Scolicidal Effects of Gallic Acid, One of the Major Compounds of Plants, on Protoscolices of Hydatid Cyst

Abstract

Background
Today’s, the recurrent of hydatidosis remain as a concern in many surgeries. Exposure of a suitable effective scolicidal agent with protoscolex-rich fluid can prevent these complications. In recent studies more have been considered to importance of natural products particularly herbal medcines to evaluate their scolicidal effects. Gallic acid a type of organic acid is one of the main known effective biological phenolic substances of plants.

Objectives
The aim of this study was to evaluate the effect of Gallic acid on protoscolices of hydatid cysts in in vitro.

Methods
In this experimental study, the protoscolices were obtained from liver hydatid cysts of infected sheep. Gallic acid solution was used at the concentration of 25, 30 and 35 mg/mL for 1, 3, and 5 minutes. The live protoscolices were detected by 0.1% eosin dye. Data analysis was performed by SPSS version 11.5 and one-way ANOVA test.

Results
The Gallic acid at the concentration of 25 mg/mL disabled 35.65%, 52.21% and 65.38% of protoscolices after 1, 3 and 5 min of faced time together, respectively. Also, the scolicidal rate of Gallic acid at concentration of 30 mg/mL was 29.92%, 63.80% and 67.76% after 1, 3 and 5 min, respectively. It was observed that concentration of 35 mg/mL Gallic acid on protoscolices caused 92.08% and 100% mortality rate of parasites after 1 and 3 minutes, respectively (compared with 9.9% in control groups).

Conclusions
The findings of present study showed that Gallic acid as an effective constituent of some herbal scolicidal agent can be considered as responsible for killing of protoscolices. However, further studies will be needed to confirm this phytochemicals active component in animal models.

Full text

Zahedan J Res Med Sci. 2017 May; In Press(In Press):e9791.
Published online 2017 May 31.
doi: 10.5812/zjrms.9791.
Research Article
Scolicidal Effects of Gallic Acid, One of the Major Compounds of
Plants, on Protoscolices of Hydatid Cyst
Sara Larki,1,* Mohammad Hosein Razi Jalali,1and Saeed Goodarzi2
1Parasitology Department, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, IR Iran
2Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
*Corresponding author: Sara Larki, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Golestan Street, 61357-43337, IR Iran. Tel: +98-6133330011-5241, E-mail:
s.larki@scu.ac.ir
Received 2016 November 24; Revised 2017 March 27; Accepted 2017 April 22.
Abstract
Background: Today’s,the recurrent of hydatidosis remain as a concern in many surgeries. Exposure of a suitable effective scolicidal
agent with protoscolex-rich fluid can prevent these complications. In recent studies more have been considered to importance of
natural products particularly herbal medcines to evaluate their scolicidal effects. Gallic acid a type of organic acid is one of the main
known effective biological phenolic substances of plants.
Objectives: The aim of this study was to evaluate the effect of Gallic acid on protoscolices of hydatid cysts in in vitro.
Methods: In this experimental study, the protoscolices were obtained from liver hydatid cysts of infected sheep. Gallic acid solution
was used at the concentration of 25, 30 and 35 mg/mL for 1, 3, and 5 minutes. The live protoscolices were detected by 0.1% eosin dye.
Data analysis was performed by SPSS version 11.5 and one-way ANOVA test.
Results: The Gallic acid at the concentration of 25 mg/mL disabled 35.65%, 52.21% and 65.38% of protoscolices after 1, 3 and 5 min of
faced time together, respectively. Also, the scolicidal rate of Gallic acid at concentration of 30 mg/mL was 29.92%, 63.80% and 67.76%
after 1, 3 and 5 min, respectively. It was observed that concentration of 35 mg/mL Gallic acid on protoscolices caused 92.08% and
100% mortality rate of parasites after 1 and 3 minutes, respectively (compared with 9.9% in control groups).
Conclusions: The findings of present study showed that Gallic acid as an effective constituent of some herbal scolicidal agent can
be considered as responsible for killing of protoscolices. However, further studies will be needed to confirm this phytochemicals
active component in animal models.
