Access to this full-text is provided by MDPI.
Content available from Molecules
This content is subject to copyright.
Citation: Zhang, J.; Chen, X.; Han, L.;
Ma, B.; Tian, M.; Bai, C.; Zhang, Y.
Research Progress in Traditional
Applications, Phytochemistry,
Pharmacology, and Safety Evaluation
of Cynomorium songaricum.Molecules
2024,29, 941. https://
doi.org/10.3390/molecules29050941
Academic Editor: Satyajit D Sarker
Received: 16 January 2024
Revised: 12 February 2024
Accepted: 13 February 2024
Published: 21 February 2024
Copyright: © 2024 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
molecules
Review
Research Progress in Traditional Applications, Phytochemistry,
Pharmacology, and Safety Evaluation of Cynomorium songaricum
Jin Zhang 1,2, Xingyi Chen 1,2, Lu Han 1,2, Biao Ma 1,2, Mengting Tian 1,2, Changcai Bai 1,2,* and Ye Zhang 3,*
1
College of Pharmacy, Ningxia Medical University, Yinchuan 750004, China; zhangjin20210911@163.com (J.Z.);
cxyfengruoli@163.com (X.C.); lulu2008han@163.com (L.H.); 15008600583@163.com (B.M.);
tianmengtjy@163.com (M.T.)
2Key Laboratory of Ningxia Ethnomedicine Modernization, Ministry of Education, Ningxia Medical
University, Yinchuan 750004, China
3College of Pharmacy, Inner Mongolia Medical University, Hohhot 010110, China
*Correspondence: changcaibai@163.com (C.B.); 20120128@immu.com (Y.Z.)
Abstract: Cynomorium songaricum Rupr. (CSR) belongs to the family Cynomoriaceae. It is a perennial
succulent parasitic herb with a reddish-brown coloration, predominantly submerged in sand and
lacking chlorophyll. Traditionally, it has been used in ethnic medicine to treat various diseases, such
as gastric ulcers, indigestion, bowel movements, and improving sexual function. To comprehensively
collect CSR data, extensive literature searches were conducted using medical, ecological, and scientific
databases such as Google Scholar, PubMed, Science Direct, Web of Science, and China National
Knowledge Infrastructure (CNKI). This article summarizes and categorizes research on the uses,
phytochemical characteristics, pharmacological activities, and toxicity of ethnic medicine, with the
aim of establishing a solid foundation and proposing new avenues for exploring and developing
potential applications of CSR. So far, a total of 98 compounds have been isolated and identified
from CSR, including flavonoids, terpenes, steroids, and other compounds. It is worth noting that
flavonoids and polysaccharides have significant antioxidant and anti-inflammatory properties. In
addition, these compounds also show good application prospects in anti-tumor, antioxidant, anti-
aging, anti-fatigue, anti-diabetes, and other aspects. Although extensive progress has been made
in the basic research of CSR, further research is still needed to enhance the understanding of its
mechanism of action and explore more unknown compounds. Our review indicates that CSR has
broad prospects and deserves further research.
Keywords: Cynomorium songaricum Rupr.; traditional uses; phytochemistry; pharmacology; toxicology
1. Introduction
Cynomorium is a genus containing two species, C. songaricum Rupr. and
C. coccineum L.
,
and is in the family Cynomoriaceae. These two types are mainly distributed in dry, rocky,
or sandy soil areas, mainly appearing in the Northern Hemisphere. For centuries, folk
medicine has been widely applied in countries such as Europe, North Africa, East Asia,
and West Asia. Cynomorium songaricum Rupr. (CSR), a dried succulent stem of a rare
endangered medicinal herb that belongs to the genus of Cynomorium L. [
1
], is mainly
distributed in Xinjiang, Qinghai, Gansu, Ningxia, Inner Mongolia, Shaanxi and other
northwestern regions in China [
2
]. At present, CSR has been classified as vulnerable (VU)
by the International Union for Conservation of Nature (IUCN), and as a Grade II protected
plant by the Convention on International Trade in Endangered Species of Wild Fauna and
Flora (CITES) [3].
As a plant with homologous medicinal and edible properties, CSR is widely used
both domestically and internationally. There are some common ways to consume CSR in
North Africa, Europe, East Asia, and West Asia due to its nutritional and health value. For
Molecules 2024,29, 941. https://doi.org/10.3390/molecules29050941 https://www.mdpi.com/journal/molecules
Molecules 2024,29, 941 2 of 33
example, fresh CSR can be used for steaming rice, pancakes, etc., while dry CSR can be
used for boiling soup, brewing wine, making health foods, etc. [4].
The medicinal history of CSR can be traced back to the Yuan Dynasty, as recorded
in the Ben Cao Yan Yi Bu Yi (Yuan Dynasty, A.D. 1347) which has the effects of tonifying
kidney yang, benefiting essence and blood, and moistening the intestines and relieving
constipation [
5
]. The dried fleshy stem of CSR can tonify kidney Qi, enhance essence blood
nourishment, and treat problems such as weakness and impotence [
6
]. CSR whole grass
can treat impotence caused by kidney deficiency, multiple dreams, spermatogenesis, waist
and knee weakness, and other symptoms. However, it can also be used in the treatment of
diarrhea, women’s leucorrhea, gum bleeding, and other diseases [7].
CSR is rich in polyphenols and polysaccharides, both with biological activities such as
scavenging free radicals in the body. As a result, CSR is also known as “the elixir of youth”
because it prevents lipid oxidation, aging, cardiovascular disease, cancer, and radiation
damage [
8
]. In recent years, the chemical composition of CSR has been gradually revealed,
and it has been reported that it contains flavonoids [
9
], triterpenoids [
10
], sugars and
glycosides [
11
], steroids [
12
], organic acids [
13
] and other components. Modern pharmaco-
logical studies have shown that the extract has the ability to promote cell regeneration and
metabolism; enhance immune regulatory function [
14
]; has anti-cancer [
15
], anti-viral [
16
],
and anti-aging properties [17]; and relieves fatigue [18].
The present paper provides a comprehensive review of the botanical characteristics,
traditional medicinal history, phytochemical composition, pharmacological research, and
toxicological research progress of CSR. This systematic analysis aims to offer valuable
insights into its clinical application and further research and development in the field of
functional foods.
2. Materials and Methods
Google Scholar (http://scholar.google.com/, accessed on 27 May 2023), PubMed
(http://www.ncbi.nlm.nih.gov/pubmed/, accessed on 27 May 2023), Science Direct (http:
//www.sciencedirect.com/, accessed on 27 May 2023), Web of Science (http://apps.
webofknowledge.com/, accessed on 27 May 2023) and China National Knowledge In-
frastructure (https://www.cnki.net/, accessed on 27 May 2023) and other medical, eco-
logical, and scientific databases were used to conduct an extensive literature search to
classify the distribution of CSR and preliminary studies. Various keyword combinations
such as “Cynomorium songaricum Rupr.” and “traditional use”, “phytochemistry”, “phar-
macology” and “isolated compounds” were used to collect scientific evidence on plant
description, traditional use, phytochemical composition, and pharmacological proper-
ties of CSR. EndNote (https://endnote.com/, accessed on 27 May 2023) was used to
collate the published literature. And we used the PubChem chemical database (https:
//pubchem.ncbi.nlm.nih.gov/search/search.cgi/, accessed on 27 May 2023), and other
open access and redraw the chemical structure of CSR compounds. The structure of CSR
compounds was plotted in Chem Draw 18.0 software.
3. Botany
3.1. Characteristics of Plants
CSR is a perennial succulent parasitic herb with a reddish-brown coloration, pre-
dominantly submerged in sand and lacking chlorophyll (Figure 1). CSR possesses a few
triangular scales in its middle and upper sections. Its inflorescence is terminal and clavate,
adorned with scaly leaves, featuring bisexual flowers consisting of petals, stamens, and an
ovary. Male flowers typically have four perianth pieces, while the pistil undergoes degra-
dation. Female flowers exhibit a lower ovary with usually 5–6 perianth pieces enclosing
one pendulous ovule at the apex, male flowers degenerate accordingly. The fruit resembles
a nut [19].
Molecules 2024,29, 941 3 of 33
Molecules 2024, 29, x FOR PEER REVIEW 3 of 35
pieces enclosing one pendulous ovule at the apex, male owers degenerate accordingly.
The fruit resembles a nut [19].
Figure 1. The overall appearance (hp://www.iplant.cn/frps/, accessed on 12 May 2023.) (a); whole
grass (b); inorescence (c); and herbal medicinal preparation (d) of Cynomorium songaricum Rupr.
3.2. Growth Environment and Regional Distribution
CSR is a rare and endangered medicinal plant mainly distributed in northwest China,
such as Inner Mongolia (Red), Gansu (Blue), Xinjiang (Orange), Qinghai (Purple), and
Ningxia (Yellow) (Figure 2). Growing in temperate and subtropical regions, it can grow in
areas with lower elevations or up to 2000 m above sea level. It likes warm and humid
climates, has strong adaptability, and can grow in areas with full or partial sunlight. The
minimum temperature is generally required to be no lower than −10 °C. It can withstand
high temperatures even in hoer summers. It can adapt to dierent types of soil but it is
best to avoid excessively humid or poor soil. Wild CSR is the main source, with a domestic
accumulation of about 30,000 tons. Under normal circumstances, about 1500 tons are
harvested annually. However, the existing wild CSR resources are only concentrated in
the Hedong sandy land of Pingluo County and their distribution area has been decreasing
year by year [20]. There are ve host plants, namely Nitraria sphaerocarpa, Nitraria sibirica,
Nitraria tangutorum, Zygophyllum xanthoxylon, and Peganum multisectum [21]. The lifecycle
of CSR mainly includes several stages: seed germination, parasitic localization, parasitic
aachment, growth cycle, and seed dispersal (Figure 3). Under natural conditions, CSR
vegetative growth does not necessitate external light, and the entire growth process takes
4–5 years. However, through articial cultivation, CSR can be harvested within 3–4 years
[22]. CSR seeds germinate under favorable conditions, producing a specialized “bud tube
organ”. The terminal regions of this structure expand and adhere to the host plant’s root
system, invading it. Once connected to the host plant’s vascular bundle, a parasitic
relationship is established, leading to new gemmules [23].
Figure 1. The overall appearance (http://www.iplant.cn/frps/, accessed on 12 May 2023.) (a); whole
grass (b); inflorescence (c); and herbal medicinal preparation (d) of Cynomorium songaricum Rupr.
3.2. Growth Environment and Regional Distribution
CSR is a rare and endangered medicinal plant mainly distributed in northwest China,
such as Inner Mongolia (Red), Gansu (Blue), Xinjiang (Orange), Qinghai (Purple), and
Ningxia (Yellow) (Figure 2). Growing in temperate and subtropical regions, it can grow
in areas with lower elevations or up to 2000 m above sea level. It likes warm and humid
climates, has strong adaptability, and can grow in areas with full or partial sunlight. The
minimum temperature is generally required to be no lower than
−
10
◦
C. It can withstand
high temperatures even in hotter summers. It can adapt to different types of soil but it is
best to avoid excessively humid or poor soil. Wild CSR is the main source, with a domestic
accumulation of about 30,000 tons. Under normal circumstances, about 1500 tons are
harvested annually. However, the existing wild CSR resources are only concentrated in the
Hedong sandy land of Pingluo County and their distribution area has been decreasing year
by year [
20
]. There are five host plants, namely Nitraria sphaerocarpa,Nitraria sibirica,Nitraria
tangutorum,Zygophyllum xanthoxylon, and Peganum multisectum [
21
]. The lifecycle of CSR
mainly includes several stages: seed germination, parasitic localization, parasitic attach-
ment, growth cycle, and seed dispersal (Figure 3). Under natural conditions, CSR vegetative
growth does not necessitate external light, and the entire growth process takes
4–5 years
.
However, through artificial cultivation, CSR can be harvested within
3–4 years
[
22
]. CSR
seeds germinate under favorable conditions, producing a specialized “bud tube organ”.
The terminal regions of this structure expand and adhere to the host plant’s root system,
invading it. Once connected to the host plant’s vascular bundle, a parasitic relationship is
established, leading to new gemmules [23].
Molecules 2024, 29, x FOR PEER REVIEW 4 of 35
Figure 2. Major producing areas in China of Cynomorium songaricum Rupr. Inner Mongolia (Red),
Gansu (Blue), Xinjiang (Orange), Qinghai (Purple), and Ningxia (Yellow).
Figure 3. Life cycle of Cynomorium songaricum Rupr.
4. Traditional Uses
The use of CSR in Asia has a long history, primarily for erectile dysfunction,
premature ejaculation, and spermatogenesis enhancement. It was rst recorded in Ben Cao
Yan Yi Bu Yi (Yuan Dynasty, A.D. 1347). Later, the use of the plant was documented in
other well-known medicinal works, including Ben Cao Meng Quan (Ming Dynasty, A.D.
1565), Ben Cao Gang Mu (Ming Dynasty, A.D. 1590), Ben Cao Qie Yao (Ming Dynasty, A.D.
1609), Ben Cao Bei Yao (Qing Dynasty, A.D. 1694). The traditional preparation of CSR
primarily involves the formulation of pills, with notable examples being Huqian wan and
Suoyang gujing wan. Its primary function lies in nourishing the kidneys and invigorating
Yang, albeit with distinct eects (Table 1).
CSR is primarily utilized in clinical practice for the treatment of andrological and
gynecological disorders. Its key therapeutic advantages include enhancing sexual
function, regulating endocrine function, and promoting gastrointestinal health. Besides
its signicant medicinal value, it also nds application in culinary preparations such as
steamed rice or pancakes when fresh. It is also incorporated into soups, wines, or health
foods when dried. Prolonged consumption can improve immunity and prevent diabetes
[24]. Additionally, CSR can serve as a supplementary source of essential trace elements
for the human body. CSR exhibits robust vitality and adaptability, thriving in arid deserts,
Figure 2. Major producing areas in China of Cynomorium songaricum Rupr. Inner Mongolia (Red),
Gansu (Blue), Xinjiang (Orange), Qinghai (Purple), and Ningxia (Yellow).
Molecules 2024,29, 941 4 of 33
Molecules 2024, 29, x FOR PEER REVIEW 4 of 35
Figure 2. Major producing areas in China of Cynomorium songaricum Rupr. Inner Mongolia (Red),
Gansu (Blue), Xinjiang (Orange), Qinghai (Purple), and Ningxia (Yellow).
Figure 3. Life cycle of Cynomorium songaricum Rupr.
4. Traditional Uses
The use of CSR in Asia has a long history, primarily for erectile dysfunction,
premature ejaculation, and spermatogenesis enhancement. It was rst recorded in Ben Cao
Yan Yi Bu Yi (Yuan Dynasty, A.D. 1347). Later, the use of the plant was documented in
other well-known medicinal works, including Ben Cao Meng Quan (Ming Dynasty, A.D.
1565), Ben Cao Gang Mu (Ming Dynasty, A.D. 1590), Ben Cao Qie Yao (Ming Dynasty, A.D.
1609), Ben Cao Bei Yao (Qing Dynasty, A.D. 1694). The traditional preparation of CSR
primarily involves the formulation of pills, with notable examples being Huqian wan and
Suoyang gujing wan. Its primary function lies in nourishing the kidneys and invigorating
Yang, albeit with distinct eects (Table 1).
CSR is primarily utilized in clinical practice for the treatment of andrological and
gynecological disorders. Its key therapeutic advantages include enhancing sexual
function, regulating endocrine function, and promoting gastrointestinal health. Besides
its signicant medicinal value, it also nds application in culinary preparations such as
steamed rice or pancakes when fresh. It is also incorporated into soups, wines, or health
foods when dried. Prolonged consumption can improve immunity and prevent diabetes
[24]. Additionally, CSR can serve as a supplementary source of essential trace elements
for the human body. CSR exhibits robust vitality and adaptability, thriving in arid deserts,
Figure 3. Life cycle of Cynomorium songaricum Rupr.
4. Traditional Uses
The use of CSR in Asia has a long history, primarily for erectile dysfunction, premature
ejaculation, and spermatogenesis enhancement. It was first recorded in Ben Cao Yan Yi Bu Yi
(Yuan Dynasty, A.D. 1347). Later, the use of the plant was documented in other well-known
medicinal works, including Ben Cao Meng Quan (Ming Dynasty, A.D. 1565), Ben Cao Gang
Mu (Ming Dynasty, A.D. 1590), Ben Cao Qie Yao (Ming Dynasty, A.D. 1609), Ben Cao Bei
Yao (Qing Dynasty, A.D. 1694). The traditional preparation of CSR primarily involves the
formulation of pills, with notable examples being Huqian wan and Suoyang gujing wan. Its
primary function lies in nourishing the kidneys and invigorating Yang, albeit with distinct
effects (Table 1).
CSR is primarily utilized in clinical practice for the treatment of andrological and
gynecological disorders. Its key therapeutic advantages include enhancing sexual function,
regulating endocrine function, and promoting gastrointestinal health. Besides its significant
medicinal value, it also finds application in culinary preparations such as steamed rice or
pancakes when fresh. It is also incorporated into soups, wines, or health foods when dried.
Prolonged consumption can improve immunity and prevent diabetes [
24
]. Additionally,
CSR can serve as a supplementary source of essential trace elements for the human body.
CSR exhibits robust vitality and adaptability, thriving in arid deserts, rocky crevices, and
harsh environments characterized by drought and wind erosion. It possesses significant
ecological value in terms of enhancing environmental conditions, preserving soil stability,
and maintaining ecological equilibrium [25].
Table 1. The traditional uses of Cynomorium songaricum Rupr. in China.
Prescription Name Main Components Traditional Uses Ancient Books References
Huqian wan
Cynomorium,Cupressus funebris,
Anemarrhena asphodeloides,
orange peel, Paeonia lactiflora,
tortoise plastron, etc.
Curing impotence Dan Xi Xin Fa (Ming
Dynasty, A.D. 1481) [26]
Guilu bushen wan
Cynomorium,Epimedium
brevicornu, common jujube
seed, Ipomoea batatas,Rubus
idaeus, orange peel, etc.
Curing impotence Chinese Pharmacopoeia 2020 [27]
Suoyang gujing wan
Cynomorium,Cuscuta chinensis,
Alisma plantago-aquatica,
Achyranthes bidentata,
Anemarrhena asphodeloides,
Poria cocos, etc.
Curing spermatorrhea
Chinese Pharmacopoeia 2020 [28]
Molecules 2024,29, 941 5 of 33
Table 1. Cont.
Prescription Name Main Components Traditional Uses Ancient Books References
Guben wan
Cynomorium,Panax ginseng,
Oxytropis xinglongshanica,
Sinocrassula indica, clam
powder, Atractylodes
macrocephala, etc.
Curing chronic
renal failure
Song Ya Zun Sheng (Qing
Dynasty, A.D. 1695) [29]
Dabuyin wan
Cynomorium,Cupressus funebris,
Anemarrhena asphodeloides,
Paeonia lactiflora, orange peel,
Stephania tetrandra, etc.
Curing diabetic
nephropathy
Tong Shou Lu (Qing
Dynasty, A.D. 1762) [30]
Xusi dan
Cynomorium,Fossilizid,Concha
ostreae,Eucommia ulmoides,
orange peel, Atractylodes
macrocephala, etc.
Curing male
infertility
Fu Ke Yu Chi (Qing
Dynasty, A.D. 1644–1911) [31]
Jiawei huqian wan
Cynomorium,Ipomoea batatas,
Schisandra chinensis,
Achyranthes bidentata,Cupressus
funebris,Angelica sinensis, etc.
