Chelidonium majus L. (Papaveraceae) morphology, anatomy and traditional medicinal uses in Turkey

Abstract

Background and Aims: Chelidonium majus is known as “kırlangıç otu” in Turkey and the different plant parts, especially the latex and aerial parts have been used as folk medicines for different purposes such as digestion, hemorrhoids, jaundice, liver, eye, and skin diseases. Despite the traditional uses of Chelidonium, there have been no detailed anatomical studies related to this species.
Methods: The description and distribution map of C. majus was expended according to herbarium materials and an ana- tomical study was made using fresh materials. The information related to traditional uses and local names of this species was evaluated from ethnobotanical literature in Turkey. For anatomical studies freehand sections were prepared using razor blades and sections were double-stained with Astra blue and safranin.
Results: In the anatomical study, epidermal sections containing trichome and stomata characters were elucidated. The leaves are bifacial and hypostomatic. The stomata are anomocytic in the paradermal section. The cross-section of the stem showed multi-layered parenchymatous cells in the cortex and a single-layered endodermis with simple eglandular trichomes. The cross-section of the root showed that the epidermis was replaced with the periderm. Under the phloem, which had few lay- ers, the xylem was composed of tracheary elements surrounded by sclerenchymatous cells.
Conclusion: Our results indicated that the morphological and anatomical characters alongside articulated laticifers and latex properties provide useful tools for the identification of this taxon from the other genera in the Papaveraceae family.
Keywords: Anatomy, Chelidonium majus, morphology, traditional uses, Turkey

Full text

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Istanbul J Pharm 51 (1): 123-132
DOI: 10.26650/IstanbulJPharm.2020.0074
Original Article
Chelidonium majus L. (Papaveraceae) morphology,
anatomy and traditional medicinal uses in Turkey
Golshan Zare , Nezha Yağmur Dker , Zekye Ceren Arıtuluk , İffet İrem Tatlı Çankaya
Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Botany, Ankara, Turkey
ORCID IDs of the authors: G.Z. 0000-0002-5972-5191; N.Y.D. 0000-0002-3285-8162; Z.C.A. 0000-0003-3986-4909;
İ.İ.T.Ç. 0000-0001-8531-9130
Cite this article as: Zare, G., Diker, N. Y., Arituluk, Z. C., & Tatli Cankaya, I. I. (2021). Chelidonium majus L. (Papaveraceae)
morphology, anatomy and traditional medicinal uses in Turkey. İstanbul Journal of Pharmacy, 51(1), 123-132.
ABSTRACT
Background and Aims: Chelidonium majus is known as “kırlangıç otu” in Turkey and the different plant par ts, especially the latex
and aerial parts have been used as folk medicines for different purposes such as digestion, hemorrhoids, jaundice, liver, eye,
and skin diseases. Despite the traditional uses of Chelidonium, there have been no detailed anatomical studies related to this
species.
Methods: The description and distribution map of C. majus was expended according to herbarium materials and an ana-
tomical study was made using fresh materials. The information related to traditional uses and local names of this species
was evaluated from ethnobotanical literature in Turkey. For anatomical studies freehand sections were prepared using razor
blades and sections were double-stained with Astra blue and safranin.
Results: In the anatomical study, epidermal sec tions containing trichome and stomata character s were elucidated. The leaves
are bifacial and hypostomatic. The stomata are anomoc ytic in the paradermal section. The cross-section of the stem showed
multi-layered parenchymatous cells in the cortex and a single-layered endodermis with simple eglandular trichomes. The
cross-section of the root showed that the epidermis was replaced with the periderm. Under the phloem, which had few lay-
ers, the xylem was composed of tracheary elements surrounded by sclerenchymatous cells.
Conclusion: Our results indic ated that the morphological and anatomical characters alongside ar ticulated laticifers and latex
properties provide useful tools for the identification of this taxon from the other genera in the Papaveraceae family.
Keywords: Anatomy, Chelidonium majus, morphology, traditional uses, Turkey
Address for Correspondence:
Golshan ZARE, e-mail: golshanzare@gmail .com
This work is licensed under a Creative Commons At tribution 4.0 International License.
Submitted: 30.07.2020
Revision Requested: 11.09.2020
Last Revision Received: 15.09.2020
Accepted: 14.10.2020
INTRODUCTION
Papaveraceae Juss. is a medicinally important family comprising 23 genera and ca. 240 species found mainly in the Northern
Hemisphere (Kadereit, 1993). All the family members arelactiferous with a well-developed duct system that produces a different
kind of latex, from milky or watery white to yellow or red juice in all parts of the plant.
Chelidonium L. (greater celandine) from the Chelidonieae tribe is a world-wide distributed genus from temperate Eurasia to
Northwest Africa and the Atlantic coasts of America (Cullen, 1965). Although this genus has been considered a monotypic ge-
nus for a long time, Krahulcová (1982) divided it into two separate species according to their different chromosome numbers
and distribution areas: Chelidonium majus L. (2n=12) distributed in Europe, Siberia and China and C. asiaticum (H. Hara) Krahulc.
(2n=10) distributed in East Asia and Japan. C. majus is one of the oldest medicinal plants, having been in use since ancient times,
and Dioscorides and Pliny describe its uses to treat different diseases (Zielinska et al., 2018).

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Istanbul J Pharm 51 (1): 123-132
Chelidonium, also known as greater celandine or devil’s milk,
has been used in various complementary and alternative med-
icine (CAM) systems including homeopathy and Traditional
Chinese Medicine (TCM) to treat various skin disorders such
as papillae, warts, condylomas, as well as ulcers, cancer, oral
infection, liver disorders, chronic bronchitis, asthma, and gen-
eral pain (EMA, 2010; Aljuraisy Mahdi & Al-Darraji, 2012; Maji &
Pratim, 2015; Hao, Gu & Xiao, 2015; Nawrot et al., 2017).
The latex of this species has been used externally for the treat-
ment of skin conditions such warts, calluses, wounds, herpes,
and cons in Iran (Miraldi, Ferri & Mostaghimi, 2001) and in Eu-
ropean countries including Croatia (Prieroni et al., 2003;Varga,
Solic, Dujakovic, Luczaj& Grdisa, 2019), Georgia (Bussman et al.
2017), Portugal (Gaspar et al., 2002; Novais, Santos, Mendes &
Pinto-Gomes, 2004; Neves, Matos, Moutinho, Queiroz & Gomes,
2009), Slovenia (Lumpert & Kreft, 2017), Albania (Pieroni, Dibra,
Grishaj, Grishaj, Maçai, 2015), Romania (Papp, Birkas-Frendl,
Farkas & Pieroni, 2013), Italy (Leporatti & Ivancheva, 2003; Bel-
lia & Pieroni, 2015; Guarrera, Forti & Marignoli, 2005; Dei Cas et
al., 2015; Menale et al., 2006; Passalacqua, Guarrera & De Fine,
2007; Cornara, La Rocca, Terrizzano, Dente, F. & Mariotti , 2014;
Fortini, Marzio, Guarrera & Iorizzi, 2016), Bosnia and Herze-
govina (Redzic, 2007; Saric-Kundalic, Dobes, Klatte-Asselmeyer
& Saukel, 2010; 2011; Savic Macukanovic-Jocic & Jaric, 2019),
Kosovo (Mustafa et al. 2012), Spain (Blanco, Macia & Morales,
1999; Gonzalez-Hernandez Romero, Rodriguez-Guitian &
Rigueiro, 2004; Benitez, Gonzalez-Tejero & Molero-Mesa, 2010;
Calvo, Akerreta & Cavero, 2011; Rigat et al., 2015;), and Monte-
negro (Menkovic et al., 2011) (Figure 1). However, the leaves,
flowers or aerial parts of C. majus are used internally in liver
and gallbladder complaints in several countries (Ivancheva &
Statcheva, 2000; Leporatti & Ivancheva, 2003; Pieroni, Dibra,
Grishaj, Grishaj & Maçai, 2005; Jaric et al., 2007; Menkovic et al.,
2011; Savikin et al. 2013; Jaric et al., 2015). Besides these, it is
used for the treatment of bronchitis, lithontriptic, stomach ul-
cers in Kosovo (Mustafa et al., 2012), for lung cancer in Bosnia
and Herzegovina (Redzic, 2007), for diarrhea, asthma, and gas-
tric disorders in Iran (Miraldi, Ferri & Mostaghimi, 2001), for cold,
asthma, bronchitis, and pneumonia in Spain (Menendez-bace-
ta et al. 2014), as abortifacient in Italy (Idolo, Motti & Mazzoleni,
2009), against cancer, for hemorrhoids and blood cleansing in
Ukraine, as well as for kidney problems in Romania (Soukand &
Pieroni, 2016) (Figure 1).
