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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="review-article" dtd-version="1.1d1">
  <front>
    <journal-meta>
      <journal-title-group>
        <journal-title>Biomedical Research and Therapy</journal-title>
      </journal-title-group>
      <issn pub-type="epub" publication-format="electronic">2198-4093</issn>
      <publisher>
        <publisher-name>BioMedPress</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="doi">10.15419/bmrat.v4i11.383</article-id>
      <article-categories>
        <subj-group subj-group-type="display-channel">
          <subject>Review</subject>
        </subj-group>
        <subj-group subj-group-type="heading">
          <subject>Biomedical Research and Therapy</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Concise review: Medicinal plants are effective against leishmaniasis</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Bahmani</surname>
            <given-names>Mahmoud</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Abbasi</surname>
            <given-names>Naser</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Hosseini</surname>
            <given-names>Masih</given-names>
          </name>
          <xref ref-type="aff" rid="aff3"/>
        </contrib>
        <contrib contrib-type="author" corresp="yes">
          <name>
            <surname>Rafieian-Kopaei</surname>
            <given-names>Mahmoud</given-names>
          </name>
          <xref ref-type="aff" rid="aff3"/>
          <xref ref-type="corresp" rid="cor1">*</xref>
        </contrib>
        <aff id="aff1">
          <institution>Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran</institution>
        </aff>
        <aff id="aff2">
          <institution>Biotechnology and Medicinal Plants Research Center, Ilam University of Medical Sciences, Ilam, Iran</institution>
        </aff>
        <aff id="aff3">
          <institution>Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="cor1"><label>*</label>For correspondence: <email>rafieian@yahoo.com</email></corresp>
        <fn fn-type="con" id="equal-contrib">
          <label>*</label>
          <p>These authors contributed equally to this work</p>
        </fn>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>29</day>
        <month>11</month>
        <year>2017</year>
      </pub-date>
      <volume>4</volume>
      <issue>10</issue>
      <fpage>1</fpage>
      <lpage>7</lpage>
      <history>
        <date date-type="received">
          <day>18</day>
          <month>11</month>
          <year>2017</year>
        </date>
        <date date-type="accepted">
          <day>22</day>
          <month>11</month>
          <year>2017</year>
        </date>
      </history>
      <permissions>
        <copyright-statement>Copyright: &#169; The Author(s) 2017</copyright-statement>
        <copyright-year>2017</copyright-year>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/CC-BY/4.0">
          <license-p>This article is published with open access by BioMedPress (BMP), Laboratory of Stem Cell Research and Application, Vietnam National University, Ho Chi Minh city, Vietnam This article is distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0) which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.</license-p>
        </license>
      </permissions>
      <self-uri content-type="pdf" xlink:href="http://www.bmrat.org/index.php/BMRAT/article/view/383/779"/>
      <abstract>
        <p>Leishmaniasis is an important zoonotic parasitic disease in tropical areas. It is a neglected disease and is a great health catastrophe in Iran. Pentavalent antimony compounds are used for its treatment, but they have adverse effects. Therefore, the use of natural herbs with low adverse effects seems necessary for treatment of Leishmaniasis. In this study, we tried to introduce the natural medicines effective against Leishmaniasis. In this review study, keywords searched included natural medicines, herbal medicines, medicinal plants, Leishmaniasis, and treatment in relevant publications published between 1990 and 2017. Searching was on databases including ISI Web of Science, PubMed, PubMed Central, Scopus, ISC, SID, Magiran and some other databases. The relevant