavanone
49 (2S)-5, 40 -dimethoxy-8- lavandulyl-7, Ma et al. (2008)
20 -dihydroxy flavanone
50 (2S)-8-(5-hydroxy-2-isopropenyl-5- Ma et al. (2008)
methylhexyl)-7-methoxy-5,20 , 40 -
trihydroxy-flavanone
51 (2S)-7, 40 -dihydroxy-5-methoxy- 8- Aldose reductase Showed marked inhibitory activity on HRAR with IC50 values of Kang et al. (2000b); Jung
(γ, γ- dimethylallyl) -flavanone inhibitory activity 0.37 μM. et al. (2008)
52 (2R)-3α,7,40 -trihydroxy-5-methoxy-8-PPARs Activated the transcription of PPARα, PPARβ(δ) and PPARγ in a dose- Quang et al. (2013)
(γ, γ-dimethylallyl)-flavanone transactivational dependent manner, with EC50 values of 5.5 7 1.8, 11.4 7 1.0 and
properties 10.5 7 2.0 mM, respectively.
0
53 (2S)-3β,7,4 -trihydroxy-5-methoxy-8- Aldose reductase Showed inhibitory activity on RLAR with IC50 values of 3.63 μM, and Quang et al. (2013); Jung
(γ, γ-dimethylally)-flavanone inhibitory activity also possessed good inhibitory activity toward AGE formation with IC50 et al. (2008)
values of 261.0 μg/mL.
54 (2S)-7,20 ,40 -triihydroxy-5-methoxy-8- Anti-angiogenesis Blocked cell cycles in the G0/G1 phase without inducing apoptosis, and Quang et al. (2013); Zhang
dimethylallylflavanone activity down regulates vascular endothelial growth factor (VEGF) expression. et al. (2013)
55 3β, 7, 40 - trihydroxy-5-methoxy 8- Li et al. (2008)
[3, 3- dimethylallyl] - flavanone
56 40 -hydroxyisolonchocarpin Lin (2006)
Flavanonols
57 Kushenol J Wu et al. (1985c)
58 Kushenol H Antiviral activity Against Herpes simplex virus types II with an EC50 of 147 78.8 mg/mL Wu et al. (1985b); Woo
et al. (1998)
Antiandrogen activity 100 mg/mL showed antiandrogen activity on 5α- reductase and 5α-DHT- Kuroyanagi et al. (1999)
receptor binding with the inhibitory rate 50.9 % and 81.4 %,
respectively.
DGAT inhibitory Dose-dependently inhibited DGAT activity with IC50 values of 142.0 μM. Chung et al. (2004)
activity
cGMP-PDE5 Showed potent cGMP-PDE5 inhibitory activity with IC50 values of Shin et al. (2002)
inhibitory activity 4.75 μM.
59 Kushenol I Wu et al. (1985b)
60 Kushenol K Antiviral activity Against Herpes simplex virus types II with an EC50 of 162 76.5 mg/mL. Wu et al. (1985c); Woo
et al. (1998)
DGAT inhibitory Dose-dependently inhibited DGAT activity with IC50 values of 250.0 μM. Chung et al. (2004)
activity
PLCγ1 inhibitory Showed potent PLCγ1 inhibitory activity with IC50 values of 34.9 mM. Lee et al. (1997)
activity
cGMP-PDE5 Showed potent cGMP-PDE5 inhibitory activity with IC50 values of Shin et al. (2002)
inhibitory activity 10.6 μM.
61 Kushenol L Antitumor activity Inhibited the proliferation of A549, SK-OV-3, SK-MEL-2, XF498 and Wu et al. (1985c); Ryu
HCT-15 with the ED50 of 11.4, 11.0, 12.4, 12.0 and 8.4 mg/mL. et al. (1997)
PLCγ1 inhibitory Showed potent PLCγ1 inhibitory activity with IC50 values of 11.6 mM. Lee et al. (1997)
activity
62 Kushenol M Antitumor activity Inhibited the proliferation of A549, SK-OV-3, SK-MEL-2, XF498 and Wu et al. (1985c); Ryu
HCT-15 with the ED50 of 5.5, 6.4, 5.5, 5.7 and 5.0 mg/mL. et al. (1997)
PLCγ1 inhibitory Showed potent PLCγ1 inhibitory activity with IC50 values of 12.2 mM. Lee et al. (1997)
activity
63 Kushenol N Antitumor activity Inhibited the proliferation of A549, SK-OV-3, SK-MEL-2, XF498 and Wu et al. (1986); Ryu et al.
HCT-15 with the ED50 of 13.1, 13.8, 6.7, 9.6 and 14.5 mg/mL. (1997)
PLCγ1 inhibitory Showed potent PLCγ1 inhibitory activity with IC50 values of 31.2 mM. Lee et al. (1997)
activity
SGLT inhibitory Showed strong inhibitory activity against SGLT1 and SGLT2 at 50 μM Sato et al. (2007)
activity with inhibition rate of 58.4 % and 87.3 %, respectively.
64 Kushenol X Antibacterial activity Against the bacteria S. aureus and B. subtilis with the MIC of 10.0 and Kuroyanagi et al. (1999)
10.0 mg/mL.
Estrogenic activity Exhibited estrogenic activity by binding to rat uterine ER with EC50 of Hillerns and Wink (2005)
4.39 7 1.26 mg/mL.
Antiandrogen activity 100 mg/mL showed antiandrogen activity on 5α- reductase and 5α-DHT- Kuroyanagi et al. (1999)
receptor binding with the inhibitory rate 84.5 % and 90.5 %,
respectively.
65 Kosamol A PLCγ1 inhibitory Showed potent PLCγ1 inhibitory activity with IC50 values of 10.2 mM. Ryu et al. (1996); Lee et al.
activity (1997)
66 (2R, 3R) -8-isopentenyl-7,40 - Cao (2007)
dihydroxy -5-methoxy-flavanonol
67 (2R, 3R)-8-lavanduly-5,7,40 - Cao (2007)
trihydroxy-20 -methoxy-flavanonol
68 (2R, 3R)-8-isopentenyl-7,20 ,40 - Cao (2007)
trihydroxy-5-methoxy-flavanonol
69 Flavenochromanes Ding et al. (2004)
 X. He et al. / Journal of Ethnopharmacology 172 (2015) 10–29 17

Table 1 (continued )

