Journal of Ethnopharmacology 257 (2020) 112829

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Journal of Ethnopharmacology
journal homepage: www.elsevier.com/locate/jethpharm

Review

Gardenia jasminoides Ellis: Ethnopharmacology, phytochemistry, and T

pharmacological and industrial applications of an important traditional
Chinese medicine
Liping Chen, Maoxing Li∗, Zhiqiang Yang, Wendi Tao, Peng Wang, Xiuyu Tian, Xiaolin Li,
Weigang Wang
Department of Pharmacy, The 940th Hospital of Joint Logistic Support Force of PLA, Lanzhou, 730050, PR China

ARTICLE INFO ABSTRACT

Keywords: Ethnopharmacological relevance: Gardenia jasminoides Ellis is a popular shrub in the Rubiaceae family. The de-
Gardenia jasminoides Ellis siccative ripe fruits of this plant (called Zhizi in China) are well known and frequently used not only as an
Ethnopharmacology excellent natural colourant, but also as an important traditional medicine for the treatment of different diseases,
Crosslinking agent such as reducing fire except vexed, clearing away heat evil, and cooling blood and eliminating stasis to activate
Pigment
blood circulation. It has also been declared as the first batch of dual-purpose plants used for food and medical
functions in China.
Aim of the study: This review aims to provide a critical and systematic summary of the traditional uses,
ethnopharmacology, phytochemistry, pharmacology, toxicity and industrial applications of Gardenia jasminoides
Ellis and briefly proposes several suggestions for future application prospects.
Materials and methods: The related information on Gardenia jasminoides Ellis was obtained from internationally
recognized scientific databases through the Internet (PubMed, CNKI, Google Scholar, Baidu Scholar, Web of
Science, Medline Plus, ACS, Elsevier and Flora of China) and libraries.
Results: Approximately 162 chemical compounds have been isolated and identified from this herb. Among them,
iridoid glycosides and yellow pigment are generally considered the main bioactive and characteristic in-
gredients. Various pharmacological properties, such as a beneficial effect on the nervous, cardiovascular and
digestive systems, hepatoprotective activity, antidepressant activity, and anti-inflammatory activity, were also
validated in vitro and in vivo. Moreover, geniposide and genipin are the most important iridoid compounds
isolated from Gardenia jasminoides Ellis, and genipin is the aglycone of geniposide. As the predominant active
ingredient with a distinct pharmacological activity, genipin is also an outstanding biological crosslinking agent.
Gardenia yellow pigment has also been widely used as an excellent natural dye-stuff. Hence, Gardenia jasminoides
Ellis has been applied to many other fields, including the food industry, textile industry and chemical industry, in
addition to its predominant medicinal uses.
Conclusions: According to this review, Gardenia jasminoides Ellis is outstanding traditional medical plant used in
medicine and food. Pharmacological investigations support the traditional use of this herb and may validate the
folk medicinal use of Gardenia jasminoides Ellis to treat different diseases. Iridoid glycosides are potential
medicines. Gardenia yellow pigment has been the most important source of a natural colourant for food, cloth
and paint for thousands of years. This herb has made great contributions to human survival and development.
Moreover, it has also achieved outstanding progress in human life and even in art. Although Gardenia jasminoides
Ellis has extremely high and comprehensive utilization values, it is still far from being completely explored.
Therefore, the comprehensive development of Gardenia jasminoides Ellis deserves further analysis.

1. Introduction have been proved to possess an extreme advantage in the treatment of

various ailments and promoting health (Alam et al., 2016). In parti-
After several thousand years of practice, Chinese herbal medicines cular, in recent years, natural products have received increasing

∗
Corresponding author.
E-mail address: luckchlp369@163.com (M. Li).

https://doi.org/10.1016/j.jep.2020.112829
Received 3 September 2019; Received in revised form 16 March 2020; Accepted 31 March 2020
Available online 18 April 2020
0378-8741/ © 2020 Elsevier B.V. All rights reserved.
L. Chen, et al. Journal of Ethnopharmacology 257 (2020) 112829

Abbreviations: IL interleukin
LPS lipopolysaccharide
Abeta amyloid beta peptide IR ischemia-reperfusion
AChE acetylcholinesterase IRS-1 insulin receptor substrate-1
AD Alzheimer's disease LDH lactate dehydrogenase
ALI acute lung injury MAO-B monoamine oxidase B
ALP alkaline phosphatase MAPK mitogen-activated protein kinase
ALT alanine aminotransferase MDA malondialdehyde
ANIT α-naphthylisothiocyanate MMPs matrix metalloproteinase
AP acute pancreatitis MPO myeloperoxidase
AS atherosclerosis MS mass spectrometry
AST aspartate transaminase NF nuclear factor
BUN blood urine nitrogen NMR Nuclear Magnetic Resonance
CAT catalase NO nitric oxide
CK creatine kinase PG prostaglandin E2
COX cyclooxygenase PL pancreatic lipase
DPPH 1-diphenyl-2-picrylhydrazyl PMA phorbol 12-myristate 13-acetate
DSS dextran sulfate sodium QC quality control
ECs endothelial cells ROS reactive oxygen species
ESI Electron Spray Ionization SAP severe acute pancreatitis
GLP-1R glucagon-like peptide-1 receptor SMC smooth muscle cells
GSH glutathione SOD superoxide dismutase
HE haematoxylin and eosin TBARS thiobarbituric acid reactive substances
HPLC high-performance liquid chromatography t-CBAs taurine-conjugated bile acids
HPLC-DAD high-performance liquid chromatography with a diode TCM traditional Chinese medicine
array detector TNF-α tumour necrosis factor-α
IC50 50% inhibitory concentration

attention due to their low toxicity and high performance. Thus, many
countries have gradually shifted to investigating medicinal plants. In
the era of the knowledge economy, the traditional herbal industry
possesses a driving developmental advantage and broad market pro-
spect.
Notably, healthy foods have entered mainstream discussions in
many countries (Guarrera and Savo, 2016). In addition to their nutri-
tional functions, they have been used to cure ailments and protect
health, which constitute the physical basis of the TCM theory called the
same source of medicine and food.
Most natural colourants possess beneficial characteristics and
medical and health care functions (Stasiak et al., 2014). Since ancient
times, natural dyes have been used in many fields, such as cotton,
textiles, beverages and food (Simon et al., 2017). Due to the public's
growing concerns about the side effects of synthetic pigment, natural
dyes are currently gaining in popularity. They also play a key role in
modern industrial system as food additives, nutritional food and pro-
mising medicines.
As an important crosslinking agent, glutaraldehyde has been applied
extensively to fix biological tissues in clinical application for many
years. However, its application is now substantially restricted by its
major drawbacks of poor biocompatibility and obvious toxicity (Sung
et al., 2003).
Gardenia jasminoides Ellis (G. jasminoides) is a popular shrub in the
Rubiaceae family. The desiccative ripe fruits of this plant have long
been applied in China for centuries as both a food and medicinal sub-
stance. As an important and potential traditional herb, an increasing
number of scientific investigations have mainly focused on the chemical
constituents, pharmacological activity, related mechanisms of action,
and safety in recent decades. To date, numerous researchers have
confirmed that G. jasminoides possesses a wide spectrum of pharmaco-
logical activities, such as a positive effect on the cardiovascular and
digestive systems, antidepressant activity, anti-inflammatory activity,
and a protective effect on the nervous system. Approximately 162
compounds have been isolated and identified from this medicinal plant.
Iridoid glycosides and yellow pigment are generally considered the
main bioactive and characteristic ingredients, and geniposide is used as
an indicator in the quantitative determination of G. jasminoides in the
Pharmacopoeia of the People's Republic of China.
The distinction between G. jasminoides and other traditional herbs is
its wide range of industrial applications. G. jasminoides has been applied
as an excellent natural colourant in many countries, including China,
Japan, Korea, India and North America. Notably, gardenia yellow was
the most popular substance of various natural pigments in the Qin and
Han Dynasties in China. Based on in-depth research, genipin, a novel,
effective and natural crosslinking agent has been proven to have var-
ious merits compared to other crosslinking agents (Yan et al., 2010).
Genipin is usually prepared from its parent compound geniposide,
which is separated and purified from G. jasminoides. Accordingly, G.
jasminoides is used not only as an important traditional medicine, but
also is applied in many other fields, such as the food, textile and che-
mical industries.
According to the relevant information, the previous literature only
reported a single compound or chemical components and biological
activities of G. jasminoides (Xiao et al., 2016). Therefore, a compre-
hensive review is necessary to advance multiple studies on G. jasmi-
noides. Here, we review the results of diverse studies of G. jasminoides
that have been published in recent years. First, we describe the bota-
nical description and ethnopharmacology of G. jasminoides. Then, we
discuss the chemical ingredients and their bioactive effects and safety.
Most importantly, we highlight the industrial applications of G. jasmi-
noides as a natural resource, including its functions as an outstanding
pigment and potent crosslinking drug. Finally, perspectives on future
possible directions for G. jasminoides are briefly discussed. We hope that
this review article will provide a better understanding of G. jasminoides
and its properties for the development of useful applications.
2. Botanical description and traditional uses
2.1. Botanical description
G. jasminoides (also named “Zhizi” in China, “Sanshishi” in Japan,

2
L. Chen, et al.
and “Cape Jasmine”in Korea), is a popular shrub in the Rubiaceae fa-
mily. According to “The Plant List”, G. jasminoides is the only accepted
name for the plant, with other 46 synonyms. The synonyms with the
highest confidence levels include Gardenia angustifolia Lodd., Gardenia
grandiflora Lour., Gardenia longisepala (Masam.) Masam., Gardenia
maruba Siebold ex Blume, Gardenia pictorum Hassk., Gardenia radicans
Thunb., Genipa florida (L.) Baill., Genipa grandiflora (Lour.) Baill.,
Genipa radicans (Thunb.) Baill., and Jasminum capense Mill. (www.
theplantlist.org). Its native range is China, India, Japan and Thailand. It
was subsequently introduced into Korea. This folk plant is mainly dis-
tributed in the tropical and subtropical regions of the world. The first
description of its distribution is in Commentaries on the Illustrations
(Song Dynasty, A.D. 960–1279). China and other countries, including
Japan, Korea, India and North America, have abundant plant resources
(http://plantsoftheworldonline.org). In China, the wild resources is
present in at least 16 provinces, particularly in provinces south of the
Yangtze River (http://frps.iplant.cn/frps/Gardenia%20jasminoides).
As shown in Fig. 1, G. jasminoides is an evergreen shrub with greyish
bark and dark green shiny leaves with distinct veins. This shrub grows
2–6 feet in height. The leaves grow in opposite directions, with a long
oval shape, lustrous appearance, and length of 2–4 inches. The white
and aromatic flowers usually bloom in spring and summer, which are
either single or double and up to 4 inches in diameter (http://blog.sina.
com.cn/s/blog_48bc561a0102vx21.html). With its splendent evergreen
leaves and heavily fragrant flowers, this plant is also extensively cul-
tivated in gardens, parks and as a house plant in warm temperate and
subtropical regions.
The fruits of this plant have been traditionally used as folk medicine
for centuries in Asian countries. In addition to its uses for medicinal
purposes, it is also widely used in food and dyestuff industries (Giménez
et al., 2015). The Compendium of Materia Medica records an inter-
esting origin of the name Zhizi. Zhi (卮) is a type of drinking vessel used
in ancient China. It is shaped like Zhi, and thus this name was obtained.
Fig. 1. The whole plant (A), flower (B), fresh fruit (C), and desiccative ripe fruit (D) of Gardenia jasminoides Ellis.
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Journal of Ethnopharmacology 257 (2020) 112829
Because the plant grows on mountain slopes and hills, it was also called
Shanzhizi in ancient times, and the name is still used today (Institute of
Botany, the Chinese Academy of Sciences. Flora of China, vol. 69). The
fruits have a vibrant colour. Based on a comparative study of the an-
cient documents and the most recent Chinese Pharmacopoeia (2015
version), the fruit follows the guideline of “harvesting after frost”. In
other words, the best harvest time is from September to November
when the fruit becomes red and yellow. For most herbs, the quality is
better with a bigger grain, but in this plant, fruits are better with a thin
skin and small grain (Shan et al., 2019).
2.2. Traditional uses
2.2.1. Pharmaceutical uses
G. jasminoides is listed as a “Middle grade” drug in Shen Nong's
Herbal (Dong Han Dynasty, A.D. 25–220), which is the earliest existing
pharmacological monograph in China. As a traditional and crucial
herbal medicine, G. jasminoides is recorded in the Chinese pharmaco-
poeia, with the effects of discharging fire, eliminating vexation, redu-
cing fever and causing diuresis, and cooling blood to remove aptho-
gentic heat. In traditional Japanese and Korean medicine, the herb has
been well known for hundreds of years as a folk medicine that reduces
fever and treats cholagogue, gastrointestinal disturbance, diuretic and
antiphlogistic effects.
Herb processing is a traditional pharmacy technology based on TCM
theory, the medicine character, and different requirements for dispen-
sing and treatment. Currently, herb processing has been extensively
applied to change the properties, increase the efficacy and alleviate side
effects of herbal medicines. Heating is an important method performed
during processing, the degree of heating exerts a crucial effect on the
properties and activity of herbal medicines. G. jasminoides is bitter and
cold. It easy damages the spleen and stomach. According to the record
in the Treatise on Febrile Diseases, the herb has been processed in China
 L. Chen, et al.

