Phytochemistry, Traditional Uses and Pharmacological Profile of Rose Hip: A Review

Abstract

Background:
The fruit of genus Rosa, known as "rose hip", is frequently used in different traditional medicines. Rose hips have long been used to treat kidney stones, gastroenteric ailments, hypertension and respiratory problems such as bronchitis, cough and cold.

Aim:
This review focused on the ethnopharmacological uses of rose hip as well as phytochemical and pharmacological aspects.

Results:
Ethno-medical uses of rose hip have been recorded in many countries since a long time. Approximately, 129 chemical compounds have been isolated and identified from rose hip. This fruit contains some major active components such as flavonoids, tannins, anthocyanin, phenolic compounds, fatty oil, organic acids and inorganic compounds. Scientific studies have suggested a wide range of pharmacological activities for rose hip includng antioxidant, anti-inflammatory, anti-obesity, anti-cancer, hepatoprotective, nephroprotective, cardioprotective, antiaging, anti H. pylori, neuroprotective and antinociceptive activities. In particular, the hip powder and extract have been reported to exert therapeutic effects on arthritis.

Conclusions:
Some of the ethnomedical indications of rose hip, such as nephroprotective and gastroproetctive actions, have been confirmed by preclinical pharmacological studies. Additional investigations on the pharmacological effects of rose hip as well as evidence from randomized controlled trials are essential to assess therapeutic value of this natural product.

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Current Pharmaceutical Design, 2018, 24, 1-24 1
REVIEW ARTICLE
1381-6128/18 $58.00+.00 © 2018 Bentham Science Publishers
Phytochemistry, Traditional Uses and Pharmacological Profile of Rose Hip: A
Review
Zahra Ayati1, Mohammad Sadegh Amiri2, Mahin Ramezani3, Elahe Delshad4, Amirhossein Sahebkar5,6,7 and
Seyed Ahmad Emami1,8,*
1Department of Traditional Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; 2Department
of Biology, Payame Noor University, Tehran, Iran; 3Nanotechnology Research Center, Mashhad University of Medical Sciences,
Mashhad, Iran; 4Department of Persian Medicine, School of Persian and Complementary Medicine, Mashhad University of Medical
Sciences, Mashhad, Iran; 5Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;
6Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran;
7School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; 8Department of Pharmacognosy, School of Pharma-
cy, Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Abstract: Background: The fruit of genus Rosa, known as "rose hip", is frequently used in different traditional
medicines. Rose hips have long been used to treat kidney stones, gastroenteric ailments, hypertension and respira-
tory problems such as bronchitis, cough and cold.
Aim: This review is focused on the ethnopharmacological uses of rose hip as well as phytochemical and pharma-
cological aspects.
Results: Ethno-medical uses of rose hip have been recorded in many countries since a long time. Approximately,
129 chemical compounds have been isolated and identified from rose hip. This fruit contains some major active
components such as flavonoids, tannins, anthocyanin, phenolic compounds, fatty oil, organic acids and inorganic
compounds. Scientific studies have suggested a wide range of pharmacological activities for rose hip including
antioxidant, anti-inflammatory, anti-obesity, anti-cancer, hepatoprotective, nephroprotective, cardioprotective,
antiaging, anti H. pylori, neuroprotective and antinociceptive activities. In particular, the rose hip powder and
extract have been reported to exert therapeutic effects on arthritis.
Conclusion: Some of the ethnomedical indications of rose hip, such as nephroprotective and gastroproetctive
actions, have been confirmed by preclinical pharmacological studies. Additional investigations on the pharmaco-
logical effects of rose hip as well as evidence from randomized controlled trials are essential to assess the
therapeutic value of this natural product.
A R T I C L E H I S T O R Y
Received: September 4, 2018
Accepted: October 6, 2018
DOI:
10.2174/1381612824666181010151849!
Keywords: Rosa canina, cornuside, anti-cancer, protocatechuic acid, gallic acid, liver and kidney protection, osteoarthritis, linoleic acid,
quercetin, palmitic acid, shikmic acid, apigenin, catechin, β- naringenin hexoside, rose hip, R. multiflora, Rosaceae.
1. INTRODUCTION
The genus Rosa is one of the most widespread members of the
Rosaceae family with more than 100 species. Rose hip (which is
also called rose haw) is a good source of different types of micronu-
trients (vitamins) and phytochemicals such as phenolic acids, tan-
nins and flavonoids. Rose hip has a long history of traditional uses
in folk medicine. Rose hip has been used for the treatment of sever-
al illnesses including ear, nose and throat problems. In the tradi-
tional European folk medicine, rose hip has been used as a laxative,
diuretic, anti-gout and anti-rheumatism medication [1].
To extend our view towards future indications of rose hip for
medicinal and clinical purposes, we reviewed traditional applica-
tions of Rosa spp. fruits and also clinical properties and pharmaco-
logical potentials of rose hip in various ethnomedical systems.
Besides the traditional uses, Rosa spp. exhibits various phar-
macological properties. Several in vitro and in vivo pharmacologi-
cal studies and clinical trials have confirmed the traditional uses of
rose hip. These studies are also discussed in this review.
*Address corrrespondence to this author at the Department of Traditional
Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences,
Mashhad, Iran; E-mail: emamia@mums.ac.ir
2. PHYTOCHEMICALS OF ROSE HIP
According to the phytochemical reports on rose hips, many
categories of phytochemicals have been identified, the most widely
known are anthocyanisn, phenolic acids (hydroxybenzoic acids,
hydroxycinnamic acids), tannins (hydrolysable tannins and ellag-
itannins), flavanols, flavonoids (dihydrochalcone), stilbenoid, ca-
rotenoids, chlorins, organic acids, sugars, fatty acids, galactolipid
(monogalactosyldiacyl glycerol), tocopherols and vitamins (Tables
1, 2). The total phenolic contents in 25 rose hip fruit types was in
the range of 20.1 to 32.2 mg gallic acid equivalents/g and Rosa
canina fruit. Flavanols are the main phenolic class in most of the
species. Fatty acid analyses show that rose hips contain nine major
fatty acids. The major fatty acid in all rose hip species is α-linolenic
acid followed by palmitic and linoleic acids. Rose hips contain
several elements such as N, P, K, Ca, Mg and Zn [2] (Table 1).
Interestingly, rose hip is also known as a rich source of vitamin C
[3]. High amounts of ascorbic acid and carotenoids in the powder
from pulp with skin and vitamin E in seeds make rosehip a good
antioxidant. Rose hip has been suggested as a supplement for me-
dicinal and prophylactic purposes in conditions such as deficiency
of vitamins C and E [4]. Currently, oral and topical products of rose
hip that are mainly derived from R. canina are produced and used.

