REVIEW Research progress on chemical composition, pharmacological effects of Forsythia suspensa (Thunb.) Vahl and predictive analysis on Q-marker ...
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
TMR Modern Herbal Medicine
homepage: https://www.tmrjournals.com/mhm
REVIEW
Research progress on chemical composition, pharmacological effects of
Forsythia suspensa (Thunb.) Vahl and predictive analysis on Q-marker
Hui Peng1,2#, Peng Lu1,2#, Yiting Liu1,2, Chuanxin Liu3, Yanquan Gao1,2, EbukaOlisaemeka Nwafor1,2,
Yuelin Zhang1,2, Zhidong Liu1,2*
1
Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese
Medicine, Tianjin, China;
2
Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique,
Ministry of Education, Tianjin, China;
3
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
#
These authors contributed equally to this work.
*Correspondence to: Zhidong Liu, Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin
University of Traditional Chinese Medicine, Tianjin 301617, China. Tel: +86-22-59596170; Email:
liuzhidong@tjutcm.edu.cn
Highlights
The new quality evaluation system takes traditional Chinese medicine (TCM) quality markers as its core
concept, and lays foundation for the future analysis of the quality markers of Lianqiao (Forsythia suspensa
(Thunb.) Vahl, Abbreviated as “F. suspensa” below), in order to establish a F. suspensa quality control and
quality traceability system.
Traditionality
F. suspensa is a common medicinal plant in China, and it grows in hillside shrubs, underwoods, grasses, or in
valleys. It can effectively improve immune functions, and have obvious curative effects in protecting nerves,
anti-inflammatory, anti-virus, delaying aging, and reduce tumorigenesis.
TMRmhm | May 2020 | Vol.3 | No.2 | 86 Submit a manuscript: https://www.tmrjournals.com/mhm
REVIEW doi: 10.12032/TMRmhm202003069 Abstract Lianqiao (Forsythia suspensa (Thunb.) Vahl, Abbreviated as “F. suspensa” below) is traditional Chinese medicine in China, widely distributed all over the country and also highly rich in resources. The Northwest Territories is a genuine producing area. There are many chemical components in F. suspensa, including lignans, phenylethanolic glycosides, flavonoids, C6-C2 natural alcohols and their glycosides, phenolic acids, terpenes and volatile oils. Among them, lignans and phenylethanolic glycosides are the main active components. Based on the review of chemical components or constituents and main pharmacological activities, according to the definition of quality marker, the components of quality marker of F. suspensa were predicted and analyzed from the aspects of plant genetics and chemical composition, traditional efficacy, traditional medicine, new efficacy, blood entering composition, measurable composition, effective composition in different compatibility, and the influence of storage conditions of extract. Further research on its medicinal active ingredients will provide scientific basis for the evaluation of F. suspensa quality. Keywords: F. suspensa, Phenylethanol glycosides, Lignans, Quality control, Q-marker Abbreviations: Q-marker, Quality marker; F. suspensa, Forsythia suspensa (Thunb.) Vahl; TCM, traditional Chinese medicine; MIC, minimum inhibitory concentration; cAMP, Cyclic adenosine monophosphate; RT-PCR, Reverse Transcription-Polymerase Chain Reaction; LPS, Lipopolysaccharide; TARC, Thymus activation regulating chemokine; MDC, Macrophage-derived chemokine; MAPK, Mitogen-activated protein kinase; IC50, half maximal inhibitory concentration; iNOS, inducible nitric oxide synthetase; PGE2, prostaglandin E2; HO-1, heme oxygenase 1; TNF- α , tumor necrosis factor- α ; IL-6, interleukin-6; MCP-1, monocyte chemoattractant protein-1; IL-1 β , interleukin-1 β ; E. coli, Escherichia coli; MDA, malondialdehyde; GalN, D-galactosamine; DPPH, 1,1-diphenyl-2-picrylhydrazyl; ABTS, 2, 2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid); EAF, the ethyl acetate extract of F. suspensa; MyD88, Myeloid differentiation primary response gene 88; TLR-4, toll like receptor-4; NE, norepinephrine. Competing interests: The authors declare that there is no conflict of interests regarding the publication of this paper. Citation: Peng H, Lu P, Liu YT, et al. Research progress on chemical composition, pharmacological effects of Forsythia suspensa (Thunb.) Vahl and predictive analysis on Q-marker. TMR Modern Herbal Medicine 2020, 3(2):86-112. Executive Editor: Chaoyong Wu Submitted: 16 February 2020, Accepted: 28 February 2020, Online: 6 March 2020. Submit a manuscript: https://www.tmrjournals.com/mhm TMRmhm | May 2020 | Vol.3 | No.2 | 87
doi:10.12032/TMRmhm202003069 REVIEW
Phenylethanoid glycosides
Background Phenylethanoside is a kind of phenolic glycoside
compound [11], which is composed of phenylethanol
Lianqiao (Forsythia suspensa (Thunb.) Vahl, and sugar. The content of this component is high in F.
Abbreviated as “F. suspensa” below) is one of the suspensa, and it is one of the important Q-marker in F.
traditional Chinese medicines (TCMs) in China, a suspensa. It mainly includes forsythiaside
plant of the genus Forsythia and its fruits widely used, (forsythoside A) [12], forsythoside B [13],
well known in TCM as “Forsythiae Fructus”. Its fruit forsythoside D [14], forsythoside E [12, 15],
signifies TCM, and its shell as the medicinal part forsythoside M [16], isoforsythiaside [17],
specified in the Pharmacopoeia [1]. F. suspensa was forsythiaside G [12], forsythiaside I [14], forsythiaside
first recorded in Shengnong Bencao Jing [2], a classic J [12], lianqiaoxinside B [18], calceolarioside C [19],
work of TCM in the Qin and Han Dynasties forsythenside K [20], plantainoside [21],
(100BC-200AD). In 2015 edition of the Chinese calceolarioside A [22], calceolarioside B [12], etc. The
Pharmacopoeia, F. suspensa has the functions of specific compound names were shown in
clearing heat and detoxification, reducing swelling, Supplemental data and the chemical structures of
dispersing and evacuating wind and heat [1] (also phenylethanolic glycosides 1-30 were shown in Figure
known as fever and common cold). It has also been 1.
used as an effective remedy for the treatment of ulcer,
gonorrhea, flu, erysipelas and nephritis for thousands Lignans
of years. Modern pharmacology [3, 4] showed that F. Lignans are a class of natural compounds polymerized
suspensa had potential medicinal value in protecting by two molecules of phenylpropanoid derivatives,
nerves [5], protecting liver and choleretic, regulating most of which are in free state, and a few of which are
immunity, antioxidant effects [6], diuretic and in the wood and resin of plants due to the synthesis of
anti-hypertensive, anti-aging, anti-tumor, anti-viral [7], glycosides with sugar. There are three types of
anti-bacterial, anti-inflammatory [8], etc. monomers that make up lignans: 1. Cinnamolic acid
The quality of TCM includes little or no adverse or cinnamaldehyde, 2. Cinyl alcohol, 3. Allylbenzene.
effect or reactions, safe and guaranteed efficacy or Lignans are an important active component of F.
effectiveness in modern clinical applications. In this suspensa, mainly including (+)-lariciresinol[28],
paper, the resources, chemical components and main isolariciresinol[29], (+)-phillygenin[27],
pharmacological activities of F. suspensa were (+)-phillyrin[27], (-)-arctiin[30], (-)-arctigenin[30],
reviewed. On this basis, the quality standards and (-)-matairesinol[31], (-)-matairesinoside[31],
quality markers (Q-marker) of F. suspensa were (+)-pinoresinol[32], (+)-epipinoresinol [30, 33],
studied potentially, providing a scientific basis for the (+)-pinoresinol-4-O-β-D-glucoside[34],
establishment of quantitative standards of material (-)-dimethylmatairesinol[31], etc. The specific
components. compound names were shown in Supplemental data
and the chemical structures of lignans 31-75 were
Resource distribution shown in Figure 2 and Figure 3.