Table 1
Some classical prescriptions associated with Gardenia jasminoides Ellis.
Preparation name Composition Formulation Traditional and clinical uses References

Zhizichi Tang Gardenia jasminoides fruit, fermented soybean Decoction Clearing heat and eliminating vexation Shang Han Lun
⟪伤寒论⟫
Yinchenhao Tang Artemisia capillaris herb, Gardenia jasminoides fruit, Rheum palmatum root Decoction Clearing away heat and dampness, used for the treatment of damp-heat Shang Han Lun
and rhizome jaundice; Now mostly used for the treatment of acute hepatitis with jaundice ⟪伤寒论⟫ http://cowork.
cintcm.com
Zhizi Dahuang Tang Gardenia jasminoides fruit, fermented soybean, Citrus aurantium fruit, Rheum Decoction Clearing heat, removing irritation and relieving constipation Jin Gui Yao Lüe
palmatum root and rhizome, Artemisia capillaris herb ⟪金匮要略⟫
Zhizi bopi Tang Gardenia jasminoides fruit, Glycyrrhiza uralensis root and rhizome, Decoction Clearing away heat and reducing damp Shang Han Lun
Phellodendron chinense cortex. ⟪伤寒论⟫
Longdan Xiegan Tang Gentiana scabra root and rhizome, Gardenia jasminoides fruit, Scutellaria Decoction and pill Removing dampness and heat of liver and gallbladder; Now used in the Yi Fang Ji Jie
baicalensis root, Clematis armandii root and rhizome, Alisma orientale treatment of the syndrome of damp-Heat accumulation in the Liver and ⟪医方集解⟫ http://cowork.
rhizome, Plantago asiatica herb, Bupleurum chinense root, Glycyrrhiza gallbladder channels associated with various emotional disorders, and cintcm.com
uralensis root and rhizome, Angelica sinensis root, Rehmannia glutinosa root chronic hepatitis
Huanglian Jiedu Tang Coptis chinensis rhizome, Scutellaria baicalensis root, Phellodendron chinense Decoction Clearing heat and detoxifying; Clinically used to treat various inflammatory Zhou Hou Bei Ji Fang
cortex, Gardenia jasminoides fruit diseases, such as gastritis, dermatitis, and aphthous stomatitis ⟪肘后备急方⟫ http://cowork.
cintcm.com
Zhizi Houpo Tang Gardenia jasminoides fruit, Magnolia officinali cortex, Citrus aurantium fruit Decoction Removing irritation and flatulence Shang Han Lun
⟪伤寒论⟫
Renshen Xiefei Tang Scutellaria baicalensis root, Gardenia jasminoides fruit, Citrus aurantium fruit, Decoction Commonly used for treatment cough, chest fullness and eliminating phlegm Xiu Zhen Fang
Panax ginseng root and rhizome, Mentha haplocalyx herb, Forsythia suspense ⟪袖珍方⟫

4
fruit, Glycyrrhiza uralensis root and rhizome, Prunus armeniaca semen, Morus
alba cortex, Rheum palmatum root and rhizome
Xiehuang San Pogostemon cablin herb, Gardenia jasminoides fruit, Glycyrrhiza uralensis root Powder Clearing away heat and reducing fire; Now used for fever and mouth sores in Xiao Er Yao Zheng ZhiJue
and rhizome, Saposhnikovia divaricata root children ⟪小儿药证直诀⟫ http://cowork.
cintcm.com
Zhizi Jinhua Wan Gardenia jasminoides fruit, Coptis chinensis rhizome, Scutellaria baicalensis Pill Clearing heat and purging fire, cooling blood and detoxification; Used for Chinese Pharmacopoeia, 2015
root, Phellodendron chinense cortex, Rheum palmatum root and rhizome, lung stomach heat, mouth sore, swollen gums, dizzy and constipation
Lonicera japonica flower, Anemarrhena asphodeloides rhizome, Trichosanthes
kirilowii root
Yueju Wan Cyperus rotundus rhizome, Ligusticum chuanxiong rhizome, Atractylodes Pill Treatment of depression and digestive system diseases Dan Xi Xin Fa
lancea rhizome, Gardenia jasminoides fruit ⟪丹溪心法⟫ http://cowork.
cintcm.com
Qinre Xiaodu San Coptis chinensis rhizome, Gardenia jasminoides fruit, Forsythia suspense fruit, Powder Clearing heat, detoxifying and swelling Wai Ke Shu Yao
Angelica sinensis root, Ligusticum chuanxiong rhizome, Rehmannia ⟪外科枢要⟫
Paeonia suffrutcosa cork, glutinosa root Lonicera japonica flower, Glycyrrhiza
uralensis root and rhizome
Qingre Xiepi San Gardenia jasminoides fruit, Coptis chinensis rhizome, Rehmannia glutinosa Powder Removing spleen-heat syndrome, Commonly used in mycotic stomatitis in Yi Zong Jin Jian
root, Scutellaria baicalensis root, Poria children ⟪医宗金鉴⟫ http://cowork.
cintcm.com
Zhiqin Qingre Heji Gardenia jasminoides fruit, Scutellaria baicalensis root, Forsythia suspensa Liquid pharmaceutical Clearing heat and detoxifying, removing wind and heat, clearing heat and Chinese Pharmacopoeia, 2015
fruit, Lophatherum gracile herb, Glycyrrhiza uralensis root and rhizome preparations detoxifying; Used for heat in san jiao meridian, fever and headache
Qinghuo Zhimai pian Andrographis paniculata herb, Gardenia jasminoides fruit, Ophiopogon tablet Removing heat and detoxifying, cooling the blood and eliminating swelling; Chinese Pharmacopoeia, 2015
japonicas root Used for sore throat, fever and toothache

The Latin names of the original plants were validated with http://mpns.kew.org/mpns-portal/or www.theplantlist.org.
Journal of Ethnopharmacology 257 (2020) 112829
 Table 2
Chemical constituents isolated from Gardenia jasminoides Ellis.
No. Compound Molecular formula Appearance herb materials Source Reference
L. Chen, et al.

Flavonoids
1 Rutin C27H30O16 Yellow powder Leaves 95% methanol extract Uddin et al. (2014);
Fruits 95% ethanol extract Wang et al. (2016)
2 Isoquercitrin C21H20O12 Needle yellow crystal Fruits 95% ethanol extract Wang et al. (2016)
3 Hyperoside C21H20O12 Needle pale yellow crystal Fruits 95% ethanol extract Wang et al. (2016)
4 Nicotiflorin C27H30O15 Fruits 95% ethanol extract Wang et al. (2016)
5 Genistein C15H10O5 Off white powder Fruits 95% ethanol extract Wang et al. (2016)
6 5,7,3’,4’-tetrahydroxy-6, 8-dimethoxy flavone C17H14O8 Fruits 95% ethanol extract Wang et al. (2016)
7 5,7,3′,5′-tetrahydroxy-6, 4′-dimethoxy flavone C17H14O8 yellowish amorphous powder Flower 95% ethanol extract Song et al. (2013)
8 Quercetin C15H10O7 yellowish amorphous powder Flower 95% ethanol extract Song et al. (2013);
Leaves fruits 95% methanol extract Uddin et al. (2014);
95% ethanol extract Wang et al. (2016)
9 4’,5,6,7-tetrahydroxy-3,3’,5’-trimethoxyflavone C15H10O7 Fruits 95% ethanol extract Wang et al. (2016)
10 5,7,3′-trihydroxy- 6, 4′,5′-trimethoxyflavone C18H16O8 yellowish amorphous powder Flower 95% ethanol extract Song et al. (2013)
11 Luteolin-7-O-β-D-glucopyranoside C21H20O11 Fruits 60% ethanol extract Yang et al. (2013)
12 Catechin C15H14O6 White needle Leaves 95% methanol extract Uddin et al. (2014)
13 Kaempferol C15H10O6 Yellow powder Flower 95% ethanol extract Song et al. (2013)
14 3-hydroxy-urs-12-ene-11-ketone C30H48O2 Needle white crystal Fruits 80% ethanol extract Luo et al. (2014)
15 5,4′-dihydroxyl-7,3′,5′-trimethoxyflavone C18H16O7 Pale yellow powder Fruits 80% ethanol extract Luo et al. (2014)
16 5,7,3′,4′,5′-pentame-thoxyflavone C20H20O7 Pale yellow powder Fruits 80% ethanol extract Luo et al. (2014)
17 3,5,6,4′-tetrahydroxy-3′,5′-dimethoxyflavone C17H14O8 Yellow powder Fruits 80% ethanol extract Luo et al. (2014)
Iridoid glycosides
18 Geniposide C17H24O11 White crystal Fruits 50% methanol extract Oshima et al. (1988)
19 Geniposidic acid C16H22O10 White crystal Fruits 50% methanol extract Oshima et al. (1988)
20 Gardenoside C17H24O11 White crystal Fruits 50%methanol extract Oshima et al. (1988)

