A review on chemical constituents and bioactivities of Viburnum odoratissimum / Asian

Journal of Traditional Medicines, 2020, 15(5)

Review

A review on chemical constituents and bioactivities of

Viburnum odoratissimum
Xiaobian Xuea, Guodong Yaoa,b*
a
Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research &
Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang
Pharmaceutical University, Shenyang 110016, China;
b
Jiangsu Kanion Pharmaceutical Company Ltd., Lianyungang 222001, China

Abstract

Viburnum odoratissimum belongs to viburnum genus of the Caprifoliaceae family. Previous studies reported many chemical
constituents in this plant, including monoterpenoids, sesquiterpenoids, vibsane-type diterpenes, triterpenes, coumarins, and
lignans, and various pharmacological bioactivities the extracts of V. odoratissimum such as anti-tumor, neuroprotective, anti-
inflammatory, ichthyism and anti-oxidant activity. Besides, the total synthesis of vibsane-type diterpenes and their derivatives
have attracted considerable attention because of their wide-ranging anti-tumor activity. This present study not only systematically
summarizes the compounds isolated from V. odoratissimum, and the structure-activity relationship of these compounds.

Keywords: Viburnum odoratissimum; compound structures; vibsane-type diterpenes; pharmacological effects

1 Introduction Previous studies on the chemical components of this

Vi b u r n u m o d o r a t i s s i m u m , k n o w n a s
“shanhushu” in China, is a landscape plant. It is
divided into two types, Viburnum odoratissimum
var. sessiliflorum (Geddes) Fukuoka and Viburnum
odoratissimum var. awabuki (K. Koch) Zabel ex
Rumpl.
Vi b u r n u m o d o r a t i s s i m u m , r i c h i n
monoterpenoids, sesquiterpenoids, vibsane-type
diterpenes, triterpenes, coumarins, and lignans.
* Author to whom correspondence should be addressed. Address:
School of Traditional Chinese Materia Medica, Shenyang
Pharmaceutical University, 103 Wenhua Rd., Shenyang 110016,
China; Tel.: +86-24-23986510; E-mail: guodong_yao@163.com.
Received: 2020-05-20   Accepted: 2020-08-06
plant have identified vibsane-type diterpenes with
anti-tumor activities, which has attracted increasing
attention to the total synthesis of these compounds
as well as their derivatives.
Moreover, modern pharmacological studies
have shown that these compounds isolated from this
plant possess various pharmacological effects, such
as anti-tumor, neuroprotective, anti-inflammatory,
ichthyic and anti-oxidant activity. Its branches and
leaves of Viburnum odoratissimum are used as the
traditional Chinese medicine for clearing heat and,
removing dampness, activating the channels and
collaterals and detoxicating [1]. Hence, the plant
may have a wide prospect of development and
utilization.

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2 Research progress of chemical constituents 2.1 Monoterpenoids

V. odoratissimum contains a variety of chemical To date, about 5 monoterpenoids have been

constituents, including mainly monoterpenoids, isolated from V. odoratissimum, namely loliolide
sesquiterpenoids, vibsane-type diterpenes, triterpenes, (1), menthiafolic acid (2) vibsansuspenside A
coumarins, and lignans. They have been reported to (3), vibsansuspenside B (4), and 7,10,2′,3′ tetra-
be the main secondary metabolites of this plant [2]. acetylsuspensolide F (5) (Fig. 1).

