1. The paper reviewed toxicology research on traditional medicine from 2019. It found that the liver, kidney, and heart are mainly targeted for toxicity. 2. Safety research has also focused on different populations like infants, children, and those who are pregnant. Zebrafish embryos are now commonly used in addition to rodents to evaluate safety. 3. New technologies in 2019 included using multispectral optoacoustic tomography to image liver injury and integrating microRNA profiles to explain toxicity mechanisms. Overall research continues to improve understanding of toxicity targets and mechanisms.

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doi: 10.12032/TMR20200214161
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Toxicological advances of traditional medicine in 2019
Yuan Yao1
, Gen-Bei Wang2, 3
, Shu-Li Man1*
, Long Ma1
, Wen-Yuan Gao2
1
State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin
Key Laboratory of Industry Microbiology, China International Science and Technology Cooperation Base of Food
Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin
300457, China; 2
Tianjin Key Laboratory for Modern Drug Delivery and High Efficiency, School of Pharmaceutical Science and
Technology, Tianjin University, Tianjin 300072, China; 3
State Key Laboratory of Core Technology in Innovative Chinese
Medicine, Tasly Academy, Tasly Holding Group Co., Ltd., Tianjin 300410, China.
*Corresponding to: Shu-Li Man. College of Biotechnology, Tianjin University of Science & Technology, Tianjin Economic and
Technological Development, the 13th street, Tianjin 300457, China. E-mail: msl@tust.edu.cn.
Highlights
The paper reviewed researches concerning toxicology of traditional medicine (TM) and active natural
products during the past 12 months, and find that liver, kidney and heart are the mainly toxic target organs
of TM. In addition, the drug safety for the maternal and child began to be focused on in 2019, and safety
assessment of Aconitum carmichaeli Debx, Tripterygium wilfordii Hook. f., Strychnos nux-vomica L.,
Fallopia multiflora (Thunb.) Harald, etc. is still hot issue.
Traditionality
This annual review summarized the new toxicology study technology, common evaluated models, toxic
target organs, safety evaluation of TM in different kinds of people and popular research issues and herbs in
2019. Compared to 2018, many counties like Australia, Germany and UK start to pay attention to the safety
evaluation of TM.
Toxicological advances of traditional medicine in 2019

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Abstract
There were many researches concerning toxicology of traditional medicine (TM) and active natural products during
the past 12 months. This annual toxicology review summarized target organs of TM like liver, kidney and heart.
Safety medication of TM has been concerned to different kinds of people, including infants, children, pregnancy
and the postnatal period. Besides rodents, zebrafish embryoes have been regarded as common models to evaluate
the safety of TM. New technologies in toxicology focus on rapidly screening and identification of toxins in TM.
Multispectral optoacoustic tomography imaging the precise location of TM-induced liver injury with 3D
information and integrating serum exosomal microRNA and liver microRNA profiles are used to explain the
mechanism of TM-induced hepatotoxicity. Taken together, study on the toxicity mechanism of other target organs,
drug safety in elders, new models and methods should be paid attention to in the prevention of TM toxicology in
the future.
Keywords: Traditional medicine (TM), Natural product, Herb, Toxicity, Toxic target organs, Risk assessment,
Safety evaluation
Acknowledgments:
This work was supported by grants 81673647 and 81503086 from National Natural Science Foundation of China
and Tianjin Municipal Science and Technology Committee (No.18PTSYJC00140 and 19JCYBJC27800).
Abbreviations:
MSOT, multispectral optoacoustic tomography; TM, traditional medicine.
Competing interests:
The authors declare that they have no conflict of interest.
Citation:
Yuan Yao, Gen-Bei Wang, Shu-Li Man. Toxicological advances of traditional medicine in 2019. Traditional
Medicine Research 2020, 5 (2): 83–89.
Executive Editor: Xiao-Hong Sheng.
Submitted: 1 February 2020, Accepted: 14 February 2020, Online: 20 February 2020.

