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Anticancer Evaluation of Adiantum venustum Don

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Cancer is a malignant disease that is characterized by rapid and uncontrolled formation of abnormal cells which may mass together to form a growth or tumor, or proliferate throughout the body. Next to heart disease, cancer is a major killer of mankind. This study aims at a preliminary phytochemical screening and anticancer evaluation of Adiantum venustum Don against Ehrlich Ascites Carcinoma in animal model. The findings indicate that ethanolic extract of A. venustum Don possesses significant anticancer activity and also reduces elevated level of lipid peroxidation due to the presence of terpenoids and flavonoids. Thus, ethanolic extract of A. venustum Don could have vast therapeutic application against cancer.
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48 Journal of Young Pharmacists Vol 3 / No 1
observed from Ayurvedic literature and ethanobotanical
studies that the plant Adiantum venustum Don is very useful
in treating tumor, prevention of hair from falling, and as
a diuretic, but no scientic investigation has been carried
out.
[2-4]
Therefore, it was thought worthwhile to carry out
preliminary phytochemical screening and screening of A.
venustum Don for anticancer activity against Ehrlich Ascites
Carcinoma in animal model.
MATERIALS AND METHODS
Plant source
The leaves and stem of A. venustum Don [Figure 1] were
collected from Kolli Hills, Namakkal District, Tamilnadu,
India, and were authenticated. Reference number of the
authentication report is BSI/SC/5/23/05.06/Tech/603.
Extraction procedure
The leaves and stem of A. venustum were dried under shade,
mixed together, and then made in to a coarse powder in
INTRODUCTION
The chemotherapy of neoplastic disease has become
increasingly important in recent years. The relatively
high toxicity of most anticancer drugs has fostered the
development of supplementary drugs that may alleviate
this toxic effect or stimulate the regrowth of depleted
normal cells. Plants have a long history of use in the
treatment of cancer, and they have played a vital role as a
source of effective anticancer agent. It is signicant that
over 60% of currently used anticancer agents are derived,
in one way or another, from natural sources, including
plants, marine organism, and microorganisms.
[1]
It was also
Pharmacology
Anticancer Evaluation of Adiantum venustum Don
Viral D, Shivanand P, Jivani NP
Department of Pharmaceutical Chemistry, Smt. R. B. P. Mahila Pharmacy College, Atkot, India
Address for correspondence: D. Viral; E-mail: viraldev1985@gmail.com
ABSTRACT
Cancer is a malignant disease that is characterized by rapid and uncontrolled formation of abnormal cells which
may mass together to form a growth or tumor, or proliferate throughout the body. Next to heart disease, cancer
is a major killer of mankind. This study aims at a preliminary phytochemical screening and anticancer evaluation
of Adiantum venustum Don against Ehrlich Ascites Carcinoma in animal model. The ndings indicate that
ethanolic extract of A. venustum Don possesses signicant anticancer activity and also reduces elevated level
of lipid peroxidation due to the presence of terpenoids and avonoids. Thus, ethanolic extract of A. venustum
Don could have vast therapeutic application against cancer.
Key words: Adiantum venustum, Cancer, avonoids, lipid peroxidation, terpenoids
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DOI:
10.4103/0975-1483.76419
Journal of Young Pharmacists Vol 3 / No 1 49
a mechanical grinder. The powder was passed through
sieve no. 40 and stored in an airtight container for further
use. The dried powder material (150 g) was defatted with
petroleum ether (60–80°) to remove waxy substances and
chlorophyll. The marc, after defatted with petroleum ether,
was dried and extracted with ethanol (99.9% v/v) in a
Soxhlet extractor for 72 h. The solvent was then distilled
off, and the resulting semisolid mass was dried in a vacuum
evaporator to get a yield of 14% w/w.
[5,6]
Phytochemical identication tests
Various chemical tests were performed for the identication
of phytoconstituents in Pet. ether and ethanolic extract of
the leaves and stem of A. venustum following the standard
procedure.
[7,8]
Anticancer activity
Toxicity evaluation (LD
50
): (Karber’s methods)
[9–11]
Swiss albino mice weighing 20–25 g were used for the study.
Animals were fed a standard pellet and water and maintain
at 24–28 °C temperature, 60–70% relative humidity and
12 h day and night cycle. Animals ascribed as fasted were
deprived of food for 16 h, but had free access to water.
Fifty-four mice including both male and female weighing
20–25 g were selected for the study. Overnight faster mouse
were divided into nine groups including four for PEETR
and four for EETR and one control group each consists
of six mice. Different doses of extract (200, 500, 1000,
and 2000 mg/kg) were administered to nine experimental
groups and control group received vehicle.
The animals observed continuously for their general
behavior, such as motor activity, tremors, convulsions,
straub reaction, Pilo eraction, loss of lighting reex,
sedation, muscle relaxation, hypnosis, analgesia, ptosis,
lacrimation, diarrhea, skin color, and mortality intermittently
for next 24 h.
Animals
Male Swiss albino mice, weighing between 18 and 25 g, were
used for this study. They were maintained under standard
environmental conditions and were fed with standard
pellet diet of water ad libitum. The mice were acclimatized
to laboratory condition for 10 days before commencement
of experiment. All procedure described were reviewed and
approved by the Institutional Animal Ethical Committee of
Smt R. B. P. Mahila Pharmacy College (rbpmpc/09/1025).
