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Bioactive Compounds from Plants Used in
Peruvian Traditional Medicine
Article in Natural product communications · March 2016
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Department of Organic Chemistry, University of Granada,
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Dipartimento di Chimica Bioorganicae Biofarmacia,
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National Engineering Laboratory for TCM Standardization Technology,
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Bioactive Compounds from Plants Used in Peruvian Traditional
Medicine
Olga Locka*
, Eleucy Perezb
, Martha Villarc
, Diana Floresd
and Rosario Rojase
a
Sociedad Química del Perú, Nicolás de Aranibar 696, Santa Beatríz, Lima 01, Perú
b
Facultad de Ciencias Biológicas, Universidad Nacional Mayor de San Marcos, Av. Germán Amézaga 375,
Lima 01, Perú
c
Dirección de Medicina Complementaria, Seguro Social de Salud, Lima 11, Perú
d
Consultant, International Trade Centre ITC (UNCTAD/WTO), Geneva, Switzerland
e
Unidad de Investigación en Productos Naturales, Laboratorios de Investigación y Desarrollo, Facultad de
Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, Lima 34, Perú
olock2006@yahoo.es
Received: January 28th
, 2015; Accepted: February 2nd
, 2016
It is estimated that there are as many as 1400 plant species currently used in traditional Peruvian medicine; however, only a few have undergone scientific
investigation. In this paper, we make a review of the botanical, chemical, pharmacological and clinical propierties of the most investigated Peruvian medicinal
plants. The plant species selected for this review are: Smallanthus sonchifolius (yacon), Croton lechleri (sangre de grado), Uncaria tomentosa/U. guianensis
(uña de gato), Lepidium meyenii (maca), Physalis peruviana (aguaymanto), Minthostachys mollis (muña), Notholaena nívea (cuti-cuti), Maytenus macrocarpa
(chuchuhuasi), Dracontium loretense (jergon sacha), Gentianella nitida (hercampuri), Plukenetia volubilis (sacha inchi) and Zea mays (maiz morado). For
each of these plants, information about their traditional uses and current commercialization is also included.
Keywords: Croton lechleri, Lepidium meyenii, Peru, Physalis peruviana, Smallanthus sonchifolius, Traditional medicine, Uncaria tomentosa.
INTRODUCTION
Traditional medicine, as an essential part of the cultures, was for
centuries the only health system guardian of the past generations.
According to the World Health Organization, about 80% of the
world population today relies on traditional systems of medicine for
their primary health needs [1].
Medicinal plants are part of the legacy of Peruvian traditional
medicine, a heritage of pre-Columbian cultures. They were
represented in the ceramics of different pre-Inca and Inca cultures,
and colonial chronicles show us that our old settlers achieved a set
of knowledge that allowed them to use plants not only to cure body
diseases, but also ailments of the soul. To date, they remain the first
choice for consultation and treatment in our country [2].
A contribution from traditional Peruvian medicine to the world
pharmacotherapy is the alkaloid quinine – one of the most important
drugs for the treatment of malaria over three centuries. This active
ingredient was found in the bark of the cinchona tree (Cinchona
officinalis), a native tree of the Rubiaceae family that grows in
humid Andean forests. It was used as an antipyretic by natives.
Thus, in 1649 the Jesuits published the first report on quinine and
cinchona in the book "Sheula Romana" [3]. Other important
contribution to current pharmacopoeia, especially to anesthesiology,
is the coca plant (Erytroxylum coca), from which cocaine was first
isolated in 1859 and later led to local anesthetics (lidocaine). Another
important contribution was the balsam of Peru (Myroxylon
balsamum), which was used worldwide for the treatment of wounds.
Peru possesses 28 of the 32 existing climates in the world and 84 of
the 103 life zones known on earth [4]. It is considered one of the 12
megadiverse countries, with a varied flora calculated in
approximately 25,000 species. Thus, around 10% of the world´s
flora grows in Peru and 30% of these plants are endemic.
Approximately 5000 Peruvian plants are being used by the
population for 49 different purposes or applications (1400 species
are described as medicinal). The majority of these useful native
species are not being cultivated; only 222 can be considered to be
domesticated or semidomesticated [5].
