Ecam2019 9458676

Hindawi
Evidence-Based Complementary and Alternative Medicine

Volume 2019, Article ID 9458676, 15 pages
https://doi.org/10.1155/2019/9458676
Review Article
Systematic Review of Herbal Tea (a Traditional Chinese Treatment
Method) in the Therapy of Chronic Simple Pharyngitis and
Preliminary Exploration about Its Medication Rules
Chengxian Li ,1 Fucang Wu ,1 Weiling Yuan ,1 Qi Ding ,2 Min Wang ,1

QingQing Zhang ,1 Ju Zhang ,1 Jingyu Xing ,1 and Shang Wang 1
1
Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
2
Beijing University of Chinese Medicine Dongfang College, Beijing 065001, China
Correspondence should be addressed to Weiling Yuan; yweiling_000@163.com
Received 5 June 2019; Revised 25 July 2019; Accepted 21 August 2019; Published 19 September 2019
Academic Editor: Armando Zarrelli
Copyright © 2019 Chengxian Li et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background. Chronic simple pharyngitis (CSP) is a common clinical chronic respiratory inflammation with persistent and
intransigent symptoms. We analyzed the clinical data to find the evidence that herbal tea, a traditional Chinese medicine
treatment in China, could improve the symptoms of CSP patients in a simple way. Methods. We systematically reviewed the
clinical data of randomized controlled treatments from April 2019 and evaluated the results using the improved Jadad scale and
the Cochrane bias risk assessment tool. RevMan 5.3 software was used for chart analysis. In addition, we used Excel to conduct
frequency statistics on Chinese herbs from included articles and analyze its medication rules. Results. Among the collection of 161
articles, 6 RCTs published in Chinese journals were included in this review. The methodological quality of the treatments was low,
and most of them only provide diagnostic criteria. Inclusion and exclusion criteria were not specified, and none of the 6 RCTs used
the blind method on the result evaluator. Furthermore, only one RCT evaluated the baseline level variance. For these reasons, we
did not make a network meta-analysis. Conclusions. The traditional Chinese herbs involved in herbal tea did have ingredients to
alleviate CSP symptoms. However, our research showed that the current research could not draw any credible conclusions on the
curative effect of herbal tea, which indicated that the overall level of TCM clinical research needs to be improved to evaluate the
efficacy of herbal tea.
1. Introduction repeated attack of acute pharyngitis is the main cause. Upper

respiratory tract lesions adjacent to the pharynx, climate and
Chronic simple pharyngitis, a kind of chronic pharyngitis, is regional environmental changes, occupational factors, sys-
a common disease in the otolaryngology field. It is char- temic factors, and allergic factors can also cause the disease
acterized by diffuse chronic inflammation of the pharyngeal [2, 3]. In addition, an Indian scholar, Kumari, reported that
mucosa, submucosa, and lymphoid tissue and is also a part group A streptococcal pharyngitis (GASP) was one of the
of chronic inflammation of the upper respiratory tract. Its culprits of chronic pharyngitis [4]. There are also reports
incidence rate is from 10% to 20% in pharyngeal diseases. indicated that the virus was detected in the pharynx of
Among the clinical manifestations, which primarily include patients with CSP, and the pathogenesis was related to viral
pharyngeal pain, foreign body sensation, itching, coughing, infection which mainly referred to EB virus and adenovirus.
etc., the reflex nausea and vomiting while brushing teeth in In the United States, over 11 million people are suffering
the morning has seriously lowered the quality of life of from pharyngitis every year. Unsurprisingly, due to various
patients [1]. Modern medicine believes that the occurrence factors such as Chinese diet and environmental pollution,
of this disease is related to a variety of factors, of which the the incidence of chronic pharyngitis in China is also high
2 Evidence-Based Complementary and Alternative Medicine
[5–7]. According to the report of 2012, one-third of the 2019, using the search strategy “TI � (Chinese medicinal herbal
patients in the otolaryngology clinic suffered from chronic tea or medicinal tea) AND TI � (chronic simple pharyngitis or
pharyngitis [8]. chronic throat inflammation)” and imposing no language or
Conventional treatment of CSP chiefly includes antibiotics publication restrictions.
and aerosol inhalation. Antibiotics may lead to drug resistance,
and the abuse of it can result in dysbacteriosis of the throat and
2.3. Inclusion and Exclusion Criteria. The studies were in-
consequently give rise to double infection, in which the pa-
cluded if they met the following criteria as follows: (1) The
tient’s condition may even deteriorate further. The aerosol
study subjects were limited to patients with chronic simple
inhalation treatment tends to be repeated more than once and
pharyngitis (primarily caused by chronic hyperemia of the
still cannot treat CSP effectively [9]. Considering the current
pharyngeal mucosa, submucosal connective tissue, and
curative effect, it is imperative to find another solution.
lymphoidal tissue hyperplasia); there was no requirement in
Herbal tea, a traditional therapy in China, refers to a kind
terms of age and sex. (2) The study was a randomized
of brewed tea along with single or multiple flavors of Chinese
controlled trial comparing the treatment group with the
herbs [10]. It has a long history in the development of
control group. (3) The treatment group was treated with only
traditional Chinese medicine and is generally believed to be
herbal tea, and the control group was treated with con-
beginning in the Tang dynasty, flourishing in the Song
ventional medicine. (4) The article had the description of
dynasty, and matured in the Qing dynasty. Chen Cangqi
symptoms after treatment. Studies were excluded if they met
(687–757 A.D.), a medical scientist in the Tang dynasty, first
any of the following criteria: (1) The study subjects were
put forward the concept of “herbal tea therapy” in his fa-
patients mixed with different types of chronic pharyngitis.
mous medical book A Supplement to Materia Medica and
(2) The study was a review, case report, fundamental re-
said that tea was the remedy for all kinds of diseases. By the
search, or patent. (3) Herbal tea was used in combination
time of Qing dynasty, herbal tea had been fully developed
with other treatments in the treatment group. (4) The article
and highly praised; Chen Keji, an academician of the Chi-
had no record on variations in symptoms. The inclusion and
nese Academy of Sciences, had found at least 8 kinds of
exclusion process is detailed in Figure 1.
herbal tea in the original medical files of the emperor in the
Qing dynasty, including Nectar tea, Ganoderma lucidum tea,
Shenqu tea, Sophora japonica tea, Chrysanthemum indicum 2.4. Data Extraction. Two review authors (Chengxian Li and
tea, Stereulia lychnophora tea, Nelumbo nucifera tea, and Fucang Wu) filtered articles according to the inclusion and
Isatis indigotica tea, which was recorded in Imperial Med- exclusion criteria. Then, we extracted the following study
icaments—medical prescriptions written for Empress characteristics from the included articles (Table 1):
Dowager Cixi and Emperor Guangxu with commentary ∗
[11, 12]. Herbal tea is effective in the treatment of chronic (i) Author, Year
∗
diseases and is convenient and economical enough for long- (ii) Number of treatment group and control group
term use [13]. ∗
(iii) Gender composition
However, herbal tea has drawn little worldwide attention (iv) ∗
Age distribution
and been lack of systematic reviews on its curative effects on ∗
CSP until now. In addition, there was no specific and (v) Interventions
unanimous composition of herbal tea for CSP treatment in
current studies. Based on these questions, the article was 2.5. Data Analysis (Quality Assessment of Trials Included).
written to provide a preliminary image on herbal tea in the Quality in a systematic review essentially refers to the ab-
treatment of CSP. sence of biases, so we used the modified Jadad scale for
evaluating the quality of trials and the Cochrane collabo-
2. Materials and Methods ration’s tool (Cochrane Handbook for Systematic Reviews of
Interventions) for assessing risk of bias (Table 1). Articles
2.1. Types of Studies. We included randomized controlled were assessed by two reviewers (CXL and FCW) in-
trials (RCTs) only. dependently, and disagreements were resolved by consul-
tation with the third reviewer (WLY). RevMan 5.3 was used
to output chart, detailed in Figures 2 and 3.
2.2. Search Strategy. In order to find out all the literature, an
extensive search was performed. We searched the Cochrane 3. Results
Library (The Cochrane Library 2019, Issue 4; https://www.
cochranelibrary.com), PubMed (https://www.ncbi.nlm.nih. 3.1. Search Flow. According to the search strategy, we
gov/pubmed/), Web of science (http://apps.webofknowledge. identified 161 potentially relevant studies. By reading titles
com), EBSCO (http://search.ebscohost.com), Elsevier (https:// and abstracts, we excluded 127 studies that were clearly
www.sciencedirect.c-om/), Springer (http://link.springer.com/), duplicates, basic researches, reviews, case reports, disserta-
CNKI (China National Knowledge Infrastructure, http://www. tions, patents, and conference papers. After the full-text
cnki.net/), Wanfang (http://www.wanfangdata.com.cn/), and reading, 14 articles were excluded for including nonchronic
VIP (Chongqing VIP Information Co., Ltd, http://www.cqvip. simple pharyngitis, containing mixed interventions or being
com/) from the year that each database was created to April inconsistent with our subject; 12 were excluded for having
Evidence-Based Complementary and Alternative Medicine 3
Potential relevant articles

(n = 161)
Exclusion reasons: duplicates
(n = 44)
Primary screening according
to title (n = 117)
Exclusion reasons: basic research, review, case reports,
dissertations, patents, conference papers (n = 83)
Articles retrieved for detailed
selection (n = 34)
Exclusion reasons: nonchronic simple pharyngitis, mixed
interventions or inconsistent with our subject (n = 14)
RCTs retrieved for detailed
evaluation (n = 20)
Exclusion reasons: no control group or the control group
did not meet our original intention (n = 12)
RCTs potentially include in
the review (n = 8)
Exclusion reasons: the therapeutic outcomes was not involved
or unclearly (n = 2)
RCTs include in the review
(n = 6)
Figure 1: Inclusion process and results of the relevant articles.
Table 1: General characteristics of the included articles and score of the modified Jadad scale.
Study N (T/C) Gender (M/F) Age (years) Treatment measure Jadad scale score
T: 12/13 T:25.54 ± 48.64 C: cefuroxime axetil; loquat dew; Yan Li Shuang
Zhao [14] 25/25 3
C: 12/13 C:24.31 ± 46.51 Mouth containing dropping pills
C: gentamicin injection; dexamethasone injection;
Wang [15] 100/100 125/75 20–50 3
chymotrypsin injection; atomization inhalation
C: cefprozi capsule; atomization inhalation;
Zeng et al. [16] 67/59 51/75 21–72 3
Yinhuang buccal tablet
Liu et al. [17] 45/41 55/31 18–60 C: Yinhuang buccal tablet 2
Zhang and Liu [18] 60/60 Unknown 18–65 C: Qingyan pill 3
Wang and Li [19] 52/16 Unknown 18–58 C: Cao Shan Hu Hanpian 2
Random sequence generation (selection bias)