In Turkey, C. majus is called “kırlangıç otu” (Güner, Aslan, Ekim,
Vural & Babaç, 2012) and it has been used as a traditional me-
dicinal plant for 26 different purposes in ten provinces mainly
located in the Northwestern parts of Turkey.
The aerial parts, leaves and flowers of the plant are used both
externally and internally, while the latex is used only externally
for the treatment of skin diseases. Applying the latex directly to
remove warts is the most common medicinal use of the plant
(Uzun et al., 2004; Kültür, 2007; Ünsal, Vural, Sarıyar, Özbek &
Ötük 2010; Kızılarslan & Özhatay, 2012; Akbulut & Özkan, 2014;
Sargın, Akçicek & Selvi, 2013; Saraç, Ozkan & Akbulut, 2013;
Sargın, Selvi & Lopez, 2015; Polat, Cakilcioglu, Kaltalioğlu, Ulu-
san & Türkmen, 2015; Mumcu & Korkmaz, 2018). The traditional
medicinal uses ofC. majusin Turkey are presented in Table 1.
The greater celandine herb has been approved by both the
European Pharmacopoeia and Turkish Pharmacopoeia. In ad-
dition, it has also been included in Commission E monographs
for its use in spastic discomfort of the bile ducts and gastroin-
testinal tract, gall bladder and skin diseases (EMA, 2010; WHO,
2010; Görsöz, 2018). Pharmacological studies indicated Cheli-
donium extracts have anti-viral (Zuo, 2008; Gilca, Gamana, Pa-
naita, Stoian & Atanasiu 2010), anti-microbial (Kokoska, 2002),
anti-tumor, anti-inflammatory (Lee, 2007) and analgesic prop-
erties (Huang, 1999).
Chelidonium is a particularly well-known genus because of the
presence of numerous therapeutically important alkaloids lo-
cated in the different parts of the plant, especially in the latex.
More than forty alkaloids including phenanthridine (3,4-ben-
zylisoquinoline), protoberberine, protopine, quinolizidine,
aporphine) have been isolated from Chelidonium (Kedzia,
Łozykowska, & Gryszczynska, 2013; Hao, Gu & Xiao, 2015; Zie-
linska et al., 2018). Isoquinoline alkaloids are pharmacologically
relevant substances of this taxon (Grosso et al., 2014; Zielinska
et al., 2018).
According to the therapeutic potential and traditional uses of
C. majus and its hepatotoxic effect in chronic administration
(EMA, 2010; WHO, 2010; Pantano et al., 2017), it is important to
conduct morphological and anatomical studies to provide reli-
able diagnostic characters for the identification of raw material
and commercial samples to avoid any unwanted toxic harm.
Despite the medicinal uses of Chelidonium species, there has
not been any detailed research on the anatomical and mor-
phological properties of the genus in Turkey. In this study, we
provide detailed anatomical properties of C. majus, expanded
morphological information and a distribution map based on
Turkish samples. In addition, the traditional uses of this plant in
Turkey are discussed in detail.
MATERIAL AND METHODS
Fresh plant materials at the flowering period were collected
from Ankara, Turkey in June 2019 by Golshan Zare (GZ1309).
Voucher specimens were deposited in the Hacettepe Univer-
sity Faculty of Pharmacy Herbarium under the classification
code HUEF20008. For morphological investigation, 44 speci-
Figure 1. Distribution map of countries with traditional use of
Chelidonium.

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Zare et al. Chelidonium majus L. (Papaveraceae) morphology, anatomy and traditional medicinal uses in Turkey
mens of C. majus from the Ankara University Faculty of Science
Herbarium (ANK), Hacettepe University Faculty of Science Her-
barium (HUB), Ankara University Faculty of Pharmacy Herbari-
um (AEF), Hacettepe University Faculty of Pharmacy Herbari-
um (HUEF) and Edinburgh (E) Virtual Herbarium were studied
and Flora of Turkey and the East Aegean Islands (Cullen, 1965)
were followed for terminology and description order. The dis-
tribution information related to herbarium samples, records of
flora in Turkey and the East Aegean Islands and the collected
fresh materials of C. majus were plotted on a map (Figure 2).
Determination and measurement of microscopic characters
were done by means of direct observation under Leica Stereo
Microscopes (Model EZ4) and photographed.
Fresh specimens (GZ1309) were used for the anatomical in-
vestigations and cross-sections were prepared from leaves (at
middle), stems (basal and top), pedicels and roots. Paradermal
Table 1. Traditional medicinal uses of C. majus in Turkey.
Province Local name Parts Used Preparation Administration* Use Literature
Afyonkarahisar Kırlangıç otu Aerial part s Infusion Int. Digestion, hemor-
rhoids, jaundice,
liver, eye disease,
skin diseases
Arı et al.,
2015
Bilecik Kırlangıç otu Latex Raw Ext. Warts Unsal et al.,
2010
Giresun Kına otu Flowers Decoction Ext. Warts Polat et al.,
2015
Leaves
Izmit Temre otu Aerial part s Infusion Int. Diuretic Kızılarslan
and Özha-
tay, 2012
Latex Raw Ext. Wounds, eczema
Kırklareli Sarılık otu,
Sultan otu,
yara otu,
temra otu,
mayasıl otu
Herba Decoction Ext. Hepatitis Kültür, 2007
Int.
Latex Raw Ext. Inflamed wounds,
wounds, warts,
itching, hemo-
static
Leaves Decoction Ext. Rheumatism,
sciatica
Manisa Siğil otu,
Bostan otu
Aerial part s Infusion Int. Spasm, dyspepsia,
gastrointestinal
diseases
Sargın et
al., 2013;
Sargın et
al., 2015
Raw Ext. Carminative, cos-
tiveness, war ts,
corns
Leaves Mash Ext. Warts Sargın et
al., 2013;
Rize Mecmenuk
çayırı
Aerial part s Raw Ext. Eczema, warts,
acne
Saraç et al.,
2013
Sakarya --- Aerial part s Infusion Int. Eczema Uzun et al.,
2004
Samsun Kır langıç otu Aerial part s --- Int. Diuretic, purga-
tive, caustic
Mumcu and,
Korkmaz,
2018
Latex --- Ext. Warts, ringworm
Trabzon Temre Latex Raw Ext. Skin diseases Akbulut
and Ozkan,
2014
*Int.: Internal; Ext: External
Figure 2. Distribution map of C. majus in Turkey.

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Istanbul J Pharm 51 (1): 123-132
sections were also performed for leaves. Freehand sections
were prepared using razor blades and sections were cleared
with sodium hypochlorite and then stained by double stain
with Astra blue and safranin. Slides were observed with a Leica
CME light microscope and photographed.