In China, F. suspensa is mainly produced in Hebei, C6-C2 natural alcohols and their glycosides
Shanxi, Shaanxi, Shandong, Western Anhui, Henan, Currently, the separation products of C6-C2 natural
Hubei, Sichuan and other provinces (regions). In alcohol and its glycosides are isorengyol [40], rengyol
addition, it also grows in Korea, Japan and Europe [9]. [47], rengyolone [47], rengyoxide [47], rengyoside A
[48], rengyoside B [48], rengyoside C [48], suspenol
Chemical composition [49], rengynic acid [52], forsythenside A [54],
forsythenside B [54], etc. The specific compound
More than 200 compounds have been isolated and names were shown in Supplemental data and the
identified from F. suspensa [10]. Studies on the chemical structures of C6-C2 natural alcohol and their
chemical constituents of F. suspensa. are mainly glycosides 76-99 were shown in Figure 4 and Figure
focused on phenylethanolic glycosides and lignans, 5.
followed by C6-C2 natural alcohols and their
glycosides, terpenes, volatile oils, flavonoids, phenolic Flavonoids
acids, sterols and alkaloids. Among them, There are more than 20 flavonoids in F. suspensa,
phenylethanol glycosides and lignans, the main mainly including quercetin [25, 57], isoquercetin [30],
medicinal ingredients, have the highest content. astragalin [30], rutin [57], wogonin-7-O-β-D-
glucuronide [30], cymaroside [43], luteolin [43],
TMRmhm | May 2020 | Vol.3 | No.2 | 88 Submit a manuscript: https://www.tmrjournals.com/mhm
REVIEW doi: 10.12032/TMRmhm202003069
kaempferol [24], isorhamnetin [57], hesperidin [59], drug, which can inhibit many kinds of bacteria. It is
isorhamnetin-3-O-α-L-ranorhamnoside-(1→2)-β-D- mainly used in the treatment of upper respiratory tract
glucopyranoside [43], potengriffioside A [43], infection and acute nephritis [78]. The results [38]
hyperoside [59], etc. The specific compound names showed that caffeoyl phenylethanoid glycosides,
were shown in Supplemental data and the chemical forsythiaside and isoforsythiaside were the main
structures of flavonoids 100-120 were shown in antibacterial components of F. suspensa. In addition,
Figure 6 and Figure 7. the volatile oil in F. suspensa had a good antibacterial
effect on Staphylococcus aureus, Bacillus subtilis,
Phenolic acids Pseudomonas aeruginosa, Candida albicans,
So far, the phenolic acids isolated from F. suspensa Aspergillus niger and other sensitive microorganisms
mainly include caffeic acid [63], ferulic acid [25], in vitro [70]. Shuanghuanglian Oral Liquid is a
p-hydroxyphenylacetic acid [25], palmitic acid [64, proprietary Chinese medicine, which consists of
65], vanillic acid [63], succinic acid [63], etc. The Rendongteng (Lonicera japonica), Huangqin
specific compound names were shown in (Scutellaria baicalensis Georgi), and F. suspensa, and
Supplemental data and the chemical structures of it is mainly used to treat colds and fevers, coughs and
phenolic acids 121-162 were shown in Figure 8 and sore throats. The study of Bai YE [79] showed that
Figure 9. compared with Shuanghuanglian Oral Liquid, water
extract of F. suspensa was more sensitive to
Terpenoids and Volatile oils Staphylococcus aureus and Streptococcus pneumoniae,
The volatile oils in F. suspensa are monoterpenes, but it is not sensitive to Escherichia coli (E. coli) and
monoterpenols, sesquiterpenes, triterpenes, and Candida albicans. Han X and others [80]tested the
cycloterpenoids. Among them, α-pinene [70], antibacterial activity of 80% methanol extract of F.
β-pinene [70], α-phellandrene [70], camphene [70], suspensa on E. coli K88 (MIC=25.00mg/ml),
limonene [70], sabinene [70], p-cymene [70], linalool Staphylococcus aureus (MIC=12.50mg/ml) and
[70], terpinen-4-ol [70], (+)-carene[71], oleanolic acid Salmonella (MIC=1.56mg/ml) in vitro by a
[72], ursolic acid [27, 73], 2,3-hydroxyursolic acid[74, well-diffusion assay procedure and a 2-fold dilution
75], etc. The specific compound names were shown in method. And in-vivo tests on 252 broilers for 42 days
Supplemental data and the chemical structures of showed that the extract (100 mg/kg) could reduce the
terpenoids and volatile oils 163-217 were shown in level of E. coli and was a potential antibacterial agent.
Figure 10, Figure 11 and Figure 12. Some researchers have pointed out that forsythiaside
[81] could significantly reduce the mortality of model
Other compounds
animals infected with Staphylococcus aureus,
Other compounds were isolated and identified as well.
Pseudomonas aeruginosa, and E. coli through
Mainly including sterols and alkaloids such as
experiments. Meanwhile, the body temperature of the
suspensine A [76], (–)-7ʹ-O-methylegenine [76],
rabbit model of fever caused by endotoxin and the rat
(–)-egenine [76], (–)-bicuculline [76], taraxasterol
model of yeast fever were significantly reduced.
[25], β-sitosterol [56], etc. The specific compound
Therefore, it can be confirmed that forsythiaside has
names were shown in Supplemental data and the
antipyretic and anti-infective effects.
chemical structures of other compounds 218-225 were
shown in Figure 13. Anti-inflammatory effects
The anti-inflammatory activity of F. suspensa ranks
Pharmaceutical effects first among many TCMs, and it is the most effective
and promising anti-inflammatory drug for inhibiting
In recent years, there are more and more studies on the
inflammation [82]. The main anti-inflammatory
activity screening of some compounds in F. suspensa.
components of F. suspensa are phenylethanolic
Their pharmacological effects are also obvious, with
glycosides and lignans. Wang TT [83] have done the
antibacterial, anti-inflammatory, antiviral, anti-tumor,
related in vitro bacteriostatic test and
liver protection, nerve protection, anti-allergic,
anti-inflammatory activity research, which showed
anti-oxidative effects and regulating body immunity,
that both forsythoside A and phillyrin have significant
etc.
bacteriostatic effect. Modern pharmacology showed
that the anti-inflammatory activity of F. suspensa
Antibacterial effects
Antibacterial activities of F. suspensa contribute to its supported traditional effects of heat-clearing and
detoxification effects in terms of traditional efficacy. F. detoxifying, reducing swelling, dispersing, and
suspensa is a kind of broad-spectrum antibacterial evacuating wind and heat.
