Phytochemistry Letters 47 (2022) 1–17

Contents lists available at ScienceDirect

Phytochemistry Letters
journal homepage: www.elsevier.com/locate/phytol

Mini review

Review on Pregnane Glycosides and Their Biological Activities

Yuan Si a, 1, Xiao-Song Sha b, 1, Lei-Ling Shi c, 1, Hong-Yan Wei c, Yue-Xian Jin a, Guo-Xu Ma c, d, **,
Jing Zhang a, *
a
College of Chinese Medicine Material, Jilin Agricultural University, Changchun, 130118, China
b
Department of Neurosurgery, Shenzhen Key Laboratory of Neurosurgery, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital,
3002# Sungang Road, Futian District, Shenzhen, 518035, China
c
Xinjiang Institute of Chinese and Ethnic Medicine, Urumqi, 830002, China
d
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China

A R T I C L E I N F O A B S T R A C T

Keywords: Pregnane glycosides are exist in Asclepiadaceae, Apocynaceae, Malpighiaceae, Ranunculaceae and Zygophyllaceae.
pregnane glycosides This is a class of substances with steroids as the mother nucleus and containing a glyosidic bond structure.
biological activities Modern pharmacology has shown that these compounds are a class of compounds with different structures and
multiple biological activities. It has a good development prospect in anti-cancer and anti-tumor directions. This
article reviews the chemical structures and biological activities of 345 compounds from 1984 to 2019.

1. Introduction Asclepiadaceae, Apocynaceae, Malpighiaceae, Ranunculaceae and Zygo­

Plants have been a hinge source in the discovery of new drugs for
thousands of years. But the potential of plants as sources for new drugs is
still mostly unexplored. Among the plants species existing world-wide,
only a small percentage have been investigated phytochemical.
Among the biologically interesting naturally occurring compounds,
polysaccharides, oligosaccharides, steroidal compounds are being used
for medicinal treatments, frequently.
There have been three comprehensive review articles on pregnane
glycosides up till the present moment. The first is a literary work re­
ported by Reichstein T, which reviews such substances before 1967
(Reichstein, 1967). Next document was reported by Deepak et al.
covering the literature from 1968 to 1997(Deepak et al., 1997a). The
third was reported by Mukul R. Gupta et al. which summarizes the
chemical transformation of such structural substances and modern
physical chemistry techniques from 1998 to 2014(Gupta et al., 2015). In
this review systematically reports the structure and biological activity of
pregnane glycosides based on these documents from medicinal plants
and covers the broad literature survey from 1984 till 2019 (Fig. 1).
Pregnane glycosides have considerable significance in natural med­
icine and are well known for their distinctive structural features and
significant diverse bioactivities. They are distributed in the plants of
phyllaceae (Table 1). Researchers have isolated pregnane glycosides
from plants and have studied their biological activities in detail. Up to
now, 347 kinds of pregnane glycosides have been isolated and identi­
fied. They have exhibited good biological activities as immunosup­
pressant (Gao et al., 2017), in cytotoxicity (Abdel-Sattar et al., 2008), as
antidepressants (Li et al., 2016), in anti-inflammatory abilities (Lee
et al., 2013), as anti-oxidants (Ounaissia et al., 2016), as antibacterial
agents (Song et al., 2014), as antifungal agents (Zhao et al., 2016), in
anti-proliferative activity (Plaza et al., 2005), as anti-tumor agents
(Huang et al., 2015) and as anti-tobacco mosaic virus agents (Yan et al.,
2014). Pregnane glycosides have attracted considerable attention in
recent years due to their remarkable antitumor activity. Pregnane gly­
cosides are a class of compounds with
cyclopentane-perhydrophenanthrene as the basic mother nucleus. A-C
rings are six-membered rings, and D ring is a five-membered ring. There
are six chiral carbon rings in the four rings. Because the four rings can be
interconnected, the carbon atoms are relatively fixed and cannot rotate
or flip. Pregnane glycosides are mostly linked to ligand at C-3 in the form
of chains, usually consisting of one to six sugar units. In this study, the
pregnane glycosides are classified into two major types based on link­
ages: monodesmoside-type pregnane glycosides and bidesmoside-type
pregnane glycosides. According to the different types of substituents

* Corresponding author at: Jilin Agricultural University, Changchun, 130118, China; Institute of Chinese and Ethnic Medicine, Urumqi, 830002, China.
** Corresponding author at: Xinjiang Institute of Chinese and Ethnic Medicine, Urumqi, 830002, China.
E-mail addresses: shileiling@sina.com (L.-L. Shi), mgxfl8785@163.com (G.-X. Ma), zhjing0701@163.com (J. Zhang).
1
These authors contributed equally to this work.

https://doi.org/10.1016/j.phytol.2021.10.007
Received 4 September 2020; Received in revised form 18 June 2021; Accepted 9 October 2021
Available online 2 November 2021
1874-3900/© 2021 Phytochemical Society of Europe. Published by Elsevier Ltd. All rights reserved.
Y. Si et al.
Fig. 1. Monosaccharide names and structures of C21 steroidal.
on the ring and the degree of oxidative cracking of the ring,
monodesmoside-type pregnane glycosides are divided into four cate­
gories: polyoxypregnane glycosides, epoxy-polyoxypregnane glycosides,
polyhydroxy pregnane glycosides, and 17-furan pregnane glycosides.
Polyoxyprenane glycosides usually have two oxygen-containing sub­
stituents in the C ring, and their positions are usually C-10, C-11, C-12,
C-15, and C-20. Epoxy-polyoxypregnane glycosides mainly have a
lactone structure and epoxy ring structure. Polyhydroxy pregnane gly­
cosides usually contain three or more hydroxyl groups, most of which
are located at C-5, C-8, C-14, C-16, and C-17. 17-furan pregnane gly­
cosides can be divided into seco type and diseco type according to the
connection mode at the C-17 position. Bidesmoside-type pregnane gly­
cosides have an oligosaccharide chain at C-3 and C-20 of the ligand
(Fig. 2). Because of the diverse structures and excellent biological ac­
tivities of pregnane glycosides, considerable amount of synthetic work
has been undertaken for the construction of their core structures.
However, few studies have reported the total synthesis of pregnane
glycosides. Isolation from natural plants is still the only source of
pregnane glycosides. Considering the extensive interest in pregnane
glycosides, we reviewed the structure and biological activity of preg­
nane glycosides, focusing on the latest progress in structure identifica­
tion and biological activity evaluation of pregnane glycosides. In this
study, the structure and biological activity of pregnane glycosides in 60
studies from 1984 to 2019 are reviewed.
2. Occurrence
Natural pregnane glycosides are mainly distributed in the genus
Caralluma and Cynanchum of Asclepiadaceae (Table 1). These plants
mainly grow in arid areas such as India, Arabia, and southwest China.
Various pregnane glycosides have been isolated from following plants:
the whole plant of Caralluma tuberculate (Abdel-Sattar et al., 2008), the
roots of Cynanchum paniculatum (Zhao et al., 2016), the leaves and
pericarps of Solenostemma argel (Plaza et al., 2005), the stems of Gym­
nema sylvestre (Xu et al., 2015), the twigs of Pergularia pallida (Khare
et al., 1984), the leaves of Oxystelma esculentum (Hamed et al., 2004),
the aerial parts of Ecdysanthera rosea (Zhu et al., 2011), and the seeds of
Adonis aestivalis Linné (Minpei et al., 2018).
3. Species of pregnane glycosides and their bioactivities
3.1. Monodesmoside-type pregnane glycosides
Monodesmoside-type pregnane glycosides possess an oligosaccha­
ride chain at C-3 of the aglycon consisting of one to six sugar units.
3.1.1. Polyoxypregnane glycosides
Polyoxyprogegnane glycosides usually have two oxygen-containing
substituents in the C ring, and their positions are usually C-10, C-11,
C-12, C-15, and C-20 (Table 2, Fig. 3). It is suggested that the cytotoxic
2
Phytochemistry Letters 47 (2022) 1–17
activities of pregnane glycosides are related to their C-3 sugar chains.
Caratubersides C-G (1-5) and russelioside E (6) were obtained from
whole plant of Caralluma tuberculata. Caratubersides C (1) and D (2),
caratubersides F (4) and G (5), and russelioside E (6) showed weak in
vitro antimalarial activity, whereas caratuberside E (3) was inactive
(Abdel-Sattar et al., 2008). Obcordatas A-I (7-15) were isolated from
Aspidopterys obcordata Hemsl vines. Compounds 7-15 showed signifi­
cant cytotoxicity against HuH-7 cells, with IC50 values of 8.7, 10.2, 7.5,
12.1, 16.5, 14.3, and 17.4 μM, respectively. Obcordatas A-I (7-15)
exhibited moderate cytotoxicity against AGS and SW480 cell lines, with
IC50 values ranging from 35.4 to 94.3 μM, and all displayed mild or no
cytotoxicity against the MCF-7 cell line (Hu et al., 2018). Compounds
16-40 were extracted from the whole plant of Caralluma dalzielii.
Moderate to high potency of cytotoxicities were found in all tested
compounds except compounds 17, 19, 31, and 38. Compounds 16, 18,
20, 21, 23, and 33 showed the highest activity towards the J774.A1 cell
line (Leo et al., 2005). Compounds 41-55 were obtained from the whole
plant of Caralluma negevensis, and compound 46 showed the highest
activity towards inhibited tumor cell (LoVo and HT29) (Braca et al.,
2002). Compounds 56 and 57 were isolated from the whole plant of
Caralluma quadrangular. Compounds 56 and 57 showed promising
cytotoxic activity against MCF-7 cell lines with IC50 values of 4.8 and 2.0
μM (Abdallah et al., 2013). Compounds 58-68 were extracted from the
whole plant material (aerial parts and roots) of Caralluma sinaica. The
bioassays showed that some of these compounds were QR inducers with
weak cytotoxicity (Al-massarani et al., 2012). Cundurango A (69) and
cundurango B (70) were isolated from the bark of Marsdenia cundurango.
Compounds 69 and 70 exhibited relatively potent and tumor-selective
cytotoxicity against HL-60 cells, with IC50 values of between 3.75 and
6.09 μM. A549 solid cells were less sensitive to these compounds, with
IC50 values between 12.2 and 16.9 μM. Compound 70 induced apoptotic
cell death in HL-60 cells through the loss of mitochondrial membrane
potential, followed by the activation of caspase-3 (Tatsuno et al., 2019).
Desmiflava-sides C (71) and D (72) were obtained from the sap of Des­
midorchis flava. Desmiflavasides C (71) and D (72) have potent anti­
proliferative activity against breast cancer (MDA-MB-231) and ovarian
cancer (SKOV-3) cell lines. However, only desmiflavaside D (72) showed
selective cytotoxicity towards cancer cells, without affecting the growth
of normal breast epithelial cells. Desmiflavaside C (71) was slightly
cytotoxic towards normal cells at higher concentrations while exhibiting
a growth promoting effect at a lower concentration (Raees et al., 2016).
Stavaroside C (73), D (74), F (75), I (76), J (77), and K (78) have been
extracted from the aerial parts of Stapelia varieoata (Sayed et al., 1995).
(CG)E (79), (CG)E0 (80), (CG)E2 (81), (CG)E3 (82), (CG)A (83), (CG)A0
(84), and (CG)C (85) have been isolated from the dried bark of Mars­
denia cundurango (Berger et al., 1987). Bouceroside AI (86), bouceroside
BI (87), bouceroside AII (88), and bouceroside BII (89) were obtained
from Boucerosia aucheriana (Hayashi et al., 1988). Bouceroside-BNC (5)
(90), bouceroside-BNC (7) (91), bouceroside-BNC (9) (92),
bouceroside-BNC (10) (93), bouceroside-BNC (6) (94), and
Y. Si et al. Phytochemistry Letters 47 (2022) 1–17

Table 1
Species of pregnane glycosides.
Family Genus Species Part Type Ref.