Keywords: Hydatid Cyst, Gallic Acid, Protoscolices
1. Background
Hydatidosis or cystic echinococcosis (CE, hydatid cyst)
is one of the serious silent cyclozoonotic diseases between
humans and domestic animals caused by larval stage of
Echinococcus granulosus [1]. This disease with world-
wide distribution is more seen in Australia, South Amer-
ica, Mediterranean and the Middle East countries. Iran
is one of the endemic areas of hydatidosis [2]. Based on
WHO-IWGE (world health organization informal working
group on Echinococcosis) classification thetreatmentop-
tions to hydatidosis include; surgery, PAIR (Puncture, Aspi-
ration, Injection and Reaspiration), medicinal therapy and
watch and wait techniques [3,4]. Both surgery as preferred
method and PAIR techniques have been used for treat-
ment of cystic echinococcosis as the practical options [5-
7]. Dissemination of the live protoscolices to tissue around
can have the potential risk to growth into the new cysts
[8]. So, one of the main complications of many hyadati-
dosis surgeries and PAIR techniques is recurrence of cysts
as secondary cystic echinococcosis. The spillage of cysts
contents and use of insufficient scolicidal agents made to
be remaining protoscolices as alive. According to differ-
ent studies, the recurrence rates of disease are assessed
from4.6 to 22% [9]. Choose of a suitable effective scolicidal
agent reduce the risk of spillage of protoscolex-rich fluid
[10] which may reduce the recurrence rate. Alcohol, hy-
pertonic saline and povidone iodine are the most scolici-
dal compounds have frequently been applied for despera-
tion of protoscolices [11]. Also, there are various traditional
medicinal herbs have been exposed to protoscolices of hy-
datid cysts such as Zataria multiflora [12], Rhus coriaria L.
(sumac) [13], fruits of berberis (Berberis vulgaris) [14], black
cumin seed (Nigella sativa) [15] and Mallotus philippinensis
[16]. The natural derivatives of scolicidal plants can be re-
sponsiblefor the killing effects on protoscolices.
Gallic acid is a 3,4,5- trihydroxybenzoic acid, an organic
phenolic acid compound, has been seen widely distributed
in fruits and plants such as gallnuts, sumac, witch hazel,
tea leaves, oak bark, grapes, blueberries, apples, flaxseeds,
walnuts and watercress and other plants. Gallic acid
has antioxidant [17], anticancer [18] and anti-inflammatory
properties [19,20].
Copyright © 2017, Zahedan Journal of Research in Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons
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Larki S et al.
2. Objectives
Since Gallic acid is one of the major compounds of scol-
icidal plants with high therapeutic characteristics, present
study was examined the scolicidal features of this organic
compound.
3. Methods
3.1. Protoscolices Preparation
In this experimental study, protoscolices were ob-
tained from liver hydatid cysts of suffering sheep slaugh-
tered in slaughterhouse of Ahwaz, southwest of Iran. The
contents of cyst was drained and transmitted into the glass
cylindrical containers and leaved in a static place. After
30 minutes (min) the supernatant discarded and the re-
maining sediment contains protoscolices washed asepti-
cally with normal saline for several times.
The live protoscolices were detected by their motility
characteristics of flame cells and also the 0.1% eosin dye
(eosin powder (1 g) in distilled water (1 lit) under light mi-
croscopy. Fifteen min after contact with stain, unstaining
protoscolices to the dye were considered as alive (Figure 1),
eosin dye cannot penetrate into the live cells so remained
neutral while dead protoscolices were permeable to eosin
staining and colored red (Figure 2) [21]. For observation of
the findings of groups under microscope and imposed the
blindness in this study, we invited our parasitologist col-
league who had no information of grouping of the exper-
iments to count each samples. When viable protoscolices
rate was above 95%, that case was candidated as appropri-
ate sample for subsequent experiments and these proto-
scolices were kept in normal saline at 4°C for later use.
3.2. Preparation of Gallic Acid Solutions
Gallic acid powder was provided by Sigma-Aldrich (St.
Louis, MO). Different concentrations of Gallic acid dissolve
slowly in distilled water. To access steady solution, the con-
tainers of suspension solution were placed into water bath
up 40 - 50°C.
3.3. Scolicidal Tests
In this laboratory experimental study,three concentra-
tions (25, 30 and 35 mg/mL) of Gallic acid solutions were
examined in parallel groups for 1, 3 and 5 minutes. 500 mi-
croliter of Gallic acid solution was poured in a microtube;
then with an equal volume of enriched protoscolices was
blended slowly. After spending the designed times (1, 3, and
5 minutes) at room temperature, the supernatant of the so-
lution threw away with pipetting without any confusion of
sediment. To stop the reaction of the residual Gallic acid
Figure 1. Viable Protoscolices in the Presence of 0.1% Eosin Dye in Control Groups
Figure 2. Colored Protoscolices Died After Effect of Various Concentrations of Gallic
Acid and 0.1% Eosin
on protoscolices, rinse with normal saline step was done.
