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Journal of Pharmacy and Pharmacology, 2022, XX, 1–19
https://doi.org/10.1093/jpp/rgac053
Advance access publication 7 October 2022
Review
Pharmacological and phytochemical potential of Rubus
ellipticus: a wild edible with multiple health benefits
PushpaKewlani1, DeeptiTiwari1, SandeepRawat2, and Indra D.Bhatt1,*,
1Centre for Biodiversity Conservation and Management, G.B. Pant National Institute of Himalayan Environment, Kosi-Katarmal, Almora,
Uttarakhand, India
2Sikkim Regional Centre, G.B. Pant National Institute of Himalayan Environment, Pangthang, Gangtok, Sikkim, India
*Correspondence: Indra D. Bhatt, Centre for Biodiversity Conservation and Management, G. B. Pant National Institute of Himalayan Environment, Kosi-
Katarmal, Almora, Uttarakhand 263 643, India. Email: id_bhatt@yahoo.com; idbhatt@gbpihed.nic.in
Abstract
Objectives Rubus ellipticus (family Rosaceae) is used for its delicious edible fruits in the Himalayan region and other parts of the globe. However,
the full potential of the species is yet to be harnessed. The current review focuses on the phytochemical, traditional uses, morphological, mo-
lecular and pharmacological potential of R. ellipticus.
Key findings The review of the literature reveals that many health-promoting compounds of R. ellipticus have been reported from the species
along with the different biological properties, such as nephroprotective, anti-inflammatory, analgesic, anti-pyretic, anti-proliferative, cytotoxicity,
anti-cancer, wound healing, anti-fertility, anti-plasmodial, anti-microbial and antioxidant. Traditionally, it is used in many formulations, which are
validated through primary pharmacological assays. However, several medicinal properties are still need to be validated through detailed pharma-
cological and clinical studies.
Summary All the information is available in a scanty form, and the complete information is missing on a single platform. Such type of informa-
tion will help researchers to better utilize the available data for initiating future research on the species as it has the potential to contribute to
the food and pharmaceutical industry. The review highlights the need for further studies on the species to harness its potential in nutraceutical,
functional food, energy supplement, and beneficial therapeutic drug development program.
Keywords: Rubus; berries; nutraceutical; wild edible; Himalaya Raspberry
Introduction
The efforts to address food insecurity and improve health are
greatly acknowledged worldwide.[1,2] It is well known that
only a few crops are being utilized to fulll the food and nu-
trition need. Still, the growing population size and shrinking
agricultural land hamper the continuity, and how long it will
support is a question of debate. Therefore, there is a need
to search for alternative resources to lessen the pressure on
crops. In this context, wild resources such as wild edible
fruits can play a crucial role in meeting food and nutritional
security, as these have regional-specic diversity, adapta-
bility, and applications.[3] These wild edible plants are rich in
vitamins and essential nutrients.[4] In addition, they possess
valuable phytochemicals used for medicinal purposes.[5]
Indian Himalayan Region (IHR) is known for its rich bi-
odiversity. It supports more than 670 wild edible plant spe-
cies, many commercially utilized for nutritional supplements
and health-benecial products.[6,7] Among these, Rosaceae is
a dominant family of wild edibles in the Himalayan region
represented by many valuable species like Pyrus, Prunus,
Rubus, Fragaria, Rosa, and Potentilla, which are traditionally
being used as food supplements and genetic backup of a wild
relative of cultivated crops.[6] The Rubus genus represents a
diverse group of blackberries, and raspberries have a special
consideration among nutritionists due to their appearance,
deliciousness, and health benets.[8] Commercially impor-
tant species R. idaeus, R. occidentalis, and many others can
easily be hybridized with wild species and produce fertile
accessions. The genus is represented by more than 900 species
within its 12 subgenera.[9] Rubus fruits are gaining research
attention due to the presence of high vitamins (ascorbic acid
and others), minerals, bioactive compounds, such as antho-
cyanin, phenolics, and avonoids[7,10] antioxidants[11] and
health-promotingbenecial properties. The benecial effects
of berry phytochemicals have been reported due to their
ability to modulate gene expression through nuclear receptors
and subcellular signaling pathways and subsequently prevent
oxidative damage.[12,13]
Rubus ellipticus Smith (syn. R. avus Buch-Ham. ex D.
Don, R. gowreephul Roxb.; R. hirtus Roxb.; R. paniculatus
Moon; R. rotundifolius Wall.; R. wallchianus wight Arn.) is
an evergreen shrub distributed throughout the sub-tropical
to the sub-temperate region.[14] Geographically, the spe-
cies is found in south and south-east Asian countries within
various habitats, such as hilly terrain, roadside, mountain
valleys, forest, and slopes.[15] Its delicious edible fruits are
consumed raw in the Himalayan region,[16] while other parts
of the plant (leaves, roots, and fruits) play a vital role in
Ayurveda, traditional Chinese, and different folk medicine.
Different plant parts of this species have been used to cure
© The Author(s) 2022. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please
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Received: January 3, 2022. Editorial Acceptance: June 28, 2022
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2Pushpa Kewlani et al.
diarrhea, dysentery, cough, fever, colic, constipation, gastric
trouble, vomiting, wounds, and uterine relaxant since ancient
times.[17–23] Various health-promoting bioactive compounds
have been reported from the species[11,24,25] with many bene-
cial pharmacological activities.[26–28]
With the increase in the ow of information on the species,
there is a need to collect and compile the existing informa-
tion to highlight its potential. The present review provides
information on traditional knowledge, phytochemicals, nu-
tritional, pharmacological potential, and genomic advances
of R. ellipticus. A detailed study of the available literature
will identify the gap areas and provide complete informa-
tion in one place for improving understanding of the various
aspects of this species. Furthermore, the review highlights the
potential of the species for the development of nutraceutical,
pharmaceutical, and health-promoting products, which will
provide baseline information for future research and help to
promote the conservation and utilization of R. ellipticus.
Approach for Data Collection
For this systematic review, we conducted a literature search
related to various aspects of R. ellipticus according to
Preferred Reporting Items for Systematic Reviews and Meta-
Analysis (PRISMA), an internationally recognized guide-
line for reporting reviews. The search was carried out from
August 2020 to December 2021 using three online databases:
Google Scholar, Wiley, and Scopus. This review included the
following search terms ‘Rubus ellipticus’ AND ‘Himalayan
raspberry’, ‘ethnomedicinal uses’ OR ‘traditional uses’,
‘phytochemicals’, OR ‘secondary metabolites’ ‘nutritional
analysis’ OR ‘proximate analysis’, ‘pharmacological activity’
OR ‘biological activity, ‘socio-economic’ OR ‘molecular as-
pect’. At the initial stage of the literature search, a total of
3456 references were found for the study, of which 614 were
duplicates and excluded.
The selected articles were thoroughly read for eligibility
criteria, and 314 articles were retrieved. These ndings were
further assessed for inclusion (full papers, investigation asso-
ciated with ethnomedicinal, nutritional and phytochemical,
socioeconomic, molecular aspect and pharmacological ac-
tivities of R. ellipticus and exclusion (only abstracts, posters,
presentations, not experimental, qualitative data only, and dis-
sertation) criteria. Finally, a total of 123 studies were selected
for this review. The procedure of selecting and screening lit-
erature for PRISMA analysis is depicted in Figure 1. Some of
the papers fall within two categories; therefore, the total of
these articles may seem higher than the reviewed papers.