No. Compounds Biological activity Results References

Isoflavones
70 Formononetin PPARs Activated the transcription of PPARα, PPARβ(δ) and PPARγ with EC50 Kyogoku et al. (1973);
transactivational values of 0.9 7 0.2, 1.5 7 0.3 and 1.6 7 0.5 mM, respectively. Quang et al. (2013)
properties
Monoamine oxidase Dose-dependenly inhibited the activity of MAO-A and MAO-B with IC50 Hwang et al. (2005)
inhibitory activity values of 21.2 and 11 mM.
71 Daidzein Ding and Chen (2005)
73 Biochanin A Ding and Chen (2005)
74 7-methoxy -40 - hydroxyisoflavone Chen et al. (2011)
75 7,40 -dihydroxy-30 -methoxyisoflavone Ding and Chen (2005)
76 Calycosin Ding and Chen (2005)
77 Kushenol O Wu et al. (1986)
78 3’-hydroxykushenol O Shih (1999)
79 Ononin Shen and Zhang (2012)
80 Pseudobatigenin Lin (2006)
81 Pseudobatigenin-7-O-β-D-xylose- Shen and Zhang(2012)
(1-6)-β-D- glucopyranoside
82 Daidzein-7-O-β-D-xylose-(1-6)-β-D- Shen and Zhang(2012)
glucopyranoside
83 30 -methoxy-40 -hydroxyisoflavone-7- Shen and Zhang(2012)
O-β-D-xylose -(1-6) -β-D-
glucopyranoside
84 30 -hydroxy-40 -methoxyisoflavone-7- Hepatoprotective Exhibited weak inhibition of the cytotoxic effect of D-galactosamine on Shen et al. (2013)
O-β-D-xylopyranosyl-(1-6)-β-D- activity the human hepatic cell line HL-7702 with an inhibition rate of 36.6 %.
glucopyranoside
85 30 -hydroxy-40 -methoxyisoflavone-7- Hepatoprotective Exhibited weak inhibition of the cytotoxic effect of D-galactosamine on Shen and Zhang (2012),
O-β-D-apiofuranosyl-(1-6)-β-D- activity the human hepatic cell line HL-7702 with an inhibition rate of 46.3 %. Shen et al. (2013)
glucopyranoside
86 30 -methoxy-40 -hydroxy-isoflavone-7- Shen and Zhang(2012)
O-β-D-apiose -(1-6) -β-D-
glucopyranoside
87 40 -Hydroxy-30 -methoxyisoflavone-7- Hepatoprotective Exhibited weak inhibition of the cytotoxic effect of D-galactosamine on Shen et al. (2013)
O-β-D-xylopyranosyl-(1-6)-β-D- activity the human hepatic cell line HL-7702 with an inhibition rate of 45.8 %.
glucopyranoside
88 40 -hydroxy-30 -methoxyisoflavone-7- Shen et al. (2013)
O-β-D-apiofuranosyl-(l-6)-β-D-
glucopyranoside
89 40 -hydroxyisoflavone -7-O-β-D- Shen and Zhang(2012)
apiose -(1-6) -β-D- glucopyranoside
90 40 -methoxy-isoflavone-7-O-β-D- Shen and Zhang(2012)
apiose-(1-6) - β-D- glucopyranoside
91 30 ,40 -methylenedioxyisoflavone-7-O- Shen et al. (2013)
β-D-apiofuranosyl-(l-6)-β-D-
glucopyranoside
92 30 ,40 -dihydroxy-isoflavone-7-O-β-D- Shen and Zhang(2012)
glucopyranoside
93 5-hydroxy-40 -methoxy-isoflavone-7- Shen and Zhang(2012)
O-β-D- xylose -(1-6) -β-D-
glucopyranoside
94 5-hydroxy-40 -methoxy-isoflavone-7- Shen and Zhang(2012)
O-β-D- apiose-(1-6)-β-D-
glucopyranoside
95 50 -hydroxy-40 -methoxyisoflavone-20 - Shen et al. (2013)
β-D-glucopyranoside
96 5,40 -dihydroxy-isoflavone -7-O- β-D- Shen and Zhang(2012)
xylose -(1-6) -β-D- glucopyranoside
Isoflavanones
97 7-hydroxy-40 -hydroxy-isoflavonone- Shen and Zhang(2012)
30 -O-β-D-glucopyranoside
98 2,3-dihydroxy-40 -methoxy- Shen and Zhang(2012)
isoflavonone -7-O-β- D-xylose-(1-
6)-β- D- glucopyranoside
99 2,3-dihydroxy-40 -methoxy- Shen and Zhang(2012)
isoflavonone 7-O-β-D-apiose -(1-6)-
β- D- glucopyranoside
Homoisoflavones
100 2,3,40 - trihydroxy-homoisoflavone 7- Shen and Zhang(2012)
O- β-D- glucopyranoside
101 2,3-dihydroxy-40 -methoxy- Shen and Zhang(2012)
homoisoflavone -7-O -xyloside
Chalcones
102 20 , 4- dihydroxy -40 , 60 - Liu and Shi (2007)
dimethoxychalcone
103 Kuraridin Antitumor activity Inhibited the proliferation of A549, SK-OV-3, SK-MEL-2, XF498 and Hatayama and Komatsu
HCT-15 with the ED50 of 7.1, 5.8, 5.4, 5.8 and 5.0 mg/mL. (1971); Ryu et al. (1997)
Quang et al. (2013)
18 X. He et al. / Journal of Ethnopharmacology 172 (2015) 10–29

Table 1 (continued )

No. Compounds Biological activity Results References

PPARs Dose-dependently inhibited TNFα-induced NF-κB transcriptional

transactivational activity in HepG2 cells with IC50 values of 4.4 μM, and activated the
properties transcription of PPARα, PPARβ(δ) and PPARγ with EC50 values of
4.8 7 0.9, 10.3 7 1.2 and 15.7 7 1.0 mM.
Antibacterial activity Inhibited the growth of S. aureus and S. mutans. Yamaki et al. (1990)
PLCγ1 inhibitory Showed inhibitory activity toward PLCγ1 with IC50 values of 7.5 μM. Lee et al. (1997)
activity
Tyrosinase inhibitory Possessed potent inhibitory activity on mushroom tyrosinase with IC50 Son et al. (2003); Sasaki
activity values of 0.6 mM. Besides, it was demonstrated to be noncompetitive et al. (2014)
inhibitors of protein tyrosine phosphatase 1B based on a kinetic
analysis with IC50 o30 mM.
Glycosidase inhibitory Showed strong β-amylase inhibitory activity with IC50 values of 57 μM, Kim et al. (2006)
activity and was shown to be noncompetitive inhibitor.
Aldose reductase Showed marked HRAR inhibitory activity with IC50 values of 0.27 μM. Jung et al. (2008)
inhibitory activity
DGAT inhibitory Dose-dependently inhibited DGAT activity with IC50 values of 9.8 μM. Chung et al. (2004)
activity
cGMP-PDE5 Showed potent cGMP-PDE5 inhibitory activity with IC50 values of Shin et al. (2002)
inhibitory activity 0.64 μM.
SGLT inhibitory Showed strong inhibitory activity against SGLT1 and SGLT2 at 50 μM Sato et al. (2007)
activity with inhibition rate of 71.1 % and 100 %, respectively.
104 Kuraridinol Kyogoku et al. (1973)
105 Kushenol D Antibacterial activity Inhibited the growth of S. aureus and S. mutans. Wu et al. (1985a); Yamaki
et al. (1990)
106 Xanthohumol Komatsu et al. (1970)
107 Cyclokuraridin Shen et al. (2006)
108 (Z)-4, 20 ,40 - trihydroxy chalcone Cao (2007)
Biflavonoids
109 Sophflavone A Cao (2007)
110 Sophflavone B Cao (2007)
Pterocarpans
111 Kushecarpin A Kuroyanagi et al. (1999)
112 Kushecarpin B Kuroyanagi et al. (1999)
113 Kushecarpin C Kuroyanagi et al. (1999)
114 Kushecarpin D Anti-angiogenesis Showed antiangiogenic activity via inhibitory effects on proliferation, Pu et al. (2013)
activity migration, adhesion and tube formation of ECV340 cell line.
Meanwhile, it down-regulated ROS levels and up-regulated catalase
activity.
115 Maackiain Neuraminidase Dose-dependently inhibited the activity of neuraminidase with IC50 of Zhao et al. (1993); Ryu
inhibitory activity 3.2 mM. et al. (2008)
116 l-maackiain Yagi et al. (1989)
117 4-methoxy-maackiain Zhao et al. (1993)
118 Maackiain -7-O-β-D- apiose -(1-6) Shen and Zhang(2012)
-β-D-glucopyranoside
119 Pterocarpin Neuraminidase Dose-dependently inhibited the activity of neuraminidase with IC50 of Ryu et al. (2008)
inhibitory activity 1.4 mM.
120 3-hydroxy-4-methoxy-8,9- Lin (2006)
methylenedioxypterocarpan
121 Trifolirhizin Antitumor activity Inhibited the proliferation of A549, SK-OV-3, SK-MEL-2, XF498 and Yagi et al. (1989); Ryu
HCT-15 with the ED50 of 16.3, 24.9, 15.0, 37.8 and 21.0 mg/mL. et al. (1997)
ASM relaxation effect Inhibited acetylcholine mediated ASM contraction or directly relaxes Yang et al. (2013)
pre-contracted ASM independent of β2-adrenoceptors.
122 Trifolirhizin-60 -monoacetate Li et al. (2004)
123 Kushenin Wu et al. (1985a)
124 Medicarpin-3-O-β-D- apiose -(1-6) Shen and Zhang(2012)
-β-D- glucopyranoside
Alkaloids
125 (þ ) -matrine Bohlmann et al.(1958)
126 (þ ) -isomatrine Ueno et al. (1975)
127 (þ ) -allomatrine Sekine et al. (1993)
128 cis-neomatrine Ueno et al. (1975)
129 trans-neomatrine Zhang et al. (2003)
130 (  )  9α-hydroxy-7, 11- Liu et al. (2010)
dehydromatrine
131 (þ ) -oxymatrine Bohlmann et al.(1958)
132 (þ ) -9α-hydroxymatrine Ding et al. (2006)
133 (1) -14β-hydroxymatrine Liu et al. (2010)
134 (þ ) -Sophoranol Bohlmann et al.(1958)
135 (þ ) -Sophoranol N-oxide Sekine et al. (1993)
136 (þ ) -oxysophoranol N-oxide Zhao et al. (1994)
137 13, 14-dehydroxysophoridine Ding et al. (2006)
138 (  )-sophocarpine Okuda et al. (1965)
139 (þ ) -oxysophocarpine Wang et al. (1996)
140 (  ) -sophocarpine N-oxide Sekine et al. (1993)
141 (  ) -9α-hydroxysophocarpine Ding et al. (2006);
142 9α-hydroxysophocarpine N-oxide Wang et al. (1996)
 X. He et al. / Journal of Ethnopharmacology 172 (2015) 10–29 19