Cancer cell line
EAC cells were obtained from Amala Cancer Research
Center, Kerala, India. They were maintained by weekly
intraperitoneal inoculation of 10
6
cells/mouse.
Preparation of extract drug and mode of administration
In the present anticancer study, ethanolic extract of
Adiantum venustum (EEAV), in the dose of 150 and 250
mg/kg, were prepared as suspension by dispersing the
ethanolic extract in a mixture of propylene glycol and sterile
physiological saline containing Tween 20 (1:3) to get the
desired concentration.
[12,13]
Tumor transplantation
Ehrlichs Ascites Carcinoma was maintained by serial
transplantation from tumor-bearing Swiss Albino mice.
Ascetic uid was drawn out from tumor-bearing mice at
the log phase (day 78 of tumor bearing) of the tumor cells.
The tumor cell number was adjusted to 2 × 10
6
tumor cells/
mL. Sample showing more than 90% viability was used for
transplantation. Each animal received 0.2 mL of tumor cell
suspension containing 2 × 10
6
cells/mL intraperitoneally.
[11]
Anticancer evaluation of A. venustum Don
Figure 1: Plant images
50 Journal of Young Pharmacists Vol 3 / No 1
Drug treatment schedule
Male swiss albino mice were divided into ve groups (n
= 8). All the groups were injected with EAC cells (0.2
mL of 2 × 10
6
cells/mouse) intraperitoneally except the
normal group. This was taken as day 0. From the rst
day normal saline (0.9% NaCl), 5 mL/kg of body weight
was administered to group 1 and propylene glycol 5 mL/
kg was administered to group 2 (cancer control) for 14
days intraperitoneally. Similarly ethanolic extract of A.
venstrum don at various doses (150 and 250 mg/kg/mouse/
day) were administered to animals of groups 3 and 4,
respectively. Standard drug vincrystine (0.8 mg/kg/day/
mice) was administered to the group 5. After administration
of last dose followed by 18 h fasting, four mice form
each group were sacriced for the study of anticancer
activity, hematological, and liver biochemical parameters.
The remaining animals in each of the groups were kept to
check the mean survival lime (MST) and percent increase
in life span of the tumor-bearing hosts.
[12–14]
Various
parameters such as body weight of animals, life span of
animals, cytological studies of cell lines, hematological
parameters, RBC, WBC, hemoglobin, differential count,
and biochemical parameters were evaluated in this study.
Anticancer effect of EEAV was assayed by observation of
change with respect to body weight, ascitic tumor volume,
packed cell volume, viable and nonviable tumor cell count,
mean survived time (MST), and percentage increase in life
span (% ILS).
[12]
Tumor cell volume and packed cell volume
The mice were dissected to collect ascitic fluid from
peritoneal cavity and centrifuged to determine packed
cell volume at 1000 rpm for 5 min.
[12]
The transplantable
murrain tumor was carefully collected to measure the
tumor volume.
Viable and nonviable cell count
Viable and nonviable cell counting of the ascetic cell was
done by staining with tryphan blue (0.4% in normal saline),
dye exclusion test, and count was determined in a Neubauer
counting chamber. The cells that did not take up the dye
were viable and those that took the stain were not viable.
[14]
Mean survival time and percent increased in life span
The effect of EEAV on tumor growth was observed by
MST and % ILS. MST of each group continuing four mice
were monitored by recording the mortality daily for 6 weeks
and % ILS was calculated by using following equation.
[15,16]
MST = (Day of rst death + Day of last death)/2.
% ILS =
{
MST of treated group
MST of control group
}
1 × 100.
Effect of EEAV on hematological parameters
Blood was collected from each mice by intracardial
puncture with blood anticoagulant (heparin), white blood
cells (WBCs), red blood cells (RBCs), hemoglobin, and
differential count were determined
[
17]
in group comprise of
i. Tumor-bearing mice (control),
ii. tumor-bearing mice treated with EEAV (100 mg/kg/
mice/day),
iii. tumor-bearing mice treated with EEAV (200 mg/kg/
mice/day), and
iv. normal group.
Biochemical assay
After the collection of blood samples, the mice were killed,
and their liver was excised. The isolated liver was rinsed in
ice-cold normal saline followed by cold phosphate buffer
having pH 7.4, blotted dry, and weighed. A 10% w/v
homogenate of liver was prepared in ice-cold phosphate
buffer (pH 7.4), and a portion were utilized for estimation
of lipid. Other portion of the same, after precipitation of
proteins with trichloro acetic acid (TCA), was used for the
estimation of glutathione and the remaining homogenate
was centrifuged at 1500 rpm at 4 °C for 15 min. The
supernatant, thus obtained, was used for the estimation
of superoxide dismutase, catalase, and protein content.
[18]
Statistical analysis
The experimental result were expressed as mean ± SEM.
Data were assessed by the Student t-test, P < 0.05 was
considered as statistically signicant.
RESULTS
Phytochemical screenings suggest that ethanolic extract
of plant contain terpenoid, phytosterols, avanoid, and
saponin which are believed to be the main potential for
anticancer activity [Table 1].