Then, the contents of microtube were reached to 1 mL by
adding normal saline and the same volume of dye was
added to the test microtube and blended slowly. 15 min-
utes later, the remaining sediment protoscolices was pre-
pared smear and evaluated under a light microscope. The
mortality rate of protoscolices was calculated by counting
the minimum of 500 protoscolices.
The experiments were performed in triplicate. In ad-
dition, in control groups, normal saline was used during
of experiment instead of Gallic acid and the results were
recorded in all experiments.
2Zahedan J Res Med Sci. 2017; In Press(In Press):e9791.
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Larki S et al.
3.4. Statistical Analysis
All statistical analysis was performed by SPSS version
11.5 package. Differences between the test and control
groups were performed by one-way ANOVA test. The sig-
nificant data were determined when the p values were less
than 0.05.
4. Results
The mortality rate of protoscolices in faced to various
concentrations of Gallic acid in various exposure times are
presented in Table 1 and Table 2 and Table 3 while this rate
in control groups were 9.9%. The scolicidal activity of Gallic
acid solution in 25 mg/mL was 35.65%, 52.21% and 65.38% af-
ter 1, 3 and 5 minutes of exposure time, respectively. The
mortality rate of Gallic acid solution in 30 mg/mL was
29.92%, 63.80% and 67.76% after 1, 3 and 5 minutes of expo-
sure time, respectively. When protoscolices were exposed
to Gallic acid solution at concentration of 35 mg/mL, in-
creased mortality rate observed to 92.08% and 100% after
1 and 3 minutes, respectively. The protoscolicidal effect of
Gallic acid solution was significant against to the control
groups at all exposure times (P < 0.05).
5. Discussion
In present study, the scolicidal activity of Gallic acid
solution in 35 mg/mL was 92.08% and 100% after 1 and
3 minutes of exposure times, respectively, so the scolici-
dal property of some plants can be attributed to this ma-
jor compound of plants. Today’s, nevertheless of efforts
and progress in therapeutic managements of hydatid cyst,
cystic echinococcosis has known as an emerging or re-
emerging disease, yet and caused public health concerns
in several countries [22].
Although various synthetic protoscolicidal solutions
have been applied in surgery and PAIR techniques to inac-
tivate the cysts contents, recurrence of disease was seen.
Loss of efficacy and effectiveness of scolicidal agents, rate
of adverse reactions, relapse rate and cost of agents were
caused the concern of this disease continues [3]. Al-
though formalin as the most frequently used agent [8,23]
povidone-iodine [24], alcohol [25], hypertonic saline 10% -
20% [8,23], H2O2[10] and cetrimide [8] investigated as ef-
fective scolicidal agents in various studies [26], but some
complication and adverse side effects following the use of
these scolicidal agents were reported. On the other hand
species resistance to antimicrobial synthetic anthelmintic,
the appearance some side effects and insufficient effective-
ness of chemical scolicidal agents stimulate the research of
natural alternative therapies [27]. Since the past decades,
the use of natural compounds derived from plant has been
frequently seen in traditional remedies [10]. Various inves-
tigations have examined the scolicidal effects of essential
oils or extracts of plants in today’s climate [12,21,28-31].
Phenolic compounds are one of the most widely oc-
curring groups of phytochemicals which play a significant
role in reproduction and growth of plants and also act as
protection mechanisms against microorganisms such as
parasites and predators [32]. Various bioactivities of nat-
ural phenolic compounds possess some chemopreventive
properties such as antioxidant, anticancer, antibacterial,
antiviral and anti-inflammatory activities [32-35].
Phenolic compound found in some scolicidal agents
such as Satureja khuzistanica essential oils [36], Peganum
harmala [29], garlic [21], ginger oil (Zingiber officinale) [30],
Berberis vulgaris L. [31], aqueous extracts of Olea europaea
leaves [37], methanolic fruit powder extract of Mallotus
philippinensis [16], extract of Cardaria draba (L.) [38]. ajowan
(Trachyspermum ammi L.) essential oil [39], Lepidium sativum
essential oil [40], sumac (Rhus coriaria) [13,41], Sambucus
ebulus [28,42].