Fig. 1 Monoterpenoids from V. odoratissimum

2.2 Sesquiterpenoids were identified as cyperenolacid (6), spathulenol (7),

awabukinol (8), 4-hydroperoxyawabukinol (9), and
It was reported that 5 sesquiterpenoids compounds 3-hydroperoxyawabukinol (10) [3-5]. (Fig. 2)
were isolated from V. oddratissimum. Their structures

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Fig. 2 Sesquiterpenoids from V. odoratissimum

2.3 Vibsane-type diterpenes 2.3.2 7-membered ring

Vibsane-type diterpenes are quite rare natural
products, existing only in some species of Viburnum
genus [6]. Diterpenes from this plant can be
categorized into 11-membered ring, 7-membered
ring and rearranged types.
2.3.1 11-membered ring
At present, 26 11-membered ring type vibsane-
type diterpenes have been isolated, including
vibsanin F (11), 14-hydroxyVibsanin F (12), vibsanin
V (13), vibsanin H (14), vibsanin B (15), vibsanol
A (16), vibsanol B (17), vibsanin U (18), vibsanin
A (19), vibsanin P (20), vibsanin Q (21), vibsanin
L (22), vibsanin E (23), vibsanol G (24), vibsanin
D (25), vibsanol F (26), 15-O-methylvibsanin U
(27), 15,18-O-diacetyl-15-O-methylvibsanin U
(28),vibsanin R (29), vibsanin S (30), vibsanol C
(31), vibsanin X (32), vibsanin T (33), 6-O-methyl-
6,7-dihydroxyvibsanin B (34), 4-hydroxyvibsanin A
(35), and vibsanum A (36) [7-12]. (Fig. 3)
It was reported that 43 7-membered
ring type diterpenes were obtained, and their
structures were identified as vibsanin C (37),
vibsanin G (38), vibsanin I (39), vibsanin H (40),
vibsanin K (41), (14S*)-14,15-epoxyvibsanin
C (42), vibsanin W (43), dehydrovibsanin
G (44), 15,18-di-O-methylvibsanin H (45),
18-O-methylvibsanin K (46), 18-O-methylvibsanin
G (47), 18-O-methylvibsanin C (48), cyclovibsanin
A (49), 15-O-methylcyclovibsanin A (50),
15-O-methylcyclovibsanin B (51), 3-hydroxy-15-O-
methylcyclovibsanin A (52), 5-epivibsanin C (53),
5-epivibsanin G (54), (14R*)-14,15-epoxyvibsanin
C (55), 5-epivibsanin H (56), 5-epivibsanin K (57),
3-hydroxyvibsanin E (58), 5-epivibsanin E (59),
furanovibsanin A (60), 3-O-methylfuranovibsanin A
(61), furanovibsanin B (62), 7-epifuranovibsanin B
(63), 7-epialdovibsanin A (64), aldovibsanin A (65),
aldovibsanin B (66), aldovibsanin C (67), vibsanin
D (68), vibsaniguration A (69), 18-O-methyl-5-
epivibsanin K (70), vibsanin M (71), vibsanin E

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(72), furanovibsanin F (73), furanovibsanin D (80), 2-O-methylneovibsanin I (81), neovibsanin H (82),

(74), furanovibsanin C (75), furanovibsanin E
(76), furanovibsanin G (77), vibsanin O (78), and
vibsaniguration B (79) [7-9,11,13-21]. (Fig. 3)
2.3.3 Rearranged type
Compounds 80-97 were isolated from V.
odoratissimum, including 2-O-methylneovibsanin H
neovibsanin I (83), neovibsanin A (84), neovibsanin
B (85), neovibsanin D (86), 7-epineovibsanine D
(87), 15-O-methylneovibsanin F (88),15-O-methyl-
14-epineovibsanin F (89), neovibsanin J (90),
neovibsanin P (91), neovibsanin C (92), 15-O-methyl-
18-epineovibsanin F (93), 14-epineovibsanin G
(94), neovibsanin G (95), spirovibsanin A (96), and
neovibsanin K (97) [22-27]. (Fig. 3)

Fig. 3 Vibsane-type diterpenes from V. odoratissimum

(to be continued)

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Continued fig. 3
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Continued fig. 3
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Continued fig. 3
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Continued fig. 3

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2.4 Triterpenes oic acid (107), 20-dihydroxy-3-oxo-lupane-20(29)-