[19,20]
Anticancer activity
Toxicity evaluation (LD
50
)
In acute toxicity study, the given extract of A. venustum
Table 1: Result of phytoconstituent identication tests
of ethanol extract of
Adiantum venustum
Don
Phytoconstituent Phytosterol Flavonoids Triterpenoids Saponin
Ethanol extract + + + +
+ represents present, – represents absent
Viral, et al. J Young Pharm. 2011;3(1): 48-54
Journal of Young Pharmacists Vol 3 / No 1 51
Anticancer evaluation of A. venustum Don
Table 2: Effect of ethanol extract of
Adiantum
venustum
on survival time on EAC-bearing mice
Experimental groups Mean survival time
(MST), days
% Increase in life
span
Normal control
GRP 1
EAC control
GRP 2
22 ± 0.25
150 mg/kg
GRP 3
24 ± 0.33 9.09
250 mg/kg
GRP 4
29 ± 0.49 31.81
STD
GRP 5
31 ± 0.55 40.90
Values are mean ± SEM. Number of mice in each group (n = 8), P < 0.001.
Experimental group was compared with EAC control
Table 3: Effect of ethanol extract of
A. venustum
on tumor volume, packed cell volume, viable, and nonviable tumor
cell count of EAC-bearing mice
Parameters Normal
GRP 1
EAC Control
GRP 2
150 mg/kg
GRP 3
250 mg/kg
GRP 4
Standard
GRP 5
Body weight 26.11 ± 0.12 26.11 ± 0.12 24.34 ± 0.16 23.28 ± 0.13 23.9 ± 0.02
Tumor volume (mL) 0 5.82 ± 0.042 4.22 ± 0.051 3.42 ± 0.082 2.42 ± 0.13
Packed cell volume (mL) 0 2.12 ± 0.104 1.75 ± 0.043 1.05 ± 0.092 1.15 ± 0.03
Viable tumor cell count, % 10
7
cells /mL 0 11.25 ± 0.098 7.78 ± 0.18 4.85 ± 0.23 4.90 ± 0.015
Nonviable tumor cell count, ×10
7
cells/mL 0 0.5 ± 0.017 0.92 ± 0.023 1.47 ± 0.021 1.23 ± 0.81
Values are mean ± SEM. Number of mice in each group (n = 8), P < 0.01. Experimental groups was compared to EAC control weight of normal mice = 20 ± 0.15
Figure 2: Graphical representation of Mean survival time and %
increase in life span of mice
Effect of EEAV on Mean Survival Time and % Increase in Life Span
-10
0
10
20
30
40
50
1 2 3 4 5
Experimental Groups
Mean Survival Time and
% Increse in Life Span
Mean survival time
% Increase in life span
Experimental groups
1 Control (Saline)
2 Control (EAC)
3 EEAV 100 mg/kg
4 EEAV 200 mg/kg
5 Standard
(vincristine)
Figure 3: Graphical representation of effect of EEAV on tumor volume
and packed cell volume of mice, viable cell count and non viable cell
count
Effect of extract on tumor volume and packed cell
volume of mice, viable cell count and non viable cell
count
0
5
10
15
20
25
30
1 2 3 4 5
Experimental Group
Parameters
Body weight
Tumour volume (ml)
Packed cell volume (ml)
Viable tumour cell count
% 107 cells /ml
Non viable tumour cell
count X 107 cells / ml
did not show any mortality up to the dose of 2000 mg/
kg. It is safe dose that was determined by organization
for economic cooperation and development (OECD)
guidelines. The extract shows sedation, hypnosis, and mild
muscle relaxant property. Administration of EEAV reduces
the tumor volume, packed cell volume, and viable tumor
cell count in a dose-dependant manner when compared
to EAC control mice. In EAC control mice, the median
survival time was 22 ± 0.25 days. Whereas, it was signicant
increased median survival time (24 ± 0.33, 29 ± 0.49)
with different doses (150 and 250 mg/kg) of EEAV and
standard drug, respectively. The mean survival time (MST)
and the effect of EEAV (150 and 250 mg/kg) at different
doses on tumor volume, viable, and nonviable cell count,
were shown in Tables 2 and 3 and graphical representation
are shown in Figures 2 and 3.
Effect EEAV on hematological parameter
EEAV at the dose of 100 and 200 mg/kg, the hemoglobin
content in EAC-bearing mice were increased to 10.6 ±
0.057 and 11.45 ± 0.057. The hemoglobin content in the
EAC control mice (9.8 ± 0.02) was signicantly decreased
as compared to normal mice (12.85 ± 0.25). The total WBC
count was signicantly higher in the EAC-treated mice
when compared to normal mice. Whereas EEAV-treated
mice signicantly reduced the WBC count as compared
to that of control mice. Signicant changes observed on
differential count when extract-treated mice compared to
EAC control mice [Table 4] [Figure 4].
52 Journal of Young Pharmacists Vol 3 / No 1
Biochemical assay
Biochemical assay indicated that EEAV significantly
reduced the elevated levels of lipid peroxidation, and
thereby it may act as an antitumor agent. The level of
lipid peroxidation, catalase, and protein content were
summarized in Table 5 and graphical representation is
shown in Figure 5.
DISCUSSION
This study was carried out to evaluate the antitumor effect
and antioxidant status of plant extract in EAC-bearing
mice. The plant extract-treated animals at the doses of 150
and 250 mg/kg signicantly inhibited the tumor volume,
packed cell volume, tumor cell count, and brought back
the hematological parameters to more or less normal levels.