RESULTS AND DISCUSSION
Morphology
Chelidonium majus L., Sp. Pl. 505 (1753).
Kırlangıç otu (Güner, Aslan, Ekim, Vural & Babaç, 2012).
Type: Described from Europe (Hb. Linn. 668/1).
Synonyms: C. laciniatum Mill., Gard. Dict., ed. 8. n. 2 (1768). C.
majus var. grandiflorum DC., Syst. Nat. 2: 99 (1821). C. laciniatum
var. fumariifolium DC., Syst. Nat. 2: 100 (1821). C. umbelliferum
Stokes, Bot. Mat. Med. 3: 180 (1812).
Perennial herb, 30–70(–100) cm, branched at the base. Rhizome
thick, fleshy, reddish-brown. Stem erect, branched with bright
orange sap, sparsely pubescent, especially on the nodes, woody
stock covered by persistent leaf. Basal leaves petiole 2–14 (18) cm,
blade glaucous abaxially with conspicuous veins, green adaxially,
obovate-oblong or broadly obovate, 8–20 cm, abaxially sparsely
pubescent especially on the veins, adaxially glabrous, bipinnatifid
or pinnatisect, lobes 2–4 pairs, obovate-oblong, irregularly parted
or lobed; lobe margin crenate. Cauline leaves alternate, petiole
5–18 mm; blade 2–12 (–15) x 1–8 cm, leaves pinnate with 5–7
broad leaflets, the terminal leaflet often 3-fid, ovate to oblong.
Inflorescence nearly umbellate with flowers (2) –5–7 (8). Pedicel
tenuous, 2–8 cm, pubescent when young, later glabrous. Flowers
2–2.5 cm across. Sepals 2, free, caducous, ovoid, 5–8 mm, glabrous
or sparsely pubescent. Petals 4, yellow, obovate, 10 x 8–15 mm,
entire. Stamens 8 mm numerous. Filaments yellow, anthers ob-
long. Style short, with 2 spreading stigma-lobes (Figure 3). Ovary
linear, 1 cm, glabrous. Fruit slender siliqua-like capsule (2) 30–60 x
2–4 mm, torulose, glabrous, monolocular, without a septum, ba-
sipetal, opening from below by 2 valves, many seed, pedicel the
same as or usually shorter than fruit. Seeds 1–2 mm, dark brown
or black, shiny in fresh material, reticulate patterned, with a white
appendage, ovoid, alveolate (Figure 4).
Flowering time: April-August.
Habitat: Shaded ground in woods and thickets, sea level-2000
m.
Phytogeographic region: Euro-Siberian element.
World distribution: Widespread in Asia, North America and
whole Europe, Northwest Africa; it grows in forests and open
shrubby areas, shady, ruderal sites.
Turkey distribution: West and Black Sea regions (Figure 2).
Examined specimens: A2(E) Istanbul: Kestanesou, 22.06.1895
Aznavour (E!); Bursa: Uludağ to Soğukpınar, 500-1000 m,
16.05.1962, Dudley 34741(E!). A3 Bolu: Karadere to Yedigöl, 650
m, 18.06.1962, P.H.Davis & Coode, 37688 (E!); Bolu to Abant lake,
800-900 m, 14.07.193, S. Fehmi (ANK!); Yedigöller National Park,
1000 m, 13.06.1977, R. İlarslan 102 (ANK!); Düzce: Aşağıkaraköy,
Çilimli, 2000 m, 16.05.2009, A. Mine Gençler Özkan, İ. Gürbüz, G.
Akaydın, E. Miser 26472 (AEF!); Akçakoca, Küpler village, 350-370
m, 22.07.2002, A. Doğru Koca 1864 (HUB!); Ankara: between
Beypazarı and Kıbrısak, around Yiğenler village, 1050-1300
m 01.06.2001, Ali A. Dönmez 8953 (HUB!); Ankara: Çankaya,
Bülbülderesi, by the road, 945 m, 20.06.2019, G. Zare 1309
(HUEF!); A4 Zonguldak: Amasra, 14.04.1985, Venter (HUB!); An-
kara: Beypazarı, Dereli, 1300 m, 02.07.1978, Y. Akman 75 (ANK!);
Ankara: Çubuk, Karagöl, around the lake, 1500 m, 23.05.1973,
Figure 3. A, Habitus; B, flower and inflorescence; C, capsule fruit; D,
flower buds with trichomes.
Figure 4. A, Fruit; B, fruit longitudinal sections; C, fruit Transverse
sections; D, seed.

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Zare et al. Chelidonium majus L. (Papaveraceae) morphology, anatomy and traditional medicinal uses in Turkey
S. Erik 423 (HUB!); Kızılcahamam, around Güven, 1200 m,
13.06.1992, M. Koyuncu 9792 (AEF!); ibid., 22.07.2002, H. Du-
man 2291 (AEF!); Seyhamamı, stone pit, 1000 m, 27.07.1975, B.
Kasaplıgil, S. Başaran (AEF!); Maden suyu, 1000 m, 17.07.1977, K.
Karamanoğlu, M. Coşkun 14513 (AEF!); Kızılcahamam, Çamları
village, 02.07.1948, K. Karamanoğlu 522 (ANK!); Kastamonu: Az-
davay to Cide, 800 m, 31.07.1962, P.H.Davis 38690 (E!); between
Cide-Kızılca, 900 m, 12.06.1979, O. Ketenoğlu 1387 (ANK!);
İnebolu, 18.04.1932, W. Katte (ANK!). A5 Kastamonu: Yağalar vil-
lage, 1500 m, 12.06.1975, M. Kılıç 3324 (ANK!); Ayancık, Çangal,
1100 m, 11.08.1945, Bakı Kasaplıgil (ANK!); Amasya, 30.06.1893, A.
Manissadjian 754 (E!). A6 Tokat: Ar tova, Aktaş, Çal Tepe, ca. 1300-
1400 m, 16.07.19, R. İlarslan 588 (ANK!). A7 Giresun: Gengene
village, 700 m, 24.06.1977, Y. Akman 702 (ANK!); Gümüşhane:
Harava village, 1100 m, 17.08.1983, Ş. Yıldırımlı 5736 (HUB!). A8
Trabzon: Sürmene, around Köprübaşı, 700 m, 29.04.1982, A.
Güner 4292, B. Yıldız (ANK! AEF!); Uzungöl castel, 28.07.1994, N.
Tanker, M. Koyuncu, M. Yıldız, S. Kuruas (AEF!); Rize: Çamlıhemşin,
near Zilkale, c. 700 m, 16.08.1980, A. Güner 3061 (HUB!); Salarha,
Kömürcüler village, 200 m, 21.04.1985, A. Güner 6282, M. Bilgin
(HUB!); 2. km from Güneyce to İkizdere, 320 m, 26.03.1983, A.
Güner 4610, B. Yıldız, M. Bilgin (HUB!); Artvin: Arhavi, around Or-
tacalar, 750 m, 21.04.1984, M. Koyuncu 6782, T. Ekim, A. Güner,
M. Bilgin (AEF!); Dikyamaç village, 750 m, 22.04.1997, M. Coşkun
19870 (AEF!); Alaca (Tiryal) southeast slope, 163 m, 14.06.1978,
A. Düzenli 895 (ANK!); Artvin: Dikyamaç village, 05.06.1993, M.
Coşkun 184 (AEF!); Borçka, 50 m, 18.05.1985, Ş. Yıldırımlı 7876
(HUB!); Çoruh, 1100 m, 28.04.1960, Stainton 8301(E!). A9 Artvin:
Çoruh, Ardanuç to Kordevan mountain, 1450 m, 27.06.1957, D.