articles were reviewed for the review study. The results showed that medicinal plants: Ferula assafoatida (with IC50 of 0.38 mg/ml), Glycyrrhiza glabra (with IC50 of 25mg/ml), Allium sativum (with IC50 of 0.57 mg/ml), Cephalis ipecacuana (with IC50 of 0.01 mg/ml), Artemisia aucheri (with IC50 of 0.46 mg/ml) and Eucalyptus globulus (with IC50 of 0.17 mg/ml) were the natural medicines effective against the disease. Compositions with di-, tri-, tetra-Sulfide, Coumarin derivatives, Camuou-nephrole, Episamarcandine, Amblipernine, Carnephrole, Azafoetidine, Froxolicin, Azafoetidinole, Saradaferine, 1, 8 Cineole, Scopodreniole, Semen, Sabinine, Cineole, Inaleole, Eojenole, Farenzole, Borneol, Allicin, acid Glycerisic, Emetine and Cephalin can have the potential to produce potent drugs against Leishmaniasis. In sum, there are some specific medicinal plants and compounds effective against Leishmaniasis which can be used per se or following changes in their formula to prepare and introduce new drags against this disease.</p>
      </abstract>
      <kwd-group>
        <kwd>Disease</kwd>
        <kwd>Leishmaniasis</kwd>
        <kwd>Natural medicines</kwd>
        <kwd>Treatment</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec id="s1">
      <title>Introduction</title>
      <p>History of consumption of herbal drugs in treatment of diseases goes back to the first human living that has revolted and developed during centuries <xref ref-type="bibr" rid="ref18">Fankam Aime and Jules, 2014</xref><xref ref-type="bibr" rid="ref59">Rahmatullah et al., 2013</xref>. Great tendency of people toward natural treatments, which are harmless, cost-effective, and cultural compatible, has caused extensive use of pharmaceutical plants in Iranian traditional medicine <xref ref-type="bibr" rid="ref10">Bahmani et al., 2016</xref><xref ref-type="bibr" rid="ref41">Mahomoodally and Fawzi, 2013</xref><xref ref-type="bibr" rid="ref51">Mustafa et al., 2017</xref><xref ref-type="bibr" rid="ref60">Rouhi-Boroujeni et al., 2017</xref>. Although in the past half century, the use of chemical and synthetic drugs has advanced; the adverse effects of these drugs on life have caused a second trend to herbal drugs <xref ref-type="bibr" rid="ref37">Li et al., 2011</xref><xref ref-type="bibr" rid="ref63">Sarrafchi et al., 2016</xref><xref ref-type="bibr" rid="ref71">Tomlinson and Akerele, 2015</xref>. Natural substances, extracted from medicinal plants, are reliable sources of procurement of medicines and the original foundation in development of pharmaceutical compounds <xref ref-type="bibr" rid="ref55">Ntie-Kang et al., 2013</xref>. Herbal drugs have a better general compliance due to low adverse effects <xref ref-type="bibr" rid="ref43">Medagama and Bandara, 2014</xref><xref ref-type="bibr" rid="ref66">Shayganni et al., 2016</xref>. Parasitic diseases infecting humans are important and serious health problems that result in significant effects on individuals and great economic and social costs <xref ref-type="bibr" rid="ref2">Akhoundi et al., 2013</xref><xref ref-type="bibr" rid="ref13">Belkaid et al., 2002</xref>, Conceicao et al., 2016; Gutierrez et al., 2016<xref ref-type="bibr" rid="ref40">Mahmoudi et al., 2013</xref><xref ref-type="bibr" rid="ref46">Mirzaei et al., 2013</xref><xref ref-type="bibr" rid="ref58">Petitdidier et al., 2016</xref><xref ref-type="bibr" rid="ref61">Sacks and Perkins, 1984</xref><xref ref-type="bibr" rid="ref68">Soares et al., 2017</xref>. Various herbal drugs are used for the treatment of parasitic diseases <xref ref-type="bibr" rid="ref17">dos Santos Silva, 2014</xref><xref ref-type="bibr" rid="ref56">Oliveira et al., 2015</xref><xref ref-type="bibr" rid="ref70">Tahir et al., 1998</xref>. Leishmaniasis is an important parasitic zoonotic disease in tropical areas, and is considered a neglected disease <xref ref-type="bibr" rid="ref53">Ndjonka et al., 2013</xref>. Studies and statistics show that about 350 million people worldwide are at risk of being infected with the disease <xref ref-type="bibr" rid="ref73">WHO, 2010</xref>. Annually, approximately two million new cases of the disease are reported <xref ref-type="bibr" rid="ref48">Mohajery et al., 2004</xref>. Iran, Algeria, Nicaragua, Colombia, Peru, Bolivia, Afghanistan, Brazil, Syria, and