The extract also restored the hepatic lipid peroxidation
and antioxidant enzymes such as CAT in tumor-bearing
mice to near normal levels. In short-term toxicity studies,
the administration of plant extract at the dose of 150
and 250 mg/kg for 14 days did not exhibit any adverse
effect. In EAC-bearing mice, a regular rapid increase in
ascites tumor volume was noted. Ascites uid is the direct
nutritional source for tumor cells and a rapid increase in
ascitic uid with tumor growth would be a means to meet
the nutritional requirement of tumor cells.
[21]
Treatment
Table 4: Effect of ethanol extract of
Adiantum venustum
on hematological parameters of EAC-treated mice
Parameter Normal
GRP 1
EAC control
GRP 2
150 mg/kg
GRP 3
250 mg/kg
GRP 4
Standard
GRP 5
Hemoglobin (g) 12.85 ± 0.25 9.8 ± 0.02 10.6 ± 0.057 11.45 ± 0.18* 11.7 ± 0.045*
Total RBC million/mmcu 6.65 ± 0.18 3.8 ± 0.035 4.75 ± 0.032 5.42 ± 0.22* 5.8 ± 0.054
Total WBC million/mmcu 7.8 ± 0.045 20.07 ± 0.068* 11.92 ± 0.042 8.85 ± 0.059 9.12 ± 0.055
Lymphocyte 77.75 ± 0.19 33.37 ± 0.56* 52.7 ± 0.50* 60.72 ± 0.36* 59.12 ± 0.30
Monocyte 1.7 ± 0.035 0.82 ± 0.024 1.15 ± 0.014* 1.2 ± 0.045 1.32 ± 0.024
Granulocyte 29.97 ± 0.46 52.6 ± 0.37* 40.87 ± 0.2 31.72 ± 0.63* 41.65 ± 0.29
Values are mean ± SEM, (n = 8). EAC control group compared to normal group. Experimental group compared to EAC control. P < 0.01, *P < 0.05
Table 5: Effect of different doses of ethanolic extract of
Adiantum venustum
on different biochemical parameter in
EAC-bearing mice
Parameter Normal
GRP 1
EAC control
GRP 2
150 mg/kg
GRP 3
250 mg/kg
GRP 4
Standard
GRP 5
Lipid peroxidation n mole MDA/g of tissue
0.92 ± 0.02 1.36 ± 0.09* 1.27 ± 0.04* 1.13 ± 0.02 2.45 ± 0.25
Catalase (units/mg tissues) 2.51 ± 0.72 1.71 ± 0.15* 1.75 ± 0.13 2.34 ± 0.23* 3.56 ± 0.63
Protein content (g/100 mL) 12.66 ± 0.69* 17.25 ± 0.76 16.50 ± 0.70 16.10 ± 0.55 20.24 ± 0.47
Values are mean ± SEM, (n = 8). EAC control group compared to normal group. Experimental group compared to EAC control. P < 0.05, *P < 0.05
Figure 5: Graphical representation of effect of EEAV on different
biochemical parameters
Effect of extract on biochemical parameter
0
5
10
15
20
25
1 2 3 4 5
Experimental Groups
Biochemical Parameters
Lipid peroxidation n mole
MDA/gm of tissue
Catalase (units /mg
tissues)
Protein content
(gm / 100 ml)
Figure 4: Graphical representation of effect of Ethanolic Extract of
A. venstrun don on haematological parameters
Effect of EEAV on Haematologigal Parameters
0
10
20
30
40
50
60
70
80
90
1 2 3 4 5
Experimental Groups
Haematological Parameters
Haemoglobin
Total RBCs
WBCs
Lymphocytes
Monocytes
Granulocytes
Viral, et al. J Young Pharm. 2011;3(1): 48-54
Journal of Young Pharmacists Vol 3 / No 1 53
with plant extract inhibited the tumor volume, tumor
cell count, and increased the percentage of tryphan blue
positive stained dead cells in tumor-bearing mice. The
reliable criteria for judging the value of any anticancer
drug are the rolongation of the life span of animals.
[22]
The plant extract decreased the ascites uid volume, viable
cell count, and increased the percentage of life span. It
may be concluded that plant extract by decreasing the
nutritional uid volume and arresting the tumor growth
increases the life span of EAC-bearing mice. Usually, in
cancer chemotherapy the major problems that are being
encountered are of myelosuppression and anemia.
[23,24]
The
anemia encountered in tumor-bearing mice is mainly due to
reduction in RBC or hemoglobin percentage, and this may
occur either due to iron deciency or due to hemolytic or
myelopathic conditions.
[25,26]
Treatment with plant extract
brought back the hemoglobin content, RBC, and WBC
count more or less to normal levels. This indicates that plant
extract possesses protective action on the hemopoietic
system. Lipid peroxidation, an autocatalytic free-radical
chain propagating reaction, is known to be associated with
pathological conditions of a cell. Malondialdehyde (MDA),
the end product of lipid peroxidation, was reported to
be higher in cancer tissues than in nondiseased organ.
[27]
Excessive production of free radicals resulted in oxidative
stress, which leads to damage of macromolecules, for
example lipid peroxidation in vivo.
[28]
It was also reported
that the presence of tumors in the human body or in
experimental animals is known to affect many functions
of the vital organs, especially in the liver, even when the
site of the tumor does not interfere directly with organ
function.
