Fphar 09 01177
Fphar 09 01177
Fphar 09 01177
this plant is done through seeds and are sown in February–March A local inhabitant from reserve forest of Mahadevpur
or June–July (Munshi et al., 2010). (previously in Andhra Pradesh now in Telangana) widely uses
The purpose of the present review is to analyze the the fruit for diabetes treatment (Kanaka et al., 2013). Apart from
traditional uses, phytochemistry, pharmacological activity, and this, the plant is also used by the tribes of western Maharashtra
toxicological studies of plant. Moreover, the knowledge obtained on insect bite. Fruit powder is applied topically to treat swollen
from various experimental studies was critically assessed to hemorrhoids. The kernel of the seed is used as an efficient
provide justification for traditional and medicinal uses of Luffa remedy for dysentery while the juice of the fruit is applied to
acutangula. cure a headache (Dandge et al., 2010). Oral administration of
seed powder is extensively used for the treatment of urinary
bladder stone in Rajasthan (Katewa et al., 2004). Local application
BOTANICAL ASPECTS of pulverized leaves is reported to be useful in splenitis,
hemorrhoids, ringworm infection, and leprosy while the juice of
Luffa acutangula (L.) Roxb. is classed in the Cucurbitaceae, a the leaves is administered into the eye for treatment of granular
family of flowering of plants with 98 accepted genera and about conjunctivitis in children (Mahbubar, 2013). In addition, the fruit
975 species. Many of the annual or perennial species native to possesses demulcent and diuretic properties while the seeds have
temperate and tropical areas are fruit bearing or ornamental purgative, emetic and anthelmintic properties. The dried fruit
plants (Lucas et al., 2010; Encyclopaedia Britannica, 2018). powder is useful in preventing premature graying of hair. The
The synonyms of plants are Cucumis acutangulus, Cucurbita root of the plant is laxative and used in dropsy (Nadkarni, 1996).
acutangula, Luffa foetida, Luffa drastica, Cucumis operculatus
Roxb., Luffa gosa Ham. (Quattrocchi, 2012).
The plant has different names in different languages PHYTOCHEMISTRY
of India such as: English: Ridged gourd, angled loofah,
ribbed gourd, Chinese okra, silk squash (En); Hindi: Turai, The phytochemical studies have resulted in isolation and
Kadaviturai; Marathi: Dodaka; Sanskrit: Dhamargava, Koshataki; identification of approximately 50 compounds, such as
Bengali: Titotorai, Titojhinga, Titodhundal, Jhinga, Ghoshalata; flavonoids, anthraquinones, proteins, fatty acids, saponin
Kannada: Kahire, Kahi heere, Naaga daali balli; Malayalam: triterpene, volatile components, and other phytoconstituents
Athanga; Tamil: Itukari, Itukarikkoti, Kacappi, Kacappuppirkku, (Table 1).
Kaccam, Kaippuppirkku, Karniti; Telugu: Adavibira, Chedubira,
Sendubirai, Adavi beera, Chathi beera (Nadkarni, 1996). Proteins
The roots of the plant are yellowish brown in color and Various ribosome inactivating proteins (RIPs) were isolated
cylindrical in shape. Longitudinal wrinkles on root contribute from different parts of Luffa acutangula. Medicinal applications
to their rough texture. Five angled, glabrous stem is brownish of RIP have received wide attention, as they possess various
yellow in color along with tendrils up to 6-fid. Flowers are pharmacological activities including abortifacient (Jin, 1985),
regular, unisexual and consists of yellow petals. Female flowers antifungal (Leah et al., 1991), anti-tumor (Bolognesi and Polito,
are yellow colored solitary, 2–15 cm long on pedicels, with 2004), antivirus and HIV-1 integrase inhibitory activities (Au
inferior, longitudinally ridged ovary and 3-lobed stigma while et al., 2000; Wang et al., 2002).