Gallic acid a type of phenolic acids which are the main
class of phenolic compounds that frequently arising in
plant kingdom [43]. This organic acid is one of the main
biological effective phenolic compounds of plant sources
[44].
In many investigations on herbal scolicidal agents, Gal-
lic acid is one of the main constituents have been rec-
ognized by gas chromatography and massspectroscopy
analysis of scolicidal plants such as methanolic extract
of sumac (Rhus coriaria) (50 mg/mL after 10 minutes) [13],
Berberis vulgaris aqueous and hydro-alcohol extract (in 4
mg/mL and 2 mg/mL after 5 minutes, respectively) [14],
methanolic extract of Zataria multiflora (25 mg/mL after 1
minute) [12], the essential oil of black cumin seed (Nigella
sativa) seed (at 10 mg/mL after 10 minutes) [15], methanolic
fruit powder extract of Mallotus philippinensis (20 mg/mL
for only 10 minutes treatment) [16] and Sambucus ebulus
fruit extract (100 mg/mL after 60 minutes) [28,42].
This in vitro study showed that Gallic acid is an effective
scolicidal agent and can be introduced as one of the lethal
factors of protoscolices. Niho et al. (2001) showed that
Gallic acid is a no- observed-adverse-effect level (NOAEL) in
rats [45], so can be partly safe substance. According to the
antimicrobial mechanism of Gallic acid was described by
Neild and Kotecha (1990), this active compound of plants
altered the membrane characteristics of pathogens and re-
duction of negative surface charge irremeably followed by
rupture or pore created in place of cell membranes and in-
tracellular contents were discharged [46].
Further investigations will be required to isolate and
examine the other active compounds of scolicidal plants
Zahedan J Res Med Sci. 2017; In Press(In Press):e9791. 3
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Larki S et al.
Table1. Scolicidal Effect of Galli cacid in Concentration of 25 mg/mL at Different Exposure Times
Exposure Time, min Expriments Protoscolices Dead Protoscolices Mortality Rate, %
1
1 600 228 38
2 521 165 31.66
3 500 185 37
Total 1621 578 35.65
3
1 700 340 48.57
2 500 254 50.8
3 700 398 56.85
Total 1900 992 52.21
5
1 611 408 66.77
2 500 305 61
3 553 375 67.81
Total 1664 1088 65.38
Control 1000 99 9.9
Table2. Scolicidal Effect of Gallic Acid in Concentration of 30 mg/mL at Different Exposure Times
Exposure Time, min Expriments Protoscolices Dead Protoscolices Mortality Rate, %
1
1 697 206 29.55
2 1000 311 31.10
3 555 157 28.28
Total 2252 674 29.92
3
1 1000 598 59.80
2 685 471 68.75
3 520 338 65
Total 2205 1407 63.80
5
1 700 497 71
2 1073 710 66.16
3 504 336 66.66
Total 2277 1543 67.76
Control 1000 99 9.9
Table3. Scolicidal Effect of Gallic Acid in Concentration of 35 mg/mL at Different Exposure Times
Exposure Time, min Expriments Protoscolices Dead Protoscolices Mortality Rate, %
1
1 700 645 92.14
2 728 692 95.05
3 618 547 88.51
Total 2046 1884 92.08
3
1 531 531 100
2 650 650 100
3 610 610 100
Total 1791 1791 100
Control 1000 99 9.9
to comprehend of performance evaluation of traditional
medicine and produce pharmaceutical compounds. The
results of present study can confirm by investigating scol-
icidal effect of Gallic acid in an in vivo model.
Acknowledgments
The authors would like to thank research council of
Shahid Chamran University of Ahvaz, Iran, for the financial
support (Code: 80456).
4Zahedan J Res Med Sci. 2017; In Press(In Press):e9791.
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Larki S et al.
Footnotes
Authors’ Contribution: All authors had equal role in de-
sign, work, statistical analysis and manuscript writing.
Funding/Support: Research council of Shahid Chamran
University of Ahvaz, Iran.
References
1. Hashemi Tabar G, Haghparast A, Borji H. Serodiagnosis of sheep
hydatidosis with hydatid fluid, protoscolex, and whole body of
Echinococcus granulosus antigens. Comparative Clinical Pathology.
2010;21(4):429–32. doi: 10.1007/s00580-010-1112-4.