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Background
Safety, effectiveness and quality control belong to
three basic characteristics of drug. During 2019, there
were a number of papers referred to the safety
assessment of toxins [1] like metal [2], elemental
distribution [3], toxic proteins [4, 5] and special
secondary metabolites in traditional medicine (TM),
which might be also the bioactivation of herbal
constituents [6]. The herbs included Cuscuta chinensis
Lam epithymum [7], Cassiae semen [8], Ephedra
sinica Stapf [9], MeLia toosendan Sieb.et Zucc. [10],
Psoralea corylifolia Linn. [11], Gynura segetum (Lour.)
Merr. [12], Leonurus artemisia (Laur.) S.Y. Hu F [13],
Polygonum multiflorum [14–16], Tripterygium
wilfordii Hook. f. [17, 18], Telfaria occidentalis root
[19, 20] and so forth. At the same time, people paid
attention to different age groups such as infants [2],
children [21–23], adults [24], pregnancy and the
postnatal period [13, 25–27] in the use of TM. Liquid
Chinese patent drug, especial for injection received
researchers’ more attention like Xiyanping injection
[28], Tianfoshen oral liquid [29], and motherwort
injection [13]. New detection technology like
multispectral optoacoustic tomography (MSOT)
imaging the precise location of
herbal-medicine-induced liver injury with 3D
information in a noninvasive way using
conjugated-polymer-based ratiometric nanoprobe was
applied [14]. A computational toxicology approach
was also applied to screening the hepatotoxic
ingredients in TM [15]. Furthermore, China played the
key role in the promotion of the rapid upsurge in this
field. Statistical analysis of annual publications of
toxicological studies on TM by relative percentages on
different countries is showed in Figure 1. USA ranked
the second important countries, while India was tied
with Canada and Brazil ranked the third place
researching the toxicology of TM. In addition,
compared to 2018, many counties like Australia,
Germany and UK started to pay attention to the safety
evaluation of TM.
Organ toxicity
Liver is regarded as the top 1 toxic target organ in
TM
Liver is the most important organ of drug metabolism
and detoxification in the body. For herb-induced liver
injury was a growing clinical and economic problem
worldwide, there were a large amount of researches
focusing on liver toxicity in 2019. For example, new
detection technologies like MSOT imaging the precise
location of Fallopia multiflora (Thunb.)
Harald-induced liver injury with 3D information was
applied due to oxidative/nitrosative stress resulted
from hepatically-generated reactive oxygen
species/reactive nitrogen species [14]. A computational
toxicology approach was applied to screening the
hepatotoxic ingredients in Fallopia multiflora (Thunb.)
Harald [15]. Integrating serum exosomal microRNA
and liver microRNA profiles were used to disclose the
mechanism of MeLia toosendan Sieb. et Zucc.-induced
hepatotoxicity in mice [10]. Meanwhile, metabolism
was used commonly to display cholestatic liver injury
caused by psoralen [30], isopsoralen [30] and Gynura
segetum (Lour.) [12], and metabolic disorder like
glycerophospholipid metabolism, primary bile acid
biosynthesis, sphingolipid metabolism, phenylalanine,
tyrosine and tryptophan biosynthesis, and tyrosine
metabolism by Daphne genkwa Sieb. et Zucc. [31],
Glycyrrhiza uralensis Fisch. [31], Sophora flavescens
Ait. [32] and Xysmalobium undulatum [33].
Kidney is considered as the second toxic target
organ in TM
Renal blood flow is abundant, accounting for 25% of
cardiac output, so a large number of drugs can reach
the kidney with blood flow to cause pathological
changes. For example, aristolochic acid I was
recognized as the major cause of aristolochic acid
nephropathy before [34]. During 2019, untargeted
liquid chromatograph-mass spectrometer-based
metabonomics was used to reveal that aristolochic acid
I inhibited amino acids metabolism, glucose
metabolism, beta-oxidation of fatty acids and the
tricarboxylic acid cycle in male mice [35]. Aristolochic
acid I could also react with genomic DNA to form
persistent DNA adducts with purines to induced
nephrotoxicity [36]. Chemotherapy usually induced
nephrotoxicity like cisplatin [37] and doxorubicin [38].
In the year of 2019, researchers reported that grape
pomace extract did not protect against
cisplatin-induced nephrotoxicity, but accentuated the
toxic effect of cisplatin [37]. Dioscorea bulbifera L.
delayed the excretion of doxorubicin and accumulated
doxorubicin in the body, which was associated with its
inhibition of P-glycoprotein in liver and kidneys [38].
Furthermore, it was reported that the incompatible herb
pair Euphorbia kansui T. N. Liou ex S. B. Ho and
Glycyrrhiza uralensis Fisch. induced hepatotoxicity
and nephrotoxicity and attenuated the effect of Gansui
Banxia decoction [39].
Other toxic target organs of TM
In 2019, a review introduced poisoning by toxic plants
in Hong Kong. 62 cases involving 26 poisonous plant
species were identified, among which Alocasia
macrorrhizos (Giant Alocasia), Gelsemium elegans
(Graceful Jessamine), and Rhododendron (Azalea)
species were the three most commonly encountered.
Gastrointestinal toxicity (n = 30, 48%), neurological
toxicity (n = 22, 35%), and hepatotoxicity (n = 6, 10%)
were the three most common clinical problems.
Forty-nine (79%) and eight (13%) patients had mild