Botanical Description and Distribution
R. ellipticus is an evergreen shrub, which grows up to 6 m
long with a purple-brown stem having shaggy long purplish-
brown exuous bristlier or glandular hairs. The leaves of the
plant are elliptic, rough, acute at the apex, spiny below and
orbicular obviate with leathery leaets. The inorescence is
ovate, acute, bisexual ower, petals 7–8 mm long, and white
owers with yellow intermixed tomentose in clusters in leaf
axils, which are 1–1.5 cm wide. The fruits are succulent
drupes, orange-yellow, 6.0 mm long, and 7.0 mm wide.[29,30]
The Rubus species are well adapted to different habitats and
have evolved mechanisms for natural resistance to biotic and
abiotic environmental factors.[31] R. ellipticus is commonly
preferred to grow in slopes, open forests, and roadsides be-
tween 300 and 2600 m.a.s.l. It is native to south-east Asia
and distributed in south-western China, India, Bhutan, Nepal,
Laos, Myanmar, Pakistan, Philippians, Sri Lanka, Thailand,
and Vietnam. However, it is invasive in Hawaii and Australia
and naturalized in tropical Africa, tropical South America,
West Indies, and England.[32]
Traditional and Ethnobotanical Uses
In Traditional Chinese medicine, the Rubus genus has a
long history of medicinal use with remarkable therapeutic
effects in curing liver and kidney meridians due to its sweet
and warm properties. Its roots and bark are applied to re-
duce sore lower back, improve eyesight and prevent uterine,
cervical, and colon cancer in China.[33] Several species of the
genus are used to treat wounds, burns, inammation, mi-
crobial infection (anti-microbial), anticonvulsant, muscle
relaxant, and radical scavenging, ulcers, gastrointestinal
problems, and diabetes.[34] For instance, the plant part of
R. ulmifolius is used to cure ulcers, abscesses, furuncles, red
eyes, vaginal disorders, intestinal inammations, diarrhoea,
and haemorrhoids.[35] The fruits of R. fruticosus are used in
dermatological problems, such as itching, eczema, scabies,[36]
and gynecological disorders.[37] The leaves of R. idaeus are
consumed as a tablet, tea, or tincture during pregnancy to
facilitate labour and easy childbirth[38,39] and uterine relaxant
stimulants during connement.[40]
Different plant parts of R. ellipticus are used traditionally
to cure various diseases, such as diarrhoea, dysentery, cough,
fever, colic, constipation, gastric trouble, vomiting, wounds,
uterine relaxant, wound healing agents, analgesics, and anti-
pyrectics (Table 1). Its edible fruits are juicy and delicious
and have been considered astringent, febrifuge, stomachic,
laxative, and carminative. Fruits are medicinally used to
treat indigestion,[41] cholera,[42] blood and heart problems,[43]
diabetes, constipation, nausea, tonic, stomach, and abdom-
inal pain disorders.[44–49] Paste of young fruits (10–20 g) is
consumed twice or thrice a day as an antacid for treatment of
gastritis and in diarrhoea and dysentery.[50] Fruit juice is used
for gastrointestinal problems and mouth disorders, such as
leukoplakia, cold sores, and mouth ulcers.[51]
The leaves of the species are used in wound healing,[20]
diarrhoea, colic, and uterine relaxant,[17] while leaf buds
are used to treat peptic ulcers.[72] Its roots are laxative and
used in the treatment of paralysis,[67,73] bone fracture, head-
ache, urinary tract infection, stomach-warm, stomach-ache,
typhoid, measles, fevers, gastric troubles, wound, and jaun-
dice,[52,58,61,69,74] ulcer, skin infection,[56] Parkinson’s disease and
other CNS disorders.[62] The root juice is consumed against
urinary tract infection, and root paste is applied on the fore-
head to relieve headache, while root decoction is used for bel-
lyache.[75] In Nepal, some rural communities consume juice of
buds and roots to cure diabetes mellitus, whereas the juice of
buds and leaves is applied externally for cuts and wounds.[76]
Its root is an intoxicant ingredient; root juice treats fevers, gas-
tric troubles, dysentery, and root decoction. It is used as an
intoxicant during wine preparation [65,77,78], while shoots are
used for stomach warmth, stomach pain, and headache.[52,73]
The bark is used in fever, gastric troubles, diarrhea, dysen-
tery, colic,[79] common cold, and blood disorders.[54,72] Peeled
young shoots are eaten raw for the sour taste, and fruits are
eaten as snacks.[80] The whole plant is used against gastralgia,
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3A wild edible with multiple health benefits
cholera, wound healing, anti-fertility, anti-microbial, anal-
gesic, epilepsy, fever, diabetes mellitus, ulcer, skin infections,
endocrine and metabolic ailments, colic pain, diarrhea, piles,
hyperthermia and helminthic infestation in children.[81–84] All
this information on the species can be useful for developing
new therapeutic agents after validating traditional knowledge.
Proximate and Nutritional Composition of
Fruits
Proximate and nutritional studies of R. ellipticus fruits re-
vealed their high nutritive value due to the presence of
carbohydrates, crude bre, fat, protein, lipid, and minerals
(Figure 2). A high content of carbohydrate (86.4%) and crude
bre (3.53%) has been reported in the fruits of R. ellipticus,
along with a signicant amount of crude protein (4.37%),
crude lipid (2.73%), and high energy value (374.0 Kcal).
Sundriyal and Sundriyal reported carbohydrate (72.7%) and
bre (7.90%) in fruits of R. ellipticus.[4] Total sugar has been
reported as 8.73% in fruits of the species.[84] The reducing
(5.66%) and non-reducing (2.90%) sugars are found in the
fruit.[85] Similarly, the protein composition of this species
makes it a good source of amino acids as a total of 16 amino
acids have been identied in R. ellipticus fruits.[86]
Moisture content in R. ellipticus fruits has been reported
from 64.4% to 80.6%, while ash content ranged from 1.30%
Figure 1 Flow diagram of process for review of the literature used in this study.
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4Pushpa Kewlani et al.
Table 1 Traditional and indigenous uses against different diseases and modes of application of R. ellipticus in different parts of the world
S.
No
Plant part Geographic region/
community
Dose/mode of administration Used in disease References
1. Young shoot Dzongu Valley, Sikkim Chewing raw shoots Stomach pain [52]
2. Root Dzongu Valley, Sikkim Decoction Stomach warm of children [52]
3. Root Dzongu Valley, Sikkim Paste Forehead during severe
headache
[52]
4. Root Sikkim Root paste is used as a poultice Bone fracture [50]
5. Ripe fruit Sikkim Eaten raw Laxative used in constipa-
tion
[50]
6. Fruits Sikkim 10–20 g fruits twice and thrice in a day Gastritis, antacid, diarrhoea,
and dysentery
[50]
7. Root Western Nepal Juice Urinary tract infections [53]
8. Bark Bhutan – Common cold and blood
disorders resulting from
defective air
[54, 55]
9. Root Garhwal Himalaya,
Uttaranchal
Paste Skin infections and diseases,
and ulcers
[56, 57]
10. Root Nepal (Chepang) Wound, jaundice, typhoid [58]
11. Root East Nepal (Lepcha) 10–20 ml of juice taken orally Diarrhoea, cholera, gastritis,
sore throat
[71]
12. Root Bageshwar, Uttarakhand Decoction (10 ml dose) of 100 g root
with water for 5 days
Gastrointestinal problems
and fever
[21, 60]
13. Leaf Bageshwar, Uttarakhand Paste Wound healing [21]
14. Fruit Bageshwar, Uttarakhand Juice Cholera [42, 61]
15. Fruit Nainital, Uttarakhand Eaten Raw Diabetes, stomach disorders
and digestion problems
[48]
16. Root Nepal (Chitwan–
Panchase–Mustang)
Paste of roots is mixed with various
plant species, and 1 spoon (fresh) or 1/2
spoon (dry) is consumed with 1 glass of
water once a day
Mental diseases [62]
17. Ripe fruits Udhampur, Jammu &
Kashmir
Taken orally act as aperients and juice of
tender leaves
Oral ulcer [63]
18. Root Kaski, Central Nepal Decoction Typhoid and fever [64]
19. Young leaves Dronagiri, Uttaranchal Paste of leaves with cold water thrice a
day is given orally and same paste with
hot water
Acute diarrhoea and consti-
pation
[65]
20. Root Panchase, Central Nepal 1–2 spoons of root powder diluted with
a half glass of water and drunk twice a
day for 2–3 days
Fever [66]
21. Root Almora, Uttarakhand Root decoction is used with Girardinia
diversifolia root and bark of
Lagerstroemia parviora
Fever, gastric trouble,
diarrhoea and dysentery
[61]
22. Fruit Ziro valley, Arunachal
Pradesh
– Indigestion [41]
23. Fruit Jasrota hill, Jammu and
Kashmir
Juice of fruits Gastrointestinal problems
and mouth disorders
[51]
24. Root Hasanur hills, Tamil Nadu The root paste is taken internally Paralysis [67]
25. Root Indo Aryan and Gurang
communities
Ash of Eleusine coracana (L) our with
R. ellipticus root paste is externally ap-
plied once a day
Wound healing [66]
26. Fruit Gurang community During fever, typhoid fruits are eaten in
jelly form and stored for 3–4 months for
a bottle
Fever, typhoid, cut, wound,
hypothermia and appetizer
[66]
27. Young leaves Gurang community Chewed once a day for 2–3 days. Fever, cough, gastritis [66]
28. Root Gurang community Paste 1 spoon for children and 2 spoons
for young people diluted with a half
glass of water and drunk once a day for
2–3 days
Hyperthermia [66]
29. Root Kaverpalanchok, Central
Nepal
The crushed root is inhaled Rhinitis and sinusitis [68]
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5A wild edible with multiple health benefits
to 4.1%. Fruits of R. ellipticus contain a wide variety of es-
sential minerals, including Ca (450.1 mg/100 g), Mg (118.72
mg/100 g), K (680.16 mg/100 g), P (1.26 mg/100 g), N (700
mg/100 g), Na (89.43 mg/100 g), Fe (4.249 mg/100 g), Zn
(12.77 mg/100 g), Cu (0.020 mg/100 g), Pb (0.02 mg/100 g),
Mn (1.948 mg/100 g), Cr (0.47 mg/100 g) which is impor-
tant for strengthening bone and immune system.[84] Besides,
Himalayan raspberry is considered a reservoir of total vitamin
C and reported between 4.10 and 44.00 mg/100 g in different
studies.[85, 87, 88] A good amount of total sugar (39.0%) and
total soluble solids (TSS) ranging between 10.02 and 15.11
Brix,[14] has been reported from the fruits.[89] However, the TSS
of ripened fruits varied from 8.33 to 12.20 Brix.[90] TSS has
been reported as 16.11 Brix, acidity as 1.97%, ascorbic acid
as 5.67 mg/100 g, total sugar as 7.86%, reducing sugar as
5.57%, and non-reducing as 2.18 in the fruits of R. ellipticus
collected from Sikkim State.[91]
A high variability has been reported among the different
genotypes in these qualitative traits of the species. In a large-
scale genotype-wide variability study, acidity was recorded
between 1.09% and 1.72%, reducing sugar between 2.2%
and 4.9%, non-reducing sugars between 4.20% and 11.60%,
ascorbic acid between 2.4 and 5.2 mg/100 g and TSS value
between 9.60 and 18.60 Brix.[92] Similarly, ascorbic acid
among genotypes in Uttarakhand has been reported between
10.65 and 40.15 mg/100 g fresh weight (FW) of fruits.[25] The
nutrients present in the species can be used to develop new nu-
tritional products, which may help address the nutritional se-
curity of communities in the IHR and other parts of the world.