The anti-inflammatory effect of F. suspensa has
Submit a manuscript: https://www.tmrjournals.com/mhm TMRmhm | May 2020 | Vol.3 | No.2 | 89
doi:10.12032/TMRmhm202003069 REVIEW
been proved to play a role in various disease models, reduced. Forsythiaside A [96] could reduce the content
including edema [84], colitis [85] and peritonitis [86]. of influenza A virus M1 protein in model mice
Studies by Lee JJ and other studies [87] have shown infected with influenza virus, prevent the generation
that water extract of F. suspensa (mainly including and spread of new virions, and improve the survival
forsythiaside A, lariciresinol, arctigenin, etc.) rate of mice infected with influenza virus in vivo.
activated Nrf2 (Nrf2, important transcription factors More importantly, forsythiaside A [97] could control
that regulate cellular oxidative stress) and inhibited influenza A virus infection by inhibiting influenza A
NF-κB activity (NF-κB, a transcription factor that virus replication and improve the prognosis of
regulates the expression of key cytokine genes that influenza A virus infection. Yang Y [98] evaluated the
promote inflammation) and induced A20 [88](A20, a anti-swine influenza virus effect of F. suspensa.
negative regulator of NF-κB signaling pathway) Experiments have shown that it had antiviral effects,
expression to play an anti-inflammatory effect. mainly by resisting virus adsorption, interfering with
Ethanol extract of F. suspensa (such as phillyrin, virus replication, and direct killing.
phillygenin, forsythoside A, pinoresinol, suspensaside,
caffeic acid, etc.) could reduce the production of Anti-cancer effects
inducible nitric oxide synthetase (iNOS), Anti-cancer activity of F. suspensa also supports its
prostaglandin E2 (PGE2) and cyclooxygenase-2 [89]. detoxification and antioxidant effects. F. suspensa has
It has been reported that the anti-inflammatory effect multiple therapeutic effects [99] on lung cancer, colon
of forsythiaside A on BV-2 microglia (mouse cancer, liver cancer, leukemia, oral epidermoid cancer,
microglioma cells) and primary microglia in vitro was gastric cancer, breast cancer, colorectal cancer,
studied at different concentrations. And the inhibitory melanoma, esophageal cancer, lung adenocarcinoma,
effect [90] of was recognized to inhibit NF-κB melanoma, etc. Bao J et al [100] tested the
signaling pathway and higher levels of Nrf2 and heme anti-proliferative effect of F. suspensa water extract on
oxygenase 1 (HO-1). From the number of neutrophils mouse melanoma B16-F10 cells in vitro. In vivo
and the levels of tumor necrosis factor-α (TNF-α), transplantation of B16-F10 melanoma in mice, the
interleukin-6 (IL-6) and monocyte chemoattractant extract (10000 mg/kg) significantly inhibited tumor
protein-1 (MCP-1) in the peritoneal cavity, it was growth, cell proliferation and angiogenesis. Its
confirmed that forsythiaside A [86] could significantly anti-tumor effect was related to the anti-inflammatory
reduce peritonitis. In a mouse model of acute lung and anti-oxidation properties regulated by
injury [91], phillyrin could inhibit the pathological mitogen-activated protein kinase (MAPKs)/Nrf2/
changes of lung tissue, alveolar hemorrhage and HO-1.
neutrophil changes in mice. It protected lung injury by
inhibiting TNF-α, interleukin-1β (IL-1β), IL-6 and Hepatoprotective effect
peroxidase. Pan CW [101] reported that forsythiaside A (15, 30,
Lee S [92] has shown that arctiine could reduce the 60 mg/kg) at a certain concentration could be
production of NO and pro-inflammatory cytokines alleviated inflammatory response and had
such as IL-1β, IL-6, TNF-α, and PGE2, and reduce hepatoprotective effect in a model of
gene and protein levels detected by reverse lipopolysaccharide (LPS)/D-galactosamine (GalN)
transcription-polymerase chain reaction (RT-PCR) and induced acute liver injury. It could reduce the
western blot. In addition, arctiin [93] could inhibit the production of malondialdehyde (MDA) and the levels
expression of costimulatory molecules (such as B7-1, of alanine aminotransferase in serum and aspartate
B7-2), and the NF-κB signaling pathway in aminotransferase. And it could also activate Nrf2 and
macrophages to achieve anti-inflammatory purposes. inhibit the NF-κB signaling pathway. Similarly,
Arctiin has a good anti-inflammatory biological forsythiaside A, forsythiaside B, forsythiaside N, and
activity. forsythiaside O all showed survival rates with strong
liver cells.
Antiviral effects
Antiviral activities of F. suspensa also contribute to its Antioxidant effect and regulating body immunity
detoxification effects [94]. Studies [95] have shown Isoforsythiaside was isolated from F. suspensa by Qu
that in mice inoculated with H1N1 in vivo, the H [102] and its pharmacological test showed that
administration of phillyrin (20 mg/kg/day) for three isoforsythiaside had high antioxidant and antibacterial
consecutive days significantly prolonged the average activity. In vitro, isoforsythiaside and forsythiaside
survival time, and it was determined that the virus titer, had a strong scavenging effect on DPPH free radicals.
IL-6 and influenza hemagglutinin production were And the strong antioxidative effect of isoforsythiaside
significantly reduced, and lung tissue damage was was related to the ortho substitution of the hydroxyl
TMRmhm | May 2020 | Vol.3 | No.2 | 90 Submit a manuscript: https://www.tmrjournals.com/mhmREVIEW doi: 10.12032/TMRmhm202003069
group in the phenol structure. Forsythiaside B, of IL-1β and tumor necrosis factor-α, thereby
forsythiaside H, and calceolarioside B [18] also achieving a neuroprotective effect.
showed free radical scavenging activity in vitro. Lu T By processing the mouse brain homogenate in the
[103] used DPPH and ABTS free radical scavenging Wang’s model group [109], the levels of IL-1β, NO,
experiments to confirm the antioxidant capacity of MDA and norepinephrine (NE) were significantly
80% ethanol extract of F. suspensa in vitro. decreased, and the activities of total superoxide
Phillygenin, 8-hydroxypinoresinol, forsythialan and dismutase and glutathione peroxidase and the levels of
forsythialan B obviously protected the renal tubular glutamate and acetylcholine were significantly
epithelial cells LLC-PK1 in vitro [104]. Forsythiaside increased. Therefore, this study indicated that
could enhance the expression of antioxidant enzymes forsythiaside had a herapeutic effect on amnesia and
in H2O2-treated neurons cultured in vitro [105]. It has neuroprotection.
been reported that phenolic constituents also had
strong antioxidant properties and were stronger than Other pharmacological effects
ascorbic acid, such as methyl caffeate, rutin and In addition to the above effects, F. suspensa could
quercetin [106]. also promote gastric emptying, lower blood lipids and
relax blood vessels. It was reported that phillyrin [112]
Anti-allergic effects had vasodilating effect on vasoconstriction caused by
Sung YY [107] studied that forsythiaside, phillyrin, NE. The mechanism was that it protected the aorta of
lariciresinol, and phillygenin can reduce the isolated rats by limiting the inflow of calcium ions in
production of thymus activation regulating chemokine, vitro. Hao FF [113] studied that compared with the
macrophage-derived chemokine and rantes. In a blank group, the water extract of F. suspensa
mouse in vivo model, the ethanol extract of F. administration group had no effect on gastric
suspensa could alleviate the symptoms of allergic emptying and small intestinal advancing of mice
dermatitis induced by the crude extract of dust mites. under normal physiological conditions. However, it
The methanol extract of F. suspensa could reduce the had a good two-way regulation and improvement
allergic symptoms caused by β-companion soybean effect on gastric emptying and small intestine models
globulin in weaned piglets. Hao Y [108] believed that of mice under pathological conditions caused by
the mechanism may be related to inhibiting allergic dopamine, adrenaline, atropine and neostigmine.
antibodies, hindering mast cell degranulation, T
lymphocyte proliferation, histamine production and Predictive analysis of Q-marker
interleukin-4 synthesis.
