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Sains Malaysiana 49(8)(2020): 1829-1851
http://dx.doi.org/10.17576/jsm-2020-4908-07
Medicinal Uses, Phytochemistry, and Pharmacological Properties of Piper
aduncum L.
(Kegunaan Perubatan, Fitokimia dan Sifat Farmakologi Piper aduncum L.)
MUHAMMAD TAHER, MOHAMAD SHAHREEN AMRI, DENY SUSANTI*, MUHAMMAD BADRI ABDUL KUDOS, NUR
FASYA AJDA MD NOR & YANDI SYUKRI
INTRODUCTION
River
ABSTRACT
Piper aduncum L., commonly known as ‘spiked pepper’, has various uses in traditional medicine that include
treating wounds, skin boils, infections, and diarrhoea. Its properties as an anti-parasitic, antimicrobial, insecticidal,
antitumor, and anticancer agent indicates that it could have further therapeutic potential in treating infections and
cancers. The aim of this review was to provide a comprehensive summary of the traditional uses, phytochemistry and
pharmacological properties of P. aduncum. Data were collected from electronic databases from 1978 to 2019. The
plant is traditionally used for treating diarrhoea in Peru and for its wound-healing properties in Brazil and Papua New
Guinea. Phenolics, monoterpenes, sesquiterpenes, and chromene have been found in the P. aduncum plant, and these
bioactive compounds contribute to its anti-parasitic, antimicrobial, insecticidal, antitumor, and anticancer properties.
Several pharmacological activities of P. aduncum have been reported, most notably in the treatment of infectious
diseases and cancer. However, information regarding its safety and ecacy in humans is lacking. Further study is
needed to examine the benets of P. aduncum and its potential applications in a clinical setting.
Keywords: Pharmacological properties; phytochemistry; Piper aduncum; traditional uses
ABSTRAK
Piper aduncum L., yang dikenali sebagai lada berduri, mempunyai pelbagai kegunaan dalam ubat tradisi termasuk
merawat luka, bisul kulit, jangkitan dan cirit-birit. Sifatnya sebagai agen anti-parasit, antimikrob, insektisid,
antitumor dan antikanser menunjukkan bahawa ia mempunyai potensi terapeutik dalam merawat jangkitan dan
kanser. Tujuan kajian ini adalah untuk memberikan ringkasan komprehensif mengenai kegunaan tradisi, tokimia
dan sifat farmakologi P. aduncum. Data telah dikumpulkan dari pangkalan data elektronik dari tahun 1978 hingga
2019. Tumbuhan ini secara tradisinya digunakan untuk merawat cirit-birit di Peru serta menyembuhkan luka di
Brazil dan Papua New Guinea. Fenol, monoterpena, sesquiterpena serta kromena telah dijumpai dalam tumbuhan P.
aduncum, dan sebatian bioaktif ini menyumbang kepada sifatnya sebagai anti-parasit, antimikrob, insektisid, antitumor
dan antikanser. Beberapa aktiviti farmakologi P. aduncum telah dilaporkan, terutamanya dalam rawatan penyakit
berjangkit dan kanser. Walau bagaimanapun, maklumat mengenai keselamatan dan keberkesanannya pada manusia
adalah kurang. Kajian lanjut diperlukan untuk mengkaji manfaat P. aduncum dan potensi pengaplikasiannya dalam
persekitaran klinikal.
Kata kunci: Fitokimia; kegunaan tradisi; Piper aduncum; sifat farmakologi
INTRODUCTION
Many drugs that are available in the market nowadays have
been discovered from natural products including plants. It
has been known that plants have their own importance in
human history with their interesting phytochemical and
pharmacological properties (Flores et al. 2009).
The Piperaceae family comprises around 3600
species. Within this family, the large genus Piper comprises
approximately 2000 plant species, including numerous
bushes and herbs that can be found in hushed and humid
areas, such as jungles and tropical rainforests (Bernuci
et al. 2016; Gutiérrez et al. 2016). Piper aduncum is a
species in the Piper genus within the Piperaceae family
(Ahmad & Rahmani 1993). It is known as pimenta-de-
macaco in the Amazon of Brazil and aperta-ruao in the
Atlantic Forest of Brazil (de Almeida et al. 2009). It is
believed that extracts from P. aduncum, which have been
shown to have various pharmacological eects, including
anti-parasitic, antimicrobial, insecticidal, antitumor, and
anticancer properties, can cure many diseases and cancers
(Lucena et al. 2017; Mee et al. 2009; Monzote et al. 2017;
Ndjonka et al. 2013).
1830
Although many studies have examined the
pharmacological properties of P. aduncum, a systematic
literature review of this potential therapeutic agent
has not yet been conducted. This review reports on the
traditional uses, phytochemistry, and pharmacological
activities of P. aduncum in order to provide an overview
of the research and a reference for the comprehensive
therapeutic uses of this plant.
METHODS
Data on the background, traditional uses, phytochemistry,
and pharmacological properties of P. aduncum were
collected from published scientic journals from years
1978 to 2019, using the keywords ‘Piper aduncum’ and
‘Piper species’. Articles, websites, books, and electronic
data were collected from academic search engines such
as ScienceDirect, Scopus, PubMed, Google Scholar and
ResearchGate. The species name of P. aduncum L. was
validated by the database ‘The Plant List’ from www.
theplantlist.org.
CHARACTERISTICS
P. aduncum, commonly known as ‘spiked pepper’, is
considered the most invasive species of the genus Piper.
P. aduncum grows as a small tree or shrub and can reach
6 to 8 m in height, with alternate leaves with short petioles
and small fruits arranged in spikes (Ahmad & Rahmani
1993). The fruits of P. aduncum appear as berries that
contain small, black seeds. The leaves are 10 to 18 cm
long and have a narrow oval shape that tapers to a point
and display a ne network of veins and smooth hairs on
the underside (dos Santos et al. 2015). All parts of the
P. aduncum plant have a peppery smell. The branches
of the plant are commonly used as firewood and split
easily when continuously exposed to moisture (Rali et
al. 2007).
DISTRIBUTION
P. aduncum was mostly originally found in Central and
South America, where it grows throughout a large part of
the Amazon and Atlantic forests. It was introduced to
Asia during the 19th century and is now commonly found
throughout New Guinea, Indonesia, Malaysia and the
Solomon and Christmas islands (de Almeida et al. 2009;
Hartemink 2010; Orjala et al. 1994). It was introduced to
the Botanical Gardens of Bogor, Indonesia, possibly as
an ornamental (Hartemink 2010).
Due to the large amount of pollen it produces, it is
easily spread by the wind. It is also carried eciently in
the faeces of mammals and birds. It grows in areas of
evergreen vegetation and water courses in seasonally
deciduous forests (Hartemink 2010). As such, P. aduncum
can be found in increasingly large geographical areas
today.
PHYTOCHEMISTRY OF P. aduncum
Previous studies have identified several bioactive
constituents in P. aduncum, including flavonoids,
monoterpenes and sesquiterpenes, chalcones, chromenes,
phenylpropanoid, and benzoic acid derivatives (Lago et
al. 2004; Moreira et al. 1998; Orjala et al. 1994; Rali et
al. 2007). It has also been found to contain 23 essential
oil components (Oliveira et al. 2013).