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and moderate toxicity, respectively. They were all
recovered shortly with supportive treatment. The
remaining five (8%) patients experienced severe
toxicity requiring intensive care support [40].
Meanwhile, the mechanisms of reproductive injuries
induced by combination of Daphne genkwa Sieb. et
Zucc. and Glycyrrhiza uralensis Fisch. [31],
cardiotoxicity and neurotoxicity caused by diester and
monoester diterpenoid alkaloids in processed Aconitum
carmichaeli Debx. root [41], cardiotoxicity induced by
Chloranthus serratus [42], gastrointestinal injury
incurred by Gardenia jasminoides Ellis [43] and so
forth were explained in 2019. These extracts should be
used with caution. Taken together, statistical analysis
of annual publication referred to different toxic target
organs induced by TM is summarized in Figure 2.
Current advances
Zebrafish embryoes are popular for evaluating the
safety of TM
Right now, the safety evaluation has been applied in
cellular, organ & individual levels. Rodents are
regarded as the common individual models to analyze
the safety of TM or natural products. Meanwhile,
zebrafish embryoes are secondly widely used because
of its rapid, medium throughput and cost-effective.
During 2019, it was used to evaluate the liver
protection and hepatotoxicity of saikosaponin a [44],
aloe emodin [45], and triptolide [46], teratogenicity of
Momordica charantia seeds and fruits [47], heart
toxicity of Libidibia ferrea (juca) [48], reproductive
toxicity of Endopleura uchi (Huber) Cuatrec [49] and
so forth. Although caenorhabditis elegans [50] and
drosophila [51] were popular in the safety evaluation
of various chemical compounds recently, there were no
relative research in TM in 2019.
Figure 1 Statistical analysis of annual publications on toxicological studies on TM by relative percentages
on different countries. TM, traditional medicine.
Figure 2 Statistical analyses of annual publications on toxicological studies on TM by relative percentages
on different toxic target organs. TM, traditional medicine.

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Safety evaluation of TM in different kinds of people
Recently, safety medication has been concerned to
different kinds of people, such as infants [2], children
[21–23], adults [24] and maternal [13, 25–27]. During
2019, a review reported the safety of the herbal
medicinal product used during pregnancy and postnatal
period [25]. In this report, almond oil might induce
preterm birth, the use of oral raspberry leaf was related
to cesarean delivery; the application of heavy licorice
use was relative to early preterm birth by 3.07-fold.
African herbal medicine mwanaphepo was also
reported to be associated with maternal morbidity,
neonatal death or morbidity [25]. Meanwhile, other
research reported that Anastatica hierochuntica
aqueous extract [26] and Snus tobacco [27] displayed
potential toxicity during pregnancy. What’s more, it
attracted attention to the safety assessment of toxic
metals in commonly used pharmaceutical herbal
products in Jordanian market [2], a mixed extract
containing marshmallow root, chamomile flowers,
horsetail herb, walnut leaves, yarrow herb, oak bark
and dandelion herb in the treatment of acute
non-bacterial tonsillitis [21], and green tea [22] in
children.
New toxicology study technology
In 2019, new technology was used in toxicology
evaluation. For example, a computational toxicology
approach was also applied to screening the hepatotoxic
ingredients in TM [15]. Electrospray laser desorption
ionization mass spectrometry was used to rapid
identify herbal toxins [1]. MSOT imaging conjugated
with polymer-based ratiometric nanoprobe was applied
for the precise location of TM-induced liver injury
with 3D information in a noninvasive way [14].
Furthermore, integrating serum exosomal microRNA
and liver microRNA profiles were used to disclose the
mechanism of TM-induced hepatotoxicity in mice
[10].
Conclusion
Taken together, the annual research shows that liver,
kidney and heart are the mainly toxic target organs of
TM. Their toxic mechanisms include cell apoptosis,
metabolic disorder, oxidative stress, inflammatory
damage, liver and renal fibrosis and even inducing
carcinogenesis. Safety medication of TM has been
concerned to different kinds of people, such as infants,
children and maternal. Besides rodents, zebrafish
embryoes have been regarded as common models to
evaluate the safety of TM. New technologies in
toxicology focus on how to screen and identify toxin in
TM, how to image the precise location of TM-induced
tissue injury with 3D information, and how to explain
the mechanism of TM-induced toxicity. In the future,
study on the toxicity mechanism of other target organs,
drug safety in elders, new models and methods should
be used in the prevention of TM toxicology.
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