The chemical composition types of F. suspensa in
Neuroprotective effects different provinces, different places of origin, different
It was reported that forsythiaside and phillyrin [109] growth years and different harvest periods are
were considered as promising drugs for the treatment generally similar, but the contents are different.
of cognitive impairment and Parkinson's disease, and Q-marker [114, 115] was a new concept put forward
were candidates for the treatment of amnesia. Zhang S by academician Liu Changxiao [116, 117] (Researcher
[110] studied the inhibitory effect of 75% ethanol of Tianjin Institute of Pharmaceutical Research,
extract of F. suspensa (mainly including forsythoside academician of Chinese Academy of Engineering) in
A, suspensaside, rutin, etc.) on rotenone induced 2016, which closely linked the “effectiveness –
neurotoxicity in SD male rats. It could improve the material basis – quality control landmark components”
behavior of rats, protect dopamine neurons from loss of TCM. Q-marker systematically expounded the
and restore dopamine level. The results showed that relationship between the quality and efficacy of TCM
its potential function is by relieving pro-inflammatory with new perspectives, improved the quality standard
molecules of Parkinson's disease and regulating of TCM in China, and improved the scientificity,
phosphatidylinositol 3-kinase, protein kinase B, rationality and operability of the standard [118]. It
NF-κB and MAPK pathways. referred to chemical substances that were inherent in
Kim JM [111] found that phillygenin could shorten TCM and TCM products (Chinese herbal extracts,
the escape latency, reduce the level of thiobarbituric TCM decoction pieces, TCM preparations, etc.) were
acid reactive substances assay (TBARS) in rats and formed during processing and were closely related to
protect the nerves in the scopolamine-induced mouse the functional properties of TCM, as a reflection of the
memory impairment model. Its mechanism was that safety of TCM and quality control of effectiveness.
phillygenin could express its anti-inflammatory Since academician Liu Changxiao put forward,
activity through forsythia lipoproteins by inducing a scholars have conducted preliminary discussions on
decrease in glial cell activation and expression levels some Chinese medicines [119, 120] and TCM Patent
Submit a manuscript: https://www.tmrjournals.com/mhm TMRmhm | May 2020 | Vol.3 | No.2 | 91doi:10.12032/TMRmhm202003069 REVIEW
Prescriptions [121, 122]. In order to evaluate the LPS-induced LX2 cell activation and inflammation of
quality of F. suspensa objectively and scientifically, the TLR4/MyD88/NF-κB signaling pathway.
according to the definition of Q-marker, the Q-marker Phillygenin could also inhibit LX2 cell activation and
of F. suspensa is predicted, which is helpful to fibrotic cytokine expression by inhibiting the
establish a scientific quality control method of F. LPS-induced proinflammatory response. Zou SS [126]
suspensa. intravenously and orally administered forsythiaside to
rabbit models infected with parainfluenza virus, and
Predictive analysis of Q-marker based on plant tested to significantly reduce the contents of the
genetics and chemical component-specific evidence heating medium protein kinase C and cyclic adenosine
According to herbal research [123, 124], the TCM monophosphate (cAMP) in the hypothalamus.
“Forsythia” mostly used Hyperic ascyron L. as the Experiments showed that forsythia could reduce the
basis in the Song Dynasty. After the Song Dynasty, F. body temperature of rabbits after parainfluenza virus
suspensa was used as the basis of the TCM “Forsythia” infection, and its antipyretic mechanism may be
and has been used ever since. F. suspensa is derived related to the down-regulation of cAMP content in
from Forsythia of Oleaceae. Forsythia species include rabbit hypothalamus. Forsythiaside A [127] could
Lianqiao (F. suspensa Vahl), Jinzhonghua(F. prevent cigarette smoke-induced lung tissue damage
viridissima Lindl.), and Qinqiao(F. giraldiana in mice with chronic obstructive pulmonary disease by
Lingelsh.) in China. Studies on other breeds have been activating Nrf2 and inhibiting the NF-κB signaling
scarce. F. suspensa is mainly distributed in Hebei, pathway and this experiment also demonstrates that
Shanxi, Shaanxi, Shandong, Western Anhui, Henan, forsythiaside A can attenuate the penetration of
Hubei, Sichuan and other provinces in China. There inflammatory cells.
are many chemical constituents isolated from F. Phenylethanol glycosides and lignans correspond to
suspensa, including 36 phenylethanolic glycosides, 55 the traditional efficacy of F. suspensa, which were the
lignans, 58 terpenes and volatile oils, 25 C6-C2 main medicinal substance basis of traditional efficacy
natural alcohols and their glycosides, 23 flavonoids, of F. suspensa, and also the main way and important
more than 50 sterols, alkaloids and phenolic acids. basis for screening Q-marker of F. suspensa.
Among them, phenylethanol glycosides and lignans
are the main active ingredients and important Predictive analysis of Q-marker based on
chemical markers of F. suspensa. These two kinds of traditional medicinal properties
effective components are selected as the quality The classic taste of TCM [128] is the basic attribute of
indicators of F. suspensa. TCM, and it is also an important basis for the
treatment of clinical symptoms and formulating
Predictive analysis of Q-marker based on prescriptions. It should also be used as one of the
traditional efficacy bases for determining Q-marker. F. suspensa possesses
F. suspensa has the functions of clearing heat and related properties: it has a bitter taste and cold
detoxification, reducing swelling and dispersing, and attribute to lung, heart and small intestine. The
evacuating wind and heat. In modern pharmacological important material foundation of “bitter taste” should
studies, the traditional efficacy of F. suspensa is based first have the taste characteristics and functional
on the anti-inflammatory and anti-oxidation properties properties of bitterness. The taste of the medicine has
of phenylethanolic glycosides (forsythiaside A, B, C, a corresponding relationship with its chemical
D, E, etc.) and lignan compounds (phillygenin, components or constituents used in formulation. The
phillyrin, etc.) in F. suspensa. In modern glycosides and alkaloids are the main sources of the
pharmacology, the traditional efficacy of “clearing bitter taste possessed by the cold medication [129].
away heat and detoxification” is mainly reflected in Based on the above, it can be concluded that the
the pharmacological effects of antipyretic, cooling, chemical components of phenylethanol glycosides and
antibacterial and anti-inflammatory; The traditional lignans in F. suspensa should be the main material
effect of “swelling and dispersing the wind and basis of its “sexual taste” and the main choice of
dispersing wind and heat” is mainly reflected in Q-marker.
anti-virus, swelling and anti-inflammatory.
Hu NH [125] studied the inflammation model and Predictive analysis of Q-marker based on new
fibrosis model of human hepatic stellate cells (LX2) pharmacodynamic uses
induced by different concentrations of The phenylethanolic glycosides contained in F.
lipopolysaccharide (LPS), and then given high, suspensa have an effect of protecting the liver and
medium and low doses of phillygenin for intervention. eliminating jaundice, and the aglycone caffeic acid
The results showed that phillygenin could inhibit and its structural analog chlorogenic acid also have
TMRmhm | May 2020 | Vol.3 | No.2 | 92 Submit a manuscript: https://www.tmrjournals.com/mhmREVIEW doi: 10.12032/TMRmhm202003069
the effect of protecting the liver and promoting gall dehydrogenation, methylation, sulfation, etc. Bai Y
[101]. Cheng Y [130] reported that phillyrin and [133] was used to study the pharmacokinetics of
forsythiaside A had different induction effects on methanol extract of F. suspensa in rats. The liquid
cytochrome P450 in rat liver microsomal incubation chromatography, electrospray ionization tandem mass
system. Both phillyrin and forsythiaside A can spectrometry (LC-ESI-MS/MS) was established and
potentially induce cytochrome oxidase activity. Zhang validated for the determination of 9 selected
YY [131] studied that the ethyl acetate extract of F. components (forsythiaside A, forsythiaside B, rutin,
suspensa (EAF) could reduce the content of serum astragaloside, phillyrin, kaempferol, quercetin,
triglyceride and total cholesterol in streptozotocin iaorhamnetin and arctiin) in rat plasma. The
induced diabetic mice model. And it also increased the experimental results showed that only three
content of high-density lipoprotein, and significantly forsythiasides A, rutin and phillyrin are detected in the
reduced blood glucose levels in diabetic mice treated plasma after oral administration of F. suspensa
with EAF. In addition, EAF may have anti-diabetic methanol extract in rats. Li C studied the antiviral
effects by regulating gene expression and pancreatic evaluation of phillyrin and its metabolites [134].