Only when tradition and science meet, knowledge transcends. In
this sense, a review of the most promising Peruvian medicinal
plants was carried out by a multidisciplinary team. The plants
selected for this study were: Smallanthus sonchifolius (yacon),
Croton lehleri (dragon's blood), Uncaria tomentosa/U. guianensis
(cat's claw), Lepidium meyenii (maca), Physalis peruviana
(aguaymanto), Minthostachys mollis (muña), Notholaena nívea
(cuti-cuti), Maytenus macrocarpa (chuchuhuasi), Dracontium
loretense (jergon sacha), Gentianella nitida (hercampuri),
Plukenetia volubilis (sacha inchi) and Zea mays (maiz morado). The
first five plants have been discussed in more detail in the present
review because of their extensive traditional use, high number of
peer reviewed publications; as well as their increasing demand and
commercialization in local and international markets.
Smallanthus sonchifolius (Poepp. & Endl.) H. Rob.
Smallanthus sonchifolius (Poepp. & Endl.) H. Robinson, Class
Dicot, Order Asterales Family Asteraceae. The cultivation of Yacon
dates from Pre-Inca age (Nazca, Paracas and Mochica cultures) so
the historical use of this species is directly related to "traditional
knowledge" – that was possessed by native Indian people, Afro-
American and local communities, and transmitted from one
generation to the other, usually orally and outside the formal
education system [6].
NPC Natural Product Communications 2016
Vol. 11
No. 3
315 - 337

316 Natural Product Communications Vol. 11 (3) 2016 Lock et al.
SCIENTIFIC NAME [6]
Smallanthus sonchifolius (Poepp. & Endl.) H. Robinson
SYNONYM [7]
- Polymnia sonchifolia Poepp. & Endl. 1845
- Polymnia edulis Wedd. 1857
COMMON NAMES [6]
- Llacon: North of Peru
- Llakwash: Ferreñafe, Lambayeque in Peru
- Aricoma: Aymara
- Aricuma: Quechua
- Jicama: Ecuador, Venezuela, Colombia
- Xicama: Mexico, Peru
PLANT MORPHOLOGY [7,8]
Habit: herbaceous, perennial, erect, 0.8 to 2 m long, with few to
many branches.
Roots: storage roots characterized by accumulation of fructose
polymer in the parenchymatous tissue. At the top, crown buds used
in plant propagation.
Stems: cylindrical, pubescent, varying from green to purple, hollow
at maturity branched or not, depending on whether it was
reproduced vegetatively or by seed.
Leaves: petiolate, opposite decussate, triangular blade, edge
irregularly dentate, acute apex, base hastate, with three prominent
nervous, slightly pubescent on the adaxial face different from
abaxial face which have a great pubescence. Difference is obvious
leaf size before and after flowering, being smaller thereafter.
Inflorescence and flowers: capitulum arranged in dichasia.
Unisexual flowers, being female ligulate and male flowers tubular,
both corollas are gamopetalous with 5 petals fused; female flowers
have inferior ovary, fusiform and purple; male stamens with fused
anthers, which are black.
Fruit: typical in family Asteraceae, that is a Cypsela.
Habitat: it can be found both cultivated and in wild forms, in earthy
sandy clay soil and an elevation between 50-3500 m altitude [2],
from Venezuela and Colombia to northern Argentina. In recent
years, its cultivation has acquired great importance because of its
medicinal properties, so this activity is well widespread not only in
Latin America but also in Europe and Asia [9].
ETHNOMEDICINE
Through the years, Yacon has been used as an excellent product to
satisfy hunger and thirst, as well as for its various therapeutic
effects that have been passed down for generations. Both the leaves
and fruits are used. The latter is traditionally used as fresh or dried
fruit at different degrees, and occasionally (for ceremonies or
parties) as chicha or jam. The fruit is used for rehydratation due to
its high water content, it prevents fatigue and cramps. In addition, it
is also used to prevent rickets and for kidney and liver conditions.
In Bolivia, the use of the leaves by diabetics and for digestion
conditions has been reported; in the north of Peru, it is traditionally
eaten before going to bed to delay aging [10,11]. Furthermore, it is
indicated to relieve constipation, lower high-blood pressure, prevent
colon cancer and as antimicrobial and antiparasitic [7, 12].
CHEMICAL CONSTITUENTS
The key component of yacon roots is composed of oligosaccharides,
specifically the fructo-oligosaccharides, FOS, also known as
oligofructans or oligofructoses, belonging to the fructans. FOS are
made up of fructose units connected by β (2 → 1) and/or β (6 → 1)
links [13a]. FOS (1), consist of 3 to 10 fructose units and they
always contain a glucose unit at the start of each fructan chain with
a α (1→2) link. It is estimated that 50-70% of the dried root is
composed by FOS, as opposed to other roots whose main
component is starch [13b].