Orthenthera oiminea twigs polyhydroxy pregnane glycosides (Kaur et al., 1985)

Pergularia pallida twigs polyhydroxy pregnane glycosides (Khare et al., 1984)
Apocynaceae Ecdysanthera rosea stems epoxy- polyoxypregnane glycosides (Zhu et al., 2011)
aerial parts and (Cao et al., 2005)
Epiginium auritum epoxy- polyoxypregnane glycosides
leaves (Gao et al., 2017)
Adelostemma gracillimum roots seco pregnane glycosides (Gao et al., 2009)
curassavica aerial parts polyhydroxy pregnane glycosides (Li et al., 2008)
Asclepias
verticillata whole plants polyhydroxy pregnane glycosides (Araya et al., 2012)
Baseonema acuminatum aerial parts disaccharide-type pregnane glycosides (Bai et al., 2005)
(Hayashi et al., 1988)
Boucerosia aucheriana aerial parts polyoxypregnane glycosides
(Tanaka et al., 1989)
adscendens whole plants polyhydroxy pregnane glycosides (Reddy et al., 2011)
dalzielii whole plant polyoxypregnane glycosides and polyhydroxy pregnane glycosides (Leo et al., 2005)
lasiantha whole plants disaccharide-type pregnane glycosides (Qiu et al., 1999)
negevensis whole plant polyoxypregnane glycosides and polyhydroxy pregnane glycosides (Braca et al., 2002)
pauciflora whole plants polyhydroxy pregnane glycosides (Reddy et al., 2011)
Caralluma
(Abdel-sattar et al.,
penicillata aerial parts polyoxypregnane glycosides and polyhydroxy pregnane glycosides
2001)
quadrangular aerial parts polyoxypregnane glycosides (Abdallah et al., 2013)
aerial parts and (Al-massarani et al.,
sinaica polyoxypregnane glycosides
roots 2012)
(Abdel-Sattar et al.,
tuberculata whole plant polyoxypregnane glycosides
2008)
umbellate whole plants disaccharide-type pregnane glycosides (Qiu et al., 1997)
ascyrifolium roots seco pregnane glycosides (Yeo et al., 1998)
(Bai et al., 2005)
atratum roots seco pregnane glycosides and diseco pregnane glycosides
(Bai et al., 2009)
(Liu et al., 2013)
auriculatum roots polyhydroxy pregnane glycosides and seco pregnane glycosides
(Qian et al., 2017)
bungei roots seco pregnane glycosides (Qin et al., 2018)
Cynanchum forrestii roots seco pregnane glycosides (Liu et al., 2007)
Asclepiadaceae
(Zhao et al., 2018)
komarovii whole plants diseco pregnane glycosides
(Wang et al., 2004)
(Li et al., 2016)
(Zhang et al., 2015a)
otophyllum roots polyhydroxy pregnane glycosides
(Ma et al., 2007)
(Ma et al., 2011)
paniculatum roots diseco pregnane glycosides (Zhao et al., 2016)
saccatum roots epoxy- polyoxypregnane glycosides and polyhydroxy pregnane glycosides (Zhang et al., 2015a)
wilfordii roots polyhydroxy pregnane glycosides (Hwang et al., 1999)
Desmidorchis flava sap polyoxypregnane glycosides (Raees et al., 2016)
Dregea sinensis stems epoxy- polyoxypregnane glycosides (Liu et al., 2008)
(Srisurichan et al.,
griffithii fresh fruits epoxy- polyoxypregnane glycosides
Gymnema 2014)
sylvestre stems polyhydroxy pregnane glycosides (Xu et al., 2015)
Hemidesmus indicus stems polyhydroxy pregnane glycosides (Deepak et al., 1997a)
Hoodia gordonii aerial parts disaccharide-type pregnane glycosides (Shukla et al., 2009)
polyoxypregnane glycosides, polyhydroxy pregnane glycosides and (Tatsuno et al., 2019)
cundurango bark
disaccharide-type pregnane glycosides (Berger et al., 1987)
Marsdenia
roylei stems polyhydroxy pregnane glycosides (Gupta et al., 2003)
tenacissima stems epoxy- polyoxypregnane glycosides (Deng. et al., 2005)
Oxystelma esculentum leaves polyhydroxy pregnane glycosides (Hamed et al., 2004)
Periploca sepium bark disaccharide-type pregnane glycosides (Wang et al., 2011)
Solenostemma argel aerial parts epoxy- polyoxypregnane glycosides (Plaza et al., 2005)
Stapelia varieoata aerial parts polyoxypregnane glycosides polyhydroxy pregnane glycosides (Sayed et al., 1995)
Stephanotis mucronata roots polyhydroxy pregnane glycosides (Ye et al., 2005)
Vincetoxicum hirundinaria roots epoxy- polyoxypregnane glycosides diseco pregnane glycosides (Lavault et al., 1999)
Malpighiaceae Aspidopterys obcordata vines polyoxypregnane glycosides (Hu et al., 2008)
Ranunculaceae Adonis aestivalis seeds epoxy- polyoxypregnane glycosides (Minpei et al., 2018)
(Achenbach et al.,
Zygophyllaceae Tribulus cistoides roots polyhydroxy pregnane glycosides
1996)

bouceroside-BDC (8) (95) were extracted from Boucerosia aucherwma
(Tanaka et al., 1989). Penicilloside C (96) was isolated from the aerial
parts of Caralluma penicillata (Abdel-sattar et al., 2001).
3.1.2. Epoxy-polyoxypregnane glycosides
In this type of pregnane glycosides, the main structures are a lactone
structure and an epoxy ring structure (Table 3, Fig. 4). Argel A (97),
argeloside C (98) and argeloside F (99) were isolated from the pericarps
and aerial parts of Solenostemma argel and showed significant antioxi­
dant capacity with ORAC values of 5363, 3587, 9617, 6309, 9465, and
3481 μmol eq. Trolox/100 g, respectively, whereas the crude EtOH/H2O
extracts from aerial parts, fruits, and roots showed a more potent anti­
oxidant activity than the isolated compounds with ORAC values of
86263, 42368, and 41553 μmol eq. Trolox/100 g, respectively
(Ounaissia et al., 2016). Ecdysoside A (100), ecdysoside B (101),
ecdysoside H (102) and ecdysantheroside A (103) were obtained from
the stems of Ecdysanthera rosea. Ecdysoside A (100) showed moderate
antibacterial activities against E. faecalis (MIC value of 0.02 μM),
whereas ecdysoside H (102) showed anti-yeast activity against Crypto­
coccus neoformans (Song et al., 2014). Aestivaloside A-L (104-115) were

3
Y. Si et al.
Fig. 2. Types of pregnane glycoside skeletons.
obtained from the MeOH extract of seeds of Adonis aestivalis, but showed
no significant activity (Minpei et al., 2018). Marsdenosides A-H
(116-123), tenacissoside A (124), tenacissoside B (125), tenacissoside E
(126), and tenacissoside G-I (127-129) were extracted from the
CHCl3-soluble fraction of the ethanolic extract of the stems of Marsdenia
tenacissima, while showed no significant activity against A549 and
MCF-7 cell lines and anti-HIV test (Deng. et al., 2005). Two pregnane
glycosides, called epigynoside A (130) and epigynoside C (131) were
obtained from the aerial part of Epiginum auritum, but their biological
activity has not been reported reliably (Cao et al., 2005). Gymnemog­
riffithosides A-H (132-139) were extracted from fresh fruits of Gymnema
griffithii, whereas the cytotoxic test did not show any apparent cytotoxic
activity against the five-tested human tumor cell lines (BT 474, Chago,
HepG2, KATO-III, and SW620). Gymnemogriffithosides C (134) and F
(137), containing a tigloyl moiety at C-20, showed a slight in vitro
cytotoxicity against the same five human tumor cell lines and exhibited
a more potent in vitro cytotoxicity than other compounds (Srisurichan
et al., 2014). Hirundigoside D (140) was obtained from the roots of
Vincetoxicum hirundinaria. However, there is no explicit literature on the
biological activity of this compound (Lavault et al., 1999). Cyn­
saccatosides H (141) was isolated from the roots of Cynanchum sacca­
tum, but it did not show inhibitory effect on the growth of human cancer
cells (Zhang et al., 2015a). Compounds 142-150 (steroidal glycosides)
were extracted from the stems of Dregea sinensis. These compounds were
tested for anti-inflammatory activities in vivo, and compound 150
showed moderate anti-inflammatory activity (Liu et al., 2008). Such
skeletons exhibited significant biological activity in terms of antibacte­
rial, anti-inflammatory, and antioxidant properties.
3.1.3. Polyhydroxy pregnane glycosides
Polyhydroxy pregnane glycosides usually contain three or more hy­
droxyl groups, most of which are located at C-5, C-8, C-14, C-16, and C-
17 (Table 4, Fig. 5). Phytochemical investigation on the leaves of Epi­
gynum auritum led to the isolation of epigynoside F (151) which dis­
played significant inhibitory activity against Con A-stimulated mice
splenocyte proliferation in a dose-dependent manner. However, it did
not exhibit a significant inhibitory effect on mitogenstimulated spleno­
cyte proliferation at a concentration of 12.5 μM (Gao et al., 2017). Based
on the bioactive screening results, four new pregnane glycosides,
4
Phytochemistry Letters 47 (2022) 1–17
cynanotophyllosides A-D (152-155) and otophyllum A (156) were iso­
lated from the anti-depressant active fraction of cultivated Cynanchum
otophyllum (Li et al., 2016). Gymsylvestrosides A-E (157-161) were
isolated from the ethanol extract of the stems of Gymnema sylvestre and
were screened for Saccharomyces cerevisiae α-glucosidase inhibitory ac­
tivity but did not show significant inhibitory effect (Xu et al., 2015).
Pallidine (1) (162) and (7) (163) have been extracted from the dried
twigs of Pergularia pallida (Khare et al., 1984). Alpinoside A-C (164-166)
were isolated from the leaves of Oxystelma esculentum (Hamed et al.,
2004). Compounds 167-168 were isolated from the whole plant of
Caralluma dalzielii, and compound 167 showed moderate to high po­
tency of cytotoxicities in all the tests (Leo et al., 2005). Compound 169
was extracted from the whole plant of Caralluma negevensis (Braca et al.,
2002). Compounds 170-174 were isolated from the bark of Marsdenia
cundurango. Some of them showed relatively potent and tumor-selective
cytotoxicity against HL-60 cells (Tatsuno et al., 2019). Stavaroside A
(175), stavaroside B (176), stavaroside E (177), stavaroside G (178),
and stavaroside H (179) have been obtained from the aerial parts of
Stapelia varieoata (Sayed et al., 1995). Penicilloside A (180) and pen­
icilloside B (181) were extracted from the aerial parts of Caralluma
penicillata (Abdel-sattar et al., 2001). Eight pregnane glycosides named
cynsaccatol (A-G) (182-188) and saccatum A (189) were obtained from
the roots of Cynanchum saccatum. These compounds (182-189) were
tested for their cytotoxicity in vitro using three human cancer cell lines
(HepG2, Hela, and U251), and compounds 182, 185, 186, and 189
showed weak inhibitory activities against different cell lines (Zhang
et al., 2015a). Wilfoside C3N (190) and otophylloside B (191) were
obtained from roots of Cynanchum otophyllum Schneid. and showed cy­
totoxicities against HepG2, Hela, and U251 cancer cell lines at different
degrees (Zhang. et al., 2015b). The pregnane denin (192) has been ob­
tained from chloroform soluble extract of dried stem of Marsdenia roylei
(Gupta et al., 2003). Wilfoside K1N (193), wilfoside C1N (194) and
cynauricuoside A (195) were isolated from the roots of Cynanchum
wilfordii. These compounds showed a significant
multidrugresistance-reversing activity (Hwang et al., 1999). Tribulosin
(196) and cistocardin (197) were extracted from the roots of Tribulus
cistoides. Their biological activities have not been reported yet (Achen­
bach et al., 1996). Otophylloside H-M (198-203) were obtained from the
roots of Cynanchum otophyllum (Ma et al., 2007). Phytochemical
Y. Si et al. Phytochemistry Letters 47 (2022) 1–17

Table 2
The reported structures and pharmacological activities of polyoxypregnane glycosides (1-96).
Compound Name R1 R2 R3 Pharmacological activity Ref.

