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<article article-type="research-article" dtd-version="1.2" xml:lang="en" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">compa</journal-id>
      <journal-title-group>
        <journal-title>CELLMED</journal-title>
        <trans-title-group>
          <trans-title xml:lang="ko">셀메드</trans-title>
        </trans-title-group>
      </journal-title-group>
      <issn pub-type="epub">2233-8985</issn>
      <publisher>
        <publisher-name>Cellmed Orthocellular Medicine and Pharmaceutical Association</publisher-name>
        <publisher-name xml:lang="ko">셀메드 세포교정의약학회</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">cellmed-2020-10-3-20.1</article-id>
      <article-id pub-id-type="doi">10.5667/CellMed.2020.0020</article-id>
      <article-categories>
        <subj-group>
          <subject>Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>A comprehensive review on <italic>Tukhm-e-Karafs</italic> (<italic>Apium graveolens</italic> L.) with special reference to Unani System of Medicine</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author" corresp="yes">
          <name name-style="western">
            <surname>Naushad</surname>
            <given-names>﻿Mohd</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
          <xref ref-type="corresp" rid="cor1">*</xref>
        </contrib>
        <contrib contrib-type="author">
          <name name-style="western">
            <surname>Zakir</surname>
            <given-names>Mohammad</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name name-style="western">
            <surname>Sahar</surname>
            <given-names>Najmus</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <name name-style="western">
            <surname>Kazmi</surname>
            <given-names>Munawwar Husain</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">4</xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label><italic>Assistant Professor, Sanskriti Unani Medical College &#x26; Hospital, Chhata, Mathura, India</italic>
      </aff>
      <aff id="aff2">
        <label>2</label><italic>Assistant Professor, Department of Ilmul Advia, National Research Institute of Unani Medicine for Skin Disorders (NRIUMSD), Hyderabad, India.</italic>
      </aff>
      <aff id="aff3">
        <label>3</label><italic>MD Scholar, Department of Ilmul Advia, National Research Institute of Unani Medicine for Skin Disorders (NRIUMSD), Hyderabad, India.</italic>
      </aff>
      <aff id="aff4">
        <label>4</label><italic>Professor, Department of Ilmul Advia, National Research Institute of Unani Medicine for Skin Disorders (NRIUMSD), Hyderabad, India.</italic>
      </aff>
      <author-notes>
        <corresp id="cor1">
          <label>*</label>﻿Correspondence: Mohd Naushad E-mail: <email>dr.naush97@gmail.com</email>
        </corresp>
      </author-notes>
      <pub-date pub-type="ppub">
        <day>31</day>
        <month>08</month>
        <year>2020</year>
      </pub-date>
      <volume>10</volume>
      <issue>3</issue>
      <fpage>20.1</fpage>
      <lpage>20.6</lpage>
      <history>
        <date date-type="received">
          <day>15</day>
          <month>05</month>
          <year>2020</year>
        </date>
        <date date-type="accepted">
          <day>04</day>
          <month>06</month>
          <year>2020</year>
        </date>
      </history>
      <permissions>
        <copyright-statement>Copyright &#x000a9; 2020, Cellmed Orthocellular Medicine and Pharmaceutical Association</copyright-statement>
        <copyright-year>2020</copyright-year>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/">
          <license-p>﻿This is an open access article under the CC BY-NC license. (<uri>http://creativecommons.org/licenses/by-nc/3.0/</uri>)</license-p>
        </license>
      </permissions>
      <abstract>
        <p>The <italic>Karafs</italic> is a dried herb of whole plant of <italic>Apium graveolens</italic> L. from Apiaceae (carrot family). The seeds (fruits) of <italic>Apium graveolens</italic> are known as <italic>Tukhm-e- Karafs</italic> in Unani Medicine. <italic>Karafs</italic> is known as Celeri in French, Apio in Spanish, Selderiji in Dutch, Syelderey in Russian and Chin in Chinese. It is cultivated in different parts of the world for its seeds as spice and green leaves and root as salad crop. Its seeds are also used for medicinal purposes in complementary and alternative medicines. In Unani it is used as a single drug or as an ingredient in compound formulations used for management in various ailments. The seeds have various