5
21 Genipin-1-β-gentiobioside C23H34O15 Fruits 50%methanol extract Oshima et al. (1988)
22 Deacetyl-asperulosidic acid methyl ester C17H24O11 Fruits 50% ethanol extract Zhou et al. (2007)
23 Scandoside methyl ester C17H24O11 Fruits 50% ethanol extract Zhou et al. (2007)
24 10-O-(4″-O-methylsuccinoyl)geniposide C22H30O13 Amorphous solid Fruits methanol extract Akihisa et al. (2012)
25 Genipin C11H14O5 White powder Fruits 60% ethanol extracts Peng et al. (2013)
26 6β-hydroxygenipin C11H14O6 Fruits 60% ethanol extracts Peng et al. (2013)
27 Genameside D C23H34O15 Fruits 60% ethanol extracts Peng et al. (2013)
28 Genameside C C23H34O15 Fruits 60% ethanol extracts Peng et al. (2013)
29 6″-O-trans-caffeoylgenipin gentiobioside C32H40O18 yellowish amorphous powder Fruits 60% ethanol extracts Peng et al. (2013)
30 Genipin 1-O-β-D-apiofuranosyl (1 → 6)-β-D-glucopyranoside C22H32O14 White amorphous powder Fruits 60% ethanol extracts Peng et al. (2013)
31 Genipin 1-O-α-D-xylopyranosyl (1 → 6)-β-D-glucopyranoside C22H32O14 White amorphous powder Fruits 60% ethanol extracts Peng et al. (2013)
32 Ixoroside C16H24O9 Fruits methanol extract Chang et al. (2005)
33 6″-O-trans-feruloylgenipin gentiobioside C33H42O18 yellowish amorphous powder Fruits 80% ethanol extract Li et al. (2013)
34 2′-O-trans-p-coumaroylgardoside C25H28O12 Flowers 95% ethanol extract Zhang et al. (2017a)
35 7α,8β-epoxy-8α-dihydrogeniposide C17H24O11 Fruits 95% ethanol extract Wang et al. (2016)
36 8-epiapodantheroside C17H24O10 Fruits 95% ethanol extract Wang et al. (2016)
37 2′-O-trans-caffeoylgardoside C25H28O13 yellowish amorphous powder Fruits 80% ethanol extract Li et al. (2013)
38 Jasmigeniposide A C33H40O18 yellowish amorphous powder Fruits 80% ethanol extract Li et al. (2013)
39 Jasmigeniposide B C28H36O14 White amorphous powder Fruits 80% ethanol extract Li et al. (2013)
40 6′-O-trans-sinapoyl gardoside C27H32O14 Fruits 95% ethanol extract Wang et al. (2016)
41 6′-O-trans-coumaroyl geniposide C26H30O12 Fruits 95% ethanol extract Wang et al. (2016)
42 Deacetylasperulosidic acid C16H22O11 Fruits 50% ethanol extract Zhou et al. (2010)
43 Gardoside C16H22O10 Fruits 50% ethanol extract Zhou et al. (2010)
44 Shanzhisidemethyl ester C17H26O11 Fruits 50% ethanol extract Zhou et al. (2010)
45 Genipin 1-O-β-D-isomaltoside C23H34O15 White amorphous powder Fruits ethanol extract Chen et al. (2009)
46 Genipin 1,10-di-O-β-D-glucopyranoside C23H34O15 White amorphous powder Fruits ethanol extract Chen et al. (2009)
47 6-O-methyldeacetylasperulosidic acid methyl ester C18H26O11 Fruits ethanol extract Chen et al. (2009)
48 6″-O-trans-sinapoylgenipin gentiobioside C34H44O19 yellowish amorphous powder Fruits 60% ethanol extract Yu et al. (2009)
49 6″-O-trans-p-coumaroylgenipin gentiobioside C32H40O17 yellowish amorphous powder Fruits 60% ethanol extract Yu et al. (2009)
(continued on next page)
Journal of Ethnopharmacology 257 (2020) 112829
 Table 2 (continued)

No. Compound Molecular formula Appearance herb materials Source Reference

L. Chen, et al.

50 6″-O-trans-cinnamoylgenipin gentiobioside C32H40O16 Pale yellow gum Fruits 60% ethanol extract Yu et al. (2009)
51 6′-O-trans-p-coumaroylgeniposide C26H30O12 Pale yellow gum Fruits 60% ethanol extract Yu et al. (2009)
52 6′-O-trans-p-coumaroylgeniposidic acid C25H28O12 Pale brown, amorphous powder Fruits 60% ethanol extract Yu et al. (2009)
53 10-O-succinoyl geniposide C21H28O13 yellowish amorphous powder Fruits 60% ethanol extract Yu et al. (2009)
54 6′-O-acetylgeniposide C19H26O11 yellowish amorphous powder Fruits 60% ethanol extract Yu et al. (2009)
55 6′-trans-sinapoylgeniposide C29H36O13 Fruits 60% ethanol extract Yu et al. (2009)
56 10-O-acetylgeniposide C19H26O11 yellowish amorphous powder Fruits 60% ethanol extract Yu et al. (2009)
57 2′-O-trans-coumaroylshanzhiside C25H30O13 Transparent colourless gum Flowers 95% ethanol extract Zhang et al. (2017a)
58 6′-O-trans-coumaroylshanzhiside C25H30O13 Transparent colourless gum Flowers 95% ethanol extract Zhang et al. (2017a)
59 8α-butylgardenoside B C21H32O11 Transparent colourless gum Flowers 95% ethanol extract Zhang et al. (2017a)
60 6α-methoxygenipin C12H16O6 Transparent colourless gum Flowers 95% ethanol extract Zhang et al. (2017a)
61 10-O-trans-sinapoylgeniposide C27H34O13 yellowish amorphous powder Fruits 60% ethanol extract Yu et al. (2012)
62 Gardaloside C16H22O9 Pale yellowish oil Fruits acetone and methanol extract Chang et al. (2005)
63 Shanzhiside C16H24O11 Fruits acetone and methanol extract Chang et al. (2005)
64 7β-hydroxysplendoside C17H24O11 Colourless gum Fruits acetone and methanol extract Chang et al. (2005)
65 Mussaenosidic acid C16H24O10 Fruits acetone and methanol extract Chang et al. (2005)
Yellow pigment
66 Crocin-1 C44H64O24 Red amorphous powder Fruits flowers 70%methanol extract Cai et al. (2015a); Song et al. (2013)
95% ethanol extract
67 Crocin-2 C38H54O19 Red amorphous powder Fruits 70%methanol extract Cai et al. (2015a)
68 Crocin-3 C44H64O24 Red amorphous powder Fruits 70%methanol extract Cai et al. (2015a)
69 Crocin-4 C26H34O9 Red amorphous powder Fruits 70%methanol extract Cai et al. (2015a)
70 Crocetin C20H24O4 Red amorphous powder Fruits 70%methanol extract Cai et al. (2015a)
Peng et al. (2013)
71 Neocrocins A C44H64O24 Red amorphous powder Fruits 50% ethanol extract Uekusa et al. (2007)
72 Neocrocins B C48H61O22 Red amorphous powder Fruits 60% ethanol extract Ni et al. (2017)

6
73 Neocrocins C C48H61O22 Red amorphous powder Fruits 60% ethanol extract Ni et al. (2017)
74 Neocrocins D C48H60O22 Red amorphous powder Fruits 60% ethanol extract Ni et al. (2017)
75 Neocrocins E C48H60O22 Red amorphous powder Fruits 60% ethanol extract Ni et al. (2017)
76 Neocrocins F C43H54O18 Red amorphous powder Fruits 60% ethanol extract Ni et al. (2017)
77 Neocrocins G C55H75O28 Red amorphous powder Fruits 60% ethanol extract Ni et al. (2017)
78 Neocrocins H C34H48O14 Red amorphous powder Fruits 60% ethanol extract Ni et al. (2017)
79 Neocrocins I C32H44O13 Red amorphous powder Fruits 60% ethanol extract Ni et al. (2017)
80 Neocrocins J C31H42O13 Red amorphous powder Fruits 60% ethanol extract Ni et al. (2017)
81 13-cis-crocetin-8′-O-β-D-gentiobioside C32H44O14 Red amorphous powder Fruits 60% ethanol extract Ni et al. (2017)
Monoterpenoids
82 Jasminodiol C10H16O3 Colourless oil Fruits methanol extract Chen et al. (2008)
83 Jasminoside H C22H36O12 White amorphous powder Fruits methanol extract Chen et al. (2008)
84 6′-O-sinapoyljasminoside A C27H37O11 White amorphous powder Fruits methanol extract Chen et al. (2008)
85 6′-O-sinapoyljasminoside C C27H35O11 White amorphous powder Fruits methanol extract Chen et al. (2008)
86 Jasminoside I C22H36O12 White amorphous powder Fruits methanol extract Chen et al. (2008)
87 Epijasminoside A C16H26O7 Fruits methanol extract Chen et al. (2008)
88 Crocusatin-C C10H16O2 Fruits methanol extract Chen et al. (2008)
89 10-(6-O-trans-sinapoylglucopyranosyl)gardendiol C27H34O13 Brown amorphous powder Fruits 60% ethanol extract Yu et al. (2009)
90 11-(6-O-trans-sinapoylglucopyranosyl)gardendiol C27H34O13 Brown amorphous powder Fruits 60% ethanol extract Yu et al. (2009)
91 Jasminoside Q C22H36O12 Amorphous solid Fruits methanol extract Akihisa et al. (2012)
92 Jasminoside R C22H34O12 White amorphous powder Fruits 60% ethanol extract Peng et al. (2013)
93 Jasminoside S C22H36O12 White amorphous powder Fruits 60% ethanol extract Peng et al. (2013)
94 Jasminoside T C21H34O11 Yellowish oil Fruits 60% ethanol extract Peng et al. (2013)
95 Jasminoside A C17H27O9 Fruits methanol extract Chen et al. (2008)
96 Jasminoside B C16H26O8 Fruits methanol extract Chen et al. (2008)
97 Jasminoside C C16H27O7 Fruits methanol extract Machida et al. (2000)
98 Jasminoside D C16H26O8 Fruits methanol extract Machida et al. (2000)
99 Jasminoside E C17H27O9 Fruits methanol extract Machida et al. (2000)
100 Jasminoside F C16H26O8 Amorphous powder Fruits methanol extract Machida et al. (2000)
Journal of Ethnopharmacology 257 (2020) 112829

(continued on next page)

 Table 2 (continued)

No. Compound Molecular formula Appearance herb materials Source Reference

L. Chen, et al.

101 Jasminoside G C16H26O8 Pale yellowish oil Fruits acetone and methanol extract Chang et al. (2005)
102 Gardenate A C12H18O6 Amorphous powder Fruits methanol extract Machida et al. (2000)
103 2-hydroxyethyl gardenamide A C13H17NO5 Amorphous powder Fruits methanol extract Machida et al. (2000)
104 6′-O-trans-sinapoyl jasminoside L C27H36O12 Fruits 95% ethanol extract Wang et al. (2016)
105 Gadenone C12H20O3 Fruits 95% ethanol extract Wang et al. (2016)
106 (R)-linalyl-6-O-α-l-arabinopyranosyl-β-D-glucopyranoside C21H36O10 Fruits 95% ethanol extract Wang et al. (2016)
107 bornyl-6-O-β-Dxylopyranosyl-β-D-glucopyranoside C21H36O10 Fruits 95% ethanol extract Wang et al. (2016)
sesquiterpenoids
108 (1R,7R,8S,10R)-7,8,11-trihydroxyguai-4-en-3-one 8-O-β-D-glucopyranoside C21H34O9 Amorphous powder Fruits methanol extract Machida et al. (2000)
109 (1R,7R,10S)-11-O-β-D-glucopyranosyl-4-guaien-3-one C21H34O7 Yellow gum Fruits 60% ethanol extract Yu et al. (2011)
110 (1R,7R,10S)-7-hydroxy-11-O-β-D-glucopyranosyl-4-guaien-3-one C21H34O8 Yellow gum Fruits 60% ethanol extract Yu et al. (2011)
Triterpenes
111 Ursolic acid C30H48O3 Fruits 95% ethanol extract Wang et al. (2016);
60% ethanol extract Yang et al. (2013)
112 Oleanolic acid C30H48O3 Fruits 95% ethanol extract Wang et al. (2016);
60% ethanol extract Yang et al. (2013)
113 Dikamaliartanes A C30H44O6 Fruits 95% ethanol extract Wang et al. (2016)
114 Secaubrytriol C30H50O5 Fruits 95% ethanol extract Wang et al. (2016)
115 27-O-p-(E)-coumaroyloxyursolic acid C39H54O6 Fruits 95% ethanol extract Wang et al. (2016)
116 Gardeniside A C37H56O10 Amorphous solid Roots 70% ethanol extract Wang et al. (2012a)
117 Gardeniside B C37H58O10 White needle Roots 70% ethanol extract Wang et al. (2012a)
118 Gardeniside C C43H68O15 White needle Roots 70% ethanol extract Wang et al. (2012a)
119 Oleanolic acid 3-O-β-D-glucuronopyranoside-6′-O-methly ester C37H58O9 White amorphous powder Roots 70% ethanol extract Wang et al. (2012a)
120 Oleanolic acid 3-O-β-D-glucuropyranoside C36H56O9 White amorphous powder Roots 70% ethanol extract Wang et al. (2012a)
121 Hederagenin 3-O-β-D-glucuronopyranoside-6′-O-methly ester C37H58O10 White amorphous powder Roots 70% ethanol extract Wang et al. (2012a)
122 Chikusetsusaponin IVa methyl ester C43H68O14 Needle white crystal Roots 70% ethanol extract Wang et al. (2012a)