male flowers are light greenish in color, consist of three free Junkai et al. (2002) isolated two RIPs, luffaculin 1 (1) and 2 (2)
stamens with yellow corolla inserted into the receptacle tube. from seeds by using sodium dodecyl sulfate-polyacrylamide gel
Leaves are simple, alternate and orbicular in outline with electrophoresis (SDS-PAGE). The molecular mass of luffaculin 1
15–20 cm long, palmately 5–7 angled, triangular to broadly and 2 was found to be at 28 kD. Significant anticancer activity was
rounded lobes and pale green in color. Veins and vein islets shown by both RIP in human leukemia K562 cells with an IC50
◦
are prominent. Fruits are cylindrical, pale yellowish-brown in value of 1.1 × 10−6 and 2.0 × 10 7 mol/L, respectively (Junkai
color, bitter in taste, tapered toward the base and are covered et al., 2002).
with 8–10 prominent ribs. Inner part of the fruit is three Another RIP, luffangulin (3) was isolated from seed which
chambered, fibrous and easily detachable from the outer part. inhibited cell-free translation (IC50 = 3.5 nM) but showed no
Seeds are elliptical and black colored (Basu and Kirtikar, activity against HIV-1 reverse transcriptase (Wang and Ng, 2002).
1987).
Flavonoids
Schilling and Heiser (1981) isolated total 10 flavonoids from
TRADITIONAL USES AND different species of Luffa. Among these, only two flavonoids,
ETHNOPHARMACOLOGY i.e., apigenin-7-glucoside (4) and luteolin-7-glucoside (5) were
present in leaf and flower (Figure 1) (Schilling and Heiser, 1981).
Different parts of Luffa acutangula have been used extensively
by different ethnic groups in India for medicinal purposes. In Anthraquinone
Maharashtra and the tribal areas of Madhya Pradesh, leaves and Anthraquinone derivative 1,8-dihydroxy-4-methylanthracene-
fruit powder are used for the treatment of jaundice (Das and 9,10-dione (6) was isolated using bioassay-guided approach from
Basu, 1997; Samvatsar and Diwanji, 2000). the ethanolic extract of aerial parts (Figure 2). Only five fractions
(Continued)
TABLE 1 | Continued
30 β-Terpinene SPME coupled with GC-MS Flower Volatile components Fernando and Grun, 2001
31 γ-Terpinene SPME coupled with GC-MS Flower Volatile components Fernando and Grun, 2001
32 Methyl, methyl ethyl substituted SPME coupled with GC-MS Flower Volatile components Fernando and Grun, 2001
benzene
33 trans-Linalool oxide SPME coupled with GC-MS Flower Volatile components Fernando and Grun, 2001
34 trans-Dihydrocarvone SPME coupled with GC-MS Flower Volatile components Fernando and Grun, 2001
35 Linalool SPME coupled with GC-MS Flower Volatile components Fernando and Grun, 2001
36 cis-Sabinene hydrate SPME coupled with GC-MS Flower Volatile components Fernando and Grun, 2001
37 α-Thujone SPME coupled with GC-MS Flower Volatile components Fernando and Grun, 2001
38 2-methyl-6-methylene-1,7- SPME coupled with GC-MS Flower Volatile components Fernando and Grun, 2001
octadien-3-one
39 3,4-dimethyl-2,4,6-octatriene SPME coupled with GC-MS Flower Volatile components Fernando and Grun, 2001
40 Epoxylinelol SPME coupled with GC-MS Flower Volatile components Fernando and Grun, 2001
41 α-Terpineol SPME coupled with GC-MS Flower Volatile components Fernando and Grun, 2001
42 1H-Indole SPME coupled with GC-MS Flower Volatile components Fernando and Grun, 2001
43 Neryl acetate SPME coupled with GC-MS Flower Volatile components Fernando and Grun, 2001
44 2,3-dihydro,3,5-dihydroxy-6- Ethanolic extract Fruit Other Suryanti et al., 2017
methyl-(4H)-pyran-4-one
45 3,7,11,15-tetramethyl-2- Ethanolic extract Fruit Other Suryanti et al., 2017
hexadecen-1-ol
46 (3β, 20R)-cholest-5-en-3-ol Ethanolic extract Fruit Other Suryanti et al., 2017
47 9,12,15-octadecatrienoic acid Ethanolic extract Fruit Other Suryanti et al., 2017
methyl ester
48 Citronellyl tiglate Ethanolic extract Fruit Other Suryanti et al., 2017
49 Ascorbic acid Ethanolic extract Fruit Other Nagarajaiah and Prakash, 2014
50 Carotene Ethanolic extract Fruit Other Nagarajaiah and Prakash, 2014
FIGURE 2 | Anthraquinone.
