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Ethnic uses, pharmacological andphytochemical profile of genus GrewiaWali Ullah a , Ghias Uddin a & Bina Shaheen Siddiqui ba Institute of Chemical Sciences, University of Peshawar ,Peshawar , 25120 , Pakistanb International Center for Chemical Sciences, HEJ ResearchInstitute of Chemistry, University of Karachi , Karachi , 75270 ,PakistanPublished online: 01 Feb 2012.

To cite this article: Wali Ullah , Ghias Uddin & Bina Shaheen Siddiqui (2012) Ethnic uses,pharmacological and phytochemical profile of genus Grewia , Journal of Asian Natural ProductsResearch, 14:2, 186-195, DOI: 10.1080/10286020.2011.639764

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Ethnic uses, pharmacological and phytochemical profile of genusGrewia

Wali Ullaha*, Ghias Uddina and Bina Shaheen Siddiquib

aInstitute of Chemical Sciences, University of Peshawar, Peshawar 25120, Pakistan; bInternationalCenter for Chemical Sciences, HEJ Research Institute of Chemistry, University of Karachi, Karachi

75270, Pakistan

(Received 23 May 2011; final version received 20 October 2011)

A number of species of genus Grewia have been used as medicinal agents to treatseveral diseases. This review based on 45 literary sources discusses the currentknowledge of traditional uses, chemistry, biological effects, and toxicity of differentspecies of this genus. Triterpenoids, steroids, glycosides, flavones, lignans, phenolics,alkaloids, lactones, anthocyanins, flavones, and organic acids have been isolated fromvarious species of this genus. The extracts and preparations from the various plants,which are expectantly safe, exhibited various biological effects, e.g. anti-oxidant, anti-bacterial, hepatoprotective, anti-inflammatory, anti-emetic, anti-malarial, analgesic,and anti-pyretic activities.

Keywords: Grewia; pharmacological; toxicological characteristics

1. Introduction

Grewia genus (family: Tiliaceae) com-

prises approximately 150 species, small

trees or shrubs, distributed in subtropical

and tropical regions, including tropical

Africa, Arabia, Madagascar, the Himalaya,

India, Pakistan, China, Bangladesh, Myan-

mar, Thailand, Malaysia, the pacific

islands, and northern Australia. In Pakistan,

10 species of genus Grewia are identified.

They are Grewia micrcos, G. optiva, G.

tenax, G. helicterifolia, G. glabra, G.

damine, G. villosa, G. sapida, G. asiatica,

and G. elastic [1,2]. Linnaeus identified

two species of genus Grewia: G. acciden-

talis from tropical and G. orientalis from

Sri Lanka and named after Nehemiah Grew

(1641–1712), one of the founders of plant

physiology [3]. During the last few

decades, medicinal properties of many

species have been identified [4]. The

barks and roots of G. tiliaefolia are used

to treat skin diseases, hypertension, ulcers,

diarrhea, inflammatory bowel diseases,

pruritis, jaundice, burning sensation, thirst,

throat complaints, biliousness, dysentery,

infectious diseases, and diseases of the nose

and of the blood [5–7]. Traditional medical

practitioners residing in the vicinity of

the forests of the Thirtharameshwara range

and Ubbrani range of Western Ghats of

Karnataka, India, were using the stem bark

extracts and pastes for curing jaundice,

hepatic disorders, and bronchial and

urinary infections [8]. G. asiatica was

initially cultivated mainly for its sour fruits

until its high medicinal value was dis-

covered. The fruits and barks of this plant

are used for the treatment of diarrhea, blood

disorders and for reducing fever [9]. G.

bicolor is a part of Sudanese traditional

medicine and is used in the treatment of

ISSN 1028-6020 print/ISSN 1477-2213 online

q 2012 Taylor & Francis

http://dx.doi.org/10.1080/10286020.2011.639764

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*Corresponding author. Email: waliullah898@yahoo.com

Journal of Asian Natural Products Research

Vol. 14, No. 2, February 2012, 186–195

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skin lesions and sometimes also used as a

tranquilizer [9]. An extract of G. villosa is

used in the treatment of tuberculosis [10].