7
123 Chikusetsusaponin C42H66O14 Roots 70% ethanol extract Wang et al. (2012a)
124 Chikusetsusaponin IVa butyl ester C46H74O14 Roots 70% ethanol extract Wang et al. (2012a)
125 Siaresinolic acid 28-O-β-D-glucopyranosyl ester C36H58O9 Amorphous powder Roots 70% ethanol extract Wang et al. (2012a)
126 β-sitosterol C29H50O White powder Flowers 95% ethanol extract Song et al. (2013)
127 Chikusetsu saponin Ⅳa C42H66O14 roots and rhizomes Xiao et al. (2017)
Organic acids and their derivatives
128 4-O-β-D-(6′-sinapoyl)glucopyranoside C25H27O13 Fruits ethyl acetate extract Kim et al. (2006)
129 Methyl 5-O-caffeoyl-3-O-sinapoylquinate C28H30O13 Fruits ethyl acetate extract Kim et al. (2006)
130 Ethyl 5-O-caffeoyl-3-O-sinapoylquinate C29H32O13 Fruits ethyl acetate extract Kim et al. (2006)
131 Methyl 5-O-caffeoyl-4-O-sinapoylquinate C28H30O13 Fruits ethyl acetate extract Kim et al. (2006)
132 Ethyl 5-O-caffeoyl-4-O-sinapoylquinate C29H32O13 Fruits ethyl acetate extract Kim et al. (2006)
133 Methyl 3,5-di-O-caffeoyl-4-O-(3-hydroxy-3-methyl)glutaroylquinate C32H35O16 Fruits ethyl acetate extract Kim et al. (2006)
134 3,5-dicaffeoylquinic acid C25H24O12 Fruits ethyl acetate extract Kim et al. (2006)
135 4,5-dicaffeoylquinic acid C25H24O12 Fruits ethyl acetate extract Kim et al. (2006)
136 Caffeic acid C9H8O4 Fruits ethyl acetate extract Kim et al. (2006)
137 Ethyl 5-O-caffeoylquinate C18H22O9 Fruits ethyl acetate extract Kim et al. (2006)
138 3,4-dihydroxybenzoic acid C7H6O4 Fruits ethyl acetate extract Kim et al. (2006)
139 3,4-dicaffeoylquinic acid C25H24O12 Fruits 95% ethanol extract Wang et al. (2016)
140 3,5-D-O-caffeoyl-4-O-(3-hydroxy-3-methyl)-glutaroylquinic acid C31H32O16 Fruits 95% ethanol extract Wang et al. (2016)
141 5-O-caffeoyl-4-O-sinapoylquinic acid C27H28O13 Fruits 95% ethanol extract Wang et al. (2016)
142 (+)-lyoniresinol-3a-O-b-glucopyranoside C28H38O13 Fruits 95% ethanol extract Wang et al. (2016)
143 3-O-caffeoyl-4-O-sinapoylquinic acid C27H28O13 Pale yellow amorphous powder Fruits 50% aqueous acetone extract Nishizawa et al. (1987)
144 3,4-dicaffeoyl-5-(3-hydroxy-3-methylglutaroyl) quinic acid C31H32O16 Amorphous powder Fruits 50% methanol extract Bergonzi et al. (2012)
Nishizawa and Fujimoto (1986)
145 Caffeoyl sinapoylquinic acid C27H28O13 Fruits 50% methanol extract Bergonzi et al. (2012)
146 Shikimic acid C7H10O5 White powder Fruits 80% ethanol extract Luo et al. (2014)
147 1,2,4-benzenetriol C6H6O3 Colourless crystalline solid Fruits 80% ethanol extract Luo et al. (2014)
148 3,4-dimethoxybenzoic acid C9H10O4 White crystalline Powder Fruits 80% ethanol extract Luo et al. (2014)
149 Dibutyl phthalate C16H22O4 Colourless liquid Fruits 80% ethanol extract Luo et al. (2014)
Journal of Ethnopharmacology 257 (2020) 112829

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L. Chen, et al. Journal of Ethnopharmacology 257 (2020) 112829

since the Han Dynasty. More than 10 different processing methods were
used in ancient history. In fact, only three processing methods are
continuously used now and have become mainstream, including stir-
baked G. jasminoides, roasted G. jasminoides and ginger G. jasminoides.
This herb is usually stir-baked in a hot pot with moderate heat until it

Zhang et al. (2017a)

becomes yellowish-brown or dark brown (Pharmacopoeia of People's
Uddin et al. (2014)

Wang et al. (2016)

Yang et al. (2013)

Yang et al. (2013)
Song et al. (2013)
Song et al. (2013)
Song et al. (2013)
Song et al. (2013)
Song et al. (2013)
Song et al. (2013)

Song et al. (2013)

Song et al. (2013)
Republic of China, 2015). Remarkably, G. jasminoides exhibits more
moderate changes in nature after being roasted with ginger juice, which
Reference

possesses pungent and lukewarm properties. At the same time, the ef-
fects on preventing vomiting are improved. This distinction between
the raw and roasted herb is attributed to the changes in the internal
essential components (Zhang et al., 2013a, b).
The prescriptions are the main form of traditional herb applied in
clinics. By combining several herbs at different dosages, the therapeutic
methanol extract

functions are obviously intensified, and the side effects are decreased.
ethanol extract
ethanol extract
ethanol extract
ethanol extract
ethanol extract
ethanol extract
ethanol extract

extract
extract
extract
extract
extract

G. jasminoides has been applied in more than 281 traditional Chinese

medicinal preparations, and more than 2332 classic prescriptions for
ethanol
ethanol
ethanol
ethanol
ethanol

the treatment of illness (http://dbcenter.cintcm.com/channel-link.jsp?

Source

channelId=10772). Some classical prescriptions containing this herb

95%
95%
95%
95%
95%
95%
95%
95%

95%
95%
60%
60%
95%

are listed in Table 1. More importantly, this herbal medicine has a bitter
flavour, is cold in nature and targets the heart, lung and San Jiao
meridians. In the theory of traditional Chinese medicine (TCM), “cold
and bitter” herbs remarkably remove ‘‘heat’’ and “dampness”. Thus, it is
herb materials

commonly used to treat jaundice, vexation, insomnia, and various

Flowers
Flowers
Flowers
Flowers
Flowers
Flowers

Flowers
Flowers

Flowers

clinical symptoms associated with damp heat. Huanglian Jiedu Tang

Leaves

Fruits

Fruits
Fruits

(also named Hwangryun-Hae-Dok Decotion in Japan) was initially de-

scribed in Wang Tao's “Wai Tai Mi Yao” (Tang Dynasty, A.D.752) two
thousand years ago. This formula is the most famous and effective
yellowish amorphous powder
yellowish amorphous powder

among all formulas designed to clear heat. It consists of the following

White amorphous powder

four medicinal herbs: Coptis chinensis rhizome, Scutellaria baicalensis

Needle yellow crystal

root, Phellodendron chinense cortex and Gardenia jasminoides fruit (in a

Off white powder

weight ratio of 3:2:2:3). This decoction has been extensively used to

Colourless liquid

Orange powder
White powder
White powder
White powder
White powder

White powder

remove ‘‘heat’’ and ‘‘poison’’ as a treatment for various ailments, such as

White flakes
Appearance

hepatitis and gastric ulcers.

Yinchenhao Tang was initially documented in Shang Han Lun for
treating damp heat jaundice (http://cowork.cintcm.com/engine/
search?channelid=37595). This decoction is most frequently men-
Molecular formula

tioned as an anti-inflammatory, antipyretic, and choleretic agent for

liver disorders and jaundice in Taiwan and China (Lee et al., 2009b;
Hsueh and Tsai, 2018). More importantly, Yinchenhao Tang (Inchinko-
C22H32O13
C22H32O13
C30H48O4
C30H48O4
C30H48O5
C18H36O2
C16H32O2
C18H34O2
C16H18O9

C15H10O5
C16H12O5

C16H24O8
C7H6O5

to or TJ-135 in Japan) has also long been used in traditional Japanese

medicine as a treatment for acute liver failure with prolonged jaundice
and severe acute hepatitis of unknown aetiology (Arai et al., 2004;
Ohwada et al., 2009). According to the data available, Dahuang Xiaoshi
Tang, Longdan Xiegan Tang, Zhizi Dahuang Tang, Zhizi Baipi Tang are
2-methyl-L-erythritol-4-O-(6-O-trans-sinapoyl)-β-D-glucopyranoside
2-methyl-L-erythritol-1-O-(6-O-trans-sinapoyl)-β-D-glucopyranoside

also extensively used to treat different types of liver disorders in clinical

practice in China and other Asian countries.
Another famous TCM formula is Zhizichi Tang; it consists of G.
jasminoides fruit and fermented soybean. This prescription is commonly
4-methoxybenzenepropanol-3-O-β-D-glucopyranoside

used to treat febrile diseases with restlessness in China. According to

TCM theories, a special combination consisting of two or three herbs is
often described as an herb pair (named as “yaodui” in China). These
3β,19α,23-trihydroxy-urs-12-en-28-oic acid

herbs have similar or opposite properties and functions to exert in-

3β,19α-dihydroxy-urs-12-en-28-oic acid
3β,23-dihydroxy-urs-12-en-28-oic acid

creased or decreased pharmacological activities. An herb pair usually

serves as the fundamental building block and possesses unique clinical
importance in a typical formula (Wang et al., 2012b). The gardenia-
fermented soybean herb pair is extensively used in TCM formulas.
Therefore, numerous classical formulas, including Zhizi-Gancaochi
Tang, Zhizi-Shengjiangchi Tang, Zhishi-Zhizichi Tang and Zhizi-Shigao-
Chlorogenic acid

Xiangchi Tang, have been prepared to treat febrile diseases. Some

Palmitic acid
Table 2 (continued)

classical prescriptions associated with G. jasminoides are listed in

Stearic acid
Compound

Gallic acid

Oleic acid

Physcion

Table 1. In addition, other parts of this plant also possess potent ac-
Emodin

tivities. The root is customarily used to treat nephritis, oedema and

icterohepatitis in southern China. The flower is also used as a food
others

ingredient or a dietary supplement, which is mixed in tea or other

150
151
152
153
154
155
156
157

158
159
160
161
162
No.

healthy foods (Jiang et al., 2004).