[29]
Plant extract signicantly reduced the elevated
levels of lipid peroxidation and increased the glutathione
content in EAC-treated mice. The antitumerogenic effect
of plant extract may be due to the antioxidant, and the
free-radical quenching property of the phytoconstituents
of plant extract. Cells are also equipped with enzymatic
antioxidant mechanisms that play an important role in the
elimination of free radicals. SOD, CAT, and glutathione
peroxides are involved in the clearance of superoxide and
hydrogen peroxide (H
2
O
2
). SOD catalyses the diminution
of superoxide into H
2
O
2
, which has to be eliminated by
glutathione peroxidase and/or catalase.
[30]
A small amount
of catalase in tumor cells was reported.
[31]
The inhibition
of SOD and CAT activities as a result of tumor growth
were also reported.
[32]
Similar ndings were observed in this
study with EAC-bearing mice. The administration of plant
extract at different doses signicantly increased CAT levels
in a dose-dependent manner. It was reported that plant-
derived extracts containing antioxidant principles showed
cytotoxicity toward tumor cells
[33]
and antitumor activity
in experimental animals.
[34]
Antitumor activity of these
antioxidants is either through induction of apoptosis
[35]
or by inhibition of neovascularization.
[36]
The implication
of free radicals in tumors is well documented.
[37]
The free-
radical hypothesis supported the fact that the antioxidants
effectively inhibit the tumor, and the observed properties
may be attributed to the antioxidant and antitumor
principles present in the extract. This study demonstrates
that plant extract increased the life span of EAC-tumor-
bearing mice and decreased the lipid peroxidation and
thereby augmented the endogenous antioxidant enzymes in
the liver. The above-mentioned parameters are responsible
for the antitumor and antioxidant activities of A. venstrum
don. Further investigations are in progress in our laboratory
to identify the active principles involved in this anticancer
and antioxidant activity.
CONCLUSION
The EEAV possessed signicant anticancer and antioxidant
activity due to the presence of terpenoids and avonoids.
Further investigation on various biological activities of this
plant with different modes will not only validate the types
of activities claimed by Ayurvedic, Siddha, and traditional
practitioners, but also will bring out innovation in the eld
of therapeutics.
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... show notable anti-cancer properties (Lai et al., 2010). The antithiamin substances in brackens, such as astragalin, isoquercitrin, rutin, caffeic acid, and tannic acid have Lee and Lin, 1988;Silva et al., 1995;Sun et al., 1997;Lee et al., 1999;Lin et al., 2000;Su et al., 2000;Chen et al., 2005b;Gao et al., 2007;Li J et al., 2014;Li S 2014;Elda et al., 2015 35 Woerdenbag et al., 1996;Li et al., 1998Li et al., , 1999Viral et al., 2011 45 Guha et al., 1996 MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Polypodiaceae In vitro assay using platelet activating factor and leukotriene B(4) Liu et al., 1998 been identified as valuable natural constituents because of their antitumour or antioxidant properties (Kweon, 1986;Cai et al., 2004;Katsube et al., 2006). The ferns P. nipponica, Polypodium formosanum, Polypodium vulgare, Polypodium fauriei, Polypodium virginianum, Dryopteris crassirizoma, Adiantum monochlamys, and Oleandra wallichii have been shown to have anti-cancer activity (Konoshima et al., 1996). ...
... Methanol extracts of Pityrogramma calomelanos, D. quercifolia, and D. linearis exhibit antitumour and cytotoxic activity (Sukumaran and Kuttan, 1991;Shin and Lee, 2010;Zakaria et al., 2011;Milan et al., 2013). Extracts of Adiantum venustum also have anti-cancer activity, as demonstrated by Viral et al. (2011). The lycophytes, Selaginella willdenowii (Fig. 3d), Selaginella lepidophyla, Selaginella labordei, Selaginella moellendorffii, Selaginella delicatula, S. tamariscina, and Sellaginella doederleinii (Fig. 3e) were shown to have cytotoxic and antimutagenic effects due to the presence of bioflavonoids (Lee and Lin, 1988;Silva et al., 1995;Sun et al., 1997;Lee et al., 1999;Lin et al., 2000;Su et al., 2000;Chen JJ et al., 2005;Gayathri et al., 2005;Woo et al., 2005;Gao et al., 2007;Shi et al., 2008;Tan et al., 2009), while Pteris semipinnata (Fig. 4c) and P. multifida have cytotoxic effects due to the presence of diterpenes (Woerdenbag et al., 1996;Li et al., 1998Li et al., , 1999. ...
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The aim of this review was to explore the pharmacological activity of early tracheophytes (pteridophytes) as an alternative medicine for treating human ailments. As the first vascular plants, pteridophytes (aka, ferns and fern allies) are an ancient lineage, and human beings have been exploring and using taxa from this lineage for over 2000 years because of their beneficial properties. We have documented the medicinal uses of pteridophytes belonging to thirty different families. The lycophyte Selaginella sp. was shown in earlier studies to have multiple pharmacological activity, such as antioxidant, anti-inflammatory, anti-cancer, antidiabetic, antiviral, antimicrobial, and anti-Alzheimer properties. Among all the pteridophytes examined, taxa from the Pteridaceae, Polypodiaceae, and Adiantaceae exhibited significant medicinal activity. Based on our review, many pteridophytes have properties that could be used in alternative medicine for treatment of various human illnesses. Biotechnological tools can be used to preserve and even improve their bioactive molecules for the preparation of medicines against illness. Even though several studies have reported medicinal uses of ferns, the possible bioactive compounds of several pteridophytes have not been identified. Furthermore, their optimal dosage level and treatment strategies still need to be determined. Finally, the future direction of pteridophyte research is discussed.