G. microcos is reported to be used for the

treatment of indigestion, eczema and itch,

typhoid fever, dysentery, and syphilitic

ulceration of mouth [11].G. tenax is a plant

that has been used in popular medicines in

various ways in different countries for cure

of jaundice, pulmonary infections, and

asthma. Leaves are used to treat trachoma.

Decoction and fruit juice are used for their

tonic and anti-anemic properties [6]. G.

tiliafolia is a tree found in India, Sri Lanka,

tropical Africa, Burma, and Nepal. Its bark

is used in ayurvedic medicine to treat

vitiated conditions of Pitta and Kapha,

burning sensation, cough, skin diseases,

wounds, ulcers, diarrhea, seminal weak-

ness, general debility, and hypertension

[4,5,12,13]. The mucilage and the hot water

extract of the bark are used as an antidote

for opium poisoning in human adults [14].

2. Pharmacology

2.1 Anti-malarial activity

The crude extract from G. bilamellata

showed anti-malarial activity (IC50 ¼ 2.2

and 1.7mg/ml). Bioassay-directed frac-

tionation of the methanolic extract

prepared from a sample of the combined

O

1 3 4

76

H H

HO

HO

H

HOH

HO

H

HO

HO

HO

OH

O

Figure 1. Triterpenes from different species of Grewia genus.

N

HN

NHN

H3CO

10 11 12

NHN

HO

Figure 2. Alkaloids from different species of Grewia genus.

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leaves, twigs, and stems of G. bilamellata

led to the isolation of eight lignans

including two coumarinolignan, four neo-

lignans, two Haworth lignans, two triter-

penes, one quinol derivative, and one

sterol glucoside. Bioassay results indicated

that the isolates 3a,20-lupandiol, grewin,

nitidanin, 2a,3b-dihydroxy-olean-12-en-

28-oic acid, and 2,6-dimethoxy-1-aceto-

nylquinol possessed in vitro anti-malarial

activity against Plasmodium falciparum

(IC50 ¼ 19.81 M) [15].

2.2 Anti-microbial activity

G. bicolor is a part of Sudanese traditional

medicine, and is used in the treatment of

skin lesions and also sometimes as a

tranquilizer [9]. Alkaloids, harman, 6-

methoxyharman, and 6-hydroxyharman,

isolated from the methanol extract of this

plant, showed anti-bacterial properties

[16]. Fruits of G. asiatica and G. tiliafolia

possess anti-microbial activities [17,18].

Van Vuuren (2008) determined anti-

bacterial activity of G. occidentalis [19].

Crude methanolic extract from G. asiatica

was fractionated into three major fractions,

viz. phenolic acids, flavonols and antho-

cyanins, and analyzed for their total

phenolic, flavonoid contents, and anti-

microbial effects. All fractions showed a

significant anti-bacterial activity except

anthocyanin. Being the most active,

phenolic acid fractions were also tested

for their anti-fungal activity, which sub-

stantially inhibited all the tested fungal

strains [20]. Mudassir et al. found that the

methanolic extract of G. erythraea showed

a significant anti-fungal and anti-bacterial

activities [21].

2.3 Anti-emetic activity

A 70% aqueous methanolic extract of G.

lasiodiscus root was fractionated on

column chromatography using solvents

of increasing polarities to yield three

O

O

OHOH

HO

HO

HO

OH O

15 16

17

OHOHO

OH O

OH

OH

HO

HO

HO

O

O

HOOH

OH

OH

O+HO

OH

OH

OHCl–

Figure 3. Flavones and anthocyanin from Grewia species.

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OO

O

19 20

21

23

22

HO

HO

OCH3

HOO O

OH3CO

HO

OCH3

HO

OH

OCH3

HOO

H

H

OH

H

H

OH

OCH3

OH

OCH3

HO

H

OH

OH

H

H

OH

O

OH

O

O

OH3CO

HO

OCH3

HO

O

H

H

H

OCH3

Figure 4. Coumarinolignans and neolignans from Grewia species.

