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Food Science and Human Wellness 7 (2018) 34–48

Trichosanthes dioica Roxb.: A vegetable with diverse pharmacological

properties
Mahia Khandaker a,1 , Saleha Akter b,1 , Mohammad Zafar Imam c,∗,1
a Department of Biotechnology, Bangabandhu Sheikh Mujibur Rahman Agricultural University, Salna, Gazipur 1706, Bangladesh
b Department of Pharmacy, Primeasia University, HBR Tower, 9 Banani, Dhaka 1213, Bangladesh
c Department of Pharmacy, Stamford University Bangladesh, 51 Siddeswari Road, Dhaka 1217, Bangladesh

Received 15 August 2017; received in revised form 29 September 2017; accepted 27 December 2017
Available online 4 January 2018

Abstract
Trichosanthes dioica Roxb. is a climber of the Cucurbitaceae family mainly found in tropical Asia. The fruit is widely consumed as a vegetable
and different parts of this plant are used in the traditional medicine to treat various types of human ailments. In this review, we critically analyzed
and presented the scientific studies on T. dioica available in three electronic databases viz. PubMed, Web of Science and Google Scholar. Our aim
was to find the scientific basis of the traditional use to understand the plant’s potential in therapy. Studies have found promising antihyperglycemic,
antihyperlipidemic, antitumor, cytotoxic, arsenic poisoning ameliorative, anti-inflammatory, antidiarrheal, and varieties of pharmacological activ-
ities of T. dioica. Different types of bioactive compounds have been identified and isolated from T. dioica including peptides namely trichosanthin
and lectin; a number of triterpenes like cucurbitacin B, euphol, α-amyrin, ␤-amyrin, lupeol, taraxerol, betulin, and karounidiol; sterols, steroidal
saponin, tannin, flavonoids etc. T. dioica contains a number of well-known bioactive phytochemicals and the plant has shown an array of pharma-
cological activities in vivo. This review will expand our understanding of the therapeutic potential of T. dioica and their phytochemical basis which
may help in further research on this species.
© 2018 “Society information”. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article
under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Keywords: Trichosanthes dioica; Pointed gourd; Cucurbitaceae; Ethnomedicine; Ethnopharmacology

1. Introduction Cucurbitaceae family comprises of 134 genera and 965

Cucurbitaceae is a large family of vegetable crops [1].
The members of this family are annual or perennial herba-
ceous vines and are mostly found in tropical and subtropical
areas with few species in temperate regions [2]. Accord-
ing to The Plant List (http://www.theplantlist.org/), the
most comprehensive on-line plant name database [3–5],
∗ Corresponding author at: Department of Pharmacy, Stamford University
Bangladesh, 51 Siddeswari Road, Dhaka 1217, Bangladesh.
E-mail address: zafarimam@gmail.com (M.Z. Imam).
1 These authors contributed equally.
Peer review under responsibility of KeAi Communications Co., Ltd.
species. However, the numbers significantly vary among
other reports by Jeffrey [6], Kumar, et al. [7], Payel,
et al. [8] and Christenhusz and Byng [9]. Trichosanthes L.
genus of the Cucurbitaceae family comprises of 38 species
(http://www.theplantlist.org/).
Trichosanthes dioica is annual or perennial herbaceous vine
commonly known as Pointed gourd (English), Putulika (San-
skrit), Parval (Hindi) and Potol (Bengali). It grows up to
5–6 m. The stem is about 1 cm thick with simple tendrils. The
leaves are cordate, oblong, acute, sinuate-dentate not lobed
and dark green [10]. The inflorescence is racemose and the
flowers found in leaf axils are whitish green, sessile, soli-
tary, bracteate with oblong-cylindrical calyx tube [11]. Fruits
are generally globose, oblong and smooth and the pericarp
and mesocarp form the edible part [11]. The shape, size
and striation patterns of the fruit vary greatly giving rise of