Table 1 (continued )

No. Compounds Biological activity Results References

143 ( þ) -12α-hydroxysophocarpine Ding et al. (2006)

144 ( þ) -sophoramine Sekine et al. (1993)
145 (  ) -13-ethylsophoramine Okuda et al. (1965)
146 Tetrahydroneosophoramine Ibragimov et al. (1981)
147 (  ) -cytisine Wang et al. (1981)
148 (  ) -methylcytisine Okuda et al. (1965)
149 (  ) -baptifoline Bohlmann et al. (1958)
150 (  ) -anagyrine Bohlmann et al.(1958)
151 Flavascensine Liu et al. (2010)
Triterpenoids
152 Lupeol Zhao (2008)
153 Lupenone Cao (2007)
154 Monogynol B Cao (2007)
155 β-amyrenol Cao (2007)
156 Soyasaponin I Yoshikawa et al.(1985)
157 Sophoraflavoside I Yoshikawa et al.(1985)
158 Sophoraflavoside II Ding et al. (1992)
159 Sophoraflavoside III Ding et al. (1992)
160 Sophoraflavoside IV Ding et al. (1992)
Others
161 Umbelliferone Zhang et al. (2000)
162 Citrusin A Shen and Zhang(2012)
163 Citrusin B Shen and Zhang(2012)
164 Alaschanioside A Shen and Zhang(2012)
165 Sophodibenzoside A Shen et al. (2013)
166 Sophodibenzoside B Shen et al. (2013)
167 Sophodibenzoside C Shen et al. (2013)
168 Sophodibenzoside D Shen et al. (2013)
169 Sophodibenzoside E Shen et al. (2013)
170 Sophodibenzoside F Shen et al. (2013)
171 Sophodibenzoside G Shen et al. (2013)
172 Sophodibenzoside H Shen et al. (2013)
173 Sophodibenzoside I Shen et al. (2013)
174 Sophodibenzoside J Shen et al. (2013)
175 Sophodibenzoside K Shen et al. (2013)
176 Sophodibenzoside L Shen et al. (2013)
177 Kusheearpin D Cao (2007)
178 Kushequinone Wu et al. (1986)
179 β-sitosterol Zhang et al. (2000)
180 2, 4-dihydroxy benzoic acid Li et al. (2004)
181 Tetracosanoic acid Zhang et al. (2000)

identified from Sophora flavescens. The constituents are classified
into four groups: flavonoids (15 flavonols, 41 flavanones, 13 flavano-
nols, 27 isoflavones, 3 isoflavanones, 2 homoisoflavones, 7 chalcones,
2 biflavonoids, and 14 pterocarpans), 47 alkaloids, 9 terpenoids and 26
other components (Tables 1 and 2). Among these compounds,
alkaloids and flavonoids are considered to be the major active
components of this Chinese medicine (Table 1, Figs. 2 and 3).
3.1. Flavonoids
Flavonoids, which are important secondary metabolites, are wide-
spread throughout the plant kingdom. Flavonoids and their derivatives
are the main bioactive components of Sophora flavescens, and they are
therefore receiving increased attention. A series of characteristic
isoprenylated or lavandulylated flavonoids have been isolated from
this plant. To date, 124 flavonoids have been isolated from the roots of
Sophora flavescens. Among these compounds, kushenol A, B, C, E, F, H,
K, L, M, N, P, Q, R, S, T, U, V, W and X, kurarinone, isokurarinone,
norkurarinone, (2S)-20 -methoxykurarinone, kurarinol, neokurarinol,
norkurarinol, kosamol A, leachianone A, leachianone G, sophoraflava-
none G, 8-lavandulylkaempferol, formononetin, and isoxanthohumol
have been confirmed to possess various pharmacological activities
in vivo and in vitro (Table 1 and Fig. 2).
3.2. Alkaloids
There are two other major groups of active constituents in
Sophora flavescens. One of these groups of metabolites is alka-
loids, which have received a large amount of attention in recent
decades in China. Currently, 27 alkaloids (125–151) have been
isolated and identified from the roots of Sophora flavescens
(Table 1), and another 20 alkaloids have been reported from the
aerial parts, flowers and seeds of Sophora flavescens (Table 2).
Alkaloids are characteristic compounds of this plant and they can
be classified by structure into groups including matrine-type
alkaloids, cytisine-type alkaloids, anagyrine-type alkaloids, and
lupinine-type alkaloids. It is worth noting that the alkaloids, and
especially the matrine-type alkaloids, have been identified as the
bioactive component that contributes to a variety of pharmaco-
logical effects on cancers, hepatitis B and C, and cardiac diseases.
Modern pharmacological studies have shown that the most
active of these components, matrine, has multi-pharmacological
effects, including significant antitumor, antiviral, anti-inflamma-
tory, hepatoprotective, antiarrhythmic, analgesic, antipyretic,
anti- anaphylactic and antiasthma activities (Zhang et al., 2012;
Chang et al., 2013; Shao et al., 2013; Shi et al., 2013a; Tan et al.,
2013; Deng et al., 2014; Huang et al., 2014; Liu et al., 2014; Shao
et al., 2014; Zhou et al., 2014; Gong et al., 2015; Wang et al.,
2015). Oxymatrine has, in particular, been demonstrated to be
20 X. He et al. / Journal of Ethnopharmacology 172 (2015) 10–29

Table 2
The compounds isolated from the aerial parts, flowers and seeds of Sophora flavescens.