function. Leng W [132] explored the effects of Phillyrin is converted to aglycone forsythiaside by
phillyrin on renal function, inflammatory response and hydrolysis, and then converted to other metabolites
oxidative stress in diabetic nephropathy rats by mainly through a series of metabolic processes in the
establishing a diabetic nephropathy rat model, and the blood such as methylation, demethylation,
results showed that phillyrin can protect renal damage dehydroxylation, and ring opening. The results
in diabetic nephropathy. showed that phillyrin and four metabolites had
It can be concluded that phenylethanolic glycosides inhibitory effects on the H3N2 influenza virus,
and lignans are the main material foundations for F. indicating that phillygenin were the main components
suspensa to protect the liver and lower blood sugar, of phillyrin in rat plasma.
which should be taken as the Q-marker of F. suspensa. Based on the above analysis, the blood components
of F. suspensa are mainly phenylethanol glycosides
Predictive analysis of Q-marker based on and lignans, which are closely related to medicinal
blood-introducible chemical components effects, and are likely to be the basis of the main
The chemical composition of TCM is very pharmacodynamic substances, which serve as an
complicated, and its complexity is manifested in the important reference for screening F. suspensa
fact that TCM contains a large number of different Q-marker.
structural types of chemical components, and each
type has a large number of chemical components. The Predictive analysis of Q-marker based on changes
complexity of TCM ingredients is the basis for its in chemical composition content of extracts under
multiple functions and multiple pharmacological different storage conditions
effects. Although the chemical composition of TCM is The clinical efficacy of Chinese medicine is related to
complex, the chemical ingredients must be absorbed its quality, which is related to the effective active
into the blood and reach a certain blood concentration ingredients. After the TCM is harvested and processed
in the body before they can play a pharmacological for clinical applications, it is also extracted and stored.
effect directly or indirectly (except for a few At this time, temperature, humidity, and light will
components that directly affect the intestine). By affect the effective active ingredient content in it.
analyzing the components of the prototype and their Selecting a suitable storage method is of great
metabolites after administration, analyzing the significance to ensure the quality and stability of the
markedly effective ways based on the TCM. During the packaging and storage of F.
compound-target-pathway, and combining the tissue suspensa, the contents of forsythiasides A, phillyrin
distribution of the blood-injecting components with and phillygenin showed a decreasing trend [135]. In
the pathological site of the disease and the drug addition, different morphological conditions have
intervention method, the effective ingredients of F. different effects on their chemical composition
suspensa were screened and used as an important content.
basis for predicting the Q-marker of F. suspensa. Forsythiaside A in different morphological
The oral bioavailability of phenylethanolic conditions [136], has significantly different
glycosides is low, but the efficacy is significant, which influencing factors, such as humidity under solid state
means that the mixture of prototypes and metabolites conditions has a greater impact on the stability of
may be the group of active ingredients that play the forsythiaside A; In aqueous solution, acid and alkali
role of efficacy. The main reactions of phenylethanolic conditions have the greatest influence on its stability.
glycosides in vivo are hydrolysis, reduction, In order to evaluate and control the quality of
Submit a manuscript: https://www.tmrjournals.com/mhm TMRmhm | May 2020 | Vol.3 | No.2 | 93doi:10.12032/TMRmhm202003069 REVIEW
forsythia more reasonably, phillyrin, phillygenin and suspensa Extract Has the Potential to Substitute
forsythiaside A should be used as important reference Antibiotic in Broiler Chicken. ASIAN AUSTRAL J
for screening F. suspensa Q- markers under different ANIM 2012, 25: 569-76.
storage time. 5．Zhang S, Shao SY, Song XY, et al. Protective
effects of Forsythia suspense extract with
Conclusions and future perspectives antioxidant and anti-inflammatory properties in a
model of rotenone induced neurotoxicity.
F. suspensa is a TCM commonly used in China. It has NEUROTOXICOLOGY 2016, 52: 72-83.
a wide range of physiological activities and has a long 6．Chen CC, Chen HY, Shiao MS, et al. Inhibition of
history of extensive application, accurate curative Low Density Lipoprotein Oxidation by
effects, and abundant sources of medicine. There are Tetrahydrofurofuran Lignans from Forsythia
many new clinical applications, such as reducing suspensa and Magnolia coco. PLANTA MED 1999,
blood sugar, lowering blood pressure, regulating blood 65: 709-711.
lipids, and protecting the liver. The composition 7．Ko HC, Wei BL, Chiou WF. Dual regulatory effect
system of F. suspensa is complex, and the single index of plant extracts of Forsythia suspense on RANTES
component has been used as the standard to meet the and MCP-1 secretion in influenza A virus-infected
entire forsythia industry chain. However, to establish a human bronchial epithelial cells. J
scientific and reasonable quality evaluation method, ETHNOPHARMACOL 2005, 102: 418-423.
the quality of F. suspensa is evaluated 8．Kim MS, Na HJ, Han SW, et al. Forsythia fructus
comprehensively and accurately, to guide the rational inhibits the Mast-Cell-Mediated Allergic
utilization of forsythia species, is of great practical Inflammatory Reactions. INFLAMMATION 2003,
significance for healthy development of F. suspensa 27: 129-135.
industry. 9．Editorial Board of Flora of China Flora of China,
On the basis of summarizing the research status of F. Science Press, Beijing 1978, P 163.
suspensa chemical composition and modern 10．Wang Z, Xia Q, Liu X, et al. Phytochemistry,
pharmacological effects, this paper takes the Q-marker pharmacology, quality control and future research
of TCM as the core concept. As shown in Figure 14, of Forsythia suspensa (Thunb.) Vahl: A review. J
the relationship between traditional efficacy and ETHNOPHARMACOL 2018, 210:318-339.
modern pharmacological effects need be fully 11．Han J, Ye M, Guo H, et al. Analysis of multiple
understood. According to the chemical components constituents in a Chinese herbal preparation
and pharmacological effect of F. suspensa, relevant Shuang-Huang-Lian oral liquid by
literature of sexual taste, its measurable components, HPLC-DAD-ESI-MSn. J PHARMACEUT
blood composition, etc., and combined with chemical BIOMED 2007, 44: 430-438.
composition analysis and some related researches on 12．Nan WF, Qiang MZ, Ying L, et al. New
effectiveness, the literature analysis and demonstration phenylethanoid glycosides from the fruits of
of the selection and determination of F. suspensa. Forsythia suspensa (Thunb.) Vahl. MOLECULES
Q-markers were carried out, and a feasible path and a 2009, 14: 1324-1331.
reference model method for Q-marker analysis of 13．Wang Y, Guo Z, Jin Y, et al. Selective enrichment
TCM were put forward. It will lay a foundation for the with "click oligo (ethylene glycol)" column and
prediction and analysis of the Q-marker of F. suspensa TOF-MS characterization of simple
in the future, so as to establish the quality control and phenylpropanoids in the fruits of Forsythia
quality traceability system of F. suspensa. suspensa. J SEP SCI 2009, 32: 2958-2966.
14．Li C, Dai Y, Duan YH, et al. A new lignan
References glycoside from Forsythia suspensa. CHIN J NAT
MEDICINES 2014, 12: 697-699.
1．National Pharmacopoeia Commission. 15．Yan XJ, Wen J, Xiang Y, et al. Study on
Pharmacopoeia of the People's Republic of China. Chemical Composition of Forsythia Suspension.
China Medl Sci and Tech Press, 2015. (Chinese) China Tradit Herb Drugs 2017, 48: 644-647.
2．Gu GG(Qing dynasty). Shengnong Bencao Jing. (Chinese)
Xueyuan Press 2007. 16．Shao SY, Feng ZM, Yang YN, et al. Eight new
3．Wang T, Si XQ, Zhou GL, et al. In vivo anti-tumor phenylethanoid glycoside derivatives possessing
effect and in vitro anti-angiogenic effect of alcohol potential hepatoprotective activities from the fruits
extract from Euphorbia prostrata. China J Chin of Forsythia suspensa. FITOTERAPIA 2017, 122:
Mater. Med 2017, 42: 1722-1729. 132.