2 Current Pharmaceutical Design, 2018, Vol. 24, No. 00 Ayati et al.
Table 1. The main phytochemicals of rose hip.
Phytochemical class
Components
Refs.
anthocyanin
phenolic acid and derivatives
cyanidine-3-glucoside, hydroxycinnamic acid and derivatives (3-p-coumaroylquinic acid, 4-p-coumaroylquinic acid
1, 2, 5-p-coumaroylquinic acid 1, 2, p-coumaric acid hexoside 1, 2, sinapic acid hexoside 1, 2
hydroxybenzoic acids and derivatives( ellagic acid pentoside 1-3, methyl ellagic acid 1-2, methyl ellagic acid pento-
side, methyl gallate acetyl dihexoside, methyl gallatehexoside, methyl gallate rutinoside
Methyl gallate 3-O-beta-glucoside)
Taxifolin pentoside,
[2, 5, 6]
[2]
flavanols
(+)-catechin, catechin hexoside, PA dimer 1-5, PA trimer 1-8, PA tetramer, PA dimer monoglyc1-3, PA dimer glyc
1-4, (–)-Epicatechin
[2, 6]
flavonols
Isorahmnetin-3-rhamnoside, kaempferol derivative, quercetin-3-arabinofuranoside, quercetin-3-arabinopyranoside,
quercetin-3-galactoside, quercetin-3-glucoside, quercetin-3-glucuronide, quercetin-3-rhamnoside, quercetin-3-
rutinoside, quercetin-3-xyloside, quercetin-3-o-rutinoside, quercetin glucurinide, quercetin-3-O-glucoside, quercetin
hexoside, quercetin pentoside, isorhamnetin 3-O-rutinoside, quercetin rhamnoside, kaempferol rhamnosyl-hexoside
[2, 6]
flavonol-glycoside
quercetin, quercitrin
[7]
dihydrochalcone-glycoside
Phloridzin
[7]
flavanones
eriodictyol hexoside 1, 2 , naringenin hexoside 1-5, hesperidin
[2]
flavone
apigenin derivative 1, 2
[2]
carotenes
lycopene, beta-carotene, beta-chryptoxanthin, rubixanthin, zeaxanthin and lutein, epimers of neochrome
[2, 8, 9]
Fatty oil
linoleic acid, linolenic acid, palmitic acid
[10]
flavonoids
isoquercetin, kempferol, rutin, quercetin, hyperoside and tiliroside
[11]
galactolipids
sugars and organic acids
glucose, fructose, sucrose, citric acid, malic acid, quinic acid, tartaric acid, shikmic acid, fumaric acid, ascorbic acid
[2]
tanins
Elagitanins
[5]
triterpenoids
phytosterols
vitispiran
[11]
inorganic compounds
nitrogen, potassium, calcium, magnesium, iron, copper, manganese, zinc
[4]
vitamines
folates, K, ascorbic acid, vitamin E
[12]
Table 2. Chemical structure of hips of Rosa species.
No.
Name of compounds
Structures
Species
Refs.
phenolic acids
1
gallic acid
R. canina
[5-14]
R. sempervirens
[15]
2
protocatechuic acid
R. canina
[5-14]
R. sempervirens
[15]
3
salicylic acid
R. canina
[5]
(Table 2) Contd….

Phytochemistry, Traditional Uses and Pharmacological Profile of Rose Hip Current Pharmaceutical Design, 2018, Vol. 24, No. 00 3
No.
Name of compounds
Structures
Species
Refs.
4
vanillic acid
R. canina
[13, 14,
16]
5
methyl gallate
R. canina
[5]
6
syringic acid
R. canina
[14]
7
ferulic acid
R. canina
[13]
R. sempervirens
[15]
8
caffeic acid
R. canina
[14]
9
p-hydroxybenzoic acid
R. canina
[13]
R. sempervirens
[15]
10
methyl gallate 3-O-β-
glucoside
R. canina
[5]
11
ellagic acid
R. canina
[5, 14]
R. sempervirens
[15]
hyxdroxy benzoic acids
12
ellagic acid pentoside1–3
R. rugosa
R. canina
[17]
13
ellagic acid hexoside1, 2
R. rugosa
R. canina
[17]
14
methyl ellagic acid pentoside
R. rugosa
R. canina
[17]
15
methyl gallate acetyl di hexoside
R. rugosa
R. canina
[17]
16
methyl gallate hexoside
R. rugosa
R. canina
[17]
17
methyl gallate rutinoside
R. rugosa
R. canina
[17]
18
methyl gallate pentoside
R. rugosa
R. canina
[17]
(Table 2) Contd….

4 Current Pharmaceutical Design, 2018, Vol. 24, No. 00 Ayati et al.
No.
Name of compounds
Structures
Species
Refs.
hydroxyl cinnamic acids
19
3-feruloyl quinic acid
R. rugosa
R. canina
[17]
20
3-p-coumaroyl quinic
acid
R. rugosa
R. canina
[17]
21
4-p-coumaroyl quinic
acid
R. rugosa
R. canina
[17]
22
5-p-coumaroyl quinic
acid
R. rugosa
R. canina
[17]
23
p-coumaric acid hexoside
R. rugosa
R. canina
[17]
24
sinapic acid hexoside
R. rugosa
R. canina
[17]
25
trans-5-caffeoylquinic
acid (neochlorogenic
acid)
R. rugosa
R. canina
[17]
26
cis-5-caffeoylquinic
acid
R. rugosa
R. canina
[17]
27
4-caffeoyl quinic acid
R. rugosa
R. canina
[17]
28
3-caffeoyl quinic acid
(chlorogenic acid)
R. rugosa
R. canina
[17]
(Table 2) Contd….

Phytochemistry, Traditional Uses and Pharmacological Profile of Rose Hip Current Pharmaceutical Design, 2018, Vol. 24, No. 00 5
No.
Name of compounds
Structures
Species
Refs.
hydrolysable tannins
29
digalloyl HHD phexoside 1-4
R. rugosa
R. canina
[17]
30
trigalloyl hexoside 1, 2
R. rugosa
R. canina
[17]
31
trigalloyl HHDP hexoside
R. rugosa
R. canina
[17]
32
tri gallquinic acid
R. rugosa
R. canina
[17]
33
di-HHDP glucose1, 2
R. rugosa
R. canina
[17]
34
digalloyl hexoside1, 2
R. rugosa
R. canina
[17]
35
digalloyl quinicacid1–3
R. rugosa
R. canina
[17]
36
galloylbis HHDP glucose 1, 2
R. rugosa
R. canina
[17]
37
HHDP di galloyl glucose isomer1-3
R. rugosa
R. canina
[17]
38
HHDP galloyl hexoside
R. rugosa
R. canina
[17]
39
HHDP glucose isomer
R. rugosa
R. canina
[17]
ellagi tannins
40
tellimagrandin I
R. canina
[5]
41
tellimagrandin II
R. canina
[5]
(Table 2) Contd….

6 Current Pharmaceutical Design, 2018, Vol. 24, No. 00 Ayati et al.
No.
Name of compounds
Structures
Species
Refs.
gall=
42
rugosin A: R1= O-gall, R2= H
R. canina
[5]
43
rugosin B: R1= H, R2= OH
R. canina
[5]
gall=
44
rugosin D: R1= O-gall, R2= H
R. canina
[5]
45
rugosin E: R1= H, R2= OH
R. canina
[5]
Flavonoids
46
catechin
R. canina
[5-14]
R. sempervirens
[15]
47
epicatechin
R. canina
[13]
(Table 2) Contd….