2. Sadjjadi SM. Present situation of echinococcosis in the Middle East
and Arabic North Africa. Parasitol Int. 2006;55 Suppl:S197–202. doi:
10.1016/j.parint.2005.11.030. [PubMed: 16337429].
3. Junghanss T, da Silva AM, Horton J, Chiodini PL, Brunetti E. Clinical
management of cystic echinococcosis: state of the art, problems,
and perspectives. Am J Trop Med Hyg. 2008;79(3):301–11. [PubMed:
18784219].
4. Brunetti E, Kern P, Vuitton DA, Writing Panel for the W. Expert
consensus for the diagnosis and treatment of cystic and alve-
olar echinococcosis in humans. Acta Trop. 2010;114(1):1–16. doi:
10.1016/j.actatropica.2009.11.001. [PubMed: 19931502].
5. Yorganci K, Sayek I. Surgical treatment of hydatid cysts of the liver
in the era of percutaneous treatment. Am J Surg. 2002;184(1):63–9.
[PubMed: 12135724].
6. Akhan O, Ozmen MN. Percutaneous treatment of liver hydatid cysts.
Eur J Radiol. 1999;32(1):76–85. [PubMed: 10580324].
7. Canyigit M, Gumus M, Cay N, Erol B, Karaoglanoglu M, Akhan
O. Refractory cystobiliary fistula secondary to percutaneous treat-
ment of hydatid cyst: treatment with N-butyl 2-cyanoacrylate em-
bolization. Cardiovasc Intervent Radiol. 2011;34 Suppl 2:S266–70. doi:
10.1007/s00270-009-9790-5. [PubMed: 20054546].
8. Besim H, Karayalcin K, Hamamci O, Gungor C, Korkmaz A. Scolicidal
agents in hydatid cyst surgery. HPB Surg. 1998;10(6):347–51. [PubMed:
9515230].
9. Prousalidis J, Kosmidis C, Anthimidis G, Kapoutzis K, Karamanlis E,
Fachantidis E. Postoperative recurrence of cystic hydatidosis. Can J
Surg. 2012;55(1):15–20. doi: 10.1503/cjs.013010. [PubMed: 21939605].
10. Adas G, Arikan S, Kemik O, Oner A, Sahip N, Karatepe O. Use of albenda-
zole sulfoxide, albendazole sulfone, and combined solutions as scol-
icidal agents on hydatid cysts (in vitro study). World J Gastroenterol.
2009;15(1):112–6. [PubMed: 19115476].
11. Karaoglanoglu M, Akinci OF, Ulukanligil M, MET˙
IN MR, CETIN H, Cay
N. Hydatid cyst viability: the effect of scolicidal agents on the scolex
in the daughter cyst. Turk J Med Sci. 2011;41(6):1001–6.
12. Moazeni M, Roozitalab A. High scolicidal effect of Zataria multiflora
on protoccoleces of hydatid cyst: an in vitro study. Compar Clin Pathol.
2010;21(1):99–104. doi: 10.1007/s00580-010-1069-3.
13. Moazeni M, Mohseni M. Sumac (&lt;i&gt;Rhus coriaria&lt;/i&gt;
L.): Scolicidal Activity on Hydatid Cyst Protoscolices. Surg Sci.
2012;03(09):452–6. doi: 10.4236/ss.2012.39089.
14. Salehi N, Rouhani S, Kamalinejad M, Zayeri F, Motaghifar A. Scolicidal
effects of Berberis vulgaris fruit extract on hydatid cyst protoscolices.
Tehran Univ Med J TUMS Public. 2014;72(2):121–8.
15. Mahmoudvand H, Dezaki ES, Kheirandish F, Ezatpour B, Jahanbakhsh
S, Harandi MF. Scolicidal effects of black cumin seed (Nigella sativa)
essential oil on hydatid cysts. Korean J Parasitol. 2014;52(6):653–9. doi:
10.3347/kjp.2014.52.6.653. [PubMed: 25548417].
16. Gangwar M, Verma VC, Singh TD, Singh SK, Goel RK, Nath G. In-
vitro scolicidal activity of Mallotus philippinensis (Lam.) Muell Arg.
fruit glandular hair extract against hydatid cyst Echinococcus gran-
ulosus. Asian Pac J Trop Med. 2013;6(8):595–601. doi: 10.1016/S1995-
7645(13)60103-0. [PubMed: 23790329].