Volatile Components
Total 25 volatile components from flower were isolated using
solid-phase microextraction (SPME) coupled with capillary gas
chromatography/mass spectrometry (GC–MS) (Figure 5). Out
of 25 compounds, 16 volatiles were positively identified and
9 were tentatively identified as 3-methyl-1-butanol (19); 4,5-
dimethyl-1-hexene (20); α-thujene (21); α-pinene (22); sabinene
(23); β-pinene (24); β-myrcene (25); D,L-limonene (26); 1,8-
cineole (27); β-ocimene (Z) (28); β-ocimene (E) (29); β-
terpinene (30); γ-terpinene (31); methyl, methyl ethyl substituted
benzene (32); trans-linalool oxide (33); trans-dihydrocarvone
(34); linalool (35); cis-sabinene hydrate (36); α-thujone (37);
2-methyl-6-methylene-1,7-octadien-3-one (38); 3,4-dimethyl-
2,4,6-octatriene (39); epoxylinelol (40); α-terpineol (41); 1H-
FIGURE 4 | Saponin triterpene.
indole (42); neryl acetate (43) (Fernando and Grun, 2001).
Other Phytoconstituents
on normal and reversed phase to obtain designated Six compounds were isolated and analyzed from ethanolic fruit
Acutosides A to G. The triterpene saponins isolated were extract using GC-MS named as: 2,3-dihydro,3,5-dihydroxy-
named as: oleanolic acid 3-O-β-D-glucopyranosyl-(1→2)- 6-methyl-(4H)-pyran-4-one (44); 3,7,11,15-tetramethyl-2-
β-D-glucopyranoside (Acutoside-A) (12), 28-O-[O-β-D- hexadecen-1-ol (45); (3β, 20R)-cholest-5-en-3-ol (46);
xylopyranosyl-(1→4)-O-α-L-rhamnopyranosyl-(1→2)-α-L-ara- n-hexadecanoic acid (08); 9,12,15-octadecatrienoic acid methyl
binopyranosyl] ester (Acutoside-B) (13), 28-O-[O-β-D- ester (47) and citronellyl tiglate (48) (Figure 6) (Suryanti et al.,
xylopyranosyl-(1→3)-O-β-D-xylopyranosyl-(1→4)-O-α-L-rha- 2017).
Hepatoprotective Fruit Ethanolic (150 mg/kg, p.o.) and Albino rat Carbon tetrachloride induced SGPT, SGOT, serum alkaline phosphatase Ibrahim et al., 2014
activity petroleum ether (150 mg/kg, p.o.) liver necrosis (ALP), serum bilirubin, serum cholesterol,
Shendge and Belemkar
7
extract
Antidiabetic Fruit Ethanolic extract (95%); 200 mg/kg i.p. Long Evans Alloxan monohydrate induced Extract reduced glucose level by 51.10%; Sharmin et al.,
activity female rat reduced glycogen content of diabetic rat 2013
was attenuated by treatment with extract
Fruit Methanolic extract; 50, 100, 200, and Swiss albino Single dose of glucose (2 g/kg Glucose levels decreased in dose Juma et al., 2013
400 mg/kg p.o. mice of body weight) dependant manner
Fruit Lyophilized ethanolic extract (50%); 200 Diabetic Wistar Streptozotocin induced Blood glucose level was significantly Mohan Raj et al.,
and 400 mg/kg p.o. rat reduced in dose dependent manner. 2012
Biochemical estimation of serum indicated
decreased levels of SGPT, SGOT and ALP
Fruit Aqueous and methanolic extract; 200 Swiss albino Streptozotocin induced Methanolic extract of Luffa acutangula fruit Pimple et al., 2011
and 400 mg/kg p.o. mice decreased levels of fasting serum glucose,
glycosylated Hb, ALT, and AST while
increased level of liver glycogen which
contribute to attenuate hyperglycemic
condition in mice
Fruit Ether, chloroform, ethanol, and Wister rats Alloxan induced Chloroform and alcoholic extracts of fruits Patil et al., 2010
aqueous extracts; 200 mg/kg p.o. of Luffa acutangula shown significant
(p < 0.01) blood glucose reduction
Leaves Methanol extract Swiss Webster Glucose solution at the Significant glucose lowering activity in oral Quanico et al.,
mice concentration of 0.010 ml/g glucose tolerance test 2008
Antihyperlipidemic Fruit Hydro-alcoholic extract Wistar rat Alloxan induced Significant reduction in glucose Singh et al., 2014
activity
(Continued)
Fruit Ethanolic extract (95%) Long Evans female rat Alloxan induced Reduced levels of total Sharmin et al.,
Shendge and Belemkar
8
Analgesic and Leaves Ethyl acetate and ethanol − Carrageenan induced Ethanolic extract showed Iyyamperumal
anti- extracts; 250 and 500 mg/kg hind paw edema and significant activity then ethyl et al., 2013
inflammatory cotton pellet granuloma acetate extract.