1 Caratuberside C Methyl-β-D-allo(1→4)-Rb Bz Ac Cytotoxic against antimalarial activity

2 Caratuberside D Methyl-β-D-allo(1→4)-Rb Bz Ac Cytotoxic against antimalarial activity

3 Caratuberside E Methyl-β-D-allo(1→4)-Rb Bz Ac -
(Abdel-Sattar et al.,
4 Caratuberside F β-D-glc(1→4)-6-deoxy-3-O-Ra Bz Ac Cytotoxic against antimalarial activity
2008)
β-D-glc(1→4)-6-deoxy-3-O-
5 Caratuberside G Bz Bz Cytotoxic against antimalarial activity
Methyl-β-D-allo(1→4)-Rb
β-D-glc(1→4)-6-deoxy-3-O-
6 Russelioside E Bz Ac Cytotoxic against antimalarial activity
Methyl-β-D-allo(1→4)-Rb
Cytotoxic against AGS (IC50: 35.3 μM), SW480 (IC50: 71.6
7 Obcordata A Rc Bz Tig
μM), and HuH-7 (IC50: 8.7 μM)
Cytotoxic against AGS (IC50: 40.7 μM), SW480 (IC50: 55.3
8 Obcordata B Rc Tig Tig
μM), and HuH-7 (IC50: 10.2 μM)
Cytotoxic against AGS (IC50: 45.3 μM), SW480 (IC50: 61.8
9 Obcordata C Rc Tig Tig
μM), and HuH-7 (IC50: 7.5 μM)
Cytotoxic against AGS (IC50: 36.5 μM), SW480 (IC50: 57.2
10 Obcordata D Rc Tig Bz
μM), and HuH-7 (IC50: 12.1 μM)
Cytotoxic against AGS (IC50: 51.7 μM), SW480 (IC50: 63.5
11 Obcordata E Rc Bz Bz (Hu et al., 2008)
μM), and HuH-7 (IC50: 16.5 μM)
Cytotoxic against AGS (IC50: 45.3 μM), SW480 (IC50: 54.8
12 Obcordata F Rc Bz Tig
μM), and HuH-7 (IC50: 14.3 μM)
Cytotoxic against AGS (IC50: 75.2 μM) and SW480 (IC50:
13 Obcordata G Rc Bz Tig
94.3 μM))
Cytotoxic against AGS (IC50: 64.8 μM) and SW480 (IC50:
14 Obcordata H Rc Bz Bz
87.2 μM))
Cytotoxic against AGS (IC50: 69.4 μM), SW480 (IC50: 74.1
15 Obcordata I Rc Tig Bz
μM), and HuH-7 (IC50: 17.4 μM)
16 Dalzielii A β-glc(1→4)-6-deoxy-3-O-Re Ac Bz Cytotoxic against J774.A1 (IC50: 0.084 μM)
O-NH2-
17 Dalzielii B β-glc(1→4)-6-deoxy-3-O-Re Ac -
Bz
18 Dalzielii C β-glc(1→4)-6-deoxy-3-O-Re Ac Nic Cytotoxic against J774.A1 (IC50: 0.098 μM)
19 Telosmoside A2 β-glc(1→4)-6-deoxy-3-O-Re Ac Mebu -
20 Dalzielii D Re Ac Bz Cytotoxic against J774.A1 (IC50: 0.050 μM)
O-NH2-
21 Dalzielii E Re Ac Cytotoxic against J774.A1 (IC50: 0.077 μM)
Bz
22 Dalzielii F Re Ac Nic -
23 Telosmoside A1 Re Ac Mebu Cytotoxic against J774.A1 (IC50: 0.096 μM)
24 Dalzielii G β-glc(1→6)-Rg Ac Bz -
O-NH2-
25 Dalzielii H β-glc(1→6)-Rg Ac -
Bz
26 Dalzielii I β-glc(1→6)-Rg Ac Nic -
27 Dalzielii J β-glc(1→6)-Rg Ac Mebu - (Leo et al., 2005)
28 Dalzielii K β-glc(1→6)-Rg Ac Isoval -
29 Dalzielii L Rg Ac Bz -
30 Dalzielii M Rg Ac Mebu -
31 Dalzielii N β-glc(1→4)-Ri Ac Bz -
32 Dalzielii O β-glc(1→4)-Ri Ac Nic -
33 Dalzielii P Ri Ac Nic Cytotoxic against J774.A1 (IC50: 0.095 μM)
34 Dalzielii Q Rj Ac Bz -
35 Dalzielii R Rj Ac Nic -
36 Dalzielii S B-glc(1→6)-β-glc(1→4)-β-ole-Rk Ac Bz -
37 Dalzielii T B-glc(1→6)-β-glc(1→4)-β-ole-Rk Ac Nic -
38 Dalzielii U Rl Ac Bz -
o-NH2-
39 Dalzielii V Rl Ac -
Bz
40 Dalzielii W Rl Ac Mebu -
41 Negebensis A Rg(1→4)-β-D-cym H Tig -
42 Negebensis B Rg(1→4)-β-D-cym Tig Tig -
43 Negebensis C Rg(1→4)-β-D-cym Tig Ac -
O-OH-
44 Negebensis E β-D-glc(1→4)-6-deoxy-3-O-Ra H -
Bz
45 Russelioside H β-D-glc(1→4)-6-deoxy-3-O-Ra Tig Ac -
46 Negebensis F β-D-glc(1→4)-6-deoxy-3-O-Ra Tig Tig Cytotoxic against LoVo and HT29
β-D-glc(1→4)-6-deoxy-3-O-
47 Negebensis G Tig H -
methyl-β-D-allo(1→4)-Rb
(Braca et al., 2002)
48 Negebensis H β-D-glc(1→4)-Rt Tig H -
49 Negebensis I β-D-glc(1→4)-Rt Tig Tig -
o-OH-
50 Negebensis J β-D-glc(1→4)-Rt H -
Bz
51 Negebensis K β-D-glc(1→4)-Rt Ac H -
52 Negebensis L β-D-glc(1→4)-6-deoxy-3-O-Re Tig Tig -
53 Negebensis M β-D-glc(1→3)-Rp H Tig -
54 Negebensis N β-D-glc(1→3)-Rp Tig Tig -
55 Negebensis O Rp Tig Ac -
(continued on next page)

5
Y. Si et al. Phytochemistry Letters 47 (2022) 1–17

Table 2 (continued )
Compound Name R1 R2 R3 Pharmacological activity Ref.

56 Quadrangular A Rq Bz Bz Cytotoxic against MCF-7 (IC50:4.8 μM) (Abdallah et al.,

57 Quadrangular B Rs Bz Bz Cytotoxic against MCF-7 (IC50:2.0 μM) 2013)
58 Sinaica A Rt Bz Ac -
59 Bouceroside-BDC Ra Bz Ac -
60 Sinaica B Ra Bz H -
61 Sinaica C Rd Tig Ac -
62 Russelioside G Rd Bz Ac -
(Al-massarani et al.,
63 Russelioside F Rd-(1→4)-β-D-cym Bz Ac -
2012)
64 Sinaica D Methyl-β-D-allo(1→4)-Rb Tig Ac -
65 Sinaica E β-D-glc(1→4)-β-D-dig(1→4)-Rb Bz Ac -
66 Sinaica F β-D-glc(1→4)-Rt Bz Ac -
67 Sinaica G Rd Bz Tig -
68 Sinaica H Rv Bz Bz -
Cytotoxic against HL-60 (IC50: 4.64 μM) and A549 (IC50:
69 Cundurango A Rb Ac Cin
15.7 μM) (Tatsuno et al.,
Cytotoxic against HL-60 (IC50: 5.56 μM) and A549 (IC50: 2019)
70 Cundurango B Rf Ac Cin
16.3 μM)
Cytotoxic against MDA-MB -231 (IC50: 47.01 μM) and
71 Desmiflavasides C Rb Bz Bz
SKOV-3 (IC50: 64.5 μM)
(Raees et al., 2016)
Cytotoxic against MDA-MB -231 (IC50: 19.97 μM) and
72 Desmiflavasides D Rv Bz Bz
SKOV-3 (IC50: 38.32 μM)
73 Stavaroside C methyl-β-D-allo(1→4)-Rb Ac Bz -
74 Stavaroside D Methyl-β-D-allo(1→4)-Rb Ac Tig -
75 Stavaroside F Methyl-β-D-allo(1→4)-Rb Ac Ac -
β-D-glc(1→4)-Methyl-β-D-allo (Sayed et al., 1995)
76 Stavaroside I Ang Bz -
(1→4)-Rb
β-D-glc(1→4)-Methyl-β-D-allo
77 Stavaroside J Ac Bz -
(1→4)-Rb
β-D-glc(1→4)-Methyl-β-D-allo
78 Stavaroside K Ac Tig - (Sayed et al., 1995)
(1→4)-Rb
79 (CG)E β-D-glc(1→4)-Re Ac Cin -
80 (CG)E0 Rh Ac Cin -
81 (CG)E2 β-D-glc-6-deoxy-3-O-Re-β-D-cym Ac Cin -
82 (CG)E3 β-D-glc-6-deoxy-3-O-Re-β-D-cym Ac Cin -
83 (CG)A β-D-glc(1→4)-Re Ac Cin -
84 (CG)A0 Rh Ac Cin -
(Hayashi et al.,
85 (CG)C β-D-glc(1→4)-Re Ac Cin -
1988)
86 Boucerosides AI β-D-glc(1→4)-Re Bz Bz -
β-D-glc(1→4)-Methyl-β-D-allo
87 Boucerosides BI Bz Bz -
(1→4)-Rb
88 Boucerosides AII β-D-glc(1→4)-Re Bz Bz -
β-D-glc(1→4)-Methyl-β-D-allo
89 Boucerosides BII Bz Bz -
(1→4)-Rb
Bouceroside-BNC
90 Re Bz Ac -
(5)
(Tanaka et al., 1989)
Bouceroside-BNC
91 Methyl-β-D-allo(1→4)-Rb Bz Ac -
(7)
Bouceroside-BNC
92 Re Bz Bz -
(9)
Bouceroside-BNC
93 Methyl-β-D-allo(1→4)-Rb Bz Bz -
(10)
(Tanaka et al., 1989)
Bouceroside-BNC
94 Re Bz Ac -
(6)
Bouceroside-BDC
95 Re Bz Ac -
(8)
(Abdel-sattar et al.,
96 Penicilloside C Rm Bz Isoval -
2001)