PHYTOCHEMICAL CONSTITUENTS IN THE LEAVES OF
P. aduncum
P. aduncum contains a wide range of phytochemical
compounds, such as flavonoids, monoterpenes,
sesquiterpenes, chalcones and benzoic acid derivatives,
as summarised in Table 1.
TABLE 1. Compounds from the leaves of Piper aduncum
Class of compound Compound References
Flavonoids Gallic acid (1)
Catechin (2)
Chlorogenic acid (3)
Epicatechin (4)
Quercetin-3-rutinoside (5)
Quercetin-3-rhamnoside (6)
Phloridzin (7)
Quercetin (8)
Phloretin (9)
(Escudero et al. 2008)
1831
Mono- and sesquiterpenes α-pinene (10)
β-pinene (11)
Limonene (12)
(e)-ocimene (13)
(z)-ocimene (14)
Linalool (15)
α-copaene (16)
β-elemene (17)
α-gurjunene (18)
β-caryophyllene (19)
Allo-aromadendrene (20)
α-humulene (21)
Undecanone (22)
Germacrene d (23)
bicyclogermacrene (24)
α-muurolene (25)
γ-cadinene (26)
δ-cadinene (27)
Germacrene b (28)
Nerolidol (29)
Spathulenol (30)
Globulol (31)
Safrole (32)
β-gurjunene (33)
β-sesquiphellandrene (34)
Rosifoliol (35)
Humulene epoxide ii (36)
Epi-cubenol (37)
α-muurolol (38)
α-cadinol (39)
Shyobunol (40)
Piperitone (41)
(Bernuci et al. 2016; Navickiene et al. 2006; Oliveira et al.
2013; Rali et al. 2007)
Chalcones Adunctins A (42)
Adunctins B (43)
Adunctins C (44)
Adunctins D (45)
Adunctins E (46)
Cardamonin (47)
Piperaduncin A (48)
Piperaduncin B (49)
Piperaduncin C (50)
Asebogenin (51)
2’,6’-dihydroxy-4’-
methoxydihydrochalcone (52)
Uvangoletin (53)
(Orjala et al. 1994)
Phenylpropanoid Dillapiole (54) (Rali et al. 2007)
Benzoic acid derivatives 3-(3,7-dimethyl-2,6-octadienyl)-
4-methoxy-benzoic acid (55)
4-hydroxy-3-(3,7-dimethyl-2,6-
octadienyl) benzoic acid (56)
4-hydroxy-3-(3-methyl-1-oxo-2-
butenyl-5(3-methyl-2-butenyl)
benzoic acid (57)
Methyl 4-hydroxy-3-(2’-
hydroperoxy-3’-methyl-3’-
butenyl)benzoate (58)
Methyl 4-hydroxy-3-(2’-
hydroxy-3’-methyl-3’-butenyl)
benzoate (59)
Aduncumene (60)
(Flores et al. 2009; Lago et al. 2009)
1832
FLAVONOIDS
Ethanolic extracts of P. aduncum leaves have shown
the presence of large amounts of avonoids (Arroyo-
Acevedo et al. 2015). Flavonoids, which are polyphenolic
compounds, have antioxidant properties and are able
to scavenge free radicals and therefore have utility in
cancer treatment. As reported by Escudero et al. (2008),
ethanolic extracts of P. aduncum leaves originating from
the Peruvian rainforest showed avonoid compounds as
the predominant compounds in the plant. The avonoid
constituents identified in P. aduncum are shown in
Figure 1.
Gallic acid (1) Catechin (2)
Chlorogenic acid (3)
Epicatechin (4)
Quercetin-3-rutinoside (5)
Quercetin-3-rhamnoside (6)
1833
Quercetin-3-rutinoside (5)
Quercetin-3-rhamnoside (6)
Phloridzin (7)
Quercetin (8)
Phloretin (9)
FIGURE 1. Flavonoid compounds identified in Piper aduncum leaves
FIGURE 1. Flavonoid compounds identied in Piper aduncum leaves
(26), δ-cadinene (27), germacrene B (28), nerolidol (29),
spathulenol (30) and globulol (31).
Bernuci et al. (2016) showed that the essential oil
of fresh P. aduncum leaves from Santa Catrina, Brazil,
is rich in sesquiterpenes. The monoterpene compounds
identified were (E)-ocimene (13), (Z)-ocimene (14),
linalool (15) and safrole (32). The sesquiterpenes identied
were β-caryophyllene (19), β-gurjunene (33), α-humulene
(21), allo-aromadendrene (20), bicyclogermacrene (24),
γ-cadinene (26), β-sesquiphellandrene (34), spathulenol
(30), rosifoliol (35), humulene epoxide II (36), epi-cubenol
(37), α-muurolol (38), α-cadinol (39) and shyobunol (40).
Analysis conducted by Rali et al. (2007) showed that
the dominant compounds in P. aduncum leaf essential
oil from Papua New Guinea were β-caryophyllene (19),
piperitione (41) and α-humulene (21). Figure 2 shows the
monoterpenes and sesquiterpenes identied in the analysis
of P. aduncum leaves.
MONOTERPENES AND SESQUITERPENES
The presence of monoterpenes and sesquiterpenes
(Figure 2) in the phytochemical analysis of P. aduncum
leaves has been extensively reported (Escudero et al. 2008).
The results obtained in separate studies all correlated
with one another in terms of their nding that P. aduncum
leaves contain larger amounts of sesquiterpene compounds
(90.4%) than monoterpenes (7.0%). 1,8-Cineole has been
found to be the major component of P. aduncum essential
oil (Oliveira et al. 2013). The essential oil of P. aduncum
leaves originating from Brazil has been shown to contain
α-pinene (10), β-pinene (11), limonene (12), (E)-ocimene
(13), (Z)-ocimene (14) and linalool (15) (Navickiene
et al. 2006). The sesquiterpenes identied by GC-MS
analyses are α-copaene (16), β-elemene (17), α-gurjunene
(18), β-caryophyllene (19), allo-aromadendrene (20),
α-humulene (21), undecanone (22), germacrene D (23),
bicyclogermacrene (24), α-muurolene (25), γ-cadinene
1834
α-pinene (10)
β-pinene (11)
Limonene (12)
(E)-ocimene (13)
(Z)-ocimene (14)
Linalool (15)
α-copaene (16)
β-elemene (17)
α-pinene (10)
β-pinene (11)
Limonene (12)
(E)-ocimene (13)
(Z)-ocimene (14)
Linalool (15)
α-copaene (16)
β-elemene (17)
α-pinene (10)
β-pinene (11)
Limonene (12)
(E)-ocimene (13)
(Z)-ocimene (14)
Linalool (15)
α-copaene (16)
β-elemene (17)
α-pinene (10)
β-pinene (11)
Limonene (12)
(E)-ocimene (13)
(Z)-ocimene (14)
Linalool (15)
α-copaene (16)
β-elemene (17)
1835
α-gurjunene (18)
β-caryophyllene (19)
Allo- Aromadendrene (20)
α-humulene (21)
Undecanone (22)
Germacrene D (23)
Bicyclogermacrene (24)
α-muurolene (25)
γ-cadinene (26)
δ-cadinene (27)
germacrene B (28)
Nerolidol (29)
α-gurjunene (18)
β-caryophyllene (19)
Allo- Aromadendrene (20)
α-humulene (21)
Undecanone (22)
Germacrene D (23)
α-gurjunene (18)
β-caryophyllene (19)
Allo- Aromadendrene (20)
α-humulene (21)
Undecanone (22)
Germacrene D (23)
1836
Bicyclogermacrene (24)
α-muurolene (25)
γ-cadinene (26)
δ-cadinene (27)
germacrene B (28)
Nerolidol (29)
Spathulenol (30)
Globulol (31)
Safrole (32)
Β-gurjunene (33)
β-sesquiphellandrene (34)
Rosifoliol (35)
1837
Spathulenol (30)
Globulol (31)
Safrole (32)
Β-gurjunene (33)
β-sesquiphellandrene (34)
Rosifoliol (35)
Humulene epoxide II (36)
Epi-cubenol (37)
α-muurolol (38)
α-cadinol (39)
Shyobunol (40)
Piperitone (41)
F
IGURE
2. Chemical structures of mono- and sesquiterpenes found in Piper aduncum leaves
FIGURE 2. Chemical structures of mono- and sesquiterpenes found in Piper
aduncum leaves
1838
CHALCONES
Orjala et al. (1994) isolated chalcones and previously
unidentied monoterpenes-substituted dihydochalcones
from the leaves of P. aduncum, which were adunctins A-E
(42-46). Piperaduncin A-C (48-50), asebogenin (51) and
2′,6′-dihydroxy-4′-methoxydihydrochalcone (52) were
also isolated from the leaves of P. aduncum (Orjala et al.