4．Han X, Piao XS, Zhang HY, et al. Forsythia
TMRmhm | May 2020 | Vol.3 | No.2 | 94 Submit a manuscript: https://www.tmrjournals.com/mhmREVIEW doi: 10.12032/TMRmhm202003069 17．Qu H, Zhang Y, Chai X, et al. Isoforsythiaside, 32．Sun YS, Wang Yan J, Wang JH, et al. an antioxidant and antibacterial phenylethanoid Determination of four components in Forsythia glycoside isolated from Forsythia suspensa. suspensa flower from different habitats by high BIOORG CHEM 2012, 40: 87-91. performance liquid chromatography. Journal of 18．Kuang HX, Xia YG, Liang J, et al. Food Safety & Quality 2014: 2791-2795. Lianqiaoxinoside B, a novel caffeoyl 33．Luan L, Wang GL, Lin RC. Studies on the phenylethanoid glycoside from Forsythia suspensa. chemical constituents of extract with water from MOLECULES 2011, 16: 5674-5681. Forsythia suspensa. J Chin Med Mater 2010, 33: 19．Xia YG, Yang BY, Liang J, et al. Caffeoyl 220-221. phenylethanoid glycosides from unripe fruits of 34．Yan XJ, Peng Y, Liu ZX, et al. Three new lignan Forsythia suspensa. CHEM NAT COMPD+ 2015, glycosides from the fruits of Forsythia suspens. J 51: 656-659. ASIAN NAT PROD RES 2014. 20．Li C, Dai Y, Zhang SX, et al. Quinoid glycosides 35．Zou QY, Deng WL, Jiang SY, et al. Studies on from Forsythia suspensa. PHYTOCHEMISTRY chemical constituents from fruits of Forsythia 2014, 104: 105-113. suspense. China J Chin Mater Med 2012, 37: 57-60. 21．Zhao Q, Zhang HL, Zhang X, et al. Studies on 36．Feng WS, Li KK, Zheng XK. Studies on the chemical constituents of ethyl acetate in chemical constituents in Forsythia suspensa Forsythia suspensa. China J Chin Mater Med 2015, (Thunb.) Vahl. Chin Pharm J, 2009, 44: 490-492. 09: 1755-1758. (Chinese) 22．Liu DD, Zhang Y, Xu SX, et al. Phenylethanoid 37．Su W, Liu Q, Yang Q, et al. Separation of Four glycosides from Forsythia suspensa Vahl. J Chin Compounds from Forsythia suspensa by Pharm Sci 1998, 7: 103-105. Counter-Current Chromatography with Stepwise 23．Yan XJ, Bai XY, Liu QB, et al. Two new Elution. SEP SCI TECHNOL 2014, 49: 2098-2104. glycosides from the fruits of Forsythia suspensa. J 38．Kuang HX, Xia YG, Yang BY, et al. A New ASIAN NAT PROD RES 2014, 16: 376-382. Caffeoyl Phenylethanoid Glycoside from the 24．Ming DS, Yu DQ, Yu SS. Two new caffeyol Unripe Fruits of Forsythia suspensa. Chin J Nat glycosides from Forsythia suspensa. J ASIAN NAT Med 2009, 7: 278-282. PROD RES 1999, 1: 327-335. 39．Yan XJ, Wen J, Xiang Z, et al. Two new phenolic 25．Kuo PC, Chen GF, Yang ML, et al. Chemical acids from the fruits of Forsythia suspense. J constituents from the fruits of Forsythia suspensa ASIAN NAT PROD RES 2017, 19: 254-259. and their antimicrobial activity. BIOMED RES INT 40．Wang Y, Ren LL. Research progress on chemical 2014, P 1-7. constituents of Forsythia suspensa and Yinqiao 26．Chen L, Li X, Li Q, et al. Research progress on Jiedu Tablets. Modern Medicine and Health 2014, chemical constituents of Forsythia plants. Modern 09: 1333-1335. (Chinese) Medicine and Clinic 2013, 03: 441-445. (Chinese) 41．Chang MJ, Hung TM, Min BS, et al. Lignans 27．Nishibe S , Chiba M , Hisada S . Studies on the from the Fruits of Forsythia suspensa (Thunb.) Vahl Chinese Crude Drug "Forsythiae Fructus." I. On the Protect High-Density Lipoprotein during Oxidative Constituents of Forsythiae Fructus on the Market. Stress. BIOSCI BIOTECH BIOCH 2008, 72: YAKUGAKU ZASSHI 1977, 97: 1134-1137. 2750-2755. 28．Liang J, Gong FQ, Sun HM. Simultaneous 42．Piao XL, Jang MH, Cui J, et al. Lignans from the separation of eight lignans in Forsythia suspensa by fruits of Forsythia suspensa. BIOORG MED β-cyclodextrin-modified capillary zone CHEM LETT 2008, 18: 1980-1984. electrophoresis. MOLECULES 2018, 23: 1-9. 43．Xia W, Dong CM, Yang CF, et al. Research 29．Kuo PC, Hung HY, Nian CW, et al. Chemical progress on chemical constituents and constituents and anti-inflammatory principles from pharmacology of Forsythia suspensa. Modern the fruits of Forsythia suspensa. J NAT PROD 2017, Chinese Medicine 2016, 12: 1670-1674. (Chinese) 4:1055. 44．Shi T. Study on active substances of chloroform 30．Song XJ. Research progress on chemical extract of Forsythia suspensa. Xiamen University components in different parts of forsythia . 2011. (Chinese) Northwest Pharmaceutical Journal 2014, 02: 45．Ming DS. Study on Chemical Composition and 220-222. (Chinese) Biological Activity of Forsythia and Spider 31．Li C, Wei Q, Zou ZH, et al. A lignan and a lignan Fragrance. Beijing: China Union Medical College derivative from the fruit of Forsythia suspensa, 1998. (Chinese) PHYTOCHEM LETT 2019, 32: 115-118 46．Li C, Dai Y, Zhang SX, et al. Quinoid glycosides Submit a manuscript: https://www.tmrjournals.com/mhm TMRmhm | May 2020 | Vol.3 | No.2 | 95
doi:10.12032/TMRmhm202003069 REVIEW from Forsythia suspensa. PHYTOCHEMISTRY 59．Cui Y, Wang Q, Shi X, et al. Simultaneous 2014, 104: 105-113. Quantification of 14 Bioactive Constituents in 47．Endo K, Hikino H. Structures of rengyol, Forsythia Suspensa by Liquid rengyoxide, and rengyolone, new cyclohexylethane Chromatography-Electrospray Ionisation-Mass derivatives from Forsythia suspensa fruits. CAN J Spectrometry. PHYTOCHEM ANALYSIS 2010, 21: CHEM 1984, 62: 2011-2014. 253-260. 48．Seya K, Endo K, Hikino H. Structures of 60．Zhang F, Yang YN, Song XY, et al. rengyosides A, B and C, three glucosides of Forsythoneosides A-D, neuroprotective Forsythia suspensa fruits. PHYTOCHEMISTRY phenethanoid and flavone glycoside heterodimers 1989, 28: 1495-1498. from the Fruits of Forsythia suspensa. J NAT 49．Endo K, Seya K, Hikino H. Structure and PROD 2015, 78: 2390-2397. enantioselective synthesis of suspenol, a new polyol 61．Yan XJ, Xiang Y, Wen J, et al. Study on the of Forsythia suspensa. Tennen Yuki Kagobutsu chemical constituents of phenolic acids in Forsythia Toronkai Koen Yoshishu 1987, 29: 660-667. suspensa. Chinese Pharmaceutical Journal 2017, 02: 50．Shao SY, Feng ZM, Yang YN, et al. Eight new 105-108. (Chinese) phenylethanoid glycoside derivatives possessing 62．Ge Y, Wang Y, Chen P, et al. potential hepatoprotective activities from the fruits Polyhydroxytriterpenoids and Phenolic Constituents of Forsythia suspensa. FITOTERAPIA 2017, 122: from Forsythia suspensa (Thunb.) Vahl Leaves. J 132-137. AGR FOOD CHEM 2015, 64: 125-131. 