investigation of Caralluma adscendens var. gracilis and Caralluma pau­
ciflora whole plant extracts allowed isolation of one pregnane glycoside
adscendens A (204) (Reddy et al., 2011). Verticillosides A-M (205-217)
were isolated from Asclepias verticillata. The cytotoxicity of the isolates
was evaluated against paired breast cell lines Hs578 T (cancer) and
Hs578Bst (normal); however, no significant growth inhibition was
observed (Araya et al., 2012). The structures of pregnane glycosides
Cynauricosides A-I (218-226) were identified from Cynanchum auric­
ulatum; they showed significant appetite suppressing effect and led to
loss of body weight in rats (Liu et al., 2013). Medidesmine (227) and
monoglycoside (228) were extracted from the Shade-dried stems of
Hemidesmus indicus (Deepak et al., 1997b). A pregnane glycoside ornine
(229) was isolated from the dried twigs of Orthenthera viminea (Kaur
et al., 1985). Four pregnane glycosides, stemucronatosides D (230), E
(233), F (231) and G (232) were isolated from the roots of Stephanotis
mucronata and compounds 230 and 232-233 significantly inhibited Con
A- and LPS-stimulated mouse splenocyte proliferation in a
dose-dependent manner, whereas compound 231 significantly
enhanced Con A- and LPS-induced mouse splenocyte proliferation at
suitable concentrations (Ye et al., 2005). Curassavoside A-F (234-239)
were extracted from the aerial parts of Asclepias curassavica. Curassa­
voside A (234) showed weak inhibitory activity against Raji and AGZY
cell lines (Li et al., 2008). Otophyllosides N-P (240-242), otophyllum D
(243) and otophyllosides Q-S (244-246) were obtained from the roots of
Cynanchum otophyllum (Ma et al., 2011). Cynsaccatols I-W (247-261)
were obtained from the roots of Cynanchum auriculatum. In bioassay,

6
Y. Si et al.
Fig. 3. Types of polyoxypregnane glycosides (1-96).
cynsaccatols I (247), cynsaccatols U (259) and cynsaccatols W (261)
produced significant protective effects against H2O2-induced PC12 cell
damage. Among those active compounds, cynsaccatols I (247), cyn­
saccatols N (252), cynsaccatols O (263) and cynsaccatols S (257) exhibit
obvious inhibition of damaged PC12 cell apoptosis at dosages of 1 μM by
Annexin V-FITC/PI double staining assay with flow cytometry (Qian
et al., 2017). Compounds belonging to this skeleton not only exhibit
remarkable anticancer and immunosuppressive activities but also have
an effect in inhibiting cell proliferation and inducing cell death.
3.1.4. 17-Furan pregnane glycosides
17-Furan pregnane glycosides can be divided into seco type and
diseco type according to the connection mode at the C-17 position.
3.1.4.1. Seco type. Seco pregnane glycosides are mainly divided into
7
Phytochemistry Letters 47 (2022) 1–17
14,15-seco-pregnane glycosides and 8,14-seco-pregnane glycosides two
categories. 14,15-seco-pregnane-type steroidal glycosides are charac­
terized by the presence of a butenolide moiety at C-13 of the aglycones.
There is usually one carbonyl group at the C-14 position, but the posi­
tions of its substituents and other carbonyl groups determined that it has
different units. 8,14-seco-pregnane glycosides are characterized by two
carbonyls in the C-14 and C-18 positions (Table 5, Fig. 6). Saccatols D-K
(262-269) were extracted from the roots of Cynanchum auriculatum
(Qian et al., 2017). Cynanosides P1-P5 (270-274), cynanosides Q1-Q3
(275-277) and cynanosides R1-R3 (278-280) have been isolated from
the roots of Cynanchum atratum. These compounds were evaluated for
their cytotoxic activities against human myeloid leukemia cell line
HL-60, human stomach adenocarcinoma cell line KATO-III, and human
lung adenocarcinoma cell line A549. The results showed that com­
pounds 278 and 280 displayed cytotoxic activities against HL-60 cells
Y. Si et al. Phytochemistry Letters 47 (2022) 1–17

Table 3
The reported structures and pharmacological activities of epoxy-polyoxypregnane glycosides (97-150).
Compound Name R1 R2 R3 Pharmacological activity Ref.

97 Argel A β-D-ole(1→4)-β-D-can CH2- - antioxidant potential with ORAC values in the concentration
(1→4)-Rb OAc range of 3481–9617 μmol eq. Trolox/100 g
antioxidant potential with ORAC values in the concentration (Ounaissia et al.,
98 Argeloside C Ri-(1→4)-β-D-ole CH3 -
range of 3481–9617 μmol eq. Trolox/100 g 2016)
β-D-glc(1→4)- Ri-(1→4)- significantly decreased the Il-1β production by LPS- stimulated
99 Argeloside F CH3 -
β-D-ole PBMCs
100 Ecdysoside A β-D-cym - - antibacterial activities against E. faecalis
β-D-cym(1→4)-β-D-cym
101 Ecdysoside B - - antibacterial activities against E. faecalis
(1→4)-β-D-cym
(Song et al., 2014)
Rb-Rb-(1→4)-β-L-cym
102 Ecdysoside H - - antifungal activities against C. neoformans
(1→4)-β-D-glc
103 Ecdysantheroside A β-D-cym - - antibacterial activities against E. faecalis
104 Aestivaloside A β-D-ole - - -
105 Aestivaloside B β-D-ole(1→4)-β-D-ole - - -
106 Aestivaloside C Rc-(1→4)-α-L-ole - - -
B-glc(1→6)-β-glc(1→4)-
107 Aestivaloside D - - -
β-ole-Rk
108 Aestivaloside E β-D-glc(1→4)-Rg - - -
β-D-glc(1→4)-β-D-glc
109 Aestivaloside F - - - (Minpei et al.,
(1→4)-α-L-Rb
2018)
B-glc(1→6)-β-glc(1→4)-
110 Aestivaloside G - - -
β-ole-Rk-(1→4)-β-D-cym
111 Aestivaloside H Rm-(1→4)-β-D-Rb - - -
112 Aestivaloside I β-D-ole - - -
113 Aestivaloside J Rd-(1→4)-α-L-ole - - -
114 Aestivaloside K β-D-glc(1→4)-Rg - - -
115 Aestivaloside L Rd-(1→4)-α-L-ole - - -
116 Marsdenoside A Ra Bu Tig -
117 Marsdenoside B Ra Tig Tig -
118 Marsdenoside C Ra Bu Bz -
119 Marsdenoside D Ra H Bu -
120 Marsdenoside E Ra Pro Ac -
121 Marsdenoside F Ra Ac Ac -
122 Marsdenoside G Ra Tig H -
β-D-glc(1→4)-6-deoxy-3-O-
123 Marsdenoside H Bu Ac -
methyl-Ra (Deng. et al.,
β-D-glc(1→4)-6-deoxy-3-O- 2005)
124 Tenacissoside A Tig Ac -
methyl-Ra
β-D-glc(1→4)-6-deoxy-3-O-
125 Tenacissoside B Tig Tig -
methyl-Ra
β-D-glc(1→4)-6-deoxy-3-O-
126 Tenacissoside E Bu Bz -
methyl-Ra
127 Tenacissoside G Ra Bz Ac -
128 Tenacissoside H Ra Tig Ac -
129 Tenacissoside I Ra Bu Ac -
130 Epigynoside A β-D-ido H H -
(Cao et al., 2005)
131 Epigynoside C β-D-ido H CH3 -
Gymnemogriffithoside
132 Rn Ac Ac -
A
Gymnemogriffithoside
133 Rn H Ac -
B
Gymnemogriffithoside in vitro cytotoxicity against the same five human tumor cell lines
134 Rn Ac Tig
C (BT 474, Chago, HepG2, KATO-III, and SW620)
Gymnemogriffithoside
135 β-D-theve(1→4)-Ro Ac Ac -
D (Srisurichan et al.,
Gymnemogriffithoside 2014)
136 β-D-theve(1→4)-Ro H Ac -
E
Gymnemogriffithoside in vitro cytotoxicity against the same five human tumor cell lines
137 β-D-theve(1→4)-Ro Ac Tig
F (BT 474, Chago, HepG2, KATO-III, and SW620)
Gymnemogriffithoside
138 Rn Ac Ac -
G
Gymnemogriffithoside
139 β-D-theve(1→4)-Ro Ac Ac -
H
(Lavault et al.,
140 Hirundigoside D α-D-ole (1 → 4)-Ro - - -
1999)
(Zhang et al.,
141 Cynsaccatosides H Ro Cin Nic -
2015a)
142 Sinensis A Ri Ac Bz -
143 Sinensis B β-D-glc(1→4)-Ri Ac Bz -
β-D-glc(1→4)-Ri-(1→4)-
144 Sinensis C Ac Bz -
β-D-cym (Liu et al., 2008)
β-D-glc(1→4)-β-D-glc
145 Sinensis D Ac Bz -
(1→4)-Ri
146 Sinensis E Ac Bz -
(continued on next page)

8
Y. Si et al. Phytochemistry Letters 47 (2022) 1–17

Table 3 (continued )
Compound Name R1 R2 R3 Pharmacological activity Ref.

β-D-glc(1→4)-β-D-glc
(1→4)-Ri-(1→4)-β-D-cym
147 Sinensis F Ri Ac Bz -
148 Sinensis G β-D-glc(1→4)-Ri Ac Bz -
149 Sinensis H β-D-glc(1→4)-Ri-(1→4)- Ac Bz -
β-D-cym
150 Sinensis I β-D-glc(1→4)-β-D-glc Ac Bz -
(1→4)-Ri

Fig. 4. Types of epoxy-polyoxypregnane glycosides (97-150).

with IC50 values of 29.47 ± 5.38 and 52.26 ± 13.38 μM, respectively, as
compared to the positive control etoposide with the IC50 value of 0.29 ±
0.02 μM. All compounds were inactive against KATO-III 50 adenocar­
cinoma and A549 adenocarcinoma cells at 100 μM (Bai et al., 2009).
Cynaforroside Q (281) and cynaforroside P (282) were extraced from
the roots of Cynanchum forrestii (Liu et al., 2007). Cynascyrosides A-C
(283-285) were obtained from the roots of Cynanchum ascyrifolium (Yeo
et al., 1998). Six new 8,14-seco-pregnane glycosides, gracillosides A–F
(286–291) were isolated from the roots of Adelostemma gracillimum (Gao
et al., 2009). Cynabungoside A-C (292–294) were obtained from the
roots of Cynanchum bungei. These compounds showed significant activ­
ities in inhibiting the proliferation of B lymphocyte with IC50 values
ranging from 0.64 to 38.80 μM with cyclosporin A (CsA) as a positive
control (IC50 = 1.15 μM), and compounds 292-294 were active against
the proliferation of T lymphocyte with IC50 values of 1.63 to 40.93 μM
(CsA: IC50 = 0.26 μM) (Qin et al., 2018).
3.1.4.2. Diseco type. Through the different connections of the C ring,
diseco type is divided into two types: 13,14:14,15- diseco-pregnane-type
steroidal glycosides and 13,14:14,15-diseco-18-nor-pregnane-type ste­
roidal glycosides. Pregnane glycosides form the 13,14:14,15-diseco-
pregnane type through broken C/D rings and a series of oxidation re­
actions. In 13,14:14,15-diiso-18-or pregnane-type steroidal glycosides,
the furan ring and C-12 are linked by ketone-carbon and a carboxyl unit
at the C-12 position, which is the E type. The absence of the keto­
carbonyl group in the C ring and the presence of an enolactone bond are
structure F (Table 6, Fig. 7). Cynapanosides D-F (295-297), glaucoside A
(298), neocynapanogenin F (299), glaucogenin A (300), cynatratoside B

9
Y. Si et al. Phytochemistry Letters 47 (2022) 1–17

Table 4
The reported structures and pharmacological activities of polyhydroxy pregnane glycosides (151-261).
Compound Name R1 R2 R3 Pharmacological activity Ref.