https://doi.org/10.1016/j.fshw.2017.12.005
2213-4530/© 2018 “Society information”. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under
the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
 M. Khandaker et al. / Food Science and Human Wellness 7 (2018) 34–48
four categories: (1) 10–13 cm long fruit of dark green color
with white stripes; (2) 10–16 cm long and comparatively thick
fruit with dark green color with very pale-green stripes; (3)
5–8 cm long and roundish fruit of dark green color with white
stripes; and (4) 5–8 cm long fruit of green color, tapered at
the ends, and striped [11,12]. T. dioica has tuberous taproots.
The propagation usually is done by root or stem cuttings rather
than the seed because of poor germination and late flowering
[11].
Trichosanthes dioica Roxb. is one of the most con-
sumed species of Trichosanthes genus in the Asian tropical
countries particularly in Bangladesh and India as a veg-
etable from February to September [11]. T. dioica is
thought to be originated in the Indian subcontinent or
Indo-Malayan region [12–15]. It is mainly cultivated in
Bangladesh, India, Pakistan, Myanmar, Nepal and Sri Lanka
[16,17].
The unripe fruit is cooked either alone or with other
vegetables or meat [12]. It is a very nutritious vegetable
which also has potential for industrial use in making dif-
ferent types of jam, jelly, and pickles [18]. There is an
increasing demand of this vegetable in the ethnic grocery
stores of the different parts of the world [11]. Different
parts of this species are been used by the folk practition-
ers and in a number of Ayurvedic preparations. Numerous
studies have been performed to evaluate the validity of the
traditional uses. Due to its heavy consumption as vegetable
and its different folkloric uses, the present review aims to
present the ethnobotanical uses, advances in ethnopharmaco-
logical studies and phytochemistry of different parts of T.
dioica.
2. Methodology
Available original research, reviews, and reports on T. dioica
were consulted from published scientific peer-reviewed journals
and books. Literature was searched in a number of electronic
databases namely, PubMed, Web of Science and Google Scholar
using specific keywords such as “Trichosanthes”, “Trichosan-
thes dioica”, “pointed gourd”, “putulika”, “parval”, “parwal”,
“patol” and “potol”. These keywords were searched individually
as well as in combination where appropriate to get all relevant
works published up to August 2017. The literature was then
screened and only those pertaining to the T. dioica were selected.
The literature was critically read and the scientific information
on the species has been collated in this review.
3. Ethnobotanical uses
T. dioica is used in the Ayurveda as well as by the rural
and tribal folkloric practitioners in a number of human ailments
(Table 1). In Ayurveda, it is used alone or in combination with
other herbs to treat hyperacidity [19]. Nadkarni and Nadkarni
[20] described its use as antiparasitic, antiperiodics, febrifuge,
refrigerants, anticoagulants, blood purifiers, antiseptics, and
tonic. Decoction of leaves mixed with Piper nigrum fruit powder
is used to treat diarrhoea [21]. The plant is also used as stom-
35
achic, antitumor and antidiabetic agent [22]. In Ayurveda leaves
and fruits of T. dioica is used to treat alcoholism and jaundice
[7,23]. Fruit is also used in improving appetite and digestion
[24].
The raw fruit juice is taken as a remedy for spermatorrhoea
[25] while the juice of roasted fruits is applied on chicken pox
scar [26]. T. dioica fruit boiled with Coriandrum sativum seed
and Terminalia chebula kernel is taken in the treatment of teeth
and fruit skin juice mixed with honey is used to remove the
bad odor of mouth [27]. Fruits are also used in fungal infection
in nails and decoction of leaves with Terminalia chebula and
Coriandrum sativum is taken to treat acidity with constipation
[28]. The root of T. dioica is used to treat jaundice, ascites,
anasarca and as a febrifuge, tonic and hydragouge cathartic
[25,29].
4. Pharmacology
4.1. Antihyperglycemic activity
The effect of T. dioica on hyperglycemic conditions in
animals has been studied quite extensively (Table 2). Antihy-
perglycemic activity of the fruit of T. dioica was first reported
by Sharma and Pant [35] in normal albino rabbits. After a
decade later Rai, et al. [36] reported the antihyperglycemic activ-
ity of the aqueous fruit extract of T. dioica in streptozotocin
(STZ)-induced diabetic rats. In this study, the extract was orally
administered at a daily dose of 1000 mg/kg body weight in rats
for 28 consecutive days. After treatment, significant reduction
was observed in all of the tested parameters viz. fasting blood
glucose (FBG) (28.7%), postprandial glucose (PPG) (30.7%),
aspartate aminotransferase (AST) (22.6%), alanine aminotrans-
ferase (ALT) (36.5%), alkaline phosphatase (ALP) (34.2%),
serum creatinine (SC) (35.3%), urine sugar and urine protein.
In continuation to this work Rai, et al. [37] selected multiple
doses such as 500, 750, 1,000, and 1,250 mg/kg body weight for
further study. The results were significant in terms of reducing
the FBG in normoglycemic rats at 6 h observation and in oral
glucose tolerance test (OGTT) at 4 h observation. The glucose
level was reduced in sub-diabetic and mild-diabetic rats at all
the doses. However, the largest tested dose, 1250 mg/kg, did not
show a significant reduction in mild-diabetic rats. Severe dia-
betic rat models were also used to evaluate the effect by Rai, et
al. [38]. A significant reduction was observed in FBG and PPG
in 28 days study period.
Rai, et al. [39] also studied the antihyperglycemic potential of
seed extract of T. dioica at the dose range of 500–1250 mg/kg in
normal, sub-diabetic and mild diabetic rats. The extract showed
a dose-dependent fall of FBG up to 1000 mg/kg dose in normo-
glycemic rats. The effect was similar in case of STZ-induced
sub-diabetic and mild diabetic rats in OGTT. Interestingly, the
antihyperglycemic effect at 1000 mg/kg was better than that
shown by 1250 mg/kg dose and the effect was similar or better
to the effect given by standard drug tolbutamide [39]. However,
the possible reason for the better effect of 1000 mg/kg dose over
1250 mg/kg is absent in the literature.
36 M. Khandaker et al. / Food Science and Human Wellness 7 (2018) 34–48
Table 1
Traditional uses of T. dioica.
Country Region (Community) Plant part(s)
Bangladesh – Fruit
– Fruit skin
Jhenaidah Leaf
India West Bengal (Tribal) Fruit
Orissa (Tribal) Leaf
– Fruit
– Leaf
– Stalk
– Root
The leaves of T. dioica have also been evaluated in normal as
well as in diabetic animal models for its hypoglycemic potential.
Oral administration of T. dioica leaf extract at the doses of 250,
500, and 750 mg/g in normal and STZ-induced sub- and mild-
diabetic rats showed promising hypoglycemic potential [13].
Interestingly, the dose of 500 mg/kg was found to be more effec-
tive than 750 mg/kg. It lowered the FBG level by 32.9% at 6 h
in normal rats while it reduced the level by 30.9% in OGTT at
5 h. The effect of the extract was more pronounce in sub- and
mild-diabetic mice as it reduced the glucose level by 40.3 and
86.6% respectively in OGTT at 3 h period [13]. The leaf extract
was also studied at 800 and 1600 mg/kg doses and were found
effective in both normoglycemic and diabetic rats after both sin-
gle dose and repeated administration [40]. A significant loss in
weight in the two-week observation period was also reported
[40]. So it appears that the leaf alongside fruits and seeds of T.
dioica possess significant antihyperglycemic property.
4.2. Antihyperlipidemic activity
4.2.1. Animal studies
Four animal studies have been found reporting the effective-
ness of T. dioica on lipid profile (Table 2). Sharma and Pant [35]
studied the antihyperlipidemic potential of T. dioica fruit in nor-
mal albino rabbits (n = 8). 1 g of fruit powder mixed with 100 g
of rabbit feed were used for the experimental animals where the
daily feed consumption ranged between 95–100 g. The treat-
ment has shown hypocholesterolemic and hypotriglyceridemic
effect. It also increased phospholipids and HDL-cholesterol in
rabbits [35]. Similar improvement in lipid profile has also been
shown by the seed extract of T. dioica [41].
The aqueous fruit extract of T. dioica also showed a
hypocholesterolemic and hypotriglyceridemic effect in normo-
glycemic and STZ-induced diabetic rats after a single treatment
at the dose of 50 mg/kg [30]. The hypocholesterolemic effect
was similar upon repeated treatment for 2 weeks in both mod-
els. Though the triglyceride (TG) levels increased for a couple
of days, eventually it decreased significantly afterward that was
persistent up to 2 weeks. The body weight of animals of both
groups also significantly decreased after 2 weeks’ treatment
Traditional use(s) Reference
In the treatment of teeth, fungal infection in nail [27,28]
Bad smell of mouth [27]
Acidity with constipation [28]
Chicken pox scar [26]
Diarrhoea [21]
Tonic, febrifuge, boils, skin disease, spermatorrhoea, [23,30]
laxative, enlargement of liver and spleen
Alopecia, enlargement of liver and spleen, fever, [23,30,31]
hemorrhage, anal fistula, leprosy, intrinsic hemorrhage,
erysipelas, diseases of mouth, inflammations and wounds
Expectorant [23]
Febrifuge, cathartic, tonic, jaundice, anasarca, ascites [30,32–34]
[30]. The effect of fruit extract at 1000 mg/kg dose was also
tested in severely diabetic rats for a period of 4 weeks [38].
Total cholesterol (TC) and TG level reduced by 57.2 and 18.5%
respectively after 4 weeks treatment. On the other hand, HDL
level was increased by 33.0% whereas low-density lipoprotein
and very low-density lipoprotein level were decreased by 9.6
and 57.2%, respectively [38].
4.2.2. Human study
Sharma, et al. [42] carried out a human trial to observe the
antihyperlipidemic activity of seed of T. dioica. A group of mild
diabetic male human (n = 20) with no previous history of dia-
betes (FBS: 83.35 ± 6.09; age: 20–42 years; weight: 49–60 kg)
were given 7 g of seed powder of T. dioica daily for two weeks.
The lipid profiles of this group were compared with a group
of non-diabetic human subjects (n = 20) (FBS: 117.12 ± 5.34;
age: 32–62 years; weight: 55–69 kg) receiving the same treat-
ment. The treatment significantly decreased the serum level of
cholesterol and TG and increased phospholipids level in diabetic
patients. The increase of HDL-cholesterol was also noticeable.
All the parameters were also improved in the non-diabetic group
in comparison to their biochemical parameters before receiving
T. dioica treatment. This unbiased overall improvement in lipid
profiles in both human groups provides evidence for the potential
use of T. dioica seed in humans in dyslipidemia.
4.3. Antitumor activity
It has been reported that hydroalcoholic extract of T. dioica
root has antitumor and oxidative stress-reducing activity in
Ehrlich ascites carcinoma (EAC) cells in mice at 5 and 10 mg/kg
doses (Table 2). Mice were intraperitoneally injected with EAC
cells and after 24 h T. dioica was administered at 5 and 10 mg/kg
doses and the treatment were continued for 9 days [44]. Observa-
tion on the 10th day showed that T. dioica treatment significantly
decreased tumor weight, tumor volume, packed cell volume and
viable cell count as well as extended the lifespan of test ani-
mals and hematological parameters were improved [44]. Hepatic
antioxidant parameters such as lipid peroxidation, reduced glu-
tathione (GSH), glutathione S-transferase (GST), superoxide
 M. Khandaker et al. / Food Science and Human Wellness 7 (2018) 34–48 37