30140 (E!); Kars: Posof, 1600-1750 m, 29.06.1986, N. Demirkuş
3658 (HUB!). B3 Afyonkarahisar: Şuhut, Koçyatağı village,
28.05.2003, 1200 m, Ahmet Sezgin 03048 (HUEF!); Eskişehir:
Türkmen mountain, 1400 m, 07.06.1985, T. Ekim 2550 (ANK!). B5
Kayseri: Hisarak, 14.06.1944, H. Bağda (ANK!).
Anatomy
The anatomical structures of the specimen were determined
by examination of the root, stem, pedicel and leaf cross-sec-
tions. Additionally, the stomatal index of the species is present-
ed in Figures 5-8.
Trichome: The surfaces of all parts of this species contain sim-
ple, uniseriate (4-6 cell) and eglandular trichomes whose den-
sity show variation in different parts of individuals and among
the population (Figures 5 A-C). On the leaf surface, trichomes
are dorsiventral and density is higher on the veins and nods.
Leaves: Cross-sections of the leaf blades in both surfaces con-
tain epidermal cells with sinuous anticlinal walls covered by a
thin layer of cuticula. The superior epidermis of the leaf con-
sists of 4-6 angled, rectangular, anisodiametric cell layers and
stomata are absent. Mature epidermis cell size is 79.16±16.35
x 26.66±5.77µm. Leaves are hypostomatous and stomata are
confined to the lower surface (abaxial). Stomata type is ranun-
culaceous (anomocytic) and guard cells are surrounded with
4-6 cells which are not distinct from the remaining cells in the
mature epidermis (Figure 5 D-E). Upper epidermis have slightly
larger cells than lower epidermis. These cells are significantly
wavy in anticlinal walls, with 21±4.0 µm width in narrow the
Figure 5. Transverse sections of the epidermis, A-C, uniseriate hairs; D,
adaxial epidermis; E, abaxial epidermis with ranunculaceous type
stomata. Scale bars: (D, E) 50 μ.
Figure 6. Transverse sections of Leaf. A, C, and D, midrib; B, blade; ca,
cambium; ue, upper epidermis; le, lower epidermis; pa, palisade cell;
sp, spongy parenchyma cell; ph, phloem; t, trichome; xy, xylem. Scale
bars: (A), 200 μ, (B, C, D) 50 μ.
Figure 7. Transverse sections of stem and pedicel. A-F Stem; G-L,
pedicel. ca, cambium; co, cortex; ue, upper epidermis; le, lower
epidermis; pa, palisade cell; sp, spongy parenchyma cell; ph, phloem;
pi, pith region; vb, vascular bundle; sc, secretery cell; xy, xylem. Scale
bars: (A, B, G) 500 μ, (D, H), 200 μ, (C, E, F, L) 50 μ.

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Istanbul J Pharm 51 (1): 123-132
part, 73.00±9.2 µm width in the large part of the cells and
42.36±3.98 µm length. The inferior epidermis consists of nu-
merous stomata whose rounded shape and stomata index is
19.66±1.61 (mm2). Stomata size is 21.5 ± 2.1. x 21.13±2.0 µm.
In leaf cross-section slides indicated leaves have bifacial (dor-
siventral) structure and the palisade layer is restricted to the
upper side (Adaxial). Leaf thickness is between 180–200 μm
and the mesophyll structure generally includes one or several
layers of palisade parenchyma cells under the upper epidermis
and thin-walled spongy parenchyma cells with wide intercel-
lular spaces. However, the transverse region is sometimes not
distinctly differentiated into palisade and spongy regions (Fig-
ures 6). The leaf main vein thickness is 800-1100 μm, contains
1-3 layers of collenchyma under the epidermis and 3-5 layers
of thin-walled parenchyma cells with different sizes between
the collenchyma layer and the arc-shaped vascular bundles. In
this area, a few calcium oxalate crystals were seen in the cells.
Veins contain numerous collateral vascular bundles, with the
xylem located on the upper side and phloem located on the
lower side, and in main vein latex cells found in the vascular
region (Figure 6).
Stem: The stem transverse section in the young part is circular
and in the old part tends to show a pentagonal shape with
rounded corners. The outer part is covered with a single layer
of epidermal cells with a thin cuticula. Multicellular simple tri-
chomes are seen on the epidermis. Immediately under the epi-
dermis single or multi-layered collenchymatous cells were de-
tected. The cortex consists of multi-layered parenchymatous
cells that have various shapes and sizes. Vascular bundles are
collateral and 12-14 bundles are arranged in a single ring with
concentric zones. The xylems generally tend to be V-shaped.
In vascular bundles, 2-6 cambium layers between phloem and
xylem are distinguishable. The xylem part is larger than the
phloem part. The pith consists of parenchymatous cells that
are large and polygonal in shape. This tissue is torn in the lower
part of the stem and these tears form a pith cavity (Figure 7A-
B). Latex is generally present throughout all parts of the plant
and is found in articulated laticiferous tubes. Laticiferous tubes
are placed in vascular bundles close to the phloem. In some of
the cross-section slides, sieve plates related to the transverse or
lateral walls of these tube cells were found (Figures 8). Calcium
oxalate crystals occurinthe parenchymatous cells.
Petiole: The petiole cross-section is triangular and its anatomi-
cal structure is similar to the stem structure. It contains a single
layer of epidermis, one to several layers of collenchyma in the
corners, and commonly exhibits an arc of vascular bundles
without sclerenchyma. Also, there are articulated laticiferous
latex tubes and cells and crystals of calcium oxalate in the cor-
tex cells (Figures 7 G-L).
Root: The root structure indicates that this plant is annual. The
periderm is generally scratched from the cortex and the cortex
is multi-layered with 20-35 layers. Endodermis cannot be dis-
tinguished and borders are not clear. The primary structure in
the central vascular bundle is diarch and xylem places under
phloem (Figures 9).
DISCUSSION
In this study, we investigated the distribution area, morpho-
logical and anatomical properties of C. majus as one of the tra-
ditional medicinal plants in Turkey. There are lots of studies on
the phytochemical and therapeutic perspective of the genus
Chelidonium (Kedzia Łozykowska & Gryszczynska, 2013; Grosso
et al. 2014; Zielinska et al. 2018) but the distribution area, mor-
phological and anatomical features of this species have not
been taken into consideration, especially in Turkey.
The distribution area of Chelidonium in Flora of Turkey (Cullen
1965) is restricted to the Black Sea region and this taxon is known
as the Euro-Siberian element. Our findings indicated this spe-
cies grows abundantly in the transition area from Euro-Siberian
to Irano-Turanian phytogeographic area. There are two records
from Afyonkarahisar and Kayseri that are far from the natural dis-
tribution area of this species (Figure 2). This can be caused by
anthropogenic impact or seeds being carried by animals. The
habitats of this plant are forests and shady rural areas. We also
found lots of individual plants in parks and roadsides in the cities.
Our results on morphological features are in agreement with the
description of the taxon in the Flora of Turkey (Cullen, 1965). We
also expended morphological characters according to 44 ex-
amined samples from fresh material and herbarium mentioned
specimens. The shape of the leaves, umbellate inflorescence,
small, yellow flowers, basipetal dehiscence capsule shaped fruits
with deciduous valves and arillate seeds can be used to differen-
tiate this species from other members of the family.
Figure 8. A-C, Orange latex in root, stem and leaves of the Chelidonium;
D cross section of stem; E and F, Transverse and longitudinal section of
stem and articulated laticiferous tubes.
Figure 9. Transverse sections of root. a, cambium; co, cortex; pr,
periderm; ph, phloem; pi, pith region; vb, vascular bundle; xy, xylem.
Scale bars: (A) 500 μ, (B, C), 200 μ.