151 Epigynoside F β-D-ido - - - (Gao et al., 2017)

152 Cynanotophylloside β-D-glc(1→4)-β-D-cym p-OH- - -
A (1→4)-β-D-ole(1→4)-Rb Bz
Cynanotophylloside β-D-glc(1→4)-Rg- p-OH-
153 - -
B (1→4)-α-L-Rb Bz
Cynanotophylloside β-D-glc(1→4)-β-D-theve (Li et al., 2016)
154 Ikem - -
C (1→4)-Rw
Cynanotophylloside
155 β-D-glc(1→4)-Rt Ikem - -
D
156 Otophyllum A Rg-β-D-cym Ikem - -
β-D-glc(1→4)-β-D-glc
157 Gymsylvestroside A Cin Bz -
(1→4)-Ri
β-D-glc(1→4)-β-D-glc
158 Gymsylvestroside B Cin Tig -
(1→4)-Ri
β-D-glc(1→4)-β-D-glc
159 Gymsylvestroside C Cin H - (Xu et al., 2015)
(1→4)-Ri
β-D-glc(1→4)-β-D-glc
160 Gymsylvestroside D Cin Tig -
(1→4)-Ri
β-D-glc(1→4)-β-D-glc
161 Gymsylvestroside E Cin Bz -
(1→4)-Ri
162 Pallidine(1) β-D-ole Bz Bz - (Khare et al.,
163 Pallidine(7) β-D-cym (1→4)-β-D-ole Bz Bz - 1984)
β-D-glc(1→4)-β-D-glc
164 Alpinoside A Cin - -
(1→4)Rt
(Hamed et al.,
165 Alpinoside B β-D-glc(1→4)-Rt Cin - -
2004)
β-D-glc(1→4)-β-D-glc
166 Alpinoside C Cin - -
(1→4)-β-D-ole(1→4)-Rt
Cytotoxic against J774.A1 (IC50: 0.17 μM) and WEHI-164 (IC50: 0.44
167 Dalzielii X β-theve(1→4)-β-ole - -
μM) (Leo et al., 2005)
168 Dalzielii Y Rl - - -
(Braca et al.,
169 Negebensis D Rh-(1→4)- β-D-cym - - -
2002)
170 Cundurango C Re - - Cytotoxic against HL-60 (IC50: 22.0 μM)
171 Cundurango D β-D-glc(1→4)-Re - - -
172 Cundurango E Ra-(1→4)-β-D-dig - - - (Tatsuno et al.,
173 Cundurango F Ra- (1→4)-β-D-cym Cin - Cytotoxic against HL-60 (IC50: 4.18 μM) and A549 (IC50: 12.2 μM) 2019)
β-D-glc(1→4)-Ra(1→4)-
174 Cundurango G - - -
β-D-cym
175 Stavaroside A β-D-allo(1→4)-Rb Ang Bz -
176 Stavaroside B β-D-allo(1→4)-Rb Ang Tig -
(Sayed et al.,
177 Stavaroside E β-D-allo(1→4)-Rb Bz H -
1995)
178 Stavaroside G β-D-allo(1→4)-Rb Ac - -
179 Stavaroside H β-D-allo(1→4)-Rb - - -
180 Penicilloside A β-D-glc(1→4)-β-D-dig Bz - - (Abdel-sattar
181 Penicilloside B Rm Bz - - et al., 2001)
Rb-(1→4)-β-D-cym-
182 Cynsaccatol A (1→4)-β-D-ole-(1→4)- H - Cytotoxic against U251 (IC50: 35.66 μM)
Ro
β-D-cym(1→4)-β-D-ole
183 Cynsaccatol B H - -
(1→4)-Rb
184 Cynsaccatol C β-D-ole(1→4)-Ro H - -
185 Cynsaccatol D β-D-cym(1→4)-Ro Cin Nic Cytotoxic against U251 (IC50: 94.88 μM)
186 Cynsaccatol E β-D-ole(1→4)-Ro Cin Nic Cytotoxic against HepG 2 (IC50: 52.17 μM) and (IC50: 23.9 μM) (Zhang et al.,
Rb-(1→4)-α-L-cym 2015a)
187 Cynsaccatol F Cin H -
(1→4)-Ro
188 Cynsaccatol G β-D-ole(1→4)-Ru Bz Ac -
189 Saccatum A β-D-ole(1→4)-Ru Cin Nic Cytotoxic against HepG 2 (IC50: 36.21 μM) and Hela (IC50: 47.96 μM)
Cytotoxic against HepG2 (IC50: 41.82 μM), Hela (IC50: 38.69 μM), and
190 Wilfoside C3N β-D-cym(1→4)-Ru Ikem -
U251(IC50: 46.16 μM)
Cytotoxic against HepG2 (IC50: 37.87 μM), Hela (IC50: 57.69 μM) and
191 Otophylloside B Rt Ikem -
U251(IC50: 22.52 μM)
(Gupta et al.,
192 Denin α-D-glc(1→4)-O-α-L-fuc - - -
2003)
193 Wilfoside K1N Rb-(1→4)-Rv Cin - Cytotoxic against KB-3-1 (IC50: 23.3 μM) and KB-V1 (IC50: 23.9 μM)
194 Wilfoside C1N Rb-(1→4)-Rv Ikem - Cytotoxic against KB-3-1 (IC50: 34.9 μM) and KB-V1 (IC50: 37.2 μM) (Hwang et al.,
β-D-glc(1→4)- Rb- 1999)
195 Cynauricuoside A Cin - Cytotoxic against KB-3-1 (IC50: 225.0 μM)
(1→4)-Rv
196 Tribulosin Rh-(1→4)-β-D-cym Ac Anth - (Achenbach et al.,
197 Cistocardin Rh-(1→4)-β-D-cym Nic Cin - 1996)
β-D-glc(1→4)-Rd- p-OH-
198 Otophylloside H - -
(1→4)-Ro Bz
β-D-glc(1→4)-β-D-ole p-OH- (Ma et al., 2007)
199 Otophylloside I - -
(1→4)-Rw Bz
200 Otophylloside J - -
(continued on next page)

10
Y. Si et al. Phytochemistry Letters 47 (2022) 1–17

Table 4 (continued )
Compound Name R1 R2 R3 Pharmacological activity Ref.

Rd-(1→4)-β-D-ole p-OH-
(1→4)-Ro Bz
201 Otophylloside K β-D-glc(1→4)-β-D-theve p-OH- - -
(1→4)-Rw Bz
202 Otophylloside L β-D-glc(1→4)-Rd(1→4)- Ikem - -
Ru
203 Otophylloside M Rd-(1→4)-β-D-ole Ikem - -
(1→4)-Rb
204 Adscendens A Ru-(1→4)-β-dig(1→4)- Bz Bz - (Reddy et al.,
Rb 2011)
205 Verticillosides A β-D-glc(1→4)-β-D- Ac - -
theve-(1→4)-Ru
206 Verticillosides B β-D-glc(1→4)-Re Ac - -
β-D-glc(1→4)-Re-
207 Verticillosides C Ac - -
(1→4)-β-D-cym
β-D-glc(1→4)-Re-
208 Verticillosides D Ac - -
(1→4)-β-D-cym
209 Verticillosides E β-D-glc(1→4)-Ri H - -
210 Verticillosides F β-D-glc(1→4)-Re H - -
(Araya et al.,
211 Verticillosides G β-D-glc(1→4)-Ri H - -
2012)
212 Verticillosides H β-D-glc(1→4)-Re H - -
β-D-glc(1→4)-Re-
213 Verticillosides I H - -
(1→4)-β-D-cym
β-D-glc(1→4)-Re-
214 Verticillosides J H - -
(1→4)-β-D-cym
215 Verticillosides K β-D-glc(1→4)-Ri Bz - -
216 Verticillosides L β-D-glc(1→4)-Re Bz - -
β-D-glc(1→4)-Re-
217 Verticillosides M Bz - -
(1→4)-β-D-cym
218 Cynauricoside A β-D-cym-(1→4)-Rv Cin - significant appetite suppressing effect
Rb-(1→4)Rb-(1→4)-
219 Cynauricoside B Cin - significant appetite suppressing effect
β-D-dig(1→4)-β-D-dig
220 Cynauricoside C Rb-(1→4)-Rw Cin - significant appetite suppressing effect
Rb-(1→4)-Rw(1→4)-
221 Cynauricoside D Ac - significant appetite suppressing effect
β-D-dig
222 Cynauricoside E Rb-(1→4)-Rw Ac - significant appetite suppressing effect (Liu et al., 2013)
Rb-(1→4)-Rw(1→4)-
223 Cynauricoside F H - significant appetite suppressing effect
β-D-dig
224 Cynauricoside G Rb-(1→4)-Rw H - significant appetite suppressing effect
Rb-(1→4)-β-D-dig
225 Cynauricoside H H - significant appetite suppressing effect
(1→4)-β-D-dig
226 Cynauricoside I β-D-cym-(1→4)-Rw H - significant appetite suppressing effect
227 Medidesmine α-D-glc(1→4)-Rr H H -
β-D-cym(1→4)-O-(3-O- (Deepak et al.,
228 Monoglycoside methyl)-β-D-glc(1→4)- H H - 1997a)
Rd
229 Ornine Ru Cin Cin - (Kaur et al., 1985)
Stemucronatoside D inhibited Con A- and LPS-stimulated mice splenocyte proliferation in a
230 Rt H Tig
dose-dependent manner
Stemucronatoside F enhanced Con A-and LPS-induced mice splenocyte proliferation at
231 Rt Nic -
suitable concentrations
(Ye et al., 2005)
Stemucronatoside G inhibited Con A- and LPS-stimulated mice splenocyte proliferation in a
232 Rh-(1→4)-β-D-cym Ac Tig
dose-dependent manner
inhibited Con A- and LPS-stimulated mice splenocyte proliferation in a
233 Stemucronatoside E Rt H Tig
dose-dependent manner
Curassavoside A
234 Ro Bz - Cytotoxic against Raji (IC50: 0.02 μM) and AGZY (IC50: 0.03 μM)

235 Curassavoside B Ro Bz H -
β-D-ole(1→4)-β-D-can
236 Curassavoside C - - -
(1→4)-Ro (Li et al., 2008)
237 Curassavoside D Rz - - -
Rx-(1→4)-β-D-ole
238 Curassavoside E Bz - -
(1→4)-β-D-dig
239 Curassavoside F Rx-(1→4)-Ro Bz H -
Otophylloside N β-D-cym(1→4)-β-D-ole p-OH-
240 - -
(1→4)-Rw Bz
β-D-cym(1→4)-β-D-ole p-OH-
241 Otophylloside O - -
(1→4)-Rb Bz
p-OH-
242 Otophylloside P Rk-(1→4)-Rb - -
Bz
(Ma et al., 2011)
β-D-glc(1→4)-β-D-ole
243 Otophyllum D Ikem - -
(1→4)-Rb
β-D-glc(1→4)-Rd-
244 Otophylloside Q Ikem - -
(1→4)-β-D-ole(1→4)-Rb
245 Otophylloside R Rg-(1→4)-Rb-(1→4)-Rv Ikem - -
246 Otophylloside S Ikem - -
(continued on next page)

11
Y. Si et al. Phytochemistry Letters 47 (2022) 1–17

Table 4 (continued )
Compound Name R1 R2 R3 Pharmacological activity Ref.