No. Compounds Resource References

Alkaloids
1 Matrine-N-oxide Seeds Sekine et al. (1993)
2 (  ) -7, 11-dehydromatrine Flowers Murakoshi et al. (1982)
3 ( þ ) -5α,9 α-hydroxymatrine Flowers, Seeds Murakoshi et al. (1982); Sekine et al. (1993)
4 (  )-Leontalbinine N-oxide Seeds Sekine et al. (1993)
5 (  ) -sophoridine Aerial parts Morinaga et al. (1978)
6 ( þ ) -isosophoridine Aerial parts Morinaga et al. (1978)
7 Isosophocarpine Aerial parts Morinaga et al. (1978)
8 5epi-sophocarpine Aerial parts Sekine et al. (1993)
9 (  ) -5α-hydroxysophocarpine Seeds Saito et al. (1990)
10 ( þ ) -sophoramine-N-oxide Aerial parts Ueno et al. (1978)
11 (  ) -9α- hydroxysophoramine Flowers, Aerial parts Murakoshi et al. (1982); Sekine et al. (1993)
12 (  )-△7-dehydrosophoramine Aerial parts Ueno et al. (1978)
13 (  ) -N-methylcytisine Aerial parts Ueno et al. (1978)
14 (  ) -rhombifoline Flowers Murakoshi et al.(1982)
15 ( þ ) -manmanine Flowers Ibragimov et al. (1981)
16 ( þ ) -kuraramine Flowers Ibragimov et al. (1981)
17 Isokuraramine Flowers Murakoshi et al.(1982)
18 Lupanine Flowers Sekine et al. (1993)
19 (-) -5, 6-dehydrolupanine Flowers Sekine et al. (1993)
20 ( þ )-lehmannine Aerial parts Sekine et al. (1993)
Others
21 Syringin Stems, Leaves Zhang et al. (2013)
22 Corchionoside C Stems, Leaves Zhang et al. (2013)
23 Coniferin Stems, Leaves Zhang et al. (2013)
24 Benzyl O-β-D-glucopyranoside Stems, Leaves Zhang et al. (2013)
25 Piscidic acid Stems, Leaves Zhang et al. (2013)

effective as an anti-inflammatory, antitumor, antihypertensive,
antioxidant, antiapoptotic, and antiviral, and at protecting hepa-
tocytes, inhibiting the immune reaction and reducing hepatic
fibrosis (Yamazaki et al., 1984; Dong et al., 2013; Shi et al., 2013b;
Wang et al., 2013; Liu et al., 2014; Zhang et al., 2014a, 2014b; Wei
et al., 2014; Guo et al., 2015; Wu et al., 2015). The derivatives
( þ)-oxysophocarpine, ( )-sophocarpine, and ( þ)-lehmannine,
at a dose of 0.2 mmol/mL, have shown significant anti-HBV
activity with inhibitory potency against HBsAg secretion at
48.3%, 57.2%, 52.6%, respectively, and against HBeAg secretion at
24.6%, 34.6%, and 25.4%, respectively (Ding et al., 2006). Thus, of
these alkaloids, matrine and oxymatrine have most frequently
been used as a quality control marker for Sophora flavescens and
its medicinal extracts and preparations (Chinese Pharmacopoeia
Commission, 2010). Moreover, the China State Food and Drug
Administration database of drug manufacturing certificates
currently lists 20 clinical uses for matrine and oxymatrine
preparations (http://www.sda.gov.cn/WS01/CL0001/). These
pharmaceutical products, including suppositories, tablets, gran-
ules, capsules, and injectable dosage forms, have been used in
China for the treatment of cancer and infectious and cardiac
diseases (Liu et al., 2001; Long et al., 2004; Lao, 2005).
3.3. Triterpenoids
So far, only nine triterpenoid compounds have been purified
and characterized from the roots of Sophora flavescens. These are
lupeol, lupenone, monogynol B, β-amyrenol, soyasaponin І, and
sophoraflavoside І, II, III and IV (Yoshikawa et al., 1985; Ding et al.,
1992; Cao, 2007; Zhao, 2008).
3.4. Other compounds
A range of other compounds, including some lignans, phenylpro-
panoids, coumarins, and phenolic acids, have also been isolated from
the roots of Sophora flavescens (Wu et al., 1986; Zhang et al., 2000; Li
et al., 2004). Three lignans, including citrusin A, citrusin B and
alaschanioside A, have been identified in the roots of Sophora
flavescens (Shen and Zhang, 2012). In a study by Shen et al. (2013),
twelve new dibenzoyl derivatives (sophodibenzoside A-L) were been
purified from the n-butanol fraction of Sophora flavescens for the first
time. Several other compounds, including syringin, corchionoside C,
coniferin, piscidic acid and benzyl O-β-D-glucopyranoside have also
been isolated from the stems and leaves of this plant (Zhang et al.,
2013).
4. Methods of quality control
Quinolizidine alkaloids and flavonoids are considered to be the
main active components of Sophora flavescens. In the 2010 edition
of the Chinese Pharmacopoeia, only the main alkaloids matrine
and oxymatrine are included as standards for the evaluation of
Kushen quality in the pharmaceutical market. According to this
source, the matrine and oxymatrine content, analyzed by HPLC in
the roots of Sophora flavescens, should both be no less than 1.2%
(Chinese Pharmacopoeia Commission, 2010). Over the past few
years, various different methods, including TLC, HPLC (Li and
Wang, 2004), and capillary electrophoresis (Wu et al., 2006a,
2006b; Wang et al., 2011), have been used to describe the chemical
constituents and to control the quality of derivatives isolated from
the plant. However, interactions between multiple chemical com-
pounds may contribute to the therapeutic effects observed in
herbal medicine. Recently, therefore, the analysis of multiple
components (mainly matrine-type alkaloids and flavonoids) is
increasingly used to validate the quality of this herb. In 2004,
the use of reversed-phase HPLC was developed and validated for
the analysis of three bioactive alkaloids, including matrine,
sophoridine and oxymatrine, derived from Sophora flavescens.
The analysis was performed using a Kromasil C18 column
(250 mm  4.6 mm i.d.; particle size 5 mm) with a gradient elution
of 0.01 mol/L KH2PO4 buffer-methanol-triethylamine in the ratio
94:6:0.01 (v/v) and detected by ultraviolet absorbance at 208 nm.
The analysis time was 24 min per injection. The calibration for
matrine, sophoridine and oxymatrine was linear and ranged from
0.2–120.0 μg/mL, 0.2–115.2 μg/mL and 0.2–110.4 μg/mL,
 X. He et al. / Journal of Ethnopharmacology 172 (2015) 10–29 21

Fig. 2. The chemical structure of some active flavonoids from Sophora flavescens.