Bioactive Constituents
Polyphenolics and other chemical compounds
R. ellipticus fruits are a rich source of natural bioactive
compounds, such as phenolics, avonoids, anthocyanins,
terpenoids, tannins, saponins, steroids, alkaloids, and
β-carotene (Table 2). However, other plant parts of the spe-
cies are also rich in valuable phytochemicals. For instance, the
qualitative analysis of the root bark showed that R. ellipticus
is a source of polyphenols, alkaloids, glycosides, avonoids,
terpenoids, tannins, coumarins, saponins, carotenoids, etc.[93]
Phenolic acids
The berries of the Rubus are increasingly recognized due
to their bioactive compounds, such as phenolic, avonoids,
anthocyanin, and carotenoids (Table 2). In R. ellipticus, re-
covery of total phenolic content varied in different solvent
extractions, and acidied methanol showed 6.9 mg/g FW,
while acidied acetone showed 8.99 mg/g FW.
[24] However,
methanol extract exhibited total phenolic content as 401.36
mg/g dry weight fruit.[94] Different parts, such as leaf (58.26
mg/100 g in acetone extraction), stem (62.02 mg/100 g chlo-
roform extraction), and roots (80.23 mg/100 g chloroform
extraction), exhibited a varied level of total phenolic con-
tent.[102] Fruits of R. ellipticus have been reported as a rich
source of phenolic acids, for example, gallic acid, chlorogenic
acid, caffeic acid, ellagic acid, and m-coumaric acid,
3-hydroxybenzoic acid, 4-hydroxybenzoic acid, ferulic acid,
vanillic acid, trans-cinnamic acid.[11, 25] Fruits were also found
rich in tannin content and reported as 628.32 mg/g DW in
methanol[94] and 33.97 mg/g FW in acidied methanol extrac-
tion.[11] Similarly, George et al. analyzed total tannin content
in leaf, root, and stem in different solvent extraction. Leaf
showed higher content in acetone (48.00 g/100), root (52.10
g/100 g), and stem (66.20 g/100 g) in chloroform solvent
extraction.[102] Recently, various compounds, such as 2,4-bis-
(1,1-dimethylethyl), benzenepropanoic acid, 3,5-bis(1,1-
dimethylethyl)-4-hydroxy-methyl ester, and n-hexadecanoic
acid were isolated in different solvent fractions of R. ellipticus
fruits.[72] However, in-depth analysis of phenolic composition
and other phytochemicals in other plant parts using modern
techniques, such as infra-red spectra, high-resolution mass
spectrophotometry, and tandem mass spectrophotometry
(MS-MS), nuclear magnetic resonance (NMR), optical rotary
dispersal and circular dichroism techniques is lacking for ac-
curate compound identication.
Flavonoids
Flavonoids are an important group of compounds known
for their taste, colour, fragrance, and aroma. It has mul-
tiple health benets, such as anti-inammatory, antioxidant,
anti-mutagenic, and anti-carcinogenic activities; thus, it is
used in nutraceutical, cosmeceuticals, pharmaceutical, and
S.
No
Plant part Geographic region/
community
Dose/mode of administration Used in disease References
30. Root Kaverpalancho, Central
Nepal
The root juice is taken Gastrointestinal and respira-
tory problems
[68]
31 Whole plant Kaverpalanchok, Central
Nepal
The crushed plant mixed with Osbeckia
nepalensis is applied to the skin
Dermatitis [68]
32 Root Dolakha, Nepal Decoction and infusion of root with
Girardinia diversifolia root and bark
of Pyrus parsia and Rhododendron
arboreum is boiled and drunk
Typhoid and stomach pain,
gastrointestinal ailments and
respiratory tract infections
[69]
33 Root Taplejung, Nepal The paste is applied externally in piles
and root extract is consumed
Gastritis and diarrhea [70]
34 Root Ilam, Eastern Nepal R. ellipticus root juice and Docynia
indica mixed and 10–15 ml taken thrice
a day for 2–3 days.
Diarrhea and dysentery [71]
35 Root and
young shoots
Ilam, Eastern Nepal Paste taken orally Throat pain [71]
Table 1. Continue d
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6Pushpa Kewlani et al.
medicinal applications.[103] The total avonoid in fruits varied
in different solvent extraction systems, and 100% methanol
extracted 217 mg/g content in dried fruit.[94] The total avo-
noid concentration was observed between 2.76 and 4.65 mg/g
FW in the sample extracted in 80% acidied methanol and
4.335 mg/g FW in acidied acetone.[24, 25] Among the plant
parts of R. ellipticus, the leaf showed 1.89 mg/g avonoid
content in acetone extract. In contrast, in the stem and roots,
the total avonoid content was 2.2 mg/g and 3.08 mg/g in
petroleum ether extract.[102] The HPLC analysis showed that
(+)-catechin, phloridzin, and kaempferol were the main avo-
noid compounds in R. ellipticus fruits[11, 94] (Table 2). Among
these, kaempferol (17.4 mg/g) is a therapeutically important
compound in apoptosis, angiogenesis, inammation, and
metastasis.[94]
Anthocyanins, a class of avonoids, are natural plant
pigments and have potent antioxidant, anti-hypertension,
anti-diabetic and anti-inammatory activity.[104] Recovery
of total anthocyanin content varied in different solvent
extractions. Total anthocyanins were extracted maximum as
0.12 mg/g FW in 80% acidic methanol,[25] followed by 1.71
mg CGE/100 g in 70% methanol,[88] 3.18 ± 0.10 mg/100 g
DW in 100% methanol[94] in different studies. The HPLC
analysis of anthocyanin revealed that cyanin and delphinidin
were prominent anthocyanins, which are the source of anti-
oxidant potential.[11]
Triterpene, terpene glycosides, and triterpenoid
saponins
Terpenes are ve-carbon isoprene units classied into dif-
ferent subclass based on the number of units, which include
monoterpenes (C10), sesqui-terpenes (C15), di-terpenes
(C20), sester-terpenes (C25), tri-terpenes (C30) and higher
terpenes (>C30), and these terpenes responsible for vast
structural and biological diversity.[105] R. ellipticus was found
rich in various terpenes, such as leaves and roots containing
oleanane, ursane, elliptic acid, ursolic acid, and the whole
aerial part containing 3-β-hydroxy-urs-12, acuminatic acid,
tormentic acid.[40, 95–99] Aswal et al. also conrmed the pres-
ence of β-sitosterol-β--glucoside, 18-dien-28-oic acid-3-0[β-
-glucopyranosyl] (1→4)-α-L-arabinopyranoside in aerial
parts of the species.[98] Nine new ursane-type triterpenoids
(Rubuside A–G and Rubuside J) and one new lupane-type
triterpenoid (H) were isolated and identied along with 29
other known compounds from the roots of R. ellipticus var.
obcordatus.[100]
Carotenoids
Carotenoids are pigments responsible for the red, orange,
and yellow colours in fruits and vegetables. Total carotenoids
(0.20 mg/100 g) have also been reported in signicant quan-
tity in fruits of the species.[84] Total carotenoids in ready-to-
serve fruit beverages were recorded as 516 µg/100 ml[106]
and 0.2 mg/100 g FW in fruit.[85] Similarly, β carotene was
found between 0.52 to 1.81 mg/100g FW among the different
genotypes of R. ellipticus fruits.[25]
Organic acids
Organic acids are important metabolites that maintain the pH
of juice and can metabolize as an energy reservoir. Organic
acids have anti-microbial potential and are used as a food
preservative.[107] Karuppusamy et al. reported ascorbic acid in
fruit (44 ± 4.95 mg/100 g), a free radical scavenger.[88] Badhani
et al. quantied ascorbic acid in fruit using HPLC and varied
10.65–40.15 mg/100 g FW between different genotypes of
the species.[25] However, the composition of other organic
acids in juice and other parts remains unexplored in fruits
and other plant parts.
Figure 2 Nutritional components present in fruits of R. ellipticus and their major biological significance.