pharmacological actions like hepatoprotective, diuretic and lithotriptic etc. It is commonly found in Western Asia, Europe, North Africa and various parts of India like Punjab, Uttar Pradesh and Himachal Pradesh etc. In Unani its actions are described as <italic>Mudirr-i-Bawl</italic> (Diuretic), <italic>Mufattit-i-Has&#x101;h</italic> (Lithotriptic), <italic>Dafi&#x2018;-i-Tashannuj</italic> (Antispasmodic) and <italic>K&#x101;sir-i-Riy&#x101;h</italic> (Carminative). It is used for the treatment of <italic>Hasah al-Kulya</italic> (Nephrolithiasis), <italic>Nafkh al-Mi&#x2018;da</italic> (Flatulence), <italic>Istisq&#x101;&#x2019;</italic> (Oedema) and <italic>Ihtib&#x101;s al-Bawl</italic> (Retention of urine) etc.</p>
      </abstract>
      <kwd-group>
        <kwd>﻿Apigenin</kwd>
        <kwd><italic>Apium graveolens</italic></kwd>
        <kwd><italic>Karafs</italic></kwd>
        <kwd><italic>Kulya</italic></kwd>
        <kwd>Nephrolithiasis</kwd>
        <kwd>Unani</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec id="s1" sec-type="intro">
      <title>1. ﻿INTRODUCTION</title>
      <p><italic>﻿Tukhm-e- Karafs</italic> is the seeds (fruit) of the <italic>Apium graveolens</italic> L. and frequently used in Unani system of Medicine for the treatment of various diseases. It is an erect, annual or biennial, aromatic glabrous herb, with succulent, well developed tap root, branching angular or fistular stem, pinnate or trifoliate leaves and white flower. The plant occurs from November to March. Flowering and fruiting take place during the month of February to March. It is wild as well as cultivated in many countries for its seeds and whole herb as a salad crop. It is an aromatic herb and also used as a medicine in many folklore. It is a believed to be native of Europe and Western Asia but cultivated in many countries now a day (Anonymous, 2007).</p>
    </sec>
    <sec id="s2" sec-type="other">
      <title>2. ﻿GEOGRAPHICAL DISTRIBUTION</title>
      <p><italic>﻿Tukhm-e-Karafs</italic> is globally distributed in Abyssinia, Afghanistan, Europe, Western Asia, and North Africa, Persia. In India it is found in various regions like Western India, North West Himalaya, Western Himalayas, Himachal Pradesh, Uttar Pradesh, Western Uttar Pradesh, Outlying Hills in the Punjab, Bengal, Bombay and Hills of Uttrakhand (<xref ref-type="bibr" rid="r024">Kirtikar, 1995</xref>; <xref ref-type="bibr" rid="r025">Kokate 2017</xref>; <xref ref-type="bibr" rid="r014">Dymock Warden, Hooper 1891</xref>; Anonymous, 2007; <xref ref-type="bibr" rid="r030">Nadkarni, 2000</xref>; <xref ref-type="bibr" rid="r014">Dymock et al., 1891</xref>; Anonymous, 2015; <xref ref-type="bibr" rid="r016">Ghani, 2011</xref>; <xref ref-type="bibr" rid="r031">Pulliaiah, 2006</xref>; Anonymous, 1950).</p>
    </sec>
    <sec id="s3" sec-type="other">
      <title>3. ﻿SELECTED VERNACULAR NAMES</title>
      <p><def-list>
	  <def-item><term>﻿Arabic</term><def><p>Habb-ul-<italic>Karafs</italic>, Samarul <italic>Karafs, Karafs</italic>, Tukhm-e-Karafs, Fitra Saliyun</p></def></def-item>
	  <def-item><term>English </term><def><p>Celery, Marsh Parsley, Smallage, Wild celery, Apium</p></def></def-item> <def-item><term>﻿French</term><def><p>Api, Apibausguas, Ache, Ache Cultivee</p></def></def-item>
	  <def-item><term>﻿German</term><def><p>Eppich, Sellerie, Sumpfeppich, Wassereppich, Wassermark, Wasserpeterlein, Wildersellerie</p></def></def-item> <def-item><term>﻿Italian</term><def><p>Appio, Sedano</p></def></def-item> 
	  <def-item><term>﻿Persian</term><def><p>Tukhm-e-<italic>Karafs</italic>, <italic>Karafs, Karafsh</italic>, Karasb, Tukhm-e-Karasb, <italic>Karafs</italic> kohi</p></def></def-item>
	  <def-item><term>Russian</term><def><p>Dikiy Selderei</p></def></def-item> 
	  <def-item><term>﻿Spanish</term><def><p>Apio, Apiocomun</p></def></def-item> 
	  <def-item><term>﻿Unani</term><def><p><italic>Karafsa</italic>, Saalyun</p></def></def-item> 
	  <def-item><term>﻿Hindi</term><def><p><italic>Karafs</italic>, Ajmod, Ajmad, Bari Ajmod, Ajmud, Boriajmud, Ajmoda</p></def></def-item> 
	  <def-item><term>Sanskrit</term><def><p>Ajmoda, Andha Patriki, Brahmakoshi, Dipyaka, Gandhadala, Mayura, Shikkimoda, Ugragandha, Vastamoda, Vishali</p></def></def-item>
	  <def-item><term>﻿Urdu</term><def><p>Tukhm-e-<italic>Karafs</italic>, Ajmod</p></def></def-item> 
	  </def-list></p>
	  <p>﻿(Anonymous, 2007; <xref ref-type="bibr" rid="r029">Nabi, 2007</xref>; <xref ref-type="bibr" rid="r024">Kirtikar, 1995</xref>; <xref ref-type="bibr" rid="r014">Dymock et al.,1891</xref>; <xref ref-type="bibr" rid="r028">Nasir et al., 1860</xref>; <xref ref-type="bibr" rid="r018">Hakim, 2002</xref>; <xref ref-type="bibr" rid="r020">Ibne-Baytar, 2003</xref>; <xref ref-type="bibr" rid="r030">Nadkarni, 2000</xref>; <xref ref-type="bibr" rid="r031">Pulliaiah, 2006</xref>).</p>