respectively (Li and Wang, 2004). Wu et al. (2006a, 2006b)
established a simple and accurate capillary electrophoresis
method for the characterization of four quinolizidine alkaloids
(matrine, oxymatrine, sophoridine and sophocarpine) in Sophora
flavescens, as follows. Electrophoretic separation was performed on
a 75 μm i.d. uncoated fused-silica capillary (65 cm length with
56 cm effective length) with a running buffer of aqueous solution
composed of 60 mmol/L sodium borate, and the limits of detection
for the four alkaloids were determined to range from 8.8 to
48.0 μg/mL. We suggest that flavonoids should also be added into
the quality control system of Sophora flavescens due to their
favorable and crucial pharmacological activities. Fortunately, a
powerful and new method that couples HPLC-DAD-ESI with MS
has been established, providing a chemical mechanism for the
separation and characterization of flavonoids in Sophora flavescens.
Using this method, a total of 24 flavonoids, including 10
flavanones, 4 chalcones, 4 pterocarpans, 3 isoflavones, 1 isoflava-
none, 1 flavanonol and 1 flavonol were identified or tentatively
characterized by an Agilent 1100 HPLC system and Agilent 1100
series SL ion trap mass spectrometer (Zhang et al., 2007).
5. Effects of crude extract
5.1. Antitumor activity
Sophora flavescens extract has demonstrated obvious antitumor
activity in vitro and in vivo and has been commonly used in
Chinese herbal medicines to treat cancer in clinical practice. The
antitumor activity of Sophora flavescens has been confirmed in SK-
OV-3 (ovary), A549, SK-MEL-2 (skin), HT29, NCI-H460 (non-small
cell lung), XF498 (central nerve system), HCT-15 (colon), HL-60
22 X. He et al. / Journal of Ethnopharmacology 172 (2015) 10–29

Fig. 2. (continued)

(myeloid leukemia), and SPC-A-1 (lung) cell lines, in mouse et al., 1966; Li et al., 2002; Sun et al., 2007, 2008). Experimental
models, including S180, H22 and Lewis lung tumors, and in nude studies have explored the systematic activities of Sophora flaves-
mice with human H460 and Eca-109 xenografted tumors (Abbott cens and its antitumor mechanisms, including inducing apoptosis,
 X. He et al. / Journal of Ethnopharmacology 172 (2015) 10–29 23

O O
O O O
H H
H N H N
N N N
H H
H H H
H H H H
H H N H H N H H
N N N
O O
Matrine Oxymatrine (-)-sophocarpine (+) -oxysophocarpine (+) -lehmannine
Fig. 3. The chemical structure of main active alkaloids from Sophora flavescens.