1994). Cardamonin (47) and uvangoletin (53) (Figure 3)
were isolated from P. aduncum leaves originating from
Brazil by solvent extraction with CH2Cl2 (de Castro et
al. 2015).
Adunctins A (42)
Adunctins B (43)
Adunctins C (44)
Adunctins D (45)
Adunctins E (46)
Cardamonin (47)
O
O
H
3
C
HO
OH
1839
2’,6’-dihydroxy-4’-methoxydihydrochalcone
(52)
Uvangoletin (53)
Piperaduncin A (48)
Piperaduncin B (49)
Piperaduncin C (50)
Asebogenin (51)
FIGURE 3. Chemical structures of chalcones isolated from Piper
aduncum leaves
Uvangoletin (53)
1840
PHENYLPROPANOID
The essential oil of P. aduncum is rich in dillapiole (54)
(Figure 4), which is a derivative of phenylpropene. Rali
et al. (2007) identied dillapiole as the main volatile
constituent of the essential oil from the leaves of
P. aduncum from the Brazilian Amazon rainforest, Costa
Rica, Cuba, Malaysia, and Fiji. Ahmad and Rahmani
(1993) also identied dillapiole as the main constituent
(43.3%) in P. aduncum leaves from Puchong, Malaysia.
However, essential oil from the Brazilian Atlantic forest
was found to contain nerolidol and linalool as the two
main volatile components (de Almeida et al. 2009). The
variety of compounds present in P. aduncum essential
oils indicate that dierent chemical variations have led to
the formation of two chemo types. Dillapiole is produced
via the shikimate pathway, and terpenes and linalool are
produced via the mevalonate or acetate pathway.
FIGURE 4. Chemical structure of dillapiole (54)
FIGURE 4. Chemical structure of dillapiole (54)
BENZOIC ACID DERIVATIVES
Flores et al. (2009) conducted a phytochemical analysis
of the leaves of P. aduncum and isolated the prenylated
hydroxybenzoic acid derivatives namely 3-(3,7-dimethyl-
2,6-octadienyl)-4-methoxy-benzoic acid (55), 4-hydroxy-
3-(3,7-dimethyl-2,6-octadienyl) benzoic acid (56) and
4-hydroxy-3-(3-methyl-1-oxo-2-butenyl-5(3-methyl-2-
butenyl) benzoic acid (57) (Figure 5). Additional two
prenylated methyl benzoates have also been isolated
from P. aduncum leaves which are methyl 4-hydroxy-3-
(2′-hydroperoxy-3′-methyl-3′-butenyl)benzoate (58) and
methyl 4-hydroxy-3-(2′-hydroxy-3′-methyl-3′-butenyl)
benzoate (59) (Lago et al. 2009). Aduncumene (60) was
isolated after successive extractions using dierent solvents
and column chromatography.
3-(3,7-dimethyl-2,6-octadienyl)-4-methoxy-
benzoic acid (55) and 4-hydroxy-3-(3,7-
dimethyl-2,6-octadienyl) benzoic acid (56)
4-hydroxy-3-(3-methyl-1-oxo-2-butenyl-
5(3-methyl-2-butenyl) benzoic acid (57)
Methyl 4-hydroxy-3-(2’-hydroperoxy-3’-
methyl-3’-butenyl)benzoate (58)
Methyl 4-hydroxy-3-(2’-hydroxy-3’-
methyl-3’-butenyl)benzoate (59)
Aduncumene (60)
1841
PHYTOCHEMICAL CONSTITUENTS IN THE STEMS OF
P. aduncum
Several monoterpenes, including α-pinene (10), β-pinene
(11), myrcene (61), α-terpinene (62), p-cimene (63),
limonene (12), (E)-ocimene (13), (Z)-ocimene (14),
γ-terpinene (64) and linalool (15), have been identied in
the stems of P. aduncum, in addition to the sesquiterpenes
β-caryophyllene, α-humulene, germacrene D, and nerolidol
(Navickiene et al. 2006). A separate study identified
3-(3,7-dimethyl-2,6-octadienyl)-4-methoxy-
benzoic acid (55) and 4-hydroxy-3-(3,7-
dimethyl-2,6-octadienyl) benzoic acid (56)
4-hydroxy-3-(3-methyl-1-oxo-2-butenyl-
5(3-methyl-2-butenyl) benzoic acid (57)
Methyl 4-hydroxy-3-(2’-hydroperoxy-3’-
methyl-3’-butenyl)benzoate (58)
Methyl 4-hydroxy-3-(2’-hydroxy-3’-
methyl-3’-butenyl)benzoate (59)
Aduncumene (60)
FIGURE 5. Isolated benzoic acid derivatives from Piper aduncum leaves
monoterpenes and sesquiterpenes such as β-pinene (11),
myrcene (61), α-terpinene (62), α-phellendrene (65),
m-cimene (66), 1,8-cineole (67), bornyl acetate (68),
neryl acetate (69), geranyl acetate (70), and copaene (71)
(Moreira et al. 1998). The chromenes eupatoriochromene
(72) and methyl 2,2-dimethyl-8-(3-methyl-2-butenyl)-2H-
chromene-6-carboxylate (73) have also been identied.
The chemical structures of bioactive compounds isolated
from the stems of P. aduncum are shown in Figure 6.