Allocation concealment (selection bias)
Blinding of participants and personnel (performance bias)
Blinding of outcome assessment (detection bias)
Incomplete outcome data (attrition bias)
Selective reporting (reporting bias)
Other bias
0 25 50 75 100
(%)
Low risk of bias
Unclear risk of bias
High risk of bias
Figure 2: Risk of bias graph: review authors’ judgements about each risk of the bias item presented as percentages across all included studies.
no RCTs and 2, for unknown interventions effects. The 3.3. Interventions. The treatment group was treated with
inclusion and exclusion process is detailed in Figure 1. herbal tea, while the control group was treated with con-
ventional therapy. We can see details in Table 1.
3.2. Participants. Finally, we included six trials involving 650
participants, and all of the articles (the number of participants 3.4. Methodological Quality and Level of the Efficacy
varying from 68 to 200) were published in China. The age of Evaluation. The main biases in a clinical trial come from
participants in these trials ranged from 18 to 72 [14–19]. systematic differences between comparison groups in the
the baseline information and not make the number of pa-
Blinding of participants and personnel (performance bias)

tients in the control group large enough. Zhang and Liu [18]
selected a single syndrome (dry lung syndrome due to yin
Blinding of outcome assessment (detection bias)

deficiency) from CSP along with asthma; Wang [15] in-
Random sequence generation (selection bias)

cluded patients with chronic pharyngitis and chronic hy-
pertrophic pharyngitis; both of them evaluated the efficacy
Incomplete outcome data (attrition bias)

Allocation concealment (selection bias)
on CSP separately. The rest of the studies seemed to have no
Selective reporting (reporting bias)

other bias.
All the six studies divided the efficacy evaluation into
three levels.
(1) Recovery: all symptoms disappeared during the
treatment.
(2) Effective: some changes happened in traditional
Other bias
Chinese medicine signs.
(3) Inefficacy: no benefit in any symptoms by the end of
the treatment.
Bailing Wang et al. 1994 ? ? + – + + –
Chunmei Liu et al. 2012 – ? + – + ? + 3.5. Quality of the Evidence Effectiveness. The overall quality
of the evidence included is “very low.” Six included papers
Guo Zeng et al. 2013 ? ? + – + ? + scored not more than 3 on the improved Jadad scale (1–3 is
Huiqi Zhang et al. 2011 ? ? + – + ? –
grouped into low quality, and 4–7 is grouped into high
quality), and the results were consistent with the evaluation
Lishan Wang 2015 – ? + – + + – results of the Cochrane bias risk assessment tool. The studies
had glaring omissions and scored low, probably could be
Yanhua Zhao 2017 ? ? + – + ? + blamed for their early publication, in the selection of random
methods, allocation concealment, and blinding methods for
Figure 3: Using the Cochran collaboration’s tool for assessing risk evaluators. Additionally, it is doubtful whether there was a
of bias about the six studies. report bias since none of the six articles had mentioned the
occurrence of falling off and no reports of adverse reactions
selection bias, performance bias, detection bias, attrition except for Wang [15].
bias, reporting bias, and other bias.
3.6. Analysis of Clinical Effect of the Herbal Tea. The effective
3.4.1. Selection Bias. All the studies claimed to be ran- rate(ER) was the most commonly used measure to evaluate
domized, but Wang [15] and Liu et al. [17] used a wrong efficacy. In this article, it consisted of two parts: recovery rate
random method or pseudorandom method, while other and effective rate. Effective rate analysis was based on the
studies did not mention how they produced random se- improvement of at least one sign of traditional Chinese
quences. No trial described allocation concealment, so we medicine. In these 6 studies, this measure was reported as
could not make out whether they used hidden allocation or effective rate ratio (RR) and calculated as the ratio between
not. the proportion of responders in the treatment group and the
proportion of responders in the control group.
3.4.2. Performance Bias. The blind method was used both in
the treatment group and the control group. 3.7. Forest Plot. As illustrated in Figure 4, the heterogeneity
test P � 0.09 < 0.1, I2 � 48%, the overall moderate hetero-
3.4.3. Detection Bias. The blind method was not applied to geneity, the heterogeneity of Zhao [14], and the other 5
staff for the evaluation of efficacy. experiments are greater, but it was not found in the standard
and evaluation rules. There are significant differences with
the other 5 groups, which may be related to the scales of the
3.4.4. Attrition Bias. All patients did not fall off, and the data efficacy evaluation of the control group by the experimenter.
were complete. So, we used the statistical method of risk ratio (M-H,
Random, 95% CI). We did not perform a combined analysis
for the heterogeneity of the article Zhao [14] and different
3.4.5. Reporting Bias. Wang [15] and Wang and Li [19] had
formulas of herbal tea in other articles. We did not do
clear criteria for evaluating, while others did not.
subgroup analysis either since each formulation of herbal tea
was assessed in one study only.
3.4.6. Other Bias. Wang and Li [19], in which the effective Among the 6 articles included, the efficacy of each test
rate was too high to be convincing, in fact did not compare group was stronger than the control group as follows:
Study or subgroup Experimental Control Risk ratio Risk ratio

Events Total Events Total Weight (%) M-H, random, 95% CI M-H, random, 95% CI
Liu 2012 43 45 32 41 18.3 1.22 [1.03, 1.46]
Wang 1994 115 120 29 40 16.2 1.32 [1.09, 1.61]
Wang 2015 90 100 75 100 23.4 1.20 [1.05, 1.37]
Zeng 2013 64 67 46 59 21.6 1.23 [1.06, 1.42]
Zhang 2011 55 60 43 60 18.0 1.28 [1.07, 1.53]
Zhao 2017 22 25 7 25 2.5 3.14 [1.65, 5.99]
Total (95% CI) 417 325 100.0 1.27 [1.15, 1.41]