Table 2
Summary of pharmacological studies and activities of T. dioica.
Activity Species Inducer Plant part (extract) Protocol Effects Reference
Antihyperglycemic Rat STZ Leaf (aqueous) 800, 1600 mg/kg; p.o.; 15 days ↓FBG, ↑glucose tolerance, ↓weight [40]
Rat STZ Leaf (aqueous) 250, 500, 750 mg/kg; p.o.; ↓FBG, ↑glucose tolerance [13]
single dose
Rat STZ Fruit (aqueous) 1000 mg/kg; p.o.; daily; 28days ↓FBG, ↓PPG, ↓AST, ↓ALT, ↓ALP, [36]
↓creatinine, ↓urine sugar, ↓urine
protein, ↑total protein, ↑body weight
Rat STZ Fruit (aqueous) 500, 750, 1000, 1250 mg/kg; ↓FBG, ↑glucose tolerance [38]
p.o.; single dose
Rabbit Normal Fruit (powder) ∼1 g/animal; p.o.; 8 weeks ↓FBG [35]
Rabbit Normal Seed (powder) ∼1 g/animal; p.o.; 8 weeks ↓FBG, ↓TSC, ↓sTG, ↑HDLc, ↑sPL [41]
Rat STZ Seed (aqueous) 500, 750, 1000, 1250 mg/kg ↓FBG, ↑glucose tolerance [39]
Antihyperlipidemic Rat STZ Fruit (aqueous) 1000 mg/kg; p.o.; daily; 28 days ↓TC, ↓TG, ↓LDL, ↓VLDL, ↑HDLc [38]
Rabbit Normal Fruit (powder) ∼1 g/animal; p.o.; 8 weeks ↓TSC, ↓sTG, ↑HDLc, ↑sPL [35]
Rat STZ Fruit (aqueous) 50 ml/kg; p.o.; daily; 14 days ↓Plasma cholesterol, ↓TG [30]
Rabbit Normal Seed (powder) ∼1 g/animal; p.o.; 8 weeks ↓TSC, ↓sTG, ↑HDLc, ↑sPL [41]
Human Normal Seed (powder) 7 g; p.o.; daily; 14 days ↓TSC, ↓sTG, ↑HDLc, ↑sPL [42]
Antitumor Mice EAC cells Root 2, 4 mg/kg; daily; 9 days ↓Tumor weight, ↓tumor volume, [43]
↓packed cell volume, ↓viable cell
count, ↑life span
Mice EAC cells Root (hydroalcoholic) 5, 10 mg/kg; daily; 9 days ↓Tumor weight, ↓tumor volume, [44]
↓packed cell volume, ↓viable cell
count, ↑life span
Ameliorative effect Rat Sodium arsenite; 10 mg/kg; p.o.; Fruit (aqueous) 50, 100 mg/kg; p.o.; daily; 20 Normalized body weights, organ [45]
on arsenic toxicity 10 days days weights, hematological profiles,
serum biochemical profile, modulated
hepatic and renal biochemical
parameters; ↓DNA fragmentation
Rat Sodium arsenite; 10 mg/kg; p.o.; Fruit (aqueous) 50, 100 mg/kg; p.o.; daily; 20 ↓Lipid peroxidation, ↓oxidative [46]
8 days days enzymes, ↓DNA fragmentation in
brain tissue
Rat Sodium arsenite; 10 mg/kg; p.o.; Fruit (aqueous) 50, 100 mg/kg; p.o.; daily; 20 Normalized body weights, heart [47]
8 days days weights, hematological profiles,
serum biochemical profile; ↓lipid
peroxidation, ↓oxidative enzymes,
↓DNA fragmentation in myocardium
Rat Sodium arsenite; 10 mg/kg; p.o.; Root (hydroalcoholic) 5, 10 mg/kg; p.o.; alternate day; Normalized body weights, organ [48]
8 days 20 days weights, hematological profiles,
serum biochemical profile, modulated
hepatic and renal biochemical
parameters; ↓DNA fragmentation
Rat Sodium arsenite; 10 mg/kg; p.o.; Root (hydroalcoholic) 5, 10 mg/kg; p.o.; daily; 20 days Normalized body weights, heart [49]
8 days weights, hematological profiles,
serum biochemical profile; ↓lipid
peroxidation, ↓oxidative enzymes,
↓DNA fragmentation in myocardium
Anti-inflammatory Rat Carrageenan Fruit (methanolic) 100–400 mg/kg; p.o.; single ↓Paw diameter [50]
dose
Rat Carrageenan; histamine; Root (triterpenoid enriched) 50 & 100 mg/kg; p.o.; single ↓Paw volume; ↓weight of cotton [32]
serotonin; cotton pellet dose pellet
Rat Formalin Root (triterpenoid enriched) 25–100 mg/kg; p.o.; single dose ↓Ascitic fluid formation [51]
Rat Carrageenan Aerial parts (Ethanolic & 150 & 300 mg//kg; p.o.; single ↓Paw volume [52]
different fractions) dose
Antidiarrheal Mice Castor oil; magnesium sulphate Aerial parts (Pet ether, ethyl 200 & 400 mg/kg; p.o.; single ↓Fecal droppings [53]
acetate, methanol, water) dose
Antinociceptive Mice Acetic acid; heat Root (triterpenoid enriched) 50 & 100 mg/kg; p.o.; single ↓ Abdominal writhing, ↑latency [32]
dose
Mice Acetic acid; heat Root (Dichloromethane, 75& 150 mg/kg; p.o.; signle ↓ Abdominal writhing, ↑latency [33]
methanol) dose
Antipyretic Rat Brewer’s yeast Fruit (Methanol, ethyl acetate) 100–400 mg/kg; p.o.; single ↓Rectal temperature [50]
dose
Chemopreventive Mice 3-Methylcholanthrene; Root (hydroalcoholic) 2 & 4 mg/kg; p.o.; 45 days ↓Tumor incidence, ↑life [54]
200 ␮g; s.c.; single dose prolongation, restoration of
hematological profile, modulation of
hepatic biochemical parameters
Cytotoxic Allium cepa root – Root (dichloromethane, 1-16, 20-320, 100–1600 mg/ml; ↓Root length, ↓root number, ↓mitotic [29]
meristem methanol, aqueous) 4 days index
Allium cepa root – Root (triterpenoid rich fraction) 0.75–12 mg/ml; 4 days ↓Root length, ↓root number, ↓mitotic [55]
meristem index
Hepatoprotective Rat Ferrous sulphate; 30 mg/kg; - (aqueous, ethanolic) 100–400 mg/kg/p.o.; 10 days ↓ALT, ↓AST, ↓ALP, ↓TB, ↑TP, [56]
p.o.; single dose ↓necrosis, ↓infiltration,
↓degenerative changes
Immunomodulatory Rat – Whole plant (aqueous) 100 & 200 mg/kg; p.o.; 45 days ↑RBC, ↑WBC, ↑hemoglobin, [57]
↑antibody production
Laxative Mice Loperamide Root (aqueous) 100 & 200 mg/kg; p.o.; single ↑Total stool, ↑wet stool, ↑ [58]
dose gastrointestinal transit time
Mice Loperamide Root (triterpenoid enriched) 50 & 100 mg/kg; p.o.; single ↑Total stool, ↑wet stool, ↑ [59]
dose gastrointestinal transit time
Wound healing Rat Excision, incision Fruit (methanolic) 5% w/w ointment; topical; 10 ↑Wound contraction, [60]
days ↓epithelialization period,
↑hydroxyproline content, ↑tensile
strength
38 M. Khandaker et al. / Food Science and Human Wellness 7 (2018) 34–48
dismutase (SOD) and catalase (CAT) were also significantly
improved in the T. dioica treated group [44]. The triterpenoid
fraction of T. dioica root has also been tested at 2 and 4 mg/kg
doses in the same model and its antiproliferative efficacy has
been reported [43]. All these results indicate antitumor efficacy
of T. dioica root (Table 2).
It is very interesting that the same extract has been reported
to promote tumor proliferation in EAC in mice by the same
researcher group [34]. It this case, mice were intraperitoneally