Myrcene (61)
α-terpinene (62)
p-cimene (63)
γ-terpinene (64)
1842
α-Phellendrene (65)
m-cimene (66)
1,8-Cineole (67)
Bornyl acetate (68)
Neryl acetate (69)
Geranyl acetate (70)
Copaene (71)
Eupatoriochromene (72)
Methyl 2,2-dimethyl-8-(3-methyl-2-butenyl)-2-H-chromene-6-carboxylate (73)
FIGURE 6. Compounds found in Piper aduncum stems
1843
PHYTOCHEMICAL CONSTITUENTS IN THE FRUITS OF
P. aduncum
The fruits of P. aduncum have been analysed using a
chemical extraction process and have been shown to
contain both monoterpenes and sesquiterpenes (Navickiene
et al. 2006). The specic compounds identied in the fruits
are α-pinene (10), β-pinene (11), myrcene, α-terpinene,
limonene (12), 1,8-cineole, (E)-ocimene (13), (Z)-ocimene
(14), γ-terpinene (64), linalool (15), β-caryophyllene (19),
α-humulene (21), germacrene D (25) and nerolidol (29).
Other dihydrochalcone compounds, including 2′-hydroxy-
4′,6′-dimethoxydihydrochalcone (74), 2′,6′-dihydroxy-
4′-methoxydihydrochalcone (52), 2′4-dihydroxy-4′,6′,3-
trimethoxydihydrochalcone (75) and 2′,4-dihydroxy-4′-
6′-dimethoxydihydrochalcone (76), have been isolated
from hexane extracts of P. aduncum fruits (Moreira et al.
1998). The chemical structures of these dihydrochalcones
are shown in Figure 7.
2’-hydroxy-4’,6’-dimethoxydihydrochalcone (74)
2’4-dihydroxy-4’,6’,3-trimethoxydihydrochalcone (75)
2’.4-dihydroxy-4’-6’-dimethoxydihydrochalcone (76)
FIGURE 7. Chemical structures of dihydrochalcones found in Piper aduncum fruits
2’-hydroxy-4’,6’-dimethoxydihydrochalcone (74)
2’4
-dihydroxy-4’,6’,3-trimethoxydihydrochalcone (75)
FIGURE 7. Chemical structures of dihydrochalcones found in Piper
aduncum fruits
1844
Dierent phytochemical constituents have been found in
varying quantities in dierent parts of the P. aduncum
plant, and dierent parts of the plant have been shown to
contain dierent types of compounds (Table 2).
TABLE 2. Summary of the compounds from the leaves, stems, and fruits of P. aduncum
Leaves Stems Fruits
Gallic acid (1)
Catechin (2)
Chlorogenic acid (3)
Epicatechin (4)
Quercetin-3-rutinoside (5)
Quercetin-3-rhamnoside (6)
Phloridzin (7)
Quercetin (8)
Phloretin (9)
α-pinene (10)
β-pinene (11)
Limonene (12)
(e)-ocimene (13)
(z)-ocimene (14)
Linalool (15)
α-copaene (16)
β-elemene (17)
α-gurjunene (18)
β-caryophyllene (19)
Allo-aromadendrene (20)
α-humulene (21)
Undecanone (22)
α-pinene (10)
β-pinene (11) Limonene (12)
(E)-ocimene (13)
(Z)-ocimene (14)
Linalool (15)
β-caryophyllene (19)
α-humulene (21)
Germacrene d(23)
Nerolidol (29)
Myrcene (61)
α-terpinene (62)
p-cimene (63)
γ-terpinene (64)
α-phellendrene (65)
m-cimene (66)
bornyl acetate (68)
neryl acetate (69)
geranyl acetate (70)
copaene (71)
eupatoriochromene (72)
methyl 2,2-dimethyl-8-(3-methyl-2-butenyl)-
2H-chromene-6-carboxylate (73)
α-pinene (10)
β-pinene (11)
Myrcene (61)
α-terpinene (62)
Limonene (12)
1,8-cineole (67)
(E)-ocimene (13)
(Z)-ocimene (14)
γ-terpinene, linalool (15)
β-caryophyllene (19)
α-humulene (21)
Germacrene D (25)
Nerolidol (29)
2’,6’-dihydroxy-4’-
methoxydihydrochalcone (52)
2’-hydroxy-4’,6’-
dimethoxydihydrochalcone (74)
2’4-dihydroxy-4’,6’,3-
trimethoxydihydrochalcone (75)
2’.4-dihydroxy-4’-6’-
dimethoxydihydrochalcone (76)
Germacrene d (23)
Bicyclogermacrene (24)
α-muurolene (25)
γ-cadinene (26)
δ-cadinene (27)
Germacrene b (28)
Nerolidol (29)
Spathulenol (30)
Globulol (31)
Safrole (32)
Β-gurjunene (33)
Β-sesquiphellandrene (34)
Rosifoliol (35)
Humulene epoxide ii (36)
Epi-cubenol (37)
Α-muurolol (38)
Α-cadinol (39)
1845
Shyobunol (40)
Piperitone (41)
Adunctins A (42)
Adunctins B (43)
Adunctins C (44)
Adunctins D (45)
Adunctins E (46)
Cardamonin (47)
Piperaduncin A (48)
Piperaduncin B (49)
Piperaduncin C (50)
Asebogenin (51)
2’,6’-dihydroxy-4’-
methoxydihydrochalcone (52)
Uvangoletin (53)
Dillapiole (54)
3-(3,7-dimethyl-2,6-octadienyl)-4-
methoxy-benzoic acid (55)
4-hydroxy-3-(3,7-dimethyl-2,6-
octadienyl) benzoic acid (56)
4-hydroxy-3-(3-methyl-1-oxo-2-butenyl-
5(3-methyl-2-butenyl) benzoic acid (57)
Methyl 4-hydroxy-3-(2’-hydroperoxy-3’-
methyl-3’-butenyl)benzoate (58)
Methyl 4-hydroxy-3-(2’-hydroxy-3’-
methyl-3’-butenyl)benzoate (59)
Aduncumene (60)
TRADITIONAL USES OF P. aduncum
TREATMENT OF DIARRHOEA
In traditional folk medicine, P. aduncum is widely used in
Jamaica for treating stomach aches, in Peru for treating
diarrhoea and in Colombia as a remedy for dysentery
(Luyen et al. 2017; Orjala et al. 1994; Thao et al. 2016).
Traditionally, an infusion of P. aduncum leaves is used
by Peruvian people as an alternative therapy for treating
diseases with symptomatic diarrhoea, due to the plant’s
antimicrobial, astringent, diuretic, stimulant, and
stomachic properties (Duarte et al. 2007; Morandim et al.
2005). The essential oil of P. aduncum has been shown
to ameliorate diarrhoea caused by Escherichia coli.
A minimal inhibitory concentration (MIC) of 1000 µg/
mL P. aduncum essential oil successfully inhibited
enterohaemorrhagic E. coli, 900 µg/mL enteropathogenic
E. coli and enteroinvasive E. coli (Duarte et al. 2007).
TREATMENT OF WOUNDS
P. aduncum is used in traditional Brazilian and Papua
New Guinean folk medicine for treating wounds due to its
antiseptic and anti-inammatory properties (Morandim et
al. 2005). The leaves are used in herbal remedies in two
ways. The rst involves making an infusion of the leaves,
which is then used to wash the bleeding area. The second
method is to crush the leaves and sprinkle them onto a
wound (Dal Picolo et al. 2014; Mee et al. 2009). Recent
studies have found that the essential oil of P. aduncum
has strong antimicrobial activity against many common
microorganisms that cause wounds to become infected,
such as Staphylococcus epidermis, S. aureus and
Pseudomonas aeruginosa. In one study, the MIC value of
isolated compounds for P. aeruginosa, Bacillus subtillis,
and S. aureus was reported to be more than 100 µg/mL
(Okunade et al. 1997). In addition, one in vitro study
1846
demonstrated a highly signicant anti-inammatory eect
of a methanolic extract of P. aduncum, with an inhibition
value of 20 µg/mL (Thao et al. 2016).