Total events 389 232
Heterogeneity: Tau2 = 0.01; Chi2 = 9.67, df = 5 (P = 0.09); I2 = 48%
0.01 0.1 1 10 100
Test for overall effect: Z = 4.52 (P < 0.00001)
Favours [control] Favours [experimental]
Figure 4: The forest plot of the studies included.
Liu et al. [17], the effect of herbal tea is significantly Table 2: Frequency statistics of herbs appeared in six trials and ten
better than the Yinhuang buccal tablet (RR: 1.22 and patents.
95% CI: 1.03 to 1.46) Scientific name (with the author
Chinese name Frequency
Wang and Li [19], the effect of herbal tea is significantly name)
better than Cao Shan Hu lozenge (RR: 1.32 and 95% CI: Lonicera japonica Thunb. Jinyinhua 10
1.09 to 1.61) Ophiopogon japonicus Ker Gawl. Mai dong 10
Glycyrrhiza uralensis Fisch. Gancao 9
Wang [15], the effect of herbal tea is significantly better
Platycodon grandiflorum A. DC. Jie Geng 8
than gentamicin injection; dexamethasone injection; Chrysanthemum indicum L. Yejuhua 6
chymotrypsin injection; and atomization inhalation Stereulia lychnophora Hance. Pangda Hai 6
(RR: 1.20 and 95% CI: 1.05 to 1.37) Mentha haplocalyx Briq. Bohe 5
Zeng et al. [16], the effect of herbal tea is significantly Scrophularia ningpoensis Hemsl. Xuan Shen 5
better than cefprozi capsule; atomization inhalation, and Lilium brownie F. E. Brown var. Baihe 4
Yinhuang buccal tablet (RR: 1.23 and 95% CI: 1.06 to 1.42) Lophatherum gracile Brongn. Danzhuye 4
Citrus reticulata Blanco. Chenpi 4
Zhang and Liu [18], the effect of herbal tea is signifi- Mormordica grosvenorii Swingle. Luohanguo 3
cantly better than Qingyan pill (RR: 1.28 and 95% CI: Canarium album Raeusch. Ganlan 3
1.07 to 1.53) Prunus mume Sieb.et Zucc. Wumei 3
Zhao [14], the effect of herbal tea is significantly better Sheng Di
Rehmannia glutinosa Libosch. 2
than cefuroxime axetil tablets (C20H22N4O10S) and Huang
Scutellaria baicalensis Georgi. Huangqin 2
Yan Li Shuang mouth containing dropping pills (RR:
3.14 and 95% CI: 1.65 to 5.99)
chlorogenic acid and flavonoid luteolin of organic acids are
4. Further Research recognized as essential indicators, especially for the quality
inspection of many Chinese medicine preparations [20].
After the systematic review, we conducted herb frequency
statistics from the included 6 RCT articles and 10 patents for
CSP. The result showed that 60 kinds of herbs were men- 5.1.1. Organic Acids. Lonicera japonica contains a variety of
tioned in 16 articles; 43 of them appeared once, 8 of them organic acids, such as ferulic acid, protocatechuic acid, and
appeared 2–4 times, 4 of them were valued at 5–7 in frequency chlorogenic acid. [21]; the primary effective components are
and 4 (Lonicera japonica Thunb, Ophiopogon japonicus Ker chlorogenic acid compounds, including chlorogenic acid,
Gawl, Glycyrrhiza uralensis Fisch, and Platycodon grandi- isochlorogenic acid, caffeic acid, 3,5-dicaffeoylquinic acid and
florum A. DC.) were valued equal to or greater than 8. The so on, in which caffeic acid has the strongest activity [22].
details are shown in the following table (Table 2).
After looking up the relevant literature, we found that 5.1.2. Flavonoids. The flavonoids in Lonicera japonica were
these four Chinese herbs have multiple effects; to make the first reported by Gao et al. [23] in 1995, including flavonoids
article more specific, we decided to start with the etiology of and flavonoids. The isolated flavonoids [24] refers to luteolin,
CSP. We have qualitatively summarized the phytochemical luteolin-7-O-β-D-glucoside, 5-hydroxy-7, 4′dimethoxy fla-
investigations, pharmacological activities, and cytotoxic vones, luteolin-7-o-A-D-gluconicanhydride, quercetin-3-o-
activities of the top four herbs in the form as follows. β-D, and hyperoxide. In 2017, Ni et al.’s study pointed out that
quercetin-3-o-α-L-pyranorablycoside was first isolated from
5. Phytochemical Investigations Lonicera japonica [25].
5.1. Lonicera japonica. Lonicera japonica contains numerous
kinds of chemical components, mainly including flavonoids, 5.1.3. Triterpenoid Saponins. Triterpenoids and triterpenoid
organic acids, volatile oils, iridoids, and saponins. The saponins are active ingredients in Lonicera japonica. At
present, more than 30 kinds of triterpenoid saponins have 5.3.3. Polysaccharide Components. In 1954, the literature
been found in it [26]. recorded the separation and identification of more than 10
kinds of polysaccharides from Glycyrrhiza uralensis [44],
5.2. Ophiopogon japonicus. At present, various chemical and now new polysaccharides have been isolated. Zhou et al.
components such as steroidal saponins, high isoflavones, [45] with the use of high performance capillary electro-
and polysaccharides have been isolated from different parts phoresis, indicated that Glycyrrhiza uralensis poly-
of Ophiopogon japonicus [27]. Among them, steroidal sa- saccharides were composed of rhamnose, dextran (as the
ponins and high isoflavones are considered to be the main backbone), arabinose, and galactose. Glycyrrhiza poly-
active ingredients since they have multiple pharmacological saccharide has significant antiviral, antioxidant, and im-
activities [28]. mune-enhancing effects.
5.2.1. Steroidal Saponins. Reports showed that 64 kinds of 5.4. Platycodon grandiflorum. The chemical components
steroidal saponins had been found in Ophiopogon japo- contained in Platycodon grandiflorum include triterpenoid
nicus (L.f ) Ker Gawl and Liriope Lour, the saponins with saponins, polysaccharides, flavonoids, sterols, fatty acids,
ruscogenin and diosgenin account for a large proportion. and trace elements.
Currently, ruscogenin and ophiopogonin A, B, B′, C, C′,
D, and D′ have been studied in depth, and in fact, the
5.4.1. Triterpenoid Saponins. Triterpenoid saponins are the
aglycon of Ophiopogonin B′, C, and D′ is diosgenin,
first components that have been isolated from Platycodon
while the aglycon of ophiopogonin A, B, C, and D is
grandiflorum and reported [46]. At present, more than 70
ruscogenin [29].
kinds of triterpenoid saponins have been isolated and
identified [47, 48]. They were classified into platycodin,
5.2.2. Homoisoflavonoids. Homoisoflavonoids are also polyglactin, platycogenic acid, platycodin lactone, and other
major components of Ophiopogon japonicus, and more than atypical triterpenoid saponins in Fu et al. [49, 50] according
30 kinds of homoisoflavone compounds have been isolated to the type of aglycon.
from the herb [30–38].
5.4.2. Flavonoids. Flavonoids mainly exist in the aerial part
5.3. Glycyrrhiza uralensis. Glycyrrhiza uralensis contains of Platycodon grandiflorum. Piao et al. [51] using DPPH and
hundreds of compounds such as glycyrrhizic acid, gany ABTS methods, showed that the order of the flavonoid
glycyrrhizin, glycyrrhizin, 7-methylcoumarin, and umbel- glycoside content in different parts from high to low was
liferone. Flavonoids, saponins, and polysaccharides are the leaves, stem, and root, flavonoid glycosides was hardly de-
most important physiological active ingredients of Glycyr- tected in the root. Up to now, 11 kinds of flavonoids have
rhiza uralensis [39]. been isolated and identified [47]. According to research,
flavonoids have anti-inflammation, antibacteria, anti-tumor,
and other biological activities [48].
5.3.1. Saponins. Triterpenoid saponins are iconic compo-
nents in Glycyrrhiza uralensis, chiefly found in the rhizome 6. Pharmacological Activities
and root of Glycyrrhiza uralensis. They are early recog-
nized and developed for higher content, and the sweetness 6.1. Anti-Influenza Virus Effect
is 10 times higher than sucrose. Heretofore, dozens of
saponins, principally in the form of glucose glycosides with 6.1.1. Lonicera japonica. Influenza virus (Orthomyxovir-
good water solubility, have been isolated from three idae) is a phased negative-stranded RNA virus that can cause
common Glycyrrhiza uralensis, such as Ural Glycyrrhiza human and poultry infections. The influenza A virus, rec-
uralensis, Radix Glycyrrhizae Glabrae, and Glycyrrhiza ognized as the most harmful one, mutates readily and has
inflata Batalin [40]. consequently caused several pandemics.
The main active ingredients for anti-influenza virus in
Lonicera japonica are chlorogenic acid, caffeic acid, quer-
5.3.2. Flavonoids. The flavonoids in Glycyrrhiza uralensis, cetin, hibisin, and so on [52–55]. Modern pharmacological
including glycyrrhizin, isoglycyrrhizin, and neoisoglycoside, studies showed that the pharmacological actions and its
have significant medicinal functions such as antiulcer, an- mechanisms of Lonicera japonica against influenza virus
tibacterial, anti-inflammatory, and hypolipidemic. With the primarily included the inhibition of viral proliferation,
addition of its moisturized effect, Glycyrrhiza uralensis has protection of lung injury, and regulation of immunity. The
been used as an important raw material of anti-in- active constituents of Lonicera japonica could inhibit viral
flammatory and antiallergic agents for high-end skin care activities, reduce the release of inflammatory factors, and
products [41]. Until now, more than 130 kinds of flavonoids promote lymphocyte proliferation in the body [52, 56]. In
[42] have been isolated from the aerial parts, rhizomes, and addition, miR2911 in Lonicera japonica is expected to be a
roots of Glycyrrhiza uralensis, more than 30 kinds of which breakthrough of anti-influenza virus gene drugs due to its
are isoflavonoids [43]. unique structure and activity [57].
6.1.2. Glycyrrhiza uralensis. Utsunomiya et al. [58], used the rarely result in drug resistance, which can provide new ideas
mouse model to study the anti-influenza virus effect of for antibacterial [62]. Lonicera japonica has a certain in-
glycyrrhizin, turning out that vaccinated mice survived hibitory effect on a variety of bacteria and is a typical broad-
100% while others were infected and died. However, the spectrum antibacterial Chinese medicine.
inhibition of influenza virus has not been found in vitro
experiments. It is believed that the mechanism of action is (1) Effect on Gram-Positive Bacteria. The research on anti-
related to the creation of interferon-gamma by T-lympho- Gram-positive bacteria by Lonicera japonica principally
cytes induced by glycyrrhizin. focused on Staphylococcus aureus, Streptococcus pneumo-
niae, Staphylococcus epidermidis, Streptococcus hemolyticus,
Enterococcus, and Bacillus cereus [62]. Huang et al. [63]
6.2. Anti-Respiratory Syncytial Virus
studied the antibacterial activity of compound Lonicera
6.2.1. Lonicera japonica. Studies showed that Lonicera ja- japonica external lotion and Lonicera japonica water extracts
ponica had a direct inactivation effect of RSV in Hela cells [59], and found that they both had antibacterial actions against
and the inactivation was enhanced while the concentration was Staphylococcus aureus, Escherichia coli, Bacillus subtilis, and
increasing, when IC 50 was 45 mg/mL and TI was 31.2. The Pseudomonas aeruginosa. Chan et al. [64] found that
replication and proliferation of the virus were also significantly Lonicera japonica aqueous extracts (MIC ranged from 37.5
inhibited by Lonicera japonica, and the effectiveness was su- to 100 mg/mL) had a strong antibacterial effect against
perior to the control group with ribavirin, when IC 50 was Staphylococcus aureus standard strain, Staphylococcus
30 mg/mL and TI was 10.5. It had a certain inhibitory effect on anhemolyticus, Streptococcus pneumoniae, Enterococcus
the adsorption phase of the virus when IC 50 is 1 mg/mL and faecalis, Bacillus pumilus, Bacillus subtilis, Staphylococcus
TI is 5.0, yet had no blocking effect on the invasion of cells by epidermidis, Streptococcus hemolytic-β, and Staphylococcus
RSV virus. cohnii. Ruan et al. [65] reported that the water extracts of
Lonicera japonica had a significant antibacterial effect
against Staphylococcus aureus and Streptococcus; its alcohol
6.2.2. Glycyrrhiza uralensis. Glycyrrhiza uralensis and some extracts and water extracts had certain antibacterial ability
of its active ingredients have the antibacterial effect in vitro against Streptococcus suis type II.
on various pathogenic bacteria of the respiratory tract, such
as staphylococcus, streptococcus, Haemophilus influenzae, (2) Effect on Gram-Negative Bacteria. The experimental
Bacillus subtilis, Proteus, Klebsiella pneumoniae, Legionella strains of Gram-negative bacteria are mostly Enter-