129
Zare et al. Chelidonium majus L. (Papaveraceae) morphology, anatomy and traditional medicinal uses in Turkey
Although latex secretion in many unrelated families decreases
its diagnostic value, whatever the chemical nature of its con-
tents, it can be helpful in the taxonomy of taxa (Metcalfe &
Chalk, 1957). In the Papaveraceae family, the presence of la-
tex is a predominant character among members that shows
the variation in colour and chemical component (Metcalfe &
Chalk, 1957; Kadereit, 1993). The shiny orange latex found in all
organs of the plant is peculiar to C. majus and is placed in ar-
ticulated non anastomosing laticifers (Figure 8). Also, in agree-
ment with Kadereit (1993), this tube significantly associated
with the phloem of the vascular bundle and these structures
can easily be distinguished even in broken or powdered herbal
drugs (Pallag, Pasca, Taichiș, Honiges & Moisa, 2015; İşcan, Köse
& Demirci, 2019). Kadereit (1993) indicated latex tends to dis-
appear from the older parts of the plant; however, we found it
in the old parts but the amount was low.
While the trichome types provided an important diagnostic
character among the species of Papaveraceae family, the re-
sults indicated that uniseriate trichomes are diagnostic for the
whole tribe Chelidonieae. In addition, considering the diag-
nostic value of epidermal cell shape, the presence of stomata
just in the adaxial side of leaves, in contrast with other genera
such as Papaver and Roemeria (Metcalfe & Chalk, 1957) and the
stomata index can provide confirmatory evidence in the iden-
tification of this taxon.
These results can help to facilitate the identification of material
for use by people, detecting contamination of this taxon with
other herbal drugs and providing identified raw material for
scientific research in the medicinal field.
C. majus is one of the oldest medicinal species, having been in
use since ancient times. This plant was cited by Dioscorides to
treat jaundice and dermatologic disorders and Pliny the Elder
for the preparation of eye lotion (Jones, 1966; Dioscorides, Os-
baldeston & Wood, 2000). C. majus has been extensively used
to treateye diseases, ulcers and skin disorders as well as against
colic and jaundice in Europe (Mayer, Uehleke & Saum, 2003). In
Turkey, especially in the Black Sea region, a distribution area of
Chelidonium, the different parts of this plant, commonly latex
and the aerial parts of the plant have been used as folk medi-
cines for the treatment of different diseases (Table 2). The latex
is externally as hemostatic and for the treatment of skin diseases
such as wounds, eczema, warts, ringworm, and itching (Kültür,
2007; Ünsal Vural, Sarıyar, Özbek & Ötük, 2010; Kızılarslan & Özha-
tay, 2012; Akbulut & Özkan, 2014; Mumcu & Korkmaz, 2018).
The infusions of aerial parts are used internally to treat hepatitis
(Kültür, 2007), hemorrhoids, jaundice, liver, eye and skin diseases
(Arı et al. 2015). In addition, it is used for gallbladder, (Mumcu &
Korkmaz, 2018), and gastrointestinal diseases such as digestion,
spasm, dyspepsia (Sargın, Akçicek & Selvi, 2013; Sargın, Selvi &
Lopez, 2015; Mumcu & Korkmaz, 2018) and used as purgative
and diuretic (Kızılarslan & Özhatay, 2012; Mumcu & Korkmaz,
2018). It is also used externally to treat warts, corns, acne (Sargın,
Akçicek & Selvi, 2013; Saraç, Ozkan & Akbulut, 2013; Sargın, Selvi
& Lopez, 2015), eczema (Uzun et al., 2004; Saraç, Ozkan & Akbu-
lut, 2013; Polat, Cakilcioglu, Kaltalioğlu, Ulusan & Türkmen, 2015),
and rheumatism (Kültür, 2007).
In traditional medicine different parts of the plant are used
for several therapeutic purposes. Nawrot et al (2017) suggest
protein content of the Chelidonium can be affected by the bio-
logical activity of this taxa. They calm changes in the plant’s
needs at different developmental life stages from intense bio-
synthetic processes to defence against different environmen-
tal factors such as pathogens can affect latex composition.
These changes in phytochemical composition could explain
the biological activity alteration and subsequently divergent
medicinal use of the plant extracts in the different develop-
mental stages. The skin treatment properties of C. majus might
be related to antibacterial, antifungal, antiviral and anti-inflam-
mation activities of these taxa. It seems that these activities are
attributed mostly to the alkaloids and flavonoids present in
Chelidonium (Zuo et al., 2008; Zeileska et al. 2018). Stickl (1928)
proved that the bactericidal properties are related to chelery-
thrine (Taborska Bochorakova, Dostal & Paulova, 1995) and
sanguinarine (Hadaruga & Hadaruga, 2009). Also, the glycos-
aminoglycan present in the latex beside alkaloids containing
chelidonine (Monavari, Shahrabadi, Keyvani, Bokharaei-Salim,
2012), chelerythrine (Taborska, Bochorakova, Dostal & Paulova,
1995), sanguinarine (Hadaruga & Hadaruga, 2009), coptisine
(Bodalski, Pelezarskaund & Ujec, 1958) and berberine is able
to inhibit the development of human immunodeficiency virus
(HIV)(Gerencer et al., 2006) and human papilloma virus (HPV)
(Etxenagusia et al., 2000). The antifungal activity of Chelidonium
is attributed to alkaloidal compounds such as dihydrochelery-
thrine and dihydrosanguinarine which inhibit spore germina-
tion and the growth of mycelium in fungi (Maji & Pratim, 2015).
The other most reported indications of C. majus, both in Eu-
ropean/Mediterranean and East Asian (TCM) traditions were
for various liver complaints (Zielinska et al., 2018). Some of the
hepatoprotective and choleretic/cholagogue activities might
be explained by the presence of hydroxycinnamic (caffeic) ac-
ids’ esters and dihydrochelerythrine (Weiskirchen, 2016). The
in vivo research indicated that the phenolic components and
alkaloids contain chelidonine, berberine and theprotopine
showed choleretic activity and caused an increase in the bile
acid flow. It seems this effect is responsible for their hepatopro-
tective activity (Vahlensieck et al., 1995).
The main concern in Chelidonium is a possible hepatotoxic-
ity of the plant because of the presence of alkaloids (Maji &
Pratim, 2015; Zeileska et al. 2018). Research points out dose-
dependent toxicity and according to EMA the toxicity of using
dried parts of Chelidonium in a normal dose is low but severe
and irreversible hepatotoxicity can happen in a high dose or
chronic uptake (EMA, 2010). Nevertheless, further investigation
is needed to determine possible toxic effects in daily adminis-
tration and term of use.
CONCLUSION
C. majus is most commonly used for the treatment of skin dis-
eases and liver disorders in Turkey and other countries. Consid-
ering the toxicity of this species alongside its traditional uses
and common commercial materials, detailed morphological
and anatomical structures can provide a useful tool to avoid
contamination of this taxon with other drugs.

130
Istanbul J Pharm 51 (1): 123-132
Our results indicated that the morphological characters such
as leaf and flower shape, seed-specific morphology provided
useful tools for the identification of this taxon from the other
genera in the Papaveraceae family. Also, the presence of or-
ange latex in all parts of the fresh materials or articulated latici-
fers with remaining latex content can be used as authentica-
tion diagnostic characters in powdered herbal drugs or broken
plant materials. The other anatomical structures such as the
stem and root cross-section, trichomes and stomata type share
common structures across all taxa of the family and provided a
limited opportunity to support the identification of this taxon.
Peer-review: Externally peer-reviewed.
Author Contributions: Conception/Design of Study- G.Z., N.Y.D.,
Z.C.A., İ.İ.T.Ç.; Data Acquisition- G.Z., N.Y.D.; Data Analysis/Interpreta-
tion- G.Z., N.Y.D.; Drafting Manuscript- G.Z.; Critical Revision of Manu-
script- G.Z., N.Y.D., Z.C.A., İ.İ.T.Ç.; Final Approval and Accountability- G.Z.,
N.Y.D., Z.C.A., İ.İ.T.Ç.