    </sec>
    <sec id="s4" sec-type="other">
      <title>4. ﻿DESCRIPTION</title>
      <p>﻿The seeds (fruits) of <italic>Tukhm-e- Karafs</italic> (<italic>Apium graveolens</italic> L.) ﻿are mostly separated mericarp. The cremocarp is brown ovoid, laterally compressed. Each mericarp has five straight, scarcely prominent primary ridges. Seeds are branched, circular, blackish in colour, Irregular surface, strong odour, pungent in taste, resembles <italic>Zeera</italic> (caraway). Stem is cylindrical occasionally branched, succulent, nodes are distinct and swollen, show well developed scaly leaves clasping the bases of the lateral branches, surface is longitudinally ridged and furrowed; colour yellowish green, Odour faintly aromatic; taste salty. Leaf is pinnate, large, 3 partite, with large deeply lobed segments and coarsely toothed at the apex, pale green in colour, Odour aromatic; taste salty and slightly bitter. Flowers are inflorescence which is a compound umbel with short peduncle. The flowers are small and white in colour. Its root is cylindrical tap root longitudinally started, odour aromatic, and taste salty (Anonymous, 2007; <xref ref-type="bibr" rid="r016">Ghani, 2011</xref>; <xref ref-type="bibr" rid="r031">Pulliaiah, 2006</xref>). According to Unani scholar the colour of the flower is <italic>zard</italic> (yellowish) and has thin branches. According to Unani scholar root is blackish and has fibrous branches and is considered as most powerful among all parts of <italic>Karafs</italic> (<xref ref-type="bibr" rid="r016">Ghani, 2011</xref>).</p>
    </sec>
    <sec id="s5" sec-type="other">
      <title>5. ﻿TUKHM-E-<italic>KARAFS</italic> (<italic>APIUM GRAVEOLENS</italic> L.) IN UNANI SYSTEM OF MEDICINES</title>
      <p>﻿The <italic>Mijāz</italic> (temperament) of <italic>Tukhm-e-Karafs</italic> is <italic>Hārr Yabis</italic> (Hot<sup>2</sup> &#x26; Dry<sup>2</sup>) or <italic>Hārr Yabis</italic> (Hot<sup>1</sup> &#x26; Dry<sup>2</sup>) (Anonymous 2007, <xref ref-type="bibr" rid="r029">Nabi 2007</xref>, <xref ref-type="bibr" rid="r016">Ghani 2011</xref>, <xref ref-type="bibr" rid="r018">Hakim 2002</xref>, <xref ref-type="bibr" rid="r020">Ibn Baytar 2003</xref>, <xref ref-type="bibr" rid="r019">Ibn Sina 1998</xref>). According to <italic>Jalinus</italic> (Galen), <italic>Karafs</italic> (<italic>Apium graveolens</italic> L.) and <italic>Kahu</italic> (<italic>Lactuca serriola</italic> L.) when mixed then <italic>Mizāj</italic> (temperament) of the product becomes <italic>Mu‘tadil</italic> (moderate) (<xref ref-type="bibr" rid="r020">Ibne-Baytar, 2003</xref>). <italic>Miqdār-i Khurak</italic> (dose) of <italic>Tukhm-e-Karafs</italic> as mentioned in literature is 3-5 gm and 6 gm (<xref ref-type="bibr" rid="r016">Ghani, 2011</xref>; <xref ref-type="bibr" rid="r029">Nabi, 2007</xref>; Anonymous, 2007; <xref ref-type="bibr" rid="r028">Nasir et al., 1860</xref>). The <italic>Muzir</italic> (side effects) of <italic>Tukhm-e-Karafs</italic> is <italic>Suda</italic> (Headache) especially in people having <italic>Hārr Mijāz</italic> (hot temperament). It produces adverse effects in pregnancy, epilepsy and hot temperament people so may be avoided in these conditions (<xref ref-type="bibr" rid="r028">Nasir et al. 1860</xref>, <xref ref-type="bibr" rid="r001">Ahmed et al. 2015</xref>). The <italic>Muslih</italic> (corrective) is used to reduce adverse effects or to improve efficacy of the drug. <italic>Anisoon</italic> (<italic>Pimpinella anisum</italic> L.), <italic>Ajwain Khurasani</italic> (<italic>Hyoscyamus niger</italic> L.), <italic>Mastagi Rumi</italic> (<italic>Pistacia lenticus</italic> L.), <italic>Kahu</italic> (<italic>Lactuca serriola</italic> L.) and <italic>Gulqand</italic> are generally used as corrective to the adverse effects of the <italic>Karafs</italic> (<xref ref-type="bibr" rid="r016">Ghani, 2011</xref>; <xref ref-type="bibr" rid="r018">Hakim, 2002</xref>; <xref ref-type="bibr" rid="r028">Nasir et al., 1860</xref>; <xref ref-type="bibr" rid="r029">Nabi, 2007</xref>). The <italic>Badal</italic> (substitute) of <italic>Karafs</italic> in conditions where it is not available is required. The substitute for whole herb is whole herb of <italic>Badiyan</italic> (<italic>Foeniculum vulgare</italic> Gaertn.) and for seeds substitute are seeds of <italic>Ajwain Desi</italic> (<italic>Trachyspermum ammi</italic> L.) and <italic>Zeera</italic> (<italic>Cuminum cyminum</italic> L.). The shelf life (<italic>Muddat-i-Hayāt</italic>) of <italic>Tukhm</italic> (seed) is about 2 years and for its roots 3 years (<xref ref-type="bibr" rid="r016">Ghani, 2011</xref>).</p>