and Moraxella catarrhalis [60]. Glycyrrhiza uralensis has obacteriaceae bacteria, including Escherichia coli, Klebsiella
been proved to be effective in inhibiting the human re- pneumoniae, Salmonella, Shigella, and nonfermenting bac-
spiratory syncytial virus (HRSV), but it was unclear whether teria Pseudomonas aeruginosa and Acinetobacter baumannii.
Glycyrrhiza uralensis or Glycyrrhiza uralensis preparata Generally, Lonicera japonica’s antibacterial effect on Gram-
would be better and which constituent was active until Feng negative bacteria is lightly inferior to that on Gram-positive
et al. [61]. They did thrombocytopenic experiments with bacteria.
HEp-2 and A549 cell lines and detected the active constit- Studies showed that [66, 67] Lonicera japonica extracts
uents for the antirespiratory syncytial virus in the hot water and nanosilver particles had broad application prospects
extracts of Glycyrrhiza uralensis formulas, such as glycyr- with their strong inhibitory effect on Escherichia coli; Mu
rhizic acid and 18β-glycyrrhetic acid (18β-GA). The abilities et al. [68], reported that Lonicera japonica extracts had
of crude Glycyrrhiza uralensis to inhibit viral replication and certain antibacterial activities on clinically isolated pneu-
to stimulate IFN-β were evaluated by reverse transcription monia Kreb bacteria. They also claimed that using Chinese
polymerase chain reaction (RT-PCR) and enzyme-linked herbal medicine for bacterial infectious diseases could
immunosorbent assay (ELISA), respectively. The results prevent drug resistance quickly developed by bacteria and
showed that Glycyrrhiza uralensis had better effects on HEp- reduce side effects caused by excessive use of antibacterial
2 cells than Glycyrrhiza uralensis preparata, and there was no drugs.
difference on A549 cells; glycyrrhizin was ineffective, and Chlorogenic acid, the main component of Lonicera
18β-GA exhibited potent anti-HRSV activity. Therefore, japonica, has a significant effect on inhibiting the growth
they believed that both Glycyrrhiza uralensis and Glycyrrhiza of Meningococcus, Salmonella typhi, and Escherichia coli.
uralensis preparata could effectively fight against HRSV The antibacterial mechanism is related to the non-
infection of the upper respiratory tract epithelial cells; competitive inhibition of arylamine-N-acetyltransferase
Glycyrrhiza uralensis could repress viral adhesion and in- (NAT) in bacteria [69]. By detecting the conductivity,
ternalization and inhibit HRSV by stimulating the secretion alkaline phosphatase activity, absorbance, and penetra-
of interferons. 18β-GA might be one of its active tion of the hydrophobic fluorescent dye 1-N-phenyl-
constituents. naphthylamine (NPN) on the bacterial membrane and
the wall, it was found that chlorogenic acid could increase
6.3. Antibacterial Effect the permeability of the cell wall of Escherichia coli,
allowing cell electrolytes, enzymes, etc. to penetrate into
6.3.1. Lonicera japonica. Traditional Chinese herbs are the the membrane and the wall, consequently leading to
essence of nature; many of them are anti-infectives and apoptosis [70].
6.3.2. Ophiopogon japonicus. Liang et al. [71] detected the JNK in the MAPK signaling pathway and exerting significant
antibacterial effect and inhibition of peptide deformylase anti-inflammatory activity [80].
(PDF) when using the fluorescence method and MTT Total saponins of Ophiopogon japonicus could inhibit
method to the endophytic fungi of Ophiopogon japonicus. endothelial cell apoptosis and upregulate the expression of
the endothelial cell adhesion factor (CD31) to play anti-
inflammatory effect [81].
6.3.3. Glycyrrhiza uralensis. Modern experimental studies Tian et al. [82] studied the in vivo anti-inflammatory
showed that the water extracts, methanol extracts, and su- activity of water extracts (Lm-a), total saponins (Lm-s), and
percritical extracts of Glycyrrhiza uralensis had considerable main components (Lm-3) of Ophiopogon japonicus by
inhibitory effects on variety of Gram-negative and Gram- establishing the inflammatory model of mice auricle-
positive bacteria [72]. Wang et al. [73] found that glycyr- swelling and carrageenan- or histamine-induced swelling of
rhizic acid could significantly increase the production of the ankle of mice, and examined the in vitro anti-in-
reactive oxygen species and nitrogen, promote the expres- flammatory activity of Lm-3 by tumor necrosis factor-α
sion of antibacterial genes, activate chicken macrophages, (TNF-α) or phorbol ester (PMA)-induced myeloid leukemia
and enhance the ability of phagocytic cells and Salmonella. cell line (HL-60) and the human umbilical vein endothelial
cell (ECV304) adhesion model. It was found that Lm-a,
6.3.4. Platycodon grandiflorum. It was found that platycodin Lm-s, and Lm-3 could significantly alleviate p-xylylene-
D had antibacterial activity and, with the increase of con- induced ear swelling and carrageenan-induced paw swelling,
centration of platycodin D, could gradually reduce the and the mechanism might be related to the regulation of
adhesion and viability of candidosis of C. albicans, inhibit its proteinkinase C pathway.
transformation from spore to mycelial phase, decrease the Ma et al. [83] also found in vitro that ruscogenin could
content of IL-8 and HBD-2 protein in supernatant, and the strikingly inhibit the adhesion of cytokine TNF-α-induced
expression of HBD-2 mRNA in KB cells. The study indicated HL-60 cells to ECV304 cells.
that platycodin D might reduce the infection of oral mucosa
of Candida albicans by its immunosuppressive effect on oral
mucosal epithelial cells [74]. 6.4.3. Glycyrrhiza uralensis. The active ingredient of Gly-
cyrrhiza uralensis has a good anti-inflammatory effect.
Studies showed that the total saponins from wild Glycyrrhiza
6.4. Antipyretic and Anti-Inflammatory Effects uralensis in Gansu could inhibit the secretion of nitric oxide
6.4.1. Lonicera japonica. Ryu et al. [75], pointed out that (NO), tumor necrosis factor alpha (TNF-α), and interleukin
Lonicera japonica extracts had good anti-inflammatory and (IL)-6 inflammatory factors to achieve anti-inflammatory
analgesic effects and performed better when absorbed by effects [84].
intestine. Lonicera japonica could also be used in the Li et al. [85] found that Glycyrrhiza uralensis total sa-
treatment of pertussis, pneumonia, acute appendicitis, acute ponins could not only significantly reduce the release of NO,
mastitis, influenza, and other diseases. Some scholars used IL-1, and TNF-α from lipopolysaccharide (LPS)-induced
cigarette smoke extracts to stimulate KB cells, constructed an macrophage cell line RAW264.7, but also reduce the syn-
acute oral inflammation model and studied the antiacute thesis of the arachidonic acid metabolic pathway PGE 2 by
oral inflammation of Lonicera japonica [76]. It was found inhibiting the phospholipase A2 (PLA 2) enzyme activity
that the Lonicera japonica could inhibit the expression of and cyclooxygenase-2 (COX-2) expression. Matsui et al. [86]
TNF-α, IL-6, and IL-8 and promote the decrease of IL-10 studied on the structure-activity relationship of Glycyrrhiza
secretion, which was dose-dependent, suggesting that uralensis and found that glycyrrhizin itself had direct anti-
Lonicera japonica had a certain therapeutic effect on oral inflammatory effects in vitro, not depending on
inflammation. The flavonoids of Lonicera japonica could glucocorticoids.
also inhibit the inflammatory mediators TNF-α and IL-1β Xie et al. [87] used the airway instillation (LPS)-induced
through the PI3K/Akt/NF-kB signaling pathway [77]. The mouse pneumonia model to study the anti-inflammatory
extracts of Lonicera japonica and chlorogenic acid acted as mechanism of flavonoids in Glycyrrhiza uralensis. The re-
an activator of the AMPK/Nrf2 pathway and could inhibit sults showed that total flavonoids of Glycyrrhiza uralensis
phosphorylation of NF-kB, JAK-1, STAT-1, and MAPK reduced neutrophils recruitment by inhibiting inflammatory
pathways, thereby reducing acute and chronic inflammatory cell infiltration and the release of mediators and therefore
responses induced by lipopolysaccharides [78]. relieved the oxidative damage of neutrophils.
The luteolin derived from Lonicera japonica, possible by
the inhibition of ERK1/2, JNK1/2, and NF-kB pathway,
6.4.4. Platycodon grandiflorum. The anti-inflammatory ac-
could regulate TNF-α, IL-6, IL-8, and GM-CSF, decrease
tivity of Platycodon grandiflorum is mainly due to the
COX-2 expression, and intracellular Ca 2 release [79].
presence of platycodin, which has the strongest anti-in-
flammatory activity of platycodin D and D3 and the in-
6.4.2. Ophiopogon japonicus. Ophiopogon japonicus could flammatory model induced by phorbol ester (TPA), which
reduce the production of nitric oxide and proinflammatory inhibits the production of prostaglandin E2 [88]. For the
cytokines by inhibiting the phosphorylation of ERK1/2 and model of inflammation induced by lipopolysaccharide and
platycodin D and D3 could inhibit NO production and was administered orally to Wistar rats at a dose of 50 mg/kg
increase TNF-α secretion [89]. and 100 mg/kg. The results showed that glycyrrhizic acid
Studies showed that platycodon could not only effectively reduced the total number of proteins, total cells, and elas-
improve the symptoms of bronchial asthma, but also prevent ticity by inhibiting the activity of caspase in the lung tissue in
bronchitis; high dose group of Platycodon grandiflorum could lung epithelial cells. Protease activity enhanced LDH and
effectively prolong the asthmatic latency of asthmatic guinea ALP activity on phospholipids in BALF for protection.
pigs, significantly inhibit the generation and release of oxygen- Zhang et al. [97] found that Glycyrrhiza uralensis flavonoids
free radicals, effectively promote asthma guinea pig could inhibit the synthesis of proinflammatory cytokines
c—interferon (IFN-c) and human lipoxin A4 (LXA4) release, TNF-α, IL-6, and IL-1β induced by lipopolysaccharide
indirectly balance helper T cells (Th) 1/Th2, and regulate LXA4 (LPS). HE staining of the lung tissue could directly prove
in the body to exert anti-inflammatory and prodissipative effects that Glycyrrhiza uralensis flavonoids had protective effects
[90]. Platycodin saponins lowered the level of granulocyte- on acute lung injury and could improve histological changes
macrophage aggregation stimulating factor (GM-CSF), reduced such as inflammatory cell infiltration and interstitial edema
the expression of interleukin (IL-13) in cells, and inhibited the in the lungs.
activation of NF-kb and the MAPK pathway to achieve anti-
inflammation [91]. Platycodin saponins could fight with various
inflammations by inhibiting the PGE2 (prostate) pathway and 6.5.4. Platycodon grandiflorum. Liu et al. [98] found that
NO (nitric oxide) secretion. platycodin D could effectively reduce the content of CI,
In addition, total saponins of Platycodon grandiflorum, PIIIP, and HA in rat serum, down-regulate the expression of
in the antiallergic test and the skin test of mast cells in vitro, TGF-βm RNA in rat lung tissue, and effectively improve the
had significant inhibition of the release of hexosaminidase general clinical symptoms of pulmonary fibrosis induced by
and histamine and were potential to be developed as anti- bleomycin hydrochloride in rats. It was speculated that it
allergic drugs [92]. might inhibit the synthesis of extracellular matrix in the lung
tissue of mice with pulmonary fibrosis and promote its
degradation, thereby reducing collagen deposition and in-
6.5. The Role of Protecting the Lungs hibition during the formation of pulmonary fibrosis. The
expression of TGF-βm RNA in rat lung tissue reached the
6.5.1. Lonicera japonica. In an experiment evaluating the antifibrotic effect.
biological effects of Lonicera japonica on a mouse model of Chen et al. [99] found that platycodin saponins could
chronic obstructive pulmonary disease, inhalation of Lonicera significantly alleviate the pathological changes of airway
japonica microparticles reduced the levels of TNF-α and IL-6 remodeling in chronically branched mice. The intervention
in bronchoalveolar fluid of mice with chronic obstructive mechanism might be through the removal of inflammatory
pulmonary disease and allowed them to be in peripheral factors and free radicals in the lung tissue of chronically icy
