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Review Article
Mohd Afsahul Kalam*, Akhtar H. Malik, Aijaz Hassan Ganie and Tariq Ahmad Butt
Medicinal importance of Papra (Podophyllum
hexandrum Royle) in Unani System of Medicine
https://doi.org/10.1515/jcim-2020-0178
Received May 11, 2020; accepted August 10, 2020;
published online January 29, 2021
Abstract: Podophyllum hexandrum Royle [=Sinopodo-
phyllum hexandrum (Royle) T.S. Ying] is an important,
endemic medicinal plant species of Himalaya. It is used in
Unani System of Medicine under the name of ‘Papra’. The
drug was not mentioned in previous literatures, but the first
time it introduced in Unani Medicine by a great scholar
Hakim Najmul Ghani. He has mentioned its uses and
benefits in his classical book Khazainul Advia. In Unani
Medicine the plant species has been used to treat various
ailments like constipation, fever, jaundice, liver disorders,
syphilis, diseases of lymph glands etc. In Kashmir Hima-
laya it is used to treat various diseases by local medicine-
men, but now it is listed in rare drugs. Various
pharmacological studies have been done such as antioxi-
dant, antimicrobial, anti-inflammatory, antifungal, radio-
protective etc., recently it has also been reported that
podophyllotoxin or podophyllin can be used to treat some
forms of cancers also.
Keywords: ailments; cancer; medicinal systems;
physicians; Unani.
Introduction
Medicinal plants are the backbone of the traditional system
of medicine. A large population of the world is still depen-
dent on the traditional system of medicine. Unani and
Ayurvedic Systems of medicine is growing at a fast pace,
because of cost effective, high curative properties with less
side effects of its vast range of herbal based medicine.
Numerous wild and cultivated plants are the main source of
medicine in Unani System. Some very valuable medicines of
wild sources are now very difficult to obtain, as they are
endangered because of over-exploitation from their natural
habitats. Podophyllum hexandrum Royle [=Sinopodophyllum
hexandrum (Royle) T.S. Ying] which is known as Himalayan
Mayapple and ‘Papra’in Unani medicine belongs to family
Berberidaceae [1, 2]. Podophyllum is derived from the Greek
words ‘podo’a foot and ‘phyllos’a leaf. It is called so due to
the resemblance of the leaf to duck’s foot. It is named as
Mayapple due to the ripening of its fruit in spring season [3].
The leaves are 3, orbicular-reniform, 6–15 ×3.5–10 cm,
palmate, blobbed and hence named hexandrum,meaning
six lobes [4]. According to Ghani (2011) [1] among the two
species of Podophyllum:P. hexandrum and P. peltatum,only
the first one is used in Unani System of Medicine, this species
is commonly found in India that is why it is also called as
Indian Podophyllum.However, P. peltatum is found in North
America, hence called as American podophyllum [1]. One
more species is also found inSikkim named as P. sikkimensis
[5]. P. hexandrum Royle is commonly found in the Himalayan
regions, in few pockets of Indian cold dessert (Ladakh and
Lahaul-Spiti) and some parts of Asian continent [3].
This medicinal plant species is commonly used in Ay-
urveda and Chinese System of Medicine, while the medicinal
importance of its rhizome and resins is very limited to Unani
System. Hakim Najmul Ghani was first to described the
medicinal effect of this plant in Unani Medicine. According
to him, it acts as ‘mushil-i-safra’(cholagogue purgative) just
like Mercury and calomel,hence called as vegetable Mercury
or vegetable calomel. It is used for the treatment of various
ailments like, constipation, fever, jaundice, liver disorders,
syphilis, diseases of lymph glands etc. [1] Many scientific
studies regarding its pharmacological action like anti-viral,
*Corresponding author: Mohd Afsahul Kalam, Research Officer
Unani, Regional Research Institute of Unani Medicine, Central Council
for Research in Unani Medicine, Ministry of AYUSH, Govt. of India,
Naseembagh Campus, Srinagar, 190006, Jammu and Kashmir, India,
Phone: +91 7051435488, E-mail: afsahnium@gmail.com
Akhtar H. Malik, Centre for Biodiversity and Taxonomy, Department of
Botany, University of Kashmir, Srinagar, Jammu and Kashmir, India,
E-mail: ecoakhtar@gmail.com
Aijaz Hassan Ganie, Department of Botany, Kargil Campus, University
of Kashmir, Srinagar, Jammu and Kashmir, India,
E-mail: aijazku@gmail.com
Tariq Ahmad Butt, Regional Research Institute of Unani Medicine,
Central Council for Research in Unani Medicine, Ministry of AYUSH,
Govt. of India, Naseembagh Campus, Srinagar, Jammu and Kashmir,
India, E-mail: smpusrinagar@gmail.com
J Complement Integr Med 2021; ▪▪▪(▪▪▪): 20200178
anti-bacterial, pesticidal, anti-cancerous, antimitotic activ-
ities etc. have been reported. In this article, an attempt has
been made to review briefly the phytochemical composition,
pharmacological activities, its uses in Unani System of
Medicine and ethno-medicinal uses in various Himalayan
regions. This review will pave the way to conduct further
research studies so that unexplored potential of this plant
can be harnessed utmost. In essence, the traditional
knowledge about this prized species reflects many genera-
tions of experience and problem solving by the indigenous
communities [6].