Strong bones
and muscles
Yi Xue Liu Yao (Ming
Dynasty, A.D. 1609) [32]
Shenlu jianbu wan
Cynomorium,Cupressus funebris,
Anemarrhena asphodeloides,
orange peel, Zingiber officinale,
tortoise plastron, etc.
Strong bones
and muscles Chinese Pharmacopoeia 2020 [33]
Jiawei jianbu
huqian wan
Cynomorium,Pleuropterus
multiflorus,Clematis chinensis,
Cupressus funebris,Panax
ginseng,Hansenia
weberbaueriana, etc.
Curing of fall injury Jin Jian (Qing Dynasty,
A.D. 1736) [34]
Gouqi wan
Cynomorium,Lycium chinense,
Panax ginseng,Cupressus
funebris,Angelica sinensis,
Paeonia lactiflora, etc.
Curing alzheimer
disease
She Sheng Zhong Miao Fang
(Ming Dynasty, A.D. 1550) [35]
Guilingji capsule
Cynomorium,Talinum
paniculatum,Lycium chinense,
Syringa Linn,
Achyranthes bidentata,
Cistanche deserticola, etc.
Curing cognitive
dysfunction Chinese Pharmacopoeia 2020 [36]
Jiawei buyin wan
Cynomorium,Achyranthes
bidentata,Eucommia ulmoides,
Amomum villosum,Angelica
sinensis,Anemarrhena
asphodeloides, etc
Curing
hyperthyroidism
Zhun Sheng Shang Han
(Ming Dynasty, A.D. 1604) [37]
Jiajian buyin wan
Cynomorium,Cuscuta chinensis,
Angelica sinensis,Paeonia
lactiflora,Eucommia ulmoides,
Achyranthes bidentata, etc.
Curing
perimenopausal
syndrome of Yin
deficiency type
Dan Xi Xin Fa (Ming
Dynasty, A.D. 1481) [38]
5. Phytochemistry
In recent years, a diverse range of potent chemical components have been isolated
from various parts of the CSR plant. These components include flavonoids, triterpenoids,
steroids, organic acids, sugars and glycosides, amino acids, and trace elements. Most of
them have been extensively used in proprietary Chinese medicine and healthcare products.
We classify the 98 compounds isolated and identified according to their types. The basic
information and source areas of these compounds are summed up in Figure 3, while their
structures can be seen in Figures 4–11.
Molecules 2024,29, 941 6 of 33
Molecules 2024, 29, x FOR PEER REVIEW 6 of 35
sinensis, Paeonia lactiflora,
etc.
Guilingji capsule
Cynomorium, Talinum
paniculatum, Lycium
chinense, Syringa Linn,
Achyranthes bidentata,
Cistanche deserticola, etc.
Curing cognitive dysfunction
Chinese Pharmacopoeia
2020
[36]
Jiawei buyin wan
Cynomorium, Achyranthes
bidentata, Eucommia
ulmoides, Amomum villosum,
Angelica sinensis,
Anemarrhena asphodeloides,
etc
Curing hyperthyroidism
Zhun Sheng Shang Han
(Ming Dynasty, A.D.
1604)
[37]
Jiajian buyin wan
Cynomorium, Cuscuta
chinensis, Angelica sinensis,
Paeonia lactiflora, Eucommia
ulmoides, Achyranthes
bidentata, etc.
Curing perimenopausal
syndrome of Yin deficiency type
Dan Xi Xin Fa (Ming
Dynasty, A.D. 1481)
[38]
5. Phytochemistry
In recent years, a diverse range of potent chemical components have been isolated
from various parts of the CSR plant. These components include avonoids, triterpenoids,
steroids, organic acids, sugars and glycosides, amino acids, and trace elements. Most of
them have been extensively used in proprietary Chinese medicine and healthcare
products. We classify the 98 compounds isolated and identied according to their types.
The basic information and source areas of these compounds are summed up in Figure 3,
while their structures can be seen in Figures 4–11.
Figure 4. Percentage of chemical composition categories isolated from Cynomorium songaricum
Rupr.
Figure 4. Percentage of chemical composition categories isolated from Cynomorium songaricum Rupr.
Molecules 2024, 29, x FOR PEER REVIEW 7 of 35
Figure 5. The structures of compounds 1–27 from Cynomorium songaricum Rupr.
Figure 6. The structures of compounds 28–39 from Cynomorium songaricum Rupr.
Figure 5. The structures of compounds 1–27 from Cynomorium songaricum Rupr.
Molecules 2024,29, 941 7 of 33
Molecules 2024, 29, x FOR PEER REVIEW 7 of 35
Figure 5. The structures of compounds 1–27 from Cynomorium songaricum Rupr.
Figure 6. The structures of compounds 28–39 from Cynomorium songaricum Rupr.
Figure 6. The structures of compounds 28–39 from Cynomorium songaricum Rupr.
Molecules 2024, 29, x FOR PEER REVIEW 8 of 35
Figure 7. The structures of compounds 40–49 from Cynomorium songaricum Rupr.
Figure 8. The structures of compounds 50–62 from Cynomorium songaricum Rupr.
Figure 9. The structures of compounds 63–79 from Cynomorium songaricum Rupr.
Figure 7. The structures of compounds 40–49 from Cynomorium songaricum Rupr.
Molecules 2024, 29, x FOR PEER REVIEW 8 of 35
Figure 7. The structures of compounds 40–49 from Cynomorium songaricum Rupr.
Figure 8. The structures of compounds 50–62 from Cynomorium songaricum Rupr.
Figure 9. The structures of compounds 63–79 from Cynomorium songaricum Rupr.
Figure 8. The structures of compounds 50–62 from Cynomorium songaricum Rupr.
Molecules 2024, 29, x FOR PEER REVIEW 8 of 35
Figure 7. The structures of compounds 40–49 from Cynomorium songaricum Rupr.
Figure 8. The structures of compounds 50–62 from Cynomorium songaricum Rupr.
Figure 9. The structures of compounds 63–79 from Cynomorium songaricum Rupr.
Figure 9. The structures of compounds 63–79 from Cynomorium songaricum Rupr.
Molecules 2024,29, 941 8 of 33
Molecules 2024, 29, x FOR PEER REVIEW 9 of 35
Figure 10. The structures of compounds 80–85 from Cynomorium songaricum Rupr.
Figure 11. The structures of compounds 86–98 from Cynomorium songaricum Rupr.
5.1. Flavonoids
A class of natural compounds with a parent nucleus structure of 2-phenylchromogen
(avone) are called avonoids, which are the main active ingredients in CSR. Their
molecular basis as the antioxidant [39] and anti-aging [40] activities of CSR have been
widely proven, and CSR avonoids have also been found to be eective in antibacterial
activity [41].
Currently, a total of 27 types of avonoids have been isolated from CSR sinensis.
Phloridzin (1) [42], (−)-epicatechin (2), and naringenin (3) [9] were obtained from the 70%
acetone extract and chloroform extract of stems. Ethyl acetate extract was isolated from
(−)-catechin (4) [43]. Additionally, luteolin-7-O-glucoside (5) was isolated from the ethyl
acetate fraction of the methanol extract derived from stems of CSR [16]. Two anthocyanins,
procyanidin B1 (6) and procyanidin B6 (7), were extracted from the aqueous extract of
stems of CSR chinensis [16].
The procyanidin B3 (8) was isolated and identied from the 70% acetone extract of
fresh CSR stem through column chromatography. The identied compounds include
catechin-(6′-8)-catechin (9), catechin-(6′-6)-catechin (10), epicatechin-(4β-8)-epicatechin-
Figure 10. The structures of compounds 80–85 from Cynomorium songaricum Rupr.
Molecules 2024, 29, x FOR PEER REVIEW 9 of 35
Figure 10. The structures of compounds 80–85 from Cynomorium songaricum Rupr.
Figure 11. The structures of compounds 86–98 from Cynomorium songaricum Rupr.
5.1. Flavonoids
A class of natural compounds with a parent nucleus structure of 2-phenylchromogen
(avone) are called avonoids, which are the main active ingredients in CSR. Their
molecular basis as the antioxidant [39] and anti-aging [40] activities of CSR have been
widely proven, and CSR avonoids have also been found to be eective in antibacterial
activity [41].
Currently, a total of 27 types of avonoids have been isolated from CSR sinensis.
Phloridzin (1) [42], (−)-epicatechin (2), and naringenin (3) [9] were obtained from the 70%
acetone extract and chloroform extract of stems. Ethyl acetate extract was isolated from
(−)-catechin (4) [43]. Additionally, luteolin-7-O-glucoside (5) was isolated from the ethyl
acetate fraction of the methanol extract derived from stems of CSR [16]. Two anthocyanins,
procyanidin B1 (6) and procyanidin B6 (7), were extracted from the aqueous extract of
stems of CSR chinensis [16].
The procyanidin B3 (8) was isolated and identied from the 70% acetone extract of
fresh CSR stem through column chromatography. The identied compounds include
catechin-(6′-8)-catechin (9), catechin-(6′-6)-catechin (10), epicatechin-(4β-8)-epicatechin-
Figure 11. The structures of compounds 86–98 from Cynomorium songaricum Rupr.
5.1. Flavonoids
A class of natural compounds with a parent nucleus structure of 2-phenylchromogen
(flavone) are called flavonoids, which are the main active ingredients in CSR. Their
molecular basis as the antioxidant [
39
] and anti-aging [
40
] activities of CSR have been
widely proven, and CSR flavonoids have also been found to be effective in antibacterial
activity [41].
Currently, a total of 27 types of flavonoids have been isolated from CSR sinensis.
Phloridzin (1) [
42
], (
−
)-epicatechin (2), and naringenin (3) [
9
] were obtained from the 70%
acetone extract and chloroform extract of stems. Ethyl acetate extract was isolated from
(
−
)-catechin (4) [
43
]. Additionally, luteolin-7-O-glucoside (5) was isolated from the ethyl
acetate fraction of the methanol extract derived from stems of CSR [
16
]. Two anthocyanins,
procyanidin B1 (6) and procyanidin B6 (7), were extracted from the aqueous extract of
stems of CSR chinensis [16].
The procyanidin B3 (8) was isolated and identified from the 70% acetone extract of fresh
CSR stem through column chromatography. The identified compounds include catechin-(6
′
-
8)-catechin (9), catechin-(6
′
-6)-catechin (10), epicatechin-(4
β
-8)-epicatechin-(4
β
-8)-catechin
Molecules 2024,29, 941 9 of 33
(11), epicatechin-(4
β
-6)-epicatechin-(4
β
-8)-catechin (12) and
arecatannin A1 (13) [41]
. Fur-
thermore, dehydrodiconiferyl alcohol-9-O-
β
-D-glu-copyranoside (14), 3
′
,4
′
,5,7-tetrahydroxy-
flavanone-2(S)-3
′
-O-
β
-D-glucopyranoside (15), luteolin-4
′
-O-
β
-glucopyranoside (16), as-
tragalin (17), quercetin-3-O-rutinoside (18), naringenin-7-O-
β
-D-glucopyranoside (19),
naringenin-5-O-
β
-D-glucopyranoside (20) was isolated from the ethyl acetate fraction
of 95% ethanol extract obtained from fresh stems of CSR and identified through NMR
analysis [
4
]. The compound naringenin-4
′
-O-
β
-pyranoglucose (21) was isolated from the
n-butanol fraction of a 95% ethanol extract obtained from CSR whole grass [44].
Two anthocyanin pigments were isolated from a 95% ethanol extract of CSR inflores-
cences. Cyanidin 3-O-glucoside (22) was identified as the predominant pigment, accounting
for 92%, while cyanidin 3-O-rhamnosylglucoside (23) was identified as the minor compo-
nent, comprising 8% [
45
]. The compounds (+)-catechin (24), isoquercetin (25), rutin (26),
and (
−
)-epicatechin-3-O-gallate (27) were isolated from ethanol extract of CSR inflores-
cences [46] (Table 2).
Table 2. Flavonoids isolated from Cynomorium songaricum Rupr.
No. Compound
Parts of Plant
Extract Solvent Identification References
1Phloridzin Stems 70% acetone HPLC, 1H NMR, 13C NMR [42]
2(−)-Epicatechin Stems chloroform UV, MS, 1H NMR, 13 C NMR [9]
3Naringenin Stems chloroform TLC, UV, IR, 1H NMR, 13 C NMR [9]
4(−)-Catechin Stems ethyl acetate IR, ESI-MS, 1H NMR, 13C NMR [43]
5Luteolin-7-O-glucoside Stems
ethyl acetate part
1H NMR, 13C NMR [16]
6Procyanidin B1 Stems aqueous 1H NMR, 13C NMR [16]
7Procyanidin B6 Stems aqueous 1H NMR, 13C NMR [16]
8Procyanidin B3 Fresh stems 70% acetone HPLC, 1H NMR, 13C NMR [41]
9Catechin-(6′-8)-catechin Fresh stems 70% acetone HPLC, 1H NMR, 13C NMR [41]
10 Catechin-(6′-6)-catechin Fresh stems 70% acetone HPLC, 1H NMR, 13C NMR [41]
11 Epicatechin-(4β-8)-epicatechin-
(4β-8)-catechin Fresh stems 70% acetone HPLC, 1H NMR, 13 C NMR [41]
12 Epicatechin-(4β-6)-epicatechin-
(4β-8)-catechin Fresh stems 70% acetone HPLC, 1H NMR, 13 C NMR [41]
13 Arecatannin A1 Fresh stems 70% acetone HPLC, 1H NMR, 13C NMR [41]
14
Dehydrodiconiferyl alcohol-9-O-
β-D-glu-copyranoside Fresh stems
ethyl acetate part
1H NMR, 13C NMR [4]
15
3′,4′,5,7-tetrahydroxy-
flavanone-2(S)-3′-O-β-D-
glucopyranoside
Fresh stems
ethyl acetate part
1H NMR, 13C NMR [4]
16 Luteolin-4′-O-β-
glucopyranoside Fresh stems
ethyl acetate part
1H NMR, 13C NMR [4]
17 Astragalin Fresh stems
ethyl acetate part
1H NMR, 13C NMR [4]
18 Quercetin-3-O-rutinoside Fresh stems
ethyl acetate part
1H NMR, 13C NMR [4]
19 Naringenin-7-O-β-D-
glucopyranoside Fresh stems
ethyl acetate part
1H NMR, 13C NMR [4]
20 Naringenin-5-O-β-D-
glucopyranoside Fresh stems
ethyl acetate part
1H NMR, 13C NMR [4]
21 Naringenin-4′-O-β-
pyranoglucose Whole grass N-butanol part 1H NMR, 13C NMR [44]
22 Cyanidin 3-O-glucoside
Inflorescences
95% alcohol 1H NMR, 13C NMR [45]
23 Cyanidin
3-O-rhamnosylglucoside
Inflorescences
95% alcohol 1H NMR, 13C NMR [45]
24 (+)-Catechin
Inflorescences
95% alcohol TLC, 1H NMR, 13C NMR [46]
25 Isoquercetin
Inflorescences
95% alcohol 1H NMR, 13C NMR [46]
26 Rutin
Inflorescences
95% alcohol 1H NMR, 13C NMR [46]
27 (−)-Epicatechin-3-O-gallate
Inflorescences
95% alcohol TLC, 1H NMR, 13C NMR [46]
UV: Ultraviolet spectrophotometry; IR: Infrared spectroscopy; ESI-MS: Electrospray ionization mass spectrometry;
13
C NMR: Carbon-13 nuclear magnetic resonance spectrometry;
1
H NMR: Hydrogen-1 nuclear magnetic resonance
spectrometry; HPLC: High-pressure liquid chromatography; TLC: Thin layer chromatography.
Molecules 2024,29, 941 10 of 33
5.2. Terpenoids
Terpenoids, composed of isoprene polymers as the basic skeleton, exhibit diverse
structures and functions in different plants. These compounds influence plant odor and
flavor. Therefore, terpenoids have significant application value in fields such as natural
drugs and spices.
The studies have demonstrated that terpenoids are the secondary metabolites of CSR.
Twelve terpenoids were isolated, which were as follows. Malonyl ursolic acid hemiester
(28), ursolic acid (29), acetyl ursolic acid (30), oleanolic acid (31), betulinic acid (32) [
16
],
and malonyl oleanolic acid hemiester (33) [
10
] were isolated from dichloromethane extract
of CSR stem. The glutaryl ursolic acid hemiester (34), oxalyl ursolic acid hemiester (35),
succinyl ursolic acid hemiester (36), and ursolic acid methyl ester (37) were isolated from
the ethyl acetate extract of CSR stem [
47
]. Additionally, a diterpenoid compound 3
β
,
28-dihydroxyoleana-11,13(18)-diene (38)
was isolated from the ethyl acetate fraction of a
95% ethanol extract obtained from the CSR stem [
48
]. The isolation of maslinic acid (39)
was achieved from the aqueous extract of CSR [49].
The terpenoids discovered in CSR malonyl ursolic acid hemiester, ursolic acid, acetyl
ursolic acid, and malonyl oleanolic acid hemiester are commonly occurring triterpenes that
can also be found in other plant species (Table 3).
Table 3. Terpenoids isolated from Cynomorium songaricum Rupr.
No. Compound Parts of Plant Extract Solvent Identification References
28 Malonyl ursolic acid hemiester Stems dichloromethane 1H NMR, 13C NMR [16]
29 Ursolic acid Stems dichloromethane 1H NMR, 13C NMR [16]
30 Acetyl ursolic acid Stems dichloromethane 1H NMR, 13C NMR [16]
31 Oleanolic acid Stems dichloromethane IR, 1H NMR, 13C NMR, HR-MS [16]
32 Betulinic acid Stems dichloromethane 1H NMR, 13C NMR [16]
33 Malonyl oleanolic acid hemiester Stems dichloromethane HPLC, 1H NMR, 13C NMR [10]
34 Glutaryl ursolic acid hemiester Stems ethyl acetate HPLC-MS [47]
35 Oxalyl ursolic acid hemiester Stems ethyl acetate HPLC-MS [47]
36 Succinyl ursolic acid hemiester Stems ethyl acetate HPLC-MS [47]
37 Ursolic acid methyl ester Stems ethyl acetate HPLC-MS [47]
38 3β,28-Dihydroxyoleana-
11,13(18)-diene Stems
ethyl acetate part
1H NMR, 13C NMR [48]
39 Maslinic acid Stems aqueous ESI-MS, 1H NMR, 13C NMR [49]
IR: Infrared spectroscopy;
13
C NMR: Carbon-13 nuclear magnetic resonance spectrometry;
1
H NMR: Hydrogen-1
nuclear magnetic resonance spectrometry; HR-MS: High-resolution mass spectrometry; ESI-MS: Electrospray
ionization mass spectrometry; HPLC: High-pressure liquid chromatography; HPLC-MS: High-performance liquid
chromatography-mass spectrometry.
5.3. Steroids
The tetracyclic structure of cycloalkyl polyhydrophenanthrene is the parent nucleus of
this class of compounds known as steroids. There are several substances found in fauna
and flora, including cholesterol, steroid hormones (such as estrogen, androgen, and adrenal
corticosteroids), and sterols. These substances play a crucial role in physiological functions
with a wide range of biological functions.