PHARMACOLOGICAL PROPERTIES OF P. aduncum
Table 3 provides a summary of the pharmacological
properties of P. aduncum.
Pharmacological
Properties
Plant
Parts
Extracts Methods Mechanisms Concentration
/ dose
Constituents References
Anti-fungal Leaves Ethanol In vitro on C.
cladosporiodes
and C.
sphaerospermum
n.a MIC: 0.5-5.0
µg
Benzoic acid
derivatives and
chromenes
(Lago et al.
2004)
Fruits n.a Direct
bioautography
on TLC plate
against C.
cladosporiodes
and C.
sphaerospermum
n.a MIC: 10 µg Monoterpenes
(Linalool)
(Navickiene
et al. 2006)
Aerial
part
n.a In vitro against
Clinipellis
perniciosa
(witches _
broom)
n.a MIC: 0.6-
1.0ppm
Dillapiole (de Almeida
et al. 2009)
Leaves Ethanol In vitro inhibitory
activity against
Cryptococcus
neoformans and
Candida albicans
n.a MIC: > 100 µg/
mL
Benzoic acid,
chalcones and
chromenes
(Okunade et
al. 1997)
Anti-bacterial Leaves Dichloromethane In vitro on
Bacillus subtilis
and Micrococcus
luteus
n.a MIC:
Sakuranetin:
0.5-2 µg/mL
Chalcones:
0.1-3 µg/mL
Sakuranetin and
chalcones
(Orjala et al.
1994)
Leaves n.a In vitro against S.
aureus
n.a IC50: 18.2 µg/
mL
Piperitone,
camphor and
viridiorol
(Monzote et
al. 2017)
Leaves Ethanol In vitro inhibitory
activity
against
Mycobacterium
intracellulare
n.a MIC: > 100 µg/
mL
Benzoic acid,
chalcones and
chromenes
(Okunade et
al. 1997)
TABLE 3. Summary of pharmacological properties of P. aduncum
1847
Insecticidal Leaves n.a In vitro on the
larvae and pupae
of A. aegypti
Mortality of
larvae and normal
abnormalities in
cells of pupae
200-400 µg/mL Dillapiole (Rafael et al.
2008)
Leaves n.a In vitro against
larvae and
adult insects
of Anopheles
marajoara and
Aedesa egypti
n.a Mortality:
100 ppm
(larvae) 600
ppm(insects)
Dillapiole (de Almeida
et al. 2009)
Leaves Hexane and ethyl
acetate
In vitro on
Antircasia
gemmatalis
Synergistic
action of the
phenylpropanoids,
apiol and
myristicin by
inhibiting the
function of
cytochrome P450
LC50:
Hexane extract:
6.35 mg/mL
Ethyl acetate:
5.79 mg/mL
Apiol (Lucena et al.
2017)
Leaves n.a Adulticidal
bioassay
by topical
application on
Musca domestica
Alterations
in a specic
physiological
processes that take
place upon contact
with toxicant
LC50:
6.2 - 23.8 µg/y
LC90:
13.3 - 50.5 µg/
y
n.a (Mee et al.
2009)
ANTI-PARASITIC ACTIVITY AGAINST GENUS Leishmania
Leishmaniasis is an infectious disease caused by diverse
agellate kinetoplastids of the genus Leishmania (Dal
Picolo et al. 2014). The essential oil from the hydro-
distillation of fresh P. aduncum leaves showed that
the high content of sesquiterpenes present possessed
antileishmanial activity in an in vitro test on promastigote
forms of Leishmania amazonensis, where the IC50 after
24 h demonstrated a value of 25.9 µg/mL, though no
explanation for the mechanism of action was proposed
(Bernuci et al. 2016). Nerolidol, which is a sesquiterpene
compound, has been found to exert antileishmanial
activity, where the IC50 after 24 h in an in vitro test on
Leishmania braziliensis demonstrated a value of 74.3 µg/
mL, whereas the IC50 after 24 h for P. aduncum essential
oil was reported to be eective at 77.9 µg/mL (Ceole et
al. 2017). Scanning electron microscopy showed severe
morphological changes, such as cell shrinkage and
alterations in the mitochondria, nuclear chromatin, and
agella pocket on promastigotes, following treatment
with nerolidol.
Chalcone derivatives have also been reported to
possess antileishmanial activity (Dal Picolo et al. 2014;
Torres-santos et al. 1999). Adunchalcone has been
obtained from an ethanolic extract of P. aduncum leaves,
whereas 2′,6′-dihydroxy-4′-methoxychalcone has been
obtained from a dichloromethane extract of P. aduncum
leaves. An in vitro test of adunchalcone on promastigote
forms of L. amazonensis and Leishmania shawi obtained
an EC50 of 11.03 and 11.26 μM, respectively, whereas
an in vitro test on 2′,6′-dihydroxy-4′-methoxychalcone
obtained an EC50 of 0.5 µg/mL against promastigotes and
24 µg/mL against amastigotes of L. amazonensis. It has
been suggested that the presence of two aromatic rings
linked by three carbons containing carbonyl group with a
hydrophilic and lipophilic substituent forms the structure
of adunchalcone, which inhibits the growth of parasites
(Dal Picolo et al. 2014). The mechanism of action for
the cytotoxicity of 2′,6′-dihydroxy-4′-methoxychalcone
has been suggested as being due to the enlargement
and disorganisation of mitochondria in L. amazonensis
promastigote (Torres-santos et al. 1999). Flores et al.
(2009) found that benzoic acid derivatives from ethanol
and water extracts of P. aduncum leaves also possessed
antileishmanial activity and reported that the IC50 against
L. braziliensis was 6.5 µg/mL in vitro. P. aduncum
extracts from the Atlanta forest have been reported to
contain 4-hydroxybenzoic acid, dihydrochalcones and
chromenes that contribute to the plant antileishmanial
eects (de Almeida et al. 2009). However, none of these
studies discussed the potential mechanism of action for
this antileishmanial activity.
ANTI-PARASITIC ACTIVITY AGAINST Plasmodium falciparum
Pink et al. (2005) reported that the essential oil from
P. aduncum has antiprotozoal activity against P. falciparum,
1848
which is the causal agent of malaria. The essential oil from
P. aduncum collected in Cuba showed high antiprotozoal
activity, where the IC50 value was reported as 1.3 µg/
mL. The antiprotozoal activity may be attributable to the
components piperitone, camphor and viridiorol found
in P. aduncum essential oil. It has been suggested that
the mechanism of action for the cytotoxicity could be the
decrease in mitochondrial membrane potential following
treatment (Monzote et al. 2017; Villamizar et al. 2017).
ANTI-PARASITIC ACTIVITY AGAINST Trypanosoma brucei
AND T. cruzi
The parasitic protozoa for trypanosomiasis (‘morning
sickness’) have been identied as T. brucei and T. cruzi.