      <sec id="s5a">
        <title>5.1 Therapeutic actions (<italic>Afa&#x2019;al</italic>) of Tukhm-e-<italic>Karafs</italic> (<italic>Apium graveolens</italic> L.)</title>
        <p><italic>Mudirr-i-Bawl</italic> (Diuretic), <italic>Mushtah&#x12B;</italic> (Appetizer), <italic>Mudirr-i-Hayd</italic> (Emmenogogue), <italic>Mufattit-i-Has&#x101;h</italic> (Lithotriptic), <italic>K&#x101;sir-i-Riy&#x101;h</italic> (Carminative), <italic>Mufattih-i- Sudad</italic> (Remove obstruction), <italic>Mu&#x2018;arriq</italic> (Diaphoretic), <italic>Muqawwi-i-B&#x101;h</italic> (Aphrodisiac), <italic>Muhallil</italic> (Resolvent), <italic>Musakkin-i-Dim&#x101;gh</italic> (Sedative), <italic>Mulayyin-i-Am&#x2018;&#x101;&#x2019;</italic> (Laxative), <italic>Q&#x101;til-i-D&#x12B;d&#x101;n</italic> (Anthelmintic), <italic>Mukhrij-i-Jan&#x12B;n</italic> (abortifacient), <italic>Muqaww&#x12B;</italic> (Tonic), <italic>Dafi&#x2018;-i-Tashannuj</italic> (Antispasmodic), <italic>Mugharr&#x12B;, Dafi&#x2018;-i-Maghs</italic> (Anti-tenesmus), <italic>Musakkin-i-Suda</italic> (Relieve Headache) and Beneficial in ophthalmic disease (Anonymous, 2007; <xref ref-type="bibr" rid="r016">Ghani, 2011</xref>; <xref ref-type="bibr" rid="r007">Azam, 2012</xref>; <xref ref-type="bibr" rid="r028">Nasir et al., 1860</xref>; <xref ref-type="bibr" rid="r029">Nabi, 2007</xref>; <xref ref-type="bibr" rid="r024">Kirtikar, 1995</xref>; <xref ref-type="bibr" rid="r030">Nadkarni. 2000</xref>; <xref ref-type="bibr" rid="r018">Hakim, 2002</xref>; <xref ref-type="bibr" rid="r019">Ibn Sina, 1998</xref>; <xref ref-type="bibr" rid="r020">Ibne-Baytar, 2003</xref>; <xref ref-type="bibr" rid="r023">Kabiruddin,2000</xref>).</p>
        <p><italic>Karafs</italic> is beneficial in management of <italic>Waja&#x2018;al-Kuly</italic>a (renal pain), <italic>Waja&#x2018; al-Mathana</italic> (Pain in bladder) and <italic>Waja&#x2018; al-Zahr</italic> (Backache) as described by Dioscorides. According to <italic>Mas&#x12B;h</italic>, it resolves obstruction in cavity of liver and spleen. It helps in healing wound that have morbid matter. Razi suggested that in hot temperament individuals, vinegar is to be added with <italic>Karafs</italic> before using it. Israyli said that when <italic>Kahu</italic> is used with <italic>Karafs</italic>, it act as corrective to <italic>Karafs</italic> and neutralize its taste. <italic>Karafs</italic> is <italic>musakkin</italic> (neutralize the heat of humours) and helps in starting menstruation or diuresis of urine. According to <italic>Jalinus</italic> (Galen) <italic>Karafs</italic> removes <italic>Nafkh al-Mi&#x2018;da</italic> (flatulence) due to accumulation of <italic>R&#x12B;h</italic> (gases), its seeds have more beneficial actions as compared to others parts of the plant. The potent calorific actions of <italic>Karaf</italic>s result in increment of flow of urine and menses. <italic>Karafs</italic> in powder form is more effective if given with honey (<xref ref-type="bibr" rid="r020">Ibne-Baytar, 2003</xref>). It removes <italic>Tha&#x2019;alil</italic> (warts) if applied with <italic>Naushadar</italic> (ammonium chloride). <italic>Karafs</italic> increase appetite if given with common salt (<xref ref-type="bibr" rid="r016">Ghani, 2011</xref>). In Ayurveda, its actions and uses are described as Stomachic, bronchitis, ascites and toothache. The powder of seeds is used for treatment of diarrhoea, dysentery, hoarseness of voice, indigestion and loss of appetite and impurity of breast-milk caused by <italic>vata</italic> (<xref ref-type="bibr" rid="r024">Kirtikar, 1995</xref>).</p>
      </sec>
      <sec id="s5b">
        <title>﻿5.2 Therapeutic Uses of Tukhm-e-<italic>Karafs</italic> (<italic>Apium graveolens</italic> L.)</title>