... Animals with cancer may live longer if nutritive fluid volume is reduced and tumour growth is stopped. A similar effect was shown in EAC-bearing mice treated with OI extract (20). The plant extract was successful in lowering the ascites fluid volume, increasing the percentage of life span, and decreasing the number of viable cells, all of which support its anticancer capabilities. ...
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Full-text available
Introduction and Aim: Constant efforts are exerted to explore unique bioactive principles from natural sources that possess more effective and specific antineoplastic activities. In the present study, we aimed to evaluate the antitumor activity of stem bark extract of Oroxylum indicum in mice bearing Ehrlich ascites carcinoma (EAC). Materials and Methods: Ninety female Swiss albino mice were categorized into fifteen groups (n=6). The animals were inoculated with 1x106 EAC cells. Tumor control animals received sterile water once daily for 10 consecutive days. Positive control group was injected with Cisplatin (CP) (one dose – 3.5 mg/kg body weight). The treatment groups were administered with O. indicum (OI) stem bark ethanol extract once daily with 50mg/kg, 200mg/kg and 400mg/kg body weight for eleven consecutive days. The blood parameters and serum hepatic enzymes activity was determined. The percentage increase in weight, the median survival time, the increase in median life span was calculated. The cytotoxic effect of CP and OI extract was determined. Results: There was significant reduction in the white blood cells count in OI and CP treatment group compared to increased level in EAC control group. The RBC count and Hemoglobin level which was significantly decreased (p<0.05) in the tumour mice, was enhanced in the drug treatment groups. The EAC control group showed significant increase in tumour cell count (p<0.05) whereas, treatment of EAC tumor bearing mice with OI and CP significantly increased the non-viable tumor cell count (p<0.05). Conclusion: OI stem bark ethanol extract reduced the toxic implications of Ehrlich ascites carcinoma, reverted the haematological and biochemical changes induced by tumour. These results call for additional research on isolating and identifying the responsible bioactive elements in order to clarify the underlying processes of the anticancer impact.
... The plant is also used in combination with other plant species as expectorant, hypothermic, diuretic and in stomach ache (Haq 2012). Viral et al. (2011) carried out preliminary phytochemical screening and anticancer evaluation of A. venustum against Ehrlich Ascites Carcinoma in Swiss albino mice. The ethanolic extract of the plant possesses significant anticancer and antioxidant activity due to the presence of terpenoids and flavonoids. ...
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The knowledge of the use of medicinal plants has been acquired through the centuries by observing the nature and such plants are still valuable for human health care programme. Himalayan maidenhair (Adiantum venustum D.Don; Family: Pteridaceae), popularly known as 'Hansraj' or 'Hanspad', employed as an ingredient in several Ayurvedic and Unani system of medicine. The species possesses immense therapeutic as well as other potential uses and frequently grown as a decorative plant because of its delicate fronds. An overview is conducted on A. venustum with an objective to provide information on the essential aspects for further exploration in human benefits.
... Myelosuppression and anemia are the major problems in cancer chemotherapy. Anemia in tumor-bearing mice may be due to iron deficiency, hemolytic, or myelopathic condition [16]. Treatment with EASL restored the Hb levels, RBC and WBC counts to near normal levels ( Table 2), which indicates that the extract may possess protective effect on hematopoietic system. ...
Article
Objective: The present study aims to evaluate the anticancer potential of ethanolic extract of Alangium salvifolium leaves (EASL) against Ehrlich ascites carcinoma (EAC) in animal model. Methods: The ethanolic extract of A. salvifolium was prepared by continuous method using Soxhlet apparatus. Phytochemical analysis of EASL was conducted. Anticancer activity of the extract was evaluated by EAC model in Swiss albino mice. EASL was administered at the doses of 100 and 200 mg/kg body weight once a day orally for 14 days, after 24 h of tumor inoculation. Results: A. salvifolium leaves extract treatment produced significant decrease in tumor volume and body weight, and increase in total and non-viable cell count, along with elevated life span of EAC-bearing mice. The EASL exhibited potent dose-dependent antitumor activity. Further, the altered hematological parameters such as red blood cells, hemoglobin, and white blood cells levels as well as biochemical parameters such as serum glutamic oxaloacetic transaminase, serum glutamate pyruvate transaminase, alkaline phosphatase, albumin, and total protein levels in EAC mice were significantly (p<0.05) regained following treatment with EASL. The anticancer potential of EASL can be attributed to the presence of phenols and flavonoids. Conclusion: Results suggest that EASL possesses significant anticancer activity against EAC tumor-bearing Swiss albino mice.
... Guha et al., 2004;Singh et al., 2008;Reddy et al., 2001;Viral et al., 2011;Mahmoud et al., 1989;Nyarko et al., 2012 ،) ( ‫ضدمیکروبی‬ Mahran, 1999;Tantawy, 2003 ،) ( ‫ضدالتهاب‬ Mabeza & Macfarlane, 2003;Haider et al., 2011;Zhang et al., 2000 ‫ضدآلر‬ ،) ‫ژ‬ ( ‫ی‬ Yuan et al., 2013;Hussain et al., 2008 ‫ضددیابتی‬ ،) ( Ranjan et al., 2014;Ocvirk et al., 2013 ‫تنظیم‬ ،) ‫عمل‬ ‫کنندۀ‬ ‫تیروئید‬ ‫کرد‬ Vijayalakshmi & Kiran Kumar, 2013) Sundaram & Milner, 1993;Freshney, 2000;Durmaz et al., 1999;Chiba et al., 1998 . Kumar et al., 2014 ) . ...