51．Wen J, Yan XJ, Liang W, et al. Two new 63．Ming DS, Yu DQ, Yu SS, New Quinoid polyhydric alcohols from fruits of Forsythia Glycosides from Forsythia suspensa. J NAT PROD suspensa. China Tradit Herb Drugs 2018, 49: 1998, 61: 377-9. 278-281. 64．Xue J, Xie Li, Liu BR, et al. Triterpenoids from 52．Zhang GG, Song SJ, Ren J, et al. A New the Fruits of Forsythia suspensa. CHIN J NAT Compound from Forsythia suspensa (Thunb.) Vahl MEDICINES 2010, 8: 414-418. with Antiviral Effect on RSV. J Herb Pharmacother 65．Bai XL. Study on the chemical constituents of 2002, 2: 35-40. traditional Chinese medicine forsythia. 53．Wang WF, Liu DL, Xu SX, Xiao FH. New Heilongjiang Medicine 2016, 29: 601-602. compounds in forsythia. Journal of Shenyang (Chinese) Pharmaceutical University 1999, 02: 63-70. 66．El-Desouky SK, Kim YK. A phenylethanoid (Chinese) glycoside and other constituents from the Fruits of 54．Kitagawa S, Nishibe S, Baba H. Studies on the Forsythia koreana. Z NATURFORSCH B 2014, 63: Chinese Crude Drug "Forsythiae Fructus." VIII. On 90-94. Isolation of Phenylpropanoid Glycosides from 67．Ming DS, Yu DQ, Yu SS, et al. A new furofuran Fruits of Forsythia koreana and Their Antibacterial mono-lactone from Forsythia suspensa. J ASIAN Activity. YAKUGAKU ZASSHI 1987, 107: NAT PROD RES 1999, 1: 221-226. 274-278. 68．Ming DS, Yu DQ, Yu SS. Three new compounds 55．Wang L, Piao XL, Kim SW, et al. Effects of from Forsythia suspensa (Thunb.) Vahl. CHINESE Forsythia suspensa Extract on Growth Performance, CHEM LETT 1998, 01: 51-55. Nutrient Digestibility, and Antioxidant Activities in 69．Yan XJ. Research progress on chemical Broiler Chickens Under High Ambient Temperature. composition and pharmacological activity of POULTRY SCI 2008, 87: 1287-1294. Forsythia suspensa. Chinese Commodity 56．Wu YF, Wang XS, Yuan YL, et al. Studies on the Association. Proceedings of the 5th National chemical constituents of Forsythia suspensa. China Congress of Chinese Medicine Commodities of Tradit Herb Drugs2013, 44: 2052-2054. (Chinese) Chinese Commodity Association. Chinese 57．Bai Y, Li J, Liu W, et al. Pharmacokinetic of 5 Commodity Association: Chinese Commodity components after oral administration of Fructus Association 2017, P: 558-580. (Chinese) Forsythiae by HPLC-MS/MS and the effects of 70．Jiao J, Fu YJ, Zu YG, et al. Enzyme-assisted harvest time and administration times. J microwave hydro-distillation essential oil from CHROMATOGR B 2015, P:36-46. Fructus forsythia, chemical constituents, and its 58．Liu Y, Song SJ, Xu SX, Fu XH. Study on antimicrobial and antioxidant activities. FOOD Chemical Composition of Forsythia Suspense. CHEM 2012, 134: 235-243. Journal of Shenyang Pharmaceutical University 71．Yang JJ, Wei HM, Teng XN, et al. Dynamic 2003, 02: 101-103. (Chinese) ultrasonic nebulisation extraction coupled with TMRmhm | May 2020 | Vol.3 | No.2 | 96 Submit a manuscript: https://www.tmrjournals.com/mhm
REVIEW doi: 10.12032/TMRmhm202003069 headspace ionic liquid-based single-drop edema rats by serum metabolomics. BIOMED microextraction for the analysis of the essential oil PHARMACOTHER 2017, 95: 929-937. in Forsythia suspensa. PHYTOCHEM ANALYSIS 85．Hwang YH, Kim DG, Li W, et al. 2014, 25: 178-84. Anti-inflammatory effects of Forsythia suspensa in 72．Zhang Y, Xue KP, Zhao EY, et al. Determination dextran sulfate sodium-induced coliti. J of oleanolic acid and ursolic acid in Chinese ETHNOPHARMACOL 2017, 206: 73-77. medicinal plants using HPLC with PAH polymeric 86．Zhang XT, Ding Y, Kang P, et al. Forsythoside A C18. PHARMACOGN MAG 2013, 9: S19-24. modulates zymosan-induced peritonitis in mice. 73．Fang Y, Zou GA, Liu YW. Chemical MOLECULES 2018, 23: 593. Composition of Forsythia Suspense. China Natural 87．Lee JJ, Kim KH, Kim EJ, et al. Medicine 2008, 03: 235-236. (Chinese) Anti-inflammatory activity of the decoction of 74．Zhang Q, Lu Z, Li X, et al. Triterpenoids and Forsythia suspensa (Thunb.) Vahl is related to Nrf2 Steroids from the Leaves of Forsythia suspensa. and A20. J ETHNOPHARMACOL 2018, CHEM NAT COMPD+ 2015, 51: 178-180. 227:97-104. 75．Rouf AS, Ozaki Y, Rashid MA, et al. Dammarane 88．Rothschild DE, Mcdaniel DK, Ringel-Scaia VM, derivatives from the dried fruits of Forsythia et al. Modulating inflammation through the suspensa. PHYTOCHEMISTRY 2001, 56: negative regulation of NF-κB signaling. J 815-818. LEUKOCYTE BIOL 2018. 76．Dai S, Ren Y, Shen L, et al. New Alkaloids from 89．Hwang YH, Kim DG, Li W, et al. Forsythia suspensa and their anti-inflammatory Anti-inflammatory effects of Forsythia suspensa in activities. PLANTA MED 2009, 75: 375-377. dextran sulfate sodium-induced colitis. J 77．Guo Q, Wang ZM, Lin LM, et al. Research ETHNOPHARMACOL 2017, 206. Progress on Chemical Components of Medicinal 90．Wang Y, Zhao H, Lin C, et al. Forsythiaside A Plants of Forsythia. China Journal of Experimental exhibits anti-inflammatory effects in Traditional Medical Formulae 2009, 15: 74-79. LPS-Stimulated BV2 microglia cells through (Chinese) activation of Nrf2/HO-1 signaling pathway. 78．Guo YP, Lin LG, Wang YT. Chemistry and NEUROCHEM RES 2016, 41: 659-665. pharmacology of the herb pair Flos Lonicerae 91．Zhong WT, Wu YC, Xie XX, et al. Phillyrin japonicae-Forsythiae fructus. CHIN MED-UK 2015, attenuates LPS-induced pulmonary inflammation 10:16. via suppression of MAPK and NF-κB activation in 79．Bai YE, Qi XM, Yang GH, et al. In vitro acute lung injury mice. FITOTERAPIA 2013, 90: antibacterial test of forsythia extract. Journal of 132-139. Shanxi Medical University 2003, 06: 506-507. 92．Lee S, Shin S, Kim H, et al. Anti-inflammatory (Chinese) function of arctiin by inhibiting COX-2 expression 80．Han X, Piao XS, Zhang HY, et al. Forsythia via NF-κB pathways. J INFLAMM-LOND 2011, 8: suspensa extract has the potential to substitute 16. antibiotic in broiler chicken. ASIAN AUSTRAL J 93．Muluye RA, Bian Y, Alemu PN. ANIM 2012, 25: 569-576. Anti-inflammatory and antimicrobial effects of 81．