        <p><italic>Hasah al-Kulya</italic> (nephrolithiasis), <italic>Has&#x101;h al-Math&#x101;na</italic> (cystolithiasis), <italic>D&#x12B;q al-Nafas</italic> (bronchial asthma), <italic>Niqris</italic> (gout), <italic>&#x2018;Irq al-Nas&#x101;</italic> (sciatica), <italic>Waja&#x2018; al-Zahr</italic> (backache), <italic>Dh&#x101;t al-Janb</italic> (pleurisy), <italic>Istisq&#x101;&#x2019;</italic> (oedema), <italic>Nafkh al-Mi&#x2018;da</italic> (flatulence), <italic>Hud&#x16B;r</italic> (rheumatism), <italic>Ihtib&#x101;s al-Bawl</italic> (retention of urine), <italic>Waja&#x2018; al-Kulya</italic> (renal pain), <italic>Waja&#x2018; al-Math&#x101;na</italic> (cystodynia), <italic>Qay&#x2019;</italic> (vomiting), <italic>Maghs</italic> (tenesmus) and <italic>Suda</italic> (headache). If leaves of <italic>Karafs</italic> used with common salt it is effective in Diarrhoea. (Anonymous, 2007; <xref ref-type="bibr" rid="r016">Ghani, 2011</xref>; <xref ref-type="bibr" rid="r007">Azam, 2012</xref>, <xref ref-type="bibr" rid="r028">Nasir et al., 1860</xref>; <xref ref-type="bibr" rid="r029">Nabi, 2007</xref>; <xref ref-type="bibr" rid="r024">Kirtikar, 1995</xref>; <xref ref-type="bibr" rid="r030">Nadkarni, 2000</xref>; <xref ref-type="bibr" rid="r018">Hakim, 2002</xref>; <xref ref-type="bibr" rid="r019">Ibn Sina, 1998</xref>; <xref ref-type="bibr" rid="r020">Ibne-Baytar, 2003</xref>; <xref ref-type="bibr" rid="r023">Kabiruddin, 2000</xref>).</p>
      </sec>
      <sec id="s5c">
        <title>﻿5.3 Compound formulations containing Tukhm-e-<italic>Karafs</italic> (<italic>Apium graveolens</italic> L.) as an ingredient:</title>
        <p>﻿In Unani Medicine, drugs from plant, mineral and animal origin have been used either as single entity or in combination of more than one drug in specific proportioned mentioned in Unani Pharmacopoeias and National formularies. If more than one drug has been mixed in specific proportion and method then it is called compound formulation. The following compound formulations contain Tukhm-e-<italic>Karafs</italic> (<italic>Apium graveolens</italic> L.) as an ingredient in it. The actions of the formulation and their therapeutic effects are also mentioned with each:</p>
        <p><list list-type="bullet"> <list-item><p>&#xFEFF;<italic>Shiyaf-i-Kundur</italic> has <italic>Mujaffif</italic> (desiccant) action and used to treat <italic>Buth&#x16B;r-i-Chashm</italic> (eye eruptions).</p></list-item> <list-item><p>&#xFEFF;<italic>Banadiq-ul-Buzoor</italic> has <italic>Musakkin</italic> (sedative), Mudirr-<italic>i-Bawl</italic> (diuretic) and <italic>Mudammil</italic> (healing agent) actions and used to treat <italic>Qur&#x16B;h al-Kulya</italic> (ulcer of kidney), <italic>Qur&#x16B;h al- Math&#x101;na</italic> (ulcer of bladder) and <italic>Hurqa al-Bawl</italic> (burning micturition).</p></list-item> <list-item><p><italic>&#xFEFF;Jawarish-i-Falafili</italic> has <italic>Muharrik Rut&#x16B;bat Mi&#x2018;da</italic> (Gastric juice stimulant), <italic>Mulayyin</italic> (Laxative), action and used to treat <italic>Qabz</italic> (constipation), <italic>S&#x16B;&#x2019; al- H&#x101;dm</italic> (dyspepsia) and <italic>Waja&#x2018;al-Mi&#x2018;da</italic> (gastralgia).</p></list-item> <list-item><p>&#xFEFF;<italic>Jawarish-i-Safarjali</italic> has <italic>Qabiz, Muqaww&#x12B;-i- Mi&#x2018;da</italic> (stomachic), <italic>H&#x101;bis</italic> (hemostyptic, <italic>Dafi&#x2018;-i-Qay&#x2019;</italic> (antiemetics), <italic>H&#x101;dim</italic> (digestive) actions and used to treat <italic>Du&#x2018;f al-Mi&#x2018;da</italic> (weakness of stomach), <italic>Ish&#x101;l</italic> (diarrhoea) and <italic>Qay&#x2019;</italic> (vomiting).</p></list-item> <list-item><p>&#xFEFF;<italic>Jawarish-i-Shahreyaran</italic> has <italic>Mulayyin</italic> (laxative) and <italic>Mufattih-i- Sudad</italic> (remove obstruction) actions and used to treat <italic>Qabz</italic> (constipation), <italic>Q&#x16B;lanj</italic> (colic), <italic>Istisq&#x101;&#x2019;</italic> (oedema), <italic>Du&#x2018;f al-Kabid</italic> (hepatic insufficiency) and <italic>Du&#x2018;f al-Mi&#x2018;da</italic> (weakness of stomach).</p></list-item> <list-item><p><italic>&#xFEFF;Jawarish-i-Zarooni Sada</italic> has <italic>Mudirr-i-Bawl</italic> (diuretic), <italic>Mufattit-i-Has&#x101;h</italic> (lithotriptic) and <italic>K&#x101;sir-i-Riy&#x101;h</italic> (carminative) action and used to treat <italic>Du&#x2018;f al-e Kulya</italic> (renal Insufficiency), <italic>Has&#x101;h al-Math&#x101;na</italic> (baldder Stone), <italic>Hasah al-Kulya</italic> (renal Stone), <italic>Waja&#x2018;al-qutn</italic> (backache) and Waja&#x2018;al-Kulya (renal pain).</p></list-item> <list-item><p>&#xFEFF;<italic>Majoon Dabeed-ul-Ward</italic> has <italic>Mudirr-i-Baw</italic>l (diuretic), <italic>Muhallil Waram</italic> (anti-inflammatory) and <italic>Muwallid-i-dam</italic> (haemopoietic) action and used to treat<italic> Istisq&#x101;&#x2019;</italic> (oedema), <italic>Waram al- Kabid</italic> (hepatitis), <italic>Du&#x2018;f al-Kabid</italic> (hepatic insufficiency), <italic>Waram al-Rahim</italic> (uterine swelling), and <italic>Faqr al-dam</italic> (anaemia).