injected with EAC cells and after 24 h T. dioica was adminis-
tered at 25 and 50 mg/kg doses and the treatment were continued
for 8 days [44]. Tumor proliferation, hematological and hepatic
examination have shown a significant increase in tumor weight
as well as volume, packed cell volume and reduced non-viable
cells and lifespan of test animals, worsened hematological and
hepatic antioxidative parameters [44]. Both reports used the very
same experimental model and procedure, used only higher doses
of extract, and found to possess completely opposite effect! The
possible mechanism was not explained. However, trichosanthin,
a ribosome-inactivating protein, isolated from the root of T.
dioica has been found to induce apoptosis in tumor cells [61,62].
4.4. Ameliorative effect on arsenic toxicity
Effect of T. dioica on arsenic-induced toxicity has been stud-
ied on different organ system and was found effective in all the
studies. The hydroalcoholic extract of T. dioica root was evalu-
ated at 5 and 10 mg/kg doses for its potential ameliorative effect
against arsenic-induced toxicity in rats. T. dioica was orally
administered for 20 consecutive days and then sodium arsenite
for 8 days. T. dioica treatment showed significant ameliorative
effect on body weight, renal and kidney weight, hematological
and serum biochemical profile and hepatic and renal biochemi-
cal parameters against arsenic toxicity [48]. Aqueous extract of
T. dioica fruit was also tested in a similar model at the doses
of 50 and 100 mg/kg with arsenic exposure to 10 days. Signifi-
cant ameliorative effect was shown by the fruit extract also [45].
The fruit extract has also alleviated arsenic-induced brain tox-
icity [46] and myocardial toxicity [47]. The root extract also
alleviated myocardial toxicity [49].
4.5. Anti-inflammatory activity
The fruit of T. dioica was tested for anti-inflammatory effect
in carrageenan-induced paw edema in rats [50]. Methano-
lic extract was tested at 100, 200, and 400 mg/kg doses and
dichloromethane and ethyl acetate fractions were tested at
200 mg/kg doses. Methanolic extract at 200 and 400 mg/kg doses
and ethyl acetate fraction showed a significant decrease in paw
diameter. The dichloromethane fraction did not inhibit the paw
diameter significantly [50].
The root extract of T. dioica has also shown promising anti-
inflammatory activity in both acute and chronic inflammation
model in rats at the doses of 50 and 100 mg/kg [32]. The
extract reduced the carrageenan-induced paw edema in a dose-
dependent manner after 4 h. Besides, it improved the edema
induced by histamine and serotonin indicating that it also sup-
presses inflammation induced by inflammatory mediators. T.
dioica has also significantly reduced cotton pellet induced gran-
uloma formation [32]. The same extract was tested at 25, 50,
and 100 mg/kg doses in formalin-induced acute inflammatory
ascites in rats and the extract significantly reduced the ascitic
fluid formation after 7 h in a dose-dependent manner [51]. These
demonstrate the anti-inflammatory potential of T. dioica root
extract in different inflammatory animal models.
Ethanolic extract of aerial parts of T. dioica and its successive
petroleum ether, chloroform, ethyl acetate, and methanolic frac-
tions have been evaluated for anti-inflammatory effect at 150
and 300 mg/kg doses in carrageenan-induced paw edema test
in rats [52]. Except for petroleum ether fraction, all samples
showed a significant reduction in paw volume after 5 h post-
treatment. Extract and fractions have been found to attenuate
tumor necrosis factor-␣ (TNF-␣) level as well as reduced expres-
sion of cyclooxygenase-2 and nuclear transcription factor-␬B
and the ethyl acetate fraction was reported to be the most effec-
tive against inflammation and attenuation of TNF-␣ [52].
4.6. Gastrointestinal effects
Akter, et al. [53] evaluated the antidiarrheal potential of aerial
parts of T.dioica in castor oil and magnesium sulphate-induced
diarrhea in mice. Four different extracts of the plant material
were used namely petroleum ether, ethyl acetate, methanol and
water extract at 200 and 400 mg/kg doses. All four extracts
showed a significant decrease in castor oil-induced fecal drop-
pings whereas the effect of ethyl acetate and methanol extracts
in magnesium sulphate-induced diarrhea was significant [53].
Bhattacharya and Haldar [58] have tested the laxative poten-
tial of the aqueous extract of T. dioica root in mice. The extract
at 100 and 200 mg/kg doses were tested in both non-constipated
and loperamide-induced constipated mice [58]. Gastrointestinal
(GI) transit was also measured. Both doses caused a significant
increase in total stool and wet stool up to 4 h observation in
a dose-dependent manner. The extract also increased GI tran-
sit time suggesting T. dioica root extract possesses stimulant
laxative activity. Observing the effect Bhattacharya and Haldar
[59] carried out the further study with the triterpenoid enriched
fraction in same mice models at 50 and 100 mg/kg doses. The
triterpenoid fraction of T. dioica root showed promising laxative
and prokinetic effects.
4.7. Antinociceptive activity
The triterpenoid-enriched extract of T. dioica root has been
evaluated for antinociceptive activity at 50 and 100 mg/kg
doses by acetic acid-induced writing and tail flick test in mice.
The number of writhing was significantly inhibited by both
50 and 100 mg/kg doses while only 100 mg/kg dose signifi-
cantly increased the latency period in tail flick test [32]. The
dichloromethane and methanol extract of roots of T. dioica were
also tested for antinociceptive activity at 75 and 150 mg/kg
doses. Acetic acid-induced writhing was significantly inhibited
by both doses of dichloromethane and only by 150 mg/kg dose of
methanol extract. In tail flick test only dichloromethane extract