Feng SY, Li XR, Sun JN. Study on anti-infection heat-clearing Chinese Herbs: A Current Review. J and antipyretic effect of forsythiaside. Progress in TRADIT COMPLEM MED 2014, 4: 93-98. Modern Biomedicine 2006, 10: 73-75. (Chinese) 94．Guo YP, Lin LG, Wang YT. Chemistry and 82．Chen CL, Zhang DD. Anti-Inflammatory effects pharmacology of the herb pair Flos Lonicerae of 81 Chinese herb extracts and their correlation japonicae-Forsythiae fructus. CHIN MED-UK 2015, with the characteristics of Traditional Chinese 10:16. Medicine. EVID-BASED COMPL ALT 2014, 95．Qu XY, Li QJ, Zhang HM, et al. Protective P:1-8. effects of phillyrin against influenza A virus in vivo. 83．Wang TT, Zhang Y, Yang ZM, et al. Study on ARCH PHARM RES 2016, 39: 998-1005. antibacterial and anti-inflammatory activity and its 96．Law HY, Yang LH, Lau SY, et al. Antiviral effect main chemical constituents of Forsythia suspensa of forsythoside A from Forsythia suspensa (Thunb.) and Forsythia suspensa leaves. Chin Drug Clin Vahl fruit against influenza A virus through Med 2019, 19: 2380-2381. (Chinese) reduction of viral M1 protein. J 84．Yuan A, Gong L, Luo L, et al. Revealing ETHNOPHARMACOL 2017, 209: 236-247. anti-inflammation mechanism of water-extract and 97．Li D, Peng P, Ke Z, et al. Forsythoside A oil of forsythiae fructus on carrageenan-Induced Controls Influenza A Virus Infection and Improves Submit a manuscript: https://www.tmrjournals.com/mhm TMRmhm | May 2020 | Vol.3 | No.2 | 97
doi:10.12032/TMRmhm202003069 REVIEW the Prognosis by Inhibiting Virus Replication in 110．Zhang S, Shao SY, Song XY, et al. Protective Mice. MOLECULES 2016, 21:524. effects of Forsythia suspense extract with 98．Yang Y. Screening of single Chinese medicine antioxidant and anti-inflammatory properties in a against swine influenza virus in vitro. Tai an: model of rotenone induced neurotoxicity. Shandong Agricultural University 2013. (Chinese) NEUROTOXICOLOGY 2016, 52: 72-83. 99．Yuan A, Zhao MJ, Li Y, et al. A review of the 111．Kim JM, Kim S , Kim DH, et al. pharmacological effects of forsythia. Traditional Neuroprotective effect of forsythiaside against Chinese Medicine and Clinical Medicine 2015, 6: transient cerebral global ischemia in gerbil. EUR J 56-59. (Chinese) PHARMACOL 2011, 660: 326-333. 100．Bao J, Ding R, Zou L, et al. Forsythiae Fructus 112．Iizuka T, Nagai M. Vasorelaxant effects of inhibits B16 melanoma growth involving forsythiaside from the Fruits of Forsythia suspensa. MAPKs/Nrf2/HO-1 mediated anti-oxidation and YAKUGAKU ZASSHI 2005, 125: 219-224. anti-Inflammation. AM J CHINESE MED 2016, 113．Hao FF. Experimental study of Forsythia 44(05):1043-1061. suspensa and its effect on gastrointestinal motility 101．Pan CW, Zhou GY, Chen WL, et al. Protective in baohe pills. Shandong University of Traditional effect of forsythiaside A on Chinese Medicine 2018. (Chinese) lipopolysaccharide/d-galactosamine-induced liver 114．Liu CX, Chen SL, Xiao XH, et al. Q-Marker: A injury. INT IMMUNOPHARMACOL 2015, 26: New Concept of Quality Control of Traditional 80-85. Chinese Medicine Products. China Tradit Herb 102．Qu H, Zhang Y, Chai X, et al. Isoforsythiaside, Drugs 2016, 47: 1443-1457. (Chinese) an antioxidant and antibacterial phenylethanoid 115．Liu CX. Construction of Chinese Medicine glycoside isolated from Forsythia suspensa. Quality Traceability System Based on Chinese BIOORG CHEM 2012, 40: 87-91. Medicine Quality Markers. China Tradit Herb 103．Lu T, Piao XL, Zhang Q, et al. Protective effects Drugs 2017 48: 3669-3676. (Chinese) of Forsythia suspensa extract against oxidative 116．Liu CX, Chen SL, Xiao XH, et al. Q-Marker of stress induced by diquat in rats. Food & Chemical Chinese Medicine: A New Concept of Quality Toxicology An International Journal Published for Control of Traditional Chinese Medicine Products. the British Industrial Biological Research China Tradit Herb Drugs 2016, 47: 1443-1457. Association 2010, 48: 764-770. (Chinese) 104．Piao XL, Cho EJ, Cho EJ, et al. Cytoprotective 117．Liu CX. Q-marker of Traditional Chinese effect of lignans from Forsythia suspensa against Medicine: Improving the Quality Standard of peroxynitrite-induced LLC-PK1 cell damage. Traditional Chinese Medicine and Quality Control PHYTOTHER RES 2009, 23: 938-942. Theory and Promoting the Scientific Development 105．Huang CK, Lin Y, Su H, et al. Forsythiaside of Traditional Chinese Medicine Industry. China Protects Against Hydrogen Peroxide-Induced Tradit Herb Drugs 2019, 50: 4517-4518. (Chinese) Oxidative Stress and Apoptosis in PC12 Cell. 118．Zhang TJ, Bai G, Liu CX. The concept, core NEUROCHEM RES 2015, 40: 27-35. theory and research methods of quality markers of 106．Ge Y, Wang Y, Chen P, et al. traditional Chinese medicine. ACTA PHARM SIN Polyhydroxytriterpenoids and phenolic constituents B 2019, 54: 187-196 + 186. (Chinese) from Forsythia suspensa (Thunb.) Vahl Leaves. J 119．Xue QQ, Li AP, Li K, et al. Summary of Quality AGR FOOD CHEM 2015, 64 125-131. Evaluation Research of Astragalus and Preliminary 107．Sung YY, Yoon T, Jang S, et al. Forsythia Exploration of Quality Marker Research Strategy. suspensa suppresses house dust mite Drug Evaluation Research 2019, 42: 2459-2463. extract-induced atopic dermatitis in NC/Nga mice. (Chinese) PLOS ONE 2016, 11, e0167687. 120．Zhang HJ, Gong SX, Xu J, et al. Research 108．Hao Y, Li D, Piao X, et al. Forsythia suspensa Progress and Prediction and Analysis of Quality extract alleviates hypersensitivity induced by Markers of Alisma orientalis. China Tradit Herb soybean β-conglycinin in weaned piglets. J Drugs 2019, 50: 4741-4751. (Chinese) ETHNOPHARMACOL 2010,128: 412-418. 121．Hao M, Tong HJ, Zhang J, et al. Study on 109．Wang HM, Wang LW, Liu XM, et al. Quality Markers of Chinese Herbal Pieces: Study Neuroprotective effects of forsythiaside on learning on Quality Evaluation of Zedoary Rhizoma Pieces and memory deficits in senescence-accelerated and Discussion on Quality Standards. China Tradit mouse prone (SAMP8) mice. PHARMACOL Herb Drugs 2019, 50: 4673-4682. (Chinese) BIOCHEM BE 2013, 105: 134-141. 122．Zhang TJ, Xu J, Han YQ, et al. Research on TMRmhm | May 2020 | Vol.3 | No.2 | 98 Submit a manuscript: https://www.tmrjournals.com/mhm
You can also read