blood. The number of inflammatory cells including neutro- mice [100]. At the same time, it could inhibit the expression
phils is reduced. In addition, Lonicera japonica microparticles of MMP9 and TIMP-1, so as to reduce the deposition of
can induce the recovery of elastin and collagen distribution in collagen to reduce tracheal stenosis and achieve the purpose
the lung tissue of mice with chronic obstructive pulmonary of reversing airway remodeling.
disease, and reduce the expression of Caspase-3. The above Yao et al. [98] reported that total saponins of Platycodon
experimental results show that inhaled Lonicera japonica grandiflorum might significantly reduce the inflammatory
particles have a good development prospect in the treatment pathology of the lung tissue induced by PM2.5 by regulating
of chronic obstructive pulmonary disease [93]. the balance of inflammatory cytokines, and inhibiting the
process of pulmonary fibrosis by reducing the expression of
TGF-β gene and protein to protect and repair the lung tissue.
6.5.2. Ophiopogon japonicus. Ruscogenin has a remission
effect on lung injury [94]. It was observed on sacrificed ICR
mice, after one-hour oral administration of ruscogenin (0.3, 6.6. Antitussive Effect
1.0, and 3.0 mg·kg− 1) followed with eight-hour induction of
lung injury by lipopolysaccharide (LPS) 30 mg·kg− 1 (iv), 6.6.1. Ophiopogon japonicus. Studies showed that the Chi-
which ruscogenin significantly reduced the ratio of wet nese herbal formula “Maimendong Decoction” had an an-
weight/dry weight of the lungs and improved various his- titussive effect and was now used to treat dry cough caused
topathological changes (pulmonary edema, inflammatory cell by pharyngitis and bronchitis [101]. Studies have also
aggregation and infiltration, etc.), which suggested that rus- confirmed that in the animal model of bronchitis, Mai-
cogenin might inhibit the tissue factor, induce the nitric oxide mendong Decoction could inhibit the increase of tracheal
synthase expression, and improve the activation of NF-kB p65 vagal afferent nerve electrical stimulation, indicating that the
to relieve the lung injury induced by LPS [95]. site of antitussive effect of Maimendong Decoction may be
in the trachea [102].
Some foreign scholars have found that the pharmaco-
6.5.3. Glycyrrhiza uralensis. Qamar et al. [96] investigated logical effects of Maimendong Decoction on antitussiveness
the protective effects of glycyrrhizic acid (GA) on benzo(a) were consistent with OP-D, indicating that OP-D may be
pyrene-induced lung injury in Wistar rats. Glycyrrhizic acid one of the antitussive ingredients in Maimendong
Decoction, and the nystatin perforated membrane was used. 7. Cytotoxic Activity
The clamp technique was used to investigate the effect of OP-
D on the parasympathetic nerves of the acutely isolated rat 7.1. Lonicera japonica. The tetraploid was tested for acute
paratracheal ganglia. It was found that OP-D exerts hy- toxicity by diploid Lonicera japonica medicinal materials
perpolarization on paratracheal neurons by activating K [110]. The pretest was used to determine the median lethal
channels, which clarified the mechanism of action of OP-D dose. The mice with tetraploid and diploid Lonicera japonica
antitussive [101] to some extent. Tang et al. [103] studied the were calculated by the BLISS method. The median lethal
antiasthmatic and antiallergic effects of Ophiopogon japo- dose (LD50) was 72.12 g/kg and 69.92 g/kg, respectively,
nicus polysaccharide (POT) through animal experiments. which were equivalent to 412 times and 400 times of clinical
The results showed that Ophiopogon japonicus poly- doses, indicating that tetraploid and diploid Lonicera ja-
saccharide could inhibit the contraction of bronchial smooth ponica have lower acute toxicity and larger safety range.
muscle, reduce the occurrence of asthma, and had a more From the perspective of chemical composition of tetraploid
significant effect on mouse skin allergies; in addition, the Lonicera japonica, the quality of tetraploid Lonicera japonica
saponin A and the saponin B could inhibit the expression of medicinal materials is unstable and needs further study.
eosinophilic chemokines induced by IL-4 and TNF-α [104], From acute toxicity studies and related pharmacodynamic
and the prospect of these three compounds was brilliant in studies, tetraploid Lonicera japonica medicinal materials are
the treatment of allergic bronchial asthma. acutely toxic and related drugs. There is no significant
difference between diploid and Lonicera japonica, and it is
6.6.2. Glycyrrhiza uralensis. Glycyrrhiza uralensis has been safe and effective in clinical application.
a good medicine for antitussive and cough since ancient However, Lonicera japonica is cold, and if it is taken too
times. The preparation of Glycyrrhiza uralensis, such as much, it will cause adverse reactions. Pu et al. studied the
compound Glycyrrhiza uralensis tablets, is also a common toxic effects of cold Chinese medicine on mice and found
drug for the treatment of cough and asthma in clinical that the content of copper, zinc, magnesium, and phos-
practice. Han et al. [105] found that the content of gly- phorus in the liver tissue of mice was significantly increased
cyrrhetinic acid in the water extracts of Glycyrrhiza ura- after drinking Lonicera japonica. The manganese content
lensis after transformation by intestinal flora increased increased slightly, the iron content decreased significantly,
significantly, and the inhibition rate of cough latency and the color of the liver became darker, the morphology did not
cough frequency of experimental mice was higher than change significantly, the spleen became smaller, the body
that before transformation. hair was dark yellow, the body shape became thinner, and
Yu et al. [106] found that the geraniol extract, Glycyr- the activity decreased. Compared with the control group, the
rhiza uralensis flavonoids, and glycyrrhetinic acid could difference was not statistically significant [111].
obviously relieve the cough and eliminate phlegm on mice
with ammonia cough and SO2 cough test. Wu [107] found by 7.2. Ophiopogon japonicus. Lin et al. [112] studied the cy-
intravenous injection of sodium glycyrrhetinate that it had totoxicity of dextran D′ on rat cardiomyocyte H9c2 and
antitussive and expectorant effects on the mouse cough found that higher concentration of dextran D’s had a sig-
model caused by ammonia spray, and its antitussive effect nificant cytotoxic effect on H9c2 cardiomyocytes. Hu et al.
was weaker than codeine but not addictive. [113], used the mouse lymphoma cell test (MLA) and mouse
bone marrow micronucleus test (MNT) to study the gen-
otoxicity of Ophiopogon japonicus decoction and found that
6.6.3. Platycodon grandiflorum. Platycodon grandiflorum Ophiopogon japonicus decoction in ±S9 conditions (non-
has excellent antitussive and expectorant activity. According metabolic activation (− S9) and metabolic activation (+S9)
to statistics, only the Chinese pharmacopoeia contains 65 conditions could induce tk locus mutation in L5178Y cells,
kinds of antitussive and expectorant formulas containing suggesting that there might be mutagenic substances;
platycodon. Zhu et al. [108] selected 9 different origins of however, the test article had no damage to mouse bone
Platycodon grandiflorum and found that it has significant marrow cells and was activated by metabolism in vivo.
antitussive and antitussive effects, and the effects of different Genotoxic effects were not shown. In addition, the aqueous
producing areas are obviously different. extract of Ophiopogon japonicus had no significant effect on
In the Chinese Pharmacopoeia 2005 edition, the total maternal and embryo/fetal development of SD rats. There
saponin content of Platycodon grandiflorum is not less than was no obvious maternal toxicity and embryonic/fetal de-
6%; in the Chinese Pharmacopoeia 2015 edition, the content velopmental toxicity in wheat winter water extract [114].
of platycodin D (C57H92O28) is not less than 0.10%. How-
ever, studies have shown that the cough and sputum activity
of Platycodon grandiflorum has no obvious correlation with 7.3. Glycyrrhiza uralensis. In order to evaluate the toxico-
the content of platycodin D, and it has no obvious corre- logical safety of the aerial part of the Glycyrrhiza uralensis,
lation with the total saponin content of Platycodon gran- Zhao et al. [115] used the acute oral toxicity test, the mouse
diflorum, suggesting that its activity has a complex bone marrow micronucleus test, the mouse sperm abnor-
relationship. Therefore, further research is needed to clarify mality test, and the safety test method based on the in-
the memory correlation between antitussive and antispas- flammatory model. It turned out that the maximum
modic activities and components [108, 109]. tolerated dose (MTD) of water extraction on the aerial part
of Glycyrrhiza uralensis to the mice was 96 g·kg− 1, but it was and Platycodon grandiflorum all assuredly have certain
not shown to be genotoxic to mice. Its safety still needs antibacterial, antipyretic, and anti-inflammatory effects;
further study. all these herbs have the effect of protecting the lungs
As a traditional Chinese medicine, Glycyrrhiza uralensis is except for Lonicera japonica. CSP is chiefly caused by
widely used in the prescription of traditional Chinese med- pathogenic microbial infection, allergic reaction, and
icine. Therefore, Glycyrrhiza uralensis has the name of “ten- inflammation adjacent to the lungs, which indicates that
party and nine-grass.” The mechanism of toxicity and at- the aforementioned four Chinese herbs are in line with the
tenuation of Glycyrrhiza uralensis after compatibility with principle of symptomatic treatment. Additionally, in the
toxic Chinese medicine has many aspects. The mechanism of theory of traditional Chinese medicine, the throat is in-
attenuating compatibility should be utilized, and the mech- ternally related to the lung, which is the organ that
anism of toxicity and compatibility should also be paid at- controls the respiration and immunity; therefore, the
tention to. Chen [116] found that glycyrrhizic acid and Ganzi health of the throat depends on the lung to some extent. In
could form molecular complexes with Ganzi during de- the clinical, the treatment of CSP with herbal tea has been
coction, increasing the dissolution rate of toxic substances of promoted currently and the systematic evaluation showed
Ganzi and increasing the toxic components of decoction. Jin a good clinical efficacy.
et al. [117] used intraperitoneal injection of scutellaria or According to the statistical results, the frequencies of
seaweed decoction and subcutaneous injection of Glycyrrhiza Lonicera japonica, Ophiopogon japonicus, Glycyrrhiza
uralensis decoction and found that the toxicity of sassafras uralensis, and Platycodon grandiflorum are significantly
increased with the increase of Glycyrrhiza uralensis dosage. higher than other traditional Chinese herbs, which are
Studies suggested that the increase in toxicity was not due to based simply on the statistics of related literature. Thus far,
changes in the physical and chemical properties of the no efficacy evaluation of the herbal tea made with these
mixture, but might be the result of interactions between the four kinds of herbs has been reported, and the study on the
drug and the animal. The study also found that Ganzi might interaction of active ingredients in water extracts of these
increase the expression and activity of CYP2E1 in rats and four herbs is still waiting to be conducted. In our research,
promote the conversion of precarcinogens and protoxins into the Chinese herbal tea indeed contains ingredients that
carcinogens and poisons, leading to toxic effects on the body, can alleviate CSP symptoms, but the current studies on
and then confirmed that, at the level of mRNA, protein ex- herbal tea in the treatment of CSP are still at a relatively
pression and enzyme activity, there might be drug-drug in- rough stage, obviously shown by the evaluation of liter-
teractions based on the mechanism of drug metabolism ature quality. Systematic meta-analysis is difficult to be
enzymes in Ganzi and Glycyrrhiza uralensis [118]. performed as the qualities of RCT articles are generally
low.
7.4. Platycodon grandiflorum. In order to study whether the 9. Conclusion