OO

OH

24

27 32

26 28

HO

OHHO

O O

OHHO

OH

HO

O

OH

HO HHO

OH

O

OH

O

O

O

O

Figure 5. Structures of other compounds.

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Table 1. Different classes of compounds isolated from Genus Grewia.

S. No. Compounds Species Ref.

Triterpenes1 Friedelin G. tiliaefolia, G. biloba [36]2 Epi-friedelan-3-ol G. biloba [36]3 Ursene-3,19,28-triol G. villosa [38]4 a-Amyrin G. villosa [38]5 Ursolic acid G. villosa [38]6 3a,20-Lupandiol G. bilamellata [15]7 2a,3b-dihydroxyolean-

12-en-28-oic acidG. bilamellata [15]

8 Lupeol G. bicolour, G. tiliaefolia,G. damine

[14,16]

9 Betulin G. bicolour, G. tiliaefolia,G. damine

[14,16]

Alkaloids10 Harman G. bicolour [16]11 6-Methoxyharman G. bicolour [16]12 6-Hydroxyharman G. bicolour [16]

Sterols13 b-Sitosterol G. bicolour, G. biloba [16,37]14 Daucosterol G. bilamellata [15]

Flavones15 Vitexin G. damine [39]16 Isovitexin G. damine [39]

Anthocyanin17 Cyanidin 3-galactoside G. asiatica [40]

Coumarinolignans18 Grewin G. bilamellata [15]19 Nitidanin G. bilamellata [15]20 Cleomiscosin D G. bilamellata [15]

Neolignans21 8-O-40-Neolignanguaia-

cylglycerol-b-coniferylether(threo)

G. bilamellata [15]

22 8-O-40-Neolignanguaia-cylglycerol-b-coniferylether (erythro)

G. bilamellata [15]

23 Bilagrewin G. bilamellata [15]Other compounds24 Gulconic acid g-lactone G. tiliafolia [23]25 3,21,24-trimethyl-5,7-

dihydroxyhentriaconta-noic acid d-lactone

G. asiatica [23]

26 D-erythro-2-hexenoicacid g-lactone

G. tiliafolia [23]

27 Vitamin A G. asiatica [9]28 Vitamin C G. asiatica [9]29 Heneicosanoic acid G. biloba [37]30 Propyl palmitate G. biloba [37]31 Grewinol G. asiatica [41]32 2,6-Dimethoxy-1-aceto-

nylquinolG. bilamellata [15]

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fractions. The effect of the extract on

pentobarbitone-induced hypnosis was eval-

uated in mice, while the anti-emetic

activities of the extract and its fractions

were studied on anhydrous copper sulfate-

induced emesis in 1-day-old chickens.

The oral median lethal dose (LD50) of

extract was studied and estimated to be

774 mg/kg [22].

2.4 Hepatoprotective/radioprotectiveactivity

Bioassay-directed fractionation and chro-

matography of the methanolic extract from

the stem bark of G. tiliafolia have resulted

in the isolation of g-lactones, having

hepatoprotective activities [23]. The radio-

protective effect of G. asiatica fruit that

contains anthocyanin-type cyanidin 3-

galactoside, vitamins C and A, minerals,

carotenes and dietary fibers was studied.

Earlier research showed that supplemen-

tation of G. asiatica fruit extract can

improve radiation-induced depletion in

protein level and can inhibit the radi-

ation-induced lipid peroxidation in brain

[24], cerebrum [25,26], liver [27,28], and

blood [29]. A study has been performed on

assessing the histological evidence of

radioprotective efficacy of G. asiatica

fruit in liver along with its efficacy to

protect DNA and RNA damage in the liver

of Swiss albino mice [30].