Phytochemistry, Traditional Uses and Pharmacological Profile of Rose Hip Current Pharmaceutical Design, 2018, Vol. 24, No. 00 7
No.
Name of compounds
Structures
Species
Refs.
48
catechin hexoside
R. rugosa
R. canina
[17]
49
PA dimer1–5
R. rugosa
R. canina
[17]
50
PA trimer1–8
R. rugosa
R. canina
[17]
51
PA tetramer
R. rugosa
R. canina
[17]
52
PA dimermonoglyc1–3
R. rugosa
R. canina
[17]
53
PA dimerdiglyc 1–4
R. rugosa
R. canina
[17]
54
dimer PA monogallate
R. rugosa
R. canina
[17]
55
isorhamnetin pentoside1, 2
R. rugosa
R. canina
[17]
56
isorhamnetin-3-rhamnoside
R. rugosa
R. canina
[17]
57
isorhamnetin hexoside
R. rugosa
R. canina
[17]
58
kaempferol: R1= OH, R2= H, R3= OH, R4= H, R5=H, R6= OH
R. canina
[5, 18]
59
kaempferol derivative
R. rugosa
R. canina
[17]
60
kaempferol-acetyl hexoside
R. rugosa
R. canina
[17]
61
kaempferol-acetyl hexoside rhamnoside
R. rugosa
R. canina
[17]
62
kaempferol 3-O-glucoside: R1= O-glucoside, R2= H, R3= OH, R4= H, R5=H, R6= OH
R. canina
[13, 17]
R. rugosa
[17]
R. sempervirens
[15]
63
kaempferol-3-O-glucuronide: R1= O-glucuronide, R2= H, R3= OH, R4= H, R5=H, R6= OH
R. rugosa
R. canina
[17]
64
quercetin: R1= OH, R2= H, R3= OH, R4= H, R5= OH, R6= OH
R. canina
[5, 14,
18]
65
quercetin-3-O-glucoside (isoquercetin): R1= O-glucoside, R2= H, R3= OH, R4= H, R5= OH, R6= OH
R. rugosa
[17]
R. canina
[13, 17,
18]
R. sempervirens
[15]
66
quercetin-3-O-arabinofuranoside: R1= O-arabinofuranoside, R2= H, R3= OH, R4= H, R5= OH, R6= OH
R. rugosa
R. canina
[17]
67
quercetin-3-O-arabinopyranoside: R1= O-arabinopyranoside, R2= H, R3= OH, R4= H, R5= OH, R6= OH
R. rugosa
R. canina
[17]
68
quercetin-3΄-glucuronide: R1= OH, R2= H, R3= OH, R4= H, R5= glucuronide, R6= OH
R. rugosa
R. canina
[17]
(Table 2) Contd….

8 Current Pharmaceutical Design, 2018, Vol. 24, No. 00 Ayati et al.
No.
Name of compounds
Structures
Species
Refs.
69
quercetin-3-O-galactoside (hyperoside): R1= O-galactoside, R2= H, R3= OH, R4= H, R5=OH, R6= OH
R. rugosa
[17]
R. canina
[5, 13,
17, 18]
R. sempervirens
[15]
70
quercetin-3-glucuronide: R1= O- glucuronide, R2= H, R3= OH, R4= H, R5= OH, R6= OH
R. rugosa
R. canina
[17]
71
quercetin 3-O-rhamnoside (quercitrin): R1= O-rhamnoside, R2= H, R3= OH, R4= H, R5= OH, R6= OH
R. rugosa
R. canina
[17]
R. canina
[5, 13]
R. sempervirens
[15]
72
quercetin 3-O-rutinoside (rutin): R1= O-rutinoside, R2= H, R3= OH, R4= H, R5= OH, R6= OH
R. rugosa
[17]
R. canina
[14, 17,
20]
R. micrantha
[20]
R. canina
[5, 18]
73
quercetin-3-xyloside: R1= O- xyloside, R2= H, R3= OH, R4= H, R5= OH, R6= OH
R. rugosa
R. canina
[17]
74
quercetin-acetyl hexoside
R. rugosa
R. canina
[17]
75
quercetin-hexoside
R. rugosa
R. canina
[17]
76
quercetin-galloylhexoside 1, 2
R. rugosa
R. canina
[17]
77
quercetin-rhamnosyl hexoside
R. rugosa
R. canina
[17]
78
eriodictyol hexoside 1, 2
R. rugosa
R. canina
[17]
79
naringenin hexoside 1–5
R. rugosa
R. canina
[17]
80
taxifolin pentoside 1–3
R. rugosa
R. canina
[17]
81
taxifolin di-pentoside
R. rugosa
R. canina
[17]
82
dihydrokaempferol hexoside
R. rugosa
R. canina
[17]
83
apigenin derivative1, 2
R. rugosa
R. canina
[17]
84
eriodictyol hexoside
R. canina
R. micrantha
[20]
85
isorhamnetin 3-O-rutinoside: R1= O-rutinoside, R2= H, R3= OH, R4= H, R5= OMe, R6= OH
R. canina
[20]
R. micrantha
86
amentoflavone
R. canina
[13]
R. sempervirens
[15]
(Table 2) Contd….

Phytochemistry, Traditional Uses and Pharmacological Profile of Rose Hip Current Pharmaceutical Design, 2018, Vol. 24, No. 00 9
No.
Name of compounds
Structures
Species
Refs.
87
phloridzin
R. rugosa
R. canina
[17]
88
myricetin
R. canina
[14]
R. damascena
[16]
89
spiraeoside
R. canina
[5]
90
astragalin
R. canina
[5]
91
tiliroside
R. canina
[5, 18]
92
cyanidin 3-O-glucoside
R. canina
[17, 6]
R. micrantha
[6]
R. rugosa
[17]
Stilbenoid
93
resveratrol derivative
R. rugosa
R. canina
[17]
Carotenoids
94
lycopene
R. rugosa
[12, 17,
9]
R. canina
[12, 9]
95
β-carotene
R. rugosa
[17]
R. canina
[12, 17,
9]
(Table 2) Contd….

10 Current Pharmaceutical Design, 2018, Vol. 24, No. 00 Ayati et al.
No.
Name of compounds
Structures
Species
Refs.
96
lutein
R. canina
[9]
97
zeaxanthin
R. canina
[9]
98
rubixanthin
R. canina
[9]
99
neochrome
R. canina
[9]
Chlorins
100
chlorophyll a
R. canina
[12]
101
chlorophyll b
R. canina
[12]
organic acids
102
oxalic acid
R. pimpinellifolia
R. villosa
R. canina
R. dumalis
[19]
103
tartaric acid
R. pimpinellifolia
R. villosa
R. canina
R. dumalis
[19]
101
malic acid
R. pimpinellifolia
R. villosa
R. canina
R. dumalis
[19]
(Table 2) Contd….

Phytochemistry, Traditional Uses and Pharmacological Profile of Rose Hip Current Pharmaceutical Design, 2018, Vol. 24, No. 00 11
No.
Name of compounds
Structures
Species
Refs.
105
citric acid
R. pimpinellifolia
R. villosa
R. canina
R. dumalis
[19]
106
succinic acid
R. pimpinellifolia
R. villosa
R. canina
R. dumalis
[19]
107
fumaric acid
R. pimpinellifolia
R. villosa
R. canina
R. dumalis
[19]
108
shikimic acid
R. rugosa
R. canina
[17]
109
quinic acid
R. canina
[13]
Sugars
110
fructose
R. pimpinellifolia
[19]
R. villosa
[19]
R. canina
[12, 19]
R. dumalis
[19]
111
glucose
R. pimpinellifolia
[19]
R. villosa
[19]
R. canina
[12, 19]
R. dumalis
[19]
112
sucrose
R. pimpinellifolia
[19]
R. villosa
[19]
R. canina
[12, 19]
R. dumalis
[19]
113
trehalose
R. canina
[12]
114
sorbitol
R. pimpinellifolia
R. villosa
R. canina
R. dumalis
[19]
115
raffinose
R. canina
[12]
(Table 2) Contd….