Also present in yacon roots are phenolic compounds. In addition to
known acids like caffeic (2), chlorogenic, and ferulic (3) acids,
three new caffeoyl esters of atraric acid, as well as two caffeoyl
esters (mono and dicaffeoyl esters of octulosonic acid) have been
reported. The latter is classified as a keto-aldonic acid, with an
skeleton 6, 8-[3,2,1] octane, a structure that is rarely found in
natural products [14 a-d]. Other chemical constituents present in
small quantities in the roots of yacon are proteins, fats, fiber,
glucose, fructose, saccharose; and other nutrients like calcium,
phosphorous, iron, niacin, riboflavin, ascorbic acid and the L-
tryptophan amino acid [15].
From the leaves of yacon, a new melampolide- type sesquiterpene
lactone, called sonchifolin, was isolated (4), as well as the well-
known polymatin B, uvedalin (5), enhydrin (6), and fluctuanin (7),
in addition to two other structures recently reported: the methyl
esters of the acids 8β- tigloyloxymelampolid-14-oic and 8β-
metacryloyloxymelampolid-14-oic [16a,b]. Diterpenoid compounds
present are the ent-kaurenoic acid and its angeloyloxide derivatives
[16c] two new diterpenes tetrahidroxy ent-kauranes named ent-
kaurane-3β,16β,17,19-tetrol and ent-kaurane-16β,17,18,19-tetrol
[16d] and new acyclic diterpenic acids called smaditerpenic acids
A-D [16e] and E-F (8-9) [16f] (Figure 1).
Amongst the phenolic compounds present in the leaves are the
gallic, chlorogenic, caffeic and ferulic acids; as well as the
flavonoids rutin, myricetin, kaempferol and quercetin; being gallic
acid and rutin the most abundant phenolic compounds in the leaves
[17].
Figure 1: Some chemical compounds isolated from Smallanthus sonchifolius.
PHARMACOLOGY
The methanol extract of yacon roots showed good antioxidant
activity in the DPPH test. The phenolic compounds caffeic and
chlorogenic acids would be responsible for this activity [14a,17,18].

Plants used in traditional Peruvian medicine Natural Product Communications Vol. 11 (3) 2016 317
Sonchifolin, a melampolide isolated from the methanolic extract of
the leaves of yacon possess good activity against the fungus
Pyricularia oryzae; while the melampolides fluctuanin, uvedalin
and enhydrin were active against the bacterium Bacillus subtilis
[16a,b]. Ent-kaurenoic acid from the dichloromethane extract of
yacon leaves is active against Staphylococcus aureus and S.
epidermidis [19a]. Enhydrin was even active against methicillin-
resistant S. aureus [19b]. Enhydrin and uvedalin might have
potential as agents against Chagas disease, since they have
significant trypanocidal activity against the trypomastigote forms of
Trypanosoma cruzi [19c].
The topical application (0.25 mg/ear) of yacon leaves extract, rich
in sesquiterpenelactones, reduced the inflammation by 44.1%
compared to the control group [20].
Aybar et al. demonstrated that a decoction of yacon leaves have a
hypoglycemic effect in rats with diabetes induced by streptozotocin
(STZ), with a concomitant increase in circulating insulin
concentration [21a]. Aqueous extract and the ethylacetate fraction
decrease the glucose production in normal hepatocytes. This effect
could be explained by an increase of insulin synthesis and/or the
inhibition of hepatic gluconeogenesis and glycogenolysis [21b, c].
The sesquiterpene lactone enhydrin, the diterpene ent-kaurenoic
acid and a butanol extract from the leaves of yacon, rich in caffeic,
chlorogenic and three dicaffeoilquinic acids, showed good in vivo
hypoglycemic activity [21d,e]. According to Genta et al., these
compounds are responsible for the hypoglycemic activity of yacon
leaves, although their mechanisms of action are still unknown
[21d]. Other coumpounds that could be also responsible for the anti-
diabetes activity of yacon leaves are the smallanthaditerpenic acids
(A – D); all of them exhibited in vitro -glucosidase inhibitory
activity [21f].
The roots of yacon also exhibit antidiabetes activity in vivo. An
aqueous extracts of the roots reversed dyslipidaemia and
hyperglycaemia in rats with diabetes mellitus (DM) induced by
STZ. It also showed a hepatoprotective effect and an improvement
of symptoms commonly associated with DM type 1 (hyperphagia,
polydipsia and weight loss) [22a].