To date, about 31 triterpenes have been
isolated and identified from V. odoratissimum,
including 6α-hydroxy-lupane-20(29)-en-3-on-28-
oic acid (98), 6β-hydroxy-lupane-20(29)-3-on-28-
oic acid (99), lupane-20(29)-en-3-on-28-oic acid
(100), 6β,30-dihydroxy-3-oxo-lupane-20(29)-28-
oic acid (101), 6β-hydroxylupane-20(29)-en-3-oxo-
27,28-dioic acid (102), 6α-hydroxy-lupane-20(29)-
en-3-oxo-27,28-dioic acid (103), 6β-hydroxy-
3,20-dioxo-30nor-lupane-28-oic acid (104),
3,4-seco-lupane-4,20-dihydroxy-3,28-dioic acid-3-
oicacidmethylester (105), 3β-hydroxy-lupane-12-
en-28-oic acid (106), 3β,20-dihydroxy-lupane-28-
28-oic acid (108), 20-hydroxy-3-O-oxolup-28-oic
acid (109), nepeticin (110), 6α-hydroxy-lup,20(29)-
en-3-on-28-oic acid (111) , rigidenol (112),
lupeol (113), b-amyrin (114), castanopsol (115),
oleanolicacid (116), 3β-hydroxy-oleanene-12-en-
28-oic acid (117), 3β,6β-dihydroxy-oleanene-12-en-
28-oic acid (118), 3β,28-dihydroxy-12-oleanene-1-
one (119), castanopsone (120), 3β,28-dihydroxy-12-
oleanene-11-one (121), 13,28-epoxy-11-oleanene-
3-one (122), α-amyrinmargarate (123), 23-hydroxy-
3-oxo-urs-12-en-28-oicacid (124), ursolic acid
(125), ursonic acid (126), 3-acetoxyolean-12-en-28-
ol (127), and 5α,8α-epidioxy-24-norcholesta-6,22-
dien-3β-ol (128) [3,11, 28-32]. (Fig. 4)

Fig. 4 Triterpenes from V. odoratissimum

(to be continued)

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Continued fig. 4

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Continued fig. 4

2.5 Coumarins 2’,6’-di-O-acetylscopolin (129), 3’,6’-di-O-

acetylscopolin (130), 2’-O-acetylscopolin (131), and
To data, four coumarin compounds have 6’-O-acetylscopolin (132) repectively [28]. (Fig. 5)
been isolated from V. odoratissimum, named

Fig. 5 Coumarins from V. odoratissimum

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2.6 Lignans vibsanol L (135), 9’-O-methylvibsanol (136),

Lignans compounds, isolated and
identified from V. odoratissimum, include 7R,8S-
dihydrodehydrodiconferyl alcohol 4-O-β-d-
glucopyranoside (133), 7S,8R-dihydrodehydrodiconferyl
alcohol 4-O-β-d-glucopyranoside (134),
(+)-9’-O-senecioyllariciresinol (137),
(+)-9’-O-isovaleryllariciresinol (138), vibsanlignan B
(139), (+)-pinoresinol (140), secoisolariciresinol
(141), cycloolivil (142), horsfieldin (143), and
dihydrodehydrodiconiferyl alcohol (144) [33,34].
(Fig. 6)

Fig. 6 Lignans from V. odoratissimum

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2.7 Others (145), phthalic acid isodibutyl ester (146), dibutyl

There are other compounds isolated from
V. odoratissimum, including sterol, organic acids
and flavones. These compounds were named
5-hydroxy-3,4-dimethyl-5-pentylfuran-2(5H)-one
phthalate (147), 4-methoxycinnamic acid (148),
p-hydroxycinnamic acid (149), caffeic acid (150),
3,4,5-trimethoxy galic acid (151), and viburodorol A
(152) [35,36] (Fig. 7).