2.5 Anti-oxidant activity

Methanolic crude extract of G. tiliaefolia

was checked against different radical

systems comprising superoxide radical

(O22), hydroxyl radical (OH), and nitric

oxide radical (NO) and showed potential

anti-oxidant activity in the in vitro model

system [31]. Sharma and Sisodia (2009)

found that G. asiatica fruit extract has

strong radical scavenging activity in

2,2-diphenyl-1-picrylhydrazyl (DPPH)

and O22 assays [32]. Solvent extracted

fractions of G. asiatica leaves were

screened for in vitro anti-oxidant properties

using standard procedures. The solvent

extracted fractions such as petroleum

ether, benzene, ethyl acetate, methanol,

water, and 50% crude methanolic extracts

exhibited IC50 values of 249.60 ^ 7.37,

16.19 ^ 2.132, 26.17 ^ 1.49, 27.38 ^

1.80, 176.14 ^ 5.53, and 56.40 ^

3.98mg/ml, respectively in DPPH and

22.12 ^ 02.65, 27.00 ^ 01.62, 47.38 ^

05.88, 56.85 ^ 06.16, 152.75 ^ 5.76, and

72.75 ^ 13.76 mg/ml, respectively, in

nitric oxide radical inhibition assays.

These values are comparable with stan-

dards such as ascorbic acid and quercetin.

G. asiatica leaves showed an anti-oxidant

activity [33].

2.6 Anti-proliferative activity

Study on G. tiliafolia proved that the

methanolic extract has a potential tumor

cell suppression activity in the selected

in vitro cell culture system [31].

2.7 Analgesic and anti-pyretic activity

Analgesic and anti-pyretic activities of the

aqueous extract of G. tiliaefolia Vahl

leaves were detected using morphine and

paracetamol at the dose of 10 and

150 mg/kg i.p. as standard drugs. The effect

observed was comparable to that of

paracetamol [34].

2.8 Anti-inflammatory activity

The fruits of G. asiatica are used as an

astringent and as an anti-inflammatory

agent [9].

3. Nutritional value

The ripe fruits of G. optiva are edible and

the raw or cooked fruits have a pleasant

acid taste. The leaves are rated as good

fodder and the trees are heavily lopped for

this purpose in the winter months when

usually no other green fodder is available.

The green leaves constitute about 70% of

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the total green weight of the branches.

Leaf fodder yield is reported to be

9.98 £ 103 kg/ha from 2-year-old plants,

and green fodder yield from mature trees is

reported to be 12–30 kg. Leaves are fairly

rich in protein and other nutrients and do

not contain tannins. Crude protein is

highest in young leaves, and in winter

leaves, but decreases during the rainy

season [3]. G. coriacea, found in tropical

forests of central Africa, has edible

fruits, which is used for producing

species. It is one of the most important

commercial spontaneous fruit crops in the

republic of Congo (Brazzaville). However,

similar to many other spontaneous fruits of

the tropical rain forest in Africa, G.

coriacea remains poorly studied and its

nutritional potential is unknown. With the

aim of valorization of the tropical

vegetable resources, and also the diversi-

fication of the lipid resources for edible

purposes and for cosmetic industry,

evolution of the lipid contents and their

composition in the kernels of this fruit

starting from the fruit setting until its

maturation was studied. Lipid composition

was determined by soxhlet and by gas

chromatography. The study showed that

kernel oils were three times more richer

in unsaturated fatty acids than saturated.

The presence of the arachidic, stearic,

and palmitic acids gives these oils the

potentialities for human nutrition or

cosmetics [35].

4. Chemical constituents

To the best of our knowledge, the first

phytochemical investigation on Grewia

genus can be traced back to 1965.

Friedelin was the first pentacyclic triterp-

noid reported from G. tiliaefolia [36], and

its presence in G. biloba was also

confirmed [37]. Since then, plenty of

studies regarding chemical and biological

aspects of plants within the genus Grewia

have been reported. So far, 32 compounds

have been identified, some of which are of

significant biological importance (Figures

1–5, Table 1).

4.1 Triterpenoids

Friedelin was the first pentacyclic triter-

penoid reported from G. tiliaefolia [36]. It

was also reported from G. biloba along

with epi-friedelan-3-ol [37]. Ursene-

3,19,28-triol, a-amyrin, and ursolic acid

were isolated from the roots of G. Villosa

[38]. Anti-malarial bioassay-directed frac-

tionation of the methanolic extract pre-

pared from a sample of the combined

leaves, twigs, and stems of G. bilamellata

led to the isolation of compounds, includ-

ing two triterpenes 3a,20-lupandiol and

2a,3b-dihydroxy-olean-12-en-28-oic acid

[15]. Lupeol and betulin were reported

from G. bicolour, G. tiliaefolia, and

G. damine [14,16].

4.2 Alkaloids

Grewia genus is famous for alkaloids.