8
L. Chen, et al.
2.2.2. Pigment uses
In addition, G. jasminoides has a long history of being used as a
dyestuff by various cultures in Asian countries. The colourant is usually
referred to as gardenia yellow. It is a member of the natural carotenoid
family. Compared with other carotenoids, gardenia yellow has been
characterized as displaying low allergenicity and more stable chemical
properties. As a superior natural colouring material, gardenia yellow
exhibits excellent water solubility and may provide health benefits due
to its strong antioxidant and nontoxic nature (Pham et al., 2000). Ac-
cordingly, it has been extensively used in East Asian countries to colour
soft drinks, pastries, candy and noodles. However, it is not yet per-
mitted as a food colour additive in the European Union or the USA.
3. Phytochemistry
Traditional herbs possess multiple activities and excellent ther-
apeutic functions that are attributed to abundant chemical constituents.
To date, approximately 162 phytochemicals have been isolated and
identified from G. jasminoides. Previous studies of G. jasminoides have
identified the presence of chemical constituents such as flavonoids
(1–17), iridoid glycosides (18–65), gardenia yellow pigment (66–81),
monoterpenoids (82–107), sesquiterpenoid (108–110), triterpenes
(111–127), organic acids and their derivatives (128–157), and other
compounds (158–162). The phytochemicals present in G. jasminoides
are described in Table 2. The structures of compounds isolated from G.
jasminoides are illustrated in Figs. 2–9. Among these compounds, iridoid
glycosides and yellow pigment are the most abundant and main
bioactive components in G. jasminoides.
3.1. Flavonoids
To date, over twenty-two flavonoids have been isolated and iden-
tified from G. jasminoides. Compound 1 was isolated from the leaf and
fruit (Uddin et al., 2014; Wang et al., 2016). In 2013, four flavonoids,
including compounds 7, 8, 10 and 13, were obtained from the flower
(Song et al., 2013). In 2014, Luo et al. isolated and identified four
flavonoids (14, 15, 16 and 17) using nuclear magnetic resonance
(NMR), ESI-MS, and electron ionization MS (Luo et al., 2014). Fur-
thermore, compound 11 significantly inhibits nitric oxide (NO) pro-
duction in lipopolysaccharide (LPS)-initiated macrophages (Yang et al.,
2013). Compound 12 has been shown to possess antioxidant activity
(Uddin et al., 2014).
3.2. Iridoid glycosides
Iridoid glycosides are characteristic ingredients of G. jasminoides
and presumed to be responsible for the pharmacological activities of
this herbal medicine and its preparations. Forty-eight iridoid glycosides
(18–65) have been separated and identified from G. jasminoides
(Oshima et al., 1988; Zhou et al., 2007, 2010; Akihisa et al., 2012; Peng
et al., 2013; Chang et al., 2005; Li et al., 2013; Wang et al., 2016; Chen
et al., 2009; Yu et al., 2009, 2012; Zhang et al., 2017a). The names of
these iridoid glycosides are listed in Table 2 and the chemical structures
are shown in Fig. 3. Compound 38 is a rare caffeoylquinic ester acylated
at C-10 of geniposide, and compound 39 was discovered as the first bis-
genipin monosaccharide. The sugar moiety in the structure of com-
pound 45 is b-isomaltose, and a structure containing this disaccharide
has rarely been reported in plant secondary metabolites to date.
The iridoid glycosides derived from G. jasminoides have been shown
to have wide spectrum of pharmacological activities in vitro and in vivo,
such as anti-inflammatory activity, neuroprotective functions, hepato-
protective activity, and antidepressant activity (Chen et al., 2014; Zhao
et al., 2017; Lian et al., 2010; Cai et al., 2015a). In addition, compounds
22, 32 and 63 significantly inhibit IL-2 secretion by human T cells
activated with 50 μg/mL CD28. Compounds 32 and 63, which possess a
hydroxyl moiety at C-8, show more potent activity than compound 22.
9
Journal of Ethnopharmacology 257 (2020) 112829
The presence of a hydroxyl functionality at the C-8 position in iridoid
glucosides is probably responsible for increasing their inhibitory effects.
Compounds 51, 53 and 54 improve the short-term memory capacity of
an Aβ transgenic Drosophila model. Compound 24 inhibits melano-
genesis in α-melanocyte-stimulated B16 melanoma cells.
3.3. Gardenia yellow pigment
Gardenia yellow pigment is natural rare colourant that is mainly
extracted and separated from G. jasminoides. It is generally a mixture
consisting of carotenoids and related compounds (Chen et al., 2011).
Recently, many researchers have focused on these components due to
their biological characters (Lee et al., 2005). Crocin 1 66, crocin 2 67,
crocin 3 68, crocin 4 69 and crocetin 70 were subsequently isolated and
identified. Compounds 66, 69 and 70 exist as two cis-trans-isomers (Cai
et al., 2015a). Compound 66 was also isolated from the flowers (Song
et al., 2013). In addition, neocrocins A-J 71–80 and 13-cis-crocetin-8′-
O-β-D-gentiobioside 81 were initially isolated and identified using
NMR, HPLC and high-speed countercurrent chromatography techniques
(Uekusa et al., 2007; Ni et al., 2017). The chemical structures of these
yellow pigment are shown in Fig. 4.
3.4. Monoterpenoids
To date, approximately twenty-six monoterpenoids (82–107) have
been isolated and identified from G. jasminoides fruit (Chen et al., 2008;
Yu et al., 2009; Akihisa et al., 2012; Peng et al., 2013; Wang et al.,
2016; Machida et al., 2000). Their names are listed in Table 2 and the
chemical structures of these monoterpenoids are shown in Fig. 5.
Compounds 82–86 are five new pyronane-type monocyclic mono-
terpenoids that were isolated from the fruit of G. jasminoides for the first
time in 2008. In addition, compound 82 also inhibits tyrosinase ac-
tivity.
3.5. Sesquiterpenoids
According to the documents, three new guaiane-type sesquiterpe-
noid glucosides, including (1R,7R,8S,10R)-7,8,11-trihydroxyguai-4-en-
3-one8-O-β-D-glucopyranoside 108, (1R,7R,10S)-11-O-β-D-glucopyr-
anosyl-4-guaien-3-one 109 and (1R,7R,10S)-7-hydroxy-11-O-β-D-glu-
copyranosyl-4-guaien-3-one 110, were successfully isolated and iden-
tified from G. jasminoides fruits (Machida et al., 2000; Yu et al., 2011).
The chemical structures of these sesquiterpenoids are shown in Fig. 6.
3.6. Triterpenes
Seventeen triterpenes, including ursolic acid 111, oleanolic acid
112, dikamaliartanes A 113, secaubrytriol 114, 27-O-p-(E)-coumar-
oyloxyursolic acid 115, gardeniside A 116, gardeniside B 117, gar-
deniside C 118, oleanolic acid 3-O-β-D-glucuronopyranoside-6′-O-
methly ester 119, oleanolic acid 3-O-β-D-glucuropyranoside 120, he-
deragenin-3-O-β-D-glucuronopyranoside-6′-O-methly ester 121, chiku-
setsusaponin IVa methyl ester 122, chikusetsusaponin 123, chiku-
setsusaponin IVa butyl ester 124, siaresinolic acid 28-O-β-d-
glucopyranosyl ester 125 (Wang et al., 2012a), β-sitosterol 126 (Song
et al., 2013) and chikusetsusaponin IVa 127 (Xiao et al., 2017), were
isolated from the fruits, roots and flowers of G. jasminoides. The che-
mical structures of these triterpenes are shown in Fig. 7. Ten com-
pounds (116–125) were isolated from the root of this plant. Compound
127 was isolated from the roots and rhizomes of G. jasminoides. Com-
pounds 116–118 represent new oleanane-type triterpene saponins. In
addition, six compounds (116, 119–122, and 124) induced cytotoxicity
in four tumour cell lines, including human cervical cancer cells, human
malignant melanoma cells (A375-S2), human breast cancer cells (MCF-
7) and human lung carcinoma cells (A549).
L. Chen, et al. Journal of Ethnopharmacology 257 (2020) 112829

Fig. 2. The chemical structures of flavonoids isolated from G. jasminoides.

10
L. Chen, et al. Journal of Ethnopharmacology 257 (2020) 112829

Fig. 3. The chemical structures of iridoid glycosides isolated from G. jasminoides.

3.7. Organic acids and their derivatives
The organic acids present in G. jasminoides are mainly classified into
two types: phenolic acids and fatty acids. Currently, approximately
thirty organic acids and their derivatives have been obtained from this
herb, including 4-O-β-D-(6′-sinapoyl)glucopyranoside 128, methyl 5-O-
caffeoyl-3-O-sinapoylquinate 129, ethyl 5-O-caffeoyl-3-O-sinapoylqui-
nate 130, methyl 5-O-caffeoyl-4-O-sinapoylquinate 131, ethyl 5-O-
caffeoyl-4-O-sinapoylquinate 132, methyl 3,5-di-O-caffeoyl-4-O-(3-hy-
droxy-3-methyl)glutaroylquinate 133, 3,5-dicaffeoylquinic acid 134,
4,5-dicaffeoylquinic acid 135, caffeic acid 136, ethyl 5-O-caffeoylqui-
nate 137, 3,4-dihydroxybenzoic acid 138 (Kim et al., 2006), 3,4-