activity models
Seed Ethanolic extract; 100, 200, Albino rat Carrageenan induced The ethanolic extract showed Gill et al., 2011
and 300 mg/kg, oral paw edema; tail flick significant anti-inflammatory
and tail immersion activity at the dose of
method 300 mg/kg while analgesic
activity at the dose of
400 mg/kg
Antibacterial Leaves Silver nanoparticles prepared Escherichia coli, Klebsiella − The Minimum Inhibitory Moideen and
activity from aqueous extract pneumonia, Proteus vulgaris, Concentration (MIC) values Prabha, 2014
Pseudomonas aeruginosa, showed that silver nanoparticle
Salmonella paratyphi and of leaves extract was more
Staphylococcus aureus effective against Gram-positive
bacteria at lower concentration
then Gram-negative bacteria
Aerial parts Methanolic extract; 10, 25, and Earthworms − The dose of 50 mg/ml exhibited Rahman et al.,
50 mg/ml good anthelmintic activity with 2014
paralysis time nearly about
24 min and death time about
45 min
(Continued)
Kalasakar and
Chavan, 2013
Surana, 2014
and antiulcer activity. Some of these activities are discussed
Jadhav and
Reference
below.
Hepatoprotective Activity
antibacterial and antifungal activity then Various studies have reported therapeutic potential of Luffa
Behavioral changes,
direct bilirubin level while ALT, AST, and ALP levels were
−
2017).
Furthermore, Ulaganathan et al. (2010) screened
hepatoprotective activity of ethanolic extract of the leaves
Ethanolic extract; 5 and
Ethanolic extract; 100
n-hexane, chloroform
Methanolic and
10 mg/kg, p.o.
2010).
Dried fruit pulp
Fruit pericarp
extract
Fruit
extensively studied.
Antidiabetic Activity
Activity
activity
activity
performed to prove antidiabetic effect of the plant. Hypoglycemic each plant were administered orally and compared with standard
activity of ethanolic extract (95%) of Cucumis sativus, Lagenaria glibenclamide (10 mg/kg b.w.). The results of the acute study
siceraria, and Luffa acutangula fruit was evaluated in Long Evans showed significant blood glucose reduction from chloroform and
female rat against alloxan monohydrate. After 12 h, all the alcoholic fruit extract (Patil et al., 2010).
extracts (200 mg/kg i.p.) reduced fasting blood glucose level by Quanico et al. (2008) compared the hypoglycemic activity of
67.38, 65.39, and 51.10%, respectively. Reduced glycogen content methanol extract of Bixa orellana, Kyllinga monocephala, and
(75.32%) of the diabetic rat was attenuated by treatment with Luffa acutangula leaves in an OGTT in Swiss Webster mice.
Luffa acutangula (149.35%) ethanolic extract (Sharmin et al., Luffa acutangula extract showed significant glucose lowering
2013). activity when administered after 15 min of glucose load in the
In another study, dose dependant glucose-lowering effect of rat (Quanico et al., 2008).
methanolic fruit extract was observed in a Swiss albino mice In 2014, Singh et al. (2014) studied hydro-alcoholic extract of
(Juma et al., 2013). Luffa acutangula and Madhuca longifolia against alloxan-
Furthermore, Mohan Raj et al. (2012) examined the induced diabetic Wistar rat and observed a significant
antidiabetic effect of the lyophilized ethanolic fruit extract reduction in glucose level in the diabetic rat (Singh et al.,
(50%) against streptozotocin-induced diabetic Wistar rats. Two 2014).
different doses, i.e., 200 and 400 mg/kg were administered orally The results obtained under antidiabetic activity supports the
for 21 days and different biochemical parameters were evaluated. traditional use of Luffa acutangula as an antidiabetic agent.