12 Current Pharmaceutical Design, 2018, Vol. 24, No. 00 Ayati et al.
No.
Name of compounds
Structures
Species
Refs.
fatty acids
116
palmitic acid
R. agrestis
[20]
R. canina
[10, 20,
21]
R. dumalis
[10, 20]
R. rubiginosa
[20]
R. villosa
[10, 20]
R. pulverulenta
[10]
R. pisiformis
[10]
117
linolenic acid
R. agrestis
[20]
R. canina
[10, 20,
21]
R. dumalis
[10, 20]
R. rubiginosa
[20]
R. villosa
[10, 20]
R. pisiformis
[10]
R. pulverulenta
[10]
118
linoleic acid
R. agrestis
[20]
R. canina
[20, 21]
R. dumalis
[20]
R. rubiginosa
[20]
R. villosa
[20]
119
oleic acid
R. agrestis
[20]
R. canina
[20,
211]
R. dumalis
[20]
R. rubiginosa
[20]
R. villosa
[20]
120
stearic acid
R. agrestis
[20]
R. canina
[20, 21]
R. dumalis
[20]
R. rubiginosa
[20]
R. villosa
[20]
121
arachidonic acid
R. canina
[21]
122
arachidic acid
R. agrestis
[20]
R. canina
R. dumalis
R. rubiginosa
R. villosa
123
erucic acid
R. agrestis
[20]
R. canina
R. dumalis
R. rubiginosa
R. villosa
(Table 2) Contd….

Phytochemistry, Traditional Uses and Pharmacological Profile of Rose Hip Current Pharmaceutical Design, 2018, Vol. 24, No. 00 13
No.
Name of compounds
Structures
Species
Refs.
Galactolipid
124
(2S)-1, 2-di-O-[(9Z,
12Z, 15Z)-octadeca-9,
12, 15-
trienoyl]-3-O−β-D-
galactopyranosy glycerol
(GOPO®)
R. canina
[22]
tocopherols and vitamins
125
α-tocopherol
R. canina
[12]
126
β-tocopherol
R. canina
[12]
127
γ-tocopherol
R. canina
[12]
128
δ-tocopherol
R. canina
[12]
129
ascorbic acid (vitamin C)
R. pimpinellifolia
[19]
R. villosa
[19]
R. canina
[12, 19]
R. dumalis
[19]
3. ETHNOBOTANICAL AND ETHNOMEDICINAL USES
The fruits (hips) of different species of Rosa genus (family:
Rosaceae) have a long history of traditional use in folk medicine in
different parts of the world. The fruits of R. canina, the most fa-
mous species of the Rosa genus, have notable ethnobotanical and
traditional medicinal properties. It is a well-documented plant in the
European and Asian Traditional Medicine (Table 3). In Germany,
consumption of R. canina hips, known as Hakeputten, is believed to
prevent flu and colds [23]. In Romania, R. canina fruits commonly
known as "Stropacui" are used as a remedy for diarrhea [24]. Addi-
tionally, R. canina hips are used as a substitute for tea as well as
making syrup, jam and flour substitute by Hungarian ethnic groups
living in the Carpathian Basin [25]. Several species of this genus
(11 taxa) are used in Turkish traditional medicine. For example, the
hips of some of these species are known to treat cold and bronchi-
tis: R. canina L., R. dumalis Bechst., R. heckeliana Tratt. and R.
phoenicia Boiss. Moreover, the fruits of R. foetida Herrm., R. galli-
ca L. and R. pisiformis (H.Christ) Sosn. displayed laxative activity.
In Turkey and Canada, hips of R. gymnocarpa Nutt. ex Torr. &
A.Gray, R. nutkana C.Presl, R. spinosissima L. and R. villosa L. are
eaten and used as a substitute for tea (Table 3). In the Traditional
Chinese Medicine (TCM), the hips of R. roxburghii are edible and
utilized for their digestive, heat-clearing and detoxifying activities
[26]. In Korea, R. davurica fruit is reported as a traditional drug to
treatgastroenteric ailments [27]. The fruits of R. canina and R.
pulverulenta are extensively used in folk medicine for a wide range
of ailments in Lebanon. The fruit juice of the mentioned species is
orally consumed as an astringent, antidiarrhoeic, diuretic and anti-
scorbutic [28]. In the Iranian folk medicine, the fruits of R. canina
and R. beggeriana are used as diuretic and fro the treatment of hy-
pertension and kidney stones [29, 30]. Rosa webbiana is commonly
known as Shuli in India and its fruit has also been reported as a
traditional reemdy to treat jaundice and impotence [31]. In Argenti-
na, R. rubiginosa fruit is edible and used as an antitussive and for
dermatological purposes [32]. Rosa nutkana is native to British
Columbia and Canada; where it is traditionally used for children
suffering from diarrhea [33]. The most common ethnobotanical
uses of the Rosa species fruits in various countries seems to be
treatment of kidney stone, respiratory problems (cough, bronchitis
and cold), diarrhea, hypertension, diabetes and jaundice. The eth-
nobotanical and traditional uses of the Rosa species fruits in differ-
ent countries are summarized in Table 3.
4. PHARMACOLOGICAL ASPECTS OF ROSE HIP
4.1. Gastrointestinal System
As shown in Table 4, there have been some pharmacological
studies investigating the gastro-protective effects of rose hip partic-
ularly R. canina fruit. Some studies have indicated the anti-
ulcerogenic activity of R. canina fruit which was more effective
(2070 mg/kg) than the reference compound misoprostol at 0.4
mg/kg in rats [1]. Carotenoids of rose hip can protect gastric muco-
sa in peptic ulcer disease and gastroduodenal mucosal inflamma-
tion. An in vitro study showed that carotenoid from rose hip exerted
anti H. pylori effect (MIC50b=8.2 to 11 µg/ml) which was compa-
rable to that of metronidazole [9] (Table 4). However, the hydroal-
coholic crude extract of R. Canina did not show a significant anti-
ulcer effect [84].

14 Current Pharmaceutical Design, 2018, Vol. 24, No. 00 Ayati et al.
Table 3. Ethnobotanical uses of different rose hips in various countries around the world.
Refs.
Ethnobotanical uses
Part used
Country
Vernacular name
Rosa species
No.
[34]
Rose hips are used to make jelly
and jam, hips are also eaten fresh,
mostly by children
hips
Alaska
Khoh t'an
R. acicularis Lindl.
1
[35]
The fruit eaten by coastal house-
holds
fruit
Croatia
-
R. agrestis Savi
2
[36]
Fruit boil and use as tonic
fruit
Pakistan
Soori
R. beggeriana Schrenk ex Fisch. & C.A.Mey.
3
[29]
Antihypertensive, diuretic, treat-
ment of Kidney stone
fruit
Iran
Nastaran
[37]
Astringent, cold
treatment, antianemic
fruit
Spain
Tapaculos, tallos de
zarza, escaramujo, zarza
escaramujera
[38]
Cold, bronchitis, diuretic, sto-
machic
fruit
Turkey
Kusburnu
[30]
Treatment of blood pressure,
kidney stones, diuretic
fruit
Iran
Nastaran
[24]
Treatment of diarrhoea
fruit
Romania
Stropacui
[39]
diuretic, blood cell disorders,
sedation
fruit
Iraq
Shilan
[40]
treatment of common cold and
other infections, as diuretic agent
and for the treatment of various
inflammatory diseases
hips
Tunisia
Dog rose
[28]
Fruit juice is used as astringent,
antidiarrhoeic and antiscorbutic.
Decoction of fruits is taken to
treat dyspnoea and rheumatism
fruit
Lebanon
Ward Barri
R. canina L.
4
[41]
respiratory problems
(cough, bronchitis and
cold)
fruit
Macedonia
Trendafili i ege¨r
[42]
colds, vitamin C deficiency, for
disorders of the urinary tract and
kidney stones
fruit
Montenegro
ˇsipurak, divlja ruˇza
[43]
ant anemic, making jam
fruit
Switzerland
-
[44]
used to cure colds and influenza
(tea)
fruit
Serbia
Sipkinje, ˇSipak
[45]
cold, flu, cough
diabetes, appetizer
fruit
Turkey
Kusburnu, it burnu,
Okuz gotu
[23]
flu and colds prevention
hips
Germany
Hakeputten
[46]
against common cold
fruit
Uzbekistan
Nametek
[25]
making syrup, jam, preserves,
stewed fruit,
soaked drink; with yeast it was
made into wine; “cibere” soup,
enriched with bread; dried: tea;
ground: flour substitute in
famine
fruit
Hungary
Csipkerózsa, hecseli,
rózsabogyó, pecs,
bucske, seggvakaró,
istengyümőcs, vadrózsa,
csipkefa, szagrógya,
bicskerózsa
R. corymbifera Borkh.
5
(Table 3) Contd....