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7A wild edible with multiple health benefits
Table 2 Bioactive constituents present in different plant parts of R. ellipticus
Chemical class Compounds Source plant part Reference
Phenolic acid Gallic acid Fruit [11, 24, 25]
Chlorogenic acid Fruit [11, 25]
Caffeic acid Fruit [11, 25]
Ellagic acid Fruit [11,24]
m-Coumaric acid Fruit [11]
3-Hydroxybenzoic acid Fruit [11]
4-Hydroxybenzoic acid Fruit [11]
Ferulic acid Fruit [11]
Vanillic acid Fruit [11]
trans-Cinnamic acid Fruit [11]
Flavonoids and anthocyanins (+)-Catechin Fruit [11, 25]
Kaemferol Fruit [94]
Phloridzin Fruit [11]
Cyanin Fruit [11]
Delphinidin Fruit [11]
Triterpene Oleanane Leaves [95]
Ursane Leaves [95]
Elliptic acid Leaves [96]
Ursolic acid Leaves, root [97]
3-β-Hydroxy-urs-12 Whole aerial parts [98]
Acuminatic acid Whole aerial parts [98, 99]
Tormentic acid Whole aerial parts [98]
Terpene glycosides 2α,3β,19α-Trihydroxyolen-12-en-28-oic acid 28-O-β--
glucopyranosyl ester (24-deoxysericoside)
–[40]
28-β-Glucopyranosyl ester of 19α-hydroxyasiatic acid
(Niga-ichgoside-F1)
–[40]
3-β-Hydroxy-urs-12,18-diene-28-oic-acid-3-O-(β--
glucopyranosyl(1-4)-α--arabino-pyranoside
–[40]
Triterpenoid saponin 18-Dien-28-oic acid-3-0[β--glucopyranosyl](1→4)-α--
arabinopyranoside
Whole aerial parts [98]
Rubuside A–J Root [100]
2R,3,23-trihydrox-yurs-12,18-dien-28-oic acid 28-O--
glucopyranoside
Root [100]
2R,3,23-trihydroxyurs-12,19-dien-28-oic acid 28-O--glucopy-
ranoside
Root [100]
Alpinoside; 11 quadranoside VIII Root [100]
Sericoside Root [100]
Sericic acid Root [100]
Buergericic acid Root [100]
Pinfaensin Root [100]
Rosamutin Root [100]
Kaji-ichigoside F1 Root [100]
Nigaichigoside F1 and F2 Root [100]
Trachelosperoside A1 Root [100]
Pedunculoside Root [100]
Sauvissimoside R1 Root [100]
4-Epinigaichigoside F1 Root [100]
Ziyuglycoside Root [100]
Euscaphic acid Root [100]
1R,2R,3,19R-tetrahydroxyurs-12-en-28-oic acid Root [100]
19R-hydroxyasiatic acid Root [100]
2R,3,19R-trihydroxyurs-12-en-23,28-dioic acid Root [100]
Carotenoids β-carotene Fruit [25]
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8Pushpa Kewlani et al.
Other important phytochemicals
One fatty alcohol 1-octacosanol, and two saturated fatty
acid, octacosanic acid and n-hexadecanoic acid, along with
β-sitosterol and β-sitosterol-β--glucoside were isolated from
the leaves of R. ellipticus.[97] These isolated compounds from
the species are well characterized for having various biolog-
ical activities. 1-Octacosanol is reported to have antifeedant,
ovicide, and larvicide activities.[108] Similarly, β-sitosterol
exhibits anti-inammatory, anti-cancer, neuroprotective,
anti-diabetic hypo-cholesterolemic, anthelminthic, anti-
mutagenic, immune-modulatory genotoxicity, and angiogenic
activities.[109]
Pharmacological and Biological Activities
Different plant parts of R. ellipticus exhibited various bio-
logical activities, including anti-diabetic, nephroprotective ac-
tivity, anti-inammatory, analgesic, anti-pyretic, anti-fertility,
wound healing, anti-microbial and antioxidant, etc. (Table 3).
Anti-diabetic and α-amylase inhibition properties
After oral administration of petroleum ether, ethanol, and
aqueous extracts of R. ellipticus fruits (200 mg/kg) for 15
days in alloxan-induced diabetic Wistar albino rats and
Swiss albino mice, a signicant reduction in serum glu-
cose level has been recorded. However, ethanol extract was
observed most potent extract than others.[26] Inhibition of
α-amylase is another strategy for controlling the digestion
of dietary carbohydrates in diabetes. The methanolic extract
of R. ellipticus leaves exhibited signicant α-amylase inhi-
bition activity with IC50 value 269.94 ± 0.11 µg/ml.[110] Li
et al. extracted triterpenoid compounds from the leaf of R.
ellipticus and found that euscaphic acid was the most potent
α-amylase inhibitor with IC50 values of 0.65 mM, compared
with positive control acarbose (IC50 – 0.82 mM).[100]
Nephroprotective properties
In male albino rats, administration of paracetamol (750 mg/
kg body weight) elevated serum creatinine, urea, blood urea
nitrogen, and kidney weight with reduced urine volume.
Petroleum ether, ethanolic and aqueous extracts of R.
ellipticus fruits signicantly normalized these biochemical
parameters of the body. Besides, kidney histology revealed
signicant improvement after oral administration of all the
extracts.[111] Oral administration of petroleum ether, ethanolic
and aqueous extracts of R. ellipticus fruits (200 mg/kg/day)
exhibited signicant nephroprotective activity on gentamicin
(100 mg/kg/day, 8 days) and cisplatin (7.5 mg/kg/day, 10
days) induced nephrotoxicity in Wistar albino rats and Swiss
albino mice by normalizing the increased level of serum cre-
atinine, serum uric acid, blood urea nitrogen, and serum urea
levels.[28]
Chemical class Compounds Source plant part Reference
Organic acids Ascorbic acid Fruit [25]
4-Dimethylamino-2,2,6,6-tetramethylpiperidinde;
3-piperidinecarboxamide, N,N-diethyl-
Fruit [101]
Fatty alcohol 1-Octacosanol Leaves, fruit [97]
(e)-9,11-dodecadien-1-ol Fruits [101]
Sterols β-Sitosterol Leaves [97, 98]
β-Sitosterol-β--glucoside Leaves and whole plant [97, 98]
Saturated fatty acids Octacosanic acid Leaves [97]
Organooxygen compounds 3,3-Diethoxypropylamine Fruit [101]
Phenols [2-(4-Hydroxy-phenyl)-ethyl]-carbamic acid ethyl ester Fruit [101]
2,4-Bis(1,1-dimethylethyl) Fruit [72]
Phenylpropanoic acids Benzenepropanoic acid, 3,5-bis(1,1-dimethylethyl)-4-hydrox-
methyl ester
Fruit [72]
Fatty acyls n-Hexadecanoic acid Fruit [72]
Carboxylic acids and derivatives 2-Bromopropionic acid, tridecyl ester Fruit [101]
Lactones Glucurolactone Fruit [101]
Organic carbonic acids and
derivatives
Carbamic acid, hydroxy-, ethyl ester Fruit [101]
Carboximidic acids and derivatives Acetamide, N-[3-(3-dimethylaminopropylamino)propyl]-2-
hydroxyimino-2-phenyl
Fruit [101]
Organonitrogen compounds 1,3-Propanediamine, Nʹ-[3-(dimethylamino) propyl]-NN dimethyl Fruit [101]
2-Propanamine, N-methyl-1-[4-[2-(1-piperidyl)ethoxyphenyl] Fruit [101]
Organoheterocyclic compounds 3-Piperidinamine, 1-ethyl- Fruit [101]
Others 7,9-Dimethyl-1,4-dioxa-7,9-diazacycloundecan-8-one Fruit [101]
1-(Diethylamino)ethylidenimino]sulfur pentauride Fruit [101]
4-Fluoro-n-[2-(4-methyl-piperazine-1-carbonyl phenyl benzamide] Fruit [101]
1,1-(Diethylcarbamoyl)succinimide) Fruit [101]
4(Equat)-N-butyl-1,2(axial)-dimethyl-transdecahydroquinol-4-ol Fruit [101]
Table 2. Cont inued
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9A wild edible with multiple health benefits
Table 3 Pharmacological and biological activity along with extract/fraction type, dose, experimental model, experimental background, effect, and possible underlying mechanism of R. ellipticus
S.N. Pharmacological
activity
Extract/
fractions/
plant parts
Dose and experimental
details
Type of assay and model Experimental
background
Allied or related assays
conducted
Underlying mechanism/
observed parameters
Reference
1 Anti-diabetic,
α-amylase inhibi-
tion activity
Various solvent
extracts of fruits
200 mg/kg, 15 days In vivo: Wistar albino rats and
Swiss albino mice
Alloxan-induced
diabetes
Glucose tolerance test Decrease in the blood glucose
level in tested models
[26]
Methanol ex-
tract of leaves
40–1000 µg/ml extract
200 µl of 50 µg/ml
α-amylase
Acarbose (40–1000 µg/ml)
– Qualitative screening
of phytochemicals,
antioxidant activities,
and α-amylase inhibi-
tion activity
α-Amylase inhibition assay Signicant inhibition of α-amylase
inhibition
[110]
2 Nephroprotective
activity
Various solvent
extracts of fruits
100–200 mg/kg/day, 8
days, gentamicin (100 mg/
kg/day, 8 days), cisplatin
(7.5 mg/kg/day, 10 days)
In vivo: Wistar albino rats and
Swiss albino mice
Investigation of
nephroprotective
activity
Gentamicin and cisplatin-
induced nephrotoxicity
Protecting the kidney by nor-
malization of gentamicin and
cisplatin-induced increase in
serum creatinine, serum uric acid,
blood urea nitrogen and serum
urea levels
[28]
Various solvent
extracts of fruits
200 mg/kg b. wt. Aceta-
minophen (APAP) 750
mg/kg
In vivo: Wistar albino rats Investigation of
nephroprotective
activity
Acetaminophen-induced neph-
rotoxicity
Fruit extract normalized the
increased level of serum creat-
inine, serum urea, blood urea
nitrogen and kidney weight
[111]
3 Anti-inammatory,
analgesic and anti-
pyretic
Methanolic leaf
extract
200 and 400 mg/kg b. wt,
indomethacin (20, 10 mg/
kg, 7 h), aspirin (100 mg/
kg, 15 min), morphine (10
mg/kg, 120 min), Paraceta-
mol (100 mg/kg, 24 h)
In vivo: Wistar albino rats
and mice
Anti-inammatory,
analgesic and anti-
pyretic activity
Carrageenin-induced paw oe-
dema, croton oil-induced ear
oedema, acetic acid-induced
writhing test, Eddy’s hot plate
mediated pain reaction, yeast-
induced pyrexia in rats
Reduced paw and ear oe-
dema, latency period increased,
writhing responses reduced, rectal
temperatures decreased
[59]
Ethanolic root
extract
250 and 500 mg/kg In vivo: Red blood cells of
albino rats
Investigation of
anti-inammatory
activity
Carregeenin-induced rat paw
oedema
Oedema swelling reduced [81]
4 Tumour, wound
healing, anti-
proliferative, cyto-
toxicity
Ethanolic root
extract
Tumour: 50–250 mg/kg b.