Blood glucose level was significantly reduced in a dose-dependent Although it possess antidiabetic action, the effect in human is
manner along with decreased serum levels of SGPT, SGOT, and still unsatisfactory as in human diabetes treatment and should be
ALP were observed. No significant changes were observed in studied extensively.
body weight and food intake of the animal at the end of the study
(Mohan Raj et al., 2012). Antihyperlipidemic Activity
In another study, Pimple et al. (2011) investigated the Sharmin et al. (2013) compared the lipid-lowering effect of
hypoglycemic effect of an aqueous and methanolic fruit extract ethanolic extract (95%) of Cucumis sativus, Lagenaria siceraria,
against streptozotocin-induced diabetes in Swiss albino mice. and Luffa acutangula fruit against alloxan monohydrate in Long
After 21 days, decreased levels of fasting serum glucose, Evans female rats. Extract significantly reduced total cholesterol
glycosylated Hb, ALT, and AST along with improved liver (TC), TG, and low-density lipoprotein (LDL) levels by 38.38,
glycogen levels were observed which thought to be contributed to 79.64, and 85.66%, respectively, in the serum of rat (Sharmin
attenuate hyperglycemic condition in mice (Pimple et al., 2011). et al., 2013).
Patil et al. (2010) compared the antidiabetic potential of leaves In another study, Pimple et al. (2011) established
of Grewia asiatica, bark of Bombax ceiba, and fruits of Luffa antihyperlipidemic activity of an aqueous and methanolic
acutangula against alloxan-induced diabetic Wistar rats. Ether, extract of fruit (200 and 400 mg/kg) in streptozotocin-induced
chloroform, ethanol, and aqueous extracts (200 mg/kg b.w.) of diabetic mice. Oral administration of extract for 21 days,
significantly (P < 0.05) increased levels of high-density extract of leaves exert significant antimicrobial activity against
lipoprotein and reduced serum TC, TGs, low-density lipoprotein, Gram-positive bacteria than Gram-negative bacteria (Moideen
very low-density lipoprotein (Pimple et al., 2011). Only few and Prabha, 2014).
in vivo studies are available for antihyperlipidemic effect of Luffa In vitro antimicrobial potential of methanolic and aqueous
acutangula. Moreover, further preclinical and clinical studies extracts of fruit, seed, leaves, and root was examined by Jadhav
should be performed to check its profound effect on blood lipid and Chavan (2013) using well diffusion assay. The maximum
levels. zone of inhibition was shown by methanolic extract with few
exceptions. The methanolic extract of all parts showed potent
Anticancer Activity inhibitory action against E. coli and Staphylococcus aureus while
Anti-cancer potential of a methanolic and aqueous extract of that of fruit and leaves showed significant inhibition against
fruit was studied in Dalton’s Lymphoma Ascites (DLA) cell Klebsiella pneumonia. Also, inhibition of Fusarium sp. was
induced solid tumor model. In the study, Swiss albino mice more in methanolic extracts of fruit and root when compared
received two doses (200 and 400 mg/kg, oral) of each extract with other parts. Both extracts of leaves were effective against
along with DLA cells. Development of solid tumor in mice Aspergillus niger. The overall result of the study indicated that
was significantly diminished on treatment with both extracts antimicrobial activity of different parts was solvent dependent
(Dashora and Chauhan, 2015). due to phyto-constituents present in it (Jadhav and Chavan,
Furthermore, growth inhibitory effect of ethanolic extract of 2013).
leaf was investigated on human lung cancer cell line (NCI-H460). In another study, potent antimicrobial and antifungal activity
The IC50 value was found to be at 20 µg/ml in MTT assay was exhibited by fruit extract when compared with leaf extract.