inducing cancer cells to differentiate to normal cells, inhibiting
certain enzyme activities, inhibiting cancer cell DNA synthesis,
affecting cell cycle arrest and tumor metastasis, controlling the
expression levels of tumor-related factors, and affecting telomer-
ase activity. However, it is important to note that most of the
research performed to study antitumor activity has employed
in vitro-based methods and that further in vivo tests should
therefore be encouraged.
In vitro, the aqueous extract of Sophora flavescens, at concentra-
tions of 100 and 200 μg/mL, inhibited growth in Ehrlich ascites
carcinoma (EAC) cell lines with an inhibition rate of 50% and 66%,
respectively (Li et al., 2002). An ethanol extract of Radix Sophora
flavescens (95% ethanol, solid:liquid ratio of 1:9, 80 min heat
reflux) demonstrated significantly inhibited proliferation of colon
cancer HT29 cells with relatively high inhibition rates, as analyzed
by MTT assay (Xiao et al., 2013). The total extract, which had a cell
inhibition rate of 52%, must contain the matrines and flavonoids
that have been described in the literature. Additionally, a
mannose-binding lectin isolated from Sophora flavescens (SFL)
markedly inhibited the growth of MCF-7 cells in a dose- and
time-dependent manner and with an IC50 value of 20 μg/mL.
Concentrations of 12.5, 25, 50, and 100 μg/mL SFL induced an
apoptotic morphology, dose-dependently increased the sub-G1
proportion of cells and triggered G2/M phase cell cycle arrest in
the MCF-7 cell line. SFL also dose-dependently increased the
activity of both caspase-3 and caspase-9 and the release of
cytochrome C from mitochondria into the cytoplasm, up-
regulated Bax and Bid, and down-regulated Bcl-2 and Bcl-XL in
MCF-7 cells. Western blot data demonstrated that treatment of
MCF-7 cells with SFL resulted in down-regulation of protein levels
of NF-κB and ERK and up-regulation of protein levels of p53 and
p21. Finally, SFL showed a strong cytotoxic effect in HeLa cells by
inducing apoptosis in a time- and dose-dependent manner, and
SFL from 0.01 to 5 mg/mL exerted a potent inhibitory effect on the
growth of HeLa cells (Liu et al., 2008).
In vivo, the total flavonoids isolated from Sophora flavescens
(200 mg/kg, i.v.) inhibited growth in five cell lines, including H22
liver cancer, sarcoma 180 (S180), Lewis lung cancer, human esopha-
geal squamous carcinoma Eca-109 and non-small cell lung cancer
H460 cell lines, with inhibitory rates of 40%, 82.14%, 59.74%, 42.71%
and 46.8%, respectively, and with an oral or intravenous maximum
tolerated dose of the extract of more than 2.8 g/kg or 0.75 g/kg,
respectively (Sun et al., 2008). The Sophora flavescens polysaccharide
promoted splenocyte proliferation and significantly strengthened
peritoneal macrophages, which digest H22 tumor cells. The anti-
tumor effect of this polysaccharide may therefore be associated with
its potent immunostimulatory effect (Bai et al., 2012). Sophora
flavescens polysaccharide was administered once per day (p.o.) for
14 consecutive days at 25, 50 and 100 mg/kg to H22 tumor-bearing
mice. This treatment effectively inhibited tumor growth with an
inhibitory rate of 29.02%, 35.96%, and 46.06%, respectively, and the
average survival time was prolonged at least 1.9, 2.9 and 3.6 times,
respectively, compared to the control group. Intraperitoneal admin-
istration of 55 mg/kg of SFL significantly decreased subcutaneous
tumor mass volume and weight in MCF-7 bearing mice. Tumor
weights after 14 days treatment with 55 mg/kg decreased to
0.3170.09 g and 0.5370.31 g, respectively, a reduction of 49.18%
and 38.37%, respectively, whereas in the positive control group
(administered cisplatin), the inhibitory ratio was 88.52% and
79.07%, respectively. It was not determined whether NF-κB, ERK,
p53, and p21 proteins were also involved in SFL-induced apoptosis in
nude mice (Shi et al., 2014).
5.2. Anti-inflammatory and antinociceptive activity
In vivo and in vitro studies have shown that Sophora flavescens
inhibits inflammatory reactions and suppresses inflammatory
factors, including the inhibition of production of COX-2, iNOS,
NO, IL-8, IL-6 and TNF-α. Administration of 200 mg/kg of Sophora
flavescens dried root extract inhibited the mast cell-mediated
passive cutaneous anaphylaxis reaction in vivo and reduced
compound 48/80-induced histamine release from rat peritoneal
mast cells. In addition, this crude extract directly decreased the
expression of phorbol 12-myristate 13-acetate (PMA) and also
decreased stimulation of TNF-a, IL-6, and IL-8 by the calcium
ionophore A23187, indicating that Sophora flavescens may be a
source for new drugs that can treat mast cell-derived allergic
inflammatory diseases (Hong et al., 2009). In a 1-fluoro-2,4-
dinitrofluorobenzene (DNFB)-induced mouse model of contact
dermatitis, 10 mg/mL of dried root of Sophora flavescens (SR)
effectively inhibited the enlargement of ear thickness and weight
that is normally induced by repeated application of DNFB. Topical
application of SR also inhibited hyperplasia, edema, spongiosis and
infiltration of mononuclear cells in ear tissue. In addition, SR
treatment (10 mg/mL) effectively reduced production levels of
IFN-γ and TNF-α in vivo (Kim et al., 2012). SR at concentra-
tions of 50, 100 and 200 mg/mL also inhibited histamine and
β-hexosaminidase release and migration in an in vitro model using
RBL-2H3 cells. Finally, SR was also effective at reducing the
Pseudomonas aeruginosa-induced expression of IL-1β in lung
epithelial cells and macrophages (Lee et al., 2014).
Oral administration of 10–100 mg/kg/day of the alkaloid-free
prenylated flavonoid-enriched fraction (PFS) of rhizomes of
Sophora flavescens significantly inhibited arthritic inflammation
in Wistar rats in a dose-dependent manner. When paws were
treated with heat-killed Mycobacterium butyricum, PFS (100 mg/
kg/day) inhibited paw volume by 32.8% and 31.8% at 14 and 18
days, respectively, while in non-treated paws, PFS inhibited paw
volume by 92.8% and 43.9% at 14 and 18 days, respectively. It was
suggested that this inhibition was due to multiple actions by
proinflammatory enzymes and cytokines, including COX, iNOS and
IL-6 (Jin et al., 2010). PFS also inhibited cyclooxygenase-2 (COX-2)-
catalyzed PGE2 and inducible nitric oxide synthase (iNOS)-cata-
lyzed NO production in lipopolysaccharide (LPS)-treated RAW
264.7 cells at doses ranging from 10 to 50 mg/mL. These effects
occurred primarily through COX-2 inhibition and iNOS down-
regulation, respectively. Finally, PFS also inhibited production of
IL-6 and TNF-α (Jin et al., 2010). We suggest that these antiarthritic
properties of Sophora flavescens might explain its use in local and
24 X. He et al. / Journal of Ethnopharmacology 172 (2015) 10–29
traditional treatments for rheumatism, chronic bronchitis and
chronic hepatitis.
PFS has also displayed a significant antinociceptive effect in an
acetic acid-induced writhing model. PFS, administered orally at 50,
100 and 400 mg/kg, potently inhibited acetic acid-induced wri-
thing in mice, yielding an inhibition rate of 46%, 63% and 68.8%,
respectively. The inhibition rate of PFS at 400 mg/kg was stronger
than that of aspirin at 100 mg/kg (Jin et al., 2010). Advanced
studies should be performed to investigate these biochemical
pathways and to develop better antinociceptive therapeutic
agents.
5.3. Antianaphylaxis and antiasthma activity
One of the most common uses of Sophora flavescens root in
local medicine is the treatment of allergic diseases, including
atopic dermatitis and asthma. Several reports have been carried
out to support these ethnobotanical applications. In a mouse
model of atopic dermatitis, methanol extract of Sophora flavescens,
administered perorally (p.o.) at a dose of 50–200 mg/kg, dose-
dependently and significantly inhibited a serotonin (5-HT)-
induced itch-related response (scratching) and spontaneous
scratching in NC mice (Yamaguchi-Miyamoto et al., 2003). In a
separate study, Sophora flavescens was administered intragastri-
cally at a dose equivalent to a standard human adult dose twice
daily for 17 days in a murine model of allergic asthma. This
treatment significantly reduced the development of airway hyper-
reactivity (AHR), reduced airway inflammation, and decreased
serum IgE, IL-4 and IL-5 levels in splenocyte cultures of
conalbumin-treated mice (Wen et al., 2004). The antiasthma
activity of water extracted from Sophora flavescens was then
investigated. This crude extract significantly reduced allergic
asthma airway hyperreactivity in mice and inhibited acetylcholine
(ACh) induced airway smooth muscle (ASM) contractions in
tracheal rings in allergic asthmatic mice (Yang et al., 2013).
5.4. Antimicrobial activity
5.4.1. Antibacterial activity
The roots of Sophora flavescens have been used as traditional
medicines for microbial infections for thousands of years, and they
have outstanding potential as antimicrobial agents. Di et al. (2006)
showed that an aqueous extract of Sophora flavescens roots
exhibited significant antibacterial activity against Escherichia coli,
Staphylococcus aureus, Streptococcus, Bacillus dysenteriae, Salmo-
nella and Bacillus proteus. This crude Sophora flavescens extract also
exhibited remarkable inhibitory activity against the methicillin-