wt, 0.1% carboxy methyl
cellulose, 38 days
Wound healing: 100 mg/kg
and 200 mg/kg, 21 days
In vivo: Swiss albino mice,
Wistar male rats,
Tumorigenesis Dalton’s lymphoma ascites
(DLA) cell lines induced solid
tumour, Ehrlich ascites carci-
noma (EAC) induced ascites
tumour in Swiss albino mice,
incision, excision, and Staphylo-
coccus aureus-induced infected
wound
The dose of 250 mg/kg prolonged
the life span of mice with EAC
(46.76%); reduced the volume of
DLA (2.56 cm3); complete epithe-
lialization was observed during
the 13th and 19th days
[112]
Various solvent
extracts of fruits
Cervical cancer cell lines
(C33A, HeLa): 0.667, 1.66,
3.33, 5.0 and 6.67 mg/ml
peripheralblood mononu-
clear cells (PBMCs): 5.0
and 6.67 mg/ml
In vitro: C33A, HeLa, PBMCs Antioxidant and
antiproliferative
activity
3-(4,5-Dimethylthiazol-2-yl)-
2,5-diphenyl-tetrazolium bro-
mide (MTT) assay
Viability of cervical cancer cell
lines reduced, PBMCs remained
non-toxic
[24]
Methanol
extract of leaves
104 cells/200 µl/well In vitro: HEK293 Cytotoxicity MTT assay Non-toxic to HEK293 [72]
Methanol extract
of fruits
1–10 g/L penicillin,
streptomycin (100 U/ml)
In vitro: Caco-2 Cytotoxicity MTT assay Signicantly controlled the viabil-
ity of Caco-2 cells
[94]
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10 Pushpa Kewlani et al.
S.N. Pharmacological
activity
Extract/
fractions/
plant parts
Dose and experimental
details
Type of assay and model Experimental
background
Allied or related assays
conducted
Underlying mechanism/
observed parameters
Reference
5 Anti-fertility ac-
tivity
90% ethyl al-
cohol extract of
leaves
200 mg/kg PEG 400
(1000–5000 mg/kg, 72 h)
In vivo: female albino mice Validation of anti-
fertility activity
– Decreased implantation sites,
increased resorption sites
[113]
90% ethanolic
extract of root
and whole plant
50–250 mg/kg body weight Albino rats Anti-implantation
activity
In vivo Root ethanolic extract showed
60–66% anti-fertility activity at
250 mg/kg dose. Whole plant
parts without root extract showed
100% activity at 50 mg/kg dose
[114]
6 Ovi-position
deterrent, anti-
plasmodial activity
Aqueous
extracts of
leaves and silver
nanoparticles
–In vitro: Anopheles stephensi,
Aedes aegypti, Culex
quinquefasciatus
Ovicidal, larvicidal,
and adulticidal ac-
tivity
UV-Vis spectroscopy, XRD,
FTIR, SEM, TEM and EDX
Biosynthesized AgNPs showed
higher toxicity when compared
with aq. extract
[115]
Methanol ex-
tract of leaves
and stem
500 µg/ml, four days In vivo: Plasmodium berghei
(ANKA)
In vitro: Plasmodium falcipa-
rum (Pf3D7, PfINDO)
Antimalarial activity SYBRgreen I uorescence-based
assay, column chromatography,
GCMS, RP-HPLC
Signicant reduction of parasite
load, leaf extract showed signi-
cant antimalarial activity against
PfINDO
[72]
7 Antimicrobial
activity
90% ethanol
extract of the
root
250–1000 µg/ml extract,
gentamycin (10 and 20 µg/
ml), ketoconazole (10 µg/
ml), 24 h for anti-bacterial,
48 h for anti-fungal
In vitro: Staphylococ-
cus aureus, Bacillus
subtilis, Escherichia coli,
Saccharomyces cerevisiae,
Aspergillus niger, Candida
albicans, Rhizopus nigricans
Anti-bacterial and
anti-fungal activity
Agar wall diffusion method Bacterial growth signicantly
inhibited, anti-fungal activity not
observed
[121]
Petroleum ether
and various
solvents of roots
and fruits
10 and 50 mg/ml, 24 h for
anti-bacterial and 7 days
for anti-fungal
Erythromycin (10 mg/ml),
ketoconazole (10 mg/ml)
In vitro: Escherichia coli,
Klebsiella pneumoniae,
Enterobacter gergoviae,
Salmonella entericatyphim,
Shigella exneri, Staphyloccus
aureus, S. epidermidis, Strep-
tococcus pyogenes, Bacillus
cereus, Aspergillus avus, A.
paraciticus, Candida albicans
Anti-bacterial and
anti-fungal activity
Swab method, disc diffusion
method
Signicantly inhibited bacterial
and fungal growth
[86]
Ethanol extract
of leaf
500 µg/ml and 1000 µg/ml,
24 h for anti-bacterial, 40
mg/ml, 48 h for anti-fungal
Ampicillin (100 µg/ml),
clotrimazole (10 µg/ml)
In vitro: Staphylococcus
aureus, Staphylococcus
epidermidis, Pseudomonas
aeruginosa, E. coli, Aspergillus
avus, Candida albicans,
Candida krusei, Trichoderma
lignorum
Anti-bacterial, anti-
fungal
Swab method, disc diffusion
method, evaluated for the pres-
ence of bioactive compounds,
TLC
Signicant inhibition of bacterial
and fungal growth
[116]
Methanol
extract of root
bark
20 µl, 24 h, neomycin (1
mg/ml)
In vitro: Staphylococcus au-
reus, Klebsiella pneumoniae,
Escherichia coli, Salmonella
typhi
Anti-bacterial activity Disc diffusion method, resazurin
microtiter assay
The plants possessed inhibitory
effect against only Gram-positive
bacteria Staphylococcus aureus
[93]
Ethanolic ex-
tract of leaves
1000 µg/ml Streptomycin
(30 mcg)
In vitro: Pseudomonas
aeruginosa, Escherichia coli,
Salmonella typhi, Staphylococ-
cus aureus, Bacillus cereus
Anti-bacterial activity Disc diffusion method Signicant inhibition of bacterial
growth
[117]
Table 3. Cont inued
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11A wild edible with multiple health benefits
S.N. Pharmacological
activity
Extract/
fractions/
plant parts
Dose and experimental
details
Type of assay and model Experimental
background
Allied or related assays
conducted
Underlying mechanism/
observed parameters
Reference
Antioxidant, radical
scavenging activity
Methanol extract
from fruits
Gallic acid equivalents
(GAE)/100 g
In vitro Antioxidant/radical
scavenging activity
DPPH assays, quantitative
estimation of polyphenolic
compounds
Extract showed signicant
scavenging activity
[118]
Acetone extract
from fruits
2 ml, 30 min for DPPH
and 5 min for H2O2, 20
min for FRAP, 90 min for
phosphomolybdenum com-
plex assay (PMA)
In vitro Antioxidant/radical
scavenging activity
DPPH hydrogen peroxide
(H2O2) radicals scavenging
assays, FRAP, PMA, quantita-
tive estimation of polyphenolic
compounds
Signicantly scavenge DPPH and
H2O2 radicals
[49]
Various solvent
extracts of fully
ripe fruit
50–200 µg/ml, 30 min for
DPPH
100–200 mg/l, 10 min for
reducing power assay
In vitro Radical scavenging
and reducing power
activity
DPPH, reducing power assay,
qualitative phytochemical
screening
Ethanolic extract exhibits the
highest scavenging and reducing
power activities
[27]
Various solvent
extracts from
fruits
100 µl (for DPPH and
PRAA), 50 µl (for ABTS),
30 µl (for FRAP),
In vitro Radical scavenging
activity
ABTS, FRAP, PRAA, DPPH,
quantitative estimation of
phytochemicals, and cytotox-
icity
Methanol extracts possessed the
most signicant activity
[94]
Methanol extract
from leaves
1 ml, 30 min In vitro Qualitative antioxi-
dant activities
DPPH Signicant free radical scavenging
activity
[110]
Methanol extract
of root bark
50–300 µg/ml In vitro Assessment of phyto-
chemical, antioxidant
and anti-microbial
activity
DPPH Signicant scavenging capacity [93]
80% each of
various solvents
of fruits
50 µl for ABTS, 0.1 ml for
DPPH
In vitro Antioxidant and anti-
proliferative activity
DPPH, ABTS, Superoxide anion
scavenging activity, ferric reduc-
ing activity
Signicant scavenging and ferric
reducing activity
[24]
70% methanolic
extract of the
fruit
2.5 ml, 30 min In vitro Antioxidant activity DPPH Signicant scavenging activity [88]
Table 3. Cont inued
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12 Pushpa Kewlani et al.