while cell lines showed high DCF fluorescence and significantly The area of inhibition was higher in E. coli than in Staphylococcus
increased mitochondrial depolarization indicating anticancer aureus and Pseudomonas aeruginosa species (Dandge et al.,
activity of the extract (Vanajothi et al., 2012). However, not 2012).
sufficient studies were undertaken to prove anticancer activity of Chloroform and aqueous extracts of the fruit were screened
the plant, due to which it is quite early to come to any conclusion. for their antimicrobial and antifungal potential. Antimicrobial
In vitro and in vivo anticancer studies are recommended to prove activity was evaluated against Gram-positive bacteria
anticancer efficacy of plant. (Streptococcus aureus, Bacillus subtilis) and Gram-negative
bacteria (Pseudomonas aeruginosa, Escherichia coli) while
Analgesic and Anti-inflammatory Activity antifungal activity was evaluated against Candida albicans,
Anti-inflammatory effect of ethyl acetate and ethanol extracts Aspergillus niger, Aspergillus fumigates. The chloroform extract
of dried leaves was compared by Iyyamperumal et al. (2013) exhibited more potent activity against Gram-negative bacteria
using carrageenan-induced hind paw edema and cotton pellet and antifungal activity in MIC study (Torvi and Hunashal, 2012).
granuloma models. In acute carrageenan induced model, Furthermore, antibacterial activity of n-hexane, chloroform
ethanolic extract showed 67.6% and 72.5% edema inhibition, and ethyl acetate extracts of leaves were investigated by Bulbul
while ethyl acetate showed 62.5% and 65% inhibition at the et al. (2011) using disk diffusion method. n-Hexane extract
doses of 250 and 500 mg/kg, respectively. Ethanolic extract exhibited most potent inhibitory activity followed by chloroform
showed 43.5% and 56.9% edema inhibition while ethyl acetate extract whereas ethyl acetate extract showed little or no activity
showed 36.5% and 52% inhibition at the doses of 250 and (Bulbul et al., 2011).
500 mg/kg, respectively, in chronic cotton pellet granuloma The above data suggested that plant possess good antibacterial
model (Iyyamperumal et al., 2013). activity which supports its traditional use, but further research
Gill et al. (2011) investigated analgesic and anti-inflammatory is needed to isolate bioactive compounds and understand their
activity of ethanolic seed extract in the albino rats. antibacterial mechanism.
Anti-inflammatory activity (100, 200, and 300 mg/kg, oral)
was evaluated by carrageenan-induced paw edema and analgesic Immunomodulatory Activity
activity (200 and 400 mg/kg, oral) by tail flick and tail immersion Ethanolic extract (100 and 200 mg/kg, p.o.) of fruit pericarp
methods. Significant anti-inflammatory activity at the dose of were investigated for immunomodulatory activity in Swiss
300 mg/kg while analgesic activity at the dose of 400 mg/kg albino mice. The evaluation of phagocytic index revealed that
was shown by seed extract (Gill et al., 2011). Taken together administration of ethanolic extract (200 mg/kg) in Indian ink
these reports support the traditional use of Luffa acutangula intoxicated mice led to increase in phagocytosis to 0.028 ± 0.002
as pain relieving agent but the results are till unconvincing (P < 0.01). Also the % neutrophil adhesion in mice (200 mg/kg)
as humans are not involved in those studies. Hence, plant was increased to 24.63 ± 0.87% which was more than standard
should be studied extensively as analgesic and anti-inflammatory drug Levamisol (23.58 ± 0.46%) (Kalasakar and Surana, 2014).
agent. Further investigations are needed to provide evidence for its
immunomodulatory activity.
Antibacterial Activity
Recently several studies have been performed to highlight the CNS Depressant Activity
ability of various extracts of Luffa acutangula to prevent growth of Misar et al. (2004) examined CNS depressant activity of
microbial strains. Silver nano-particles prepared from an aqueous ethanolic fruit extract (5 and 10 mg/kg, p.o.) in Swiss mice.