β-D-glc(1→4)-Rb-
(1→4)-Rb-(1→4)-Rv
247 Cynsaccatols I β-D-ole(1→4)-Ro Cin H significant protective effects against H2O2-induced injury in PC12 cells
and obviously inhibit apoptosis of H2O2-damaged PC12 cells at dosages
of 1 mM
248 Cynsaccatols J β-D-ole(1→4)-Ru Cin H significant protective effects against H2O2-induced injury in PC12 cells
249 Cynsaccatols K Ro Cin H significant protective effects against H2O2-induced injury in PC12 cells
250 Cynsaccatols L β-D-dig Cin H significant protective effects against H2O2-induced injury in PC12 cells
251 Cynsaccatols M α-L-cym(1→4)-Ro Cin Nic significant protective effects against H2O2-induced injury in PC12 cells
significant protective effects against H2O2-induced injury in PC12 cells
252 Cynsaccatols N Ro Cin Nic and obviously inhibit apoptosis of H2O2-damaged PC12 cells at dosages
of 1 mM
significant protective effects against H2O2-induced injury in PC12 cells
253 Cynsaccatols O β-D-dig Cin Nic and obviously inhibit apoptosis of H2O2-damaged PC12 cells at dosages (Qian et al., 2017)
of 1 mM
254 Cynsaccatols P β-D-ole(1→4)-Ro Cin Ac significant protective effects against H2O2-induced injury in PC12 cells
255 Cynsaccatols Q β-D-ole(1→4)-Ro H H significant protective effects against H2O2-induced injury in PC12 cells
256 Cynsaccatols R Ro H H significant protective effects against H2O2-induced injury in PC12 cells
significant protective effects against H2O2-induced injury in PC12 cells
β-D-cym(1→4)-β-D-ole
257 Cynsaccatols S H - and obviously inhibit apoptosis of H2O2-damaged PC12 cells at dosages
(1→4)-Ru
of 1 mM
258 Cynsaccatols T β-D-ole(1→4)-Ru H - significant protective effects against H2O2-induced injury in PC12 cells
259 Cynsaccatols U Ru H - significant protective effects against H2O2-induced injury in PC12 cells
260 Cynsaccatols V β-D-ole(1→4)-Ro Bz - -
261 Cynsaccatols W β-D-ole(1→4)-Ro Ikem - significant protective effects against H2O2-induced injury in PC12 cells

(301) and paniculatum A (302) were obtained from the roots of Cyn­
anchum paniculatum. Compound 301 exhibited potent inhibitory activ­
ities against HL-60, HT- 29, PC-3, and MCF-7 cell lines with IC50 values
of 8.3, 7.5, 34.3, and 19.4 μM, respectively, and compounds 295–297
and 302 displayed moderate cytotoxicity against the four cell lines. The
in vitro antioxidant activities of compounds 295–297, 301, and 302
were assayed by DPPH radical scavenging activity (Zhao et al., 2016).
Cynatratoside E (303), cynatratoside C (304) and hirundigoside B-C
(305-306) were extraced from the roots of Vincetoxicum hirundinaria
(Lavault et al., 1999). Cynaforroside K-N (307-310) and cynaforroside Q
(311) were isolated from 95% ethanol extract of the roots of Cynanchum
forrestii (Liu et al., 2007). Cynanosides E-J (312-317), cynatratoside F
(318) and cynanosides A-D (319-322) were isolated from the roots of
Cynanchum atratum (Bai et al., 2005). Komarosides P-Q (323-324) were
obtained from the whole herbs of Cynanchum komarovii. Compounds
323-324 were tested for their cytotoxicities against human leukemia
HL-60 cells, with IC50 values is 0.02 and 0.03 μM (Zhao et al., 2018).
Komarosides D-G (325-328) were extracted from the ethanol extract of
the roots of Cynanchum komarovii (Wang et al., 2004).
3.2. Bidesmoside-type pregnane glycosides
Bidesmoside-type pregnane glycosides have an oligosaccharide
chain at C-3 and C-20 of the ligand, which consists of one to six sugar
units (Table 7, Fig. 8). Cundurango H (329) was isolated from the bark
of Marsdenia cundurango (Tatsuno et al., 2019). Baseonemoside A (330)
and baseone-moside B (331) were isolated from the aerial parts of
Baseonema acuminatum (Bai et al., 2005). Two new bidesmoside-type
C-21 pregnane glycosides, named lasianthosides A (332) and B (333)
were obtained from the whole plant of Caralluma lasiantha (Qiu et al.,
1999). Hoodigoside Y (334), hoodigoside V (335) and hoodigoside Z
(336) were extraced from Hoodia gordonii (Shukla et al., 2009). Peri­
seosides C-E (337-339), sepium A (340), glycoside H2 (341) and
plocoside B (342) extracted from the root barks of Periploca sepium
(Wang et al., 2011). Carumbellosides III-Ⅴ (343-345) were isolated from
the whole plant of Caraluma umbellate (Qiu et al., 1997).
4. Conclusion
It can be concluded that the bioactivities of pregnane glycosides are
obviously related to its structural types. Natural pregnane glycosides are
a large group of compounds with diverse structures and versatile bio­
logical activities, the cytotoxic activities are particularly important in
their biological activities. The most important points are as follows: (1)
In pregnane glycosides, the number of sugar units is directly related to
cytotoxicity. The more the number of sugar units, the stronger the
cytotoxicity. (2) Substituents at C-11, C-12 and C-21 are substantially
cytotoxic. In general, a polyoxypentene glycoside with a tigloyl at the C-
21 position is more active than a polyoxypregnane glycosides with a
substituent at another position. It is found that cymarose is commonly
found in compounds with stronger activity. (3) Pregnane glycosides
contain hydroxyl groups at C-8, C-12, C-14 and C-17 positions have
excellent cytotoxicity. The higher the number of hydroxyl groups, the
stronger the activity. Natural pregnane glycosides have rich activities,
researchers have not stopped exploring and researching such com­
pounds and their bioactivities.
Author Contribution Statement
G.-X. Ma and J. Zhang conceived the idea, Y. Si, X.-S. Sha and L.-L.
Shi analyzed the data and wrote the paper. The remaining authors
contributed to refining the ideas, carrying out additional analyses and
finalizing this paper.

12
Y. Si et al. Phytochemistry Letters 47 (2022) 1–17

Fig. 5. Types of polyhydroxy pregnane glycosides (151-261).

13
Y. Si et al. Phytochemistry Letters 47 (2022) 1–17

Table 5
The reported structures and pharmacological activities of seco type pregnane glycosides (262-294).
Compound Name R1 R2 R3 Pharmacological activity Ref.

262 Saccatols D Rb-(1→4)-β-D-ole(1→4)- Cin Ac -

Rb-(1→4)-Ro
β-D-cym(1→4)-Ru-(1→4)-
263 Saccatols E Cin Ac -
β-D-dig
β-D-cym(1→4)-β-D-ole
264 Saccatols F Cin Ac - (Qian et al.,
(1→4)-Ro
2017)
265 Saccatols G β-D-cym(1→4)-Ru Cin Ac -
266 Saccatols H β-D-ole(1→4)Rw Cin Ac -
267 Saccatols I β-D-cym(1→4)-Ro Cin Ac -
268 Saccatols J β-D-ole(1→4)-Ru Cin Ac -
269 Saccatols K β-D-ole(1→4)-Ro Cin Ac -
Cynanoside P1
270 β-D-cym-(1→4)-Rv H CH3 -

271 Cynanoside P2 Rd-(1→4)-Rv H CH3 -

272 Cynanoside P3 β-D-cym-(1→4)-Rv CH3 H -
273 Cynanoside P4 Rd-(1→4)-Rv CH3 H -
274 Cynanoside P5 Rd-(1→4)-Rv OCH3 CH3 -
(Bai et al.,
275 Cynanoside Q1 Rd-(1→4)-Rv - - -
2009)
276 Cynanoside Q2 α-L-ole-(1→4)-Rv - - -
β-D-glc-(1→4)-α-L-ole-
277 Cynanoside Q3 - - -
(1→4)-Rv
278 Cynanoside R1 Rw-(1→4)-β-D-cym H - Cytotoxic against HL-60 (IC50: 29.47 μM)
279 Cynanoside R2 Rw-(1→4)-β-D-cym OH - Cytotoxic against HL-60 (IC50: 52.26 μM)
280 Cynanoside R3 Rd-(1→4)-Rv OH - -
281 Cynaforroside Q Ry - - -
(Liu et al.,
β-D-glc(1→4)-Rd-(1→4)-
282 Cynaforroside P - - - 2007)
Rr
283 Cynascyroside A α-D-ole(1→4)-Rw CH3 - -
(Yeo et al.,
284 Cynascyroside B Rd-(1→4)-Rb CH3 - -
1998)
285 Cynascyroside C Rd-(1→4)-Rv CH3 - -
Rd-(1→4)-β-D-ole(1→4)-
286 Gracilloside A Cin Ac -
Ro
Rd-(1→4)-β-D-ole(1→4)-
287 Gracilloside B Cin Ac -
Ro
β-D-glc(1→4)-β-D-ole (Gao et al.,
288 Gracilloside C Cin Ac -
(1→4)-Ro 2009)
289 Gracilloside D Rd-(1→4)-Rb(1→4)-Ro Cin Ac -
Rd(1→4)-β-D-olc(1→4)-
290 Gracilloside E Cin Ac -
Ru
291 Gracilloside F Rd(1→4)-Ru Cin Ac -
Cynabungoside
inhibits the proliferation of B lymphocytes (IC50: 11.59 μM), and the
292 A Rb(1→4)-Rw Cin Ac
proliferation of T lymphocytes (IC50: 9.19 μM)
(Qin et al.,
Cynabungoside inhibits the proliferation of B lymphocyte (IC50: 12.09 μM), and the
293 Rb(1→4)-Rw Cin Ac 2018)
B proliferation of T lymphocytes (IC50: 10.76 μM)
Cynabungoside inhibits the proliferation of B lymphocyte (IC50: 0.64 μM) and the proliferation
294 β-D-cym(1→4)-Rb Cin Ac
C of T lymphocytes (IC50: 5.82 μM)

Fig. 6. Types of seco type pregnane glycosides (262-294).

14
Y. Si et al. Phytochemistry Letters 47 (2022) 1–17

Table 6
The reported structures and pharmacological activities of diseco type pregnane glycosides (295-328)
Compound Name R1 R2 R3 Pharmacological activity Ref.