Ten steroid compounds were isolated from CSR was achieved. The compounds 5
α
-
Stigmast-9(11)-en-3
β
-ol (40) and 5
α
-Stigmast-9(11)-en-3
β
-ol tetracosatrienoic acid ester
(41) were isolated from ethyl acetate extract of stems of CSR [
12
]. Daucosterol (42) and
β-sitosterol (43)
were isolated from the ethyl acetate fraction of a 95% ethanol extract
obtained stem of CSR [
13
]. The
β
-sitosteryl oleate (44),
β
-sitosteryl glucoside (45), and
β-sitosteryl
glucoside 6
′
-O-aliphatates (46) were isolated from the dichloromethane extract
of CSR stem [
16
]. Furthermore,
β
-sitosterol palmaitate (47) was isolated from the chloroform
extract [
50
]. The identification and analysis of campesterol (48) and
γ
-sitosterol (49) were
conducted using Gas chromatography–mass spectrometry (GC-MS) in addition to other
techniques [51] (Table 4).
Molecules 2024,29, 941 11 of 33
Table 4. Steroids isolated from Cynomorium songaricum Rupr.
No. Compound Parts of Plant Extract Solvent Identification References
40 5α-Stigmast-9(11)-en-3β-ol Stems ethyl acetate HR-MS, 1H NMR, 13C NMR [12]
41 5α-Stigmast-9(11)-en-3β-ol
tetracosatrienoic acid ester Stems ethyl acetate HR-MS, 1H NMR, 13C NMR [12]
42 Daucosterol Stems
ethyl acetate part
TLC [13]
43 β-Sitosterol Stems
ethyl acetate part
TLC [13]
44 β-Sitosteryl oleate Stems dichloromethane HPLC, 1H NMR, 13C NMR [16]
45 β-Sitosteryl glucoside Stems dichloromethane HPLC, 1H NMR, 13 C NMR [16]
46 β-Sitosteryl glucoside
6′-O-aliphatates Stems dichloromethane HPLC, 1H NMR, 13C NMR [16]
47 β-Sitosterol palmaitate Stems chloroform HPLC, 1H NMR, 13C NMR [50]
48 Campesterol Stems petroleum ether GC-MS [51]
49 γ-Sitosterol Stems petroleum ether GC-MS [51]
HR-MS: High-resolution mass spectrometry; HPLC: High-pressure liquid chromatography; TLC: Thin layer
chromatography;
13
C NMR: Carbon-13 nuclear magnetic resonance spectrometry;
1
H NMR: Hydrogen-1 nuclear
magnetic resonance spectrometry; GC-MS: Gas chromatography–mass spectrometry.
5.4. Saccharides and Glycosides
Saccharides are one kind of important bioactive compounds in CSR, which exhibit
diverse biological and pharmacological activities. These two polysaccharides consist of
galactose, glucose, arabinose, rhamnose, mannose, ribose, and uronic acid. Among these
components, the latter two ingredients account for 10.7% and 10.5%, respectively [
52
]. By
report, a water-soluble heteropolysaccharide called CSPA, which is a heteropolysaccharide
composed of arabinose (Ara), glucose (Glu), and galactose (Gal), was isolated from CSR. It
has a molecular weight of 1.394
×
10
5
Da. The chemical structure consisted of the following
units: “
→
3)-
α
-araf-(1
→
3)-
α
-d-glcp-(1
→
4)-
α
-d-GalpA6Me-(1
→
” [
53
]. The polysaccharide
extracted from CSR was fractionated into three components, namely CSG-F1, CSG-F2, and
CSG-F3. CSG-F1 (yield of 21%) exhibited an average molecular weight of approximately
2.4 ×105Da
and primarily consisted of galactose, glucose, arabinose, and rhamnose. Simi-
larly, the purified CSG-F2 (yield of 14%) displayed an average molecular weight of around
1.3
×
10
5
Da and contained galactose, glucose, arabinose, rhamnose, and ribose as its main
constituents. Lastly, the purified CSG-F3 (yield of 37%) had an estimated average molecular
weight of about 1.9
×
10
5
Da and glucose, arabinose, rhamnose, ribose, and mannose [
54
].
The isolation of thirteen sugars and glycosides from CSR was achieved. Glucose (50)
was isolated from the chloroform extract of CSR stem [
9
]. Zingerone 4-O-
β
-D-glucopyranosid
(51) [
10
] was isolated from the dichloromethane extract of CSR stem. Three fructosides were
isolated from the ethyl acetate extract. The structures of n-butyl-
β
-D-fructofuranoside (52) [
55
],
n-butyl-
α
-D-fructofuranoside (53) [
11
], and n-butyl-
β
-D-fructopyranoside (54) [
56
] were deter-
mined using spectroscopic methods. The compound piceid (55) [
16
] was obtained from the
ethyl acetate fraction of the methanol extract, while coniferin (56) and isoconiferin (57) [
16
]
were isolated from the n-butanol fraction. The isolation of adenosine (58) [
16
] was achieved
from the n-butanol fraction of the CSR methanol extract. The compounds (
−
)-isolariciresinol
4-O-
β
-D-glucopyranoside (59) and (7S,8R)-dehydrodiconiferyl alcohol 9
′
-
β
-glucopyranoside
(60) were isolated from the aqueous extract [
42
]. The compound nicoloside (61) [
42
] was
isolated from the aqueous fraction of the methanol extract obtained from CSR. Furthermore,
songaricumone A (62) was isolated from the ethyl acetate fraction of 95% ethanol extract
obtained from fresh stems of CSR and identified through NMR analysis [4] (Table 5).
Table 5. Saccharides and glycosides isolated from Cynomorium songaricum Rupr.
No. Compound
Parts of Plant
Extract Solvent Identification References
50 Glucose Stems chloroform TLC, GC-MS [9]
51 Zingerone
4-O-β-D-glucopyranoside Stems dichloromethane FAB-MS, 1H NMR, 13C NMR,
HMQC, HMBC [10]
Molecules 2024,29, 941 12 of 33
Table 5. Cont.
No. Compound
Parts of Plant
Extract Solvent Identification References
52 n-Butyl-β-D-fructofuranoside Stems ethyl acetate 1H NMR, 13C NMR [55]
53 n-Butyl-α-D-fructofuranoside Stems ethyl acetate 1H NMR, 13C NMR [11]
54 n-Butyl-β-D-
fructopyranoside Stems ethyl acetate 1H NMR, 13 C NMR [56]
55 Piceid Stems
ethyl acetate part
1H NMR, 13C NMR [16]
56 Coniferin Stems N-butanol part 1H NMR, 13C NMR [16]
57 Isoconiferin Stems N-butanol part 1H NMR, 13C NMR [16]
58 Adenosine Stems N-butanol part HPLC, 1H NMR, 13C NMR [16]
59 (−)-Isolariciresinol
4-O-β-D-glucopyranoside Stems aqueous
FAB-MS, CD,
1
H NMR,
13
C NMR
[42]
60 (7S,8R)-Dehydrodiconiferyl
alcohol 9′-β-glucopyranoside Stems aqueous FAB-MS, HPLC, 1H NMR, 13C
NMR, CD, 1H–1HCOSY [42]
61 Nicoloside Stems aqueous 1H NMR, 13C NMR [42]
62 Songaricumone A Fresh stems
ethyl acetate part
HR-MS, 1H-NMR, 1H–1HCOSY,
HMBC, UV, TLC, CD [4]
UV: Ultraviolet spectrophotometry; TLC: Thin layer chromatography; GC-MS: Gas chromatography–mass spec-
trometry; FAB-MS: Fast atom bombardment mass spectrometry; HMQC: Heteronuclear multiple quantum
coherence; HMBC: Heteronuclear multiple bond connectivity; HPLC: High-pressure liquid chromatography;
CD: Circular dichroism;
13
C NMR: Carbon-13 nuclear magnetic resonance spectrometry;
1
H NMR: Hydrogen-1
nuclear magnetic resonance spectrometry; 1H–1HCOSY: Homonuclear Correlation Spectroscopy.
5.5. Organic Acids and Organic Acid Ester
Organic acids and esters can serve as carriers for drug delivery systems, improving
the physical stability and solubility of drugs, regulating lipid metabolism, participating,
and regulating various physiological processes as signaling molecules, and having anti-
inflammatory and antibacterial effects.
One of the important active ingredients of CSR is an acidic organic compound called
organic acid. At present, 17 distinct types of organic acids and organic acid ester have been suc-
cessfully isolated from CSR. Protocatechuic acid (63), gallic acid (64),
n-butyric acid (65) [13]
,
and 4-methoxycinnamic acid (66) [
48
] were isolated from the ethyl acetate fraction of a 95%
ethanol extract obtained from stems of CSR. The compounds p-hydroxybenzoic acid (67) [
42
],
methyl protocatechuicate (68) [
42
] and p-hydroxybenzoic acid (69) [
16
], were isolated from
the ethyl acetate fraction of the methanol extract. The compounds 3,4-dihydroxybenzoic acid
ethyl ester (70) [
57
], 4-hydroxyphenethyl
2-(4-hydroxyphenyl)
acetate (71) [
48
], and stearic
acid
α
-monoglyceride (72) [
13
] were isolated from the ethyl acetate fraction of a 95% ethanol
extract obtained from stems of CSR. The water parts are separated by succinic acid (73) [
43
].
The compounds ferulic acid (74) [
58
] were isolated from a 70% ethanol extract of stems of
CSR. Additionally, gentisic acid (75), palmitic acid (76), and 3,4-dihydroxyphenethyl acetate
(77) were obtained from a water extract [
49
]. The vanillic acid (78) [
44
] was extracted from an
aqueous solution of 95% ethanol extract from whole grass, while the capilliplactone (79) [59]
was isolated from the ethyl acetate fraction. The structure was determined using spectroscopic
techniques (Table 6).
Table 6. Organic acids and organic acid ester isolated from Cynomorium songaricum Rupr.
No. Compound
Parts of Plant
Extract Solvent Identification References
63 Protocatechuic acid Stems ethyl acetate part 1H NMR, 13 C NMR [13]
64 Gallic acid Stems ethyl acetate part 1H NMR, 13 C NMR [13]
65 n-Butyric acid Stems ethyl acetate part 1H NMR, 13C NMR [13]
66 4-Methoxycinnamic acid Stems ethyl acetate part 1H NMR, 13C NMR [48]
67 p-Hydroxybenzoic acid Stems ethyl acetate part 1H NMR, 13C NMR [42]
68 Methyl protocatechuicate Stems ethyl acetate part 1H NMR, 13C NMR [42]
69 p-Hydroxycinnamic acid Stems ethyl acetate part 1H NMR, 13 C NMR [16]
Molecules 2024,29, 941 13 of 33
Table 6. Cont.
No. Compound
Parts of Plant
Extract Solvent Identification References
70 3,4-Dihydroxy-benzoic acid
ethyl ester Stems ethyl acetate part 1H NMR, 13C NMR [57]
71 4-Hydroxyphenethyl
2-(4-hydroxyphenyl) acetate Stems ethyl acetate part 1H NMR, 13 C NMR,
HMBC, HMQC [48]
72 Stearic acid α-monoglyceride Stems ethyl acetate part ESI-MS, 1H NMR, 13C NMR [13]
73 Succinic acid Stems aqueous part IR, 1H-NMR [43]
74 Ferulic acid Stems 70% alcohol 1H NMR, 13C NMR [58]
75 Gentisic acid Stems aqueous 1H NMR, 13C NMR [49]
76 Palmitic acid Stems aqueous EI-MS, 1H NMR, 13C NMR [49]
77 3,4-Dihydroxyphenethyl acetate Stems aqueous EI-MS, 1H NMR, 13C NMR [49]
78 Vanillic acid Whole grass aqueous part 1H NMR, 13C NMR [44]
79 Capilliplactone Whole grass ethyl acetate part IR, 1H NMR, 13C NMR,
1H–1HCOSY, HMQC [59]
HMQC: Heteronuclear multiple quantum coherence; HMBC: Heteronuclear multiple bond connectivity;
ESI-MS: Electrospray
ionization mass spectrometry; IR: Infrared spectroscopy; EI-MS: Electron impact mass
spectrometry;
13
C NMR: Carbon-13 nuclear magnetic resonance spectrometry;
1
H NMR: Hydrogen-1 nuclear
magnetic resonance spectrometry; 1H–1HCOSY: Homonuclear Correlation Spectroscopy.
5.6. Phloroglucinol Adducts
A type of compound formed by three hydroxyl groups (-OH) to replace the hydrogens
at the 1,3,5 positions in benzene, is called phloroglucinol. It is a drug widely used in the
medical field. Belonging to the class of phenobarbital drugs, it has pharmacological effects
such as sedation, hypnosis, anticonvulsant, and antianxiety. It is considered an important
drug that can be used to treat various diseases and symptoms.
Six types of phloroglucinol compounds were isolated from CSR. The identification of
three phloroglucinol compounds was achieved from the 70% acetone extract of fresh stems of
CSR using LC-MS and HPLC retention time analysis. These compounds were identified as
epicatechin-(4
β
-2)-phloroglucinol (80),
epicatechin-3-O-gallate-(4β-2)-phloroglucinol (81)
and
catechin-(4
α
-2)-phloroglucinol (82) [
41
]. Two new compounds were recently isolated from a
degraded mixture of cynomoriitannin and identified as cynomoriitannin-phloroglucinol A (83)
and cynomoriitannin-phloroglucinol B (84) based on spectroscopic analyses [
41
]. Phlorogluci-
nol (85) was isolated from the stem’s aqueous extract of CSR [49] (Table 7).
Table 7. Phloroglucinol adducts isolated from Cynomorium songaricum Rupr.
No. Compound
Parts of Plant
Extract Solvent Identification References
80 Epicatechin-(4β-2)-phloroglucinol Fresh stems 70% acetone HPLC-MS, HPLC [41]
81 Epicatechin-3-O-gallate-(4β-2)-
phloroglucinol Fresh stems 70% acetone HPLC-MS, HPLC [41]
82 Catechin-(4α-2)-phloroglucinol Fresh stems 70% acetone HPLC-MS, HPLC [41]
83 Cynomoriitannin-phloroglucinol A Fresh stems 70% acetone CD, 1H NMR, 13 C NMR [41]
84 Cynomoriitannin-phloroglucinol B Fresh stems 70% acetone CD, 1H NMR, 13C NMR [41]
85 Phloroglucinol Stems aqueous 1H NMR, 13 C NMR [49]
HPLC-MS: High-performance liquid chromatography–mass spectrometry; HPLC: High-pressure liquid chro-
matography; CD: Circular dichroism;
13
C NMR: Carbon-13 nuclear magnetic resonance spectrometry;
1H NMR: Hydrogen-1 nuclear magnetic resonance spectrometry.
5.7. Other Compounds
The qualitative and quantitative analysis of amino acids revealed the presence of
20 common
amino acids in CSR, which serve as essential nutritional elements for the human
body [
60
]. Furthermore, volatile components [
61
], trace elements [
62
], and tannins [
63
] play
a significant role in the pharmacological activity of CSR.
Mannitol (86) was isolated from the aqueous extract [
49
]. Protocatechualdehyde (87),
chrysophanol (88), emodin (89), and physcion (90) were isolated from the 70% ethanol
Molecules 2024,29, 941 14 of 33
extract [
58
]. The compounds (
−
)-lariciresinol (91) and 4-methylcatechol (92) [
57
] were
isolated from the ethyl acetate fraction of a 95% ethanol extract obtained from the CSR stem.
Additionally, the following compounds were also identified: 4
β
-(L-cysteinyl)-catechin
(93), 4
β
-(L-cysteinyl)-epicatechin (94), 4
β
-(L-cysteinyl)-epicatechin 3-O-gallate (95) three
cysteine conjugates [
64
], 4
β
-(L-acetylcysteinyl)-epicatechin (96), 4
β
-(L-acetylcysteinyl)-
epicatechin
3-O-gallate
(97), 4
β
-(L-acetylcysteinyl)-epiafzelechin (98) three acetylcysteine
conjugates [
64
], and edible reagents from CSR were isolated and purified. The structures
were elucidated via a combination of NMR and mass spectrometry techniques [
64
] (Table 8).
Table 8. Other compounds isolated from Cynomorium songaricum Rupr.
No. Compound
Parts of Plant
Extract Solvent Identification References
86 Mannitol Stems aqueous 1H NMR, 13C NMR [49]
87 Protocatechualdehyde Stems 70% alcohol 1H NMR, 13C NMR [58]
88 Chrysophanol Stems 70% alcohol 1H NMR, 13 C NMR [58]
89 Emodin Stems 70% alcohol 1H NMR, 13 C NMR [58]
90 Physcion Stems 70% alcohol 1H NMR, 13C NMR [58]
91 (−)-Lariciresinol Stems
ethyl acetate part
1H NMR, 13C NMR [57]
92 4-Methylcatechol Stems
ethyl acetate part
1H NMR, 13C NMR [57]
93 4β-(L-cysteinyl)-catechin Stems 70% acetone
ESI-MS,
1
H NMR,
13
C NMR
[64]
94 4β-(L-cysteinyl)-epicatechin Stems 70% acetone
ESI-MS,
1
H NMR,
13
C NMR
[64]
95
4
β
-(L-cysteinyl)-epicatechin 3-O-gallate
Stems 70% acetone
ESI-MS,
1
H NMR,
13
C NMR
[64]
96 4β-(L-acetylcysteinyl)-epicatechin Stems 95% alcohol
ESI-MS,
1
H NMR,
13
C NMR
[64]
97 4β-(L-acetylcysteinyl)-epicatechin
3-O-gallate Stems 95% alcohol
ESI-MS,
1
H NMR,
13
C NMR
[64]
98 4β-(L-acetylcysteinyl)-epiafzelechin Stems 95% alcohol
ESI-MS,
1
H NMR,
13
C NMR
[64]
ESI-MS: Electrospray ionization mass spectrometry;
13
C NMR: Carbon-13 nuclear magnetic resonance spectrome-
try; 1H NMR: Hydrogen-1 nuclear magnetic resonance spectrometry.
6. Pharmacology
Scholars have combined traditional Chinese medicine with modern medicinal chem-
istry to explore the biological activity of chemical components in traditional Chinese
medicine. Alcohol and water extracts exhibit significant pharmacological activities, includ-
ing anti-oxidant and anti-tumor effects, among others (Figures 12 and 13).
6.1. Anti-Tumor Effects
Inducing apoptosis serves as a method for preventing and treating tumors as it plays
an essential role in tumor progression [
65
]. Cancer stem cells are inhibited from proliferating
and dying when exposed to CSR. It can be used to treat malignant tumors such as breast
cancer, leukemia, colon cancer, and others.
6.1.1. Anti-Cancer
There are four breast cancer cell lines inhibited by CSR extracts and its ethyl acetate
extraction site, including MDA-MB-231 [
15
,
66
], MCF-7 [
15
,
66
], MB468 [
15
], and 4T1 [
15
].
Furthermore, CSR extract induces Foxo3 expression in apoptosis and prevents the transition
from G1 to S phases [
15
]. It has been found that chloroform and ethyl acetate extraction
sites from the CSR ethanol extract are capable of inhibiting the proliferation of the colon
adenocarcinoma cell line Caco-2 [
7
]. In cell research for cervical cancer treatment, Cynom-
rium songaricum polysaccharides (CSP) inhibit proliferative activity in HeLa cells [
67
]. A
further study showed that both methanol extract and anthocyanin 3-O-glucoside from
CSR inhibited KBWT cell proliferation in a dose-dependent manner [
68
]. By inhibiting
telomerase reverse transcriptase (TERT) mRNA, CSP induced apoptosis in A549 cells [
69
].