</p></list-item> <list-item><p><italic>&#xFEFF;Majoon-i-Hajr-ul-Yahood</italic> has <italic>Mudirr-i-Bawl</italic> (diuretic) and <italic>Mufattit-i-Has&#x101;h</italic> (lithotriptic) action and used to treat <italic>Hasah al-Kulya</italic> (renal Stone), <italic>Has&#x101;h al-Math&#x101;na</italic> (baldder Stone), <italic>Hurqa al-Bawl</italic> (burning micturition) and <italic>Qilla al-Bawl</italic> (oliguria).</p></list-item> <list-item><p><italic>&#xFEFF;Majoon-i-Jalali</italic> has <italic>Muqaww&#x12B; -i-A&#x2018;s&#x101;b</italic> (nervine tonic), <italic>Muqaww&#x12B; -i-A&#x2018;d&#x101;&#x2019; Ra&#x2019;isa</italic> (tonic to vital organs), <italic>Muwallid-i-Man&#x12B;</italic> (spermatogenic) action and used to treat <italic>Du&#x2018;f al-ishtih&#x101;&#x2019;</italic> (anorexia), <italic>Du&#x2018;f al-Kulya</italic> (renal insufficiency), <italic>Du&#x2018;f al-b&#x101;h</italic> (anaphrodisia), <italic>Du&#x2018;f al- Mi&#x2018;da</italic> (weakness of stomach), <italic>Qilla al-Mani</italic> (oligospermia) and <italic>Du&#x2018;f al- A&#x2018;d&#x101;&#x2019; Ra&#x2019;isa</italic> (weakness of vital organ).</p></list-item> <list-item><p>&#xFEFF;<italic>Majoon-i-Jograj Gugal</italic> has <italic>Muhallil Waram</italic> (anti-inflammatory), <italic>Muqaww&#x12B; -i-A&#x2018;s&#x101;b</italic> (nervine tonic), <italic>Mulayyin</italic> (laxative) action and used to treat <italic>F&#x101;lij</italic> (hemiplegia), <italic>Ra&#x2018;sha</italic> (tremor), <italic>Laqwa</italic> (facial palsy), <italic>Du&#x2018;f al-A&#x2018;s&#x101;b</italic> (nervine weakness), <italic>Waja&#x2018;al-Maf&#x101;sil</italic> (polyarthritis), <italic>Baw&#x101;s&#x12B;r D&#x101;miya</italic> (bleeding Piles) and <italic>Waram al-Maf&#x101;sil</italic> (rheumatism).</p></list-item> <list-item><p><italic>&#xFEFF;Majoon-i-Kalkalanaj</italic> has <italic>Muhallil Waram</italic> (anti-inflammatory), <italic>Mudirr-i-Bawl</italic> (diuretic) and <italic>Mufattih-i Sudad</italic> (deobstruent) actions and used to treat <italic>Humm&#x101;</italic> (fever), <italic>Istisq&#x101;&#x2019;</italic> (ascites), <italic>Q&#x16B;lanj</italic> (colic), <italic>D&#x12B;q al-Nafas</italic> (bronchial asthma) and <italic>Ikhtin&#x101;q al-Rahim</italic> (hysteria).</p></list-item> <list-item><p>&#xFEFF;<italic>Sikanjabeen Buzoori Motadil</italic> has <italic>Mundij</italic> (concoctive) and <italic>Mulayyin</italic> (laxative) actions and used to treat <italic>Humm&#x101;</italic> (fever), <italic>Nazla</italic> (coryza), <italic>Su&#x2018;&#x101;l</italic> (cough) and <italic>Qabz</italic> (constipation).</p></list-item> <list-item><p>&#xFEFF;<italic>Sufoof-i-Namak Sheikh-ur-Raees</italic> has <italic>H&#x101;dim</italic> (digestive) and <italic>K&#x101;sir-i-Riy&#x101;h</italic> (carminative) actions and used to treat <italic>Du&#x2018;f al-Hadm</italic> (delayed digestion), <italic>Nafkh Shikam</italic> (flatulence) and <italic>Ghathay&#x101;n</italic> (nausea).</p></list-item> </list></p>
      </sec>
    </sec>
    <sec id="s6" sec-type="other">
      <title>﻿6. CHEMICAL CONSTITUENTS OF TUKHM-E-<italic>KARAFS</italic> (<italic>APIUM GRAVEOLENS</italic> L.)</title>
      <p><italic>T&#xFEFF;ukhm-e-Karafs</italic> contain <italic>Apiin</italic> a glycoside, this glycoside split up into glucose and <italic>Apigenin</italic>. <italic>Apigenin</italic> is isomeric with quinone. The seeds and herb yield a colourless or pale yellow essential oil. The other chemical constituents found in <italic>Karafs</italic> are Apiin, luteolin, apigenin, isoquercitrin, bergapten, myristic acid, chrysoeriol, apiosylglucoside, <italic>p</italic>-coumaric and ferulic acids, kaempferol, celereoside, apigravin, psoralen, umbelliferone, apiumetin, rutaretin carvone, piperitone, eugenol, &#x3B1;-pinene, terpinolene, menthone, &#x3B2;-carotene, vitamin &#xFEFF;A palmitate, vitamin K<sub>1</sub>, &#x3B1;-tocopherol, L-3-n-butylphthalide, DL-3-n-butylphthalide, N-butylphthalide, caryophyllene, butylphthalide, &#x3B2;-sitosterol, and myrcene (<xref ref-type="bibr" rid="r014">Dymock, Warden, Hooper, 1891</xref>; Anonymous, 2015).</p>
    </sec>
    <sec id="s7" sec-type="other">
      <title>7. ﻿PHYSICOCHEMICAL STANDARDS OF TUKHM-E-<italic>KARAFS</italic> (<italic>APIUM GRAVEOLENS</italic> L.)</title>
      <p>﻿Physicochemical standards of a drug ascertain the quality of the drug because the therapeutic actions depend upon the secondary metabolites and chemical constituents of the drug. The variation in the standards may result in disparity in the therapeutic actions. To avoid batch to batch variation and to get desired therapeutic effect at specified dose the standards should be checked in the crude drug before using it. The checking of standards is necessary whether drug is used as single entity or as an ingredient in the compound formulation. The following standards has been laid down for its quality check:</p>