 M. Khandaker et al. / Food Science and Human Wellness 7 (2018) 34–48
at only 150 mg/kg dose significantly increased latency period
1 h post-treatment [33].
4.8. Antioxidant activity
Different in vitro antioxidant assays have been performed
with various parts of T. dioica and a promising antioxidant
profile of T. dioica has been reported. The leaf extract has
been reported to possess promising ferrous reducing antioxi-
dant power and phenolic compounds were estimated as 259 mg/g
[63]. Aerial parts of T. dioica has also shown antioxidant activity
in vitro in nitric oxide scavenging [53]. Fruit extracts and differ-
ent fractions have shown antioxidant activity in DPPH radical
scavenging, nitric oxide scavenging, and reducing power assay
in a dose-dependent manner [50,64].
4.9. Cytotoxic activity
In vitro cytotoxic activity of dichloromethane, methanol and
aqueous extract of T. dioica was evaluated using Allium cepa root
meristems growth test. Dose-dependent inhibition of root growth
and reduction of the mitotic index was observed in case of all
extracts amongst which dichloromethane extract was found most
potent with EC50 of 2.8 mg/ml [29]. These results demonstrate
cytotoxic and genotoxic potential of T. dioica extracts [55].
4.10. Hepatoprotective activity
Hepatoprotective potential of T. dioica was evaluated in fer-
rous sulphate-induced hepatotoxicity in a rat model. Aqueous
and ethanolic extract of T. dioica at the doses of 100, 200, and
400 mg/kg were administered for 10 days and then ferrous sul-
phate at the dose of 30 mg/kg was administered intraperitoneally
to induce hepatotoxicity [56]. On 11th day blood was tested for
different hepatic parameters such as alanine aminotransferase
(ALT), aspartate aminotransferase (AST), alkaline phosphatase
(ALP), total protein (TP) and total bilirubin (TB) and histopatho-
logical examination was performed. Both extract at 200 and
400 mg/kg doses significantly decreased the level of ALT, AST,
ALP, and TB and increased TP. Histopathological examination
showed that aqueous extract of T. dioica at 200 mg/kg dose
showed slight evidence of necrosis and at 400 mg/kg dose there
was no infiltration and no necrosis whereas the ethanolic extract
treatment at both 200 and 400 mg/kg doses showed no infiltra-
tion, necrosis or degenerative changes [56].
4.11. Chemopreventive activity
Chemopreventive potential of hydroalcoholic extract of T.
dioica root was evaluated against 3-methylcholanthrene (3-
MC)-induced carcinogenesis in mice at the doses of 2 and
4 mg/kg for 45 days. The treatment was orally given after
24 h of single-dose 3-MC (200 ␮g) administration subcuta-
neously in mice. After 15 weeks hematological and hepatic
profiles were observed and it has been found that T. dioica
reduced tumor incidence in mice and both hematological and
hepatic parameters (lipid peroxidation, reduced glutathione,
39
glutathione-S-transferase, superoxide dismutase, and catalase)
have significantly been improved indicating the extracts chemo-
preventive potential [54].
4.12. Immunomodulatory effect
Aqueous extract of T. dioica whole plant was adminis-
tered in rats at the dose of 100 and 200 mg/kg doses for 45
days. The extract has shown increased production of red blood
cells, white blood cells, and hemoglobin. A dose-dependent
increase in antibody production was also observed indicating
the immunomodulatory effect of the extract [57].
4.13. Wound healing activity
Shivhare et al. [60] have studied the wound healing activity of
T. dioica in excision and incision rat models. T. dioica ointment
(5% w/w) was administered to the rat models and the results
of the study showed improvement in all the parameters such
as wound contraction, epithelialization period, tensile strength,
and hydroxyproline content. While tensile strength assured the
mechanical strength of the healed wound, hydroxyproline con-
tent in the collagen fibers helped to understand the progression
of the healing process. Histopathological examination of the
skin sample presented significant presence of fibroblast cells,
collagen fibers, and blood vessels [60].
4.14. Antipyretic activity
Antipyretic activity of T. dioica fruit extract was tested in
rats with Brewer’s yeast-induced fever. Methanol extract at
400 mg/kg dose and ethyl acetate fraction at 200 mg/kg dose
showed significant antipyretic activity from 3rd to 5th h of treat-
ment [50].
4.15. Antifungal activity
The unsaponifiable fraction of the fixed oils of T. dioica seed
has shown antifungal activity using filter paper disc plate method
[65].
4.16. Neuropharmacological activity
The extract of roots of T. dioica was also tested for CNS
depressant activity at 75 and 150 mg/kg doses in mice. The
effect of dichloromethane and methanol extract on the loco-
motion of mice was observed using actophotometer. Only
dichloromethane extract showed a dose-dependent decrease in
the locomotion significantly [33]. Bhattacharya and Haldar [66]
have also reported that the root extract has skeletal muscle relax-
ant and sedative property.
4.17. Antiulcerant activity of polyherbal preparations
containing T. dioica
T. dioica along with other medicinally important herbs are
used to prepare Ayurvedic preparation. One such preparation
40 M. Khandaker et al. / Food Science and Human Wellness 7 (2018) 34–48
has been studied in peptic and duodenal ulcer patients. In a 10-
patient case study of peptic ulcer disease (PUD), a preparation
containing eleven herbs including T. dioica showed complete
improvement in 50% cases and partial improvement in 40%
cases [19]. The treatment was given at the dose of 10 ml thrice
daily for 3 weeks. It decreased gastric acid hypersecretion and
normalized hyposecretion. Another polyherbal formulation of
four herbs including T. dioica has also showed antiulcerant activ-