11
L. Chen, et al.
Fig. 3. (continued)
dicaffeoylquinic acid 139, 3,5-D-O-caffeoyl-4-O-(3-hydroxy-3-methyl)-
glutaroylquinic acid 140, 5-O-caffeoyl-4-O-sinapoylquinic acid 141,
(+)-lyoniresinol-3a-O-b-glucopyranoside 142 (Wang et al., 2016), 3-
Caffeoyl-4-sinapoylquinic acid 143 (Nishizawa et al., 1987), 3,4-di-
caffeoyl-5-(3-hydroxy-3-methylglutaroyl) quinic acid 144, caffeoyl si-
napoylquinic acid 145 (Bergonzi et al., 2012), shikimic acid 146, 1, 2,
4-benzenetriol 147, 3, 4-dimethoxy-benzoic acid 148, dibutyl phthalate
149 (Luo et al., 2014), gallic acid 150 (Uddin et al., 2014), 3β,23-
dihydroxyurs-12-en-28-oic acid 151, 3β,19α-dihydroxyurs-12-en-28-
oic acid 152, 3β,19α,23-trihydroxy-12-en-28-oic acid 153, stearic acid
154, palmitic acid 155, oleic acid 156 (Song et al., 2013) and chloro-
genic acid 157 (Xiao et al., 2017). The chemical structures of these
organic acids and their derivatives are shown in Fig. 8.
Compounds 129–133 exhibit potent antioxidant activity in vitro.
12
Journal of Ethnopharmacology 257 (2020) 112829
The antioxidant activity of these five compounds is mainly attributed to
the catechol moiety in their similar structures. These compounds also
exerted dominant inhibitory effects on HIV-1 integrase; the methyl
quinate compounds 129, 131, and 133 exhibited more potent HIV-1
integrase inhibition than ethyl quinate compounds 130 and 132.
3.8. Others
A few other classes of compounds have been isolated from G. jas-
minoides. Two anthraquinones, emodin 158 and physcion 159, were
obtained from the flowers (Song et al., 2013). In 2013, 2-methyl-L-er-
ythritol-4-O-(6-O-trans-sinapoyl)-β-D-glucopyranoside 160 and 2-me-
thyl-L-erythritol-1-O-(6-O-trans-sinapoyl)-β-D-glucopyranoside 161
were also isolated from G. jasminoides fruits for the first time (Yang
L. Chen, et al.
Fig. 3. (continued)
et al., 2013). In addition, 4-methoxybenzenepropanol- 3-O-β-D-gluco-
pyranoside 162 was isolated and identified from the flowers (Zhang
et al., 2017a). The chemical structures of these compounds are shown in
Fig. 9.
4. Pharmacology
G. jasminoides is reputed to possess various pharmacological activ-
ities in in vivo and in vitro. The herbal medicine has been traditionally
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Journal of Ethnopharmacology 257 (2020) 112829
characterized as exerting effects on the digestive, cardiovascular and
nervous systems, and it possesses hepatoprotective activity, anti-in-
flammatory activity, antidepressant activity, chemopreventive poten-
tial, and anti-allergic activity. Modern pharmacological research has
confirmed the folk medicinal use of G. jasminoides to treat febrile dis-
eases, jaundice, hepatitis (Lee et al., 2009b; Wang et al., 2009), neu-
rodegenerative disorders (Zhao et al., 2017), torsion contusion (Chen
et al., 2014), cerebral ischemia (Li et al., 2016) and pyogenic infections.
Iridoid constituents and yellow pigment are the most effective and main
L. Chen, et al.
Fig. 3. (continued)
chemicals components of this herb.
4.1. Hepatoprotective activity
Traditional herbal medicines have achieved a good reputation for
pharmacological efficacy with few side effects. In accordance with the
TCM theory, body fire is recognized as an element that is both dele-
terious and beneficial. Excessive internal fire will lead to infections and
inflammation in several organs, such as the liver and heart. Ben Cao Tu
Jing (Song Dynasty, A.D. 1020–1101) recorded that G. jasminoides ex-
erted dramatic heat-clearing and detoxifying effects. The herb was used
to treat fever, jaundice, insomnia and skin ulcers. The rhubarb-gardenia
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Journal of Ethnopharmacology 257 (2020) 112829
herb pair is composed of Rheum palmatum root and rhizome and G.
jasminoides fruit. The herb pair is commonly used to treat cholestatic
liver diseases. In 2015, the hepatoprotective activity of the herb pair
was investigated. Cholestasis was induced in rats by oral gavage of
75 mg/kg α-naphthylisothiocyanate (ANIT). Subsequently, the rats in
the treated group were intragastrically administered rhubarb extract, G.
jasminoides extract or the rhubarb-gardenia herb pair extract (1, 1 and
2 g/kg, respectively) five times every 12 h. Compared with the model
group, the treated group exhibited enhanced hepatoprotection. In ad-
dition, this herb pair exerted the synergistic effects on cholestatic rats at
both the pharmacodynamic and pharmacokinetic levels (Dong et al.,
2015).
L. Chen, et al.
Fig. 3. (continued)
G. jasminoides-derived iridoid glycosides exert remarkable hepato-
protective effects on different types of damage that are related to its
anti-inflammatory, antioxidant and anti-apoptotic activities. Fulminant
hepatic failure is an important clinical syndrome characterized by
massive hepatic apoptosis. Hepatic injury initiated by D-galactosamine
(D-GalN) and lipopolysaccharide (LPS) in mice is a promising model of
fulminant hepatic failure. The animal model has been widely used to
understand the underlying mechanisms of hepatic malfunction and
evaluate the hepatoprotective efficacy of various drugs (Lian et al.,
2010). In one study, the effects of genipin on fulminant hepatic failure
were evaluated in the GalN/LPS model mice. In this test, the experi-
mental group was administered G. jasminoides-derived genipin at 25,
50, 100 and 200 mg/kg through an intraperitoneal injection 1 h before
the GalN/LPS treatment. Genipin significantly decreased the mortality,
serum aminotransferase activities and lipid peroxidation, and atte-
nuated the GalN/LPS-induced apoptosis of hepatocytes (Kim et al.,
2010). According to another study, G. jasminoides-derived geniposide
(100 mg/kg) and genipin (50 mg/kg) provide obvious hepatoprotection
against ischemia/reperfusion injury. The serum alanine amino-
transferase (ALT) and hepatic lipid peroxidation (LPO) levels, as well as
the levels of the tBid, cytochrome c and caspase-3 proteins were de-
creased following geniposide and genipin administration. The under-
lying mechanisms were related to a decrease oxidative stress and
apoptosis (Kim et al., 2013). A similar experiment revealed notable
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Journal of Ethnopharmacology 257 (2020) 112829
protective effects of geniposidic acid on hepatotoxicity and cholestasis
in rats (Chen et al., 2016).
Although these investigations provide evidence that G. jasminoides
may be a potentially useful pharmacological agent for preventing he-
patic failure, the absence of a positive control in animal experiments or
the use of only a single dose of this herb in these studies are limitations,
and thus the results are worth further discussion.
4.2. Effect on the nervous system
Recently, the incidence of chronic cerebral ischemia has increased
in the aging society as an important component of neurological illness.
Because TCM contains numerous components with a multi-targeted
nature, it exerts a more noticeable effect on chronic cerebral ischemia
than single chemical drugs (Shin et al., 2015). In 2017, the effects of a
G. jasminoides water extract on improving memory and protecting the
nervous system were examined in a chronic cerebral ischemia model
(Zhang et al., 2017b). The rat model of chronic cerebral ischemia was
established through the permanent occlusion of the bilateral common
carotid arteries. The extract was administered orally at three doses
(150 mg/kg, 100 mg/kg, or 50 mg/kg) for 30 days. The escape latency,
the number of times the animals crossed platform and the percentage of
swimming time in each quadrant of the Morris water maze were re-
corded to evaluate spatial learning and memory. Histological
L. Chen, et al.
Fig. 4. The chemical structures of yellow pigment isolated from G. jasminoides.
observations were performed using HE staining. According to the re-
sults of all the detection indexes, the water extract significantly de-
creased the escape latency of rats, decreased apoptosis and necrosis in
the cortex and hippocampus, decreased the SOD content, and sup-
pressed acetylcholinesterase (AChE) and nitric oxide synthase activity
in the brain tissue. The dosage of 100 mg/kg exerted the best effect
among these three doses. G. jasminoides improved memory and ex-
hibited neuroprotection related to the reduction in NO toxicity and
AChE activity, inhibited oxygen free radical production, and protected
neurons in the brain. The brains of patients with Alzheimer's disease
(AD) are characterized by the accumulation of large amounts of
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Journal of Ethnopharmacology 257 (2020) 112829
amyloid beta peptide (Aβ). Zhao et al. used the amyloid precursor
protein/Presenilin-1 (APP/PS1) double transgenic mouse model to in-
vestigate the neuroprotective effect of G. jasminoides-derived geniposide
at doses of 12.5, 25 and 50 mg/kg after administration for 3 months. G.
jasminoides-derived geniposide reduced Aβ accumulation and improved
cholinergic deficits in the cerebral hippocampus by inhibiting the mi-
togen-activated protein kinase (MAPK) signalling pathway (Zhao et al.,
2017). However, these studies lacked a positive control, resulting in
lower reliability.
L. Chen, et al.
Fig. 4. (continued)
4.3. Anti-inflammatory activity
G. jasminoides extracts exhibit strong anti-inflammatory activity. In
2006, Koo et al. evaluated the anti-inflammatory activity of the ethanol
extract of the herb in the carrageenan-triggered rat paw oedema and air
pouch oedema models. The extracts (at doses of 50, 100, 200, and
400 mg/kg body weight) were administered to rats 30 min prior to the
carrageenan treatment. Notably, 10.2, 25.9, 28.6 and 35.8% of acute
paw oedema were inhibited 3 h after the injection of carrageenan,
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Journal of Ethnopharmacology 257 (2020) 112829
compared with the control group that received appropriate amounts of
saline alone. In the vascular permeability assay, the extract inhibited
the formation of an inflammatory infiltrate at doses of 50, 100, and
200 mg/kg by 12.5, 17.6 and 52.5%, respectively. The inhibitory effects
of the extract observed at a dose of 200 mg/kg were approximately
equal to aminopyrine (58.5% inhibition rate). Furthermore, in the
acetic acid-induced vascular permeability test, the doses of 50, 100 and
200 mg/kg inhibited the writhing movements of mice by 35.1, 59.7 and
80.1%, respectively. These findings provided additional information on
L. Chen, et al.
Fig. 4. (continued)
the acute analgesic and anti-inflammatory effects of the G. jasminoides
extract (Koo et al., 2006).
G. jasminoides-derived iridoid glycosides, particularly geniposide
and genipin, possess significant anti-inflammatory activity (Koo et al.,
2004). G. jasminoides geniposide has been reported to possess sig-
nificant analgesic and anti-inflammatory activities. Following the oral
and subcutaneous administration of different doses to mice and rats,
chronic pain was suppressed in a concentration-dependent manner,
with maximal inhibition rates of 72% and 68% observed, respectively
(Gong et al., 2014). In addition, the administration of G. jasminoides
geniposide significantly reduced the swelling ratio (21–34% reduction)
of the ankle sprain in rats (Chen et al., 2009). Based on accumulating
evidence, G. jasminoides geniposide exerts extensive therapeutic effects
on diseases associated with inflammation, including rheumatoid ar-
thritis, mastitis and acute lung injury (ALI). First, Chen et al. evaluated
the effects of G. jasminoides geniposide and relevant metabolites on RA
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Journal of Ethnopharmacology 257 (2020) 112829
in rat tissues (Chen et al., 2014). Then, Song et al. investigated the anti-
inflammatory properties using a rat experimental mastitis model and
primary mouse mammary epithelial cells stimulated with LPS. G. jas-
minoides geniposide mitigated the infiltration of inflammatory cells by
decreasing the production of tumour necrosis factor-α (TNF-α), inter-
leukin (IL)-1β, IL-6 in vivo and suppressed Toll-like receptor 4 expres-
sion in vitro, which was responsible for the decrease in the activity of
the downstream nuclear factor (NF)-κB and mitogen-activated protein
kinase (MAPK) signalling pathways (Song et al., 2014). Similar effects
were observed on the mouse model of LPS-induced ALI. The number of
inflammatory cells and protein concentration in the bronchoalveolar
lavage fluid of mice were markedly reduced, and the levels of in-
flammatory mediators, such as TNF-α, IL-6, and IL-10, were sub-
stantially decreased after the oral gavage of G. jasminoides geniposide at
different doses (Yang et al., 2012).
L. Chen, et al.
Fig. 5. The chemical structures of monoterpenoids isolated from G. jasminoides.
Fig. 6. The chemical structures of sesquiterpenoids isolated from G. jasminoides.
4.4. Antidepressant activity
Depression, one of the most prevalent and severe mental illnesses
worldwide, is a crucial cause of disability and is characterized by
feelings of sadness. It represents a major health threat in the family and
society. A number of traditional Chinese medicines have been for-
mulated to rapidly and persistently attenuate mental disorders.
Interestingly, G. jasminoides is included in a considerable number of
traditional herbal formulations, including “Yueju Wan” and “Zhi-Zi-
Hou-Pu Tang”, for the treatment of psychiatric disorders, such as ir-
ritability, anxiety and depression. In particular, Yueju pill has been
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Journal of Ethnopharmacology 257 (2020) 112829
frequently prescribed to treat depression and anxiety. According to a
pilot study, the constituent of Yueju responsible for the rapid anti-
depressant effect is G. jasminoides (Zhang et al., 2015). By performing
the tail suspension test in mice, the authors found that G. jasminoides,
but not the other constituents, produced a prominent antidepressant
effect, similar to Yueju. Furthermore, the herb produced fast anti-
depressant responses in the learned helplessness test and novelty sup-
pressed-feeding test. The antidepressant activity emerged 2 h after
treatment with the herb decoction. Interestingly, the efficacy on ex-
peditiously alleviating symptoms of depression was associated with an
increase in the levels of the brain-derived neurotrophic factor protein.
Gardenia yellow was remarkably enriched in this herbal medicine. It
also played an important role in the instant antidepressant effects of
Yueju pill (Zhang et al., 2015). In the tail suspension test, forced swim
test or learned helplessness test, a 7-day treatment with a supplement of
gardenia yellow pigment (100, 200, 400 mg/kg) resulted in remarkable
antidepressant responses and inhibited the phosphorylation of eu-
karyotic elongation factor 2 in the hippocampus. Thus, gardenia yellow
pigment might improve depressive symptoms (Wu et al., 2016). How-
ever, these researchers did not compare the efficacy of G. jasminoides
with a positive control.
Chronic stress and the hyperactivity of the hypothalamus–pituitary–
adrenal axis are related to the development of depression. G.
L. Chen, et al.
Fig. 7. The chemical structures of triterpenes isolated from G. jasminoides.
jasminoides-derived geniposide has also been shown to exert a potent
antidepressant-like effect. In a rat model of depression induced by 3
consecutive weeks of chronic stress, a 14-day administration of G. jas-
minoides geniposide (25, 50, 100 mg/kg) significantly reversed the
behavioural abnormalities in open field test, prolonged swimming and
decreased the immobility time in the forced swimming test. Based on
these findings, G. jasminoides-derived geniposide may possess anti-
depressant activity in a mouse model of depression. The underlying
mechanism might be related to the ability of geniposide to reverse the
impairment in the negative feedback of glucocorticoid receptor on
corticotrophin-releasing hormone expression and hypothalamus–pitui-
tary–adrenal axis (Cai et al., 2015b). These therapeutic effects of G.
jasminoides-derived geniposide were essentially similar to fluoxetine.
However, clinical validation of these effects is needed.
4.5. Effects on the digestive system
Because of its strong heat-clearing and detoxifying effects, G. jas-
minoides is traditionally used to treat various infection diseases. In re-
cent years, continuous infection of the gastric mucosa by Helicobacter
pylori has been confirmed to play a vital role in gastrointestinal lesions,
such as gastric ulcers and gastric cancers (International Agency for
Research on Cancer, 1994). In 2009, the effects of the ethanol extract of
G. jasminoides on gastritis in rats and the growth of human gastric
cancer cells were investigated. The ethanol extracts showed substantial
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Journal of Ethnopharmacology 257 (2020) 112829
free radical scavenging activity (IC50 = 38.46 μg/mL) and approxi-
mately 40–70% inhibition of LPO. In vitro, the extracts substantially
inhibited the colonization of Helicobacter pylori (at the dose of 100 μg/
mL), and was directly cytotoxic to gastric cancer cells (with an IC50 of
36.27 μg/mL). Thus, G. jasminoides extracts protect against gastric
diseases (Lee et al., 2009a). A high concentration of ethanol also di-
rectly damages the gastric mucosa. In 2016, the effect of G. jasminoides
methanol extracts on gastritis was assessed (Chen et al., 2016). In this
study, 7-week-old male ICR mice with stomach lesions were created by
administering HCl/ethanol. Compared with the model group, the area
of the gastric injury in mice was reduced by 76.7 ± 1.1% (P < 0.01),
after a 2-week treatment with the methanol extract of G. jasminoides.
On the other hand, the levels of pro-inflammatory cytokines (IL-6, IL-12
and TNF-α) were decreased, and surprisingly, the extract increased SOD
and GSH levels and reduced MDA levels. In addition, G. jasminoides has
been shown to alleviate the severity of acute pancreatitis (AP). AP was
induced in mice through an intraperitoneal injection of cerulean
(50 μg/kg) intraperitoneally every hour for 6 h. The mice were orally
administered G. jasminoides water extracts (1 g/kg, 0.1 g/kg) or normal
saline for one week. Compared with the normal saline-treated group, G.
jasminoides water extracts attenuated pancreatic oedema, restored
serum amylase, lipase, and cytokine levels, and restored the mRNA
expression of inflammatory mediators. Based on these findings, G. jas-
minoides water extracts may be useful treatments that alleviate the se-
verity of AP and pancreatitis-associated lung injury (Jung et al., 2008).
L. Chen, et al. Journal of Ethnopharmacology 257 (2020) 112829