Phytochemistry, Traditional Uses and Pharmacological Profile of Rose Hip Current Pharmaceutical Design, 2018, Vol. 24, No. 00 15
Refs.
Ethnobotanical uses
Part used
Country
Vernacular name
Rosa species
No.
[27]
gastroenteric disorder
fruit
Korea
Saengyeolgwinamu
R. davurica Pall.
6
[47]
laxative, diuretics, treatment of
cold and pain of menstruation,
making marmalade or jam
fruit
Turkey
-
R. dumalis Bechst.
7
[47]
used as laxative
fruit
Turkey
-
R. foetida Herrm.
8
[47]
laxative, soothing, antiseptic,
treatment of psoriasis
fruit
Turkey
Gul
R. gallica L.
9
[48]
The small hips were eaten raw
and dried for tea.
hips
Canada
Baldhip rose
R. gymnocarpa Nutt. ex Torr. & A.Gray
10
[49]
antitussive, colds
fruit
Turkey
Şilank
R. heckeliana Tratt.
11
[50]
eaten as fresh, foodstuff
fruit
Turkey
Okuz gotu
R. hemisphaerica Herrm.
12
[51]
eaten raw as fruit or a snack
fruit
Nepal
Seghu
R. macrophylla Lindl.
13
[47]
making marmalade or jam and
fruit juice
fruit
Turkey
-
R. montana Chaix ex Vill.
14
[52]
treatment of constipation
fruit
Pakistan
Gangli gulab
R. moschata Herrm.
15
[33]
A tonic tea is made from the
fruits. Fruits are used for children
suffering from diarrhea.
hips
Canada
Nootka rose
R. nutkana C.Presl
16
[45]
cold, flu and diabetes
fruit
Turkey
Kusburnu, it burnu,
Okuz gotu
R. phoenicia Boiss.
17
[47]
used as laxative
fruit
Turkey
-
R. pisiformis (H.Christ) Sosn.
18
[28]
fruit juice is orally used as astrin-
gent, antidiarrhoeic, diuretic and
antiscorbutic
fruit
Lebanon
Ward Dabek
R. pulverulenta M.Bieb.
19
[26]
Heat-clearing and detoxifying
effect, inducing saliva and slakes
thirst, digestion, edible
fruit
China
Cili
R. roxburghii Tratt.
20
[32]
Edible, antitussive, dermatologic
fruit
Argentina
Rosa musqueta
R. rubiginosa L.
21
[53]
used in ophthalmic
fruit
Italy
Reusa
R. sempervirens L.
22
[47]
used as a tea substitute
fruit
Turkey
-
R. spinosissima L.
23
[47]
Laxative, diuretics, treatment of
cold and pain of menstruation,
making marmalade and also used
as a tea substitute
hips
Turkey
-
R. villosa L.
24
[31]
Treatment of impotency and
jaundice
fruit
India
Shuli
R. webbiana Wall. ex Royle
25
[54]
Ashes of hips is mixed with
mother's milk and applied to
children's ear-ache. Decoction of
hips is applied for stomach trou-
ble, fever, bloody cough and high
blood pressure.
hips
Afghanistan
Chyrir, Röhloy
[55]
Fruits were eaten raw or used to
make jelly
fruit
USA
Champes, rosa de costil-
la
R. woodsii Lindl.
26
4.2. Liver and Kidney
As shown in Table 4, hydro-ethanolic extract of R. canina fruit
(250- 750 mg/kg) could inhibit liver injury followed by liver toxici-
ty in rats. Hepatoprotective effect of rose hip has been reported to
be correlated with oxidative stress reduction [56]. It has been sug-
gested that R. canina fruit extract can act as a growth factor for
pancreatic beta-cell line in vitro [57]. This finding is in line with the
reported reduction of Fasting Blood Sugar (FBS) in a rat model of
streptozotocin-induced diabetes after treatment with 250, 500
mg/kg of the plant extract [85].