ity where 33 operated cases of duodenal ulcers (DU) were treated
with 20 ml twice daily dose. Moreover, single herb T. dioica has
also proved efficacy in 20-patient case of DU at the dose of 50 ml
thrice daily for three weeks [19]. All these studies can be a strong
evidence for the antiulcerant potential of T. dioica.
5. Toxicology
T. dioica fruit is mainly consumed as a vegetable along with
seed in tropical Asia. No report of toxicity of the fruits in human
has been documented. There is only one report that evaluated the
toxicity of the seeds of T. dioica in male albino Wistar rat .The
rats were given 10 and 15 g of the extracts and were observed
for gross behavioral neurologic, autonomic, and toxic effects
constantly. Consumption of foods, feces, and urine were also
examined at 2 h and then at 6-h intervals for 24 h. Behavior of
the treated rats appeared normal with no toxic effect at doses
up to 10 and 15-times the effective dose and no death in any of
these groups were observed [39]. Besides, T. dioica root extracts
have shown wormicidal activity against Pheretima posthuma
and Ascaridia galli [67].
6. Phytochemistry and bioactive compounds
Phytochemical analyses of different parts of T. dioica have
led to isolation of great number of compounds (Table 3) (Fig. 1).
Chopra, et al. [68] reported the presence of trichosanthin in Tri-
chosanthes about sixty years ago. Trichosanthin has also been
found in the root of T. dioica which is known as a ribosome-
inactivating protein (RIP) and for its anti-HIV activity [23,69].
Besides, significant amount of peptides, ranging in 2–8 kDa,
have been isolated from the seeds of T. dioica [70]. These pep-
tides are unique in nature being resistant to silver nitrate’s action
which generally stains protein [70]. Lectin, a carbohydrate-
binding protein, has been found in the seeds of T. dioica using
affinity chromatography on cross-linked guar gum [71]. This
protein is galactose-specific and it consists of two subunits of 37
and 24 kDa size covalently connected by disulfide bond [71].
This lectin is thought to be similar to type-2 RIP consider-
ing its subunit size, disulfide linkage, galactose-specificity and
secondary structure [71].
Sterols and tetra- and pentacyclic triterpenes are the most
abundant group of chemical compounds found in T. dioica. In
the late nineties, 14 sterols and 13 triterpenes were isolated
from the unsaponifiable lipids from the root (Table 3) and the
composition was compared with the other cucurbits [72,73].
Euphol, α-amyrin, ␤-amyrin, lupeol, and taraxerol are the most
important bioactive triterpenes among them. The same group of
researchers also reported the isolation of another six triterpenes
including betulin and karounidiol from seed [74]. Cucurbitacin
B, an oxygenated tetracyclic triterpenoid, with promising anti-
cancer potential has been found in the fruit [75].
A steroidal saponin namely 24-␣-ethyl-20-ene-7-hydro-
stigmast-8␤:14␤-di-3-O-␤-d-xylofuranoside has been found in
the leaf [22]. The leaf also contains phenols and flavonoids which
have been quantified [63,76].
The fruit has been reported to contain a higher concentration
of calcium, magnesium, iron [37], and free amino acids, nico-
tinic acid, riboflavin, vitamin C, thiamine, 5-hydroxytryptamine
[25]. It has been reported that root contains colocynthin, hentri-
acontane, cucurbita-5,24-dienol [25], an amorphous saponin, a
non-nitrogenous bitter glucosidic principle, essential oil, fixed
oil and tannin [10]. Seed fatty acids contain elaeostearic, linoleic,
oleic and saturated acids [25].
6.1. Cucurbitacin B
Cucurbitacins are a group tetracyclic triterpenoids mainly
found in the plants of Cucurbitaceae. So far 17 cucurbitacins
have been identified in different cucurbits [77]. Cucurbitacin
B has been isolated from the fruits of T. dioica [75]. This
compound has been extensively studied and found effective in
different types of cancers including breast cancer, ovarian can-
cer, lung cancer, prostate cancer, osteosarcoma, and melanoma,
[78–86] and in sepsis-induced acute lung injury [87]. Besides,
different molecular mechanisms have been identified in differ-
ent types of cancer cell lines that contribute to its anticancer
activity [77,79,80,83–85,88–94]. In a recent study, low-dose
cucurbitacin B and low-dose methotrexate exhibited a syner-
gistic anticancer effect in the treatment of human osteosarcoma
[78]. Synergism in activity has also been observed with cucur-
bitacin B and curcumin in multidrug resistance human hepatoma
cells [95]. It also exhibited chemosensitizing property in cis-
platin and paclitaxel-resistant ovarian cancer [86,96].
6.2. Trichosanthin
Trichosanthin is a protein known for its abortifacient,
immunosuppressant and antitumor activity [97]. It is a 27-
kDa protein having a single chain of 247 amino acids residues
[61]. It was primarily isolated from Trichosanthes kirilowii
root [97] and it has been reported in the roots of Trichosan-
thes dioica [25]. This ribosome inactivating protein has already
shown antitumor, anti-HIV-1, anti-HSV-1 and immunoregula-
tory properties [98–100]. It has been studied in numerous types
of cancer cell lines and found effective in choriocarcinoma,
cervical cancer, lymphoma, hepatoma, colon carcinoma, stom-
ach cancer, lung cancer, breast cancer, prostate cancer, and
melanoma [62,101,102]. Induction of apoptosis (e.g., by acti-
vating caspase-3, caspase-8 pathway, increasing reactive oxygen
species, arrest of cell cycle G1 phase), calcium level increase in
cytosol, decrease in cyclic adenosine monophosphate as well as
protein kinase C and inhibition of telomerase activity is thought
to be involved in its anticancer activity observed in different cell
lines [61,101,103,104].
 M. Khandaker et al. / Food Science and Human Wellness 7 (2018) 34–48 41