Materials and methods
Relevant literature regarding Papra (Podophyllum hexan-
drum) was collected from classic book (Khazainul Advia)of
Unani medicine [1], from the Library of RRIUM, Srinagar
and information also retrieved from published papers on
various database like Web of Science, Google Scholar,
Researchgate, Springer, and PubMed.
Observation
Distribution
Podophyllum hexandrum Royle is believed to be originated
in Himalaya region; it is found in the interior range of
Himalaya at 2,500–4,600 m (amsl) from Sikkim to Hazara
descending to 2,000 m (amsl) in Kashmir; distributed in the
west to Afghanistan and S.W. China [7, 8]. It is also found in
Arunachal Pradesh, Punjab, Uttaranchal, and Himachal
Pradesh [7, 9]. Generally, it is found in the vicinity of spe-
cies like Rhododendron, Salix, Viburnum and Juniperus but
it is also located in open alpine meadows [7].
Botanical description
Podophyllum hexandrum Royle [=Sinopodophyllum hexan-
drum (Royle) T.S.Ying; Podophyllum emodi Wall.exHook.f.&
Thomson] is an erect, glabrous, succulent, perennial herb
35–60 cm tall with creeping, knotted rhizomes bearing
numerous roots; color yellowish brown to earthy brown;
roots easily broke off, brittle, odor slight but distinct, taste
bitter acrid and starchy; leaves 2–3 umbrella like, 10–20 cm
long, rounded in outline and deeply cut into three ovate
lobes; stem approximately 30–90 cm tall; flowers white or
pale pink, borne at the ends of stout stem during May to
August. It has six petals and six stamens; fruit is berry which
is oblong,elliptic, 2.5–5.0 cm in diameter, green when unripe
and red on ripening and containing many seeds embedded
in the red pulp (Figure 1).
Cultivation and collection
Seeds sown with the pulp in June or July immediately after
collection, the seeds remain dormant for 9–10 months and
show germination in the following spring after the melting
of snow. The rhizome and roots of the plant are obtained
entirely from wild plants. The underground rhizomes
remain dormant during winter and produce aerial shoot in
April or May after melting of snow. Propagation by rhizome
cutting, 1.0–2.5 cm in length has also been reported [7]. The
plant prefers moist and shady localities. The flowering
period commences in spring and fruiting period during
summer and senescence occurs during October-November
months. Rhizome which bear 3–5 aerial shoots are
considered suitable for collection. The rhizomes are
collected in spring or autumn, cleaned, dried in sun,
packed and stored in gunny bags; sometimes they are cut
into cylindrical pieces and carefully dried. Rhizomes which
are collected in May contain higher resin content than
those obtained in November. Freshly collected rhizomes
possess more amounts of active compounds which are lost
on prolonged storing [7].
Vernacular names
The plant is known by various names according to different
places and languages. Most commonly it is known as
Podophyllum and ‘Mayapple’but also called Podophillum
and Papra in Unani Tibb; Bakrachimyaka, Bhavanbakra,
Papra, Papri in Hindi; Wunwagun, Banwangan, Bankakdi,
Bankakri in Kashmir; Lagu Petra in Nepali; Laghupatra in
Sanskrit; Bankakra, Gulkakru, Papri in Panjabi; Wenivel in
Gujrati; Padwel, Patvel in Marathi and Rhizoma Podiphylli
indici and P. emodi in Latin [1, 10, 11]. In Ayurveda, it is
known as Aindri, Bantrapushi or Giriparpat [12], and in
Ladakh it is known as Ol-mo-se which means the remedies
for women problems [13]. In some parts of Ladakh it is also
called Drenmookushu.