      <p><list list-type="bullet"> <list-item><p>﻿Foreign organic matter: Not more than 1%</p></list-item> <list-item><p>﻿Ash: Not more than 10 %</p></list-item> <list-item><p>﻿Acid insoluble ash: Not more than 2%</p></list-item> <list-item><p>﻿Volatile oil: Not less than 1.5%</p></list-item> <list-item><p>﻿Specific gravity: 0.870 to 0.895</p></list-item> <list-item><p>﻿Optical rotation: +670 to +79<sup>0</sup></p></list-item> <list-item><p>﻿Moisture: 5 - 11% (seeds), 80.3-93.5% ( leaves),</p></list-item> <list-item><p>﻿Total ash: 6.9 - 11.0% (seeds)</p></list-item> <list-item><p>﻿Fibers: 1.4 - 10.2% (seeds)</p></list-item> <list-item><p>﻿Cold water extract: 5.9 - 12.9 % (seeds) (<xref ref-type="bibr" rid="r015">Fazal &#x26; Singla, 2012</xref>; <xref ref-type="bibr" rid="r004">Al-Snafi, 2014</xref>).</p></list-item> </list></p>
    </sec>
    <sec id="s8" sec-type="other">
      <title>﻿8. PHARMACOLOGICAL ACTIVITIES OF <italic>KARAFS</italic> (<italic>APIUM GRAVEOLENS</italic>)</title>
      <p>﻿Various pharmacological activities have been studies in animal studies and it has shown very promising actins. Some important studies and findings are given bellow:</p>
      <p>﻿Aqueous and Hexane extracts of seeds has shown anti-inflammatory activity (<xref ref-type="bibr" rid="r027">Momin R, 2002</xref>), its seed as a whole have demonstrated analgesic activity (<xref ref-type="bibr" rid="r001">Ahmed et al., 2015</xref>). Hydro-alcoholic extract of whole plant confirmed increase in spermatogenesis (<xref ref-type="bibr" rid="r026">Kooti et al., 2014</xref>). It has revealed anticancer effects when crude extract of plant is used (<xref ref-type="bibr" rid="r040">Varadharajan et al., 2011</xref>). Methanolic extract of seeds has shown antidepressant activity (<xref ref-type="bibr" rid="r012">Desu &#x26; Sivaramakrishna, 2012</xref>). Antihypertensive activity has been revealed by whole plant extract (<xref ref-type="bibr" rid="r022">Jorge et al., 2013</xref>) and hydro-alcoholic extract of whole plant and ethanolic extract of seeds has shown antihyperlipidemic activity (<xref ref-type="bibr" rid="r041">Wesam Kooti et al., 2014</xref>; <xref ref-type="bibr" rid="r002">Ahmed &#x26; Sayedda, 2012</xref>). Aqueous and Ethanol extract of leaves has shown spasmolytic activity (<xref ref-type="bibr" rid="r037">Suzana et al., 2015</xref>) while Methanolic extract of whole plant anti-Parkinson activity (<xref ref-type="bibr" rid="r010">Chonpathompikunlert et al., 2018</xref>). Hydro-alcoholic extract of seeds has revealed beneficial effects on Infection of kidney and bladder (UTI) (<xref ref-type="bibr" rid="r034">Sarshar et al., 2018</xref>). Gastric antiulcer, antisecretory and cytoprotective activity was demonstrated by its ethanol extract of aerial part of fresh herb (<xref ref-type="bibr" rid="r003">Al-Howiriny et al., 2010</xref>). Anti hyperuricemic activity has shown by hydro-alcoholic extract of whole plant (<xref ref-type="bibr" rid="r013"><underline>Dolati</underline> et al., 2018</xref>). Antihyperlipidemic and antitumor activity by ethanolic extract of seeds (<xref ref-type="bibr" rid="r021"><underline>Iyer D</underline> &#x26; Patil, 2019</xref>) and antidepressant and cognitive function improving activity by its Crude drug extract of whole plant was revealed (<xref ref-type="bibr" rid="r009">Boonruamkaew et al., 2017</xref>). Methanolic and aqueous extract of aerial part of herb has confirmed anti-ulcerogenic and antibacterial activities (<xref ref-type="bibr" rid="r008">Baananou et al., 2013</xref>). Methanolic extract of seeds has shown ﻿anti hepato-carcinogenesis activity (<xref ref-type="bibr" rid="r036">Sultana et al., 2005</xref>) while Methanolic extract of seeds has shown hepatoprotective activity (<xref ref-type="bibr" rid="r035">Singh &#x26; Handa, 1995</xref>). Crude seed extract has revealed anti-mosquito potential (<xref ref-type="bibr" rid="r011">Choochote et al., 2004</xref>).</p><table-wrap id="t001" position="float"> <label>Table 1.</label> <caption> <title>Pharmacological activities of Butylphthalide (a chemical constituent) obtained from <italic>Apium graveolens</italic> L.</title> </caption> <table rules="all" frame="box"> <thead> <tr valign="middle"> <th align="center">S. No.