resistant Staphylococcus aureus and methicillin-sensitive Staphylo-
coccus epidermidis, with MIC50 values of 286 and 143 mg/mL,
respectively, and MIC90 values of 1185 and 286 mg/mL, respectively,
displaying particularly strong antibacterial activity against Staphy-
lococcus epidermis (Yang et al., 2007). Moreover, using double
dilution methods, total alkaloids, total flavonoids and mixtures of
these compounds from Sophora flavescens potently inhibited
Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus,
Shigella, Shigella flexneri, Staphylococcus citreus, Staphylococcus
albus and Bacillus paratyphosus B in vitro with MIC values of 9.0,
3.38, 8.25, 9.0, 4.50, 13.50, 6.75, 7.13 mg/mL, 3.0, 2.63, 3 56, 3.38,
1.50, 2.44, 3.56, 2.35 mg/mL and 2.25, 2.07, 3.28, 3.94, 1.22, 2.44,
2.07, 1.97 mg/mL, respectively (Du et al., 2010). These findings
suggest that antibacterial activity is an important property of
Sophora flavescens and that this plant is a potential source of
preservatives for the food and pharmaceutical industries.
5.4.2. Antiviral activity
Oral administration of Sophora flavescens has been used in
remedies against infectious viral diseases in China, but existing
studies have been performed using mixtures instead of pure
compounds. An ethyl acetate extract demonstrated weak antiviral
activity against Herpes simplex virus types I and II (HSV-1 and 2),
with EC50 values of 4125 mg/mL and 93.3 712.5 mg/mL, respec-
tively (Woo et al., 1998). Ma et al. (2002) selected forty-four
medicinal herbs that are used for the treatment of respiratory
tract infectious diseases in China, and tested the antiviral activities
of these herbs against respiratory syncytial virus (RSV) using the
cytopathogenic effect assay. The aqueous extract of Sophora
flavescens roots showed potent antiviral activity against RSV, with
an IC50 of 50.0 mg/mL and a selectivity index of 16 (Ma et al., 2002).
In 2014, Alfajaro et al. used a porcine rotavirus G5[P7] strain to
examine the antirotaviral activities of Sophora flavescens extracts
(SFE) and stevioside, either singly or in various combinations,
in vitro and in vivo. The results suggested that drug-mixtures of
SFE and stevioside inhibited in vitro virus replication more
efficiently than each single treatment. Moreover, in a piglet model,
SFE improved rotavirus enteritis but did not completely cure it.
Interestingly, piglets given a combination therapy of 1.6 g SFE and
12 g stevioside displayed a rapid decrease in viral copy number, a
marked improvement in small intestinal lesion scores and fecal
virus shedding, and a reduction in diarrhea (Alfajaro et al., 2014).
5.4.3. Insecticidal activity
A number of pharmacological tests and clinical observations
have shown that different extract and/or compound prescriptions
derived from Sophora flavescens have significant insecticidal effects
against diseases and organisms including trichomoniasis, schisto-
somiasis, and Toxoplasma gondii. The methanolic extract of Sophora
flavescens had high anti-T. gondii activity (EC50 ¼0.2 mg/mL) and
high selective toxicity (Choi et al., 2008). The alcoholic extract of
Sophora flavescens from South Korea was effectively used in vitro to
reduce the replication of Toxoplasma gondii and Neospora caninum
(Youn et al., 2003). Sophora flavescens inhibited T. gondii prolifera-
tion by 98.7%, 83.0% and 27.2%, in a range from 0.156 to 0.039 mg/
mL. Sophora flavescens inhibited N. caninum proliferation by 98.6%,
97.0%, 69.5% and 14.0% in the range from 0.16 to 0.02 mg/mL. The
active antineosporal constituents in Sophora flavescens extracts
were sophoridane, furosardonin A, and tetraisopropylidene-
cyclobutane (Seo et al., 2013). The aqueous extract of Sophora
flavescens roots demonstrated inhibitory effects against Eimeria
tenella (Youn and Noh, 2001) and Giardia lamblia (Zhu et al., 2005).
5.4.4. Antifungal activity
In 2012, Liu et al. found that acetone extract of Sophora
flavescens at a concentration of 0.2 g/mL had in vitro antifungal
activity against Candida albicans and Saccharomyces cerevisiae
growth, with inhibition rates of 33% and 23%, respectively. These
results provided more scientific evidence supporting the clinical
use of these plants in Chinese popular medicine (Liu et al., 2012).
Moreover, the flavonoids of Sophora flavescens were demonstrated
to have antifungal activity against Aspergillus niger, Penicillium
chrysogenum and Saccharomyces cerevisiae, with MIC values of
0.28, 0.56 and 0.56 g/L, respectively (Zheng et al., 2008).
5.5. Effect on the cardiovascular system
5.5.1. Antiarrhythmic activity
A total alkaloid solution derived from Sophora flavescens dis-
played preventive effects against chloroform- and isoproterenol-
induced arrhythmia in anesthetized cats. It also significantly
improved arrhythmia caused by ouabain, barium chloride and
 X. He et al. / Journal of Ethnopharmacology 172 (2015) 10–29
strophanthin in neonatal rats (Zha et al., 1981; Zhang et al., 1985).
In addition, the total flavonoids solution derived from Sophora
flavescens had a significantly preventive effect against chloroform-
induced atrial fibrillation in mice, and it showed the same
preventive effect in a rabbit model of arrhythmia caused by
chloroform and/or isoproterenol. In vitro cultured myocardial cell
experiments showed that the total flavonoids (125–250 mg/mL)
derived from Sophora flavescens significantly slowed down spon-
taneous pulsation frequency in suckling mouse myocardial cells
and improved strophanthin-induced arrhythmia (Wang et al.,
1981, 1983).
5.5.2. Antimyocardial fibrosis activity
Total flavonoids derived from Sophora flavescens inhibited
myocardial fibrosis and protected the myocardium in rats. In an
isoprenaline (5 mg/kg)-induced myocardial fibrosis rat model, 200
and 400 mg/kg flavonoids from Sophora flavescens markedly
decreased the activity of CK in blood serum and increased SOD
activity in the left ventricle. It also markedly reduced hydroxypro-
line and angiotensin II levels in the left ventricle and increased NO
content and decreased MDA content in blood serum (Fan et al.,
2013).
5.5.3. Effect on myocardial contractility
The ethanol extract of Sophora flavescens decreased atrial ANP
secretion concomitant with an increase in atrial dynamics, includ-
ing stroke volume and pulse pressure, in euthyroid atria of sham-
treated rabbits. However, in rabbits with hyperthyroid atria
induced by daily administration of sodium L-thyroxine (0.5 mg/
kg) for 12 days, the SF-induced decrease in atrial ANP secretion
was attenuated, and the SF-induced increase in atrial dynamics
was heightened (Wen et al., 2009). Moreover, the ethanol extract
of Sophora flavescens decreased cardiac parameters including LVSP,
LVEDP, þ dp/dtmax,  dp/dtmax and heart rate in both euthyroid and
hyperthyroid groups (Wen et al., 2011).
5.5.4. Vascular relaxing and antimyocardial hypoxic activity
The ethanol extract of the roots of Sophora flavescens
(0.1–100 mg/mL) induced relaxation of the phenylephrine-precon-
tracted aortic rings in isolated rat aorta in a dose-related manner.
These vasorelaxation effects were mediated by the release of NO
from endothelium and activation of sGC-cGMP signaling (Jin et al.,
2011). Intragastric administration of the aqueous extract of
Sophora flavescens at a dose of 10 and 20 g/kg significantly
prolonged survival time (by 26.08% and 45.85%, respectively) and
reduced oxygen consumption in isoprenaline-induced hypoxic
cardiomyocyte mice (Xu et al., 2008). The aqueous extract of
Sophora flavescens exhibited a positive antimyocardial hypoxic
effect, but the dosage used in this study was excessive, equaling
a human equivalent dosage of 813 mg/kg, which would be
equivalent to a dose of approximately 48 g aqueous extract/day
for a 60 kg person. Therefore, the protective effect of this extract
against myocardial ischemia remains to be investigated.
5.6. Immunoregulatory activity
Studies have shown that root extracts of Sophora flavescens may
have immunoregulatory effects and that they could be recom-
mended for use as a potential supplements to enhance other
treatments for immunity and prevention of various diseases. A diet
supplement containing 0.025%, 0.05%, 0.1%, 0.2%, or 0.4% Sophora
flavescens significantly increased serum lysozyme, antiprotease
activity, natural hemolytic complements and cellular myeloperox-
idase activity (Wu et al., 2013). Administration (p.o.) of 25, 50 and
100 mg/kg of Sophora flavescens polysaccharide once per day for
25
consecutive 14 days significantly strengthened peritoneal macro-
phages that ingest H22 tumor cells and stimulated macrophages to
produce nitric oxide (NO) by up-regulating inducible NO synthase
(iNOS) activity, suggesting that the polysaccharide is a strong
natural immunomodulator (Bai et al., 2012). Advanced studies
should be performed to explore the composition and structure of
polysaccharide derived from this plant with a goal of developing a
potent new immunomodulator.
5.7. Other activities
A number of extracts from Sophora flavescens have reported
roles in the regulation of hair growth, skin whitening, and the
lowering of cholesterol, in addition to documented neuroprotec-
tive effects. The methanol extract of this herb displayed a strong
hair growth promoting effect. It also induced an earlier conversion
of telogen-to-anagen in female C57BL/6 mice and affected mRNA