... In addition to the promising results discussed above, an ethanol extract of Adiantum venustum Don. was shown to increase the mean survival time in carcinoma-bearing mice relative to a positive control group treated with the established drug vincristine (Viral et al. 2011). ...
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Ferns are an important phytogenetic bridge between lower and higher plants. Historically they have been used in many ways by humans, including as ornamental plants, domestic utensils, foods, and in handicrafts. In addition, they have found uses as medicinal herbs. Ferns produce a wide array of secondary metabolites endowed with different bioactivities that could potentially be useful in the treatment of many diseases. However, there is currently relatively little information in the literature on the phytochemicals present in ferns and their pharmacological applications, and the most recent review of the literature on the occurrence, chemotaxonomy and physiological activity of fern secondary metabolites was published over 20 years ago, by Soeder (Bot Rev 51:442–536, 1985). Here, we provide an updated review of this field, covering recent findings concerning the bioactive phytochemicals and pharmacology of fern species.
... was closely observed for the first 3hrs then at an mice. Prolongation of life span of animals is the steadfast Hematological parameters (Figure 1) of tumor bearing criteria for judging the potency of any anticancer drug mice were found to be significantly altered compared to [16]. It can therefore be inferred that MAPV increased the the normal group. ...
Article
The present study is aimed to evaluate the methanolic fractions of the aerial parts of Polygonum viscosum (MAPV) for antitumor activity against Ehrlich ascites carcinoma (EAC) in Swiss albino mice. Twenty four hours after intraperitoneal inoculation of tumor (EAC) cells in mice, MAPV was administered at 50, 100 and 200 mg/kg body weight for nine consecutive days. On day 10 half of the mice were sacrificed and rest were kept alive for assessment of increase in life span. The antitumor effect of MAPV was assessed by evaluating tumor volume, packed cell count, viable and non-viable tumor cell count, median survival time and increase in life span of EAC bearing mice. Hematological profiles and serum biochemical parameters were estimated. MAPV showed a significant (p<0.05) decrease in tumor volume, packed cell volume and viable cell count and increased the life span of EAC bearing mice. Hematological and serum biochemical profiles were restored to normal levels in MAPV treated mice as compared to EAC control mice. The present study demonstrates that ethylacetate fraction of Polygonum viscosum leaves exhibited remarkable antitumor activity that is plausibly attributable to its augmenting endogenous antioxidant mechanisms.
Chapter
Ferns are good resource of medication for a variety of infirmities. Even though they possess immense medicinal potential, ferns are less used as medicine compared to angiosperms. Medicinal properties of some ferns are mentioned in various ancient literatures by Theophrastus, Sushruta, Charaka, Dioscorides, etc. Information regarding few ferns used as drugs is available in pharmacopoeias of different countries. Ethnic communities all over the world use ferns for various ailments such as dysentery, malaria, stomach ache, urinary disorders, burns, etc. Ayurvedic, Homeopathic and Unani medicines utilise ferns for various medicinal preparations. Recently, many phytochemical and pharmacological studies of ferns are carried out by various workers, and information with respect to the bioactive components of important medicinal ferns is also available. The chapter delineates the traditional ethnomedicinal uses of ferns along with potential medicinal properties like antimicrobial, anti-inflammatory, antidiabetic, anticancerous, etc. In addition to this, the chapter reviews various chemical compounds isolated and characterised from ferns and analyses future prospects of fern research.
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Aim: The aim of this study was to compare the anti-proliferative and apoptotic effects of hydroalcoholic extracts of different herbal medicines (Achillea wilhelmsii, Silybum marianumseed, Echinacea purpurea, Adiantum capillus-venerisand apricot kernel) against breast cancer cells (Mcf-7). Material and method: For this purpose, the plants were dried and milled, then, soaked in 70% ethanol for 72 hours and their extracts were extracted using a rotary vaporator. Different concentrations of herbal extracts (12.5, 25, 50 and 100 μg/ml) were added to the cancer cell culture medium and their cytotoxicity and apoptotic effects were investigated after 24h by MTT assay and acridine orange - ethidium bromide staining, respectively.Data was analyzed by SPSS software at the significant level of 5%. Results: Addition of the highestconcentration of all extracts to the culture mediumshowed the most significant anti-proliferative and apoptotic effects (P<0.05) compared to other concentrations of the same extracts.Also, among the high concentrations (100μg/ml), the highest cell cytotoxicity effects were related to the extracts of Echinacea purpureaand Adiantum capillus-veneris (P<0.05). Conclusion: The results of this study indicated that the addition of Echinacea purpurea and Adiantum capillus-venerisextractsto the cell culturesin high concentrationshad the most significant anti proliferative and apoptotic effects on breast cancer cells in comparison with other plant extractsand concentrations. Keywords: Apoptosis, Breast cancer cells, Cytotoxicity, Herbal extracts
Chapter
Cancer is one of the most serious illnesses of our civilization. The International Agency for Research on Cancer estimated that 14.1 million new cancer cases were diagnosed and that 8.2 million patients died from this disease worldwide in 2012 alone. Therefore, there is an urgent need for novel anticancer agents as well as new treatment strategies. Natural products have been valuable sources of new therapeutic agents. Thus, the aim of present chapter is to provide an overview of the anticancer natural compounds highlighting the successful cases with clinical application such as Taxol, vincristine and omacetaxine mepesuccinate; those involved in clinical trials such as parthenolide, betulinic acid, ingenol mebutate and curcumin; and the ones with high degree of activity and safety profile such as resveratrol, ursolic acid, tetrandrine and triptolide. For each one of these compounds, it will be presented and discussed its natural origin, cell target, mechanism of action, pharmacologic aspects as well as the structural modifications that improve its anticancer properties in order to summarize the recent medicinal advances of natural anticancer compounds and their analogues. All these aspects aim to draw our readers’ attention to the plants and/or their secondary metabolites therapeutic potential and in consequence value the plants’ role in anticancer drug discovery.