Anti-inflammatory and analgesic properties
The ethanolic extract of R. ellipticus roots signicantly (P <
0.01) decreased the edema swelling with the dose of 250 and
500 mg/kg after 3 hours (h) in carrageenan (0.1 ml) induced
paw edema in albino rats. High concentration dose (500
mg/kg) was more active than 250 mg/kg, which was equally
potent as Indomethacin (10 mg/kg) treated animals.[81] The
extract in concentrations of 200 mg/kg and 400 mg/kg
prevented (45.43% and 66.47%, respectively) the increased
thickness of paw edema in the rats. However, standard drug
indomethacin (10 and 20 mg/kg body weight) showed a
higher inhibitory effect (80.89%) after 7 h. Similarly, in
croton oil-induced ear inammation the methanolic extract
signicantly reduced the inammation of ear from 36.66%
(200 mg/kg) to 45.78% (400 mg/kg) when compared with
the control (76.52%) Indomethacin (10 mg/kg).[59] The anal-
gesic activity of methanolic extract showed signicant protec-
tion against acetic acid induced writhing in mice. The dose of
200 mg/kg and 400 mg/kg signicantly reduced the writhing
frequency from 19.40% and 32.84%, respectively when
compared with standard drug (73.13% inhibition) Aspirin
(100 mg/kg). The dose of 400 mg/kg produced the signicant
analgesic activity tested by Eddy's hot plate mediated pain re-
action which showed the animal could withstand on the hot
plate for 11.2, 13.6 and 7.7 second at 30, 60 and 120 min
reaction time which is comparable with the standard drug
(10 mg/kg) morphine (7.8, 9.6 and 12.4 second).[59] The root
contains anti-inammatory property, which shows potent -
broblast proliferation and anti-ageing. The active ingredient
of the roots is kaji-ichigoside F1.
Anti-pyretic properties
The methanolic extract of R. ellipticus leaf exhibited strong
anti-pyretic properties against yeast (Brewer’s yeast) induced
hyperpyrexia in rats at the concentration of 200 and 400 mg/
kg. A signicant reduction in hyperpyrexia was observed in
yeast-induced rats body temperature from third to seventh
hours after administration, and the activity was comparable
to standard drug paracetamol (100 mg/kg).[59]
Anti-tumor, anti-proliferative, cytotoxicity and anti-
cancer properties
The methanolic extract of R. ellipticus leaf exhibited pro-
tective effects against Dalton’s lymphoma ascites (DLA) cell
lines induced solid tumour and Ehrlich ascites carcinoma
(EAC) induced ascites tumour in Swiss albino mice. The
dose of 250 mg/kg extract prolonged the life span of mice
with EAC (46.76%) and reduced the volume of DLA (2.56
cm3).[112] Anti-proliferative activity of R. ellipticus fruits was
analyzed in human cervical cancer cell lines (C33A and HeLa)
and one normal cell line (peripheral blood mononuclear cells
[PBMCs]) with 80% each of methanol, acid methanol, ac-
etone, acid acetone using MTT ([3-(4,5-dimethylthiazol-
2-yl)-2,5-diphenyl-tetrazolium bromide) assay. It was
observed that acetone (EC50 value 5.04 mg/ml) and meth-
anol (EC50 value 4.9 mg/ml) extracts possessed the highest
anti-proliferative activity against C33A. In contrast, none
of the extracts showed cytotoxicity to PBMC cells.[24] Also,
the methanolic extract signicantly controlled the viability
of tested cell lines in a dose-dependent manner, and only
50% of Caco-2 cell lines were viable at 10 μg/μl concentra-
tion.[94] Sachdeva et al. evaluated the cytotoxic activity of the
methanolic extract of R. ellipticus leaves in the HEK293 cell
line and revealed a non-toxic effect on HEK293 with TC50
values of 90 µg/ml.[72]
Wound healing properties
The methanolic extract of R. ellipticus leaf (dose 100 mg/
kg and 200 mg/kg) exhibited healing properties against
Staphylococcus aureus-induced wounds in Wistar male rat
models. The remarkable healing property of the extract
observed in S. aureus-induced wound models compared with
the control (Betadine, Neomycin) and the complete epithelial-
ization period was reported during the 13th and 19th day.[112]
Anti-fertility properties
Different plant parts of R. ellipticus have been used as an
abortifacient since ancient times.[119] The ethanolic extract
of R. ellipticus roots (250 mg/kg) exhibits signicant anti-
implantation activity during 1–7 days of pregnancy, while the
ethanolic extract of the aerial part of R. ellipticus (whole plant
without root) showed 100% activity even at the lower dose
(50 mg/kg body weight) during 1–3 days of pregnancy.[114]
The whole plant (without root) extracted with 90% ethanol
showed potent anti-fertility activity and at the dose of 250
showed 100% early pregnancy and strong oestrogenic ac-
tivity.[120] The ethanolic extract of R. ellipticus leaves (200 mg/
kg) evaluated for anti-fertility activity on male-female albino
mice revealed a signicant decrease in implantation sites and
increased resorption sites.[113]
Ovi-position deterrent and anti-plasmodial
properties
R. ellipticus-fabricated AgNPs synthesized using the aqueous
leaf extract of R. ellipticus are potential ovi-deterrents and
showed signicant ovicidal, larvicidal, and adulticidal ac-
tivity against the eggs, larvae, and adults of Anopheles
stephensi, Aedes aegypti and Culex quinquefasciatus.[115]
The methanolic leaf and seed extract of R. ellipticus tested
for in vitro anti-plasmodial activity against Plasmodium fal-
ciparum (Pf3D7 and PfINDO) and in vivo anti-plasmodial
effect of methanolic leaf extract against P. berghei (ANKA)-
infected mice. R. ellipticus leaf extract showed remarkable
antimalarial activity against Pf3D7 with IC50 = 14.26 µg/ml.
The results of in vivo anti-plasmodial activity showed that
the oral dose (500 mg/kg) of methanolic extract suppressed
P. berghei parasitemia by 64% (P < 0.05) and signicantly
reduced the parasite load.[72]
Toxicological properties
Petroleum ether, ethanolic and aqueous extracts of R.
ellipticus fruit exhibited non toxic neurological and behav-
ioral symptoms up to a dose of 2000 mg/kg on Wistar albino
rats and Swiss albino mice.[26] Also, the methanolic extract
of R. ellipticus leaves administered to Wistar albino rats,
and mice up to a dose of 2000 mg/kg showed neither any be-
havioral change nor the death of tested animals. Moreover,
acute oral and dermal toxicity studies of methanolic extract
of R. ellipticus leaf reported being safe for the tested ani-
mals up to a dose of 2 g/kg.[112] The ethanolic extract of R.
ellipticus roots showed no toxicity and mortality in albino
rats.[81] These toxicity studies on R. ellipticus suggested that
the species is well tolerated by the animals and exhibited a
high safety prole.
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13A wild edible with multiple health benefits
Anti-microbial, anti-bacterial and anti-fungal
properties
In various studies, different plant parts of R. ellipticus showed
anti-microbial, anti-bacterial, and anti-fungal properties. The
ethanolic extract of R. ellipticus roots exhibited mild anti-
bacterial activity using agar diffusion method at the different
concentrations from 250 to 1000 μg/ml exhibited remarkable
activity when compared with the standard drug gentamycin
(10–20 μg/ml).The signicant activity was observed at the
1000 μg/ml against S. aureus, Bacillus subtilis, Escherichia
coli, Shigella but there was very less antifungal activity
against Saccharomyces cerevisiae, Aspergillus niger, Candida
albicans, and Rhizopus nigricans.[121] The ethanolic extract
of R. ellipticus fruits (50 mg/ml) has the highest antibac-
terial activity against food poisoning bacteria viz. E. coli
(MTCC 729) with an inhibitory zone of 16.0 mm followed
by Streptococcus pyogenes (MTCC 1925) and E. coli (MTCC
443) with an inhibitory zone of 15.0 mm each.[86]The anti-
microbial activity of R. ellipticus leaf extracted in different
solvents was evaluated against bacterial strains (E. coli and S.
aureus) and fungal strains (C. albicans) by broth microdilution
method. Maximum growth inhibition for anti-bacterial ac-
tivity was observed in the ethanolic extract of S. aureus strain
(100%). In contrast, the acetone extract observed maximum
anti-fungal activity with growth inhibition (100%). The max-
imum antibacterial activity of R. ellipticus was shown in an
aqueous extract of E. coli (MIC50 as 450 μg/ml). In contrast,
acetone was the most suitable solvent for anti-fungal ac-
tivity against C. albicans (MIC50 as 240 μg/ml).[122] Similarly,
R. ellipticus extract was evaluated against eight common
foodborne pathogens and fungal strain (C. albicans) by broth
microdilution method. Maximum growth inhibition of R.