extract of Platycodon grandiflorum as a feed additive and
long-term application in the livestock and poultry industry In the theory of traditional Chinese medicine, the concept of
will cause toxic reactions, the toxicological test of the water “seven emotions” refers to seven methods in compatibility of
extract of Platycodon grandiflorum was carried out [119]: In ingredients, including using alone, mutual reinforcing,
the acute toxicity test, when LD50 > 30360 mg/kg, there were assisting, detoxifying, being detoxified, inhibiting, and an-
no deaths or other abnormal behaviors in the mice, indicating tagonizing. Generally, the compatibility of two or more
that the water extract of the platycodon is an actual nontoxic Chinese herbs does not simply give rise to an additive effect;
substance. In the accumulation toxicity test, during the ob- the interactions are still in the study when it comes to
servation period and during the 7-day withdrawal period, traditional Chinese medicine compounds. Moreover, tra-
there was no death in the mice of each test group and no ditional Chinese medicine believes that syndromes can vary
abnormality in spirit, diet, and drinking water, and no other considerably with the cause, which literally means different
abnormal behavior occurred. After 20 days of administration, prescriptions for different syndromes; thus, more attention
there was no abnormality and death in the mice of each test should be paid in the clinical diagnosis and treatment of
group and control group. At the same time, the average body CSP.
weight gained, and the average material consumption and In the field of Chinese herbal botany, further studies on
organ coefficient of the mice in the experimental group were the components of the water extracts of those four kinds of
not significantly different from those of the control group. The herbs are expected because the active constituents would be
difference indicated that the water extract of Platycodon the closest way to understanding herbal tea. Besides, most of
grandiflorum had no accumulation effect. It proved that the the toxicological studies on those four kinds of herbs were
water extract of Platycodon grandiflorum was nontoxic and focused on animal experiments. Although testing on human
has a better application prospect than antibiotics. body is, to some extent, unethical, yet the abnormal per-
formance of medicine on mice is still different from that on
8. Discussion human beings. The gap needs to be discussed.
In clinic, the overall quality of clinical research on
As was presented above, the water extracts of Lonicera Chinese medicine still needs to be improved, and the various
japonica, Ophiopogon japonicus, Glycyrrhiza uralensis, elements of randomized controlled trials have to be
standardized so that reliable articles could be obtained to [11] L. T. Liu, “Herbal tea in the Qing dynasty medical archives,”
accurately evaluate the efficacy of Chinese herbal tea. Chinese Journal of Integrated Traditional and Western
Herbal tea in the treatment of CSP has the characteristics Medicine, vol. 37, no. 11, pp. 1290-1291, 2017.
of convenience, economy, relative safety, and certainly ef- [12] J. N. Zhu, Preliminary Investigation on the Law of Medication
fective. It is indeed worth popularization and further study Used in the Qing Dynasty on Herbal Tea Essence and the
Modern Application of Herbal Tea, China Academy of
in clinic.
Chinese Medical Sciences, Beijing, China, 2017.
[13] Q. Bian and Y. An, “Research progress of herbal tea in the
Conflicts of Interest treatment of chronic pharyngitis,” Xinjiang Traditional
Chinese Medicine, vol. 34, no. 5, pp. 117–120, 2016.
The authors declare that there are no conflicts of interest [14] Y. H. Zhao, “Evaluation on the effect of Qingyan- herbal tea
regarding the publication of this paper. in the treatment of chronic pharyngitis,” Clinical Medical
Literature E-Magazine, vol. 4, no. 61, Article ID 12028, 2017.
[15] L. S. Wang, “Clinical observation on 100 cases of chronic
Authors’ Contributions pharyngitis treated with herbal tea decoction,” Chinese
Modern Pharmaceutical Applications, vol. 9, no. 15,
Chengxian Li did most of the work, Wu and Yuan’s
pp. 257-258, 2015.
workload was the second, and Yuan was the author of the [16] G. Zeng, Z. L. Qu, and P. Niu, “Clinical observation on 67
communication. Additionally, Shang Wang was involved in cases of chronic pharyngitis treated with self-made tradi-
searching the pharmacological-related literature, Jingyu tional Chinese medicine,” Chinese General Practice, vol. 11,
Xing was responsible for the translation and modification of no. 4, pp. 589-590, 2013.
the article, Qi Ding, Min Wang, QingQing Zhang, and Ju [17] C. M. Liu, L. X. Zhang, and P. D. Dong, “Clinical observation
Zhang were responsible for the fluency of the text. on treatment of chronic pharyngitis with Shuang-Yuan
herbal tea,” Chinese Practical Medicine, vol. 7, no. 3,
pp. 152-153, 2012.
Acknowledgments [18] H. Q. Zhang and G. Y. Liu, “Effect of Qingyin decoction on
chronic pharyngitis in asthmatic patients with long-term
This work was supported by the National Natural Science
inhalation of sulpiride,” Chinese Journal of Integrated Tra-
Foundation of China (NSFC no. 81273613), Special Research ditional and Western Medicine, vol. 37, no. 11, pp. 1290-1291,
Project of Chinese Medicine Industry (no. 201107006), and 2011.
Tianjin University of Traditional Chinese Medicine pre- [19] B. L. Wang and Z. D. Li, “120 cases of chronic pharyngitis
ventive treatment project (no. XJ201801). treated with traditional Chinese herbal tea,” Journal of
Changchun College of Traditional Chinese Medicine, vol. 4,
p. 51, 1994.
References [20] X. Y. Ding, Z. J. Lin, and D. Wang, “Advances in studies on
[1] Y. T. Hu, Otolaryngology Book, Shanghai Science and the components and pharmacological effects of Lonicera
Technology Press, Shanghai, China, 2000. japonica-forsythia,” Shandong Science, vol. 32, no. 3,
[2] W. J. Kong, L. Zhou, B. Q. Wang et al., Otolaryngology pp. 36–41, 2019.
Book, People’s Medical Publishing House, Beijing, China, [21] Y. L. Song, F. Y. Ni, Y. W. Zhao et al., “Advances in research
3rd edition, 2015. on chemical constituents of Lonicera japonica,” Chinese
[3] R. Weber, “Pharyngitis,” Primary Care: Clinics in Office Herbal Medicine, vol. 45, no. 24, pp. 3656–3664, 2014.
Practice, vol. 41, no. 1, pp. 91–98, 2014. [22] Y. L. Song, H. M. Wang, F. Y. Ni et al., “Study on phenolic
[4] J. O. Kumari and R. Rajendran, “Effect of topical nasal acids and their anti-inflammatory activities in Lonicera ja-
steroid spray in the treatment of non-specific recurrent/ ponica,” Chinese Herbal Medicine, vol. 46, no. 4, pp. 490–495,
chronic pharyngitis—a trial study,” Indian Journal of Oto- 2015.
laryngology and Head & Neck Surgery, vol. 60, no. 3, [23] Y. M. Gao, M. Z. Wang, J. P. Wang et al., “Study on chemical
pp. 199–201, 2008. constituents of Lonicera japonica,” Chinese Herbal Medicine,
[5] M. G. Kalra, K. E. Higgins, and E. D. Perez, “Common vol. 26, no. 11, pp. 568-569, 1995.
questions about streptococcal pharyngitis,” American Family [24] Y. F. Liu, L. P. Li, H. Y. Zhu et al., “Advances in research on
Physician, vol. 94, no. 1, pp. 24–31, 2016. chemical constituents and pharmacological action of Loni-
[6] C. R. Murray and K. S. Chennupati, “Chronic streptococcal and cera japonica,” Journal of Liaoning University (Natural Sci-
non-streptococcal pharyngitis,” Infectious Disorders—Drug ence Edition), vol. 45, no. 3, pp. 255–262, 2018.
Targets, vol. 12, no. 4, pp. 281–285, 2012. [25] F. Y. Ni, J. H. Wen, M. Li et al., “Study on chemical con-
[7] B. A. Choby, “Diagnosis and treatment of streptococcal stituents of Lonicera japonica,” Chinese Herbal Medicine,
pharyngitis,” American Family Physician, vol. 79, no. 5, vol. 48, no. 18, pp. 3689–3692, 2017.
pp. 383–390, 2009. [26] J. Wu, C. Wang, and H. C. Yu, “Advances in studies on
[8] H. Zhang, J. Zhang, Q. J. Zhang et al., “Summary of mis- chemical constituents and pharmacological effects of Loni-
diagnosed diseases of chronic pharyngitis,” Modern Chinese cera japonica,” Chinese Journal of Experimental For-
Doctor, vol. 50, no. 27, pp. 13-14, 2012. mulaology, vol. 25, no. 4, pp. 225–234, 2019.
[9] L. D. Zhao, H. L. Zhang, M. G. Li et al., “Treatment analysis [27] X. Y. Sun, F. Yu, W. Xiao et al., “Research progress on
of patients with chronic pharyngitis,” The World’s Latest modern application of Ophiopogon japonicus,” Modern
Medical Information Digest, vol. 14, no. 4, p. 109, 2014. Chinese Medicine, vol. 20, no. 11, pp. 1453–1458, 2018.
[10] Y. Chai and Z. Y. Gao, “Not inferior to the decoction of the [28] W. Peng, X. Ma, J. Wang et al., “Research progress on
herbal tea,” TCM Health, vol. 11, pp. 9–11, 2017. chemical constituents and pharmacological effects of
Ophiopogon japonicus,” Chinese Herbal Medicine, vol. 49, [43] X. J. Yong, Study on Extraction and Separation of Isoflavones
no. 2, pp. 477–488, 2018. and Chlorophyll from the Aboveground of Glycyrrhiza Ura-
[29] H. B. Ma, Study on Chemical Constituents of Ophiopogon lensis, Ningxia University, Yinchuan, China, 2005.
Japonicus, Beijing University of Traditional Chinese Medi- [44] Q. Zhang and M. Ye, “Chemical analysis of the Chinese
cine, Beijing, China, 2013. herbal medicine Gan-Cao (licorice),” Journal of Chroma-
[30] J. Guan and S. P. Li, “Discrimination of polysaccharides from tography A, vol. 1216, no. 11, pp. 1954–1969, 2009.
traditional Chinese medicines using saccharide mapping- [45] R. Zhou, L. Qi, Y. F. Wang et al., “Isolation, purification and
enzymatic digestion followed by chromatographic analysis,” high-performance capillary electrophoresis analysis of Gly-
Journal of Pharmaceutical and Biomedical Analysis, vol. 51, cyrrhiza uralensis,” Analytical Chemistry, vol. 27, no. 2,
no. 3, pp. 590–598, 2010. p. 245, 1999.
[31] A. Tada, R. Kasai, T. Saitoh, and J. Shoji, “Studies on the [46] A. Tada, Y. Kaneiwa, J. Shoji, and S. Shibata, “Studies on the
constituents of Ophiopogonis tuber. V. isolation of a novel saponins of the root of Platycodon grandiflorum A. De