levels of growth factors such as IGF-1 and KGF in human hair
dermal papilla cells. Moreover, the extract displayed a potent
inhibitory effect on type II 5α-reductase activity and thus could
potentially be used in hair growth products (Roh et al., 2002). The
ethanol extract showed a whitening effect that acted by strongly
inhibiting tyrosinase activity, with an IC50 value of 10.4 μg/mL.
DNA microarray, immunohistochemistry and immunofluorescence
analyses showed that the extract dramatically down-regulated
melanosomes at both the mRNA and protein level in keratinocytes.
In a clinical trial of a formula containing 0.05% Sophora flavescens
extract used for 8 weeks on human skin, the formula had a
significant effect on skin whitening, as evaluated both mechani-
cally and visually (Shin et al., 2013). The ethanol extract also
reduced the short circuit current in forskolin-activated rat ileal
epithelia, measured using an Ussing chamber and voltage  cur-
rent technique, implying that this extract may affect ion transport
in the rat ileum epithelia and that this may be critical to the
therapeutic effects of antidiarrheal agents (Tsai et al., 2004).
The ethyl acetate (EtOAc) extract from Sophora flavescens
displayed antihyperlipidemic effects. When orally administered
at doses of 250 and 100 mg/kg, once daily for 3 days, to poloxamer
407-induced hyperlipidemic rats, the extract significantly
increased HDL-C levels and decreased total cholesterol (TC),
triglycerides (TG), and low-density lipoprotein-cholesterol (LDL-C)
levels in rat serum (Kim et al., 2008). It could therefore be used as
an effective cholesterol- lowering agent and could also be useful
for preventing hypercholesterolemic atherosclerosis. Furthermore,
an EtOAc extract enriched in flavonoids from the root of Sophora
flavescens had neuroprotective effects in a model of focal cerebral
ischemia. The flavonoids in this formula might therefore be
responsible for its neuroprotective activity in rats, either alone or
in part (Park et al., 2009).
6. Toxicity
Despite the long use of Sophora flavescens root in traditional
medicine to treat numerous diseases, it has also known been known
to be harmful when used at an excessive dosage. The alkaloids from
Sophora flavescens, in particular, cause spasms and palsies of the
respiratory center in both cold- and warm-blooded animals. The
intravenous administration of the sophocarping of Sophora flavescens
at doses of 150 mg/kg in rabbits caused venous congestion, lowered
blood pressure, breathing difficulties and death. The injection of
matrine into rabbits was found to induce central nervous paralysis
and spasms, with a minimum lethal dose of 0.4 g/kg. An intramuscular
injection of oxymatrine in mice was found to be lethal at 256.747
573.6 mg/kg, while its intravenous LD50 value was 144.2722.8 mg/kg.
An injection of matrine to a frog could induce slow and irregular
26 X. He et al. / Journal of Ethnopharmacology 172 (2015) 10–29
breathing, and sometimes respiratory arrest resulting in death. The
LD50 values of matrine administered orally or by subcutaneous
injection in mice were found to be 1.18 g/kg70.1 and 571.27
48.8 mg/kg, respectively (State Administration of Traditional Chinese
Medicine, 1999). In addition, administration of larger doses of matrine
in mice caused irritability, restlessness and spasmodic tics. Matrine
may also inhibit sperm activity and lead to sperm malformation in
mice after long-term oral administration (Su et al., 2007). However, no
significant poisoning symptoms were found in dogs treated with an
intramuscular injection of matrine (200 mg/kg) and Sophora flavescens
extract (100 mg/kg, 13 days). An intramuscular injection of matrine
was also non-toxic to pigeons at a dose of 100 mg/kg (Xia et al., 1979;
State Administration of Traditional Chinese Medicine, 1999).
Compared to alkaloids, the crude extract and flavonoids derived
from Sophora flavescens have less pronounced side effects, and related
systematic toxicity and safety evaluations have been rare. The oral and
intramuscular injection LD50 values of the extract of Sophora flavescens
roots in mice were found to be 14.5 g/kg and 14.4 g/kg, respectively.
The intravenous LD50 value of the total flavonoids of Sophora flavescens
in mice was found to be 103.177.66 g/kg. Furthermore, treatment
with the ethanol extract of Sophora flavescens at 1.25 g/kg or 2.5 g/kg
twice daily for 3 days significantly elevated alanine aminotransferase
and aspartate aminotransferase levels in the serum. The changes in the
levels of transaminases were supported by the remarkable fatty
degeneration observed in liver histopathology. Histopathological
photomicrographs of the liver showed remarkable fatty degeneration,
with numerous micro and macro vesicles in the portal area of the
2.5 g/kg ESF treated rats compared to the control group. The 1.25 g/kg
ESF-treated group exhibited moderate fatty infiltration. Further inves-
tigations using bioassay-guided isolation and analysis indicated that
prenylated flavanones accounted for the positive hepatotoxic results
(Yu et al., 2013).
The above analysis shows that studies of the side effects and
toxicity associated with the use of Sophora flavescens are not
systematic or sufficiently comprehensive. To guard against toxic
effects, the 2010 edition of the Chinese Pharmacopoeia describes
an exact dosage of the root as 4.5–9 g and includes this precau-
tion: incompatible with the root and rhizome of Veratrum nigrum
L. (Chinese Pharmacopoeia Commission, 2010). Although daily
clinical administration of this extract usually does not result in
any significant adverse effects in humans, systemic toxicity and
safety issues are in urgent need of further attention and study.
Large scale clinical trials are also required to assess the potential of
this extract or its derivates as an alternative to current treatments
of tumors and infectious diseases.
7. Future perspectives and conclusions
The present review summarizes the multifaceted uses and recent
findings regarding studies of the phytochemistry, traditional use,
pharmacology and toxicity of different extracts and compounds of
Sophora flavescens. Sophora flavescens has been traditionally and
popularly used in various indigenous populations to treat disease.
Recent reports have focused primarily on evaluating the anticancer,
antibacterial, anti-inflammatory, and antiasthmatic activities of the
herbal medicines derived from this plant. The alkaloids and flavonoids
are the two major groups of plant derivatives, and they have been
demonstrated to be the main active ingredients in this plant. In
particular, the lavandula and prenyl flavonoids (e.g., sophoraflavanone
G and kurarinone), have been confirmed to be hypotoxic and to have
high medicinal value through various pharmacological activities in vivo
and in vitro.
Much of the work on Sophora flavescens during the last five
decades has focused on obtaining more extracts and active
compounds from the root of this plant, in addition to studying
the various biological properties and traditional uses of the plant
in herbal medicine. However, there are also a number of points
and aspects that need to be improved and researched further: b
Limited work has been performed on the aerial parts of the
Sophora flavescens plant, and further extensive phytochemical
investigation on these are necessary. (ii) The flavonoids, and
especially lavanduly and prenyl flavonoids, have received heigh-
tened public attention due to their hypotoxicity and high medic-
inal value, and further research on these compounds should be a
priority. More specifically, the mechanisms responsible for the
anti-tumor, anti-inflammatory, antibacterial and PLCγ1 inhibitory
effects of these flavonoids need to be fully defined and studied. We
also suggest that the active flavonoids should be used as controls
in studies of Sophora flavescens compounds. (iii) Although Sophora
flavescens root is officially listed in the Chinese Pharmacopoeia and
is used widely and successfully in clinics across China, the
experimental animal studies and randomized clinical trials invol-
ving this plant and its derivatives are still in the exploration stage,
and the exact mechanisms for their therapeutic effects are
unknown. (iv) Although matrine and oxymatrine compounds
derived from Sophora flavescens have been used as effective
human drug products for the treatment of various diseases, there
are more than 50 other main constituents with prominent
biological activity, including other alkaloids, lavanduly and pre-
nylated flavonoids, flavonols, and flavanones, that have not been
developed for use in clinical practice. Further research should be
encouraged to study these components or their analogues. We
expected that more safe, effective and quality-controlled compo-
nents will be widely used in the pharmaceutical, food, and
cosmetics industries in the future. (v) Because the Sophora
flavescens plant contains potentially toxic compounds, reliable
analytical methods are required for proper quality control of
product development to ensure that potentially toxic components
are kept below tolerance levels in Sophora flavescens products.
Future studies should include the identification of any side effects
and/or toxicity.
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