16 Current Pharmaceutical Design, 2018, Vol. 24, No. 00 Ayati et al.
It has been reported, in a rat model of nephrolithiasis, that rose
hip extract (250-500 mg/kg) has the potential to be used for kidney
stone prevention [58]. R. canina fruit extract also possesses protec-
tive effects against kidney function disturbances, oxidative stress
and histological damages induced by reperfusion injury [59]
(Table 4).
4.3. Central and Peripheral Nervous System
Table 4 shows the pharmacological activities of rose hip on the
nervous system. Rose hip extract has neuroprotective activities in
brain ischemia [60]. A potential anti-Alzheimer activity has been
reported for R. canina fruit extract. Antioxidant and anti-
inflammatory activities seem to be the main mechanisms through
which rose hip exert its neuroprotective effects [61]. However, only
two studies in rat models, reporting intraperitoneal administration,
are available (Table 4). Therefore, further investigations and clini-
cal trials are necessary to improve our understanding of the neuro-
protective activities of rose hip and its constituents (Table 4).
4.4. Heart and Arterials
Clinical and experimental studies have shown that administra-
tion of rose hip can reduce the risk of cardiovascular diseases [62,
63] (Table 4, 5). Rose hip which is rich in antioxidants with high
amounts of ascorbic acid and phenolic compounds that possess anti-
obesity, anti-inflammatory and antioxidative effects. Rose hip low-
ered plasma cholesterol and attenuated atherosclerotic plaque for-
mation in a hypercholesterolemic mouse model [63]. Administra-
tion of rose hip extract to high-fat diet (HFD)-fed mice could in-
crease fecal cholesterol content and liver expression of LDLR gene
as well as selected reverse cholesterol transport (RCT) genes, and
reduced blood pressure, oxidized LDL, total cholesterol and athero-
sclerotic plaque volume [63] (Table 4). In a randomized double
blind placebo-controlled trial, administration of R. Canina powder
(40 gr, 6 weeks) reduced markers of cardiovascular risk in obese
non-diabetic individuals [62].
4.5. Skin and Hair
One of the most frequent uses of rose hip in modern medicine is
its application in cosmetic products such as creams and soaps. In a
clinical study, topical administration of seed and shell powder of R.
canina fruit had significant effects on crow's-feet wrinkles im-
provement, and also increased skin moisture and elasticity [64]. In
some other clinical trials, R. canina seed oil could prevent
epithelitis after radiotherapy and erythema of surgical scars (Table
5) [65, 66]. Some other studies showed that proanthocyanidins from
rose hip methanolic extract could prevent melanogenesis in guinea
pig skin as well as mouse melanoma cells, and exerted beneficial
effects on skin-whitening factor when taken orally [67]. Quercetin
from rose hip could inhibit melanogenesis due to the inhibition of
both protein expression and activity of tyrosinase [68] (Table 4).
4.6. Joints and Muscles
Preclinical and clinical studies have demonstrated the anti-
arthritis and analgesic activities of rose hip [69, 70, 71, 72, 73, 74]
(Table 4, 5). In particular, these effects were observed in subjects
with osteoarthritis, rheumatoid arthritis and chronic musculoskeletal
pain (Table 5). Although a meta-analysis of RCTs found changes in
pain scores and ‘rescue medication’ after treatment with R. canina
hip powder compared to placebo, authors pointed out that the in-
cluded studies (287 patients: powder 145 patients and placebo 142
patients; median trial-duration of 3 months) were supported by the
manufacturer [72].
4.7. Anti-cancer Properties
Due to its high contents of antioxidant compounds such as phe-
nols, β-carotene, glutathione, tocopherol, ascorbate and anthocya-
nins, rose hip had gained attention as a possible anticarcinogenic
plant [75, 76]. Interestingly, R. canina extract prevented the growth
of tumor cell lines (colon, breast, lung, cervical and hepatocellular
carcinomas) but did not exert any toxicity in non-tumor liver prima-
ry culture [77] (Table 4).
4.8. Antioxidant Properties
Several in vitro studies have indicated antioxidant activities of
rose hip. These antioxidant activities are not only due to the high
amount of vitamin C but also due to a rich content of polyphenols,
proanthocyanidins, flavonoids, vitamin E and carotenoids [4, 75].
The total phenolics’ content of R. canina fruit is about 609.19 (mg
gallic acid 100 g-1), the total carotenoids content is 18.07 (mg þ-
carotene 100 g-1) and that of ascorbic acid is 27.49 (mg 100 g-1).
The ability of rose hip in scavenging H2O2 is about 87.26 % which
is much more than that of BHA (0.03 %) and BHT (0.14 %). Also,
the TEAC of this fruit is about 416 (µM Trolox g-1FW) which is
near to that of BHA (462 (µM Trolox g-1FW)) and more than BHT
(0.35 (µM Trolox g-1FW)) [78] (Table 4).
4.9. Anti-obesity Activities
In vivo preclinical studies have demonstrated significant inhibi-
tory effect of R. canina and rose hip fruit and seed extracts on
weight gain after oral administration. The extract of fruits and seeds
markedly decreased visceral fat weight in mice, without affecting
food intake [79, 80, 81]. Trans-tiliroside, one of the active constitu-
ents of the seed extract, was also shown to significantly suppress
body weight gain, liver TG levels and visceral adiposity at the dose
of 0.1-10 mg/kg/day [79]. It inhibited plasma glucose elevation
after 1 hour of glucose administration and increased the expression
of peroxisome proliferator-activated receptor α (PPAR- α) mRNA
levels in the liver tissue [79]. The anti-obesity effect of trans-
tiliroside was stronger than that of orlistat [79]. Also, in three small
clinical trials (subject number between 31 and 60), R. canina pow-
der or extracts was reported to reduce abdominal adiposity [81] as
well as cardiovascular risk factor associated with obesity such as
FBS [80] and circulating cholesterol levels [62].Therefore, it has
been suggested that R. canina could be potentially useful for the
development of a new class of anti-obesity agents [79, 80, 81] (Ta-
ble 4, 5).
4.10. Anti-inflammatory Activity
Rose hip extract and a number of its bioactive compounds have
been shown to reduce inflammation. Various molecular mecha-
nisms have been suggested for the inflammatory action of rose hip,
such as inhibition of the NF-kappaB signaling pathway which could
attenuate pro-inflammatory enzymes (e.g. MMPs and COX-2) and
decrease the production of pro-inflammatory cytokines (e.g. TNF-
alpha, IL-1beta, IL-6 and CCL5) [82]. Galactolipids are probably
important for the anti-inflammatory activity of R. canina fruit [83]
(Table 4). However, only preclinical studies are available and in
rats the administered dose ranged between 100 [84] and 500 [98]
mg/kg.
5. TOXICITY AND SIDE EFFECTS
Except for two cases of allergic contact dermatitis to rose hip
oil [102], no toxicity has been reported for this plant. Regarding
side effects, loose stools, flatulence and mild gastrointestinal dis-
comfort were reported in some of the clinical trials with rose hip
powder [62, 80].
CONCLUSION
In this review, the folklore applications, phytochemicals and
pharmacological properties of rose hip were evaluated. Rose hip
contains various constituents such as anthocyanins, phenolic deriva-
tives and vitamins. This plant has been used in traditional medicines
around the world for different purposes such as laxative, diuretic
and treatment of cold and pain. Although various pharmacological

Phytochemistry, Traditional Uses and Pharmacological Profile of Rose Hip Current Pharmaceutical Design, 2018, Vol. 24, No. 00 17
Table 4. in vitro and in vivo studies of rose hip activities.
NO.
Activity/
disease
Rosa spp.
Active constitu-
ents/preparations
Study design
Results
Refs.
gastrointestinal
1
ethanol 96%induced
peptic ulcer
R. canina
fresh fruits aqueous
extract
rats model, 2070 mg/kg, orally
15 min before induction
gastro-protective effect through ↓ainflammation,
↓edema, ↓epithelial injury, ulcer preventive
effect
[1]
2
anti-Helicobacter
pylori activity
R. canina
carotenoids
in vitro study
anti-H. pylori effects (MIC50b=8.2 to 11 µg/ml ),
comparable to metronidazole.
[9]
3
ethanol 96%-induced
gastric damage
R. canina
hydro alcoholic
crude extract of
fruits
rat model, 100 and 200 mg/kg of
aqueous solution of extract
reduced gastric damage, not significant anti-ulcer
genic effectiveness
[84]
liver and kidney
4
chronic carbon tetra-
chloride-induced
hepatotoxicity
R. canina
hydro-ethanolic
fruit extract
rat model, 250, 500, and 750
mg/kg, six weeks, orally
↓liver injury, ↓oxidative stress
[56]
5
antidiabetic (acting as
growth factor for
pancreatic beta-cell
line)
R. canina
hydro extract
in vitro on ß cell lines
↑ßtc6 cells at 24, 48, 72, 96 h.; significant cell
alteration
[57]
6
CaOx kidney stones
prevention
R. canina
hydromethanol
extract
rat model, nephrolithiasis with
ethylene glycol (1% EG), 250-
500 mg/kg, 30 days
↓kidney and liver lipid peroxides, ↓renal and
urinary calcium contents, ↓size and number of
CaOxe calculi in the kidneys, ↑citrate excretion
[58]
7
renal disturbances
induced by reperfusion
injury
R. canina
fruit extracts
rat model
↓creatinine clearance, ↓absolute excretion of
potassium, ↓urine osmolarity, ↓increase in abso-
lute excretion of sodium, ↓blood creatinine and
urea concentrations, ↓degree of histological
damages and level of malondialdehyde; ↑cferric
reducing/antioxidant power level
[59]
8
streptozotocin induced
diabete
R. canina
ethanolic extract
rat model, 250, 500 mg/kg,
orally
↓FBSd
[85]
central and peripheral nervous system
9
neuroprotective effects
against ischemic brain
injury
R. canina
Setarud® (Rosa
canina, Urtica
dioica, Tanacetum
vulgare with sele-
nium)
rat model, 0.66 mL/kg, intraperi-
toneal, 30 minutes after middle
cerebral artery occlusion.
↓ cerebral infarct volume
↑motor function
[60]
10
neuroprotective effect
in alzheimer
R. canina
with some
other ex-
tracts
extract
rat model, intraperitoneal, 21
days
↑spatial learning, better expression of Sypf and
Psen1g
[61]
heart and arteries
11
antiatherosclerotic
effects
R. canina
extract
hypercholesterolemic mouse model,
6 months
↓blood pressure, ↓plasma cholesterol;
↓atherosclerotic plaques formation; ↑nitric
oxide dependant vasodilation
[63]
(Table 4) Contd….