Saudi Arabia are the inhabitant countries of cutaneous leishmaniasis <xref ref-type="bibr" rid="ref24">Gramiccia and Gradoni, 2005</xref>. Cutaneous Leishmaniasis is the most important parasitic disease in Iran and even in Middle East area <xref ref-type="bibr" rid="ref6">Governorate, 1985</xref>. Leishmaniasis is a great health catastrophe in Iran <xref ref-type="bibr" rid="ref67">Shirazi et al., 2006</xref>. In Iran, the regions like Khorasan, Yazd, Bushehr, Fars, Khuzestan, Ilam, and Esfahan have the highest rate of this disease in the country <xref ref-type="bibr" rid="ref69">Tabatabaei et al., 2007</xref>. Leishmaniasis imposes a great economic burden on the community in developing countries <xref ref-type="bibr" rid="ref7">Ashford et al., 2010</xref>. Cutaneous Leishmaniasis causes skin lesions with remaining scars. Pentavalent antimonies are used for its treatment, but have high level of adverse effects <xref ref-type="bibr" rid="ref48">Mohajery et al., 2004</xref>.</p>
      <p>Therefore, using herbal drugs with natural source and low adverse effects seems necessary for the treatment of cutaneous Leishmaniasis. In this study, we introduce natural medicines against Leishmaniasis.</p>
    </sec>
    <sec id="s2">
      <title>Methods</title>
      <p>In this review study, keywords searched included natural medicines, herbal medicines, medicinal plants, Leishmaniasis, and treatment. Searching was on databases including ISI Web of Science, PubMed, PubMed Central, Scopus, ISC, SID, Magiran and some other databases. The relevant articles were reviewed for this review article.</p>
    </sec>
    <sec id="s3">
      <title>Results</title>
      <p>The results of the literature review showed that medicinal plants, including Ferula assafoatida, Glycyrrhiza glabra, Allium sativum, Cephalis ipecacuana, Artemisia aucheri, and Eucalyptus globulus were the herbal medicines effective against the disease. The results of the present study showed that herbal plants such as Ferula assafoatida with IC50 of 0.38 mg/ml, Glycyrrhiza glabra plant with IC50 of 25mg/ml, Allium sativum plant with IC50 of 0.57 of mg/ml, Cephalis ipecacuana plant with IC50 of 0.01 mg/ml, Artemisia aucheri plant with IC50 of 0.46 mg/ml and Eucalyptus globulus herb with IC50 of 0.17 mg/ml were the natural medicines effective against leishmanisis (<xref ref-type="fig" rid="tab1"> Table 1 </xref>).</p>
      <fig id="tab1">
        <label>Table 1</label>
        <caption>
          <p>The most important herbal medicines effective against Leishmaniasis with IC50 values in mg/ml</p>
        </caption>
        <graphic xlink:href="bmrat.v4i11.383/tab1.png"/>
      </fig>
    </sec>
    <sec id="s4">
      <title>Discussion</title>
      <p>In this study, it was found that herbal medicines, including Ferula assafoatida, Glycyrrhiza glabra, Allium sativum, Cephalis ipecacuana, Artemisia aucheri and Eucalyptus globulus were medicinal plants effective against Leishmaniasis. In traditional medicine, Asafoetida plant is used against seizures, worms, neural diseases, intestinal dysmotility, renal pain, rheumatism, muscular clench, and hypertension, and for elimination of fatty foods&#8217; harms, as well as for enhancing appetite and memory <xref ref-type="bibr" rid="ref32">Lee et al., 2009</xref><xref ref-type="bibr" rid="ref35">Leung, 1996</xref><xref ref-type="bibr" rid="ref49">Mohammadi, 2009</xref><xref ref-type="bibr" rid="ref62">Sadraei et al., 2003</xref>. Asafoetida has di-, tri-, and tetra-sulfide, coumarin derivatives, camuonephrole, episamarcandine, amblipernine, carnephrole, azafoetidine, froxolicin, azafoetidinole, saradaferine, and foetidine <xref ref-type="bibr" rid="ref1">Abd El-Razek et al., 2001</xref><xref ref-type="bibr" rid="ref11">Bandyopadhyay, 2006</xref><xref ref-type="bibr" rid="ref12">Banerji et al., 1998</xref><xref ref-type="bibr" rid="ref20">Fraga, 1999</xref><xref ref-type="bibr" rid="ref29">Kajimoto et al., 1989</xref><xref ref-type="bibr" rid="ref31">Kojima et al., 2000</xref><xref ref-type="bibr" rid="ref52">Nassar et al., 1995</xref>. Eucalyptus has antibacterial, antifungal, antioxidan, anti-infectious, and antispasmatic effects. It is also fever palliative and putative, hypoglycemic and