Methanol extract and aqueous extract from CSR inhibited the growth of B16 cells, which are
used for studying skin cancer in humans [
15
]. Further, CSR ethyl acetate extract inhibited
both LNCaP and HepG2 cells, showing that it may have therapeutic effects on prostate
cancer and liver cancer [
66
]. Research has shown that the anticancer ingredients in CSR
Molecules 2024,29, 941 15 of 33
are concentrated in the ethyl acetate extraction site, and it may be related to activating and
enhancing autophagy processes in cells to trigger. In autophagy and apoptotic cell death,
mitochondrial-related proteins Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3)
and Bcl-2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L) play a critical
role [66].
Molecules 2024, 29, x FOR PEER REVIEW 16 of 35
Table 8. Other compounds isolated from Cynomorium songaricum Rupr.
No.
Compound
Parts of Plant
Extract Solvent
Identification
References
86
Mannitol
Stems
aqueous
1H NMR, 13C NMR
[49]
87
Protocatechualdehyde
Stems
70% alcohol
1H NMR, 13C NMR
[58]
88
Chrysophanol
Stems
70% alcohol
1H NMR, 13C NMR
[58]
89
Emodin
Stems
70% alcohol
1H NMR, 13C NMR
[58]
90
Physcion
Stems
70% alcohol
1H NMR, 13C NMR
[58]
91
(−)-Lariciresinol
Stems
ethyl acetate part
1H NMR, 13C NMR
[57]
92
4-Methylcatechol
Stems
ethyl acetate part
1H NMR, 13C NMR
[57]
93
4β-(L-cysteinyl)-
catechin
Stems
70% acetone
ESI-MS, 1H NMR, 13C NMR
[64]
94
4β-(L-cysteinyl)-
epicatechin
Stems
70% acetone
ESI-MS, 1H NMR, 13C NMR
[64]
95
4β-(L-cysteinyl)-
epicatechin 3-O-gallate
Stems
70% acetone
ESI-MS, 1H NMR, 13C NMR
[64]
96
4β-(L-acetylcysteinyl)-
epicatechin
Stems
95% alcohol
ESI-MS, 1H NMR, 13C NMR
[64]
97
4β-(L-acetylcysteinyl)-
epicatechin 3-O-gallate
Stems
95% alcohol
ESI-MS, 1H NMR, 13C NMR
[64]
98
4β-(L-acetylcysteinyl)-
epiafzelechin
Stems
95% alcohol
ESI-MS, 1H NMR, 13C NMR
[64]
ESI-MS: Electrospray ionization mass spectrometry; 13C NMR: Carbon-13 nuclear magnetic
resonance spectrometry; 1H NMR: Hydrogen-1 nuclear magnetic resonance spectrometry.
6. Pharmacology
Scholars have combined traditional Chinese medicine with modern medicinal
chemistry to explore the biological activity of chemical components in traditional Chinese
medicine. Alcohol and water extracts exhibit signicant pharmacological activities,
including anti-oxidant and anti-tumor eects, among others (Figures 12 and 13).
Figure 12. The main pharmacological action of Cynomorium songaricum Rupr.
Molecules 2024, 29, x FOR PEER REVIEW 17 of 35
Figure 12. The main pharmacological action of Cynomorium songaricum Rupr.
Figure 13. Other pharmacological action of Cynomorium songaricum Rupr.
6.1. Anti-Tumor Eects
Inducing apoptosis serves as a method for preventing and treating tumors as it plays
an essential role in tumor progression [65]. Cancer stem cells are inhibited from
proliferating and dying when exposed to CSR. It can be used to treat malignant tumors
such as breast cancer, leukemia, colon cancer, and others.
6.1.1. Anti-Cancer
There are four breast cancer cell lines inhibited by CSR extracts and its ethyl acetate
extraction site, including MDA-MB-231 [15,66], MCF-7 [15,66], MB468 [15], and 4T1 [15].
Furthermore, CSR extract induces Foxo3 expression in apoptosis and prevents the
transition from G1 to S phases [15]. It has been found that chloroform and ethyl acetate
extraction sites from the CSR ethanol extract are capable of inhibiting the proliferation of
the colon adenocarcinoma cell line Caco-2 [7]. In cell research for cervical cancer
treatment, Cynomrium songaricum polysaccharides (CSP) inhibit proliferative activity in
HeLa cells [67]. A further study showed that both methanol extract and anthocyanin 3-O-
glucoside from CSR inhibited KBWT cell proliferation in a dose-dependent manner [68].
By inhibiting telomerase reverse transcriptase (TERT) mRNA, CSP induced apoptosis in
A549 cells [69]. Methanol extract and aqueous extract from CSR inhibited the growth of
B16 cells, which are used for studying skin cancer in humans [15]. Further, CSR ethyl
acetate extract inhibited both LNCaP and HepG2 cells, showing that it may have
therapeutic eects on prostate cancer and liver cancer [66]. Research has shown that the
anticancer ingredients in CSR are concentrated in the ethyl acetate extraction site, and it
may be related to activating and enhancing autophagy processes in cells to trigger. In
autophagy and apoptotic cell death, mitochondrial-related proteins Bcl-2/adenovirus E1B
19 kDa-interacting protein 3 (BNIP3) and Bcl-2/adenovirus E1B 19 kDa protein-interacting
protein 3-like (BNIP3L) play a critical role [66].
Figure 13. Other pharmacological action of Cynomorium songaricum Rupr.
6.1.2. Leukemia
CCRF-CEM and CCRF-SB cells were inhibited by methanol extract and anthocyanin
3-O-glucoside
from CSR [
68
]. Similarly, mitochondrial pathways modulate caspase-3
Molecules 2024,29, 941 16 of 33
activity. Therefore, CSR ethanol extract causes apoptosis in leukemia cells by causing
apoptosis in HL-60 cells [70].
The above studies indicate that CSR has a certain inhibitory effect on two types of tumor
cells, cancer, and leukemia. In cancer, it inhibits the growth of cancer cells by inducing
the expression of Foxo3 and inhibiting telomerase reverse transcriptase mRNA to activate
mitochondrial-related proteins BNIP3 and BNIP3L. Regulating caspase-3 activity through the
mitochondrial pathway in leukemia induces cell apoptosis. In contrast, there is more research
data on adenocarcinoma and less research on leukemia. However, it cannot be concluded
with certainty that CSR has a better therapeutic effect on cancer than on leukemia. Therefore,
more in-depth research is still needed (Table S1, Supplementary Materials).
6.2. Anti-Oxidation Function
Different parts of CSR have different antioxidant activities when extracted from
methanol. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radicals are best scavenged in the central
part, hydroxyl radicals are best inhibited in the lower part, and superoxide anions are
highly resisted in the upper part [
71
]. Multiple solvent extracts of CSR exhibit antioxidant
activity. A methanol extract of the CSR and an ethyl acetate extraction site strongly inhibit
superoxide anions [
72
,
73
]. DPPH radicals, 2,2
′
-Azino-bis (3-ethylbenzothiazoline-6-sulfonic
acid) diammonium salt (ABTS) radicals, and hydroxyl radicals are also scavenged by the
aqueous extract and ethyl acetate extraction site [
4
]. Additionally, the aqueous extract was
able to scavenge DPPH free radicals and inhibit superoxide anion formation [74].
Different extracts exhibit significantly different antioxidant and radical scavenging
properties. CSR aqueous extract scavenges DPPH free radicals and nitrates more effec-
tively than ethanol extract. In contrast, ethanol extract inhibits xanthine oxidase (XO) and
superoxide dismutase (SOD) more effectively than aqueous extract [75].
To examine the categories of substances with superior antioxidant effects, compounds
of the same type extracted from CSR were compared to their antioxidant activity. This
was performed to clarify the strong antioxidant activity of CSR extract. Within a certain
concentration range, CSP exhibits effective scavenging ability against superoxide anion
radicals, DPPH radicals, and hydroxyl radicals [
6
]. CSR flavonoids also scavenge DPPH
and hydroxyl radicals [76].
Crude polyphenols exhibited significantly higher antioxidant activity than crude
polysaccharides when measured against DPPH radicals, ABTS free radicals, and crude
polysaccharides in CSR [
77
]. According to another study, microwave-extracted procyani-
dins exhibited superior scavenging activity against DPPH and hydroxyl free radicals [39].
The main antioxidant component in the CSR ethyl acetate extraction site is catechin,
which was isolated from protocatechuic acid, gallic acid, and catechins [
78
]. The aqueous
extract of CSR was separated into catechin, epicatechin, and olive saponin to determine the
DPPH free radical scavenging capacity [79].
In vivo
experiments were used to verify the CSR extract’s significant antioxidant
activity. CSR extracts (0.22 g/kg, 0.44 g/kg, 0.88 g/kg) can enhance the serum DPPH free
radical scavenging ability of KM mice, and reduce oxidative damage caused by free radicals
and lipid peroxides [80].
Some
in vivo
and
in vitro
experiments have shown that the antioxidant components
in CSR exert antioxidant effects by clearing free radicals, as well as inhibiting XO and SOD,
etc. The antioxidant activity of CSR is one of its main functions, which can slow down the
oxidative state of the body and fight against diseases (Table S2, Supplementary Materials).
6.3. Anti-Aging Effects
Several studies have demonstrated the anti-aging effects of CSR through a variety
of mechanisms. According to reports, adding CSR to the diet can extend the average
and maximum lifespans of adult female flies. Ethanol extract of CSR suppresses age-
related learning disabilities in elderly flies by reducing hydrogen peroxide levels and
increasing antioxidants, extending their lifespan, improving mating readiness, increasing
Molecules 2024,29, 941 17 of 33
fertility, and inhibiting age-related learning disabilities [
81
]. A transcriptome sequencing
study found that CSR extract impacted wild-type Caenorhabditis elegans aging. The
lifespan of Caenorhabditis elegans was extended and motor abilities were enhanced by
ethyl acetate extract (0.4 mg/mL). Multiple pathways and genes collaborate to produce
the effects of the ethyl acetate extract [
82
]. Various research results have shown that
extracts, CSP, and preparations from CSR can delay aging by inhibiting telomere length
shortening [
83
], enhancing telomerase activity [
84
], improving immune function [
85
–
87
],
inhibiting neuronal apoptosis [
17
,
84
], improving hippocampal CA1 neurons [
88
], enhancing
antioxidant capacity [17,40,85,87,89].
The aqueous extract of CSR can also improve the energy metabolism of liver mitochon-
dria in aging model KM mice. It can also alleviate free radical damage to mitochondrial
membrane structure and function and play a role in delaying aging [90].
These findings not only reveal the potential of the polysaccharide and extract in combat-
ing aging but also lay the groundwork for future clinical research. It would be beneficial to
further investigate the chemical composition of CSR and the mechanism underlying anti-aging
as well as their safety and effectiveness to offer novel insights and possibilities for delaying
the aging process in the future (Table S3, Supplementary Materials).
6.4. Anti-Fatigue and Anti-Hypoxia Activities
The aqueous extract and ethanol extract of CSR are responsible for its anti-fatigue
properties. By lowering the lactate index [
91
], inhibiting amino acid protein breakdown,
and increasing glycogen reserves [
92
–
94
], they can improve energy metabolism. It also
possesses the ability to increase the level of cyclic adenosine monophosphate (cAMP),
reduce cyclic adenosine monophosphate/cyclic guanosine monophosphate (cAMP/cGMP)
ratio [
18
], improve free radical metabolism [
94
,
95
]. In addition, CSR flavonoids (CSF)
reduce MAO activity and reactive oxygen species (ROS) levels by improving free radical
metabolism [96–98].
Oxygen deficiency can cause abnormal tissue metabolism, function, and morphology.
The main cause of death is hypoxia of the brain and heart. CSR aqueous extract has positive
atmospheric pressure anti-hypoxia and anti-acute cerebral ischemia and hypoxia effects [
99
],
which increases blood hemoglobin content and enhances oxygen-carrying function [
100
].
As well as reducing brain edema, it increases myocardial protein content [101].
CSR exhibits remarkable anti-fatigue and anti-hypoxia properties. Research on anti-fatigue
effects focuses on its active ingredients, such as water extract, ethanol extract, and flavonoids.
Currently, hypoxic resistance studies are primarily focused on CSR water extract. Developing
highly potent and pharmaceutically viable compounds from CSR for anti-fatigue and anti-
hypoxia purposes will require further investigation (Table S4, Supplementary Materials).
6.5. Effects on Nervous System
Ethyl acetate extract and methanol extract are both effective against A
β25–35
, hypox-
anthine/xanthine oxidase (HPX/XO) [
102
], Xanthine dehydrogenase/xanthine oxidase
(XDH/XO) [
72
] induced SK-N-SH cells have protective effects. Among them, ethyl ac-
etate extract is more effective against Amyloid
β
-Protein 25–35 (A
β25–35
) and has an anti-
Starosporin-induced injury effect [
73
]. CSP and ethyl acetate extraction sites of CSR can
protect PC12 cells against damage by H
2
O
2
[
103
] and A
β25–35
[
104
]. Ethyl acetate extract
has cytotoxicity to Neuro2A cells (EC
50
= 116 mg/L) and increases the expression of synap-
tophysin through the mitogen-activated protein kinases (MAPK) pathway [
105
]. In another
study, the methanol extract of CSR inhibits A
β25–35
induced phosphorylation of dynamin-
related protein 1 (Drp1) at Ser637 in HT22 cells and reduced the expression of Fission 1
Protein (Fis1) in H
2
O
2
induced model for the treatment of Alzheimer’s disease (AD) [
106
].
Based on neuroprotective effects at the cellular level, scholars have further explored
them through animal models. The ethyl acetate fraction of CSR improves the behavior of
C57BL/6 male mice by reducing mitochondrial dynamics imbalance. It also downregulated
the expression of the Drp1 protein and upregulated the expression of Optic Atrophy 1
Molecules 2024,29, 941 18 of 33
(OPA1) and Mito Fusin 1 (MFN1) proteins [
107
]. It also improves the spatial memory and
learning ability of AD model mice by regulating fecal microbiota disorder [
108
]. In the
ovariectomized Sprague–Dawley (SD) rat model, it increased the expression of Growth-
Associated Protein 43 (GAP-43) protein in the hippocampus [
109
], regulated the MAPK
pathway, increased the expression of phosphorylation-cAMP response element-binding
protein (p-CREB), and decreased the expression of p38, thereby promoting the survival and
repair of hippocampal neurons.
Other studies have shown that CSR ethyl acetate extract increases the expression
levels of synaptic plasticity-related proteins Syn and postsynaptic density protein-95
(PSD-95) [110]
while upregulating the protein expression levels of phosphor-extracellular
regulated protein kinases 1/2 (P-Erk1/2) and P-CREB in the MAPK/ERK1/2 signaling
pathway [
111
]. It increases the effect of Long-term Potential (LTP) in Morris water maze
and neuroelectrophysiology, further improving cognitive dysfunction in chronic stress
Institute of Cancer Research (ICR) mice after ovariectomy [112].
The ethanol extract of CSR increased cAMP response element-binding protein /Brain-
Derived Neurotrophic Factor (CREB/BDNF) expression in ovariectomized SD rats by
inhibiting the p38MAPK/ERK pathway [
113
]. It also reduced serum corticosterone levels,
increased the expression of BDNF mRNA in this region, promoted the proliferation of
mouse dentate gyrus cells and differentiation of neuroblasts, enhanced the potential for
hippocampal plasticity in male C57BL/6J mice [
114
], and thus achieved neuroprotective
effects on the nerves.
The aqueous extract of CSR has a significant improvement effect on the learning and
memory of scopolamine-induced KM male mice. Its mechanism may be related to reducing
oxidative stress in brain tissue [115].
In Wistar male rats, through upregulating the Brain-Derived Neurotrophic Factor/Tyrosine
Kinase receptor B (BDNF/TrkB) signaling pathway, enhancing cognitive function, increasing
acetylcholine (ACH) content in the central cholinergic system, inhibiting cell apoptosis, and
enhancing synaptic plasticity, CSF improves the AD model induced by A
β1–42
[
116
]. In addition,
CSF inhibits oxidative stress and inflammatory reactions. It can also downregulate the expres-
sion of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, ROS, and NOD-like
receptor thermal protein domain associated protein 3 (NLRP3) in the hippocampus, exerting
neuroprotective effects [117].
The main component of CSR, ursolic acid, at a concentration of 5–15
µ
M, can effectively
protect SD rat hippocampal neurons from damage induced by kainic acid by regulating
α
-amino-3-hydroxy-5-methy1-4-isoxazole propionic acid (AMPA) receptors, protecting
mitochondria, and reducing free radical generation [118,119].
In summary, the neuroprotective active ingredients are mainly concentrated in the
methanol, ethanol, and ethyl acetate extracts of CSR. However, the main components that
play a key neuroprotective role are not yet clear because of the complex components in
CSR extract. Therefore, future studies should explore compounds that play a major role in
protecting the nervous system (Table S5, Supplementary Materials).
6.6. Effects on Reproductive System
In geriatrics, benign prostatic hyperplasia (BPH) is a common genitourinary disorder
characterized by prostate gland enlargement and urinary dysfunction [
120
]. There is an
inhibitory effect of ethanol extract of CSR (2.5 mg/mL) on testosterone 5
α
-reductase [
121
].
Moreover, it interferes with estrogen/androgen signals to inhibit prostate hyperplasia
in Wistar rats [
58
] and improves the disorder of prostate epithelial cells and abnormal
proliferation of connective tissue in Wistar rats with BPH model, inhibiting Proliferating
Cell Nuclear Antigen (PCNA), Androgen Receptor (AR), and estrogen receptor
α
(Er
α
)
Protein expression while promoting estrogen receptor
β
(ER
β
) Protein expression while
promoting ER
β
Protein expression [
122
]. Meanwhile, Wistar male rat protein expression of
prostate AR, ER
α
/
β
,and 3-oxo-5-alpha-steroid 4-dehydrogenase 1/2 (SRD5A1/2) were
regulated to inhibit BPH [
123
]. Additionally, CSR aqueous extract inhibits prostate hyper-
Molecules 2024,29, 941 19 of 33
plasia, increases SOD and glutathione (GSH) activities, decreases malondialdehyde (MDA)
content, and significantly reduces prostate wet weight and prostate index by improving
testosterone propionate-induced oxidative stress levels [124].
In vitro
experiments, Luteolin, Gallic acid, Ferulic acid, Protocatechualdehyde from
CSR suppressed BPH by downregulating the expression of AR and ER
α
in BPH-1 cells and
upregulation ER
β
expression [
123
]. CSRs containing luteolin, epicatechin, and epicatechin
gallate all improve the contractility of Wistar male rats’ bladder detrusors [125].
Infertility in men is complex and multifactorial, with idiopathic infertility accounting
for approximately 30% of cases [
126
]. It has been shown that CSR improves sexual hormone
levels as a kidney tonifying traditional Chinese medicine [
113
]. Under the intervention of
CSR aqueous extract, serum testosterone and Follicle-stimulating Hormone (FSH) levels
are reduced, and interstitial cell-stimulating hormone (ICSH) levels are increased to directly
affect the spermatogenic effect of immature seminiferous tubules of Wistar rats [
127
]. It can
also promote the secretion of testosterone in SD rats and inhibit abnormal secretion of FSH
and Luteinizing hormone (LH) by regulating gonadal hormone levels [
128
]. Glial Cell Line-
derived Neurotrophic Factor (GDNF) production in testes of SD rats and undifferentiated
spermatogonia proliferation stimulates, increases testosterone levels, and improves sperm
motility [
129
]. Relieving sperm damage and serum testosterone levels are increased through
the MAPK-3-mediated GDNF signaling pathway, thereby enhancing sperm motility [
130
].