Yacon root extracts and one of its constituents (chlorogenic acid)
produced a significant hypoglycemic effect in STZ-induced diabetic
rats. Also, they decreased total cholesterol and triglyceride
concentrations [22b].
The fructooligosaccharides (FOS) present in yacon roots behave as
prebiotics by promoting the growth of probiotic organisms.
Pedrechi et al. demonstrated that FOS of yacon are metabolized by
3 strains of known probiotics (Lactobacillus acidophilus NRRL-
1910, Lactobacillus plantarum NRRL B-4496 y el Bifidobacterium
bifidum ATCC 15696) [13b].
Yacon roots flour has a prebiotic effect in vivo by stimulating the
growth of bifidobacteria and lactobacilli, and by increasing the
concentrations of short chain fatty acids [23].
CLINICAL ASPECTS
There are no clinical studies on safety and tolerance, however, some
pilot studies have been reported, the same being aimed at proving
the hypoglycemic effect and prebiotic action of both the leaves and
fruits of Smallanthus sonchifolius. Regarding the use of the leaves,
there is a clinical trial conducted in 206 adults who were divided
into two groups: one experimental group (diabetic patients on
glibenclamide) which was subdivided into two subgroups, one on
glibenclamide and the other on glibenclamide plus yacon. The other
group was the control group made up of apparently healthy people;
it was subdivided into two subgroups, one group receiving no
treatment and the other only yacon leaves. The plant was prepared
as an infusion, with 1g of yacon leaves in teabags, to be drunk 3
times daily. All groups were evaluated before and after treatment
forBody Mass Index (BMI), fasting blood glucose, glycosylated
hemoglobin (HbA1c) and fructosamine. It was observed that in the
subgroups who were given yacon leaves, fasting blood glucose
decreased by 42.7%, glycosylated HbA1c by 21.7%, and
fructosamine by 33.78% [24a].
With respect to the use of the fresh root of Samallanthus
sonchiofolius, there is an unblinded pilot clinical trial with a before
and after design, involving 6 apparently healthy subjects whose
BMI was 21.75. All subjects underwent biochemical tests (liver
function and lipid profile, complete blood count), in addition, all
received Oral Glucose Tolerance Test (OGTT). The results were
within the normal range. Next, they were administered 300 g of
fresh yacon root orally and received OGTT, the results showed a
reduction of 79.8% (p = 0.001) in postprandial glycemic response
[24b].
Furthermore, a comparative clinical trial of the effect of the leaves
and fresh root of Samallanthus sonchiofolius on seric glucose and
glycosilated hemoglobin was conducted on 30 patients with type II
diabetes receiving pharmacological treatment and with an ad
libitum diet. These patients were divided into 3 groups: the first
group received 500 g/day of yacon fresh root; the second group,
lyophilized yacon extract equivalent to 500 g/day of the fresh fruit;
and the third group was given yacon-leaf teabags (each teabag
equivalent to 1g of leaves) to drink three times per day. With
respect to HbA1c, an average decrease of 1.98%, 1.84% and 1.14%
was observed in each group, respectively; and seric glucose
decreased considerably, in greater extent in the third group and in
lesser extent in the fresh fruit group [24c].
Another important characteristic of yacon is its prebiotic effect. In
order to evaluate this characteristic, a study was conducted with 16
healthy subjects (8 men and 8 women) who received 20 g of fresh
yacon (equivalent to 6.4 g of FOS) daily. A two-week crossover
design was used. The evaluation measured the colonic transit time
using radio-opaque markers, and showed that the time reduced
significantly from 59.7 +/- 4.3 to 38.4 +/- 4.2 hours with p< 0.0001.
The frequency of bowel movement increased from 1.1 to 1.3. Very
few adverse effects were observed, only a slight increase in
meteorism. The study concluded that yacon accelerates intestinal
transit significantly [25].
ECONOMIC IMPORTANCE
The first introduction of yacon in Europe was made in 1927 by
Calvino, with the aim of finding an alternative fuel (alcohol) and
development of forage production in Northern Italy. After
adaptation research, it was recommended to use yacon as a nutrition
source, as a feeding crop, and mainly, as a material for sugar
industry. A couple years later, yacon was introduced in Germany in
1941, in Hamburg and Wulfsdorf. Yacon was also introduced in the
Czech Republic, where it has been grown since 1994 [26].