Fig. 7 Sterol, organic acids and flavones from V. odoratissimum

3 To t a l s y n t h e s i s o f v i b s a n e - t y p e 3.1 The total synthesis of vibsane-type diterpenoid

diterpenoids and their derivatives
Vibsane-type diterpenoid, a rare natural
product, exhibited significant anti-tumor activities
in various cancer cell lines. Because of the novel
structure and strong cytotoxicity of vibsane-type
diterpenoids, more and more researchers have
designed and realized the total synthesis of vibsane-
type diterpenoids as well as their derivatives.
A c c o r d i n g t o t h e r e p o r t , Ta k a o e t a l .
have synthesized a 11-membered vibsane-type
diterpenoid, named (+)-vibsanin A (19) [37]. And
vibsanin E (23) has been successfully synthesized
through 14 steps reaction [38].
Jeffrey et al. reported the total synthesis
of five vibsane-type diterpenoids. Davies and
Williams groups eventually synthesized vibsanin

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E (23) and 5-epi-vibsanin E (59). In addition,
Williams group completed the synthesis of
(±)-2-O-methylneovibsanin H (80). Based on the
synthetic route of 2-O-methylneovibsanin H (80),
they also synthesized 14-epi-neovibsanin G (94) and
neovibsanin G (95) with the same structure [39].
Neovibsanins A (84) and B (85) exhibited good
biological activities. At concentrations ranging
from 20 to 40 µM, neovibsanins A (84) and B
(85) significantly promoted the neurite outgrowth
of NGF-mediated PC12 cells [40]. Imagawa and
Nishizawa completed the first total synthesis of
neovibsanin B (85). Fukuyama group investigated a
method that demonstrated the formal enantioselective
synthesis of (+)-neovibsanin B (85) [39].
Yoshiyasu Fukuyama et al. found vibsanin E (23)
could be derived from vibsanin C (37) [41].
3.2 The structural modifications of vibsane-type
diterpenoids
More importantly, in addition to the synthesis
of vibsane-type diterpenoids, derivatives of this type
were also obtained by structural modification.
Compounds vibsanin A (19), analog A (153)
and analog B (154) were produced as synthetic
intermediates during the synthesis of compounds.
Vibsanin A (19) and analog B (154) were oxidized
to give obtained analog D (156) and analog C (155),
respectively [42]. (Fig. 8)

Fig. 8 Vibsanin A derivatives from V. odoratissimum

Besides, 54 vibsanin B derivatives were also
obtained by structural modifications, including
vibsanin B-7 (157), vibsanin B-8 (158), vibsanin
B-11 (159), vibsanin B-12a (160), vibsanin B-12b
(161), vibsanin B-12c (162), vibsanin B-12d (163),
vibsanin B-12e (164), vibsanin B-12f (165), vibsanin
B-13a (166), vibsanin B-13b (167), vibsanin B-13c
(168), vibsanin B-15 (169), vibsanin B-16 (170),
vibsanin B-17 (171), vibsanin B-18 (172), vibsanin
B-19 (173), vibsanin B-8a (174), vibsanin B-8b
(175), vibsanin B-8c (176), vibsanin B-8d (177),
vibsanin B-8e (178), vibsanin B-27b (179), vibsanin
B-27c (180), vibsanin B-27d (181), vibsanin
B-27e (182), vibsanin B-27f (183), vibsanin B-28b

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(184), vibsanin B-28c (185), vibsanin B-28d (186),
vibsanin B-28e (187), vibsanin B-28f (188), vibsanin
B-24a (189), vibsanin B-24b (190), vibsanin B-24c
(191), vibsanin B-24d (192), vibsanin B-24e (193),
vibsanin B-24f (194), vibsanin B-23a (195), vibsanin
B-23b (196), vibsanin B-23c (197), vibsanin B-20a
(198), vibsanin B-20b (199), vibsanin B-25b
(200), vibsanin B-25c (201), vibsanin B-26b (202),
vibsanin B-26c (203), vibsanin B-29b (204),
vibsanin B-29c (205), vibsanin B-9 (206), vibsanin
B-10 (207), vibsanin B-14 (208), vibsanin B-8f
(209), vibsanin B-22 (210), and vibsanin B-21
(211) [43]. (Fig. 9)