The dose of the extract was safe up to 50 mg/kg treatment compared to the control group. The biochemical parameters such
without any morbidity. CNS depressant activity was evaluated as SGOT, SGPT, cholesterol, creatinine, urea, uric acid, protein,
using behavioral changes, exploratory activity and barbiturates glucose and serum ALP also remained unchanged at the end of
sleeping time animal models. The result of the study showed the study (Arunachalam et al., 2012).
that CNS depressant activity of extract is dose dependant Lyophilized ethanolic extract (50%) of fruit was investigated
(Misar et al., 2004). More in vitro and in vivo studies for its safety by Mohan Raj et al. (2012) using OECD-423
should be performed to confirm the CNS depressant action of guideline. The lyophilized formulation was found to be safe up
plant. to dose of 2,000 mg/kg without any mortality (Mohan Raj et al.,
2012).
Antiulcer Activity In a study performed by Pimple et al. (2012), methanolic and
Gastroprotective effect of dried fruit pulp extract (methanolic and aqueous extracts were safe in Swiss albino mice up to the dose
aqueous) was investigated in NIDDM rat. Diabetes was induced of 2,000 mg/kg p.o. No autonomic or behavioral changes were
by streptozotocin (65 mg/kg i.p.) along with nicotinamide detected during first 24 h. At the end of study no mortality was
(125 mg/kg, i.p.) and ulcer in the diabetic rat was induced reported in animals even after 14 days of observation (Pimple
by aspirin (200 mg/kg, p.o.). Increased cellular SOD and et al., 2012).
catalase level while restored mucosal glycoprotein levels were The cytotoxicity of n-hexane, chloroform, and ethyl acetate
observed in gastric mucosa of rat treated with methanolic extract of leaves were studied by Bulbul et al. (2011) using
extract. The aqueous extract was less effective than methanolic brine shrimp lethality bioassay with n-hexane extract of leaves
extract in altering delayed healing of gastric ulcer in diabetic showing significant LC50 value (20.40 µg/ml) when compared
rats. In addition, methanolic extract exhibited dose-dependent with chloroform (21.25 µg/ml) and ethyl acetate (23.09 µg/ml)
glucose lowering and mucosal defensive action (Pimple et al., (Bulbul et al., 2011).
2012). Furthermore, abortifacient effect of fruit tea was evaluated
by Fernandes et al. (2010) in pregnant Wistar female rats. On
15th gestational day, pregnant female rats were treated with Luffa
TOXICITY STUDIES acutangula fruit tea (10 ml/kg, p.o.) and the cesarean was done
on the 21st day. No significant changes in body weight and no
The LD50 value of an aqueous and methanolic fruit extract signs of maternal toxicity in the female rat were observed, but
was obtained at 4 g/kg body weight (Dashora and Chauhan, reduced fetus weight was reported. Since, weight is an important
2015). No mortality was observed for both extract during parameter in the fetus development, therefore, Luffa acutangula
study period. The result indicated LD50 value for ethanolic considered as fetoxic in nature (Fernandes et al., 2010).
extract at 500 mg/kg, while that of petroleum ether extract In another study, acute toxicity of hydro-alcoholic (70%)
at 350 mg/kg (Ibrahim et al., 2014). In another study, the extract of fruit was investigated using OECD guideline no. 425
cytotoxic activity of ethanolic and pet ether extracts of aerial in mice. Animals were administered with different doses (500,
parts was evaluated in brine shrimp (Artemia salina) lethality 750, 1,000, and 2,000 mg/kg) of hydro-alcoholic (70%) extract
model. Different concentrations of both extracts ranging from and observed for 72 h for clinical signs, symptoms, and mortality.
1 to 500 µg/kg were used for the study and the LC50 value of Result depicted that no mortality was observed up to 10 g/kg dose
ethanolic and pet ether extract was found to be at 32.8 ± 1.62 level, even after 72 h (Jadhav et al., 2010).
and 175.65 ± 10.80 µg/kg, respectively. The cytotoxic activity Ulaganathan et al. (2010) evaluated ethanolic extract of leaves
of Luffa acutangula was attributed to the presence of tannin in for acute toxicity study in Wistar rats. The extract was dissolved
the extract (Rahman et al., 2014). Furthermore, ethanolic and in Tween 80 solution and administered at the concentrations of
ethyl acetate extract of leaves were investigated for acute oral 50, 100, 250, 500, 1,000, and >2,000 mg/kg by the oral route and
toxicity as per OECD guideline no. 423. Both extracts were the animals were observed for 72 h for any mortality or toxic
found to be safe at dose of 2,000 mg/kg (Iyyamperumal et al., symptoms. The result indicated that ethanolic extract of leaves
2013). did not show any toxic symptoms or mortality up to dose of
Arunachalam et al. (2012) examined for the safety of an 2,000 mg/kg (Ulaganathan et al., 2010).