In the 80s, it entered New Zealand as a new crop [27]. However, it
has not been demanded directly as a commercial vegetable. During
the last thirty years, yacon was again enhanced in a production of
processed foods, extracts and syrups. In New Zealand, the
commercialization of novel foods is regulated by the Standard 1.5.1

of the Australia New Zealand Food Standards Code. Yacon is
valued in Japan and Korea as food and Food Ingredient and it is
used in a variety of products.
In addition, the U.S. Environmental Protection Agency (EPA)
includes yacon in its lists of food crops for purposes of establishing
pesticide residue tolerances [28]. In Canada, yacon root extract is
permitted for use as a non-medicinal sweetening agent [29]. In
European market, the situation of yacon changed at the beginning of
2014. A history of significant food use of yacon roots or
Smallanthus sonchifolius in the EU before 1997 has been
demonstrated, and thus it is no longer considered novel food [30].
In the meantime, the Peruvian Anti-Biopiracy Commission has the
task of developing actions to identify, prevent and avoid acts of bio-
piracy with the aim of protecting the interests of the Peruvian State
[31]. Until now, the Peruvian National Commission against Bio-
piracy found 2800 patents applications. Japan is the country that has
researched yacon for more than 10 years. The Peruvian Commission
against Bio-piracy mentions 50 Japanese patents involving yacon,
in some of which it constitutes the primary component of the
invention [32]. Mainly, yacon patents refer to preparation as food,
pharmaceuticals and cosmetics ingredients uses.
Croton lechleri Muell. Arg.
INTRODUCTION
Croton lechleri Muell. Arg. (1974), Class Dicot, Order
Euphorbiales, Family Euphorbiaceae. This species is primarily used
because of its healing properties in the treatment of gastric ulcers,
puerperium, tonsillitis, pharyngitis, tumors, for birth control, and
others. The use of sangre de grado came from the 1600s so it is
widely distributed and is being continued up to day [33].
SCIENTIFIC NAME [34]
Croton lechleri Muell. Arg. (1974)
SYNONYM [7]
- Croton palanostigma Klotrch (1951)
- C. tarapotensis Muell. Arg. (1951)
- C. draconoides Muell. Arg.
COMMON NAMES [6,35,36]
- Sangre de grado, dragon's blood, stick drago, dragon blood
- Irare, jimi mosho, shawan karo: Shipibo-Conibo
- Pocure, racurana, uksavakiro, widnku: Amarakaeri
Habit: tree 10-15 m tall, with a broad and rounded crown.
Stem: the trunk with whitish bark and glabrous, which when cut
secretes a vinous red latex which is used in the pharmaceutical
industry. The branches are covered with stellate hairs.
Leaves: cordate to ovate, 10-15 cm long and 7-11 cm wide, apex
acuminate, margin entire, glabrous, with 2 glands at the base of the
leaf, penninervia.
Inflorescence and flowers: flowers arranged in loose clusters
terminal, with the male flowers located at the top of the
inflorescence and female flowers at the bottom. Calyx with 5
granulated sepals, corolla with 5 elliptic petals, the pistil with bifid
stigma, superior ovary; stamens 15-18 cm long, with pubescent
filaments.
Fruit: pubescent capsule 5 mm in length and 4-6 mm wide.
Habitat: this species is found in both high and low jungle in Peru
and Ecuador, below 1000 m. In Peru is in Departments of
Amazonas, Cuzco, Huanuco, Loreto, Madre de Dios and San
Martin [36].
ETHNOMEDICINE
Over the years, dragon's blood has been used to heal wounds
mainly, but anti-inflammatory, antiseptic and hemostatic properties
have also been reported [36,37]. Other uses include: treatment of
diarrhea, gastrointestinal ulcers, pyorrhea, menstrual cramps, fevers
from digestive causes, vaginal baths before delivery, for bleeding
after childbirth, urinary retention (when taken in small doses), and
skin conditions. In addition, anticancer action is attributed to C.
lechleri. About 8 drops are administered in all these uses of folk
medicine – although there are doses which may reach up to 20 or 30
drops – and are usually added to an infusion of any aromatic plant.
[3,38].