Uses in Unani System of Medicine
The rhizomes are used in Unani medicine for its ‘mushil-i-
safra’(cholagogue purgative), ‘muharrik-i-kabid’(hepatic
stimulant), dafi-i-tap (antipyretic), daf-i-suda-i-ghathayani
(headache occurs due to nausea) and muqi (emetic) prop-
erties etc. It has a long history being used as intestinal
2Kalam et al.: Podophyllum hexandrum as a valuable medicinal herb
purgative and in cases of ‘Qabd muzmin’(chronic con-
stipation) and ‘Adati qabd’(habitual constipation), and
also for constipation which occurs due to the involvement
of liver diseases [1]. The drug is also useful in ‘Atashak’
(syphilis), ‘Khanazir’(diseases of lymph glands), chest
pain etc. It is used as a salve for infection and necrotic
wounds [11].
Dosage
The therapeutic dose of roots is 5–10 grain; podophyllin,
1/4th −1 grain and tincture is used in a dose of 15 minum-1
fluid dram [1]. (minum = 0.0616 mL; grain = 64.8 mg; fluid
dram = 60 drops).
Adverse effect
If taken above the therapeutic dose, it causes spasmodic
pain, sloughing and excoriation in the stomach [1].
Correctives
Curd mixed with water, honey or sugar-based syrup, ‘lu’ab
behdana’(mucilage of Cydonia oblonga Mill. seeds),
‘aspghol’(Plantago ovata Forsk.) or ‘ashjau’(barley water)
is used to counter excessive purgation which occurs due to
the side effect of P. hexandrum.‘Ajwain Khurasani’
(Hyoscyamus niger L.) and ‘Qinnab’(Cannabis sativa L.)
is added to manage the spasmodic action caused by
P. hexandrum [1].
Ethno-medicinal uses in Kashmir Himalaya
Since ages, through trial and error, local healer in Hima-
layan region have learned and are practicing the medicinal
use of plants growing in their close vicinity for treating
various ailments. Kashmir has its own medicinal system in
place practiced by local medicinemen called ‘Hakims’. The
ethno-medicinal uses of Podophyllum hexandrum in
Kashmir are as under:
Figure 1: Podophyllum heaxandrum
(a) Plant; (b) Unripe fruit; (c & d) Ripen fruits
and seeds; (e & f) Flowering stages.
Kalam et al.: Podophyllum hexandrum as a valuable medicinal herb 3
A. The crushed leaves and roots are applied to cure skin
diseases [14].
B. The fruit is claimed as a laxative and stops bilious
vomiting; it is eaten raw for chest congestion and
gastric problems [14, 15]; ripe fruit juice is taken in
stomach ulcers and dyspepsia [16].
C. Powder obtained from the dried root is administered
orally along with water to counter tumors [16]; a paste
made with root powder mixed with oil is used as a
remedy to skin diseases such as rashes and eczema
[16].
D. Resin is used in veterinary medicine as cathartic for
dogs [15].
E. Pericarp of mature red fruit is used to treat eye wounds
of cattle [17].
Ethno-medicinal uses in other regions of Himalaya
The rhizomes and resin of Podophyllum hexandrum are
used for its alterative, laxative, purgative and antineo-
plastic properties. Externally it is applied for removal of
condyloma, anogenital warts, veneral warts, verrucae and
similar conditions [18]. It is also useful against various
diseases like wilm’s tumours, genital tumors, ‘molluscum
contagiosum’, psoriasis vulgaris, non-Hodgkin lymphoma
and other lymphomas, cancer of brain, lung, bladder,
leukemia [19, 20]. In Ladakh and Tibetan System of Medi-
cine the rhizome is used against various gynecological
problems [13].
Bio-active compounds
The resin obtained from Podophyllum speciesiscalled
podophylloresin (a neurotoxin) which can be processed to
extract podophyllotoxin or podophyllin11.Therhizomesand
roots also contain antitumor lignans such as podophyllo-
toxin, 4-dimethyl podophyllotoxin and podophyllotoxin 4-O-
glucoside [21, 22]. Wani et al.,[23] reported that it contain
glycosides, flavonoids, saponins, D-glycoside,terpenes and
proteins also. The highest percentage of resin is obtained in
the May-June during the flowering stage [24]. Commonly it is
known for its valuable drug podophyllotoxin, which is used
as starting compound for the synthesis of anticancer drug
etoposide, etopophose and teniposide [25]. Indian podo-
phyllum has more than double amount of podophyllotoxin,
however; the active principal alpha and beta peltatins iso-
lated from P. peltatum, whichare absent in P. hexandrum [26].