Conflict of Interest: The authors have no conflict of interest to de-
clare.
Financial Disclosure: Authors declared no financial support.
REFERENCES
• Akbulut, S., & Ozkan, Z. C. (2014). Traditional Usage of Some Wild
Plants in Trabzon Region (Turkey). Kastamonu Uni., Orman Fakül-
tesi Dergisi, 14(1), 135–145.
• Aljuraisy, Y. H., Mahdi, N. K., & Al-Darraji, M. N. J. (2012) Cytotoxic
effect of Chelidonium majus on cancer cell. Al-Anbar Journal of
Veterinary Sciences, 5(1), 85–90.
• Arı, S., Temel, M., Kargıoğlu, M., & Konuk, M. (2015). Ethnobotanical
survey of plants used in Afyonkarahisar-Turkey. Journal of Ethnobi-
ology and Ethnomedicine, 11(84), 2015.
• Bellia, G., & Pieroni, A. (2015). Isolated, but transnational: the local
nature of Waldensian ethnobotany, Western Alps, NW Italy. Eth-
nobiology and Ethnomedicine, 11, 37.
• Benitez, G., Gonzalez-Tejero, M. R., & Molero-Mesa, J. (2010). Phar-
maceutical ethnobotany in the Western part of Granada province
(Southern Spain): Ethnopharmacological synthesis Journal of Eth-
nopharmacology, 129, 87–105.
• Blanco, E., Macia, M. J., & Morales, R. (1999). Medicinal and vet-
erinary plants of El Caurel (Galicia, Northwest Spain). Journal of
Ethnopharmacology, 65, 113–124.
• Bodalski, T., Pelezarskaund, H., & Ujec, M. (1958). Action of some
alkaloids of Chelidonium majus on Trichomonas vaginalis in vitro.
Archivum Immunologiae et Therapiae Experimentalis, 6,705–711.
• Bussman R.W., Paniagua Zambrana, N.Y., Sikharulidze, S.,
Kikvidze, Z., Kikodze, D., Tchelidze, D.B.K., & Robbie, E. (2017).
Ethnobotany of Samtskhe-Javakheti, Sakartvelo (Republic of
Georgia), Caucasus. Indian Journal of Traditional Knowledge,
16(1), 7–24.
• Calvo, M. I., Akerreta, S., & Cavero, R.Y. (2011). Pharmaceutical eth-
nobotany in the Riverside of Navarra (Iberian Peninsula). Journal
of Ethnopharmacology, 135, 22–23.
• Cavero, R.Y., Akerreta, S., & Calvo, M. I. (2011). Pharmaceutical eth-
nobotany in the Middle Navarra (Iberian Peninsula). Journal of
Ethnopharmacology, 137, 844–855.
• Cornara, L., La Rocca, A., Terrizzano, L., Dente, F., & Mariotti, M.G.
(2014). Ethnobotanical and phytomedical knowledge in the
North-Western Ligurian Alps. Journal of Ethnopharmacology,
155(1), 463–484.
• Cullen, J. (1965). Chelidonium. In: Davis PH (ed.) Flora of Turkey and
the east Aegean Islands (vol.1, pp. 213–214). UK: Edinburgh Uni-
versity Press.
• Dei Cas, L., Pugni, F., & Fico, G. (2015). Tradition of use on medicinal
species in Valfurva (Sondrio, Italy). Journal of Ethnopharmacology,
163, 113–134.
• Dioscorides, P., Osbaldeston, T. A., & Wood, R. P. A. (2000). Di-
oscorides de Materia Medica, Being a Herbal with Many other
Materials Written in Greek in the First Century of the Common
Era. An Indexed Version in Modern English. Johannesburg:
Ibidis Press.
• European Medicines Agency (EMA). (2011, September 13) Com-
mittee on Herbal Medicinal Products (HMPC): Public statement on
Chelidonium majus L., herba EMA/HMPC/743927/2010.Retrieved
from https://www.ema.europa.eu/en/documents/public-state-
ment/final-public-statement-chelidonium-majus-l-herba_en.pdf.
• Etxenagusia, M. A., Anda, M., Gonzalez-Mahave, I., Fernandez, E., &
Fernandez de Corres, L., (2000) Contact dermatitis from Chelido-
nium majus (greater celandine). Contact Dermat, 43, 47.
• Fortini, P., Di Marzio, P., Guarrera, P. M., & Iorizzi, M. (2016). Ethnobo-
tanical study on the medicinal plants in the Mainarde Mountains
(Central-Southern Apennine, Italy). Journal of Ethnopharmacol-
ogy, 184, 208–218.
• Gaspar, N., Godinho, J., Vasconcelos, T., Caldas, D., Mendes, P., &
Barros, O. (2002). Ethnobotany in the center of portugal (Santa-
rem) In: Rauter A.P., Palma F.B., Justino J., Araújo M.E., dos Santos
S.P. (eds) Natural Products in the New Millennium: Prospects and
Industrial Application. Proceedings of the Phytochemical Society of
Europe, (vol. 47, pp.271–284) Springer, Dordrecht.
• Gerencer, M., Turecek, P. L., Kistner, O., Mitterer, A., Savidis- Dacho,
H., & Barrett, N.P. (2006) In vitro and in vivo anti-retroviral activity of
the substance purified from the aqueous extract of Chelidonium
majus L. Antiviral Research, 72(2),153–156.
• Gilca, M., Gamana, L., Panaita, E., Stoian, I., & Atanasiu, V. (2010).
Chelidonium majus – an Integrative Review: Traditional Knowledge
versus Modern Findings, Forsch Komplementmed, 17, 241–248.
• Gonzalez-Hernandez, M. P., Romero, R., Rodriguez-Guitian, M., &
Rigueiro, A. (2004). Medicinal use of some plants in Galicia (NW-
Spain). Acta horticulture, 629, 63–75.
• Görsöz, H. (2018). Türk Farmakopesi-2017. Ankara, Turkey: Artı 6
Reklam Matbaa.
• Grosso, C., Ferreres, F., Gil-Izquierdo, A., Valentão, P., Sampaio, M.,
Lima, J., & Andrade, P. B. (2014). Box-Behnken factorial design to
obtain a phenolic-rich extract from the aerial parts of Chelido-
nium majus L. Talanta, 130, 128–136. https://doi.org/10.1016/j.
talanta.2014.06.043
• Guarrera, P. M., Forti, G., & Marignoli, S. (2005). Ethnobotanical and
ethnomedicinal uses of plants in the district of Acquapendente
(Latium, Central Italy). Journal of Ethnopharmacology, 96, 429–444.
• Güner, A., Aslan, S., Ekim, T., Vural, M., & Babaç, M.T. (Eds). (2012).
Türkiye Bitkileri Listesi (Damarlı Bitkiler) (pp. 281–282). Istanbul,
Turkey: N. Gökyiğit Botanik Bahçesi & Flora Araştırmaları Derneği
Yayınları.
• Hadaruga, D. I., & Hadaruga, N. G. (2009) Antioxidant activity of
Chelidonium majus L. extracts from the Banat county. Journal of
Agroalimentary Processes and Technologies, 15(3), 396–402.
• Hao, D., Gu, X., & Xiao, P. (2015) Medicinal Plants Chemistry, Biology
and Omics (pp.171–216). UK: Woodhead Publishing.
• Huang, C. K. (1999). The Pharmacology of Chinese Herbs (2nd ed.).
USA: CRC Press.
• Idolo, M., Motti, R., & Mazzoleni, S. (2009). Ethnobotanical and
phytomedicinal knowledge in a long-history protected area, the
Abruzzo, Lazio and Molise National Park (Italian Apennines). Jour-
nal of Ethnopharmacology, 127, 379–395.