17. Asnaashari M, Farhoosh R, Sharif A. Antioxidant activity of gal-
lic acid and methyl gallate in triacylglycerols of Kilka fish oil
and its oil-in-water emulsion. Food Chem. 2014;159:439–44. doi:
10.1016/j.foodchem.2014.03.038. [PubMed: 24767079].
18. Maurya DK, Nandakumar N, Devasagayam TP. Anticancer property
of gallic acid in A549, a human lung adenocarcinoma cell line,
and possible mechanisms. J Clin Biochem Nutr. 2011;48(1):85–90. doi:
10.3164/jcbn.11-004FR. [PubMed: 21297918].
19. Kroes BH, van den Berg AJ, Quarles van Ufford HC, van Dijk H,
Labadie RP. Anti-inflammatory activity of gallic acid. Planta Med.
1992;58(6):499–504. doi: 10.1055/s-2006-961535. [PubMed: 1336604].
20. Locatelli C, Filippin-Monteiro FB, Ariana C. In: Handbook onGallic
acid: Natural Occurrences, Antioxidant Properties and Health Impli-
cations. Thompson MA, Collins PB, editors. Hauppauge: Nova science
publishers; 2013. pp. 1–23.Antioxidant, Antitumoral and Anti Inflam-
matory Activities of GA.
21. Moazeni M, Nazer A. In vitro effectiveness of garlic (Allium sativum)
extract on scolices of hydatid cyst. ;34(11):2677–81.
22. Moro P, Schantz PM. Echinococcosis: a review. Int J Infect Dis.
2009;13(2):125–33. doi: 10.1016/j.ijid.2008.03.037. [PubMed: 18938096].
23. Topcu O, Aydin C, Arici S, Duman M, Koyuncu A, Sen M. The Effects of
Various Scolicidal Agents on the Hepatopancreatic Biliary System. Vis-
cer Med. 2006;22(3):185–90. doi: 10.1159/000094710.
24. LeVeen HH, LeVeen RF, LeVeen EG. The mythology of povidone-iodine
and the development of self-sterilizing plastics. Surg Gynecol Obstet.
1993;176(2):183–90. [PubMed: 8421809].
25. Yetim I, Erzurumlu K, Hokelek M, Baris S, Dervisoglu A, Polat C, et al.
Results of alcohol and albendazole injections in hepatic hydatidosis:
experimental study. J Gastroenterol Hepatol. 2005;20(9):1442–7. doi:
10.1111/j.1440-1746.2005.03843.x. [PubMed: 16105134].
26. Kilicoglu B, Kismet K, Kilicoglu SS, Erel S, Gencay O, Sorkun K, et al. Ef-
fects of honey as a scolicidal agent on the hepatobiliary system. World
J Gastroenterol. 2008;14(13):2085–8. [PubMed: 18395911].
27. Harris JC, Plummer S, Turner MP, Lloyd D. The microaerophilic flagel-
late Giardia intestinalis: Allium sativum (garlic) is an effective anti-
giardial. Microbiology. 2000;146 Pt 12:3119–27. doi: 10.1099/00221287-
146-12-3119. [PubMed: 11101670].
28. Gholami SH, Rahimi-Esboei B, Ebrahimzadeh MA, Pourhajibagher M.
In vitro effect of Sambucus ebulus on scolices of Hydatid cysts. Eur Rev
Med Pharmacol Sci. 2013;17(13):1760–5. [PubMed: 23852900].
29. Hammoshi MH, Shareef AY, Younis GT. Effect of Ethanolic Extract
and Crude Alkaloides of Peganum harmala Seeds on The Viabil-
ity of Echinococcus granulosus Protoscolices in vitro. Raf Jour Sci.
2005;16(6):1–8.
30. Feizi F, Moradkhani S, Matini M, Parandin F, Roushan A, Fallah M. To
Study the Solicidal Effects of the Extracts of Ginger (Zingiber offici-
nale) and Artemisia (Artemisia aucheri) on Protoscoleces of Hydratid
Cyst in vitro. AMUJ. 2015;18(101):45–52.
31. Rouhani S, Salehi N, Kamalinejad M, Zayeri F. Efficacy of
Berberis vulgaris aqueous extract on viability of Echinococcus
granulosus protoscolices. J Invest Surg. 2013;26(6):347–51. doi:
10.3109/08941939.2013.818746. [PubMed: 23978263].