Table 3
Compounds reported in different parts of T. dioica.
Classification Chemical compounds Plant parts References

Triterpenes Cucurbitacin B (1) Fruit [75]

Euphol (2) Root [73]
Tirucallol (3) Root [73]
Cycloartanol (4) Root [73]
Taraxerol (5) Root [73]
␤-Amyrin (6) Root [73]
Butyrospermol (7) Root [73]
Isomultiflorenol (8) Root [73]
24-Methylene-24-dihydrolanosterol Root [73]
α-amyrin (9) Root [73]
Lupeol (10) Root [73]
24-Methylene-24-dihdyroparkeol Root [73]
24-Methylenecycloartanol (11) Root [73]
Multiflorenol (12) Root [73]
7-Oxodihydrokarounidiol-3-benzoate Seed [74]
Karounidiol-3-benzoate Seed [74]
Karounidiol (13) Seed [74]
7-Oxodihydrokarounidiol (14) Seed [74]
Betulin (15) Seed [74]
29-Hydroxylupeol Seed [74]
Cucurbita-5,24-dienol Seed [25]
Sterols 24-Methylcholesterol (16) Root [72]
24-Methylenecholesterol (17) Root [72]
24-Methylcholesta-7,22-dienol Root [72]
24-Ethylcholesta-5,22-dienol Root [72]
24-Ethylcholesta-5,22,25-trienol Root [72]
24-Ethylcholesta-8,22-dienol Root [72]
24-Methylenecholest-7-enol Root [72]
24-Ethylcholesterol (18) Root [72]
24-Ethylcholesta-8,22,25-trienol Root [72]
24-Ethylcholesta-5,25-dienol Root [72]
24-Ethylcholesta-7,22-dienol Root [72]
24-Ethylcholesta-7,22,25-trienol Root [72]
28-Isofucosterol (19) Root [72]
24-Ethylcholest-7-enol Root [72]
24-Ethylcholesta-7,25-dienol Root [72]
28-Isoavenasterol Root [72]
Avenasterol (20) Root [72]
Saponin 24-␣-Ethyl-20-ene-7-hydro-stigmast-8␤:14␤-di-3-O-␤-d-xylofuranoside Leaf [22]
Protein Trichosanthin Root [25]
Lectin Seed [71]
Glycoside Colocynthin (21) Root [25]
Minerals Calcium Fruit [37]
Iron Fruit [37]
Magnesium Fruit [37]
Organic acids Elaeostearic acid Seed [25]
Linoleic acid Seed [25]
Oleic acid Seed [25]
Saturated acids Seed [25]
Vitamins Vitamin A [68]
Vitamin C Fruit [25]
Nicotinic acid Fruit [25]
Riboflavin Fruit [25]
Thiamine Fruit [25]
Hydrocarbon Hentriacontane Seed [25]
Miscellaneous 5-Hydroxytryptamine Fruit [25]
Carotene Fruit [23]
Essential oil Root [10]
Fixed oil Root [10]
Tannin Root [10]
Peptide Seed [70]
42 M. Khandaker et al. / Food Science and Human Wellness 7 (2018) 34–48