class of homoisoflavonoids and determination of their Candolle. I. isolation and the structure of platycodin-D,”
structures. 1,” Chemical & Pharmaceutical Bulletin, vol. 28, Chemical & Pharmaceutical Bulletin, vol. 23, no. 11,
no. 5, pp. 1477–1484, 1980. pp. 2965–2972, 1975.
[32] C.-X. Zhou, L. Zou, J.-X. Mo et al., “Homoisoflavonoids from [47] Y. L. Deng, H. G. Ren, X. W. Ye et al., “Advances in research
Ophiopogon japonicus,” Helvetica Chimica Acta, vol. 96, on the history, chemical composition and pharmacological
no. 7, pp. 1397–1405, 2013. effects of Platycodon grandiflorum,” Chinese Journal of Ex-
[33] T. Asano, T. Murayama, Y. Hirai, and J. Shoji, “Comparative perimental Traditional Medical Formulae, pp. 1–12, 2019.
studies on the constituents of Ophiopogonis tuber and its [48] X. X. Xie, C. Zhang, J. X. Zeng et al., “Advances in studies on
congeners. VII. studies on the homoisoflavonoids of the chemical constituents and pharmacological activities of
subterranean part of Ophiopogon japonicus Ker-Gawler cv. Chinese medicine Platycodon grandiflorum,” Chinese Med-
Nanus. 2,” Chemical & Pharmaceutical Bulletin, vol. 41, icine Bulletin, vol. 17, no. 5, pp. 66–72, 2018.
no. 3, pp. 391–393, 1993. [49] W. W. Fu, D. Q. Dou, and Y. H. Pei, “Advances in studies on
[34] C.-L. Duan, Z.-Y. Kang, C.-R. Lin, Y. Jiang, J.-X. Liu, and chemical constituents and biological activities of Platycodon
P.-F. Tu, “Two new homoisoflavonoids from the fibrous grandiflorum,” Journal of Shenyang Pharmaceutical Uni-
roots of Ophiopogon japonicus (Thunb.) Ker-Gawl,” Journal versity, vol. 23, no. 3, pp. 184–191, 2006.
[50] Q. Liu, W. Li, Y. N. Zheng et al., “Advances in studies on
of Asian Natural Products Research, vol. 11, no. 10,
triterpenoid saponins and pharmacological activities in
pp. 876–879, 2009.
Platycodon grandiflorum,” Journal of Jilin Agricultural
[35] S. Lan, F. Yi, L. Shuang, W. Chen Jie, and X.-W. Zheng,
University, vol. 35, no. 2, pp. 221–228, 2013.
“Chemical constituents from the fibrous root of Ophiopogon
[51] X. M. Piao, Y. Yu, H. H. Sin et al., “In vitro antioxidant
japonicus, and their effect on tube formation in human
activity and total polyphenols and flavonoid aglycone con-
myocardial microvascular endothelial cells,” Fitoterapia,
tent of Platycodon grandiflorum,” Journal of Jilin Agricultural
vol. 85, no. 1, pp. 57–63, 2013.
University, vol. 39, no. 5, pp. 579–584, 2017.
[36] J.-M. Chang, C.-C. Shen, Y.-L. Huang et al., “Five new
[52] J. X. Lu, R. X. Liang, and H. B. Lin, “Advances in research on
homoisoflavonoids from the tuber of Ophiopogon japonicus,”
the role of Lonicera japonica against influenza virus,” Re-
Journal of Natural Products, vol. 65, no. 11, pp. 1731–1733, search and Practice on Chinese Medicines, vol. 32, no. 5,
2002. pp. 77–81, 2018.
[37] Y. Watanabe, S. Sanada, Y. Ida, and J. Shoji, “Comparative [53] K. J. Hu, K. X. Sun, J. L. Wang et al., “In vitro antiviral effect
studies on the constituents of Ophiopogonis tuber and its of chlorogenic acid,” Journal of Harbin Medical University,
congeners. IV. studies on the homoisoflavonoids of the vol. 35, no. 6, pp. 430–432, 2001.
subterranean part of Ophiopogon ohwii okuyama and [54] V. Sinisi, A. Stevaert, F. Berti et al., “Chlorogenic compounds
Ophiopogon jaburan (Kunth) lodd,” Chemical & Pharma- from coffee beans exert activity against respiratory viruses,”
ceutical Bulletin, vol. 33, no. 12, pp. 5358–5363, 1985. Planta Medica, vol. 83, no. 7, pp. 615–620, 2016.
[38] T. H. Nguyen, S. T. Van, A. Porzel, K. Franke, and [55] Z. K. Liu, J. P. Zhao, W. C. Li et al., “Computational screen
L. A. Wessjohann, “Homoisoflavonoids from Ophiopogon and experimental validation of anti-influenza effects of
japonicus Ker-Gawler,” Phytochemistry, vol. 62, no. 7, quercetin and chlorogenic acid from traditional Chinese
pp. 1153–1158, 2003. medicine,” Scientific Reports, vol. 6, article 19095, 2016.
[39] H. H. Li, M. Qing, J. Yu et al., “Research progress on Gly- [56] M. L. Zhang, F. Li, W. Liu et al., “Advances in research on
cyrrhiza uralensis,” Journal of Inner Mongolia Medical antiviral effect of Chinese medicine Lonicera japonica,”
University, vol. 37, no. 2, pp. 199–204, 2015. Journal of Liaoning University of Traditional Chinese Med-
[40] W. He, J. Ning, J. J. Wu et al., “Advances in studies on the icine, vol. 18, no. 9, pp. 156–158, 2016.
interaction between chemical constituents of Glycyrrhiza [57] Z. Zhou, X. Li, J. Liu et al., “Honeysuckle-encoded atypical
uralensis and cytochrome P450,” Chinese Herbal Medicine, microRNA2911 directly targets influenza A viruses,” Cell
vol. 47, no. 11, pp. 1974–1981, 2016. Research, vol. 25, no. 1, pp. 39–49, 2015.
[41] Y. N. Han, X. Y. Cheng, J. L. Hou et al., “Process for purifying [58] T. Utsunomiya, M. Kobayashi, R. B. Pollard, and F. Suzuki,
total flavonoids from the aboveground of Glycyrrhiza ura- “Glycyrrhizin, an active component of licorice roots, reduces
lensis by macroporous resin,” Jilin Traditional Chinese morbidity and mortality of mice infected with lethal doses of
Medicine, vol. 34, no. 1, pp. 82–86, 2014. influenza virus,” Antimicrobial Agents and Chemotherapy,
[42] W. Li, X. B. Song, L. J. Zhang et al., “Research progress on vol. 41, no. 3, pp. 551–556, 1997.
chemical constituents in Glycyrrhiza uralensis,” Journal of [59] X. Zhang, M. X. Zheng, Z. B. Zhu et al., “Study on the anti-
Liaoning University of Traditional Chinese Medicine, vol. 14, respiratory virus infection of Lonicera japonica in vitro,” New
no. 7, pp. 40–42, 2012. Chinese Medicine, vol. 46, no. 6, pp. 204–206, 2014.
[60] M. F. Zhang and Y. Q. Shen, “Advances in studies on an- Biotechnology, and Biochemistry, vol. 74, no. 10, pp. 2022–
tibacterial and antiprotozoal pharmacology of Glycyrrhiza 2028, 2010.
uralensis,” Journal of Clinical Drug Therapy, vol. 7, no. 2, [76] P. L. Li, L. L. He, C. Y. Li et al., “Comparison of anti-acute
pp. 49–53, 2009. oral inflammation between Lonicera japonica and sinensis,”
[61] Y. C. Feng, W. K. Chih, C. L. Chai, D. E. Shieh, M. H. Yen, Journal of Sun Yat-Sen University (Natural Science Edition),
and J. S. Chang, “Water extract of licorice had anti-viral vol. 55, no. 4, pp. 118–122, 2016.
activity against human respiratory syncytial virus in human [77] M. H. Han, W. S. Lee, A. Nagappan et al., “Flavonoids
respiratory tract cell lines,” Journal of Ethnopharmacology, isolated from flowers of Lonicera japonica Thunb. Inhibit
vol. 148, no. 2, pp. 466–473, 2013. inflammatory responses in BV2 microglial cells by sup-
[62] Y. W. Li, Z. S. Wang, and X. W. Liu, “Advances in anti- pressing TNF-α and IL-β through PI3K/akt/NF-kb signaling
infective effects of Lonicera japonica,” Chinese Modern pathways,” Phytotherapy Research, vol. 30, no. 11,
Doctors, vol. 57, no. 12, pp. 165–168, 2019. pp. 1824–1832, 2016.
[63] K. Y. Huang, Z. X. Xie, Q. H. Wu et al., “In vitro transdermal [78] P. S. Young, J. M. Ling, Y. E. Hye, Y. Kim, and G. Park,
test and antibacterial activity of compound Lonicera japonica “Neochlorogenic acid inhibits against LPS-activated in-
external lotion and its single-flavored drug,” Modern Chinese flammatory responses through up-regulation of Nrf2/HO-1
Medicine, vol. 19, no. 6, pp. 798–803, 2017. and involving AMPK pathway,” Environmental Toxicology
[64] E. C. Chan, S. Tan, and Y. Lim, “Standardised herbal extract and Pharmacology, vol. 62, no. 1, pp. 1–10, 2018.
of chlorogenic acid from leaves of Etlingera elatior (Zingi- [79] O.-H. Kang, J.-G. Choi, J.-H. Lee, and D.-Y. Kwon, “Luteolin
beraceae),” Pharmacognosy Research, vol. 3, no. 3, pp. 178– isolated from the flowers of Lonicera japonica suppresses
184, 2011. inflammatory mediator release by blocking NF-κB and
[65] Z. Y. Ruan, Z. M. Wang, J. J. Li et al., “Study on antibacterial MAPKs activation pathways in HMC-1 cells,” Molecules,
activity of Lonicera japonica volatile oil and residue extract,” vol. 15, no. 1, pp. 385–398, 2010.
Modern Food Technology, vol. 33, no. 10, pp. 77–82, 2017. [80] J. W. Zhao, D. S. Chen, C. S. Deng, Q. Wang, W. Zhu, and
[66] L. Yang, F. Qu, Z. P. Aguilar, H. Wei, H. Xu, and H. Xu, L. Lin, “Evaluation of anti-inflammatory activity of com-
“Enhanced antimicrobial activity of silver nanoparticles- pounds isolated from the rhizome of Ophiopogon japonicas,”
Lonicera japonica Thunb combo,” IET Nanobiotechnology, BMC Complementary and Alternative Medicine, vol. 17,
vol. 10, no. 1, pp. 28–32, 2016. no. 1, p. 7, 2017.
[67] J. Han, Q.-Y. Lv, S.-Y. Jin et al., “Comparison of anti-bac- [81] L.-Q. Bi, R. Zhu, H. Kong et al., “Ruscogenin attenuates
terial activity of three types of di-O-caffeoylquinic acids in monocrotaline-induced pulmonary hypertension in rats,”
Lonicera japonica flowers based on microcalorimetry,” International Immunopharmacology, vol. 16, no. 1, pp. 7–16,
Chinese Journal of Natural Medicines, vol. 12, no. 2, 2013.
pp. 108–113, 2014. [82] Y. Q. Tian, J. P. Kou, L. Z. Li et al., “Anti-inflammatory effects
[68] T. J. Mu, F. L. Yang, H. H. Jin et al., “Experimental study and of aqueous extract from Radix Liriope muscari and its major
clinical application of Chinese herbal medicines such as active fraction and component,” Chinese Journal of Natural
forsythia on the antibacterial activity of Klebsiella pneu- Medicines, vol. 9, no. 3, pp. 222–226, 2011.
moniae,” Western Journal of Traditional Chinese, vol. 28, [83] L. Ma, J. P. Kou, Y. Huang et al., “Effect of russaponin on
no. 9, pp. 19–21, 2015. adhesion of HL-60 to ECV304 cells,” Chinese Pharmaco-
[69] P. Wei, A. J. Tan, S. M. Lu, et al., “Study on elimination of logical Bulletin, vol. 22, no. 6, pp. 706–709, 2006.
drug resistance of pathogenic Escherichia coli by traditional [84] J. X. Dong, Y. Deng, L. Liu et al., “Effects of endophytic
Chinese medicine,” Jiangsu Agricultural Sciences, vol. 45, fermentation broth and host decoction, total flavonoids and
no. 11, pp. 127–129, 2017. total saponins from Gansu wild Glycyrrhiza uralensis on the
[70] Z. E. Zhou, Q. S. Luo, J. H. Xiong et al., “Antibacterial secretion of inflammatory factors induced by LPS in RAW
mechanism of chlorogenic acid and isochlorogenic acid a 264.7,” Journal of North Pharmacy, vol. 13, no. 7, pp. 137-138,