The antiprotozoal activity of the essential oil from
P. aduncum leaves showed high activity against T. brucei
and T. cruzi, where the IC50 gave values of 2.0 and 2.1 µg/
mL, respectively (Monzote et al. 2017). The antiprotozoal
activity may be attributable to the presence of piperitone,
camphor, and viridiorol. It has been suggested that the
mechanism of action for the antiprotozoal activity could
be the reduction in mitochondrial membrane potential of
the parasite after treatment (Villamizar et al. 2017).
ANTI-PARASITIC ACTIVITY AGAINST Rhipicephalus
(boophilus) microplus
Silva et al. (2009) reported that a hexane the extraction of
P. aduncum leaves possessed anti-parasitic activity and
reported an LC50 of 9.3 mg/mL test against R. microplus
larvae and adult females in vitro. GC-MS analysis indicated
that the main compound responsible for the anti-
parasitic activity was dillapiole. The cytotoxic eect
was shown to be caused by alterations in development
and physiological disturbances in the metabolism of the
parasite (Silva et al. 2009).
ANTI-PARASITIC ACTIVITY AGAINST Schistosoma mansoni
de Castro et al. (2015) showed that dichloromethane
extracts of P. aduncum at concentrations of 25, 50, and
100 μM caused 100% mortality in S. mansoni adult
worms in vitro. GC-MS analysis showed that chalcone
was the major compound responsible for the anti-parasitic
activity. Treatment with cardamonin caused mortality,
and tegumental altered and reduced the oviposition and
motor activity of S. mansoni worms by inhibiting AT P
diphosphohydrolase (de Castro et al. 2015).
ANTIMICROBIAL PROPERTIES
ANTIFUNGAL
Research conducted by Lago et al. (2004) showed that
an ethanolic extract of P. aduncum leaves possesses
fungicidal activity against Cladosporium sphaerospermum
and Cladosporium cladosporioides, where the MIC values
have been reported to be between 0.5 and 5.0 µg/mL.
Nerolidol obtained from the essential oil of the fruits of
P. aduncum has also demonstrated antifungal properties
with an MIC value of 10 µg/mL against C. cladosporioides
and C. sphaerospermum (Navickiene et al. 2006).
A hydro-distillation of the aerial parts of P. aduncum
showed that dillapiole possesses antifungal activity,
where MIC values in an in vitro test against Clinipellis
perniciosa (‘witches-broom’) were reported to be between
0.6 and 1.0 ppm (de Almeida et al. 2009). In addition,
benzoic acid, chalcone, and chromene from ethanolic
extracts of P. aduncum were shown to kill Cryptococcus
neoformans and Candida albicans with MIC values
of more than 100 µg/mL (Okunade et al. 1997). No
mechanism of action for the antifungal properties of these
compounds was proposed in these studies.
ANTIBACTERIAL PROPERTIES
The crude of P. aduncum leaves from a dichloromethane
extract demonstrated significant antibacterial activity
towards Bacillus subtilis and Micrococcus luteus
(Orjala et al. 1994). In addition, the in vitro inhibitory
activity against Mycobacterium intracellulare has been
demonstrated with an MIC value of higher than 100 µg/
mL (Okunade et al. 1997). P. aduncum taken from the
Ciego de Avila Province, which is rich in camphene and
isoborneol constituents, has also been shown to have
moderate to poor antimicrobial activity against E. coli
and S. aureus (Gutiérrez et al. 2016). The mechanism of
action for the antibacterial properties was not discussed
in these studies.
INSECTICIDAL PROPERTIES
INSECTICIDAL ACTIVITY AGAINST MOSQUITOES
Previous studies have shown that the genus Piper is an
important pesticide against the genus Aedes due to the
presence of phenylpopanoids, lignoids, and avonoids.
Rafael et al. (2008) reported that dillapiole treatment
at concentrations of 200 and 400 µg/mL reduced survival
and reproduction in Aedes aegypti. The chromosal
damaged and nuclear alterations have been induced by
dillapiole treatments in larvae and pupae (Rafael et al.
2008). Dillapiole has also been shown to cause mortality
in Anopheles marajoara and A. aegypti, where one study
found that 100 and 600 ppm killed larvae and adult
insects, respectively (de Almeida et al. 2009). However, no
explanation for the mechanism of action was proposed in
this study. Oliveira et al. (2013) reported an anti-larvicidal
activity of P. aduncum essential oil against A. aegypti.
Research on the topical application of P. aduncum
against Musca domestica has found that the essential
oil from P. aduncum leaves has insecticidal properties
against houseflies (Mee et al. 2009). However, this
study did not discuss the compounds responsible for the
insecticidal properties of the essential oil. The mechanism
could be explained as resulting from alterations in a
specic physiological process that occurs upon contact
1849
with the toxicant. The insecticidal activity was tested on
male and female houseies of the same species, which were
collected from either Chow Kit or the Institute of Medical
Research. Houseies from Chow Kit showed a lower
susceptibility to the insecticidal eect of the P. aduncum
extract. Cossolin et al. (2019) reported that the essential
oil from P. aduncum showed toxicity against the brown
stink bug Euschistus heros, which usually attacks soy bean
plants. It exerted its eect by changing the insects’ tissues
and mitochondria population and through glycogen and
lipid reduction in the body fat cells (Cossolin et al. 2019).
INSECTICIDAL ACTIVITY AGAINST CATERPILLARS
Hexane and ethyl acetate crude extracts of P. aduncum
leaves have been shown to possess insecticidal activity
against Antircasia gemmatalis caterpillars (Lucena et al.
2017). GC-MS analysis showed that apiol is the major
bioactive compound responsible for the insecticidal
properties, as it inhibits the function of cytochrome P450.
The LC50 of both hexane and ethyl acetate extracts were
reported as 6.35 and 5.79 mg/mL, respectively.
ANTITUMOR AND ANTICANCER PROPERTIES
Research on the avonoid constituents of the ethanolic
extracts of P. aduncum leaves showed that concentrations
of 50 to 300 mg/kg body weight had anticancer
properties in DMBA-induced rats in vivo (Arroyo-Acevedo
et al. 2015). Dihydrochalcone from the dichloromethane
extract of P. aduncum leaves was also found to possess
anticancer activity, inhibiting human glioma and carcinoma
of the nasopharynx, human large cell lung carcinoma
and human breast cell carcinoma (Wang et al. 2014). In
an in vitro study on the cytotoxic activity of P. aduncum
against human nasopharynx carcinoma cells, the IC50 was
reported as 2.3 µg/mL, whereas in vitro cytotoxic activity
on glioma and carcinoma of human large cell lung and
human breast cell tissues obtained an IC50 of between 23
and 27 µg. The antioxidant capacity of an ethanolic extract
of the leaves of P. aduncum was tested using a DPPH
radical scavenging assay, and IC50 values of between 82
and 220 µg/mL were obtained (Escudero et al. 2008). The
antioxidant properties were said to be attributable to gallic
acid, chlorogenic acid, catechin and quercetin, which act
as free radical scavengers.
OTHER ACTIVITIES
The major component of P. aduncum essential oil,
dillapiole exhibited antiviral against West Nile virus (WNV)
is a mosquito-borne avivirus (Radice et al. 2019) and
poliovirus (Lohézic-Le Dévéhat et al. 2002). The ethanolic
extracts of P. aduncum has a gastroprotective eect in
mice and antisecretory eect in rats (Arroyo et al. 2013).