anthelmintic plant <xref ref-type="bibr" rid="ref45">Ministry of health and medical education, 2004</xref><xref ref-type="bibr" rid="ref74">Zargary, 1996</xref>. Eucalyptus plant contains a compound called 1, and 8 cineole or Eucalyptole that is the main composition of this plant <xref ref-type="bibr" rid="ref50">Mulyaningsih et al., 2010</xref><xref ref-type="bibr" rid="ref57">Oyedeji et al., 1996</xref>. Artemisia has astringent property, disinfectant activity, antimicrobial, antiparasite, anti-poisoning, and anti-insect effects <xref ref-type="bibr" rid="ref5">AliAbadi et al., 2010</xref><xref ref-type="bibr" rid="ref8">AzadBakht, 2003</xref>. Artemisia contains scopodreniole, semen, sabinine, cineole, inaleole, eojenole, farenzole, and borneol <xref ref-type="bibr" rid="ref5">AliAbadi et al., 2010</xref><xref ref-type="bibr" rid="ref8">AzadBakht, 2003</xref>. Garlic has cardiovascular effects, prevents cancer, has antidiabetic effects, and anti-microbial activity. The main active ingredient of this plant is called allicin <xref ref-type="bibr" rid="ref27">Heinrich and Larry, 1996</xref><xref ref-type="bibr" rid="ref33">Leistner and Gorris, 1995</xref>. Licorice is used to treat bloating, respiratory infections, peptic ulcers and gastritis. It is also used as antitussive, anti-hepatitis, and anti-tumor agent <xref ref-type="bibr" rid="ref9">Baba and Shigeta, 1993</xref><xref ref-type="bibr" rid="ref34">Lentihet and Nygren, 1997</xref><xref ref-type="bibr" rid="ref64">Sato et al., 1996</xref><xref ref-type="bibr" rid="ref37">Li et al., 2011</xref><xref ref-type="bibr" rid="ref26">Haraguchi et al., 1998</xref><xref ref-type="bibr" rid="ref16">Csuk et al., 2010</xref><xref ref-type="bibr" rid="ref21">Fukai et al., 2002</xref>. The major component of licorice is glycerisic acid <xref ref-type="bibr" rid="ref3">Alan Teck et al., 2007</xref><xref ref-type="bibr" rid="ref44">Mehravar, 1991</xref><xref ref-type="bibr" rid="ref42">Marzi et al., 1993</xref>. Cephalis ipecacuana is used in the treatment of cough, children&#8217;s bronchitis, and amoebic diarrhea. This plant has active compounds including emetine, and cephaline <xref ref-type="bibr" rid="ref72">Vetrichelvan et al., 1996</xref>.</p>
      <p>Asafoetida plant with compositions such as di-, tri-, tetra-Sulfide, coumarin derivatives, camuonephrole, episamarcandine, amblipernine, carnephrole, azafoetidine, froxolicin, azafoetidinole, saradaferine, 1, 8 cineole, scopodreniole, semen, sabinine, cineole, inaleole, eojenole, farenzole, borneol, allicin, acid glycerisic, emetine and cephalin has the potential for production of potent drugs against Leishmaniasis.</p>
      <p>Other compounds of these plants may also be involved in anti-leishmania activities of these plants. Phenolic compounds are a group of compounds which have been shown to be effective against a wide variety of microbial infections as well as other diseases <xref ref-type="bibr" rid="ref28">Hosseinzadeh et al., 2015</xref><xref ref-type="bibr" rid="ref39">Lorigooini et al., 2014</xref><xref ref-type="bibr" rid="ref38">Lorigooini et al., 2015</xref><xref ref-type="bibr" rid="ref22">Ghasemi and Lorigooini, 2016</xref>. They should be examined for treatment of Leishmaniasis and for preparation of new drugs.</p>
    </sec>
    <sec id="s5">
      <title>Conclusion</title>
      <p>There are some specific medicinal plants or compounds effective against Leishmaniasis which can be used per se or following changes in their formula to prepare and introduce new drags against Leishmaniasis.</p>
    </sec>
    <sec id="s6">
      <title>Abbreviations</title>
      <p>IC50= The half maximal inhibitory concentration</p>
    </sec>
    <sec id="s7">
      <title>Author Contribution</title>
      <p>All authors contributed to the design of the research. MB, NA, MH and MRK collected the data. MRK write, edited and revised it. All authors reviewed and commented on final draft</p>
    </sec>
  </body>
  <back>
    <ack id="ack">
      <title>Acknowledgements</title>
      <p>The authors would like to express their gratitude for financial support of the Research and Technology Deputy of Shahrekord University of Medical Sciences, Shahrekord, Iran.</p>
    </ack>
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