The phytochemical characterization of the sap of dragon’s blood
has led to the finding that the oligomeric proanthocyanidins
(catechin, epicatechin, gallocatechin (10), epigallocatechin (11) at a
different degree of polymerization constitute almost 90% of its dry
weight; among them are dimeric procyanidins B-1 and B-4, dimers
and trimers as catechin-(4α→8)- epigallocatechin, gallocatechin-
(4α→8)-epicatechin, gallocatechin-(4α→6)-epigallocatechin,
catechin-(4α→8)-gallocatechin-(4α→8)-gallocatechin and
gallocatechin-(4α→8)-gallocatechin-(4α→8)-epigallocatechin and
other higher oligomers [39a]. SP-303. a mixture of basic monomers
obtained from the sap of dragon’s blood, consists mainly of (+)-
gallocatechin and (-)-galloepicatechin and to a lesser amount, of
(+)-catechin and (-)-epicatechin [39b].
Various minor compounds have also been found: one is the alkaloid
taspine (12) found in the sap of mature tree [40]. Others are the
dihydrobenzofuran lignans 3’,4-O-dimethylcedrusin and 4-O-
methylcedrusin (13) [41], 1,3,5-trimethoxybenzene (14) and 2,4,6,-
trimethoxyphenol, various diterpenoids clerodane type: korberin A
(15) and B (16), [42a,b] and norisoprenoids blumenols B and C,
4,5-dihydroblumenol A and floribundic acid glucoside [43].
Clerodanes as crolechinol and crolechinic acid have been also
isolated from the bark [42b].
Figure 2: Some chemical compounds isolated from Croton lechleri.

Ethyl propianate, as well as 2-methyl butanol, 3-methyl-2-pentanol
and eucalyptol have been found as volatile components of the latex
[44a]. The analyses of the essential oil from stem bark of C. lechleri
from Amazonian Ecuador demonstrated a remarkable sesquiterpene
prevail characterized, in order of abundance, by sesquicineole, α-
calacorene, 1,10-di-epi-cubenol, β-calacorene and epi-cedrol; other
minor components are the monoterpenes limonene, borneol and p-
cymene [44b]. The leaves also contain taspine and the alkaloid
sinoacutine (17) known as morphinan-7-one [45a]; as well as the
aporphines magnoflorine, isoboldine, norisoboldine, glaucine, and
thaliporphine (18) [45b]. Flavonoids, mainly rutin and vitexin, were
also reported [46] (Figure 2).
PHARMACOLOGY
A bioassay-guided fractionation study of C. lechleri (CL) sap
showed that the n-BuOH fraction had the highest antioxidant
activity in the DPPH test. The antioxidant activity is explained by
the high concentration of phenolic compounds, especially
epigallocatechin. This compound had even a lower IC50 than the
controls ascorbic acid, quercetin and trolox [43].
According to Desmarchelier et al. [47a,b] and Risco et al. [47c], the
sap of CL can act as an antioxidant or a prooxidant, depending on
the concentration used in several in vivo assays.
CL sap showed good activity against Bacillus subtilis and
Escherechia coli [48]. The compounds accounted responsible for
these activities were 1,3,5-trimethoxybencene; 2,4,6-
trimethoxyphenol and korberins A and B [42a].
Itokawa et al. performed a bioassay-guided fractionation of the sap
of CP (Croton palanostigma) and isolated taspine as the main
cytotoxic compound against KB and V-79 cells [49a]. Taspine is
also cytotoxic against melanoma SK23 and colon cancer HT29 cells
[49b].
A methanol extract of Croton lechleri leaves is cytotoxic against
HeLa cells, without being toxic to normal human cells. It also
showed anticancer effect in vivo by inhibiting tumor growth in mice
with HeLa tumor [46].
Fayad et al. demonstrated that the alkaloid taspine inhibits both
topoisomerases I and II in cells overexpressing drug efflux
transporters [49c].
In the Ames/Salmonella test, the CL sap showed no mutagenic
activity on the Salmonella typhimurium strains T98 and T10 [50a];
however, it was mutagenic against strain TA1535 in the presence of
metabolic activation [50b].
In an in vitro model, the sap of CL behaved as a potent inhibitor of
cutaneous neurogenic inflammation by suppressing the release of
substance P by sensory afferent nerves [51a,b].
Topical administration of sangre de grado balm reduced rat paw
edema and caused relief of itching, pain and redness caused by
insect bites in a small group of pest control workers [51b].
Risco et al. evaluated the antiinflammatory activity of taspine and
the sap of SG. The sap was almost as active as naproxen in rat paw
edema caused by carragenin [52a]. Taspine (20 mg/Kg) was
equivalent to indomethacin (1 mg/Kg) in an in vivo adjuvant
polyarthritis model [52b].
