Background
Cystic echinococcosis (CE), as well known as the echinococcal disease is an infection occurred by
Echinococcus granulosus which is observed in the small intestine dogs [
1]. CE has been documented as a significant monetary and community well-being worry in various parts of the word particularly in developing countries [
2,
3]. Humans along with domestic livestock can be the intermediary hosts in whose various organs it creates hydatid cysts [
2,
3]. Because cysts are gentle-developing, infections with CE cannot create any symptoms for many years. However, the burst of cyst fluid may result in allergic responses or even death [
3]. Currently, clinical managements for CE are based on surgery, percutaneous methods and chemotherapy for live cysts, as well as “watch and wait” method for silent cysts [
4]. Likewise, chemotherapy with benzimidazoles has been applied to take care of hydatid cysts and demonstrated effectiveness against CE. However, they represented a range of complications such as hepatotoxicity and alopecia [
4,
5]. Up to now, surgery is the favored treatment for CE, however, it has threats including those of surgical involvement, anaphylactic shocks, and secondary CE because of spilling of the contents of cyst which called protoscoleces [
5,
6]. To date, available chemical drugs including 20% hypertonic saline, Ag-nitrate, and cetrimide have been applied in surgical and percutaneous methods, but they have shown severe complications for example biliary tract fibrosis, necrosis of the liver, and methemoglobinemia [
7,
8]. Thus, it is compulsory to discover a perfects scolicidal agent with high effectiveness and no local or systemic complications for hydatid cyst surgery.
The use of herbs and spices has a very long history in folk medication to cure of various diseases and illnesses. Nowadays, herbal medicines supply boundless chances for discovering novel agents for therapy an extensive range of diseases as a result of possessing few complications, a low cost, and high accessibility [
9]. Spices have been applied for centuries to get better the flavor and aroma of foods as well as for their medicinal properties. Spices are also famous for their antimicrobial features and are the most frequently used natural antimicrobial agents in foods [
10]. In modern medicine, essential oils from various spices have been found to possess different antimicrobial effects, and the majority of them are categorized as ‘Commonly Recognized as Safe’ [
11].
Curcuma longa L. from the family of Zingiberaceae with the familiar name of “turmeric” is extensively cultivated in tropical parts of Asia and Africa [
11]. The plant possesses various biological activities such as anti-inflammatory, hepatoprotective, antimicrobial, wound healing, anticancer, antitumor, and antiviral ones [
12‐
14]. Previous investigations exhibited the chemical composition of
C. longa essential oil (CLEO) in detail [
15,
16].; however, this composition is depended on a number of factors such as geographical origin, collecting period, and environment situations are able to affect the chemical composition and bioactivity of the herbs [
17]. Based on what was said we decided to evaluate the composition of CLEO, its scolicidal activity on hydatid cyst protoscoleces in vitro and ex vivo, and its safety in animal.
Discussion
Historically, herbal medicines have been a popular form of complementary and alternative medicine worldwide [
9]. Based on the World Health Organization (WHO) reports, in excess of 70% of the world’s people trust in folk remedy for their some health care requirements.
Since protoscolicidal agents used during hydatid cyst surgery have side effects such as sclerosing cholangitis, so more attention is paid to the toxicity of these drugs, as well as the search for a suitable alternative drug [
2]. This is the first known study to evaluate the efficacy of
C. longa essential oil against hydatid protoscoleces and also its safety in the mice. Results demonstrated that
C. longa essential oil killed 100% of protoscoleces at the doses of 200 and 100 μL/mL after 5 and 10 min of treatment, respectively.
In this study, we established the PAIR technique, with some changes, by hydatid cysts collected from sheep livers. The scolicidal agent should fill the complete cyst cavity, seeking interaction with the protoscoleces, which occasionally are placed in the cyst. Ex vivo assay displayed that although CLEO at the doses of 50, and 100 μL/mL showed potent effects in vitro; but did not show the similar effect in the ex vivo analysis, needing a more time to approve a notable protoscolicidal activity. While, C. longa essential oil at the dose of 200 μL/mL and an treatment time of 5 min, approximately killed all the protoscoleces inside the cyst. These findings discovered that the scolicidal activity of C. longa essential oil is as good as to the current scolicidal agents such as 20% hypertonic saline, and silver nitrate, etc.
The previous study confirmed that an appropriate protoscolicidal agent is characterized by its capability at lesser doses, high efficiency in a lower time, and steadiness in the cystic contents, high accessibility, minor toxicity, and capacity for fast preparation [
11]. The findings suggested that
C. long might be a natural resource for producing a novel protoscolicidal drug which can used in hydatid cyst surgery.
By GC/MS analysis, The key constituents were α-turmerone (27.1%), β- turmerone (21.8%), l-phellandrene (8.8%), and ρ-cymene (5.4%), respectively. Similarly, the essential oil of
C. longa rhizome has been studied in detail in a number of studies [
15,
16]. and the main constituents were found to be ar-turmerone and turmerol. However, the previous studies have demonstrated that the chemical composition of EO rely on species, typical weather, harvest time, and growth step, which could change the biological characteristics of plants [
17].
Turmerone and ar-turmerone are, according to their chemical structure, oxygenated sesquiterpenes of the bisabolene type, responsible for turmeric’s aroma and smell [
24]. Regarding the antimicrobial mechanism of some terpenoid constituents, researchers have demonstrated that these constituents exhibit their antimicrobial mechanisms through penetration into the microbe and extinction of its cell wall [
25]. On the other hand, some studies have shown that these contituents, after entering the pathogens, can display their antimicrobial mechanisms by breaking down important and vital intracellular reactions and activities [
26,
27].
The obtained results revealed that the LD
50 value of the
C. longa essential oil was 1.93 mL/kg/bw, and the maximum nonfatal dose was 1.16 mL/kg/bw. In the present study, we examined clinical and hematological parameters in the treatment of mice receiving essential oil for 14 days to assess the sub-acute toxicity of
C. longa essential oil. Liver and renal enzyme activities such as ALT, AST, ALP, Bilirubin (total, direct), Cr, and BUN are the most important characteristics of liver and renal function. Here, we observed no considerable difference (
P > 0.05) in the clinical chemistry and hematological factors following intraperitoneal administrations of
C. longa essential at the doses of 0.15, 0.3, and 0.6 mL/kg for 2 weeks. Therefore, based on the standard classification of toxicity,
C. longa essential oil did not show any considerable toxicity against NIH mice [
28].
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