131
Zare et al. Chelidonium majus L. (Papaveraceae) morphology, anatomy and traditional medicinal uses in Turkey
• İşcan, G., Köse, Y. B. & Demirci, F. (2019) Bitkisel Drogların Makros-
kobik ve Mikroskobik Özellikleri (pp 88-89). Türkiye: Antalya Eczacı
Odası Yayını No :1.
• Ivancheva, S. & Statcheva, B. (2000). Ethnobotanical inventory of
medicinal plants in Bulgaria. Journal of Ethnopharmacology, 69,
165–172.
• Jaric, S., Macukanovic-Jocic, M., Djurdjevic, L., Mijatovic, M., Kostic,
O., Karadzic, B. & Pavlovic, P. (2015). An ethnobotanical survey of
traditionally used plants on Suva planner mountain (Southeast-
ern Serbia). Journal of Ethnopharmacology, 175, 93–108.
• Jaric, S., Popovic, Z., Macukanovic-Jocic, M., Djurdjevic, L., Mijato-
vic, M., Karadzic, B. & Pavlovic, P. (2007). An ethnobotanical study
on the usage of wild medicinal herbs form Kopaonik Mountain
(Central Serbia). Journal of Ethnopharmacology, 111, 160–175.
• Jones, W.H.S. (1966). Pliny Natural History with an English Trans-
lation in Ten Volumes, Vol. VII, Libri XXIV–XXVII. London: Harvard
University Press.
• Kadereit, J.W. (1993). Papaveraceae. In: K. Kubitzki, J.G. Rohwer & V.
Bittrich (eds.) The families and genera of vascular plants (vol.2, pp.
494–506). Berlin: Springer-Verlag.
• Kedzia, B., Łozykowska, K. & Gryszczynska, A. (2013). Chemical
composition and contents of biological active substances in
Chelidonium majus L. Postepy Fitoterapii, 3, 174–181.
• Kızılarslan, Ç. & Özhatay, N. (2012). Wild Plants Used as Medici-
nal Purpose in the South Part of Izmit (Northwest Turkey), Turkish
Journal of Pharmaceutical Science, 9(2), 199–218.
• Kokoska, L., Polensky, Z., Rada, V., Nepovim, A. & Vanek, T. (2002)
Screening of some Siberian medicinal plants for antimicrobial ac-
tivity. Journal of Ethnopharmacology, 82(1), 51–53.
• Krahulcova A. (1982). Cytotaxonomic study of Chelidonium majus
L. s. l. Folia Geobotanica et Phytotaxonomica, 17, 237–268.
• Kültür, Ş. (2007). Medicinal plants used in Kırklareli Province (Tur-
key). Journal of Ethnopharmacology, 111, 341–364.
• Lee, Y.C., Kim, S.H., Roh, S.S., Choi, H.Y. & Seo, Y.B. (2007) Suppres-
sive effects of Chelidonium majus methanol extract in knee joint,
regional lymph nodes, and spleen on collagen-induced arthritis
in mice. Journal of Ethnopharmacology, 112(1), 40–48.
• Leporatti, M.L. & Ivancheva, S. (2003). Preliminary comparative
analysis of medicinal plants used in the traditional medicine of
Bulgaria and Italy. Journal of Ethnopharmacology, 87, 123–142.
• Linnaeus, C. (1753) Chelidonium, Species Plantarum, vol. 1. (pp.505).
Stockholmiae.
• Lumpert, M. & Kreft, S. (2017). Folk use of medicinal plants in Karst
and Gorjanci, Slovenia. Journal of Ethnobiology and Ethnomedi-
cine, 13,16.
• Maji, A., K. & Pratim, B. (2015). Chelidonium majus L. (Greater celan-
dine) – A Review on its Phytochemical and Therapeutic Perspec-
tives. International Journal of Herbal Medicine, 3(1), 10–27. https://
doi.org/10.22271/flora.2015.v3.i1.03.
• Mayer, J. G., Uehleke, B. & Saum, K. (2003). Handbuch der
Klosterheilkunde (pp.213–221). Muenchen: Verlag Zabert Sand-
mann.
• Menale, B., Amato, G., Di Prisco, C. & Muoio, R. (2006). Traditional
uses of plants in North-Western Molise (Central Italy). Delpinoa,
48, 29–36.
• Menendez-baceta, G., Aceituno-mata, L., Molina, M., Reyes-garcia,
V., Tardio, J. & Pardo-de-santayana, M. (2014). Medicinal plants tra-
ditionally used in the Northwest of the Basque Country (Biscay
and Alava), Iberian Peninsula. Journal of Ethnopharmacology, 152,
113–134.
• Menkovic, N., Savikin, K., Tasic, S., Zdunic, G., Stesevic, D., Milosav-
ljevic, S. & Vincek, D. (2011). Ethnobotanical study on traditional
uses of wild medicinal plant in Prokletije Mountains (Montene-
gro). Journal of Ethnopharmacology, 133, 97–107.
• Metcalfe, C.R. & Chalk, L. (1957). Anatomy of the Dicotyledons
(vol. 1., pp.74–78). London: Oxford Univ. Press. https://doi.
org/10.1111/j.2042-7158.1950.tb13008.x
• Miraldi, E., Ferri, S. & Mostaghimi, V. (2001). Botanical drugs and
preparations in the traditional medicine of West Azerbaijan (Iran)
Journal of Ethnopharmacology, 75, 77–87.
• Monavari, S.H., Shahrabadi, M.S., Keyvani, H., Bokharaei- Salim, F.
(2012) Evaluation of in vitro antiviral activity of Chelidonium majus
L. against Herpes simplex virus type-1. African Journal of Microbiol-
ogy Research, 6(20), 4360–4364.
• Mumcu, Ü. & Korkmaz, H. (2018) Ethnobotanical uses of alien and
native plant species of Yeşilırmak Delta, Samsun, Turkey, Acta Bio-
logica Turcica, 31(3), 102–113.
• Mustafa, B., Hajdari, A., Krasniqi, F., Hoxha, E., Ademi, H., Quave,
C.L., Pieroni, A. (2012). Medical ethnobotany of the Albanian Alps
in Kosovo. Journal of Ethnobiology and Ethnomedicine, 8:6.
• Mustafa, B., Hajdari, A., Pajazita, Q., Syla, B., Quave, C.L. & Pieroni,
A. (2012). An ethnobotanical survey of the Gollak region, Kosovo.
Genetic Resources and Crop Evolution, 59, 739–754.
• Nawrot, R., Jozefiak, D., Sip, A., Kuzma, D., Musidlak, O., Gozdzicka-
Józefiak, A. (2017). Isolation and characterization of a non-specific
lipid transfer protein from Chelidonium majus L. latex. Interna-
tional Journal of Biological Macromolecules, 104(Pt A), 554–563.
https://doi.org/10.1016/j.ijbiomac.2017.06.057
• Neves, J.M., Matos, C., Moutinho, C., Queiroz, G. & Gomes, L.R.
(2009). Ethnopharmacological notes about ancient uses of me-
dicinal plants in Tras-os-Montes (Northern of Portugal) Journal of
Ethnopharmacology, 124, 270–283.
• Novais, M.H., Santos, I., Mendes, S. & Pinto-Gomes, C. (2004). Stud-
ies on pharmaceutical ethnobotany in Arrabida Natural Park (Por-
tugal) Journal of Ethnopharmacology, 93, 183–195.
• Pallag, A., Pasca, B., Taichiș, D. I., Honiges, A., Moisa, C., (2015) Mi-
croscopic studies of some Chelidonium majus L. populations.