18 Current Pharmaceutical Design, 2018, Vol. 24, No. 00 Ayati et al.
NO.
Activity/
disease
Rosa spp.
Active constitu-
ents/preparations
Study design
Results
Refs.
skin and hair
12
melanin biosynthe-
sis
R.
canina
aqueous extract
In vitro on B16 mouse melanoma
cells
In vivo on brown guinea pigs with
UVB-induced pigmentation, oral
administration
the 50% ethanol eluate: ↓Production of melanin
↓intracellular tyrosinase
[67]
13
melanin biosynthe-
sis
R.
canina
quercitin
B16 mouse melanoma cells
↓tyrosinase expression
↓intracellular tyrosinase activity
[68]
joints and muscles
14
arthritis
R. multiflora
petroleum ether
extract
rat collagen-induced arthritis
model, (12, 36 or 120mg/kg/day,
orally), 28 days
↓arthritis severity score, ↓paw swelling, ↓joint
inflammation, ↓cartilage surface erosion
[69]
anti-cancer
15
colon and breast
cancer
R. villosa
hydroalchoholic
extract
in vitro model, colon cancer
cells HT29 and breast cancer
cells MCF-7
↓proliferation
[86]
16
cytotoxic effect
R. canina.
aqueous, ethanolic and
petroleum ether ex-
tracts
in vitro, sarcoma cells
ether extract had cytotoxic effect
[87]
17
antioxidant and
antineoplastic activity
R. canina
vitamin C, flavonoids,
phenolic acids
in vitro, HeLa, MCF7 and HT-
29 cell line, vitamin C, 39.17
mg/kg, flavonoids, 451.05
microg/kg, phenolic acids,
504.69 microg/kg
flavonoids and vitamin C posed antioxidant
activity. flavonoids ↓ cell growth, while vitamin
C did not.
[88]
antioxidant
18
antioxidant activity
R. canina
fruit extract derived
of vitamin C
in vitro, neutrophil respiratory
burst
↓reactive oxygen species
[77]
19
total antioxidant
activity
R.
canina
extracted lyophi-
lized powdered
fruit
in vitro, hydroxyl radical, hydro-
gen peroxide and Trolox equiva-
lent antioxidant capacity
higher antioxidant activity than BHAh,
except in the TEACi assay
[78]
20
antiproliferative and
antioxidant effects
R.
canina
total extract, vita-
min C, neutral
polyphenols, acidic
polyphenols
in vitro, ABTSj method, human
colon cancer cell lines (Caco-2)
high cytotoxicity and antioxidant properties
[89]
21
correlation of antioxi-
dant effect mecha-
nisms and polyphenol
content
R. canina
polyphenol
in vitro
superoxide anion and DPPHk radical scav-
enging effect.
↓concentration → ↑metal ion chelating
activity
[90]
22
antioxidant activity
R. canina
R. moscha-
ta
crude extract,
CHCl3 extract,
ascorbate-free
extract
in vitro, FRAPl assay, ABTS
assay, lipid peroxidation
antioxidant properties in all samples, inhibi-
tory effect against lipid peroxidation
[91]
(Table 4) Contd….

Phytochemistry, Traditional Uses and Pharmacological Profile of Rose Hip Current Pharmaceutical Design, 2018, Vol. 24, No. 00 19
NO.
Activity/
disease
Rosa spp.
Active constitu-
ents/preparations
Study design
Results
Refs.
antinociceptive
23
antinociceptive activi-
ty
R. canina
aqueous, ethanol
extract, ethylace-
tate , n-butanol
fraction
mice model, p-benzoquinone-
induced abdominal constriction
test
antinociceptive properties (with ethylacetate
and n-butanol fractions)
[92]
lipid accumulation and body fat reduction
24
fat weight and lipid
profile
R. canina
80%aqueous
acetone extracts of
fruit and seeds
mice model, fruit extract (25, 50
mg/kg/day) and seeds extract
(12.5 and 25 mg/kg/d), trans-
tiliroside (0.1-10 mg/kg/day)
extracts of seeds and fruits: ↓gain of body
weight, ↓visceral fat weight, without affecting
food intake, ↓ TGm and free fatty acid
trans-tiliroside: significant anti-obese effect
[79]
25
anti-hyperlipidemic
effect
R. canina
ethanolic extract
rat model, streptozotocin induced
diabete, 250, 500 mg/kg, orally
↓serum TG and Choln;.
LDLo and HDLp not changed significantly.
Islets necrotic and regenerated pancreatic islet
cells were improved
[85]
26
lipid accumulation
R. canina
extract
mice model, high-fat diet (HFD)
with 1% extract (RH), 8 weeks
↓body weight, ↓less visceral fat, ↓Liver
weight, ↓total hepatic lipid, ↓triglyceride,
↓expression of peroxisome proliferator-
activated receptor gamma (PPARgamma) in
epididymal fat
[93]
27
weight gain prevention
not known
powder
mice model, high fat diet, 295 g,
3 months
↓(body weight, FBS, total chol., insulin
levels); ↑((EE (energy expenditure), VO2,
VCO2) ↑metabolic rate during treadmill
exercise. upregulated of Ucp1and other BAT
and brite markers
[94]
anti-inflammatory and immunomodulatory effect
28
anti-inflammatory
R. canina
hydroalcoholic
extract
rat model, paw edema assay;100
and 200 mg/kg, oral administra-
tion
↓edema in both doses
[84]
29
inflammatory
R. canina
aqueous, ethanol
extract, ethylace-
tate, n-butanol
fraction
mice, carrageenan-induced and
PEG –induced hind paw edema
model
anti-inflammatory properties (with
ethylacetate and n-butanol fractions)
[92]
30
chemotaxis inhibition
of blood neutrophils
R. canina
galactolipid
in vitro, PMNsq isolated from
peripheral blood, Boyden cham-
ber technique
↓migration of PMNs
[95]
31
immunomodulatory
effect
R. canina
triterpene acids
in vitro, Mono Mac 6 cell line (as
a model for human macrophages)
↓lipopolysaccharide induced interleukin-6
release.
[96]
32
cytokine production
and proliferation of T
cells and B cells
R. canina
triterpene acid
mixture
in vitro, normal mononuclear
cells, human thyroglobulin and
lipopolysaccharide
↓production of tumor necrosis factor-alpha
and IL-6r, ↓CD4s(+) T-cell and CD19(+) B-
cell proliferation
[97]
33
immunomodulatory
R. canina
extract
rat model, 250-500 mg/kg, orally,
4weeks
↑(gamma globulin level, neutrophil, monocyte
counts, phagocyte activity), ↑Thiobarbituric
acid reactive substances (TBARSt), ↓GSHu
levels
[98]
34
anti-inflammatory
R. canina
choloroform
extract
in vitro, chondrocytes treated
with IL-1beta, 72 hours
↓IL-1beta-induced NF-kappaB activation
downregulation of NF-kappaB targets includ-
ing COX-2v and MMPsw
[99]
a. ↓: decrease