Fig. 9 Vibsanin B derivatives from V. odoratissimum

(to be continued)

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Continued fig. 9

4 Research progress of pharmacological extracts of V. odoratissimum have different inhibitory

effects effects on tumor cells. The typical metabolites of
V. odoratissimum are vibsane-type diterpenoids
4.1 Anti-tumor which were reported to possess significant anti-
tumor activities. The detailed cytotoxicity of these
Previous pharmacological studies showed the types of compounds is as followed:

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Vibsanol C (31) exhibited stronger inhibitory
activity against all the tested cell lines HL-60,
SMMC-7721, A-549, MCF-7 and SW-480, with
IC50 values of 3.35, 4.41, 5.18, 11.30 and 3.70 µM.
Vibsanol F (26) and vibsanol G (24) also showed
strong inhibitory activity against SMMC-7721
cell line, with IC 50 values of 3.69 and 3.52 µM,
respectively [9]. Remarkably, vibsanin K (41)
was identified as a Hsp90 inhibitor and showed
significant cytotoxicity against HL-60 cell line
with an IC 50 value of 19.16 µM. In addition,
15,18-O-diacetyl-15-Omethylvibsanin U (28)
displayed significant inhibitory effects HL-60, A-549,
SMMC-7721, MCF-7 and SW480 cell lines, with
IC50 values of 0.15 ± 0.01, 0.69 ± 0.01, 0.41 ± 0.02,
0.75 ± 0.03, and 0.48 ± 0.03 µM, respectively [36].
These compounds were isolated from the leaves and
twigs of V. odoratissimum.
Dehydrovibsanin G (44) and (+)-9’-O-senecioyl-
lariciresinol (137) were also isolated and identified
from the leaves and twigs of the V. odoratissimum.
Most of them have good inhibitory effects on skin
and breast cancer. Dehydrovibsanin G (44) was
found to exhibit significant cytotoxicity against
A431 and T47D cell lines by sulforhodamine
B (SRB) method, with IC 50 values of 20.60 and
15.60 µM. While (+)-9’-O-senecioyllariciresinol
(137) exhibited moderate inhibition against
these two cell lines with IC50 values of 33.80 and
44.80 µM, respectively [12].
Moreover, vibsanin B (15) and vibsanin
C (37) were also isolated from the leaves of
V. odoratissimum. Their cytotoxicity against KB
cell lines was evaluated, with IC50 values of 3.50
and 11.30 µM, respectively. 5-epi-vibsanin C (53)
and 5-epi-vibsanin H (56) also showed cytotoxicity
against KB cell lines, with IC50 values of 10.70 and
45.50 µM, respectively [13,15]. In addition, anti-
tumor activity of vibsanin B-12f (165) against SK-
BR-3, MDA-MB-468, HepG2, AGS, Huh-7, HeLa,
BT474 and BEAS-2B cell lines was also tested, with
279
IC50 values of 1.12 ± 0.15, 0.76 ± 0.44, 2.26 ± 0.10,
0.86 ± 0.06, 0.86 ± 0.06, 0.59 ± 0.10, 2.64 ± 0.72,
and 2.84 ± 0.13 µM, respectively [43].
5-Epi-vibsanin G (54), vibsanol A (16) and
6β-hydroxylup-20(29)-en-3-oxo-27,28-dioic acid
(102) were isolated from the leaves and flowers of
V. odoratissimum. Remarkably, 5-epi-vibsanin G
(54) was evaluated to have a weak inhibitory effect
against NUGC cells [14]. Comparatively, vibsanol
A (16) and 6β-hydroxylup-20(29)-en-3-oxo-27,28-
dioic acid (102) showed obvious cytotoxicity against
NUGC tumor cells with IC 50 values of 3.00 and
4.00 µM, respectively [10].
In addition, the anti-tumor effect of MeOH
extracts from leaves and twigs of V. odoratissimum
and V. awabuki were investigated. Vibsanin P (20)
exhibited moderate inhibitory activity against A549
and HT-29 cell lines with IC50 values of 11.05 and
13.39 µM respectively. Vibsanin W (43) had similar
effects on the two cells with IC50 values of 22.20 and
18.15 µM, respectively. These compounds displayed
excellent cytotoxicity against P-388 cell lines with
IC50 values of 5.38 and 4.85 µM, respectively [7].
Besides, vibsanin O (78) also exhibited cytotoxicity
against P-388 cell with an IC50 value of 8.25 µM [19].
At the same time, 3β-hydroxyolean-12-en-28-
oic acid (106) and 3β,20-dihydroxy lupane-28-oic
acid (107) were isolated and identified. The two
compounds cytotoxicity against P388 and HT29
cell lines, with IC50 values of 14.31 and 77.09 µM,
for the first compound and IC50 values of 18.94 and
61.05 µM, for the second [28].
Meanwhile, the cytotoxicy of compounds
lupeol (113) and 3-acetoxyolean-12-en-28-ol (127),
extracted from V. odoratissimum, to SMMC-7721,
HeLa, and K562 cell lines were studied by using
the MTT assay. Compound lupeol (113) showed
significant cytotoxic activity against SMMC-
7721 and HeLa cells, with IC 50 values of 55.32
and 46.59 µM, respectively, while the compound
3-acetoxyolean-12-en-28-ol (127) displayed
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Journal of Traditional Medicines, 2020, 15(5)