against Escherichia coli,” Food Science and Technology, 2016.
vol. 39, no. 3, pp. 228–232, 2014. [85] X. H. Li, Y. Qi, R. L. Cai et al., “Anti-inflammatory mech-
[71] H. Liang, Y. Xing, J. Cheng, D. Zhang, S. Guo, and C. Wang, anism of total saponins of Glycyrrhiza uralensis,” Chinese
“Antimicrobial activities of endophytic fungi isolated from Journal of Experimental Formulaology, vol. 16, no. 5,
Ophiopogon japonicus (liliaceae),” BMC Complementary and pp. 110–113, 2010.
Alternative Medicine, vol. 12, pp. 238–243, 2012. [86] S. Matsui, H. Matsumoto, Y. Sonoda et al., “Glycyrrhizin and
[72] X. H. Nie, G. Y. Yin, B. J. Shi et al., “Antitumor activity and related compounds down-regulate production of in-
immunological activity of active components of Glycyrrhiza flammatory chemokines IL-8 and eotaxin 1 in a human lung
uralensis fisch in vitro,” Chinese Medicine, vol. 26, no. 7, fibroblast cell line,” International Immunopharmacology,
pp. 507–509, 2003. vol. 4, no. 13, pp. 1633–1644, 2004.
[73] B.-K. Wang, Y.-L. Mao, L. Gong et al., “Glycyrrhizic acid [87] Y.-C. Xie, X.-W. Dong, X.-M. Wu, X.-F. Yan, and Q.-M. Xie,
activates chicken macrophages and enhances their Salmo- “Inhibitory effects of flavonoids extracted from licorice on
nella-killing capacity in vitro,” Journal of Zhejiang Univer- lipopolysaccharide-induced acute pulmonary inflammation
sity-Science B, vol. 19, no. 10, pp. 785–795, 2018. in mice,” International Immunopharmacology, vol. 9, no. 2,
[74] L. F. Zhu and B. Wang, “Effect of platycodin D on oral pp. 194–200, 2009.
mucosal epithelial cells infected with Candida albicans,” [88] Y. P. Kim, E. B. Lee, S. Y. Kim et al., “Inhibition of pros-
Chinese Journal of Pathophysiology, vol. 33, no. 1, pp. 161– taglandin E2 production by platycodin D isolated from the
165, 2017. root of Platycodon grandiflorum,” Planta Medica, vol. 67,
[75] K. H. Ryu, H. I. Rhee, J. H. Kim et al., “Anti-inflammatory no. 4, pp. 362–364, 2001.
and analgesic activities of SKLJI, a highly purified and in- [89] C. Wang, G. B. Schuller Levis, E. B. Lee et al., “Platycodin
jectable herbal extract of Lonicera japonica,” Bioscience, D and D3 isolated from the root of Platycodon
grandiflorum modulate the production of nitric oxide and Chinese Journal of Modern Applied Pharmacy, vol. 16, no. 2,
secretion of TNF-α in activated RAW 264.7 cells,” In- pp. 16–19, 1999.
ternational Immunopharmacology, vol. 4, no. 8, [104] T. M. Hung, C. V. Thu, N. T. Dat et al., “Homoisoflavonoid
pp. 1039–1049, 2004. derivatives from the roots of Ophiopogon japonicus and their
[90] W. Y. Yu and H. J. Zhu, “Study on pharmacological in vitro anti-inflammation activity,” Bioorganic & Medicinal
mechanism of Platycodon grandiflorum in treating bronchial Chemistry Letters, vol. 20, no. 8, pp. 2412–2416, 2010.
asthma,” Chinese Medicine and Pharmacology, vol. 40, no. 3, [105] J. Han, J. Zhao, W. Y. Tian et al., “Effects of extra-intestinal
pp. 38–40, 2012. transformation on the components and antitussive effects of
[91] B. Wang, Y. Gao, G. Zheng et al., “Platycodin D inhibits Glycyrrhiza uralensis,” Journal of Anhui Medical University,
interleukin-13-induced the expression of inflammatory cy- vol. 47, no. 4, pp. 422–424, 2012.
tokines and mucus in nasal epithelial cells,” Biomedicine & [106] T. F. Yu, X. D. Tian, R. Li et al., “Antitussive and expectorant
Pharmacotherapy, vol. 84, pp. 1108–1112, 2016. effects of Glycyrrhiza uralensis flavonoids, Glycyrrhiza ura-
[92] E. H. Han, J. H. Park, J. Y. Kim, Y. C. Chung, and lensis extract and glycyrrhetinic acid,” Chinese Traditional
H. G. Jeong, “Inhibitory mechanism of saponins derived Patent Medicine, vol. 15, no. 3, pp. 32-33, 1993.
from roots of Platycodon grandiflorum on anaphylactic re- [107] Y. J. Wu, “Study on antitussive, phlegm-eliminating and
action and IgE-mediated allergic response in mast cells,” airway resistance-reducing effects of sodium glycyr-
rhetinate,” Journal of Lanzhou Medical College, vol. 22, no. 2,
Food and Chemical Toxicology, vol. 47, no. 6, pp. 1069–1075,
pp. 23–26, 1996.
2009.
[108] J. X. Zhu, J. X. Zeng, Y. M. Zhang et al., “Comparative study
[93] Y.-C. Park, M. Jin, S.-H. Kim, M.-H. Kim, U. Namgung, and
on the effects of cough and phlegm on Platycodon grandi-
Y. Yeo, “Effects of inhalable microparticle of flower of
florum in different producing areas,” Modernization of
Lonicera japonica in a mouse model of COPD,” Journal of
Traditional Chinese Medicine and Materia-World Science
Ethnopharmacology, vol. 151, no. 1, pp. 123–130, 2014.
and Technology, vol. 17, no. 5, pp. 976–980, 2015.
[94] Q. Sun, L. Chen, M. Gao et al., “Ruscogenin inhibits lipo-
[109] X. X. Fang, B. T. Huang, J. X. Zeng et al., “Comparison of
polysaccharide-induced acute lung injury in mice: in- total saponins and platycodin D in Platycodon grandiflorum
volvement of tissue factor, inducible NO synthase and from different producing areas,” Chinese Journal of Exper-
nuclear factor (NF)-κB,” International Immunopharmacol- imental Traditional Medical Formulae, vol. 22, no. 1,
ogy, vol. 12, no. 1, pp. 88–93, 2012. pp. 78–81, 2016.
[95] Z. H. Cheng, T. Wu, L. Z. Li et al., “Study on the fat-soluble [110] X. Hu, Study on Auality Evaluation of Tetraploid Lonicera
chemical composition of traditional Chinese medicine Japonica Medicinal Materials Combining Chemical Compo-
Ophiopogon japonicus,” Journal of Chinese Pharmaceutical nents with Acute Toxicity and Pharmacodynamics, Beijing
Sciences, vol. 40, no. 5, pp. 337–341, 2005. University of Chinese Medicine, Beijing, China, 2013.
[96] W. Qamar, R. Khan, A. Q. Khan et al., “Alleviation of lung [111] H. L. Pu, H. Jiang, and R. R. Chen, “Toxicity study of Lonicera
injury by glycyrrhizic acid in benzo(a)pyrene exposed rats: japonica and dried ginger on mice,” Practical Pharmacy and
probable role of soluble epoxide hydrolase and thioredoxin Clinical Remedies, vol. 14, no. 4, pp. 277-278, 2011.
reductase,” Toxicology, vol. 291, no. 1–3, pp. 25–31, 2012. [112] Y. Y. Lin, S. H. Gu, Y. L. Song et al., “Cytotoxicity of
[97] J. Y. Zhang, M. M. Wei, X. Chu et al., “Protective mechanism ophiopogon D' on H9c2 cells in cardiomyocytes,” China
of Glycyrrhiza flavonoids on acute lung injury in mice,” Pharmaceuticals, vol. 28, no. 3, pp. 10–12, 2019.
Chinese Agricultural Science Bulletin, vol. 28, no. 8, pp. 56– [113] Y. P. Hu, J. Song, X. Wang et al., “Study on genetic toxicity of
62, 2012. ophiopogon decoction,” Chinese Journal of Information on
[98] L. Yao, J.W. Zhang, Q.J. Meng et al., “Study on lung injury Traditional Chinese Medicine, vol. 16, no. 7, pp. 38–40, 2009.
induced by PM2.5 and the intervention of total saponins in [114] M. Zhang, “Teratogenic effects of Ophiopogon japonicus
Platycodon grandiflorum,” Chinese Journal of Information decoction on rats,” in Proceedings of the 2010 National
on Traditional Chinese Medicine, vol. 24, no. 12, pp. 38–41, Conference on Drug Toxicology, Beijing, China, August 2010.
2017. [115] Z. H. Zhao, L. Zhang, L. Yong et al., “Safety evaluation of the
[99] Q. Chen, M. Zhu, Y. Li et al., “Interventional effect of upper part of the Glycyrrhiza uralensis,” Chinese Journal of
Platycodon saponins on airway remodeling in mice with Experimental Traditional Medical Formulae, vol. 25, no. 3,
chronic bronchitis,” Journal of Anhui University, vol. 37, pp. 74–80, 2019.
no. 3, pp. 1–8, 2013. [116] X. C. Chen, “The antagonism between Glycyrrhiza uralensis
[100] B. Yao, J. W. Zhang, Q. J. Meng et al., “Study on the effects of and euphorbiae kansui and its molecular complexes,” Chi-
PM2.5-induced lung injury and total saponins in Platycodon nese Traditional Patent Medicine, vol. 7, no. 5, p. 41, 1984.
grandiflorum,” Chinese Journal of Information on Traditional [117] E. B. Jin, M. H. Jiang, Q. F. Huang et al., “Pharmacological
Chinese Medicine, vol. 24, no. 12, pp. 38–41, 2017. study on eighteen reversal of traditional Chinese medicine,”
[101] H. Ishibashi, T. Mochidome, J. Okai, H. Ichiki, H. Shimada, Chinese Traditional Patent Medicine, vol. 5, no. 2, pp. 30–33,
and K. Takahama, “Activation of potassium conductance by 1982.
ophiopogonin-D in acutely dissociated rat paratracheal [118] F. G. Dai, R. Luo, Y. G. Wang et al., “Effect of euphorbiae
neurons,” British Journal of Pharmacology, vol. 132, no. 2, kansui compatibility with Glycyrrhiza uralensis on CYP3A2
in rat liver,” Journal of the Fourth Military Medical Uni-
pp. 461–466, 2010.
versity, vol. 26, no. 10, pp. 951-952, 2005.
[102] T. Miyata, “Pathopharmacological evaluation of Baku-
[119] X. J. Jin, M. Zhang, and B. Nie, “Acute and cumulative
mondo-to(Mai-Men-Dong-Tang) as a curative for chronic
toxicity test of extract of Platycodon grandiflorum,” Feed
inflammatory airway disease,” Kampo Medicine, vol. 51,
Industry, vol. 20, pp. 33-34, 2007.
no. 3, pp. 375–397, 2000.
[103] J. Tang, H. Qian, Q. Huang et al., “Study on antiasthmatic
and antiallergic effect of ophiopogon polysaccharide,”

Ecam2019 9458676

Uploaded by

Copyright:

Available Formats

Ecam2019 9458676

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Ecam2019 9458676

Uploaded by

Copyright:

Available Formats

Hindawi

Evidence-Based Complementary and Alternative Medicine

Chengxian Li ,1 Fucang Wu ,1 Weiling Yuan ,1 Qi Ding ,2 Min Wang ,1

Correspondence should be addressed to Weiling Yuan; yweiling_000@163.com

Academic Editor: Armando Zarrelli

1. Introduction repeated attack of acute pharyngitis is the main cause. Upper

Potential relevant articles

Figure 1: Inclusion process and results of the relevant articles.

Random sequence generation (selection bias)

the baseline information and not make the number of pa-

Blinding of participants and personnel (performance bias)

Blinding of outcome assessment (detection bias)

Random sequence generation (selection bias)

Incomplete outcome data (attrition bias)

Selective reporting (reporting bias)

Study or subgroup Experimental Control Risk ratio Risk ratio

Total (95% CI) 417 325 100.0 1.27 [1.15, 1.41]

Figure 4: The forest plot of the studies included.

7.4. Platycodon grandiﬂorum. In order to study whether the 9. Conclusion

You might also like