CONCLUSION AND PERSPECTIVES
P. aduncum is used as an alternative medicine in the
world. It is the most ethnobotanical uses among Piper
species. It is particularly important as a traditional
medicine for diarrhoea caused by E. coli infection and for
inducing wound healing. Studies on the phytochemistry
of P. aduncum have shown that the plant contains
many bioactive constituents, including flavonoids,
monoterpenes and sesquiterpenes, chalcones, chromenes,
phenylpropanoid, and benzoic acid derivatives. Extracts
of P. aduncum leaves, stems, and fruits have been found
to possess anti-parasitic properties against Leishmania,
Plasmodium falciparum, Trypanosoma brucei, T. cruzi,
Rhipicephalus microplus and Schistosoma mansoni, in
addition to their antifungal, antibacterial, insecticidal,
antitumor, and anticancer properties. However, the
mechanism of action and specic constituents responsible
for the biological properties of P. aduncum are yet to be
fully explored. Further studies on P. aduncum, which
shows potential utility in treating and preventing
infectious diseases are warranted.
ACKNOWLEDGEMENTS
The authors are thankful to the International Islamic
University Malaysia for funding through grant no
P-RIGS18-028-0028. MT and DS designed the study,
wrote the lay out and approved the nal version of the
manuscript. MSA, MBAK, and YS involved in literature
search and screened the paper. NFAMN wrote the main
text and revised the draft into the paper.
REFERENCES
Ahmad, F. & Rahmani, M. 1993. Chemical constituents of Piper
aduncum Linn (Piperaceae). Pertanika Journal of Science &
Technology 1(2): 185-188.
Arroyo-Acevedo, J., Chávez-Asmat, R.J., Anampa-Guzmán, A.,
Donaires, R. & Ráez-Gonzáles, J. 2015. Protective eect of
Piper aduncum capsule on DMBA-induced breast cancer in
rats. Breast Cancer: Basic and Clinical Research 9: 41-48.
Arroyo, J., Bonilla, P., Morena-Exebino, L., Ronceros, G.,
Tomas, G., Huamán, J., Raez, E., Quino, M. & Rodriguez-
Calzado, J. 2013. Gastroprotective and antisecretory eect of
a phytochemical made from matico leaves (Piper aduncum).
Revista Peruana de Medicina Experimental y Salud Pública
30(4): 608-615.
Bernuci, K.Z., Iwanaga, C.C., Fernandez-Andrade, C.M.,
Lorenzetti, F.B., Torres-Santos, E.C. Faiões, V.D.S.,
Gonçalves, J.E., Do Amaral, W., Deschamps, C., Scodro,
R.B.D.L., Cardoso, R.F., Baldin, V.P. & Cortez, D.A.G. 2016.
Evaluation of chemical composition and antileishmanial and
antituberculosis activities of essential oils of Piper species.
Molecules 21(12): E1698.
Ceole, L.F., Cardoso, M.D.G. & Soares, M.J. 2017. Nerolidol,
the main constituent of Piper aduncum essential oil, has
anti-Leishmania braziliensis activity. Parasitology 144(9):
1179-1190.
Cossolin, J.F.S., Pereira, M.J.B., Martínez, L.C., Turchen, L.M.,
Fiaz, M., Bozdoğan, H. & Serrão, J.E. 2019. Cytotoxicity of
Piper aduncum (Piperaceae) essential oil in brown stink bug
Euschistus heros (Heteroptera: Pentatomidae). Ecotoxicology
28(7): 763-770.
1850
Dal Picolo, C.R., Bezerra, M.P., Gomes, K.S., Passero, L.F.D.,
Laurenti, M.D., Martins, E.G.A., Sartorelli, P. & Lago, J.H.G.
2014. Antileishmanial activity evaluation of adunchalcone,
a new prenylated dihydrochalcone from Piper aduncum L.
Fitoterapia 97: 28-33.
de Almeida, R.R., Souto, R.N., Bastos, C.N., da Silva, M.H.
& Maia, J.G. 2009. Chemical variation in Piper aduncum
and biological properties of its dillapiole-rich essential oil.
Chemistry & Biodiversity 6(9): 1427-1434.
de Castro, C.C., Costa, P.S., Laktin, G.T., de Carvalho, P.H.,
Geraldo, R.B., de Moraes, J., Pinto, P.L., Couri, M.R.,
Pinto, P.D.F. & Da Silva Filho, A.A. 2015. Cardamonin,
a schistosomicidal chalcone from Piper aduncum L.
(Piperaceae) that inhibits Schistosoma mansoni ATP
diphosphohydrolase. Phytomedicine 22(10): 921-928.
dos Santos, V.L.P., Franco, C.R.C., Amano, E., Messias-Reason,
I.J. & Budele, J.M. 2015. Anatomical investigations of Piper
amalago (Jaborandi-Manso) for the quality control. Revista
Brasileira de Farmacognosia 25(2): 85-91.
Duarte, M.C.T., Leme, E.E., Delarmelina, C., Soares, A.A.,
Figueira, G.M. & Sartoratto, A. 2007. Activity of essential
oils from Brazilian medicinal plants on Escherichia coli.
Journal of Ethnopharmacology 111(2): 197-201.
Escudero, M.R., Escudero, D.F.R., Remsberg, C.M., Takemoto,
J.K., Davies, N.M. & Yáñez, J.A. 2008. Identication of
polyphenols and anti-oxidant capacity of Piper aduncum L.
The Open Bioactive Compounds Journal 1: 18-21.
Flores, N., Jiménez, I.A., Giménez, A., Ruiz, G., Gutiérrez, D.,
Bourdy, G. & Bazzocchi, I.L. 2009. Antiparasitic activity
of prenylated benzoic acid derivatives from Piper species.
Phytochemistry 70 (5): 621-627.
Gutiérrez, Y., Montes, R., Scull, R., Sánchez, A., Cos, P.,
Monzote, L. & Setzer, W.N. 2016. Chemodiversity associated
with cytotoxicity and antimicrobial activity of Piper aduncum
Var. Ossanum. Chemistry & Biodiversity 13(12): 1715-1719.
Hartemink, A.E. 2010. The invasive shrub Piper aduncum in
Papua New Guinea: A review. Journal of Tropical Forest
Science 22(2): 202-213.
Lago, J.H.G., Chen, A., Young, M.C.M., Guimarães, E.F., de
Oliveira, A. & Kato, M.J. 2009. Prenylated benzoic acid
derivatives from Piper aduncum L. and P. hostmannianum
C. DC. (Piperaceae). Phytochemistry Letters 2(3): 96-98.
Lago, J.H.G., Ramos, C.S., Casanova, D.C.C., Morandim,
A.D.A., Bergamo, D.C.B., Cavalheiro, A.J., Bolzani, V.D.S.,
Furlan, M., Guimaraes, E.F., Young, M.C.M. & Kato, M.J.
2004. Benzoic acid derivatives from Piper species and their
fungitoxic activity against Cladosporium cladosporioides
and C. sphaerospermum. Journal of Natural Products 67(11):
1783-1788.
Lohézic-Le Dévéhat, F., Bakhtiar, A., Bézivin, C., Amoros, M.
& Boustie, J. 2002. Antiviral and cytotoxic activities of some
Indonesian plants. Fitoterapia 73(5): 400-405.