295 Cynapanoside D Rr H H in vitro antioxidant activities

296 Cynapanoside E Rb(1→4)-β-D-ole H OH in vitro antioxidant activities
297 Cynapanoside F α-L-ole(1→4)-Rr H OH in vitro antioxidant activities
298 Glaucoside A β-D-ole OH H -
Neocynapanogenin
299 β-D-ole H OH - (Zhao et al.,
F
2016)
300 Glaucogenin A Rr OH H -
in vitro antioxidant activities and cytotoxicity against HL-60 (IC50: 8.3
301 Cynatratoside B α-cym(1→4)-Rr H H μM), HT-29(IC50: 7.5 μM), PC-3 (IC50: 34.3 μM), and MCF-7 (IC50: 19.4
μM)
302 Paniculatum A α-cym(1→4)-Rr H OH in vitro antioxidant activities
303 Cynatratoside E β-D-glc(1→4)-β-D-ole(1→4)-Rr H - -
α-D-ole(1→4)-Rr
304 Cynatratoside C H - - (Lavault
et al., 1999)
305 Hirundigoside B β-D-glc(1→4)-α-D-ole(1→4)-Rr OH - -
306 Hirundigoside C α-D-ole(1→4)-Rr OH - -
307 Cynaforroside K Rk-(1→4)Rb-(1→4)β-D-ole - - -
Rk-(1→4)β-D-ole(1→4)β-D-ole
308 Cynaforroside L - - -

Rk(1→4)β-L-cym(1→4)-β-D-3-
(Liu et al.,
309 Cynaforroside M demethyl-2- deoxytheve(1→4)- - - -
2007)
β-D-ole
Rk-(1→4)-Ru(-1→4)β-D-3-
310 Cynaforroside N - - -
demethyl-2-deoxy-theve
311 Cynaforroside Q Ry - - -
312 Cynanoside E β-D-cym(1→4)-Rv OH - -
313 Cynanoside F Rd-(1→4)-Rv OH - -
314 Cynanoside G α-L-cym(1→4)-Rv OH - -
315 Cynanoside H α-L-ole(1→4)-Rv OH - -
316 Cynanoside I Rd-(1→4)-Rv H - -
(Bai et al.,
317 Cynanoside J α-L-cym(1→4)-Rv H - -
2005)
318 cynatratoside F β-D-cym(1→4)-Rv H - -
319 Cynanoside A β-D-cym(1→4)-Rv - - -
320 Cynanoside B Rd-(1→4)-Rv - - -
321 Cynanoside C α-L-cym(1→4)-Rv - - -
322 Cynanoside D Rd-(1→4)-Rv - - -
323 Komaroside P β-D-Ole - - Cytotoxic against HL-60 (IC50: 0.02 μM) (Zhao et al.,
324 Komaroside Q β-D-Ole OH - Cytotoxic against HL-60 (IC50: 0.03 μM) 2018)
Komaroside D
325 β-D-glc(1→4)α-D-ole(1→4)-Rr OH - -

326 Komaroside E Rd-(1→4)-Rr OH - - (Wang et al.,

327 Komaroside F Rj OH - - 2004)
β-D-glc(1→4)α-L-Rw(1→4)β-D-3-
328 Komaroside G OH - -
demethyl-2-deoxy-theve

Fig. 7. Types of diseco type peegnane glycosides (298-328).

15
Y. Si et al. Phytochemistry Letters 47 (2022) 1–17

Table 7 (1 → 4)-β-D-ole, Rs β-D-cym(1→4)- β-D-can(1→4)-β-D-cym, Rt β-D-theve(1→4)-

The reported structures of disaccharide-type pregnane glycosides (329-345). β-D -cym(1→4)-β-D-cym, Ru β-D-ole(1→4)-β-D-cym, Rv β-D-dig(1→4)-β-D-cym,
Rwβ-D-cym(1→4)-β-D-dig, Rxβ-D-glc(1→4)-β-D-ole(1→4)-β-D-can, Ryβ-D-ole
Compound Name R1(C-3) R2(C-20) R Ref.
(1→4)-β-D-3-demethyl-2- deoxy-theve(1→4)-β-D-theve, Rz β-D-ole(1→4)-β-D-
329 Cundurango H Re β-D-glc 11β,12β, (Tatsuno can(1→4)-β-D-can(1→4) -β-D-dig;
14β-OH et al.,
2019)
330 Baseonemoside Rw β-D-glc -
A (1→2)-
β-D-dig
(Bai
β-D-cym
et al.,
(1→4)- β-D-glc
Baseonemoside 2005)
331 β-D-cym (1→2)- -
B
(1→4)- β-D-dig
β-D-dig
β-D-glc α-L-rha
332 Lisianthoside A (1→4)- (1→6)- -
(Qiu
β-D-dig β-D-glc
et al.,
β-D-glc α-L-rha
1999)
333 Lisianthoside B (1→4)- (1→6)- 14β-OH
β-D-dig β-D-glc
β-D-
theve
334 Hoodigoside Y β-D-glc 14β-OH
(1→4)-
β-D-ole
β-(4-O- Fig. 8. Types of disaccaride-type pregnane glycosides (329-345).
tigloyl)-
335 Hoodigoside V D-theve β-D-glc 14β-OH
(Shukla
(1→4)- Declaration of Competing Interest
et al.,
β-D-ole
2009)
β-(4-O-
The authors declared that they have no conflicts of interest to this
tigloyl)-
D-theve
work. We declare that we do not have any commercial or associative
336 Hoodigoside Z (1→4)- β-D-glc 14β-OH interest that represents a conflict of interest in connection with the work
β-D-cym submitted
(1→4)-

Acknowledgments
β-D-cym
337 Periseoside C β-D-glc β-D-glc -
β-D-glc(1
338 Periseoside D → 4)- glc-glc - This research was funded by the National Natural Science Founda­
β-D-dig tion of China [grant number 81860759], 2018 Chinese Medicine Public
339 Periseoside E β-D-glc β-D-glc 16β-OH Health Service Subsidy Special "National Chinese Medicine Resources
(2-O- β-D-glc
acetyl- (1→6)-
General Survey Project" (Caishe [2018] No. 43), and the National
340 Sepium A β-D-dig) β-D-glc - Traditional Chinese Medicine Administration National Chinese Medi­
(1 → 4)- (1→2)-
(Wang
cine Resource Census Project (No. GZY-KJS-2018-004).
β-D-cym β-D-dig
et al.,
(2-O-
References
β-D-glc
2011)
acetyl- (1→6)-
341 Glycoside H2 β-D-dig) β-D-glc 16β-OH
Abdallah, H.M., Osman, A.M., Almehdar, H., Abdel-sattar, E., 2013. Acylated pregnane
(1→4)- (1→2)-
glycosides from Caralluma quadrangula. Phytochemistry 88, 54–60.
β-D-cym β-D-dig
Abdel-sattar, E., Al-yahya, M.A., Nakamura, N., Hattori, M., 2001. Penicillosides A–C, C-
β-D-glc
15 oxypregnane glycosides from Caralluma penicillata. Phytochemistry 57,
β-D-dig (1→6)- 1213–1217.
342 Plocoside B (1→4)- β-D-glc 16β-OH Abdel-Sattar, E., Harraz, F.M., Al-Ansari, S.M.A., El-Mekkawy, S., Ichino, C.,
β-D-cym (1→2)- Kiyohara, H., Ishiyama, A., Otoguro, K., Omura, S., Yamada, H., 2008. Acylated
β-D-dig pregnane glycosides from Caralluma tuberculata and their antiparasitic activity.
β-D-glc Phytochemistry 69, 2180–2186.
Carumbelloside
343 (1→4)- β-D-glc 14β-OH Achenbach, H., Hubner, H., Reiter, M., 1996. Cholestane-and pregnane-type glycosides
III
β-D-dig from the roots of Tribulus cistoides. Phytochemistry 41, 907–917.
β-D-glc (2-O- Al-massarani, S.M., Bertrand, S., Nievergelt, A., El-shafae, A.M., Al-howiriny, T.A., Al-
Carumbelloside musayeib, N.M., Cuendet, M., Wolfender, J., 2012. Acylated pregnane glycosides
344 (1→4)- benzoyl)- 14β-OH (Qiu
Ⅳ
β-D-dig β-D-glc et al., from Caralluma sinaica. Phytochemistry 79, 129–140.
6-O- 1997) Araya, J.J., Binns, F., Kindscher, K., Timmermann, B.N., 2012. Verticillosides A-M:
Polyoxygenated pregnane glycosides from Asclepias verticillata L. Phytochemistry 78,
benzoyl- (2-O-
Carumbelloside 179–189.
345 β-D-glc benzoyl)- 14β-OH
Ⅴ Bai, H., Li, W., Asada, Y., Sato, T., Wang, Y., Koike, K., 2009. Twelve pregnane glycosides
(1→4)- β-D-glc from Cynanchum atratum. Steroids 74, 198–207.
β-D-dig Bai, H., Li, W., Koike, K., Satou, T., Chen, Y., Nikaido, T., 2005. Cynanosides A-J, ten
novel pregnane glycosides from Cynanchum atratum. Tetrahedron 61, 5797–5811.
Abbreviations : Raβ-D-allo(1→4)-β-D-ole, Rbβ-D-cym(1→4)-β-D-cym, Rcβ-D-
Berger, S., Junior, P., Kopanski, L., 1987. Structural revision of pregnane ester glycosides
ole(1→4)-β-D-allo, Rdβ-D-glc(1→4)-β-D-cym, Remethyl-β-allo(1→4) -β-ole from Condurango cortex and new compounds. Phytochemistry 27, 1451–1458.
(1→4)-β-cym, Rfmethyl-β-D-allo(1→4)-β-D-ole(1→4)-β-D-dig-β-D-cym, Rgβ-glc Braca, A., Bader, A., Morelli, I., Scarpato, R., Turchi, G., Pizza, C., Tommasi, N.D., 2002.
(1→4)-β-ole(1→4)-β-cym, Rhβ-D-glc(1→4)-β-D-6 -deoxy-3-O-methyl-allo(1→4)- New pregnane glycosides from Caralluma negevensis. Tetrahedron 58, 5847–5848.
β-D-cym, Riβ-theve-(1→4)-β-ole-(1→4)-β-cym, Rjβ-glc(1→6)-β-glc(1→4)- Cao, J.X., Pan Lu, Y., Wang, C., Zheng, Q.T., Luo, S.D., 2005. Three novel pregnane
glycosides from Epigynum auritum. Tetrahedron 61, 6630–6633.
β-theve(1→4)-β-ole, Rkβ-glc (1→6)-β-glc(1→4)-β-ole, Rlβ-glc(1→4)-6-deoxy-3-
Deepak, D., Srivastav, S., Khare, A., 1997a. A Pregnane Glycosides. Prog. Chem. Org.
O-methyl-β-allo(1→4)-β-cym(1→4)-β-ole(1→4)-β-cym, Rm β-D-glc(1→6)-β-D- Nat. Prod. 71, 169–325.
glc(1→4)-β-D-dig, Rnβ-D-theve(1→4)-β-D-can(1→4)-β-D-dig, Roβ-D-ole(1→4)- Deepak, D., Srivastav, S., Khare, A., 1997b. Pregnane glycosides from Hemidesmus
β-D-dig, Rpβ-D-glc(1→4)-6-deoxy-3-O-methyl-β-D-allo (1→4)-β-D-theve(1→4)- indicus. Phytochemistry44 145–151.
β-D-cym(1→4)-β-D- cym, Rq β-D-dig(1→4)-β-D-can(1→4)- β-D-cym, Rr β-D-dig-