CL sap decreases the cellular immune response and is also a potent
inhibitor of the classical and alternative complement pathways [6a].
Vaisberg et al. demonstrated that the topical application for a period
of 17 months of either CL sap or taspine to the skin of rats is not
tumorogenic [53a].
Using a mice model of wound healing, Vaisberg et al. found that
taspine has a dose-response cicatrizant effect [53a]. The activity of
taspine was greater than the sap and its mechanism of action might
be the enhancement of fibroblasts migration [53a,b].
On the other hand, in an in vitro model Pieters et al. found that 3´,4-
O-dimethylcedrusin stimulates the proliferation of endothelial cells.
In this model, taspine was rather cytotoxic [41,54a].
In an in vivo model, the sap (rich in proanthocyanidins) stimulates
wound contraction, formation of the crust and synthesis of collagen.
The compound 3',4-O-dimethylcedrusin also improved wound
healing, but was less active than the sap. According to Pieters et al.,
taspine has no influence in the cicatrization even at high
concentrations [54b].
In a rat model of gastric ulcers the oral treatment with CL reduced
ulcer size, myeloperoxidase activity and bacterial content of the
ulcer. The expression of proinflammatory genes (TNF-, iNOS, IL-
1β, IL-6 y COX-2) was also reduced during SG treatment [55].
In vitro and in vivo studies demonstrate that SP-303, a large
proanthocyanidin oligomer isolated from the sap of C. lechleri, has
good activity against respiratory syncytial, influenza A and
parainfluenza viruses. These activities are comparable to ribavirin.
SP-303 is also active against herpes virus type 1 and 2, as well
against hepatitis virus A and [39b].
SP-303 in vivo decreases intestinal secretion caused by cholera
toxin and in vitro reduces cAMP-mediated Cl-
secretion [56a,b].
A double blind, placebo-controlled clinical trial in 169 patients with
travelers´ diarrhoea showed that, compared to placebo, SP-303 was
able to shorten the duration of the diarrhea by 21% [57a].
SP-303 was eventually named crofelemer and patented by Napo
Pharmaceuticals. Crofelemer displays its intestinal antisecretory
activity by inhibiting two secretory channels: the cystic fibrosis
conductance regulator and calcium-activated chloride cannel [57b].
Following phase III clinical trials, Crofelemer was the first drug
approved by the FDA for the symptomatic relief of non-infectious
diarrhoea in patients with HIV/AIDS on antiretroviral therapy
[57c].
CLINICAL ASPECTS
Regarding its antidiarrheal effect, in 2013 a pilot study on the use of
the pharmaceutical product approved by WHO "Crofelemer" (made
from red latex of Croton lechleri tree) in the treatment of not
infectious diarrhea was held in HIV-infected patients. This study
found that Sangre de Drago has a unique mechanism that leads to
the inhibition of chloride ion secretion by blocking the chloride
channels in the gastrointestinal lumen. This reduces the flow of
sodium and water, which in turn reduces the frequency and
consistency of diarrhea. This drug based on Sangre de Drago is well
tolerated due to minimal systemic absorption and has a good safety
profile. Therefore, it is considered important in the symptomatic
relief of non-infectious diarrhea caused by antiretroviral therapy in
HIV-infected people, improving their quality of life and
contributing to adherence to antiretroviral therapy [58a].

Furthermore, in 1999 a multicenter, phase II, double-blind,
randomized, placebo-controlled trial evaluating the safety and
efficacy of SP-303 (made from Sangre de Drago) was performed for
the symptomatic treatment of diarrhea in HIV patients. HIV positive
subjects were admitted to an inpatient unit of study, patients for the
study discontinued all antidiarrheal agents 24 h before enrollment.
Subjects in the experimental group (26 patients) received 500 mg
orally every 6 hours for 96 hours (4 days), the same pattern was for
the placebo group (25 patients). During the study the frequency and
stool weight was evaluated. Moreover subjects were monitored for
symptoms and side effects. The treatment group SP-303 showed an
average reduction in stool weight baseline of 451 g/24 h versus 150
g/24 h with placebo on day 4 of treatment (p = 0.14) and a mean
reduction in the frequency of abnormal stools three stools in 24 h
against two stools per 24 h in the placebo group (p = 0.30). Finally,
it was concluded that SP-303 is safe and well tolerated.