In addition, enhancing sperm production in Wistar rats and upregulating the expres-
sion pathway of GDNF in the testes to improve male fertility [
131
], enhancing sperm
production in golden hamsters, and blocking the impact of short photoperiod on reproduc-
tive function [132] by CSR aqueous extract.
In summary, active compounds from CSR that inhibit BPH mainly exist in its ethanol
extract, while the active ingredients that promote spermatogenesis are mainly concentrated
in the aqueous extract, which has been proven to have good therapeutic effects in treating
male infertility (Table S6, Supplementary Materials).
6.7. Anti-Virus
Despite a significant increase in the number of approved antiviral drugs, these existing
drugs are not always effective or well tolerated. It is becoming increasingly common
for viruses to develop drug resistance. As of now, many polysaccharides have been
approved as drugs as independent or major bioactive components [
133
]. The methyl
thiazolyl tetrazolium (MTT) method was used to detect the toxicity of CSP on MT-4 cells,
which showed that only sulfated polysaccharides (SCSP-M, SCSP-1, SCSP-2) are anti-
HIV. Due to the interaction between sulfated polysaccharides and poly L-lysine, sulfated
polysaccharides have antiviral properties [134].
In addition to the CSP, the triterpenoids contained in CSR also have antiviral activity.
Ursolic acid, half ursolic malonate, malonyl oleanolic acid hemiester [
10
], acetyl ursolic
acid, and condensed tannin extracted from CSR all have the function of inhibiting human
immunodeficiency virus (HIV) protease [
16
]. Furthermore, triterpenoids in CSR also have
inhibitory activity against hepatitis C virus (HCV) protease, with malonyl ursolic acid
hemiester having the maximum inhibitory effect [47].
The main components of CSR are polysaccharides and triterpenoids, which are po-
tentially useful for developing antiviral drugs. Additionally, it is worth noting that the
antiviral efficacy of CSR has predominantly been tested
in vitro
with limited reports on its
in vivo
effects. Consequently, the precise mechanism by which CSR is antiviral remains
unclear. Future studies should explore this aspect further to uncover the antiviral mecha-
nism of CSR and establish solid foundations for its application (Table S7, Supplementary
Materials).
6.8. Anti-Diabetic Properties
CSP as one of the pivotal active constituents in CSR, exhibits significant therapeutic
effects on several diseases. Consequently, CSR is being considered a potential candidate
Molecules 2024,29, 941 20 of 33
for the development of novel anti-diabetic drugs [
135
]. Oral administration of CSR water-
soluble polysaccharide (CSPA) significantly reduced the blood glucose level, glutamic
oxaloacetic transaminase, glutamic pyruvic transaminase, blood urea nitrogen, creatinine
activity in streptozotocin (STZ) induced diabetes model rats, effectively increased the
serum insulin level and liver glycogen content and promoted the recovery of pancreatic
islet cells in the pancreas to near normal levels [
53
]. CSP (300 mg/kg) can upregulate
the expression of protein kinase B (AKT) and endothelial nitric oxide synthase (eNOS),
and downregulate tumor necrosis factor
α
(TNF-
α
) expression [
136
]. It can also regulate
phospholipid metabolism, including phosphatidylcholine, Lys phosphatidylcholine, phos-
phatidylethanolamine, and sphingomyelin to play a role in the treatment of diabetes [
137
].
In addition to polysaccharides, the flavonoids and their amino acid derivatives con-
tained in CSR can also exert hypoglycemic effects. Flavan-3-ol derivatives prepared from
CSR and other reagents, including 3 cysteine conjugates and 3 acetylcysteine conjugates,
were found to have significant effects on
α
-glucosidase, sucrase, and maltase have in-
hibitory effects [
64
]. Furthermore, the flavane-3-ol oligomer and compound Pentamers
(pentamer) in the stem have inhibitory effects on
α
-Glucosidase has inhibitory effects [
138
].
The investigation of CSR’s anti-diabetic activity is limited to
in vitro
and
in vivo
exper-
iments. It plays an anti-diabetes role by regulating blood sugar levels, improving insulin
sensitivity, protecting islet cells, controlling the risk of complications, etc. While these studies
have demonstrated some anti-diabetic effects of CSR, further clinical trials are necessary to
confirm its efficacy and safety for human use (Table S8, Supplementary Materials).
6.9. Anti-Osteoporosis Effect
A few studies have demonstrated the favorable anti-osteoporotic effects of CSR. After
screening the methanol and water extracts of 60 natural medicinal herbs, it was found that
the methanol extract of CSR has a stimulating effect on the proliferation ability of osteoblast
UMR106 and an inhibitory activity on osteoclast formation [
139
]. CSP (100
µ
g/mL) in-
duces osteogenic differentiation in MC3T3-E1 cells by activating Phosphatidylinositide
3-kinases/AKT/glycogen synthase
kinase-3β/β-Catenin
(PI3K/AKT/GSK3
β/β-Catenin
)
pathway and upregulates mRNA, PI3K, phos-pho-phosphatidylinositide 3-kinases
(p-PI3K)
,
AKT, phospho-protein kinase B (p-AKT), GSK3
β
, phosphor-glycogen synthase kinase-3
β
(p-GSK3
β
),
β
-catenin protein expression [
140
]. Ethanol extract of CSR can promote the
differentiation of osteoblasts from MC3T3-E1 while inhibiting osteoblast apoptosis, up-
regulating the expression of Bax and caspase-3, and downregulating the expression of
B-cell lymphoma-2 (Bcl-2) [
141
]. CSR aqueous extract containing serum can promote the
proliferation and differentiation of MC3T3-E1 osteoblasts, increase alkaline phosphatase
(ALP) activity, and increase the number of calcified nodules [142].
In
in vitro
experiments, CSP was administered to ovariectomized SD rats. The results
express that CSP can increase the osteoclastogenesis inhibitory fac-tor/Receptor Activator
for Nuclear Factor-
κ
B Ligand (OPG/RANKL) ratio, inhibit osteoclast activity by activating
the OPG/Receptor Activator for Nuclear Factor-
κ
B (RANK)/RANKL signaling pathway,
regulate osteocalcin levels to reduce bone turnover rate, restore the balance between bone
formation and bone resorption, reduce bone loss, increase bone density, improve tibial
biomechanical properties, reduce bone fragility and fracture risk, and promote osteoblast
differentiation [143].
The ethanol extract of CSR can accelerate bone formation, inhibit bone resorption, and
alleviate oxidative stress. It can also increase ALP levels in ovariectomized SD rats and
reduce the levels of bone resorption-related biomarkers tartrate-resistant acid phosphatase
(TRAP), Cathepsin K, and DPD [
144
]. At the same time, it can also mediate PI3K/AKT
and Nuclear Factor-
κ
B (NF-
κ
B) through RANKL/RANK/ TNF receptor-associated factor 6
(TRAF6) pathway to play an anti-osteoporosis role [145].
To summarize, the anti-osteoporotic effect of CSR is primarily attributed to its extract
and polysaccharide constituents. By increasing bone density, slowing down the process of
osteoporosis, enhancing the resistance to fractures, reducing the risk of fractures, improving
Molecules 2024,29, 941 21 of 33
blood circulation, and increasing the nutrient supply of bones, it plays its role. However,
there are currently no mechanisms of action for specific components. Further investigations
are still required to clarify the underlying anti-osteoporosis mechanisms associated with
the active constituents of CSR (Table S9, Supplementary Materials).
6.10. Liver Protection
Among its many functions, the liver plays a crucial role in immunity, metabolism,
detoxification, and digestion. Fibrosis of the liver is an injury-repair response, which can be
partially reversed. However, persistent damage can lead to chronic inflammation, which
triggers the formation of liver fibers [146].
In order to effectively treat patients with chronic liver disease, liver fibrosis must be
halted or slowed down [
147
]. Blood levels of glutamic oxalate transaminase (GOT) and
glutamic pyruvate transaminase (GPT) increase when the liver is damaged. In liver injury
induced by Streptozocin (STZ) in Wistar rats, CSPA (200 mg/kg, 150 mg/kg) reduces levels
of GOT and GPT [
53
]. By increasing white blood cell (WBC) levels, hematocrit (HCT) levels,
red blood cells (RBCs), mean corpuscular volumes (MCVs), and red blood cell distribution
width (RDW) levels in the blood cells of SD male rats induced by carbon tetrachloride.
CSR extract regulates the transforming growth factor
β
1 (TGF-
β
1) expression [
148
] and
increases levels of WBC, HCT, RBC, MCV, and RDW in the blood cells of SD male rats
induced by carbon tetrachloride, to impact blood cell typing and alleviate symptoms of
liver fibrosis [
149
]. Furthermore, it can also reduce the liver’s exposure to the inflammatory
factors TGF-
β
1, TNF-
α
,and interleukin 1 (IL-1) stimulation, thereby reducing liver fibro-
sis [
150
]. CSR aqueous extract (3.5 g/kg) alleviates the lipid peroxidation damage caused
by free radicals attacking the liver cell membrane of male Wister rats and protects the liver
tissue from normal physiological operation [92].
The use of 60% ethanol extract from CSR has been found to reduce serum levels of
aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydro-genase
(LDH), and laminin (LN) in KM male mice induced by carbon tetrachloride. Additionally,
the extract of CSR reduced the content of Hyp and MDA in liver tissue, while increasing
SOD and GSH. By increasing the body’s antioxidant level and scavenging free radicals,
reducing collagen fiber production, and reducing extracellular matrix deposition, the
extract of CSR protects the liver [151].
HCY2 and ursolic acid isolated from the ethanol extract of CSR can enhance mitochon-
drial function and glutathione antioxidant status in liver tissue, inhibit plasma aspartate
aminotransferase (AST) and alanine aminotransferase (ALT) activities, and protect SD
female rats from carbon tetrachloride damage [
152
]. CSF enhances the activity of SOD
and Glutathione peroxidase (GSH-Px) in formaldehyde-induced T6 cells [
153
], reduces the
protein concentration and MDA content of H
2
O
2
-induced damage to T6 cells, increases the
expression level of nitric oxide synthase (NOS) protein [
154
], and has a protective effect on
oxidative damage to T6 cells.
Along with the current increasing demand for hepatoprotective drugs, CSR has demon-
strated promising potential in the field of drug development for liver protection. However,
due to the intricate physiological functions of the liver, further investigations are required
to elucidate more specific mechanisms underlying hepatoprotection. Additionally, it is also
imperative to conduct comparative analyses of CSR constituents to assess their respective
hepatoprotective abilities (Table S10, Supplementary Materials).
6.11. Other Pharmacological Effects
6.11.1. Intestinal Effects
A specific effect of CSR is to promote intestinal peristalsis, facilitate bowel movement,
and maintain intestinal moisture. CSP (14.28 mg/kg, 28.57 mg/kg, 57.14 mg/kg) coun-
teracted atropine’s inhibitory effect on intestinal peristalsis in KM mice by modulating
parasympathetic nervous system function, reducing phenol red residue, and increasing
intestinal propulsion rates [
155
]. Comparing the effects of aqueous extract with ethyl
Molecules 2024,29, 941 22 of 33
acetate, methanol, and the aqueous extraction site of CSR on intestinal defecation in KM
mice, it was observed that the aqueous extract (3.9 g/kg) showed significant activity [
43
].
As demonstrated by the aqueous extracts of CSR (0.01 g/mL, 0.015 g/mL, 0.02 g/mL), the
CSR augments smooth muscle contraction frequency while attenuating smooth muscle con-
traction amplitude in New Zealand white rabbits, resulting in mild “intestinal moistening
and purging” effects [156].
6.11.2. Mitigate Obesity
Ursolic acid (UA), an active component of CSR, HCY2 significantly reduced both
body weight gain and fat pad weight in ICR mice [
157
]. Furthermore, the expression of
mitochondrial uncoupling protein 3 in skeletal muscle can be increased by ursolic acid
through the regulation of the Adenosine phosphate-activated protein kinase/peroxisome
proliferator-activated receptor
γ
coactivator-1 (AMPK/PGC1) pathway, thereby potentially
contributing to the treatment of obesity [158].
6.11.3. Renal Protective Effects
With the aggravation of diabetes and the side effects of hypoglycemic drugs, kidney
damage is gradually caused. Serum levels of blood urea nitrogen (BUN) and creatinine
(Cr) are significantly increased, which is considered to be an important indicator of renal
dysfunction. HCY2 (0.5 mg/kg, 1.0 mg/kg) and ursolic acid (0.35 mg/kg, 0.70 mg/kg),
derived from the CSR, resulted in a reduction in BUN and Cr levels and provided protection
against gentamicin-induced nephrotoxicity in female SD rats [
152
]. CSPA (200 mg/kg,
150 mg/kg)
in vivo
significantly reduces the levels of BUN and Cr, thereby ameliorating
renal dysfunction in streptozotocin-induced Wistar rats [
53
]. The CSP concentrations
(
0.25 mg/mL
, 0.5 mg/mL, 1.0 mg/mL) indirectly attenuated H
2
O
2
-induced apoptosis of
VERO cells by suppressing caspase-3 activity
in vitro
, indicating the potential of CSR for
the prevention and treatment of kidney-related diseases [159].
In summary, CSR protects kidney function from further damage by improving renal
blood circulation, anti-fibrotic, antioxidant, and anti-inflammatory effects. For acute kidney
injury, renal protection can promote the repair and regeneration of kidney tissue, reduce
oxidative damage and inflammatory reactions, and help alleviate the degree of kidney
injury and restore kidney function. For chronic renal failure, renal protection can delay the
progression of the disease and reduce the loss of renal function.
6.11.4. Immune System Modulation
Studies have demonstrated that CSR exine levels effectively inhibit the autoimmune
antibodies and enhance humoral immune function, thereby improving overall immune
competence in the body.
The 75% alcohol extract (0.1 g/kg, 0.2 g/kg, 0.4 g/kg) and aqueous extract (0.18 g/kg,
0.36 g/kg, 0.72 g/kg) of CSR significantly augmented the thymus index and spleen index
in immunosuppressed KM mice while also enhancing phagocytic function within the im-
mune system. They promoted hemolysin antibody production and increased serum levels,
interferon-
γ
(IFN-
γ
), and TNF-
α
secretion, thereby bolstering both humoral and cellular
immunity responses; notably, aqueous extract to the ethanol extract [
14
]. The aqueous
extract of CSR part III (300 mg/kg) demonstrated a protective effect on BALB/C mice
immunosuppressed by cyclophosphamide (CTX). It enhanced the phagocytic capacity of
macrophages towards foreign bodies and resulted in an elevation in serum, effectively
improving the humoral immune function of mice [
160
]. In addition to the immunomodula-
tory effects observed with CSR aqueous extract and ethanol extract, CSP exhibits significant
immunomodulatory effects
in vitro
experiments. Specifically, CSP polysaccharide demon-
strates remarkable potential as it promotes the proliferation and enhances the phagocytic
activity of RAW264.7 macrophages at concentrations ranging from 25 to 400
µ
g/mL. More-
over, CSP also induces an increase in the secretion levels of IL-6, TNF-α, and NO [161].
Molecules 2024,29, 941 23 of 33
6.11.5. Anti-Ulcer Effect
In recent years, despite the efficacy of antiplatelet drugs such as aspirin and clopidogrel
in managing arterial circulation disorders caused by excessive platelet aggregation, it
is crucial to consider potential gastrointestinal complications like gastric bleeding and
ulceration when administering these medications.
CSR has also demonstrated positive outcomes in the restoration and optimization
of digestive functionality. The following examples are provided. The administration of
CSP (100 mg/kg, 200 mg/kg, 400 mg/kg) effectively inhibits the development of water
immersion restraint stress-induced gastric ulcers and pyloric ligation-induced gastric ulcer
index in Wister rats. It also enhances the microcirculation of the gastric mucosa and
improves its defensive capabilities, thereby exerting an anti-ulcer effect [
162
]. Additionally,
CSR can stimulate the synthesis and release of endogenous prostaglandin E2 (PGE2) and
epidermal growth factor (EGF), enhance mucosal blood defense and repair functions
of gastric mucosa, suppress the inflammatory mediator platelet-activating factor (PAF),
mitigate its damage to mucosa, and restore the balance and defense factors for achieving
an anti-gastric ulcer effect [163].
6.11.6. Anti-Depressant Effect
The therapeutic potential of CSF has garnered significant attention in research studies.
The administration of CSF at doses of 0.2 g/kg, 0.1 g/kg, and 0.05 g/kg has mitigated
perimenopausal depression in female SD rats by modulating the hypothalamic-pituitary-
gonadal axis through an increase in E2 levels [
164
]. Not singly but in pairs, CSF (400 mg/kg,
200 mg/kg, 100 mg/kg) also effectively demonstrates significant therapeutic efficacy in
perimenopausal depression KM female mice, ameliorating the pathological alterations in
the uterus, thymus, spleen, and hypothalamus [165].
6.11.7. Anti-Epileptic
The maximum electroconvulsive seizure (MES) model is widely regarded as a robust
experimental model for grand mal epilepsy. The clinical efficacy of drugs with potent
anti-MES effects extends to grand mal seizures. Based on this, CSR aqueous extract (1
g/mL), which exhibits a potent anti-MES effect in KM mice, holds promising potential for
the treatment of grand mal epilepsy [99].
6.11.8. Anti-Bacterial
For good measure, the polyphenolic compounds and polymeric procyanidins present
in CSR exhibit antibacterial properties. Cynomoriitannin (MIC = 64
µ
g/mL) demonstrates
higher efficacy against methicillin-resistant staphylococcus aureus (MRSA) than other
compounds separated from CSR [41] (Table S11, Supplementary Materials).
7. Toxicity
A growing awareness of food safety has led to a growing focus on CSR, which is a
homology between medicine and food. The evaluation of a new potential drug’s safety
is crucial not only in the concept of fitness and healthcare but also in its research and
development. Several studies were conducted to evaluate the safety of CSR, including the
contents of heavy metal ions detection and toxicity studies in vivo.
7.1. Heavy Metal Ions Detection
The levels of Cu, Pb, Cd, Cr, As, and Hg in CSR have been determined by microwave
digestion and high-resolution continuous light source atomic absorption spectrometry [
166
].
The results indicated that the concentrations of these metals in CSR were far below the
limitations of both the Green Industry Standard for Importing Medicinal Plants and Prepara-
tions as well as the national food safety standard named Maximum Levels of Contaminants
in Foods (GB2762–2012).
Molecules 2024,29, 941 24 of 33
7.2. Toxicity Studies In Vivo
Currently, CSR aqueous extract has been confirmed to have no obvious toxicity by
experiments on acute toxicity tests, teratogenicity tests, and subchronic toxicity tests.
In acute toxicity experiments, the oral LD
50
of CSR aqueous extract exceeded
21.5 g/kg
in all cases [
167
]. The results of another study indicated that the maximum tolerable dose
of CSR in KM mice is greater than 15 g/kg [
168
], also providing evidence of CSR aqueous
extract nonobvious toxicity.
Salmonella typhimurium reverse mutation test, bone marrow polychromatic red blood
cell micronucleus test, and sperm aberration test in KM mice were adopted to further
investigate the genetic toxicity of CSR aqueous extract. One of the studies indicated that
CSR aqueous extract (7.5 g/kg, 3.75 g/kg, and 1.875 g/kg) could not induce tested strains
(TA97, TA98, TA100, TA102) to form colonies, as well as did not cause any mutagenic
effects against the somatic cells and germ cells [
169
]. The results of the experiment are
proved by another study conducted with CSR aqueous extract (2.25, 4.50, 9.00 g/kg), with
the difference being the type of experimental strains (TA97, TA98, TA100, TA102, and
TA1535) [167].