Hexanedioic acid, Oleic acid, and Octadecanoic acid are the
other constituents of the rhizome [27]; Tannin was noticed in
the root of this plant by Wallis [28]. Chawla et al. [29], reported
that polyphenols and lignans were rich in P. hexandrum
rhizome. The lignin compounds of Podophyllin from
P. hexandrum are podophyllotoxin, podophyllotoxingluco-
side, picropodophyllin, 1-O glucopyranosyl-picropodophyllin,
4′-glucoside, dihydropodophyllotoxin, 4′-demethylpodo-
phyllotoxin glucoside, dihydropodophyllotoxin, podophyllol,
podophyllic acidand 4′-dimethyl deoxypodophyllotoxin
glucoside [7]. In addition to these compounds, podophyllic
acid, podophylloquercin, starch, picropodophyllin, calcium
oxalate, kaempferol, astragalin, wax, mineral salts and an
essential oil also present which is responsible for its odor [7, 12].
Pharmacological studies
Antitumor activity
In the past few years podophyllin resin and its active
constituent podophyllin, have received significant atten-
tion for their tumor necrotizing properties. Scientific evi-
dence for antitumor activity of podophyllotoxin was first
reported by Kaplan in 1942 [30] and also for its significant
anti-tumor effect at sub-toxic, well-tolerated, sequential
doses of aqueous extracts [31].
Antioxidant activity
The various extract of the rhizome, petiole and leaves of
Podophyllum hexndrum have been examined for antioxidant
activity in vitro and in vivo. The ethyl acetate extract of the
rhizome was investigated by using DPPH scavenging assay,
hydroxyl assay, H2O2 assay, superoxide assay, and reducing
power under in vitro conditions. For in vivo study albino rats
were used for antioxidant enzyme activities and glutathione
levels in the liver tissue homogenate. Both the method have
proven the effectiveness of the ethyl acetate extract
compared to known antioxidants BHT and α-tocopherol [32].
Antimicrobial activity
Methanolic and aqueous extract of Podophyllum hexan-
drum (60 mg/mL) were reported to have antimicrobial ef-
fect against the bacteria and fungi in vitro. Both the extract
inhibited Bacillus megaterium MTCC 1684 and Pseudo-
monas aeruginosa MTCC 3541 with zone of inhibition
ranging between 0.9 and 1.4 cm against disc diffusion
method; and inhibited the fungi Aspergillus flavus and
Fusarium solani with zone of inhibition ranging between
0.9 and 1.8 cm [33]. In other study it is also reported to have
antibacterial effect against Staphylococcus aureus, Salmo-
nella typhi, Klebseilla pneumonia and Enterococcus faecalis
by Sabzar [34].
4Kalam et al.: Podophyllum hexandrum as a valuable medicinal herb
Antivirus activity
In vitro and In vivo studies showed that podophyllotoxin
and related lignans are active against viruses [35].
Anti-inflammatory effects
The anti-inflammatory potential of aqueous extract of
P. hexandrum rhizome has been evaluated on liposaccharide
(LPS) induced inflammation in Balb/c mice [36].
Radio-protective effect
P. hexandrum is a promising candidate plant for develop-
ment of radio protective drugs. According to a study done
by Raj Kumar et al. (2008), the extract of P. hexandrum
administered prior to irradiation, has been shown to pro-
vide approximately 80% whole-body radioprotection in
mice [37].
Antifungal activity
Two aryltetralin lignans (4-O-demethyl-dehydropodophyllo-
toxin and picropodophyllon), isolated from leaves showed
strong antifungal activity against Allescheria boydii, Curvul-
laria lunata, Epidermophyton floccosum, Microsporum canis,
Nigrospora oryzae, Pleurotus ostreatus [38].
Conclusions
Podophyllum hexandrum Royle has got importance in
various traditional systems of medicine because of its
extensive therapeutic potential. Realizing it’s highly value
medicinal importance as reported by various researchers;
the sustainable utilization of the prized plant species is
need of the hour. The documentation of medicinal impor-
tance of such plants is necessary for the discovery of new
drugs. Similarly, lesser-known plant species may also
prove useful in phyto-pharmacological research for the
discovery of new bioactive compounds and their applica-
tion to treat challenging diseases of the world.
Acknowledgments: The authors are thankful to Director
General CCRUM- New Delhi, Assistant Director/In-charge,
RRIUM Srinagar and Head, Department of Botany, Uni-
versity of Kashmir, Srinagar for providing the necessary
facilities.
Research funding: None declared.
Author contributions: All authors have accepted
responsibility for the entire content of this manuscript
and approved its submission.
Competing interests: The authors declare that there is no
conflict of interest.
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