moderate inhibitory effect against K562 cells with messages, including the positive control, cell lines,
an IC50 value of 37.68 µM [44]. To make the results time and IC50 value (Table 1).
more intuitive, we use a table to describe these

Table 1 The detailed information of anti-tumor activities

Compounds Positive control Cell lines Time/h IC50/µM
vibsanol C HL-60 3.35
SMMC-7721 4.41
cisplatin A-549 48 h 5.18
MCF-7 11.30
SW-480 3.70
vibsanol F cisplatin SMMC-7721 48 h 3.69
vibsanol G cisplatin SMMC-7721 48 h 3.52
dehydrovibsaninG A431 20.60
72 h
T47D 15.60
(+)-9’-O-senecioyllariciresinol A431 33.80
72 h
T47D 44.70
5-epi-vibsanin C KB 10.70
5-epi-vibsanin H KB 45.50
vibsanol A antinomycin D NUGG 3.00
6β-hydroxylup-20(29)-en-3-oxo-27,28-
antinomycin D NUGG 4.00
dioic acid
vibsanin K taxol HL-60 48 h 19.16
15,18-O-diacetyl-15-Omethylvibsanin U HL-60 0.15
A-549 0.69
taxol SMMC-7721 0.41
MCF-7 0.75
SW480 0.48
vibsanin B KB 3.50
vibsanin C KB 11.00
vibsanin P A-549 144 h 11.05
HT-29 144 h 13.39
P-388 72 h 5.38
vibsanin W A549 144 h 22.02
HT-29 144 h 18.15
P388 72 h 4.85
vibsanin O P388 72 h 8.25
3β-hydroxyolean-12-en-28-oic acid P388 72 h 14.31
HT-29 144 h 77.09

(to be continued)

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Continued table 1
Compounds Positive control Cell lines Time/h IC50/µM
3β,20-dihydroxy lupane-28-oic acid P388 72 h 18.94
HT-29 144 h 61.05
lupeol SMMC-7721 55.32
HeLa 46.59
3-acetoxyolean-12-en-28-ol K562 37.68
vibsanin B-12f SK-BR-3 1.12
MDA-MB-468 0.76
HepG2 2.26
AGS 0.86
cisplatin 48 h
Huh-7 0.86
Hela 0.59
BT474 2.64
BEAS-2B 2.84
Note: Different colors represent different compounds.