Fig. 8. The chemical structures of organic acids and their derivatives isolated from G. jasminoides.

However, these studies have apparent limitations—only one or two
doses of G. jasminoides extracts were used, and thus the information on
the dose-dependent activity is limited.
4.6. Effects on the cardiovascular system
Cardiovascular disease is another serious disease with high
morbidity and mortality rates. According to the World Health
Organization, it is the primary cause of death worldwide. Natural
products have been widely used to prevent and treat cardiovascular
diseases. G. jasminoides is used to treat cardiovascular illness in China,
probably due to its homeostatic and antiphlogistic effects. Gardenia
yellow pigment is a major active compound in this herb. Consistent
with the literature, some carotenoids exert protective effects on

21
L. Chen, et al.
Fig. 8. (continued)
cardiovascular diseases and endothelial dysfunctions (Riccioni, 2009).
In 2014, Higashino et al. (2014) studied the potential role of G. jasmi-
noides-derived crocetin in attenuating hypertension and endothelial
dysfunction in stroke-prone, spontaneously hypertensive rats. The re-
search identified the ability of G. jasminoides-derived crocetin to treat
anesis, hypertension and thrombosis through a mechanism character-
ized by increased bioavailable NO levels. Crocetin treatments (15 or
30 mg/kg) administered to rabbits fed a high cholesterol diet for 8
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Journal of Ethnopharmacology 257 (2020) 112829
weeks dose-dependently improved endothelium-dependent relaxation.
Moreover, this treatment increased serum NO levels and increased
vessel activity. In subsequent tests, the administration of G. jasminoides-
derived crocetin (0.1, 1, or 10 mM) to bovine aortic endothelial cells
with oxidized LDL significantly increased NO production and upregu-
lated both the activity and mRNA expression of eNOS in a dose-de-
pendent manner (Tang et al., 2006). However, these studies have cru-
cial limitations, such as the lack of positive controls. In another study,
L. Chen, et al. Journal of Ethnopharmacology 257 (2020) 112829

Fig. 8. (continued)

the administration of G. jasminoides-derived crocin (25, 50, or 100 mg/

kg) to rats fed a high-lipid diet for 10 days significantly decreased
serum triglyceride, total cholesterol and low-density lipoprotein levels
and increased the faecal excretion of fat and cholesterol in rats. Thus, G.
jasminoides-derived crocin exerts a hypolipidaemic effect by suppres-
sing pancreatic lipase activity, resulting in the malabsorption of fat and
cholesterol (Sheng et al., 2006).

4.7. Anti-allergic activity

Atopic dermatitis is a major, chronic, and inflammatory skin disease

characterized by severe relapsing eczematous lesions. Due to its anti-
phlogistic, analgesic, antipyretic and detoxifying effects reported in
traditional medicine theory, G. jasminoides has also been used to alle-
viate allergic skin inflammatory responses and ameliorate atopic der-
matitis symptoms. As a generalized animal model, the pathophysiolo-
Fig. 9. The chemical structures of other compounds isolated from G. jasmi- gical characteristics of Nc/Nga mice with atopic dermatitis triggered by
noides. Dermatophagoides farinae were analogous to humans, and this model is
well recognized. In mice with atopic dermatitis induced by
Dermatophagoides farinae, the topical application of G. jasminoides
ethanol extracts (400 μg/mouse) noticeably decreased the symptoms of