Three alkaloids, harman, 6-methoxyhar-

man, and 6-hydroxyharman, isolated from

the methanolic extract of this plant have

anti-bacterial properties [16].

4.3 Sterols

Two sterols including b-sitosterol and

daucosterol are reported from different

species of this genus [15,16,37].

4.4 Flavones

Two flavone C-glycosides, vitexin and

isovitexin, have been isolated from n-

butanol fraction of the methanolic extract

of leaves of G. damine [39].

4.5 Anthocyanins

Only one anthocyanin, cyanidin, 3-galac-

toside, has been reported from the fruits of

G. asiatica [40].

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4.6 Lignans

Lignans isolated from the plants of the

genus Grewia covered coumarinolignans

and neolignans being the major

components.

4.6.1 Coumarinolignans

Three coumarinolignans grewin, nitidanin,

and cleomiscosin D were isolated from

G. bilamellata [15].

4.6.2 Neolignans

Three neolignans have been reported from

genus G. bilamellata. They were isolated

and characterized from chloroform fraction

of G. bilamellata as 8-O-40 neolignans,

guaiacylglycerol-b-coniferyl ether isomers

(threo and erythro) and bilagrewin [15].

4.7 Lactones

Three lactones, gulonic acid g-lactone,

3,21,24-trimethyl-5,7-dihydroxyhentria-

contanoic acid d-lactone, and D-erythro-2-

hexenoic acid, g-lactone are reported from

G. tiliaefolia and G. asiatica [23].

4.8 Vitamins

The presence of vitamins A and C has also

been reported from G. asiatica [9].

4.9 Organic acids

Heneicosanoic acid, an organic acid, was

reported from G. biloba [37].

4.10 Others

Propyl palmitate, 2,6-dimethoxy-1-aceto-

nylquinol, and grewinol are reported from

G. biloba, G. bilamellata, and G. asiatica,

respectively [15,37,41].

5. Toxicology

Phytochemical and histopathological

studies were carried out by Onwuliri et al.

(2006) on the leaves and stem bark extracts

of G. mollis and the result revealed the

presence of tannins, saponins, flavonoids,

glycosides, phenols, terpenes, steroids, and

the absence of alkaloids in G. mollis bark,

while toxicological result showed that the

plant is safe for human consumption [42].

G. mollis stem bark used locally in Nigeria

as a food additive was mixed with the

normal diet at 0%, 1%, 5%, and 10% and

fed to male Wister rats over a 4-week

period. No deaths or remarkable changes

in general appearance or behavior were

observed in the animals treated. Signifi-

cant ( p , 0.05) increases in serum trans-

aminase activities, accompanied by

decreased food intake, were observed in

rats that were fed with the stem bark at

10% dietary level. Treatments had no

effect on serum alkaline phosphatase

activity, urea, creatinine, triglycerides,

cholesterol, glucose concentrations and,

body and organ weights were determined.

These studies proved that at high concen-

trations, G. mollis stem bark may cause

liver injury [43].

6. Conclusion

Since some species of genus Grewia have

been used as folk medicines for a long time

in Asian countries, pharmacological inves-

tigations have revealed that the extracts of

this genus are highly bioactive. The

knowledge of the extent and mode of

inhibition of specific compounds, which

are present in the plant extracts, may

contribute to the successful application of

such natural compounds for treatment of

infection disorder like fungal and bacterial

diseases. The present status of medicinal

plants and their products provide an

opportunity for the developing countries

to benefit from the emerging marks, as the

developing countries possess the most

biodiversity of medicinal plants. It is

concluded that in coordination with the

chemical literature finding resistant strains

of plant organism, biodiversity may lead to

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an unexpected research findings [44]. The

present findings will facilitate the research-

ers as a basic data for future research in

exploiting the hidden potential of this

important genus which has not been

explored so far.

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