6.3. α-Amyrin and β-amyrin extracts have shown antimicrobial and antifungal activity [105].
Extracts containing α-amyrin and/or ␤-amyrin also exhibited
These compounds are pentacyclic triterpene which has been anti-inflammatory activity [105,106]. ␤-amyrin also exhibited
reported in the roots of T. Dioica [73]. α-amyrin containing plant anti-lipoxygenase activity [107].

Fig. 1. Chemical structures of major compounds in T. dioica. (Structures were obtained from the PubChem database at https://pubchem.ncbi.nlm.nih.gov/).
 M. Khandaker et al. / Food Science and Human Wellness 7 (2018) 34–48 43

Fig. 1. (Continued)

6.4. Euphol 6.5. Taraxerol

The triterpenoid alcohol euphol was first isolated from the
dried latex of Euphorbia tirucalli [108]. Later it has been
reported in other plants including T. Dioica root [73]. It exhibits a
number of biological activities such as hypotensive [109], anti-
colitis [110], anti-inflammatory [111] and anti-viral activities
[112]. Euphol also showed spinal and supraspinal antinoci-
ception by inhibiting inflammatory mediators and largely by
interacting with the cannabinoid system [113–115]. In more
recent studies, the anticancer activity of euphol has been reported
in T47D breast cancer and human gastric cancer cell lines. The
effect was due to the arrest of cell cycle and ERK1/2-mediated
apoptosis [116,117].
Akihisa, et al. [73] isolated taraxerol from the roots of T.
dioica. Taraxerol, an oleanane triterpenes, has been isolated
from different types of plants including common dandelion
Taraxacum officinale and different mangrove plants [118–120].
Taraxerol possesses antitumor, anti-inflammatory, antimicrobial
and anti-snake venom activity [119,121]. It has shown activity
against sarcoma 180 cell line and inhibited spontaneous mam-
mary tumors in mice [121]. Taraxerol also induces cell cycle
arrest and promote apoptosis in human gastric epithelial cell line
AGS cells [122]. Besides these two mechanisms induction of
autophagy as well as cell migration inhibition are also involved
it’s (taraxerol acetate) anticancer activity in U87human glioblas-
44 M. Khandaker et al. / Food Science and Human Wellness 7 (2018) 34–48
toma cell line [123]. In HeLa cell line the apoptosis is mediated
by the mitochondrial pathway [124]. It also induces apoptosis,
inhibits cyclo-oxygenase and acetylcholinesterase and reverses
insulin resistance in 3T3L1 adipocytes [119,121].
6.6. Lupeol
It is mainly a dietary triterpene found in different vegetables
and fruits as well as in numerous medicinal plants [125]. In the
last two decades, lupeol has been extensively studied for differ-
ent biological activities and as a result, its efficacy in diverse
human ailments such as inflammation, hepatic toxicity, arthri-
tis, renal damage, diabetes, cardiovascular ailments, microbial
infections and cancer has been reported [125–127].
6.7. Karounidiol
This compound is a multiflorane-type triterpenoid that has
been isolated from the seeds of T. dioica and some other Tri-
chosanthes species. Karounidiol was found to inhibit tumor
promotion induced by 12-O-Tetradecanoylphorbol-13-acetate
in mice [128]. Akihisa, et al. [129] also reported the cytotoxic
potency of this compound against human renal cancer cell lines.
6.8. Betulin
Betulin (Lup-20(29)-ene-3␤,28-diol) is a naturally occurring
triterpene of lupane structure mainly found in the bark birch tree
but it has been reported in at least twenty different plant species
of the different family [130]. Akihisa, et al. [74] isolated betulin
from the seeds of T. dioica. Antiseptic and antirachitic prop-
erties of betulin were the first bioactivities that were reported.
Later investigations on extracts containing betulin confirmed
numerous properties of betulin including cholesterol lowering,
anti-inflammatory, hepatoprotective, wound healing, antitumor
and choleretic properties [130–132]. The antitumor potential of
betulin has been studied in different types of cell lines. Though
it has been reported less active in different types of human
melanoma cell lines, it has been found effective in colorectal,
prostrate, breast, lung and other cancer cell lines [133,134]. The
potent antitumor activity of betulin is due to the apoptosis of can-
cer cells by mitochondrial, caspase-activated and other cellular
protein-mediated pathways [134]. A recent work also reports its
chondroprotective activity in rat [135].
6.9. 24-Methylcholesterol and 28-isofucosterol
Though a number of sterols have been reported in the
unsaponifiable lipids from the root of T. dioica, only two of them,
namely 24-methylcholesterol and 28-isofucosterol, were found
bioactive. 24-Methylcholesterol and 28-isofucosterol isolated
from the soft coral extracts have shown antibacterial activity
against Bacillus spp. and Ochrobactrum pseudogrignonese in
disc-diffusion assay in a similar pattern of Cu2 O used as posi-
tive control [136]. This activity has shown the potential of these
sterols as an antifouling agent but their activities against human
pathogenic organism are yet to be explored.
7. Conclusions
T. dioica is of considerable importance as it possesses
a wide spectrum of pharmacological properties such as
antihyperglycemic, antihyperlipidemic, antitumor, cytotoxic,
arsenic poisoning amelioration, anti-inflammatory, antidiar-
rhoeal activities etc. These properties are associated with
diverse groups of chemical constituents including peptides
(trichosanthin and lectin), triterpenes (cucurbitacin B,euphol,
α-amyrin, ␤-amyrin, lupeol, taraxerol, betulin and karounidiol),
sterols (24-methylcholesterol, 24-methylenecholesterol, 24-
ethylcholesterol, 28-isofucosterol, avenasterol) etc. Although
pharmacological properties of extracts, triterpene rich fraction
or compounds isolated from T. dioicaare substantiated by the
in vitro and in vivo studies in different animal models, the mech-
anisms of these activities are yet to be addressed. An emphasis
should be given on further mechanistic studies using animal
models and cell cultures. Besides, the only human trial report-
ing its therapeutic potential dates back almost three decades ago
and in a small group of patients [42]. Adequate well-defined clin-
ical trials with large patient groups are required to substantiate
the significant role of this edible species in health care.
Conflict of interest statement
The authors declare that the research was conducted in the
absence of any commercial or financial relationships that could
be construed as a potential conflict of interest.
Author contributions
MK, SA and MZI contributed equally in preparing the
manuscript.
Acknowledgement
No funding was received for this work from any organization.
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