As the third stage of food safety toxicological evaluation, a subchronic toxicity test
was conducted for a ninety-day feeding trial. No significant toxicological findings were
detected in hematological parameters or clinical and pathological examinations when feed-
ing various concentrations of CSR aqueous extract (1.04 g/kg, 2.08 g/kg, 4.16 g/kg) to SD
rats [
168
]. Three Doses of CSR aqueous extract (2.83 g/kg, 5.66 g/kg, 8.49 g/kg) were fed to
Wistar rats in the same year’s research. Fu. Et [
170
] found that the medium (5.66 g/kg) and
high (8.49 g/kg) dose groups exhibited significantly increased plasma prothrombin time
(PT), as well as testicular organ coefficient and epididymal organ coefficient. The maximum
no-observed-adverse-effect level (NOAEL) was determined to be 2.83 g/kg, while the
minimum lowest-observed-adverse-effect level (LOAEL) was identified at
5.66 g/kg
in this
subchronic transoral toxicity study.
However, according to clinical reports, a patient was diagnosed with acute renal
function injury after taking a single Chinese medicine CSR 100–150 g aqueous extract for
about 0.5 h, experiencing nausea and vomiting 4–6 times, non-jet like, with all vomit being
gastric contents, without abdominal pain or diarrhea, headache, or fever. Therefore, it is
still essential to exercise caution and avoid an overdose of CSR [167].
Based on the current situation, most studies about the toxicity of CSR focus on its
aqueous extract, and few on other extracts and extract components. In order to build a
more comprehensive toxicity evaluation, subsequent studies are required to focus on CSR
extracts from other solvents. Furthermore, further exploration of toxic compounds in CSR
is also necessary. These will provide a more reliable scientific basis for the safe use of CSR.
8. Conclusions
In recent years, due to China’s aging population and growing demand for healthcare,
CSR has emerged as a highly valuable Chinese herbal medicine. It is currently being
investigated for its medicinal properties. A few studies have highlighted the beneficial
effects of CSR on overall health. This has led to its incorporation into various compound
preparations and health supplements, expanding its potential applications [171].
This study summarizes various studies on Cynomorium songaricum Rupr. (CSR) from
various aspects such as botany, ethnic pharmacology, phytochemistry, modern pharmacol-
ogy, and toxicology. Compared with previous reviews describing the effects of CSR, the data
on phytochemistry and pharmacology in this study are complete and more comprehensive,
which helps to provide a data reference for professionals studying CSR.
Traditional Chinese medicine CSR remains an outstanding kidney yang and tonifying
remedy. Additionally, it nourishes the essence and blood, as well as moistening the
intestines and bowel movements. Consequently, several traditional CSR prescriptions have
been included in the Chinese Pharmacopoeia as modern clinical medications. Various active
compounds such as flavonoids, terpenoids, and polysaccharides may be the molecular basis
Molecules 2024,29, 941 25 of 33
for CSR pharmacological activity. A portion of the 98 compounds isolated from CSR have
pharmacological properties, including anti-tumor, antioxidant, neuroprotective, antiviral,
and anti-diabetic properties, etc. However, most studies involving CSR mainly focus
on simple validation of its effectiveness in extract administration.
In vitro
studies rarely
involve
in vivo
mechanisms and there is a lack of modern pharmacological mechanism
research on traditional Chinese medicine compound formulations.
Looking back at the entire article, there are also some shortcomings in this study.
The literature collection work is up to June 2023. Afterwards, more recently published
CSR-related studies may not be included. Although CSR has become a well-known health
medication in China, its popularity internationally is still insufficient. This may be related
to its limited distribution in other countries. Therefore, it is inevitable that foreign research
cited is relatively scarce. We hope that this study can attract more people to be interested
in and involved in the study of CSR. Furthermore, we look forward to the future where
traditional Chinese medicine of this kind will be included in foreign pharmacopoeias.
Furthermore, in phytochemistry, there is a lack of research on the pharmacological activities
of some compounds isolated from CSR, so their IC50 values were not included in this study.
In a nutshell, the future direction of CSR should focus on further research into the
pharmacology and toxicity of compounds. Further exploration of the pharmacological
mechanisms underlying CSR needs to be conducted to address the current lack of research
data, as well as the development of functional health products.
Supplementary Materials: The following supporting information can be downloaded at: https:
//www.mdpi.com/article/10.3390/molecules29050941/s1. Table S1. Cynomorium songaricum anti-
tumor effects. Table S2. Cynomorium songaricum anti-oxidation function. Table S3. Cynomorium
songaricum anti-aging effects. Table S4. Cynomorium songaricum anti-fatigue and anti-hypoxia activi-
ties. Table S5. Cynomorium songaricum effects on nervous system. Table S6. Cynomorium songaricum
effects on reproductive system. Table S7. Cynomorium songaricum anti-virus. Table S8. Cynomo-
rium songaricum anti-diabetic properties. Table S9. Cynomorium songaricum anti-osteoporosis ef-
fect.
Table S10.
Cynomorium songaricum liver protection. Table S11. Cynomorium songaricum other
pharmacological effects.
Author Contributions: J.Z., C.B. and Y.Z. conceptualization and original draft preparation. X.C.,
L.H., B.M. and M.T. were responsible for collecting the available materials. All authors have read and
agreed to the published version of the manuscript.
Funding: This study was funded by the Inner Mongolia Autonomous Region Scientific Research
Project. Project ID NJZY21613.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Data are contained within the article and Supplementary Materials.
Conflicts of Interest: The authors declare no conflicts of interest.
Abbreviations
CSR Cynomorium songaricum Rupr. HPLC-MS High-performance liquid
chromatography–mass spectrometry.
VU Vulnerable TLC Thin layer chromatography
IUCN International Union for Conservation of Nature HR-MS High-resolution mass spectrometry
CITES Convention on International Trade in Endangered
Species of Wild Fauna and Flora GC-MS Gas chromatography–mass spectrometry
UV Ultraviolet spectrophotometry FAB-MS Fast atom bombardment mass spectrometry
IR Infrared spectroscopy HMQC Heteronuclear multiple quantum coherence
ESI-MS Electrospray ionization mass spectrometry HMBC Heteronuclear multiple bond connectivity
13C NMR Carbon-13 nuclear magnetic resonance spectrometry CD Circular dichroism
1H NMR Hydrogen-1 nuclear magnetic resonance
spectrometry 1H–1HCOSY Homonuclear Correlation Spectroscopy
Molecules 2024,29, 941 26 of 33
HPLC High-pressure liquid chromatography CSP CSR polysaccharides
CSF CSR flavonoids ABTS 2,2′-Azino-bis(3-ethylbenzothiazoline-
6-sulfonic acid) diammonium salt
TERT Telomerase reverse transcriptase XO Xanthine oxidase
BNIP3 Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 SOD Superoxide dismutase
BNIP3L Bcl-2/adenovirus E1B 19 kDa protein-interacting
protein 3-like KM mice Kunming mice
DPPH 2,2-Diphenyl-1-picrylhydrazyl cAMP Cyclic adenosine monophosphate
cGMP Cyclic guanosine monophosphate BDNF Brain-Derived Neurotrophic Factor
MAO monoamine oxidase TrkB Tyrosine Kinase receptor B
ROS Reactive oxygen species ACH Acetylcholine
HPX/XO Hypoxanthine/Xanthine oxidase NADPH Nicotinamide adenine dinucleotide phosphate
XDH/XO Xanthine dehydrogenase NLRP3 NOD-like receptor thermal protein domain
associated protein 3
Aβ25–35 Amyloidβ-Protein 25–35 AMPA Amino-3-hydroxy-5-methy1-4-isoxazole
propionic acid
MAPK Mitogen-activated protein kinases BPH Benign prostatic hyperplasia
Drp1 Dynamin-related protein 1 PCNA Proliferating Cell Nuclear Antigen
Fis1 Mitochondrial Fission 1 Protein AR Androgen Receptor
AD Alzheimer’s disease ErαEstrogen receptor α
OPA1 Optic Atrophy 1 ErβEstrogen receptor β
MFN1 Mitofusin 1 SRD5A 1/2 3-oxo-5-alpha-steroid 4-dehydrogenase 1/2
SD rat Sprague-Dawley rat GSH Glutathione
GAP-43 Growth-Associated Protein 43 MDA Malondialdehyde
p-CREB Phosphorylation-cAMP response element-binding
protein FSH Follicle-stimulating Hormone
PSD-95 Postsynaptic density protein-95 ICSH Interstitial cell-stimulating hormone
p-Erk Phosphor-extracellular regulated protein kinases LH Luteinizing hormone
LTP Long-term Potential GDNF Glial Cell Line-derived Neurotrophic Factor
ICR Institute of Cancer Research MTT Methyl thiazolyl tetrazolium
CREB cAMP response element-binding protein HIV Human immunodeficiency virus
HCV Hepatitis C virus p-GSK3βphosphor-glycogen synthase kinase-3β
CSPA CSR water-soluble polysaccharide Bcl-2 B-cell lymphoma-2
STZ Streptozotocin ALP Alkaline phosphatase
AKT American karate tae OPG Osteoclastogenesis inhibitory factor
eNOS endothelial nitric oxide synthase RANKL Receptor Activator for Nuclear Factor-κ
B Ligand
TNF-αTumor necrosis factor αRANK Receptor Activator for Nuclear Factor-κB
PI3K Phosphatidylinositide 3-kinases TRAP Tartrate-resistant acid phosphatase
p-PI3K phospho-phosphatidylinositide 3-kinases DPD Dihydropyrimidine dehydrogenase
p-AKT phospho-american karate tae TRAF6 TNF receptor-associated factor 6
GSK3βGlycogen synthase kinase-3βNF-κB Nuclear Factor-κB
GOT Glutamic oxalate transaminase MCV Mean corpuscular volume
GPT Glutamic pyruvate transaminase RDW Red blood cell distribution width
NOAEL No-observed-adverse-effect level TGF-β1 Transforming Growth Factor β1
WBC White blood cell IL-1 Interleukin 1
HCT Hematocrit AST Aspartate aminotransferase
RBC Red blood cell ALT Alanine aminotransferase
LDH Lactate dehydrogenase IFN-γInterferon-γ
LN Laminin CTX Cyclophosphamide
GSH-Px Glutathione peroxidase IL-6 Interleukin-6
NOS Nitric oxide synthase NO Nitric oxide
AMPK Adenosine phosphate-activated protein kinase PGE2 Prostaglandin E2
PGC1 Peroxisome proliferator-activated receptor
γcoactivator-1 EGF Epidermal growth factor
BUN Blood urea nitrogen PAF Platelet-activating factor
Cr Creatinine MES Maximum electroconvulsive seizure
MRSA Methicillin-resistant staphylococcus aureus LOAEL Lowest-observed-adverse-effect level
Molecules 2024,29, 941 27 of 33
References
1.
Han, D.; Meng, H.; Zhang, Y. Research and development and utilization of ‘Desert Ginseng‘ Cynomorium songaricum plant
resources. Chin. Wild Plant Resour. 2003,4, 42–46.
2.
Meng, J.; Ding, C.; Peng, S.; Liu, Y.; Yan, J.; Cui, P. Simultaneous determination of seven different components in Cynomorium
songaricum Rupr. by QAMS. Acta Pharm. Sin. 2023,58, 2763–2770.
3.
Ren, M.; Yang, G.; Du, L.; Liu, F.; Zhang, D.; Shen, Q.; Guan, X.; Zhang, Y. Research advances in medicinal plants of Cynomorium
songaricum.J. Biol. 2018,35, 95–98.
4.
Ma, F.-P.; Yu, L.; Yang, Y.; Li, D.-X.; Shen, C.-Y.; Zhao, X.-S.; Luo, Q. Glycoside constituents with various antioxidant effects from
fresh Cynomorium songaricum.J. Asian Nat. Prod. Res. 2021,24, 784–793. [CrossRef]
5.
Cui, Z.; Guo, Z.; Miao, J.; Wang, Z.; Li, Q.; Chai, X.; Li, M. The genus Cynomorium in China: An ethnopharmacological and
phytochemical review. J. Ethnopharmacol. 2013,147, 1–15. [CrossRef]
6.
Zhang, W.; Zheng, N.; Rui, Y.; Fan, Q.; Duan, Y. Extraction technology and
in vitro
antioxidant activity of polysaccharide from
wild of Cynomorium songaricum Rupr in Ningxia. Sci. Technol. Food Ind. 2014,35, 279–284.
7.
Tohuti, R.; Kasimu, G.; Zhang, Q.; Rehman, A. Effect of different extraction parts from the Cynomorium songarium Rupr. on Caco-2
and study of the chemical constituents. J. Xinjiang Med. Univ. 2011,34, 362–365.
8.
Ma, L.; Chen, G. The Differences of the Active Components from the Different Segments of the Succulent Stem of Cynomorium
Songaricum Rupr. Lishizhen Med. Mater. Medica Res. 2008,19, 2913–2914.
9.
Zhang, S.; Wang, Y.; Liu, L.; Yu, J.; Hu, J. Studies on Chemical Constituents of Herba Cynomorii. Chin. Pharm. J. 2007,42, 975–977.
10.
Ma, C.M.; Nakamura, N.; Hattori, M.; Cai, S. Isolation of malonyl oleanolic acid hemiester as anti-HIV protease substance from
the stems of Cynomorium songaricum.Chin. Pharm. J. 2002,37, 18–20.
11. Qu, S.H.; Wu, H.P.; Hu, S.X. Study on chemical constituents of herba Cynomorii. J. Xinjiang Med. Univ. 1991,14, 207.
12. Xu, X.; Zhang, C.; Li, C. Chemical components of Cynomorium songaricum Rupr. China J. Chin. Mater. Medica 1996,21, 676–677.
13.
Wang, X.; Li, H.; Liu, M.; Jiao, H. Chemical constituents from Cynomorium songaricum Rupr. Chin. Tradit. Pat. Med. 2015,
37, 1737–1739.
14.
Li, M.; Abulizi, R.; Yang, J.; Hu, J. Immune function of different polar extracts from Cynomorium songaricum Rupr. in mice. J.
Xinjiang Med. Univ. 2021,44, 1379–1384.
15.
Sdiri, M.; Li, X.; Du, W.W.; El-Bok, S.; Xie, Y.Z.; Ben-Attia, M.; Yang, B.B. Anticancer Activity of Cynomorium coccineum.Cancers
2018,10, 354. [CrossRef] [PubMed]
16.
Ma, C.M.; Nakamura, N.; Miyashiro, H.; Hattori, M.; Shimotohno, K. Inhibitory effects of constituents from Cynomorium
songaricum and related triterpene derivatives on HIV-1 protease. Chem. Pharm. Bull. 1999,47, 141–145. [CrossRef]
17.
Tian, X.; Wang, M.; Zhang, T.; Ou, Q.; Wei, X.; Bai, D.; Yang, J. Experimental study of Cynomorium songaricum on the expression of
NO, NOS, bcl-2 and bax gene in neurons of aging mice. Chin. J. Gerontol. 2005,25, 446–447.
18.
Jia, H.; Ge, B.; Di, D.-L. Comparative study on anti-stress effect of different extracts from Cynomorium songaricum.Chin. J. Hosp.
Pharm. 2009,29, 1977–1980.
19. Chen, J.; Lu, S. Flora of China; Science Press: Beijing, China, 2000; Volume 53, pp. 152–154.
20.
Mao, X.; Gu, Z.; Lv, X.; Qi, M.; Ge, B. Research Progress on Resource Chemistry, Pharmacological Effects and Development of
Cynomorium cynomorium.Chin. Wild Plant Resour. 2022,41, 50–54.
21.
Chen, Y.; Han, D.H.; Gao, H.; Luo, G.H.; Wang, J. Distribution and Utilization on Germplasm Resources of Host Plants of
Cynomorium songaricum.Chin. Wild Plant Resour. 2013,32, 45–47.
22.
Yuan, Y.; Yu, F.; Wang, X.; Song, C. Wild Cynomorium songaricum artificial domestication cultivation technology. Mod. Agric. 2011,
10, 054. [CrossRef]
23.
Chen, J.; Chen, X. The similarities and differences of parasitic plants Cynomorium songaricum and Cistanche breeding methods.
Bull. Biol. 2016,51, 11–13.
24.
Yang, H.; Gu, Z.; Guo, Y.; Mao, X.; Qi, M.; Ge, B. Research Progress in the Development and Application of Cynomorium songaricum
Related Preparations and Health Products. Chin. Wild Plant Resour. 2023,42, 83–88.
25.
Gao, Y. The development and utilization prospect of parasitic plant Cynomorium songaricum.J. Inn. Mong. For. Coll. 1996,
18, 45–49.
26. Li, R.; Meng, Y.; Niuniu, G. The current clinical application status of Hu Qian Wan. Clin. J. Chin. Med. 2017,9, 137–139.
27. Cai, Z.; Lv, L. Guilu Bushen Pills in the treatment of 86 cases of impotence. Clin. J. Med. Off. 2004,03, 122.
28. Wang, W. Pharmacological study of Suoyang Gujing Pills. Sci. Technol. Innov. 2014,05, 45.
29. Wu, S. Curative Effects of Nephritis in Favor of Pills Treatment of Chronic Renal Failure. Guide China Med. 2011,9, 188–189.
30.
Wu, X.; Qu, M.; Song, H.; Guan, Z.; Zhang, T. Improving Effect of Dabuyin Pill on Renal Function in DN Mice. Acta Chin. Med.
Pharmacol. 2022,50, 39–43.
31.
Pang, B.; Zhao, H. Clinical study on Ziyin Xusidan navel sticking in the treatment of male infertility. Mod. Chin. Med. 2004,02, 34.
32.
Huifeng, W. Exploration of the effect of traditional Chinese medicine combined with locking steel plate treatment on comminuted
intertrochanteric fractures in the elderly. Med. Forum 2016,20, 1961–1962.
33.
Luo, X. Clinical efficacy of Shenlu Jianbu Pill in treating ischemic necrosis of the femoral head. J. Contemp. Clin. Med. 2022,
35, 101–102.
Molecules 2024,29, 941 28 of 33
34.
Chaokai, C.; Guofen, L. 17 cases of femoral neck fracture were treated with modified Jianbu-Huqian pill combined with V-shaped
intramedullary nail. J. Emerg. Tradit. Chin. Med. 2002,05, 376.
35.
Peng, W.; Huang, J. Effect of modified lycium barbarum pill on cognitive function in patients with Alzheimer’s disease. Chin.
Med. Mod. Distance Educ. China 2013,11, 20–21.
36.
Tan, L.; Tang, M.; Gao, H.; Wang, W.; Ouyang, H.; Feng, X. A randomized double-blind positive-controlled clinical trial of
Guilingji for treating mild-to-moderate elderly cognitive impairment with kidney deficiency and marrow reduction syndrome.
Mod. J. Integr. Tradit. Chin. West. Med. 2022,31, 3392–3397.
37.
Xue, K. Clinical Study on Modified Dabuyin Pill in the Treatment of Hyperthyroidism Complicated with Type 2 Diabetes. China
Health Ind. 2012,9, 174.
38.
Zhang, Z.; Yan, X.; Zhang, Y. Clinical Study on the Treatment of Perimenopausal Syndrome of Yin Deficiency Type with Modified
Dabuyin Pill. J. Zhejiang Chin. Med. Univ. 2022,46, 1363–1366.