Recently, modern pharmacological surveys
indicated that vibsane-type diterpenoids had novel
biological activities. For example, vibsanin A (19),
a promising new antileukemic lead, was reported
to inhibit acute myeloid leukemia (AML); Tyrosine
kinase inhibitors (TKIs) could induce differentiation
of AML cells; and the combination of vibsanin A (19)
and TKIs could activate PKC, upregulate of Lyn,
activate MAPK signaling pathway, and has induced
tumor cells differentiation [45,46]. (Fig. 10)

Fig. 10 The molecular mechanisms of the vibsanin A on AML

Vibsanin A analog C (155) had extensive anti- biology experiments, molecular docking and
proliferative activity against various cancer cell structure−activity relationships (SARs) demonstrated
lines, and the underlying mechanism was related that vibsanin B (15) could directly combine with
to the inhibition of Hsp90 [50]. Multiple molecular Hsp90 C-terminus. Vibsanin B-12f (165), one of

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Journal of Traditional Medicines, 2020, 15(5)

the vibsanin B derivatives, was also proven to be
Hsp90 C-terminus inhibitor since, it could decrease
the expression of Hsp90 client proteins, including
c-Raf, Her2, p-Akt, and CDK4. Besides, it could
also lead to G2/M cell cycle arrest. Hence, some
compounds with vibsanin B (15) scaffolds were
considered potential anticancer agents. It’s anti-
cancer mechanism could be related to the inhibition
of Hsp90 activities [42]. (Fig. 11)

Fig. 11 Vibsane-type diterpenoids and derivative inhibit Hsp90 in tumor cells

Meanwhile, it was reported that vibsanol
A (16) could inhibit AML, but unlike vibsanin A
(19), it caused cell cycle arrest. It also induced cell
differentiation via controlling protein kinase C (PKC)
and downregulating the extracellular signal regulated
kinase (ERK) pathway. Besides, reactive oxygen
species (ROS) levels also played an important role
in the treatment of AML. In conclusion, vibsanol A
(16), a differentiation agent against AML, inhibited
AML cell differentiation by activating the PKC/ERK
signaling pathway and inducting ROS. In a word,
these results demonstrated vibsanol A (16) could
enhance differentiation when combined with all-
trans retinoic acid in AML cells [47]. (Fig. 12)
Moreover, through network pharmacology,
bioinformatics analysis and molecular biology
experiments, vibsanol C (37) was proved to have
significant cytotoxicity against lung cancer A549
cell line. It also inhibited A549 cell lines via
inhibition the EGFR and subsequent inactivation of
the proteins of PI3K/AKT signaling pathway [45].
(Fig. 13)
4.2 Neuroprotective
Recently, the extracts from the dry leaves
of V. odoratissimum have been shown to have
neuroprotective effects. Two new iridoids were
isolated and identified from this plant, along
with five known terpenoids. These compounds
were elucidated as vibsansuspenside A (3) and
vibsansuspenside B (4), 23-hydroxy-3-oxo-urs-12-
en-28-oic acid (124), cyperenolacid (5), spathulenol
(6), and loliolide (1). With the exception of
loliolide (1) and 23-hydroxy-3-oxo-urs-12-en-28-
oic acid (124), they all showed neuroprotective
effects on H 2 O 2 -induced damage in SH-SY5Y
cells. Among them, 20-hydroxy-3-oxolup-28-oic
acid (109) exhibited the strongest neuroprotective
effect [49].