Lucena, D.C., Bertholdo-Vargas, L.R., Silva, W.C., Machado,
A.F., Lopes, T.S., Moura, S. & Barros, N.M. 2017. Biological
activity of Piper aduncum extracts on Anticarsia gemmatalis
(Hübner) (Lepidoptera: Erebidae) and Spodoptera frugiperda
(J.E. Smith) (Lepidoptera: Noctuidae). Anais Da Academia
Brasileira de Ciencias 89(3): 1869-1879.
Luyen, B.T.T., Thao, N.P., Widowati, W., Fauziah, N., Maesaroh,
M., Herlina, T. & Kim, Y.H. 2017. Chemical constituents of
Piper aduncum and their inhibitory eects on soluble epoxide
hydrolase and tyrosinase. Medicinal Chemistry Research
26(1): 220-226.
Mee, C.K., Sulaiman, S. & Othman, H. 2009. Efficacy of
Piper aduncum extract against the adult housey (Musca
domestica). The Journal of Tropical Medicine Parasitology
32(2): 52-57.
Monzote, L., Scull, R., Cos, P. & Setzer, W. 2017. Essential
oil from Piper aduncum: Chemical analysis, antimicrobial
assessment, and literature review. Medicines 4(3): 49.
Morandim, A.D.A., Bergamo, D.C.B., Kato, M.J., Cavalheiro,
A.J., Bolzani, V.D.S. & Furlan, M. 2005. Circadian rhythm of
anti-fungal prenylated chromene in leaves of Piper aduncum.
Phytochemical Analysis 16(4): 282-286.
Moreira, D.D.L., Guimarães, E.F. & Kaplan, M.A.C. 1998.
A chromene from Piper aduncum. Phytochemistry 48(6):
1075-1077.
Navickiene, H.M.D., Morandim, A.D.A., Alécio, A.C., Regasini,
L.O., Bergamo, D.C.B., Telascrea, M., Cavalheiro, A.J.,
Lopes, N.M., Bolzani, V.D.S., Furlan, M., Marques, M.O.M.,
Young, M.C.M. & Kato, M.J. 2006. Composition and
antifungal activity of essential oils from Piper aduncum,
Piper arboreum and Piper tuberculatum. Quimica Nova
29(3): 467-470.
Ndjonka, D., Rapado, L.N., Silber, A.M., Liebau, E. & Wrenger,
C. 2013. Natural products as a source for treating neglected
parasitic diseases. International Journal of Molecular
Sciences 14(2): 3395-3439.
Okunade, A.L., Huord, C.D., Clark, A.M. & Lentz, D. 1997.
Antimicrobial properties of the constituents of Piper
aduncum. Phytotherapy Research: An International Journal
Devoted to Medical and Scientic Research on Plants and
Plant Products 11(2): 142-144.
Oliveira, G.L., Cardoso, S.K., Júnior, C.R.L., Vieira, T.M.,
Guimarães, E.F., Figueiredo, L.S., Martins, E.R., Moreira,
D.L. & Kaplan, M.A.C. 2013. Chemical study and larvicidal
activity against Aedes aegypti of essential oil of Piper
aduncum L. (Piperaceae). Anais Da Academia Brasileira de
Ciencias 85(4): 1227-1234.
Orjala, J., Wright, A.D., Behrends, H., Folkers, G., Sticher, O.,
Rüegger, H. & Rali, T. 1994. Cytotoxic and antibacterial
dihydrochalcones from Piper aduncum. Journal of Natural
Products 57(1): 18-26.
Pink, R., Hudson, A., Mouriès, M.A. & Bendig, M. 2005.
Opportunities and challenges in antiparasitic drug discovery.
Nature Reviews Drug Discovery 4(9): 727-740.
Radice, M., Pietrantoni, A., Guerrini, A., Tacchini, M., Sacchetti,
G., Chiurato, M., Venturi, G. & Fortuna, C. 2019. Inhibitory
eect of Ocotea quixos (Lam.) Kosterm and Piper aduncum
L. essential oils from Ecuador on West Nile virus infection.
Plant Biosystem - An International Journal Dealing with all
Aspects of Plant Biology 153(3): 344-351.
Rafael, M.S., Hereira-Rojas, W.J., Roper, J.J., Nunomura, S.M.
& Tadei, W.P. 2008. Potential control of Aedes aegypti
(Diptera: Culicidae) with Piper aduncum L. (Piperaceae)
extracts demonstrated by chromosomal biomarkers and
toxic eects on interphase nuclei. Genetics and Molecular
Research 7(3): 772-781.
Rali, T., Wossa, S.W., Leach, D.N. & Waterman, P.G. 2007.
Volatile chemical constituents of Piper aduncum L. and Piper
1851
gibbilimbum C. DC (Piperaceae) from Papua New Guinea.
Molecules 12: 389-394.
Silva, W.C., de Souza Martins, J.R., de Souza, H.E.M., Heinzen,
H., Cesio, M.V., Mato, M., Albrecht, F., de Azevedo, J.L.
& de Barros, N.M. 2009. Toxicity of Piper aduncum L.
(Piperales: Piperaceae) from the Amazon forest for the cattle
tick Rhipicephalus (Boophilus) microplus (Acari: Ixodidae).
Veterinary Parasitology 164(2-4): 267-274.
Thao, N.P., Luyen, B.T.T., Widowati, W., Fauziah, N., Maesaroh,
M., Herlina, T., Manzoor, Z., Ali, I., Koh, Y.S. & Kim, Y.H.
2016. Anti-Inammatory avonoid C-glycosides from Piper
aduncum leaves. Planta Medica 82(17): 1475-1481.
Torres-santos, E.C., Moreira, D.L., Kaplan, M.A., Meirelles,
M.N. & Rossi-Bergmann, B. 1999. Selective effect of
2’,6’-dihydroxy-4-methoxychalcone isolated from Piper
aduncum on Leishmania amazonensis. Antimicrobiral Agents
and Chemotherapy 43(5): 1234-1241.
Villamizar, L.H., Cardoso, M.D.G., Andrade, J.D., Teixeira, M.L.
& Soares, M.J. 2017. Linalool, a Piper aduncum essential
oil component, has selective activity against Trypanosoma
cruzi Trypomastigote forms at 4°C. Memórias do Instituto
Oswaldo Cruz 112(2): 131-139.
Wang, Y.H., Morris-Natschke, S.L., Yang, J., Niu, H.M.,
Long, C.L. & Lee, K.H. 2014. Anticancer principles from
medicinal Piper (Hú Jiāo) plants. Journal of Traditional and
Complementary Medicine 4(1): 8-16.
Muhammad Taher, Mohamad Shahreen Amri, Muhammad Badri
Abdul Kudos & Nur Fasya Ajda Md Nor
Department of Pharmaceutical Technology
Faculty of Pharmacy, International Islamic University Malaysia
Jalan Sultan Ahmad Shah
25200 Kuantan, Pahang Darul Makmur
Malaysia
Deny Susanti*
Department of Chemistry
Faculty of Science, International Islamic University Malaysia
Jalan Sultan Ahmad Shah
25200 Kuantan, Pahang Darul Makmur
Malaysia
Yandi Syukri
Department of Pharmacy
Islamic University of Indonesia
Yogyakarta, 55584
Indonesia
*Corresponding author; email: deny@iium.edu.my
Received: 6 March 2019
Accepted: 25 March 2020