ellipticus leaf for anti-bacterial activity was observed in the
ethanolic extract (1 mg/ml) against E. coli strain. In contrast,
water extract showed maximum growth inhibition against
B. cereus, L. innocua and M. luteus. Comparatively, ampi-
cillin as a controlled drug produced a 26.0 mm zone of inhibi-
tion. The maximum antibacterial activity of R. ellipticus using
the MIC method was exhibited in an aqueous extract for E.
coli and B. cereus (MIC50 as 559 µg/ml), Listeria innocua
(MIC50 as 560 µg/ml), and ethanol was the most suitable sol-
vent against Bacillus cereus (MIC50 as 273 µg/ml) and E. coli
(MIC50 as 527 µg/ml). In contrast, acetone was the most suit-
able solvent against Micrococcus luteus (MIC50 as 282 µg/
ml).[123] However, signicant anti-fungal activity was reported
against various fungal strains.[116] Overall, the anti-bacterial
and anti-fungal activities of the fruits and roots remain low
(MIC50 value > 500 µg/ml), which signies the identication
of the most potent molecule as an anti-microbial agent rather
than the direct plant extract.
The methanolic extract of root bark of R. ellipticus
was investigated for antibacterial activities against S. au-
reus (gram-positive), Klebsiella pneumoniae, E. coli, and
Salmonella typhi (gram-negative) by using disc diffusion and
Resazurin microtiter assay. The methanolic extract of root
bark of R. ellipticus exhibited signicant antibacterial activity
against S. aureus with a 17 mm zone of inhibition, but no
effect was observed with gram-negative strains by disc diffu-
sion method. The MIC (minimum inhibitory concentration)
and MBC (minimum bactericidal concentration) values of R.
ellipticus were reported as 3.125 mg/ml and 12.5 mg/ml by
Resazurin microtiter assay.[93] Similarly, the ethanolic extract
of R. ellipticus leaves has the highest zone of inhibition and
maximum activity against Enterococcus faecalis and lowest
against E. coli, which is studied for MIC highest activity
against E. facecalis (16 mg/ml) at 1000 µg/ml concentration
and the minimum of S. typhi (10 mg/ml).[117] The whole plant
(except the root) of R. ellipticus is reported to have antibac-
terial activity against S. aureus, E. coli, Streptococcus faecalis,
K. pneumoniae, Pseudomonas aeruginosa; anti-fungal activity
against C. albicans, Cryptococcus neoformans, Trichophyton
mentagrophytes, Aspergillus fumigates, Sporotrichum
schenckii; antiprotozoal activity against Entamoeba
histolytica, Giardia lamblia and anti-viral activity against
Ranikhet disease-causing agent, Vaccinia virus.[98]
Anthelmintic activity, and anti-enteroviral activity of R.
ellipticus leaf in three different extracts reported by Panda
et al.[122] Anthelmintic activity studied by 96-well microplate
by relative percentage movement compared with the solvent
(Nematode growth medium) showed promising activity over
50% inhibition. The anti-viral activity was tested against
EV71 and BrCr, ethanol, acetone and aqueous extract, which
showed that aqueous (EC50 = 5 ± 5 and EC90 = 8 ± 6 μg/ml)
and ethanol exract (EC50 = 13 ± 6 and EC90: 15 ± 0 μg/ml) are
potent inhibitors for enterovirus. The maximum inhibition
was observed in aqueous (88 ± 18%) and ethanol (74 ± 1%)
extract which showed the R. ellipticus is the best inhibitions
for enterovirus. It proves that R. ellipticus could be a source
for broad-spectrum antibiotics.[122]
Antioxidant and radical scavenging activity
Himalayan raspberry has high antioxidant potential meas-
ured by in vitro assays, such as radical scavenging DPPH
(2,2ʹ-diphenyl-1-picryl-hydrazyl-hydrate), the ferric-
reducing activity of plasma (FRAP), 2,2ʹ-azino-bis(3-
ethylbenzthiazoline-6-sulfonic acid) (ABTS), superoxide,
nitric oxide (NO), hydroxyl radicals, lipid peroxidation and
β-carotene bleaching activity (Figure 3; Table 3) as reported
by various workers.[27,88,90,93,94,102,110] For instance, Saini et al.
investigated free radical scavenging activities (DPPH, ABTS,
superoxide anion scavenging activity, inhibition of β-carotene
bleaching activity) and ferric-reducing activity with different
solvent systems and reported that highest DPPH (619.3 ±
32.14 (mg CE/100 g FW) and ABTS (1072.6 ± 42.11 mg
BHAE/100 g FW) scavenging activity was found in acetone
extract, whereas the highest superoxide anion scavenging ac-
tivity (1083.0 ± 2.23 mg AAE/100 g FW) and ferric-reducing
activity (1389.8 ± 49.22 mg AAE/100 g FW) was exhibited
in acidic acetone extract. Inhibition of β carotene bleaching
activity was much higher in acetone, acidic acetone, and
acidic methanol extract when compared with standard bu-
tylated hydroxyanisole (BHA) (10 mg), control and methanol
extract.[24]
Sasikumar et al. examined polyphenolic compounds and
in vitro antioxidant activity of ripened fruit extract of R.
ellipticus and revealed that the total phenolic content (6100
± 0.082 mg GAE/100 g FW) and total avonoid content (320
± 0.120 mg QE/100 g FW) were the major antioxidants.
Signicant scavenging activity towards DPPH (EC50 9.85 ±
1.33 µg/ml), superoxide anion (EC50 64.65 ± 0.82 µg/ml), hy-
droxyl ion radicals (EC50 79.98 ± 1.02 µg/ml) and NO (EC50
75.21 ± 1.32 µg/ml) was observed. The reduction capacity
of the extract caused signicant reducing power (increased
OD value 1.435 ± 0.021), strong Fe2+ chelation (EC50 value
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14 Pushpa Kewlani et al.
45.24±1.42 µg/ml) and lipid peroxidation (EC50 71.1 ± 0.22
µg/ml). The antioxidant activity of the extract was comparable
to butylhydroxytoluene (BHT), ethylenediaminetetraacetic
acid disodium salt (EDTA-Na2) and catechin.[118] Water and
acetone extract of R. ellipticus fruit was evaluated for free
radical scavenging activity (DPPH, OH-and, and H2O2),
and total antioxidant activity (FRAP and phosphorous-
molybdenum (PM) complex). Remarkably highest scavenging
activity was reported through the DPPH assay (94.65a ±
9.87%) in acetone extract, whereas the highest total antioxi-
dant activity was shown in acetone extract (76.42c ± 9.11%)
through (261.27 ± 17.49 µM AAE/100 g FW) through PM
assay.[49] Hexane, ethyl acetate, and methanol extract of R.
ellipticus were evaluated for free radical scavenging activity
through ABTS and FRAP assay. The hexane extract contains
the highest scavenging activity against DPPH with an IC50
value of 615.08 ± 1.76 μg/ml and ABTS with an IC50 value of
163.89±1.32 μg/ml.[124] Similarly, George et al. demonstrated
that methanol extract showed the highest 57.05 mM Fe(II)/
mg extract when compared with hot water (24.35 mM), ethyl
acetate (23.05 mM), and petroleum ether (0.44 mM).[101]
Genetic Variability and Genomic Resources for
Crop Improvement
There is taxonomic confusion among genetic resources, and
comprehensive investigations are required to resolve this issue.
For instance, a comparative karyotypic, palynological, and
RAPD (random amplied polymorphic DNA) analysis of 12
taxa belonging to subsections Idaeobatus in Rubus L. revealed
that all the taxa except R. ellipticus and R. pinfaensis could
be distinguished from each other by markers. Furthermore, R.
ellipticus var. obcordatus should be treated as R. obcordatus,
and R. ellipticus and R. pinfaensis should be combined as R.
ellipticus to resolve the taxonomical confusion.[125]
The genus Rubus is highly variable, and the morphological
characteristics vary from young and small canes to spring,
and autumn foliage of the same cane; even the plant may re-
spond differently in habitats like shade, moist, sun, and dry
conditions and showed high hybridization compatibility
among species.[126] Maikhuri et al. demonstrated that fruit
yield in small, medium and large bushes are 0.475, 0.976, and
2.625 kg/plant, respectively, for R. ellipticus.[135] Plant mor-
phological characteristics, such as leaf length (3.32–10.52
cm), leaf width (2.17–9.80 cm), petal length (0.30–1.36 cm);
petal width (0.15–1.00 cm), ower diameter (0.56–3.26 cm),
owers/truss (2–23 fruit) vesicles/fruit (5–72), fruit length
0.55–1.92 cm), fruit width (0.64–1.82 cm), fruit weight
(0.332–1.43 g) and fruit volume (0.213–1.020 cm3) signi-
cantly varied among genotypes.[14] Among the nine Rubus spe-
cies, a high variation in number of branches/plant (5.8–10.2);
leaf length (5.69–8.90 cm); leaf width (2.23–9.81 cm); leaf
petiole length (1.02–4.98 cm); petal length (0.43–1.44 cm);
petal width (0.32–0.97 cm); plant canopy (12 320.2–73 317.3
cm2); ower diameter (0.53–3.26 cm); number of trusses/
plant (38–115); number of owers truss/plant (10.4–15.2);
number of vesicles/fruit (23–82); fruit length (0.46–1.55 cm);
fruit width (0.46–1.11 cm); fruit weight (0.422–2.212 g);
fruit volume (1.132–2.471 cm3) was recorded.[90] Similarly,
the species have already reported phytochemical variability in
fruits among the different genotypes.[25] The signicant varia-
bility in morphological traits in R. ellipticus offers the scope
for identifying and selecting superior genotypes, which could
be utilized for elite selection, commercialization, and domes-
tication of this underutilized fruit plant.