Analele Universitii din Oradea, Fascicula: Ecotoxicologie, Zoo-
tehnie şi Tehnologii de Industrie Alimntar, 14B, 391–396.
• Pantano, F., Mannocchi, G., Marinelli, E., Gentili, S., Graziano, S.,
Busardò, F.P. & Di Luca, N.M. (2017). Hepatotoxicity induced by
greater celandine (Chelidonium majus L.): a review of the litera-
ture. European Review for Medical and Pharmacological Sciences,
21(1), 46–52.
• Papp, N., Birkas-Frendl, K., Farkas, A. & Pieroni, A. (2013). An ethno-
botanical study on home gardens in a Transylvanian Hungarian
Csango village (Romania). Genetic Resources and Crop Evolution,
60, 1423–1432.
• Passalacqua, N.G., Guarrera, P.M. & De Fine, G. (2007). Contribution
to the knowledge of the folk plant medicine in Calabria region
(Southern Italy). Fitoterapia, 78, 52–68.
• Pieroni, A., Dibra, B., Grishaj, G., Grishaj, I. & Maçai, S.G. (2005). Tra-
ditional phytotherapy of the Albanians of Lepushe, Northenr Al-
banian Alps. Fitoterapia, 76, 379–399.
• Pieroni, A., Ibraliu, A., Abbasi, A.M. & Papajani-Toska, V. (2015). An
ethnobotanical study among Albanians and Armenians living in
the Rraice and Mokra area of Eastern Albania. Genetic Resources
and Crop Evolution, 62, 477–500.
• Polat, R., Cakilcioglu, U., Kaltalioğlu, K., Ulusan, M.D. & Türkmen,
Z. (2015). An ethnobotanical study on medicinal plants in Espiye
and its surrounding (Giresun-Turkey). Journal of Ethnopharmacol-
ogy, 163, 1–11.
• Prieroni, A., Giusti, M.E., Münz, H., Lenzarini, C., Turkovic, G. &
Turkovic, A. (2003). Ethnobotanical knowledge of the Istro-Roma-
nians of Zejane in Croatia. Fitoterapia, 74, 710–719.
• Redzic, S.S. (2007). The ecological aspect of ethnobotany and
ethnopharmacology of population in Bosnia and Herzegovina.
Collegium Antropologicum, 31(3), 869–890.

132
Istanbul J Pharm 51 (1): 123-132
• Rigat, M., Valles, J., D’Ambrosio, U., Gras, A., Iglesias, J. & Garnatje,
T. (2015). Plants with topical uses in the Ripples district (Pyrenees,
Catalonia, Iberian Peninsula): Ethnobotanical survey and pharma-
cological validation in the literature. Journal of Ethnopharmacol-
ogy, 164, 162–179.
• Saraç, D.U., Ozkan, Z.C. & Akbulut, S. (2013). Ethnobotanic features of
Rize/Turkey province. Biological Diversity and Conservation, 6(3), 57–66.
• Sargin, S.A., Selvi, S. & Lopez, V. (2015). Ethnomedicinal plants of
Sarigöl district (Manisa), Turkey. Journal of Ethnopharmacology,
171, 64–84.
• Sargın, S.A., Akçicek, E. & Selvi, S. (2013). An ethnobotanical study
of medicinal plants used by the local people of Alaşehir (Manisa)
in Turkey. Journal of Ethnopharmacology, 150(3), 860–874.
• Saric-Kundalic, B., Dobes, C., Klatte-Asselmeyer, V. & Saukel, J.
(2010). Ethnobotanical study on medicinal use of wild and culti-
vated plants in middle, South and West Bosnia and Herzegovina.
Journal of Ethnopharmacology, 131, 33–55.
• Saric-Kundalic, B., Dobes, C., Klatte-Asselmeyer & V. & Saukel, J.
(2011). Ethnobotanical survey of traditionally used plants in hu-
man therapy of east, North and Northeast Bosnia and Herzegovi-
na. Journal of Ethnopharmacology, 133, 1051–1076.
• Savic, J., Macukanovic-Jocic, M. & Jaric, S. (2019). Medical ethno-
botany on the Javor Mountain (Bosnia and Herzegovina). Euro-
pean Journal of Integrative Medicine, 27, 52–64.
• Savikin, K., Zdunic, G., Menkovic, N., Zivkovic, J., Cujic, N., Teres-
cenko, M. & Bigovic, D. (2013). Ethnobotanical study on traditional
use of medicinal plants in South-Western Serbia, Zlatibor district.
Journal of Ethnopharmacology, 146, 803–810.
• Soukand, R. & Pieroni, A. (2016). The importance of a border:
Medical, veterinary, and wild food ethnobotany of the Hutsuls liv-
ing on the Romanian and Ukrainian sides of Bukovina. Journal of
Ethnopharmacology, 185, 17–40.
• Stickl, O. (1928) Die bactericide Wirkung der Extrakte und Alka-
loide des Schöllkrautes (Chelidonium majus) auf gram positive.
Pathogene Mikroorganismen. Zeitschrift für Hygiene und Infektion-
skrankheiten, 108, 567–577. https://doi.org/10.1007/BF02201625
• Taborska, E., Bochorakova, H., Dostal, J. & Paulova, H. (1995) The
greater celandine (Chelidonium majus L.) - review of present
knowledge. Ceska a Slovenska Farmacie, 144(2), 71–75.
• Ünsal, Ç., Vural, H., Sarıyar, G., Özbek, B. & Ötük, G. (2010) Tradi-
tional Medicine in Bilecik Province (Turkey) and Antimicrobial
Activities of Selected Species. Turkish Journal of Pharmaceutical
Science, 7(2), 139–150.
• Uzun, E., Sarıyar, G., Adsersen, A., Karakoc, B., Ötük, G., Oktayoğlu,
E. & Pirildar, S. (2004) Traditional medicine in Sakarya province
(Turkey) and antimicrobial activities of selected species. Journal
of Ethnopharmacology, 95, 287–296.
• Vahlensieck, U., Hahn, R., Winterhoff, H., Gumbinger, H.G.,
Nahrstedt, A. & Kemper, F.H. (1995) The effect of Chelidonium ma-
jus herb extract on choleresis in the isolated perfused rat liver.
Planta Medica, 61(3), 267–271.
• Varga F., Solic, I., Dujakovic, M.J., Luczaj, L.& Grdisa, M., (2019) The
first contribution to the ethnobotany of inland Dalmatia: medici-
nal and wild food plants of the Knin area, Croatia. Acta Societatis
Botanicorum Polonaise, 88(2), 3622.
• Weiskirchen, R., (2016) Hepatoprotective and anti-fibrotic agents:
it’s time to take the next step. Frontiers in Pharmacology, 6(303),
1–40. https://doi.org/10.3389/ fphar.2015.00303
• World Health Organization. (2010) WHO Monographs on medici-
nal plants commonly used in the Newly Independent States (NIS)
(pp.73–91). Geneva: WHO Press.
• Zielinska, S., Jezierska-Domaradzka, A., Wójciak-Kosior, M., Sowa,
I., Junka, A. & Matkowski, A.M. (2018). Greater Celandine’s Ups and
Downs−21 Centuries of Medicinal Uses of Chelidonium majus
From the Viewpoint of Today’s. Pharmacology. Frontiers Pharma-
cology, 9, 299. https://doi.org/10.3389/fphar.2018.00299
• Zuo, G.Y., Meng, F.Y., Hao, X.Y., Zhang, Y.L., Wang, G.C. & Xu, G.L.
(2008) Antibacterial alkaloids from Chelidonium majus Linn (Pa-
paveraceae) against clinical isolated of methicillin resistant Staph-
ylococcus aureus. Journal of Pharmacy and Pharmaceutical Science,
11(4), 90–94. https://doi.org/10.18433/J3D30Q