16
Y. Si et al.
Deng, J., Liao, Z., Chen, D., 2005. Marsdenosides A-H, polyoxypregnane glycosides from
Marsdenia tenacissima. Phytochemistry 66, 1040–1051.
Gao, F., Yao, Y.C., Cai, S.B., Zhao, T.R., Yang, X.Y., Fan, J., Li, X.N., Cao, J.X., Cheng, G.
G., 2017. Novel immunosuppressive pregnane glycosides from the leaves of
Epigynum auritum. Fitoterapia 118, 107–111.
Gao, Z.L., He, H.P., Di, Y.T., Fang, X., Li, C.S., Liu, H.Y., Zhou, Q.L., Mu, Q.Z., Hao, X.J.,
2009. Gracillosides A-F, six new 8,14-seco-pregnane glycosides from Adelostemma
gracillimum. Steroids 74, 694–700.
Gupta, M., Gupta, V., Khare, N.N., 2015. Structural studies of biologically important
steroidal pregnane glycosides from medicinal plants. Trends Carbohydr. Res. 7,
53–97.
Gupta, V.S., Kumar, A., Deepak, D., Khare, A., Khare, N.K., 2003. Pregnanes and
pregnane glycosides from Marsdenia roylei. Phytochemistry 64, 1327–1333.
Hamed, A.I., Sheded, M.G., Shaheen, A.E.M., Hamada, F.A., Pizza, C., Piacente, S., 2004.
Polyhydroxypregnane glycosides from Oxystelma esculentum var. alpini.
Phytochemistry 65, 975–980.
Hayashi, K., Iida, I., Nakao, Y., Nakao, Y., Kaneko, K., 1988. Four pregnane glycosides,
boucerosides AI, AII, BI and BII from Boucerosia aucheriana. Phytochemistry 27,
3919–3924.
Hu, M.G., Li, Y.H., Sun, Z.C., Huo, X.W., Zhu, N.L., Sun, Z.H., Liu, Y.Y., Wu, H.F., Xu, X.
D., Ma, G.X., Li, G., 2018. New polyoxypregnane glycosides from Aspidopterys
obcordata vines with antitumor activity. Fitoterapia 129, 203–209.
Huang, L.J., Wang, B., Zhang, J.X., Yan, C., Mu, S.Z., Hao, X.J., 2015. Studies on
cytotoxic pregnane sapogenins from Cynanchum wilfordii. Fitoterapia 101, 107–116.
Hwang, B.V., Kim, S.E., Kim, Y.H., Kim, H.S., Hong, Y.S., Ro, J.S., Lee, K.S., Lee, J.J.,
1999. Pregnane Glycoside Multidrug-Resistance Modulators from Cynanchum
wilfordii. Journal of Natural Products 62, 640–643.
Kaur, K.J., Khare, M.P., Khare, A., 1985. A pregnane ester and its glycosides from
Orthenthera viminea. Phytochemistry 24, 3007–3009.
Khare, N.K., Khare, M.P., Khare, A., 1984. Two pregnane ester glycosides from Pergularia
pallida. Phytochemistry 23, 2931–2935.
Lavault, M., Richomme, P., Bruneton, J., 1999. Acetophenones and new pregnane
glycosides from the roots of Vincetoxicum hirundinaria. Fitoterapia 70, 216–220.
Lee, C.L., Hwang, T.L., He, W.J., Tsai, Y.H., Yen, C.T., Yen, H.F., Chen, C.J., Chang, W.Y.,
Wu, Y.C., 2013. Anti-neutrophilic inflammatory steroidal glycosides from Solanum
torvum. Phytochemistry 95, 315–321.
Leo, M.D., Tommasi, N.D., Sanogo, R., Autore, G., Marzocco, S., Pizza, C., Morelli, L.,
Braca, A., 2005. New pregnane glycosides from Caralluma dalzielii. Steroids 70,
573–585.
Li, J.Z., Liu, H.Y., Lin, Y.J., Hao, X.J., Wei, N., Chen, C.X., 2008. Six new C21 steroidal
glycosides from Asclepias curassavica L. Steroids 73, 594–600.
Li, X., Luo, Y., Li, G.P., Yang, Q.X., 2016. Pregnane glycosides from the antidepressant
active fraction of cultivated Cynanchum otophyllum. Fitoterapia 110, 96–102.
Liu, S.Z., Chen, Z.H., Wu, J., Wang, L.Y., Wang, H.M., Zhao, W.M., 2013. Appetite
suppressing pregnane glycosides from the roots of Cynanchum auriculatum.
Phytochemistry 93, 144–153.
Liu, Y., Qu, J., Yu, S.S., Hu, Y.C., Huang, X.Z., 2007. Seven new steroidal glycosides from
the roots of Cynanchum forrestii. Steroids 72, 313–322.
Liu, Y., Qu, J., Yu, S., Tang, W., Liu, J., Hu, Y., Ma, S., 2008. Nine novel C-21 steroidal
glycosides substituted with orthoacetate from Dregea sinensis var. corrugata. Steroids
73, 184–192.
Ma, X.X., Jiang, F.T., Yang, Q.X., Liu, X.H., Zhang, Y.J., Yang, C.R., 2007. New pregnane
glycosides from the roots of Cynanchum otophyllum. Steroids 72, 778–786.
Ma, X.X., Wang, D., Zhang, Y.J., Yang, C.R., 2011. Identification of new
qingyangshengenin and caudatin glycosides from the roots of Cynanchum otophyllum.
Steroids 76, 1003–1009.
Minpei, K., Satoshi, K., Daichi, M., Yukiko, M., Hiroshi, S., Yoshihiro, M., 2018.
Aestivalosides A-L, twelve pregnane glycosides from the seeds of Adonis aestivalis.
Phytochemistry 150, 75–84.
Ounaissia, K., Pertuit, D., Mitaine-offer, A.C., Miyamoto, T., Tanaka, C., Delemasure, S.
P., Dutartre, P., Smati, D., Lacaille-dubois, M.A., 2016. New pregnane and phenolic
glycosides from Solenostemma argel. Fitoterapia 114, 98–104.
Plaza, A., Perrone, A., Balestrieri, M.L., Felice, F., Balestrieri, C., Hamed, A.I., Pizza, C.,
Piacente, S., 2005. New unusual pregnane glycosides with antiproliferative activity
from Solenostemma argel. Steroids 70, 594–603.
17
Phytochemistry Letters 47 (2022) 1–17
Qian, X., Li, B., Li, P., Wang, D., Dai, W., Zhang, M., 2017. C21 steroidal glycosides from
Cynanchum auriculatum and their neuroprotective effects against H2O2-induced
damage in PC12 cells. Phytochemistry140 1–15.
Qin, J.J., Chen, X., Lin, Z.M., Xu, Y.S., Li, Y.M., Zuo, J.P., Zhao, W.M., 2018. C21-steroidal
glycosides and sesquiterpenes from the roots of Cynanchum bungei and their
inhibitory activities against the proliferation of B and T lymphocytes. Fitoterapia
124, 193–199.
Qiu, S.X., Cordell, G.A., Kumar, B.R., Rao, Y.N., Ramesh, M., Kokate, C., Rao, A.V.N.A.,
1999. Bisdesmosidic pregnane glycosides from Caralluma lasiantha. Phytochemistry
50, 485–491.
Qiu, S.X., Lin, L.Z., Cordell, G.A., Ramesh, M., Kumar, B.R., Radhakrishna, M.,
Monhan, G.K., Reddy, B.M., Rao, Y.N., Srinivas, B., Thomas, N.S., Rao, A.V.N.A.,
1997. Acylater C-21 steroidal bisdesmosidic glycosides from Caraluma umbellata.
Phytochemistry 46, 333–340.
Raees, M.A., Hussain, H., Al-rawahi, A., Csuk, R., Muhammad, S.A., Khan, H.Y.,
Rehman, N.U., Abbas, G., Al-broumi, M.A., Green, I.R., Elyassi, A., Mahmood, T., Al-
harrasi, A., 2016. Anti-proliferative and computational studies of two new pregnane
glycosides from Desmidorchis flava. Bioorg Chem 67, 95–104.
Reddy, K.D., Rao, B.V.A., Babu, G.S., Kumar, B.R., Braca, A., Vassallo, A., Tommasi, N.D.,
Rao, G.V., Narasimha, A.V., 2011. Minor pregnanes from Caralluma adscendens var.
gracilis and Caralluma pauciflora. Fitoterapia 82, 1039–1043.
Reichstein, T., 1967. Cardenolid- und Pregnanglykoside. Naturwissenschaften. 54,
53–67.
Sayed, K.A.E., Halim, A.F., Zaghloul, A.M., Mcchesney, J.D., Stone, M.P., Voehler, M.,
Hayashi, K., 1995. Pregnane glycosides from Stapelia variegata. Phytochemistry 39,
395–403.
Shukla, Y.J., Pawar, R.S., Ding, Y., Li, X.C., Ferreira, D., Khan, I.A., 2009. Pregnane
glycosides from Hoodia gordonii. Phytochemistry 70, 675–683.
Song, C.W., Lung, P.K., Qin, X.J., Cheng, G.G., Gu, J.L., Liu, Y.P., Luo, X.D., 2014. New
antimicrobial pregnane glycosides from the stem of Ecdysanthera rosea. Fitoterapia
99, 267–275.
Srisurichan, S., Puthong, S., Pornapakakul, S., 2014. Pregnane-type steroidal glycosides
from Gymnema griffithii Craib. Phytochemistry 106, 197–206.
Tanaka, T., Tsukamoto, S., Hayashi, K., 1989. Pregnane glycosides from Boucerosia
aucheriana. Phytochemistry 29, 229–237.
Tatsuno, S., Yokosuka, A., Hatauma, F., Mashiko, Y., Mimaki, Y., 2019. Pregnane
glycosides from the bark of Marsdenia cundurango and their cytotoxic activity. J Nat
Med 73, 93–103.
Wang, L., Shen, Y., Xu, X., Wei, Y., Zhou, J., 2004. Five new C21 steroidal glycosides
from Cynanchum komarovii Al. Iljinski. Steroids 69, 319–324.
Wang, L., Yin, Z.Q., Zhang, Q.W., Zhang, X.Q., Zhang, D.M., Liu, K., Li, Y.L., Yao, X.S.,
Ye, W.C., 2011. Five new C21 steroidal glycosides from Periploca sepium. Steroids 76,
238–243.
Xu, R., Yang, Y., Zhang, Y., Ren, F., Xu, J., Yu, N., Zhao, Y., 2015. New pregnane
glycosides from Gymnema sylvestre. Molecules 20, 3050–3066.
Yan, Y., Zhang, J.X., Liu, K.X., Huang, T., Yan, C., Huang, L.J., Liu, S., Mu, S.Z., Hao, X.J.,
2014. Seco-pregnane steroidal glycosides from the roots of Cynanchum atratum and
their anti-TMV activity. Fitoterapia 97, 50–63.
Ye, Y., Sun, H., Li, X., Chen, F., Qin, F., Pan, Y., 2005. Four new C-21 steroidal glycosides
from the roots of Stephanotis mucronata and their immunological activities. Steroids
70, 791–797.
Yeo, H., Kim, K., Kim, J., Chio, Y., 1998. Steroidal glycosides of the 14,15-seco-18-nor-
pregnane series from Cynanchum ascyrifolium. Phytochemistry 49, 1129–1133.
Zhang, M., Rao, L.L., Xiang, C., Li, C.B., Li, P., 2015a. C21 steroidal glycosides from the
roots of Cynanchum saccatum. Steroids 101, 28–36.
Zhang, M., Li, X., Xiang, C., Qin, Y., He, J., Li, B.C., Li, P., 2015b. Cytotoxicity of
pregnane glycosides of Cynanchum otophyllum. Steroids 104, 49–60.
Zhao, D., Feng, B., Chen, S., Chen, G., Li, Z., Li, X., Sang, X., An, X., Wang, H., Pei, Y.,
2016. C21 steroidal glycosides from the roots of Cynanchum paniculatum. Fitoterapia
113, 51–57.
Zhao, D., Su, S.S., Chen, S.F., Lu, X., Chen, G., Wang, Y.B., Su, G.Y., Pei, Y.H., 2018. Two
new C21 steroidal glycosides isolated from Cynanchum komarovii. Chinese Journal
of Natural Medicines 16, 610–614.
Zhu, X.D., Wu, G.S., Xiang, J.Y., Luo, H.R., Luo, S.D., Zhu, H.M., Wang, Y.F., 2011. New
pregnane saponins from Ecdysanthera rosea and their cytotoxicity. Fitoterapia 82,
632–636.