Recent advancement in molecular biology has provided a
platform to plant breeders to identify the genetic variation of
traits among genotypes and identify the function of gene and
associated bioactive compounds.[127,128] Genetic diversity anal-
ysis of 21 genotypes of R. ellipticus using ISSRs (inter simple
sequence repeats) and EST-SSRs (expressed sequence tags-
based simple sequence repeats) showed high polymorphism
(100%), which can be used for future breeding programs.[129]
Similarly, the transferability of EST-SSRs was studied in 10
Rubus species (including four R. ellipticus collections of
different geographical origin, R. ulmifolius, R. hypargyrus,
R. panniculata, R. nutans, R. macilentus and R. strigosus)
revealed a high level of polymorphism (98.36%).[130] Inter-
specic and inter-generic cross-transferability among these
genotypes and species indicated that in the absence of genomic
resources in R. ellipticus, inter-specic and inter-generic re-
source data could be used for genotyping and genetic genomic
Figure 3 Antioxidant activities of R. ellipticuswere determined in different assays.
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15A wild edible with multiple health benefits
mapping genetic characterization and phylogenetic analysis.
Sharma et al. analyzed variability among 21 R. ellipticus
genotypes from different locations in India using morpholog-
ical and EST-SSR markers and found a highphenotypic vari-
ation in genetic polymorphism (89.7%).[131] Recently, Sharma
et al. developed 7870 SSRs in the species using transcriptome
sequencing of leaf tissue. Among these, 68 randomly selected
primers provided 90% amplication in R. ellipticus, whereas
95% of primer pairs were informative in the ve tested genera
of Rosaceae, pear, peach, apple, rose, and strawberry, with
95.3% and 93.5% polymorphism. Such genomic resources
can further be harnessed for molecular breeding for variety
development in the species in a shorter period.[132]
Economic Importance and Market Potential
Besides edible value, R. ellipticus fruits are commercially culti-
vated to collect nectar sugar as honey.[133,134]Thevalue-added
edible products, such as squash, jam, jelly, alcoholic beverages,
herbal wines, toothpaste, health beverage, yogurt and ‘Haanj’
(rice-based alcoholic beverage), and ice cream prepared from
R. ellipticus fruits have economic benets.[78,106,124,135–139] Cost-
benet of jam prepared from R. ellipticus fruit indicated a net
return of 117.0 rupees per person, while fruit has Rs. 50.0/
kg in rural areas.[135] Similarly, Negi et al. also analyzed the
input (Rs. 203.0), and output (Rs. 420.0) costs with a net
benet of Rs. 217.0 per/person per day.[78] Comrep syrup pre-
pared from the ripe fruits of R. ellipticus and R. paniculatus
and roots is used to treat colds and coughs in Northeastern
India.[140] Recently, Assam State Biodiversity Board xed the
market value of R. ellipticus fruits as Rs. 30.0–40.0/kg, while
the global price has been estimated asaround $1.54/kg.[141] In
Nepal, fresh fruits of species have a price of Rs. 50.0–55.0/
kg in the local market to make wine.[142] The Maruzen phar-
maceutical and other cosmetic industries use the root of
R. ellipticus for clinically tested products, like BG80 (cos-
metic and pharmaceutical products), to protect skin from
UV-induced damage and wrinkle improvement.[143]
Conclusion and Recommendations
R. ellipticus is used for multiple purposes, including edible
fruits, processed products, and traditional medicines. The re-
view revealed that R. ellipticus is well investigated in pharma-
cological properties, such as anti-diabetic, nephroprotective,
anti-inammatory, analgesic, anti-pyretic, anti-proliferative,
wound healing, anti-fertility, insecticidal, anti-microbial and
antioxidant properties. Most of these studies validated its
traditional uses, such as gastritis, liver and kidney problems,
wound healing, urinary infections, etc.[94] suggesting its huge
biological potential. However, many other uses in traditional
medicine for many diseases (such as diarrhea, peptic ulcers,
heart- and blood-related diseases, typhoid, CNS troubles,
etc.) have not been validated through pharmacological ac-
tivity and need further research. Furthermore, in-depth phy-
tochemical investigations need to be carried out to identify
active molecule(s), which are necessarily required for drug or
formulation for cosmeceutical or pharmaceutical purposes.
While identifying a molecule as a novel drug, identifying the
molecular target responding to the drug is the rst insight to
discovering the molecular mechanism of drug action, which
faces multiple hurdles due to the complexity of the biological
system. There is a need to understand the role and mech-
anism of each bioactive compound and the therapeutic ef-
fect that can lead to drug development. The pharmacological
studies are not entirely explored, only performed through
in vitro screening and very few animal model-based studies,
which do not include comprehensive investigations into the
molecular mechanisms of action. Proteomic analysis of the
disease prevention mechanism of R. ellipticus can generate
large data, including the expression of proteins, functioning,
interaction and networking with other proteins, their biosyn-
thetic pathways, etc., during drug discovery. Such large data-
generating approaches will be more effective in diagnosing
multiple targets of R. ellipticus-based drugs against com-
plex diseases, such as diabetes, cancers, aging-related
degenerations, and blood pressure-associated complications.
Fruits of the species have colossal potential, and various
nutritional investigations[84] support that species have huge
nutraceutical potential and need popularization for their
wide acceptability among society. Fruit sensory character-
istics must be further optimized to improve quality-related
parameters. The detailed composition of fatty acids, organic
acids, sugars, vitamins, etc., needs further investigation. The
berries are tasty and nutritional data on berries can be used
as health supplements, nutraceuticals, and nutria-cosmetics
supplements, which can reduce the risk of health problems
such as skin aging and can be used as an immunity booster. As
the food industry always demands new products, the Indian
Himalayan raspberry can be a source of food supplements
and beverages with functional properties and improved liveli-
hood and socioeconomic status.
The selected species might be introduced for mass cultiva-
tion. Small fruit size, short shelf-life, long ripening time, and
multiple picking efforts are a few major concerns for its do-
mestication. The short shelf-life of fruits can be encountered
by processing and value addition of products, which will
increase economic benets from the species. The plantation of
the species in degraded land can also help provide a resource
for pollinators, which will be benecial for making honey and
other products. In this way, the species could be one of the
important means for improving income generation and land
stabilization in hilly terrain.
Overall, the edible fruits of the species are a good source of
important essential nutrients and metabolites. The wide ge-
netic variability in R. ellipticus could help the plant breeders to
identify a superior accession among other species and utilize
it either as a cultivar or as a suitable parent for the breeding
program having desirable vegetative and reproductive traits.
Modern advanced sequencing tools and improved computa-
tional simulation provide rapid method for accelerated de-
velopment of genomic information, facilitating identication
of molecular targets for drug discovery, trait improvement,
and potential parental genotype identication for molecular
breeding.[131] Developing varieties with improved traits can
improve yield, productivity, and quality of fruits during com-
mercial cultivation. Standardization of fruit quality is neces-
sary for breeding particular plants to investigate variation in
traits among genotypes coupled with an enhanced level of bi-
oactive compounds, antioxidant activity, taste, and nutrients.
Basic pharmacological assays of solvent extracts indicated
the potential of the species against different diseases, such as
nephroprotective, anti-inammatory, analgesic, anti-pyretic,
anti-proliferative, cytotoxicity, anti-cancer, wound healing,
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16 Pushpa Kewlani et al.
anti-fertility, anti-plasmodial properties, anti-microbial, anti-
oxidant properties. Furthermore, in-depth research on phar-
macological properties, such as identication of potential
molecules, identication of drug target, and interaction with
potential receptor molecules, can be helpful for its potential
application as therapeutics. Overall, it can be concluded that
species have immense potential to improve the dietary system
of rural people and can be used in developing nutraceutical
and energy supplement.
Author Contributions
P.K. and I.D.B. conceived the idea and designed the study.
P.K., D.T., and S.R. compiled the database and wrote the
manuscript. I.D.B. critically reviewed and improved the MS.
All authors contributed to editing and critical revision of the
manuscript.
Funding
Support for this research work provided by NMSHE TF-3
phase I&II (Forest resources and plant biodiversity, CSIR-
SRF-Direct fellowship, Delhi, India under the grant no-
09/560/0001/19-EMR-1, and In-house Project 4 is greatly
acknowledged.
Conflict of Interest
The authors declare that they have no conicts of interest to
disclose.
Data availability
In this review paper, no primary data was generated.
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