32. Baidez AG, Gomez P, Del Rio JA, Ortuno A. Dysfunctionality of the
xylem in Olea europaea L. Plants associated with the infection pro-
cess by Verticillium dahliae Kleb. Role of phenolic compounds in
plant defense mechanism. J Agric Food Chem. 2007;55(9):3373–7. doi:
10.1021/jf063166d. [PubMed: 17394331].
33. Han X, Shen T, Lou H. Dietary Polyphenols and Their Biological Signif-
icance. Int J Mol Sci. 2007;8(9):950–88. doi: 10.3390/i8090950.
34. Veeriah S, Kautenburger T, Habermann N, Sauer J, Dietrich H, Will
F, et al. Apple flavonoids inhibit growth of HT29 human colon can-
cer cells and modulate expression of genes involved in the bio-
transformation of xenobiotics. Mol Carcinog. 2006;45(3):164–74. doi:
10.1002/mc.20158. [PubMed: 16369997].
Zahedan J Res Med Sci. 2017; In Press(In Press):e9791. 5
Uncorrected Proof

Larki S et al.
35. Owen RW, Giacosa A, Hull WE, Haubner R, Spiegelhalder B, Bartsch
H. The antioxidant/anticancer potential of phenolic compounds iso-
lated from olive oil. Eur J Cancer. 2000;36(10):1235–47. [PubMed:
10882862].
36. Moazeni M, Saharkhiz MJ, Hoseini AA, Alavi AM. In vitro scolicidal ef-
fect of Satureja khuzistanica (Jamzad) essential oil. Asian Pac J Trop
Biomed. 2012;2(8):616–20. doi: 10.1016/s2221-1691(12)60107-5.
37. Ryan D, Antolovich M, Prenzler P, Robards K, Lavee S. Biotransforma-
tions of phenolic compounds in Olea europaea L. Scientia Horticul-
turae. 2002;92(2):147–76.
38. Sharifi-Rad J, Hoseini-Alfatemi S, Sharifi-Rad M, Teixeira da Silva J,
Rokni M, Sharifi-Rad M. Evaluation of Biological Activity and Pheno-
lic Compounds of Cardaria draba (L.) Extracts. J Biol Today’s World.
2015;4(9) doi: 10.15412/j.jbtw.01040901.
39. Chatterjee S, Goswami N, Bhatnagar P. Estimation of Phenolic
Components and in vitro Antioxidant Activity of Fennel (Foenicu-
lum vulgare) and Ajwain (Trachyspermum ammi) seeds. Adv Biores.
2012;3(2):109–18.
40. Bahrami S, Razi Jalali MH, Ramezani Z, Pourmehdi Boroujeni M,
ToeimepourF. In vitro Scolicidal Effect of Lepidium sativum Essential
Oil. J Ardabil Univ Med Sci. 2016;15(4):395–403.
41. Kosar M, Bozan B, Temelli F, Baser KHC. Antioxidant activity and phe-
nolic composition of sumac (Rhus coriaria L.) extracts. Food Chem.
2007;103(3):952–9. doi: 10.1016/j.foodchem.2006.09.049.
42. Karami M, Ale-Nabi SS, Nosrati A, Naimifar A. The protective effect of
Sambucus ebulus against lung toxicity induced by gamma irradia-
tion in mice. Pharm Biomed Res. 2015;1(1):48–54. doi: 10.18869/acad-
pub.pbr.1.1.48.
43. Cai Y, Luo Q, Sun M, Corke H. Antioxidant activity and phenolic com-
pounds of 112 traditional Chinese medicinal plants associated with
anticancer. Life Sci. 2004;74(17):2157–84. doi: 10.1016/j.lfs.2003.09.047.
[PubMed: 14969719].
44. Karamac M, Kosinska A, Pegg RB. Content of gallic acid in selected
plant extracts. Polish J Food Nutr Sci. 2006;15(1):55.
45. Niho N, Shibutani M, TamuraT, Toyoda K, Uneyama C, Takahashi N, et
al. Subchronic toxicity study of gallic acid by oral administration in
F344 rats. Food Chem Toxicol. 2001;39(11):1063–70. [PubMed: 11527565].
46. Neild TO, Kotecha N. Actions of neuropeptide Y on arterioles of the
guinea-pig small intestine are not mediated by smooth muscle depo-
larization. J Auton Nerv Syst. 1990;30(1):29–35. [PubMed: 2348052].
6Zahedan J Res Med Sci. 2017; In Press(In Press):e9791.
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