ethanolic extract of whole plant using acute and chronic toxicity Furthermore, ether, chloroform, ethanol, and aqueous fruit
studies. The acute toxicity study was performed according to extracts were screened for safety using OECD guideline 423
OCED guideline no. 423 where defined doses (2,000, 1,000, 500, and the study results exhibited 50% mortality with oral dose of
50, 5 mg/kg) were administered to Wistar rats and parameters like 2,000 mg/kg (Patil et al., 2010).
change in body weight, changes in skin and fur, motor pattern
and behavior pattern of animals were observed for 14 days. No
toxicity and deaths were observed at the dose of 2,000 mg/kg CONCLUSION AND FUTURE
level, therefore 1/20th (100 mg/kg), 1/10th (200 mg/kg) and 1/5th PERSPECTIVES
(400 mg/kg) doses were selected for chronic toxicity study for 6
weeks. The hematological parameters (Hb concentration, clotting The current review documented existing information on
time, neutrophils, eosinophils, lymphocytes, monocytes, RBC, the ethnobotanical uses, phytochemistry, pharmacology, and
and WBC) evaluation of treated group showed no changes when toxicology of Luffa acutangula. The amount of data gathered
from different studies revealed that the plant is rich in many From present compilation, it is observed that researchers
nutrients and vast biological active constituents. need to establish the relationship between structure and function
Various modern pharmacological studies have been conducted along with clinical studies on the efficacy of plants chemical
to appraise the traditional uses of Luffa acutangula and research components. Furthermore, validating the link between the
data obtained supported the traditional claims. Plant possess traditional uses and therapeutic effects should be carried out
the potential multiple biological and therapeutic activities in further, and the toxicity of this plant also should be studied
the management of hepatoprotective, antidiabetic, antiulcer, systematically. Well designed and strictly controlled clinical trials
anticancer, CNS depressant, fungistatic, analgesic, antimicrobial, are also needed to validate safety and efficacy of dose before its
immunomodulatory, etc., which can be deciphered by the recommendations for human consumption.
presence of various constituents like RIPs, flavonoids, fatty acid,
triterpenoids, and volatile components in it.
However, extensive investigations are required to formulate AUTHOR CONTRIBUTIONS
co-relations between the biological activities and chemical nature
of the bioactive compounds deracinated from herb. Toxicity SB and PS conceived the review. PS drafted the manuscript. SB
evaluation of plants is very important to understand their safety was involved in the editing process. Both the authors read and
profile. To this end, no human studies have been performed approved the final version of the manuscript.
to evaluate toxic effects of Luffa acutangula. The acute toxicity
studies of the plant in preclinical models revealed fetotoxic nature
as it reduces the weight of the fetus during pregnancy. However, ACKNOWLEDGMENTS
further clinical evaluation must be performed to perceive the
detailed effect of plant on human fetus. No other toxic effects We acknowledge School of Pharmacy and Technology
were observed in preclinical studies indicating the safe use of Management, SVKM’s NMIMS, Shirpur Campus, Maharashtra,
plant. India for providing support and assistance for this review article.
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activity of Luffa acutangula fruit extracts in streptozotocin induced NIDDM conducted in the absence of any commercial or financial relationships that could
rats. Asian J. Pharm. Clin. Res. 4, 156–163. be construed as a potential conflict of interest.
Pimple, B., Kadam, P., and Patil, M. (2012). Protective effect of Luffa acutangula
extracts on gastric ulceration in NIDDM rats: role of gastric mucosal glycol- Copyright © 2018 Shendge and Belemkar. This is an open-access article distributed
proteins and antioxidants. Asian Pac. J. Trop. Med. 5, 610–615. doi: 10.1016/ under the terms of the Creative Commons Attribution License (CC BY). The use,
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