39.
Zhang, X.; Chen, Y.; Cui, J.; Cheng, W. Extraction of Proanthocyanidins from Cynomorium songaricum Rupr. and Its Antioxidant
and Antiglycation Activities. Nat. Prod. Res. Dev. 2018,30, 2039–2048.
40.
Guo, Y.; Zhao, J.; Luan, N.; Zhang, J.; Li, D. Antioxidant Function of Flavonoids from Cynomorium songaricum Rupr. J. Anhui Agric.
Sci. 2011,39, 19763–19764.
41.
Jin, S.; Eerdunbayaer; Doi, A.; Kuroda, T.; Zhang, G.; Hatano, T.; Chen, G. Polyphenolic constituents of Cynomorium songaricum
Rupr. and antibacterial effect of polymeric proanthocyanidin on methicillin-resistant Staphylococcus aureus. J. Agric. Food Chem.
2012,60, 7297–7305. [CrossRef]
42.
Jiang, Z.H.; Tanaka, T.; Sakamoto, M.; Jiang, T.; Kouno, I. Studies on a medicinal parasitic plant: Lignans from the stems of
Cynomorium songaricum.Chem. Pharm. Bull. 2001,49, 1036–1038. [CrossRef]
43.
Tao, J.; Tu, P.; Xu, W.; Chen, D. Studies on Chemical Constituents and Pharmacological Effects of the Stem of Cynomorium
songaricum Rupr. China J. Chin. Mater. Medica 1999,24, 36–38.
44.
Wang, X.M.; Zhang, Q.; Kasimu, R.; Wang, X.L.; Wang, X.Q. Chemical constituents in whole plant of Cynomorium songaricum.
Chin. Tradit. Herb. Drugs 2011,42, 458–460.
45.
Meng, H.-C.; Wang, S.; Li, Y.; Kuang, Y.-Y.; Ma, C.-M. Chemical constituents and pharmacologic actions of Cynomorium plants.
Chin. J. Nat. Med. 2013,11, 321–329. [CrossRef]
46.
Zhang, Q.; Kasimu, R.; Wang, X.M.; Wang, X.L.; Wang, X.Q. Studies on the chemical constituents of flavonids in the inflorescences
of Cynomorium songaricum Rupr. J. Xinjiang Med. Univ. 2007,30, 466–468.
47.
Ma, C.M.; Wei, Y.; Wang, Z.G.; Hattori, M. Triterpenes from Cynomorium songaricium--analysis of HCV protease inhibitory activity,
quantification, and content change under the influence of heating. J. Nat. Med. 2009,63, 9–14. [CrossRef]
48.
Xie, S.; Li, G.; Wang, H.; Huang, J.; Kasimu, R.; Tan, Y.; Zhang, K.; Wang, J. Study on Chemical Constituents in Cynomorium
songaricum.China Pharm. 2012,15, 911–914.
49.
Zhang, L.; Pei, D.; Huang, Y.-R.; Wei, J.-T.; Di, D.-L.; Wang, L.-X. Chemical Constituents from Cynomorium songaricum.J. Chin.
Med. Mater. 2016,39, 74–77.
50.
Ma, C.M.; Jia, S.S.; Sun, T.; Zhang, Y.W. Triterpenes and steroidal compounds from Cynomorium songaricum.Acta Pharm. 1993,
28, 152–155.
51.
Zhou, Y.B.; Ye, R.R.; Lu, X.F.; Lin, P.C.; Yang, S.B.; Yue, P.P.; Zhang, C.X.; Peng, M. GC-MS analysis of liposoluble constituents
from the stems of Cynomorium songaricum.J. Pharm. Biomed. Anal. 2009,49, 1097–1100. [CrossRef]
52.
Zhang, S.-J.; Zhang, S.-Y.; Hu, J.-P. Studies on polysaccharide of Cynomorium songaricum Rupr. China J. Chin. Mater. Medica 2001,
26, 409–411.
53.
Wang, J.; Zhang, J.; Zhao, B.; Wu, Y.; Wang, C.; Wang, Y. Structural features and hypoglycaemic effects of Cynomorium songaricum
polysaccharides on STZ-induced rats. Food Chem. 2010,120, 443–451. [CrossRef]
54.
Shi, G.; Jiang, W.; Cai, L.; Sui, G. Molecular characteristics and antitumor capacity of Glycan extracted from Cynomorium
songaricum.Int. J. Biol. Macromol. 2011,48, 788–792. [CrossRef]
55.
Zhang, C.Z.; Xu, X.Z.; Li, C.; Zhang, C.Z.; Lanzhou, M.C. Fructosides from Cynomorium songaricum.Phytochemistry 1996,
41, 975–976. [CrossRef]
56.
Shin, M.; Munekazu, I. Study on the Constituents of Useful Plant: IV. Constituents of the calyx of diosryrose kaki, and carbon-13
nuclear magnetic resonance spectrs of flavonol glycosides. Chem. Pharm. Bull. 1978,26, 1936–1941.
57.
Xie, S.; Li, G.; Zhang, K.; Wang, H.; Tan, Y.; Wang, J. Isolation and identification of chemical constituents from Cynomorium
songaricum.J. Shenyang Pharm. Univ. 2012,29, 525–528.
58.
Wang, X.; Tao, R.; Yang, J.; Miao, L.; Wang, Y.; Munyangaju, J.E.; Wichai, N.; Wang, H.; Zhu, Y.; Liu, E.; et al. Compounds from
Cynomorium songaricum with Estrogenic and Androgenic Activities Suppress the Oestrogen/Androgen-Induced BPH Process.
Evid. Based Complement. Altern. Med. 2017,2017, 6438013. [CrossRef] [PubMed]
59.
Qian, Z. Fundamental Studies of Chemical Constituents of Cynomorium songaricum RUPR; Xinjiang Medical University: Ürümqi,
China, 2007.
60.
Yao, J.; Niu, S.; Da, W.Y.; Zeng, J.Y.; Wang, L.Z. Component analysis on alcoholic beverage brewed from Cynomorium sougaricam.J.
Northwest Norm. Univ. 2001,37, 73–75.
61. Zhang, S.; Zhang, S. Studies on the Volatile Components of Herba Cynomorii. China J. Chin. Mater. Medica 1990,15, 39–41.
Molecules 2024,29, 941 29 of 33
62.
Xue, G.Q.; Liu, Q.; Ren, X.F.; Han, Y.Q. Determination of Fifteen Metal Elements in Cynomorium Songaricumi by Flame Atomic
Absorption Spectrophotometry (FAAS). Spectrosc. Spectr. Anal. 2004,24, 1461–1463.
63.
Li, Z.H.; Guo, J.X.; Cui, Z.H.; Xu, J.P.; Zhang, C.H.; Li, M.H. Phytochemical and Pharmacological Progress and Resource
Conservation Review of Cynomorium songaricum Rupr. Mod. Chin. Med. 2014,16, 861–869.
64.
Meng, H.C.; Ma, C.M. Flavan-3-ol-cysteine and acetylcysteine conjugates from edible reagents and the stems of Cynomorium
songaricum as potent antioxidants. Food Chem. 2013,141, 2691–2696. [CrossRef]
65.
Wang, S.; Gao, S.; Li, W. Study on the Extraction, Purification and Pharmacological Activity of Astragalus Polysaccharide. Spec.
Wild Econ. Anim. Plant Res. 2021,170, 1–8.
66.
Li, X.; Sdiri, M.; Peng, J.; Xie, Y.; Yang, B.B. Identification and characterization of chemical components in the bioactive fractions
of Cynomorium coccineum that possess anticancer activity. Int. J. Biol. Sci. 2020,16, 61–73. [CrossRef] [PubMed]
67.
Nishida, S.; Kikuichi, S.; Yoshioka, S.; Tsubaki, M.; Fujii, Y.; Matsuda, H.; Kubo, M.; Irimajiri, K. Induction of apoptosis in HL-60
cells treated with medicinal herbs. Am. J. Chin. Med. 2003,31, 551–562. [CrossRef] [PubMed]
68.
Yang, F.; Zhao, P.-W.; Sun, P.; Ma, L.-J.; Zhao, P.-W. Effect of Cynomorium songaricum polysaccharide on telomere of lung cancer
A549 cells. China J. Chin. Mater. Medica 2016,41, 917–921.
69.
Vascellari, S.; Zucca, P.; Perra, D.; Serra, A.; Piras, A.; Rescigno, A. Antiproliferative and antiviral activity of methanolic extracts
from Sardinian Maltese Mushroom (Cynomorium coccineum L.). Nat. Prod. Res. 2021,35, 2967–2971. [CrossRef] [PubMed]
70.
Zhang, H.; Luo, G.; Hao, J.; Yang, S.; Cui, W.; Zhang, J. Optimization of Ultrasonic-Assisted Enzymatic Extraction of Polysaccha-
rides from Cynomorium songaricum and Their Antitumor Activity. Food Sci. 2016,37, 59–64.
71.
Rina, S.; Yu, D. Research on Antioxidant Activity of the Alcohol Extract from Different Parts of Cynomorium songaricum.J. Inn.
Mong. Norm. Univ. 2016,45, 384–391.
72.
Lu, Y.; Cheng, F.; Wang, X.; Zhong, X.; Wang, Q. Antioxidant Activities of Different Extracts of Cynomorium Songaricum and Their
Protective Effects against Hypoxanthine/Xanthine Oxidase-Induced Cell Injury: A Comparative Study. J. Anhui Univ. Chin. Med.
2012,31, 57–60.
73.
Lu, Y.; Wang, Q.; Melzig, M.F.; Jenett-Siems, K. Extracts of Cynomorium songaricum protect SK-N-SH human neuroblastoma cells
against staurosporine-induced apoptosis potentially through their radical scavenging activity. Phytother. Res. 2009,23, 257–261.
[CrossRef]
74.
Wang, N.; Wei, J.; Pei, D.; Hu, Q.; Zhang, L.; Di, D.; Liu, Y. Evaluation of antioxidative activity for aqueous extract from
Cynomorium songaricum Rupr. Food Sci. Technol. 2016,41, 237–240.
75.
Seo, S.-J.; Han, M.-R.; Lee, Y.-S. Antioxidant and Xanthine Oxidase Inhibition Activities of Cynomorium songaricum Extracts. Prev.
Nutr. Food Sci. 2011,16, 307–312. [CrossRef]
76.
Zhang, X.; Zhang, F.; Luo, G. Aqueous two phase system based on C_4mim BF_4/MgSO_4 for isolation of total flavonoids from
Cynomorium Songaricum and its antioxidation activity analysis. Sci. Technol. Food Ind. 2016,37, 242–246.
77.
Duan, Y.; Ma, Y.; Chen, G. Comparation of Antioxidant Activity of Crude Polyphenol and Polysaccharide in Cynomorium
songaricum.Mod. Chin. Med. 2012,14, 43–46.
78.
Jin, S.-W.; Chen, G.-L.; Du, J.-J.-M.; Wang, L.-H.; Ren, X.; An, T.-Y. Antioxidant Properties and Principal Phenolic Compositions of
Cynomorium Songaricum Rupr. Int. J. Food Prop. 2013,17, 13–25. [CrossRef]
79.
Wang, G.; Huang, X.; Pei, D.; Duan, W.; Quan, K.; Li, X.; Di, D. DPPH-HPLC-DAD analysis combined HSCCC for screening and
identification of radical scavengers in Cynomorium songaricum Rupr. New J. Chem. 2016,40, 3885–3891. [CrossRef]
80.
Li, L.; Liu, Y.; Li, H.; Zhang, G.; Wang, X.; Di, D. Effect of Cynomorium songaricum Rupr. Extracts on Antioxidative System in Mice.
Lishizhen Med. Mater. Medica Res. 2011,22, 2093–2095.
81.
Liu, H.P.; Chang, R.F.; Wu, Y.S.; Lin, W.Y.; Tsai, F.J. The Yang-Tonifying Herbal Medicine Cynomorium songaricum Extends Lifespan
and Delays Aging in Drosophila. Evid. Based Complement. Alternat. Med. 2012,2012, 735481. [CrossRef]
82.
Hu, M.; Su, L.; Zhang, X.; Zhang, Y.; Li, L.; Lu, Y. Effects of Cynomorium extract on aging of Caenorhabditis elegans based on
transcriptome sequencing. Mod. J. Integr. Tradit. Chin. West. Med. 2022,31, 2488–2495.
83.
Ma, L.; Chen, G.; Nie, L.; Ai, M. Effect of Cynomorium songaricum polysaccharide on telomere length in blood and brain of
D-galactose-induced senescence mice. China J. Chin. Mater. Medica 2009,34, 1257–1260.
84.
Ma, L.; Chen, G.; Jia, H.; Xie, J. Anti-senescence effect of Cynomorium Songaricum polysaccharide on D-galactose-induced aging
mice. Chin. J. Hosp. Pharm. 2009,29, 1186–1189.
85.
Su, Y.; Liu, Y.-Q.; Wu, J.-J.; Zhang, Y.; Yan, C.-L.; Nie, L. Effect of Cynomorium Songaricum Rupr. chewable tablets on immunopatho-
logic changes and free radical of spleen in aging rats. Chin. J. Gerontol. 2009,29, 927–929.
86.
Su, Y.; Liu, Y.-Q.; Zhang, Y.; Yan, C.-L.; Wu, J.; Zheng, W. Effects of Cynomorium Polysaccharide Chewable Tablets on NO
Metabolism and Immune Function of D-galactose-induced Aging Rats. Tradit. Chin. Drug Res. Clin. Pharmacol. 2008,19, 458–461.
87.
Liu, Y.-Q.; Su, Y.; Wu, J.; Zhang, Y.; Wei, S.; Nie, L.; Yan, C.-L. Effects of Cynomorium songaricum extract on immune function and
free radical metabolism in aging model mice. Chin. J. Cell. Mol. Immunol. 2009,25, 55–57.
88.
Cao, J.; Han, R.; Luo, H.; Guo, J.; Zheng, L. Effects of different extracts of Cynomorium songaricum on neurons in hippocampal CA1
region of aging model mice induced by D-galactose. Lishizhen Med. Mater. Medica Res. 2017,28, 1326–1328.
89. Shang, L.; Li, J.; Shang, J. Anti-aging effect of Cynomorium songaricum polysaccharide. Chin. J. Gerontol. 2018,38, 1458–1460.
90.
Li, L.; Zhang, T. Effect of Cynomorium songaricum water extract on energy metabolism of liver mitochondria in aging model mice.
Chin. J. Gerontol. 2010,30, 1713–1714.
Molecules 2024,29, 941 30 of 33
91.
Wang, Z.; Guo, D.; Fu, Y.; Li, D. The effect of Cynomorium songaricum Rupr on endurance and antioxidative status of skeletal
muscle in trained mice. J. Northwest Norm. Univ. 2006,42, 100–102.
92.
Li, D.; Ma, W. Effects of Cynomorium songaricum decoction upon the metabolism of free radical and liver glycogen of liver tissue
of exercise rats. Mod. Prev. Med. 2013,40, 1478–1482.
93.
Guo, W.; Cao, J.; Zhou, H. Effect of Cynomorium songarium Rupr on Testosterone Content, Substance Metabolism and Anti-fatigue
Capacity of Rats After Exercise Training. Nat. Prod. Res. Dev. 2014,26, 27–32.
94.
Wan, L.; Wang, J.; Du, Y.; Sun, J.; Meng, W.; Lu, X.; Zhou, Y. Effect of ethanol extract of Cynomorium songaricum Rupr. on
anti-fatigue ability in exercise mice. J. Gansu Agric. Univ. 2019,54, 23–30.
95.
Rui, F.; Li, D. Effect of Cynomorium songaricum decoction on free radical metabolism and exercise ability of skeletal muscle in rats.
J. Chifeng Univ. 2010,26, 114–115.
96.
Yu, F.-R.; Liu, Y.; Cui, Y.-Z.; Chan, E.-Q.; Xie, M.-R.; McGuire, P.P.; Yu, F.-H. Effects of a Flavonoid Extract from Cynomorium
songaricum on the Swimming Endurance of Rats. Am. J. Chin. Med. 2010,38, 65–73. [CrossRef] [PubMed]
97.
Yu, F.; Feng, S.; Xie, M.; Lian, X. Anti-fatigue Effect of Cynomorium Songaricum Flavone on Old Rats. Chin. J. Rehabil. Theory Pract.
2008,14, 1141–1142.
98.
Yu, F.; Feng, S.; Xie, M.; Lian, X. Effects of Cynomorium songaricum flavones on the exercise tolerance and antixidation in rats.
Drugs Clin. 2009,24, 52–54.
99.
Hu, Y.; Wang, Z.; Xiao, W. Studies on Anti-anoxia and Anti-epilepsy of Cynomorium songaricum.J. Shihezi Univ. 2005,23, 302–303.
100.
Yuan, Y.; Zhao, G.; Guo, H. Effects of Cynomorium songaricum on anti-tiredness and anti-oxygen-deficiency and their influence on
the content of hemoglobin. J. Tianshui Norm. Univ. 2001,2, 49–50.
101.
Zhang, R.X.; Jia, Z.P.; Li, M.X.; Wang, J.; Yin, Q.; Luo, J.D.; Liu, H.Y. Effect of aqueous extract part III from Cynomorium songaricum
Rupr. on the protein level and pathomorphology of cerebra and cardia in hypoxia mice. Med. J. Natl. Defending Forces Northwest
China 2008,29, 241–243.
102.
Lu, Y.; Wang, Q.; Melzig, M.F.; Jenett-Siems, K. Extracts of Cynomorium songaricum protect human neuroblastoma cells from
beta-amyloid(25–35) and superoxide anion induced injury. Pharmazie 2009,64, 609–612. [PubMed]
103.
Wang, F.; Liu, Q.; Wang, W.; Li, X.; Zhang, J. A polysaccharide isolated from Cynomorium songaricum Rupr. protects PC12 cells
against H2O2-induced injury. Int. J. Biol. Macromol. 2016,87, 222–228. [CrossRef] [PubMed]
104.
Cao, J.; Han, R.; Guo, J.; Zhang, Y. The effect of Cynomorium ethyl acetate extract containing serum on the Injured PC12 Cells
Induced by Aβ25–35. Pharmacol. Clin. Chin. Mater. Medica 2018,34, 88–91.
105.
Zheng, J.; Ma, S.; Yu, X.; Hu, J.; Liu, Y.; Tian, F.; Lu, Y. Estrogen-like Effect of Ethyl Acetate Extract of Cynomorium songaricum Rupr.
Nat. Prod. Res. Dev. 2016,28, 1687–1690.
106.
Cheng, D.; Su, L.; Wang, X.; Li, X.; Li, L.; Hu, M.; Lu, Y. Extract of Cynomorium songaricum ameliorates mitochondrial ultrastructure
impairments and dysfunction in two different
in vitro
models of Alzheimer’s disease. BMC Complement. Med. Ther. 2021,21, 206.
[CrossRef]
107.
Li, X.; Cheng, D.; Li, L.; Su, L.; Lu, Y. Study on mechanism of action of Cynomorium on Alzheimer’s disease based on mitochondrial
dynamics imbalance regulation. Drug Eval. Res. 2020,43, 451–456.
108.
Li, X.; Chen, J.; Lu, Y. Regulatory Effect of Ethyl Acetate Extract of Cynomorium Songaricum on Intestinal Flora Disorder in
Alzheimer’s Disease Mice. Acta Chin. Med. 2022,37, 126–134.