23
L. Chen, et al.
atopic dermatitis, reduced the infiltration of inflammatory cells, and
significantly decreased the serum levels of immunoglobulin E and the
expression of cytokines in ear lesions. Moreover, in MC/9 mast cells
stimulated with compound 48/80, the ethanol extract inhibited the
release of histamine from mast cells (Sung et al., 2014). Treatment with
G. jasminoides ethanol extracts (100 mg/mouse) treatment also alle-
viated the severity of skin lesions, such as the frequency of scratching
and ear swelling. In addition, the extract also decreased the serum IgE
and chemokine levels, significantly reduced the inflammatory response,
decreased the infiltration of inflammatory cells, and increased the levels
of proteins involved in maintaining the skin barrier. Based on these
findings, G. jasminoides ethanol extracts may be particularly useful as
supplementary interventions for atopic dermatitis (Park et al., 2019).
However, further explicit clinical trials should be performed to evaluate
the effectiveness of this herbal medicine as a treatment for atopic der-
matitis.
4.8. Other activities
In addition to the biological activities described above, G. jasmi-
noides possesses other activities. The aqueous extracts of G. jasminoides
exert remarkable antithrombotic effects on several experimental models
of thrombosis, including tail thrombosis induced by carrageenan in
mice and an arteriovenous shunt thrombus model in rats. Carrageenan-
induced thrombosis in mice is a simple model that does not kill the
animals. In one study, the extracts (67, 133 and 266 mg/kg body
weight), aspirin (50 mg/kg body weight), or solvent were administered
by oral gavage 1 h before the carrageenan injection and then the mice
were treated for another 3 days. The length of the tail thrombus was
measured 24, 48 and 72 h after the carrageenan injection in mice. G.
jasminoides remarkably inhibited the formation of the venous thrombus,
and its effects were better than aspirin. Meanwhile, G. jasminoides sig-
nificantly improved thrombosis induced by an arteriovenous shunt in
rats. Thus, the G. jasminoides aqueous extract possesses significant an-
tithrombotic activity (Zhang et al., 2013a, b). However, the molecular
mechanisms require further study and detailed clinical trials are
needed.
The development of effective anti-tumour therapies is a tremendous
task in medical research. According to experimental studies, genipin
may become a promising chemopreventive agent used to prevent or
alleviate cancer. As one of the major iridoid glycosides isolated from G.
Fig. 10. The conversion process of gardenia colourant.
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Journal of Ethnopharmacology 257 (2020) 112829
jasminoides, geniposide is usually hydrolysed to the aglycone genipin by
β-D-glycosidases in the intestines and liver. G. jasminoides-derived
genipin has been used to treat different cancer cells in several studies. A
24 h administration of G. jasminoides-derived genipin (50–1000 μm) to
FaO rat hepatoma cells and human hepatocarcinoma Hep3B cells sig-
nificantly increased ROS levels, inhibited the activation of caspase-3, -7
and -9, promoted apoptotic cell death (Kim et al., 2005). G. jasminoides-
derived genipin has also been shown to induce apoptosis in MDA-MB-
231 human breast cancer cells (at the dose of 200 μM for 24 h). It also
down-regulated the expression of Bcl-2, up-regulated the expression of
Bax and induced the proteolytic activation of caspase-3. In addition, G.
jasminoides-derived genipin distinctly supresses the invasive and mi-
gratory phenotypes of MDA-MB-231 cells (Kim et al., 2012). However,
in vivo experiments and clinical trials are needed.
5. Industrial applications
5.1. Crosslinking agent
Genipin is formed by geniposide hydrolysed with β-glucosidases and
has been widely used in many fields as a natural biological crosslinking
agent with excellent biocompatibility and low toxicity. Genipin cross-
links proteins, collagen, gelatin and chitosan (Lauto et al., 2004; Liang
et al., 2003; Jin et al., 2004). Thereby, it is able to fix biological tissues,
resulting in the production of biomaterials such as artificial bones,
wound dressing material and blood substitute. And hence, genipin
played a vital role in drug delivery system (Liu et al., 2004; Norowski
et al., 2012; Chang et al., 2004). In general, genipin might form in-
tramolecular and intermolecular crosslinks with a heterocyclic struc-
ture within collagen fibres in tissues through two reactions: ① a reaction
with 1,6-hexanediamine through the nucleophilic attack on the olefinic
carbon atom at C-2 of deoxyloganin aglycone and ② subsequently
opening the dihydropyran ring to shape heterocyclic amine compounds.
Genipin has also been used as a fingerprint collection reagent and a
crosslinker for the preparation of immobilized enzymes (Mi et al., 2010;
Pujana et al., 2014).
Through in-depth investigations, the potential toxic effects of che-
mical prothesis have been gradually recognized. Therefore, an in-
creasing number of researchers have focused on novel, efficient, natural
and low-toxicity crosslinking agents. Genipin-fixed tissues displayed
fewer inflammatory reactions and the greatest ultimate tensile stress,
L. Chen, et al.
toughness and resistance against in vivo degradation. It also possessed
better stability and biocompatibility than the counterparts glutar-
aldehyde and epoxy. These promising advantages have attracted in-
creasing attentions to this material. Tissues fixed with genipin, glutar-
aldehyde and epoxy compound produce different crosslinked structures
that affect the crosslinking characteristics and mechanical properties of
the fixed tissues (Huang et al., 1998; Sung et al., 1999).
To date, crosslinking technology has been widely used to modulate
both the mechanical properties and chemical stability of collagenous
tissues and biomaterials. Genipin potentially decreases the bioburden
and produces a powerful sporicidal effect on bone allograft sterilization
via a crosslinking reaction. During the surgical repair of ruptured ten-
dons and ligaments, tendons treated with genipin-delivering sutures
exhibit a significant amelioration of the failure load, a decrease in en-
ergy required for pull-out failure, and a decrease in stiffness (Sundararaj
et al., 2017). As a type of exogenous crosslinker, genipin crosslinks the
cornea and sclera to prevent myopic progression in vivo and in vitro
(Avila et al., 2012; Wong et al., 2012; Liu and Wang, 2017).
5.2. Pigment
Food additives, particularly pigments, are commonly used in food
processing to improve the colour and sensory characters. Currently,
edible pigments mainly include synthetic and natural colourants. As the
awareness of the relation to health has increased, synthetic colourants
have received increasing attention in recent years due to their safety
properties (Giménez et al., 2015). Various synthetic colourants may be
transformed into harmful derivatives and represent a potential threat to
human health (Yolmeh et al., 2014).
Due to their nutritional effects and lower toxicity, natural colour-
ants have played an important role in improving the health of humans
when used as additives in foods, beverages, and sugars. Therefore, the
trend of natural alternatives to artificial dyes is becoming the fashion-
able trend (Zhou et al., 2016).
G. jasminoides is also a unique plant source of a series of yellow, blue
and red colourants (Park et al., 2002). Gardenia yellow is mainly a
mixture of excellent water-soluble carotenoids consisting of crocin and
crocetin. Similar to other carotenoids, the yellow colourant may pro-
vide health benefits due to its strong antioxidant properties. The nu-
tritional property and negligible toxicity make it a superior candidate
that is suitable for food applications (Tu et al., 2010; Watanabe and
Terabe, 2000). Gardenia yellow is extracted from this herb, and geni-
poside is always extracted simultaneously. Because of the coexistence of
geniposide, gardenia yellow easily to fades and turns green when used
as a food additive. Gardenia blue is obtained through a simple reaction
of primary amines with genipin (Park et al., 2002). Although genipin is
colourless, a reaction with capita amino acids and protein hydrolysates
results in a blue colour (Hobbs et al., 2018). The natural red colourant
is also prepared from the hydrolysis of the methyl ester of iridoid glu-
coside (Sato and Maitani, 2003). The conversion process of gardenia
pigments is shown in Fig. 10. Due to their high water solubility, neg-
ligible toxicity and good stability at neutral and basic pH, these natural
pigments have extensively been utilized in frozen desserts, confections,
baked goods, noodles, wine and liqueurs, cosmetics, textiles and agri-
cultural products in East Asia (Dan et al., 2012). The commercial dis-
tribution of gardenia yellow is approximately 750 tons/year in Japan
(Sato et al., 2007).
In addition, many natural colourants, such as anthocyanin, chlor-
ophyll and carotene extracted from all parts of the plant, have suc-
cessfully been used as sensitizers in dye-sensitized solar cells (Al-Alwani
et al., 2017). However, the energy conversion efficiencies of a single
pigment are usually very low. In 2013, Park et al. investigated the
differences in the light harvesting capacity over a wide range of wa-
velengths using a double layer of natural dyes extracted from G. jas-
minoides and cochineal as sensitizers on a nanoporous TiO2 surface
(Park et al., 2014).
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Journal of Ethnopharmacology 257 (2020) 112829
6. Toxicity
With the wide use of G. jasminoides, its safety has gradually attracted
increasing attention in recent years, but the toxicity of this herb and its
related formulas has rarely been reported in animal studies and clinical
applications. Based on the available animal trial data, analyses of the
safety of this herbal medicine are mainly focused on its hepatotoxicity.
In a study published in 2007, male and female SD rats were orally
administered a G. jasminoides aqueous extract (at maximum doses of
30 g/kg) for a 14-week period. The high dose of the aqueous extract
significantly increased the liver indexes of rats (Wang et al., 2007).
Another acute toxicity study reported the same result at a dosage of
3.08 g/kg in rats (Yang et al., 2006). G. jasminoides is also a key in-
gredient in the Zhi-Zi-Hou-Po decoction. The hepatotoxicity of the
prescription may be associated with the accumulation of geniposide in
the liver (Wang and Feng, 2019).
A considerable amount of toxicological data has indicated that the
hepatotoxicity of G. jasminoides is likely related to geniposide. G. jas-
minoides-derived geniposide may cause liver toxicity due to overdosing
(Cui et al., 2017; Yang et al., 2006; Yamano et al., 1990; Wang et al.,
2007). However, the use of this component at the pharmacological
dosage or consumption of gardenia colourant in food products did not
damage any major organ in the body in previous studies (Yamano et al.,
1988; Ding et al., 2013; Hobbs et al., 2018). According to Sato et al.
(2007), oral administration of gardenia yellow powders containing
geniposide (approximately 60 mg/kg/day as geniposide intake) do not
exert any severe toxic effects. A 13-week subchronic toxicity study of
gardenia blue was performed in rats after the administration of 5.0, 2.5,
1.25 and 0.6% of the colourant in the diet. All treated groups survived
for the duration of the study and did not show decreases in body weight
and food consumption.
In the clinic, the recommended dose of G. jasminoides used in an
adult is 6–10 g daily. Although G. jasminoides appears to be nontoxic or
hypotoxic to the human body, the TCM theory proposes that a bitter
and cold medicine may promote spleen and stomach diseases. G. jas-
minoides may affect the normal gastrointestinal functions because of its
bitter-cold property (Zhou et al., 2019). This finding is consistent with
the point that has been emphasized in TCM theory. Therefore, G. jas-
minoides should be used with caution in patients with a gastrointestinal
disorder.
7. Conclusions and future perspectives
In summary, G. jasminoides is a supereminent medicinal plant that
has extensively been used in TCM in China for over 2000 years.
Numerous modern pharmacological studies have revealed various
biological properties of G. jasminoides, such as beneficial effects on the
nervous, cardiovascular and digestive systems, hepatoprotective ac-
tivity, antidepressant activity, and anti-inflammatory activity. As a
traditional and crucial herbal medicine, G. jasminoides is commonly
used as an agent to relieve heat and eliminate vexation. In vitro and in
vivo pharmacological investigations have increasingly validated the
traditional use of this herb. Approximately 162 chemical compounds
have been isolated and identified from this herb. Iridoid glycosides and
yellow pigment are considered the main bioactive constituents of G.
jasminoides. This herb has many differences from other traditional
medicines, and the most obvious characteristic is its wide industrial
applications. Gardenia yellow pigment has been an important resource
as a natural colourant for food, cloth and paint for thousands of years in
many countries. Genipin has been widely used in many fields as a
natural biological crosslinking agent with excellent biocompatibility.
Substantial progress has been made in the phytochemistry, phar-
macological and industrial applications of G. jasminoides. However,
gaps still remain in the existing literature. First, an understanding of
whether pharmacological studies on G. jasminoides are available is
important to validate its traditional uses. Among the constituents
L. Chen, et al.
extracted from G. jasminoides, iridoid glycosides are the most frequently
investigated compounds in many in vitro and in vivo studies. Modern
pharmacological research has shown that this compound is responsible
for some traditional uses, including clearing heat and eliminating
dampness. These studies also provided many reasonable explanations
for the effects and mechanisms of action related to multiple biological
activities. However, regarding the phytochemistry and pharmacology,
the existing reports have mainly focused on its modern pharmacological
effects rather than other traditional uses. Thus, researchers have not
been able to easily identify the connections between the major active
constituents and traditional uses. In addition, the mechanism of action
underlying the traditional uses remains unclear and in-depth studies are
needed. Second, according to the classical medicinal books, G. jasmi-
noides is bitter and cold, which might easily damage the stomach, but
the gastrointestinal injury caused by G. jasminoides and the related
mechanisms are unknown and should be studied systematically. Third,
herb processing is applied to change this adverse effects. Currently, few
modern pharmacological investigations have been conducted to analyse
this property of G. jasminoides and further studies are needed.
Meanwhile, G. jasminoides is also commonly used to treat ankle sprains
through external application in the Chinese Pharmacopoeia. However,
modern pharmacological investigations on external applications are
insufficient. Finally, gardenia yellow has been broadly used as a natural
colourant, but commercial gardenia yellow pigment contains genipo-
side that may exert negative effects (Inoue et al., 2014). Therefore,
some adverse effects have been identified in evaluations of the safety of
gardenia yellow pigment due to a lack of highly purified colourant. The
methods used to isolate G. jasminoides also require in-depth analyses.
In addition, although the safety of G. jasminoides has been confirmed
by numerous studies and this herb has been widely used in China and
many other countries worldwide as both a food and medicine, tox-
icological studies on this herb are far from sufficient. Hence, numerous
questions remain and must be resolved and verified by conduction
further in vivo studies and clinical trials.
In conclusion, G. jasminoides is an excellent herb that represents a
potential source of natural pigments and a potent crosslinking drug.
Additional efforts are needed to obtain insights from modern in vivo
pharmacological studies designed to estimate the validity of traditional
uses of G. jasminoides. In addition, the isolation and identities of the
major active components of G. jasminoides must be analysed further
using advanced chemical and pharmacological techniques to further
broaden their potential applications. Finally, additional in vivo animal
studies and clinical trials are required to verify and determine the safety
of diverse applications of G. jasminoides.
Acknowledgements
All authors developed the concept for the study. Maoxi Li designed
this manuscript. Zhiqiang Yang conducted the literature survey and
drafted the paper. Wendi Tao and Xiuyu Tian provided some data on
the traditional uses of Gardenia jasminoides Ellis. Other authors re-
viewed the manuscript and provided suggestions. The authors grate-
fully acknowledge the financial support of the project of the Medical
and Health Research, PLA (CLZ15JA05).
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://
doi.org/10.1016/j.jep.2020.112829.
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