Article
Objective: To study the effect of copper benzohydroxamic acid complex (Cu-BHA) against Ehrlich ascites carcinoma (EAC) in Swiss A mice. Methods: Cu-BHA complex was synthesized from benzohydroxamic acid and CuSO4 solution. Swiss A mice inoculated with EAC cells were treated with the Cu-BHA complex and their longivity was compared with the untreated control group. Different biochemical parameters (alkaline phosphatase activity and lipid peroxidation in serum) and haematological parameters were noted. Transplantability of Cu- BHA complex treated EAC cells were observed. Results: Cu-BHA complex (25 mg./kg) enhanced longivity of tumour bearing mice significantly. Transplantability of EAC cells were reduced by Cu-BHA treatment. Haematological parameters and serum alkaline phosphatase activity in turnout bearing mice were found to be significantly altered but, Cu-BHA treatment recovered those parameters towards normal values. The Cu-BHA complex was found to be a potential antitumour drug. The tumour bearing mice treated with this complex showed negligible host-toxicity.
Article
Objective: To evaluate the therapeutic activity of cyclophosphamide alone and in combination with ascorbic acid against murine ascites Dalton's lymphoma. Materials and Methods: Cyclophosphamide (CP) is an anticancer drug with immunosuppressive activity, while ascorbic acid (AA) is an antioxidant. Ascites Dalton's lymphoma (DL) was maintained by intraperitoneal (i.p.) transplantation of tumor cells in Swiss albino mice. Tumor transplanted mice were divided into four groups. Group-I mice received normal saline only and served as control. Group-II mice were given 1% ascorbic acid through drinking water from the 5th to the 10th day. Group-III mice were injected i.p. with a single dose of CP (200 mg/kg) on the 10th day of tumor transplantation. Group IV mice received 1% ascorbic acid from the 5th day onwards and, then, a single dose of CP, i.p., on the 10th day of tumor transplantation. In groups III and IV, after 24, 48, 72, and 96 h of CP treatment the liver, kidneys, spleen, and tumor tissue were collected for biochemical determinations. In group II, which received AA only from the 5th to the 10th day, the same tissues were collected on the 10th day of tumor transplantation. The changes in reduced glutathione (GSH) and carbohydrate in tumor cells as well as the liver, kidney, and spleen of tumor-bearing mice in relation to the antitumor activity of CP alone or in combination with AA were evaluated. The quantitative changes in sialic acid level of DL cells under these treatment conditions were also determined. Results: AA and CP combination in tumor-bearing mice was found to be more effective against DL as it caused a 257% increase in life span compared with control, while it was 106% with AA and 188% with CP alone (ANOVA, P < 0.001). The reduced glutathione (GSH) level increased in DL cells with tumor growth. Compared with CP alone, the combination treatment (AA + CP) resulted in a more pronounced effect causing decreases in non-protein thiol (NPSH) as well as sialic acid levels in DL cells (ANOVA, P < 0.001). Conclusion: The drug-mediated lowering of GSH levels in DL cells may be involved in the cytotoxicity due to CP (group-III) as well as AA + CP combination (group-IV). An overall decrease in the sialic acid content of DL cells after combination treatment may also play a role to bring about alterations in the tumor cells, cell-cell interaction and enhanced tumor regression.
Article
Objectives: To investigate the chemopreventive potential and antilipidperoxidative effects of ethanolic root extract of Tephrosia purpurea (Linn.) Pers. (TpEt) on 7,12-dimethylbenz(a)anthracene (DMBA)- induced hamster buccal pouch carcinoma. Materials and Methods: Oral squamous cell carcinoma was developed in the buccal pouch of Syrian golden hamsters, by painting with 0.5% DMBA in liquid paraffin, thrice a week, for 14 weeks. The tumor incidence, volume and burden were determined. Oral administration of TpEt at a dose of 300 mg/kg, b.w., to DMBA (on alternate days for 14 weeks)- painted animals significantly prevented the incidence, volume and burden of the tumor. Results: TpEt showed potent antilipidperoxidative effect, as well as enhanced the antioxidant status in DMBA- painted animals. Conclusion: TpEt has potent chemopreventive efficacy and significant antilipidperoxidative effect, in DMBA-induced oral carcinogenesis. Further studies are needed to isolate and characterize the bioactive principle.