20 Current Pharmaceutical Design, 2018, Vol. 24, No. 00 Ayati et al.
b. MIC: minimum inhibitory concentration
c. ↑: increase
d. FBS: fasting blood sugar
e. CaOx: calcium oxalate
f. Syp: Synaptophysin
g. Psen1: Presenilin-1
h. BHA: butylated hydroxyanisole
i. TEAC: tetraethylammonium chloride
j. ABTS: 2, 2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)
k. DPPH: 2, 2-diphenyl-1-picrylhydrazyl
l. FRAP: ferric reducing ability of plasma
m. TG: triglyceride
n. Chol: cholesterol
o. LDL: low-density lipoprotein
p. HDL: high-density lipoproteins
q. PMN: polymorphonuclear leukocytes
r. IL: Interleukin
s. CD: cluster of differentiation
t. TBARS: thiobarbituric acid reactive substances
u. GSH: glutathione
v. COX-2: cyclooxygenase-2
w. MMPs: matrix metalloproteinases
Table 5. Clinical trials and meta-analysis related to reported medicinal uses of rose hip.
No.
Activity/
Disease
Rosa spp.
Active constitu-
ents/preparations
Study design
Dose
Participants
Description
Refs.
1
cell longevity, skin wrinkles,
moisture, and elasticity
R. canina
seeds and shells
powder (Hyben Vital®)
randomized, double-
blind
45 gr/day, 8
weeks
34 healthy subjects
Age: 35-65 years
Crow's-feet wrinkles
improvement, ↑skin mois-
ture, ↑elasticity
↑satisfaction
↑cell longevity of erythro-
cyte cells during storage for
5 weeks
[64]
2
pain reduction in osteoar-
thritis
R. canina
powder
meta-analysis of
randomized con-
trolled trials (RCTs).
primary outcome:
reduction in pain
calculated as effect
size (ES)
---
---
↓pain
[72]
3
acute exacerbations of
chronic pain
R. canina
powder (Litozin®)
pilot study
providing up
to 3 mg
galacto-
lipid/day, 54
weeks
152 men
overall improvement,
changes were greater in
patients with grater degrees
of disability and pain
[71]
4
pain reduction and general
wellbeing improvement in
osteoarthritis patients
R. canina
Hyben Vital®(stand.
powder of fruits)
double-blind, place-
bo-controlled, cross-
over
5 gr/day, 3
months
112 patients with
osteoarthritis
↓symptoms of osteoarthritis,
general wellbeing, ↓joint
pain and stiffness
[70]
5
cell injury inhibition in hip
and knees in Osteoarthritis
R. canina
standardized rose-hip
powder of seeds and
husks
double-blind, ran-
domized, placebo-
controlled
0.5-gr, BIDa,
4 months
100 patient
↑hip joint mobility ↓pain
[73]
6
symptom reduction in
rheumatoid arthritis
R. canina
powder
double-blind placebo-
controlled, Primary
outcome variable
5gr/day, 6
months
89 patient
pain scale not changed;
↑physical scores, mental
score remained unchanged
[100]
8
chronic musculoskeletal
pain
R. canina
powder of hip and seed
compared to
pseudofruit powder
(Litozin®)
pilot study
up to 20
gr/day in
yoghurt, 3
months
52 patients with
acute exacerbation
of low back pain or
knee pain
no differences
[74]
(Table 5) Contd....

Phytochemistry, Traditional Uses and Pharmacological Profile of Rose Hip Current Pharmaceutical Design, 2018, Vol. 24, No. 00 21
No.
Activity/
Disease
Rosa spp.
Active constitu-
ents/preparations
Study design
Dose
Participants
Description
Refs.
9
osteoarthritis
R. canina
standardized rose-hip
powder
randomized, double
blind, placebo-
controlled
five 0.5 gr
capsules,
BID, 4
months
100 patients
↑hip joint mobility,
↓ pain
[101]
9
glycemia and lipid profile
R. canina
aqueous extract
randomized, double
blind, placebo-
controlled
750 mg BID,
3 months
60 patients with type
2 diabetes
↓(FBS, cholesterol/HDL-C)
[80]
10
human abdominal visceral
fat reduction in preobese
subjects
R. canina
extract
double-blind and
randomized
100 mg/day ,
12 weeks
32 subjects, BMIb
>= 25 , <30
↓(abdominal total fat area,
abdominal visceral fat area,
body mass and body weight
index at week 12 , ab-
dominal subcutaneous fat
area)
[81]
11
risk of cardiovascular
disease
R. canina
powder
randomized, double
blind, placebo-
controlled
40 gr, 6
weeks
31 obese non
diabetic individuals,
↓systolic blood, ↓(LDL)
cholesterol levels,
↓LDL/HDL ratio, ↓reynolds
risk assessment score for
cardiovascular disease
[62]
12
epithelitis prevention after
radiotherapy
different
plant
species
seed oil (Repavar®)
prospective, explora-
tory, controlled and
open clinical study
topically, BID
28 patients with
head and neck
cancer treated with
intensity modulated
radiotherapy
effective in prevention of
severe epithelitis
[65]
13
post-surgical scars
different
plant
species
seed oil
(Repavar ®)
comparative, single-
center, prospective,
double blinded
topically,
BID, 6 weeks
108 patients with
open surgical
procedures for skin
tumor removal
↓erythema, ↓atrophy,
↓discoloration
[66]
a: BID: twice a day
b: BMI: body mass index
activities including anti-arthritis, anti-obesity and antioxidant ef-
fects have been reported for rose hip in preclinical studies, still
more studies are necessary to fill existing gaps in our knowledge of
the pharmacological effects and bioactive ingredients of rose hip.
LIST OF ABBREVIATIONS
ABTS = 2, 2'-azino-bis(3-ethylbenzothiazoline-6-
sulphonic acid)
BHA = butylated hydroxyanisole
BHT = butylated hydroxytoluene
BID = twice a day
BMI = body mass index
CaOx = calcium oxalate
CCL5 = chemokine (C-C motif) ligand 5
CD = cluster of differentiation
Chol = cholesterol
COX-2 = cyclooxygenase-2
DPPH = 2, 2-diphenyl-1-picrylhydrazyl
FBS = fasting blood sugar
FRAP = ferric reducing ability of plasma
GSH = glutathione
HDL = high-density lipoproteins
HFD = high-fat diet
HHDP = hexahydroxydiphenoyl
IL = Interleukin
IL-1beta = interleukin-1beta
IL-6 = interleukin-6
LDL = low-density lipoprotein
MMP = matrix metalloproteinase
PA = Proanthocyanidin
PMN = polymorphonuclear leukocytes
PPAR- α = peroxisome proliferator-activated receptor α
Psen1 = Presenilin-1
RCT = reverse cholesterol transport
Syp = Synaptophysin
TBARS = thiobarbituric acid reactive substances
TEAC = tetraethylammonium chloride
TG = triglyceride
TNF-alpha = tumor necrosis factor-alpha
CONSENT FOR PUBLICATION
Not applicable.
CONFLICT OF INTEREST
The authors declare no conflict of interest, financial or other-
wise.

22 Current Pharmaceutical Design, 2018, Vol. 24, No. 00 Ayati et al.
ACKNOWLEDGEMENTS
This study has been supported by the Deputy of Research of
Mashhad University of Medical Sciences.
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