109.
Tian, F.; Chang, H.; Zhou, J.; Lu, Y. Effects of ethyl acetate extract from Cynomorim songaricum Rupr. on learning and memory
function and hippocampal neurons in ovariecto-mized rat model with Alzheimer’s disease. J. Beijing Univ. Tradit. Chin. Med.
2014,37, 763–766.
110.
Ma, S.; Zheng, J.; Chang, H.; Tian, F.; Cheng, D.; Wang, X.; Lu, Y. Effect of Cynomorium songaricum Ethyl Acetate Extract on
Cognitive Dysfunction Induced by Chronic Stress. Nat. Prod. Res. Dev. 2017,29, 1302–1306.
111.
Ma, S.; Zheng, J.; Cheng, D.; Tian, F.; Chang, H.; She, G.; Lu, Y. Mechanisms of the Ethyl Acetate Extract of Cynomorium Songaricum
on the MAPK/ERK1/2 Signal Pathway for the Improvements in Cognitive Dysfunction Induced by Chronic Stress. World J.
Integr. Tradit. West. Med. 2017,12, 1381–1385.
112.
Ma, S.; Chang, H.; Zheng, J.; Cheng, D.; She, G.; Wang, X.; Lu, Y. Effects of ECS in improving long-term potentiation and chronic
stress cognitive dysfunction. China J. Tradit. Chin. Med. Pharm. 2017,32, 4608–4610.
113.
Tian, F.Z.; Chang, H.S.; Liu, J.X.; Zheng, J.; Cheng, D.; Lu, Y. Cynomorium songaricum Extract Alleviates Memory Impairment
through Increasing CREB/BDNF via Suppression of p38MAPK/ERK Pathway in Ovariectomized Rats. Evid. Based Complement.
Alternat. Med. 2019,2019, 1–10. [CrossRef]
114.
Yoo, D.Y.; Choi, J.H.; Kim, W.; Jung, H.Y.; Nam, S.M.; Kim, J.W.; Yoon, Y.S.; Yoo, K.-Y.; Won, M.-H.; Hwang, I.K. Cynomorium
songaricum extract enhances novel object recognition, cell proliferation and neuroblast differentiation in the mice via improving
hippocampal environment. BMC Complement. Altern. Med. 2014,14, 1–8. [CrossRef]
115.
Wu, M.; Liu, L.; Hu, Y.; Liu, J. Effect of Cynomorium songaricum water extract on scopolamine-induced learning and memory
impairment in mice. Xinjiang J. Tradit. Chin. Med. 2015,33, 29–31.
116.
Lyu, X.; Gu, Z.; Qi, M.; Guo, Y.; Mao, X.; Ge, B. Effects of Cynomorium songaricum Flavonoids on Learning and Memory Ability of
Alzheimer Disease Model Rats Based on BDNF/TrkB Signaling Pathway. Chin. J. Inf. Tradit. Chin. Med. 2023,30, 94–100.
117.
Lyu, X.; Gu, Z.R.; Qi, M.; Guo, Y.; Mao, X.W.; Ge, B. Effects of Cynomorium Songaricum Flavonoids on the Expressions of NADPH
Oxidase, ROS and NLRP3 in the Hippocampus of Alzheimer’s Disease Rats. Chin. J. Inf. Tradit. Chin. Med. 2023,30, 82–87.
Molecules 2024,29, 941 31 of 33
118.
Shih, Y.H.; Chein, Y.C.; Wang, J.Y.; Fu, Y.S. Ursolic acid protects hippocampal neurons against kainate-induced excitotoxicity in
rats. Neurosci. Lett. 2004,362, 136–140. [CrossRef]
119.
Tian, F.; Chang, H.; Zhou, J.; Zheng, J.; Gao, Y.; Xu, H.; Lu, Y. Effect of Ethyl Acetate Extract of Songaricum Rupr on p38 and CREB
Characteristics of Ovariectomized Rats. Chin. Pharm. J. 2015,50, 868–871.
120.
Wang, X.; Zhu, J.; Yan, H.; Shi, M.; Zheng, Q.; Wang, Y.; Zhu, Y.; Miao, L.; Gao, X. Kaempferol inhibits benign prostatic hyperplasia
by resisting the action of androgen. Eur. J. Pharmacol. 2021,907, 174251. [CrossRef]
121.
Zhang, B.; Zhang, R.W.; Yin, X.Q.; Lao, Z.Z.; Zhang, Z.; Wu, Q.G.; Yu, L.W.; Lai, X.P.; Wan, Y.H.; Li, G. Inhibitory activities of
some traditional Chinese herbs against testosterone 5alpha-reductase and effects of Cacumen platycladi on hair re-growth in
testosterone-treated mice. J. Ethnopharmacol. 2016,177, 1–9. [CrossRef]
122.
Tao, R.; Wang, F.; Miao, L.; Zhang, H.; Zhang, J.; Fan, G. Effect and its mechanism of Cynomorium songaricum Rupr inhibiting
benign prostatic hyperplasia. Chin. J. Clin. Pharmacol. 2018,34, 2847–2850.
123.
Tao, R.; Miao, L.; Yu, X.; Orgah, J.O.; Barnabas, O.; Chang, Y.; Liu, E.; Fan, G.; Gao, X. Cynomorium songaricum Rupr demonstrates
phytoestrogenic or phytoandrogenic like activities that attenuates benign prostatic hyperplasia via regulating steroid 5-alpha-
reductase. J. Ethnopharmacol. 2019,235, 65–74. [CrossRef]
124.
Fu, X.; Li, H.; Lang, D.; Zhang, X. Experimental Study on Effect of Cynomorium Deeoet in Rats with Benign Prostatic Hyperplasis.
Asia-Pac. Tradit. Med. 2013,9, 20–22.
125.
Yun, X.; Wang, Z.; Zhou, W.; Liu, E.; Tao, R.; Miao, L.; Jiao, C.; Wang, X. Relaxed effect of Cynomorium songaricum Rupr and its
active ingredients on detrusor muscle strip tension in rats. Chin. J. Clin. Pharmacol. 2017,33, 1938–1941.
126.
Zhou, S.H.; Deng, Y.F.; Weng, Z.W.; Weng, H.W.; Liu, Z.D. Traditional Chinese Medicine as a Remedy for Male Infertility: A
Review. World J. Mens. Health 2019,37, 175–185. [CrossRef]
127.
Abdel-Magied, E.M.; Abdel-Rahman, H.A.; Harraz, F.M. The effect of aqueous extracts of Cynomorium coccineum and Withania
somnifera on testicular development in immature Wistar rats. J. Ethnopharmacol. 2001,75, 1–4. [CrossRef] [PubMed]
128.
Gu, J.; Li, Z.; Qi, Y.; Cao, Y. The effect of Cynomorium on the semen quality and sex hormone level in the oligospermia rat model.
Contemp. Med. 2021,27, 14–16.
129.
Cao, Y.-J.; Li, Z.-B.; Qi, Y.-J.; Liu, Y.; Gu, J.; Hu, F.-F.; Zhang, W.-d.; Hao, L.; Hou, J.-Q.; Han, C.-H. Cynomorium songaricum
improves sperm count and motility and serum testosterone level and promotes proliferation of undifferentiated spermatogonia
in oligoasthenospermia rats. Natl. J. Androl. 2016,22, 1116–1121.
130.
Han, X.; Zhou, R.; Zheng, W.; Wang, X.; Mao, S.; Li, Z.; Hao, L.; Shi, Z.; Chen, B.; Zhang, Z.; et al. Cynomorium Songaricum
may protect against spermatogenic damage caused by cyclophosphamide in SD rats. Rev. Romana Med. Lab. 2019,27, 291–303.
[CrossRef]
131.
Yang, W.M.; Kim, H.Y.; Park, S.Y.; Kim, H.M.; Chang, M.S.; Park, S.K. Cynomorium songaricum induces spermatogenesis with glial
cell-derived neurotrophic factor (GDNF) enhancement in rat testes. J. Ethnopharmacol. 2010,128, 693–696. [CrossRef] [PubMed]
132.
Lee, J.S.; Oh, H.A.; Kwon, J.Y.; Jeong, M.H.; Lee, J.S.; Kang, D.W.; Choi, D. The Effects of Cynomorium songaricum on the
Reproductive Activity in Male Golden Hamsters. Dev. Reprod. 2013,17, 37–43. [CrossRef]
133.
He, X.; Fang, J.; Guo, Q.; Wang, M.; Li, Y.; Meng, Y.; Huang, L. Advances in antiviral polysaccharides derived from edible and
medicinal plants and mushrooms. Carbohydr. Polym. 2020,229, 115548. [CrossRef] [PubMed]
134.
Tuvaanjav, S.; Shuqin, H.; Komata, M.; Ma, C.; Kanamoto, T.; Nakashima, H.; Yoshida, T. Isolation and antiviral activity of
water-soluble Cynomorium songaricum Rupr. polysaccharides. J. Asian Nat. Prod. Res. 2016,18, 159–171. [CrossRef]
135.
Gao, Q.H.; Fu, X.; Zhang, R.; Wang, Z.; Guo, M. Neuroprotective effects of plant polysaccharides: A review of the mechanisms.
Int. J. Biol. Macromol. 2018,106, 749–754. [CrossRef]
136.
Wang, Y.; Tian, Z. The effect of aerobic exercise and Cynomorium Songaricum Polysaccharide intervention for dilatation function of
aorta in diabetes rats and involved mechanisms. J. Shaanxi Norm. Univ. 2017,45, 117–124.
137.
Shi, Z.Q.; Wang, L.Y.; Zheng, J.Y.; Xin, G.Z.; Chen, L. Lipidomics characterization of the mechanism of Cynomorium songaricum
polysaccharide on treating type 2 diabetes. J. Chromatogr. B Anal. Technol. Biomed Life Sci. 2021,1176, 122737. [CrossRef] [PubMed]
138.
Ma, C.-M.; Sato, N.; Li, X.-Y.; Nakamura, N.; Hattori, M. Flavan-3-ol contents, anti-oxidative and
α
-glucosidase inhibitory
activities of Cynomorium songaricum.Food Chem. 2010,118, 116–119. [CrossRef]
139.
Yin, J.; Tezuka, Y.; Kouda, K.; Le Tran, Q.; Miyahara, T.; Chen, Y.J.; Kadota, S. Antiosteoporotic activity of the water extract of
Dioscorea spongiosa. Biol. Pharm. Bull. 2004,27, 583–586. [CrossRef]
140.
Hu, J.; Tan, R.; Yuan, Z.; Yang, P.; Zhang, C.; Zhang, B.; Shen, Y. Cynomorium songaricum polysaccharide promotes osteogenic
differentiation of MC3T3-E1 cells by activating PI3K/Akt/GSK3
β
/
β
-catenin signaling pathway. J. Pract. Med. 2022,38, 2774–2779.
141.
Xue, W.; Dai, N.; Feng, F.; Wang, F.; Luo, L.; Huang, J.; Cheng, Z. Cynomorium songaricum extract promotes osteoblast differentiation
and inhibits lipopolysaccharide induced apoptosis of osteoblast. Biomed. Res. India 2017,28, 6567–6570.
142.
Wu, H.; Zhang, L.; Feng, X. Effects of cynomorium-containing serum on proliferation, differentiation and mineralization of
osteoblasts MC3T3-E1 cultured in vitro. Pharm. Clin. Chin. Mater. Medica 2019,10, 23–26.
143.
Shi, P.; Zhu, W.; Li, X. Cynomorium Songaricum polysaccharide improves osteoporosis in ovariectomized rats. J. Third Mil. Med.
Univ. 2015,37, 2360–2363.
Molecules 2024,29, 941 32 of 33
144.
Zhang, X.; Xu, L.; Xu, X.; Ma, X. The effect of Cynomorium songaricum Rupr. on osteoporosis in ovariectomized rats. Pharmacol.
Clin. Chin. Mater. Medica 2017,33, 101–104.
145.
Ma, X.; Liu, J.; Yang, L.; Zhang, B.; Dong, Y.; Zhao, Q. Cynomorium songaricum prevents bone resorption in ovariectomized rats
through RANKL/RANK/TRAF6 mediated suppression of PI3K/AKT and NF-kappaB pathways. Life Sci. 2018,209, 140–148.
[CrossRef] [PubMed]
146.
Borkham-Kamphorst, E.; Weiskirchen, R. The PDGF system and its antagonists in liver fibrosis. Cytokine Growth Factor Rev. 2016,
28, 53–61. [CrossRef]
147. Roskams, T. Different types of liver progenitor cells and their niches. J. Hepatol. 2006,45, 1–4. [CrossRef]
148.
Li, R.; Wang, H.; Lin, Y.; Liu, Y.; Li, H.; Huang, X.; Tang, L.; He, H.; Cui, L.; Deng, F. Effects of Cynomorium songaricum Extract on
Liver Fibrosis Model Rats and Its Mechanism Study. China Pharm. 2016,27, 3903–3906.
149.
Li, H.; Huang, X.; Guo, L.; Li, R.; Li, C.; Chen, J.; Huang, D.; Lin, Y.; Wang, H.; Liu, Y.; et al. Effect of Cynomorium on the Blood
Cell Type of Rats with Hepatic Fibrosis. J. Chengdu Med. Coll. 2017,12, 21–23.
150.
Huang, X.; Guo, L.; Li, C.; Li, R.; Li, H.; Kong, D.; Hu, K.; Lin, Y.; Deng, F.; Wang, H.; et al. Antagonism Effect of Cynomorium
on CCl
4
induced Liver Fibrosis by Inhibiting the Expression of Inflammatory Cytokines in Mice. J. Chengdu Med. Coll. 2018,
13, 249–261.
151.
Li, S.; Zhang, K.; Li, G.; Wang, H.; Chen, Y.; Peng, H.; Wang, J. The preventive effect of Cynomorium Songaricum on carbon
tetrachloride induced liver fibrosis in mice. J. Shihezi Univ. 2017,35, 368–372.
152.
Chen, J.; Wong, H.S.; Leung, H.Y.; Leong, P.K.; Chan, W.M.; Chen, N.; Ko, K.M. An ursolic acid-enriched extract of Cynomorium
songaricum protects against carbon tetrachloride hepatotoxicity and gentamicin nephrotoxicity in rats possibly through a
mitochondrial pathway: A comparison with ursolic acid. J. Funct. Foods 2014,7, 330–341. [CrossRef]
153.
Duan, X.; Qu, X.; Bai, L.; Zhao, H.; Shang, J. Protective effect of flavonoids from Cynomorium songaricum on oxidative damage
induced by formaldehyde in rat hepatic stellate cells. Asia-Pac. Tradit. Med. 2019,15, 26–28.
154.
Li, L.; Huang, M.; Guo, J.; Chen, Z. Effect of Cynomorium songaricum Flavone on Rat Liver Cells after Oxidation Injury. Biol. Chem.
Eng. 2022,8, 36–39.
155.
Li, L. Effect of Cynomorium songaricum polysaccharide on mice of gastric emptying and intestinal propulsion. J. North Pharm. 2013,
10, 43–44.
156.
Li, H. The Effect of Cynomorium songaricum on the Contractile Function of Isolated Rabbit Jejunum Smooth Muscle. J. Med. Inf.
2020,33, 82–84.
157.
Chen, J.; Wong, H.S.; Leung, H.Y.; Leong, P.K.; Chan, W.M.; Ko, K.M. An ursolic acid-enriched Cynomorium songarium extract
attenuates high fat diet-induced obesity in mice possibly through mitochondrial uncoupling. J. Funct. Foods 2014,9, 211–224.
[CrossRef]
158.
Chen, J.; Leong, P.K.; Leung, H.Y.; Chan, W.M.; Wong, H.S.; Ko, K.M. 48Biochemical mechanisms of the anti-obesity effect of a
triterpenoid-enriched extract of Cynomorium songaricum in mice with high-fat-diet-induced obesity. Phytomedicine 2020,73, 153038.
[CrossRef]
159.
Liu, Q.; Song, S.; Guo, J.; Luo, S.; Zhang, J. Protective effect of polysaccharide from Cynomorium songaricum Rupr on oxidative
damage of VERO cells induced by H2O2.Chin. Tradit. Pat. Med. 2014,36, 2023–2028.
160.
Zhang, R.-X.; Jia, Z.-P.; Li, M.-X.; Wang, J.; Yin, Q.; Luo, J.-D.; Liu, H.-Y. Study on the effect of Part III from Cynomorium songaricum
on immunosuppressive mice induced by cyclophosphamide. J. Chin. Med. Mater. 2008,31, 407–409.
161.
Abliz, R.; Li, M.; Hu, J.-P. Effect of polysaccharide from Cynomorium songaricumon on the immunoregulatory effect of RAW264.7
macrophages cell. J. Food Saf. Qual. 2018,9, 5694–5698.
162.
Yang, Y.; Ma, C.; Dong, P.; Lei, L.; Nie, Y.; Yu, X.; Ren, C.; Qian, Z. Effects of Cynomorium songaricum polysaccharide on acute
gastric ulcer in model rats. Anhui Med. Pharm. J. 2011,15, 1204–1206.
163.
Yang, Y.; Ma, C.; Lei, L.; Dong, P.; Li, J. Effects of Cynomorium Songaricum Polysaccharide on Experimental Gastric Ulcer in Rats by
Acetic Acid. Chin. Arch. Tradit. Chin. Med. 2012,30, 385–387.
164.
Miao, M.; Yan, X.; Guo, L.; Li, P. Effect of Cynomorium total flavone on depression model of perimenopausal rat. Saudi J. Biol. Sci.
2017,24, 139–148. [CrossRef] [PubMed]
165.
Wang, T.; Miao, M.; Li, Y.; Li, M.; Zhang, Y.; Tian, S. Effect of cynomorium flavonoids on morphology of perimenopausal
depression mice model. Saudi Pharm. J. 2016,24, 322–328. [CrossRef]
166.
Hu, Y.; Ding, Y.; Gao, X.; Li, X.; Shao, S. Determination of Heavy Metal Elements in Cynomorium and Leek Seeds by High
Resolution Continuum Source Atomic Absorption Spectrometry with Microwave Digestion. Anal. Test. Technol. Instrum. 2016,
22, 90–95.
167.
Nie, L.; Ma, L.; Ai, M. Modern research progress on medicinal properties and functions of Cynomorium songaricum.Chin. J.
Ethnomedicine Ethnopharmacy 2009,18, 17–18.
168.
Wei, F.; He, Q.; Wang, W.; Pei, D.; Zhang, B. Toxicity Assessment of Chinese Herbal Medicine Cynomorium songaricum Rupr. Evid.
Based Complement. Alternat. Med. 2019,2019, 9819643. [CrossRef] [PubMed]
169. Qu, L.; Yin, X.; Fan, S.; Qian, Y. Genetic Toχicity of Cynomorium Songaricum Rupr. J. Med. Pest Control 2016,32, 275–278.
Molecules 2024,29, 941 33 of 33
170.
Fu, S.; Xu, S.; Pei, D.; Qu, W.; Qu, J.; Tian, J. Subchronic toxicity test of Cynomorium songaricum herb aqueous extract in rat. J. Hyg.
Res. 2019,48, 104–108.
171.
Wu, J. The function and efficacy of traditional Chinese medicine Cynomorium songaricum and its development and utilization.
Lishizhen Med. Mater. Medica Res. 2015,26, 2492–2494.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual
author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to
people or property resulting from any ideas, methods, instructions or products referred to in the content.
Available via license: CC BY
Content may be subject to copyright.