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Journal of Traditional Medicines, 2020, 15(5)

Fig. 12 The molecular mechanisms of the vibsanol A on AML

Fig. 13 The molecular mechanisms of the vibsanol C on A549 cells

4.3 Anti-inflammation phenocopied the inhibitory effect of vibsanin B

Interstitial leukocyte migration plays a vital
role in inflammation and provides a therapeutic
target for the treatment of inflammation-related
diseases. Ye et al. investigated how vibsanin B
(15) targeteds Hsp90 and inhibiteds interstitial
leukocyte migration. Their investigation revealed
that vibsanin B (15) preferentially targeteds Hsp90β
rather than Hsp90α. Besides, inactivation of Hsp90
(15) on leukocyte migration in THP-1 cells, dHL60
cells, and zebrafish embryos. At the molecular level,
vibsanin B (15) inhibit inflammation related to
interstitial leukocyte migration by inhibitng Hsp90β
and PI3K/AKT signaling pathway. In this study, they
also demonstrated that vibsanin B (15) improved
experimental autoimmune encephalomyelitis (EAE)
in mice and inhibited leukocyte infiltration into the
CNS of mice [50] (Fig. 14).

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Journal of Traditional Medicines, 2020, 15(5)
Fig. 14 The molecular mechanisms of the vibsanin B as a Hsp90β inhibitor
4.4 Other activities
Modern pharmacological results have shown
that the extracts from V. odoratissimum also have
anti-oxidant and ichthyism activities. Flavones
and organic acid were isolated from the leaves of
V. odoratissimum Ker by Su [51]. The experiment
demonstrated that 6α-hydroxy-lup20(29)-en-3-on-
27,28-oic acid (98) from V. odoratissimum could
restore the glucose absorption in DXMS-induced
insulin resistant 3T3-L1 cells. Ma et al. found that
this compound could significantly stimulate glucose
absorption in insulin resistant HepG2 cells without
affecting cell viability [32].
In the past, people used V. odoratissimum
to fish, because it could make fish unconscious.
Kawazu K et al. reported the constituents of leaves
of V. odoratissimum Ker, among which, vibsanin A
(19) showed ichthyism activity, with a TLm value
of 0.18 µg/mL [6]. Kubo et al. found the compounds
from leaves of V. odoratissimum had a lethal effect
with an LD50 value of 76 ppm [20].
5 Conclusion
V. odora tis s im um is a w idely cultured
284
landscape plant in many provinces of China. Our
review shows that there are 152 compounds in this
plant, including many types of compounds, such
as monoterpenoids, sesquiterpenoids, vibsane-
type diterpenes, triterpenes, coumarins, and lignans
with promising anti-tumor, neuroprotective, anti-
inflammatory, ichthyism and anti-oxidant activities.
Some of them have different degrees of inhibitory
effect on various cancer cells and we have mapped
their pharmacological mechanism of action.
Vibsane-type diterpenoids is a natural product
with diverse structure, exclusively found in a few
viburnum species. We also found that vibsane-type
diterpenoids possess strong potential anti-tumor
activities, and summarized the total synthesis of
vibsane-type diterpenoids. Structural modification,
gave 58 vibsane-type diterpenoids derivatives.
Our review also indicates that some vibsane-type
diterpenoids, as well as their derivatives, are a new
class of Hsp90 inhibitors. As compounds have great
anti-cancer potential, more and more researchers
begin to pay attention to the total synthesis of
vibsane-type diterpenoids, which provides novel
insights for developing new drugs.
However, the current studies on the activity of
these compounds are limited to simple drug efficacy,
 A review on chemical constituents and bioactivities of Viburnum odoratissimum / Asian
Journal of Traditional Medicines, 2020, 15(5)
and the in-depth study on their mechanism is far
from enough. There is no doubt that the research
on the plant is still promising. Therefore, we
summarized the current research status and revealed
that V. odoratissimum possesses strong potential
a source of new drugs, in order to provide novel
insights into further study and development of this
plant.
Conflict of interest
The authors have declared that there is no
conflict of interest.
Acknowledgments
This work was supported by National Natural
Science Foundation of China [Grant No. 81703385].
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