</th> <th align="center">Action/Disease</th> <th align="center">Form</th> <th align="center">References</th> </tr> </thead> <tbody> <tr valign="middle"> <td align="center">1</td> <td align="left">Alzheimer&#x2019;s disease</td> <td align="left">L-3-n-butylphthalide</td> <td align="left"><xref ref-type="bibr" rid="r047">Yu Zhang et al. 2016</xref> &#x26; <xref ref-type="bibr" rid="r042">Xiang et al. 2014</xref></td> </tr> <tr valign="middle"> <td align="center">2</td> <td align="left">Parkinson&#x2019;s disease</td> <td align="left">DL-3-n-butylphthalide</td> <td align="left"><xref ref-type="bibr" rid="r017">ZHOU et al. 2019</xref></td> </tr> <tr valign="middle"> <td align="center">3</td> <td align="left">Chronic epilepsy</td> <td align="left">L-3-n-butylphthalide</td> <td align="left"><xref ref-type="bibr" rid="r044">Ye et al. 2018</xref>, <xref ref-type="bibr" rid="r046">Zhang et al. 2017</xref></td> </tr> <tr valign="middle"> <td align="center">4</td> <td align="left">Protective effect on the neurotoxicity</td> <td align="left">L-3-n-butylphthalide</td> <td align="left"><xref ref-type="bibr" rid="r043">Yang et al. 2017</xref></td> </tr> <tr valign="middle"> <td align="center">5</td> <td align="left">Progressive cerebral infarction</td> <td align="left">DL-3n-butylphthalide</td> <td align="left"><xref ref-type="bibr" rid="r046">Zhang et al. 2017</xref></td> </tr> <tr valign="middle"> <td align="center">6</td> <td align="left">Antifungal</td> <td align="left">N-butylphthalide</td> <td align="left"><xref ref-type="bibr" rid="r045">Gong et al. 2019</xref></td> </tr> </tbody> </table> </table-wrap>
    </sec>
    <sec id="s9" sec-type="conclusions">
      <title>9. ﻿CONCLUSION</title>
      <p><italic>Karafs (Apium graveolens)</italic> is an important and useful drug of the Unani system, it has variety of actions and used as a single entity or with other drugs in compound formulation. It has Hot and dry temperament and as per Unani philosophy it can be used for diseases of cold temperament. It is successfully investigated for its action and uses in kidney diseases like, nephroprotective activity, diuretic activity, lithotriptic activity etc. in animal models. It has several bioactive secondary metabolites which are responsible for its various actions. As Unani system believes in holism and whole body is treated as a unit in case of any disease so it has been used in its crude form. Its antihypertensive activity may be due to its diuretic activity. It&#x2019;s anticancer, antitumor and cytoprotective activities suggest that it can be used successfully in treatment of carcinoma without destroying normal healthy cells. Antiparkinson, antidepressant and memory improving activity suggests its possible therapeutic use in depression, insomnia, amnesia and alzheimer disease. Its anti-inflammatory and antimicrobial activities suggest its use in infectious diseases and fevers. Due to its proven antihyperlipidemic activity it can be used in obesity, polycystic ovarian syndrome and many cardiac problems.</p>
      <p>﻿According to Unani literature, it may be used to treat backache, bronchial asthma, cystolithiasis, flatulence, gout, headache, nephrolithiasis, oedema, pleurisy, renal pain, retention of urine, rheumatism, sciatica, tenesmus and vomiting as a single drug. The modern work on its activity on respiratory system to treat bronchial asthma, pleurisy may be explored on animal model to validate Unani claim. Its action on joint pains and rheumatism may also be explored by animal studies. The validated claims in animal studies may be further authenticated by clinical trials or studies to confirm it. The pharmacological activities depends upon various phytochemical in plants but In Unani, whole plant or its part or its product is used in natural form because body can digest, metabolize and retain natural ingredients easily without producing adverse effects. The natural drugs have some micronutrients also and these may be helpful to replenish the deficiency of these nutrients. The natural drugs also have some ingredients which may provide some energy to the tissue and body during the digestion process. ﻿It also helps body to improve immunity and to fight the disease properly. The phytochemicals may be explored and tested for different actions produced by each constituent to validate the Unani claims of its action but it should be used as a whole in natural form to avoid adverse effects.</p>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="conflict">
        <p><bold>﻿CONFLICT OF INTEREST</bold> Authors have no conflict of interest to declare.</p>
      </fn>
    </fn-group>
    <ack>
      <p>﻿None.</p>
    </ack>
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