Furthermore, these results suggest that SP-303 can be effective in
reducing stool weight and frequency in patients with AIDS and
diarrhea [58b].
In 1997, a multicenter double-blind, placebo-controlled, phase II
study was conducted to evaluate the safety and efficacy against
lesions of recurrent genital herpes in patients with AIDS. The
primary endpoints of this study were the complete healing of
injuries and healing time. Eligible patients had a history of genital
herpes or recurrent anogenital with at least one injury. Treatment in
the experimental group (24 patients) consisted of implementing the
Virend® ointment three times a day for 21 days in the placebo
group the same pattern (21 patients) was used. Excluding two
patients in the group receiving Virend® with initial treatment, but
was lost to follow up, 9 of 22 (41%) of patients treated with
Virend® experienced complete healing of lesions compared with
three (14%) patients in the placebo group (P = 0.053). Viral culture
revealed that 50% of patients treated with Virend® and 19% of
placebo treated patients became negative cultures during treatment
(P = 0.06) [58c].
ECONOMIC IMPORTANCE
The initial interest of a US company for dragon’s blood croton tree
sap for treating diarrhea through ethnobotanical field research got a
good result because the FDA approved the First-Ever Oral
Botanical Drug Amazon tree-derived medicine cleared for usage in
HIV patients with diarrhea on January 2013 [59]. An extract of
Croton lechleri introduced to the pharmaceutical market for use in
treatment of chronic diarrhea in people living with HIV/AIDS,
following the adoption of this statement represents a great market
opportunity as announced by ITC [60]. However, dragon’s blood
latex has been available in various products in the United States
since the passage of the Dietary Supplements Health and Education
Act (DSHEA) in 1994, and it is listed on the old dietary ingredients
list of plants submitted by the Utah Natural Products Alliance to the
US Food and Drug Administration as part of the Administration’s
premarket notification program for New Dietary Ingredients [61]. In
2000, Shaman, a company that was working in reforestation of 2000
trees, licensed their dragon’s blood product to the General Nutrition
Corporation (GNC), a member of the Numico family of companies,
which then enabled the new product to be featured in 4,200 GNC
health food stores as well as over 500 Rite AID pharmacies [62].
On the other hand, after years of research, the cosmetic application
companies also include dragon's blood sap in skin elixirs, creams,
and other special preparations. According to one producer, this is
considered a multi-functional ingredient, being the source of many
other beauty products.
Uncaria tomentosa (Willd) DC. / Uncaria guianensis (Aubl.) J.F.
Gmel.
INTRODUCTION
Uncaria tomentosa (Willd.) DC. (1830) and Uncaria guianensis
(Aubl.) J. F. Gmel. (1796), Class Dicot, Order Gentianales Family
Rubiaceae. It is important to clarify that there are no ethnomedical-
statistical studies about the differentiated use of both species in
traditional medicine for the treatment of certain diseases; thus,
information should be observed under this criterion.
Comparative
morphology
Uncaria tomentosa (Willd.) DC.
(1830)
Uncaria guianensis (Aubl.)
Gmel. (1796)
Habit Climbing shrub, grows up to 20
m approximately, the young
branches are quadrangular
Climbing or creeping shrub that
can reach 30 m in length
Stem With solid thorns, woody, up to
2 cm in length, directed
downward, not twisted
When adult diameter of 10-30
cm, with adult curved spines as
"ram horns"
Leaves Oblong, membranous, the beam
opaque yellowish tomentose or
only the underside nerve with 7-
10 nerves
Ovate or elliptic, coriaceous,
bright beam of dark green,
glabrous beneath, with 8-9
nerves.
Flowers 1.5 to 2 cm, arranged in clusters
of capitulum, sessile, glabrous
corolla
Of 2-3 cm, arranged in clusters
of capitulum, stalked, hairy
corolla pubescent
Fruit Bivalve capsules, narrowly
oblong ovate, up to 9 mm in
length
Capsules of 2-3 cm without
pedicel
Habitat Earthy-clay soils, from 0-500 m
altitude
It is found in Loreto: Santiago
river mouth; San Martin:
Mariscal Cáceres; Junin:
Chanchamayo, La Merced;
Pasco: Oxapampa, Pozuzo;
Madre de Dios: Manu,
Tahuamanu; Cusco: La
Convencion, Paucartambo
Earthy-clay soils, from 0-500 m
altitude
It is found in Loreto:
Yurimaguas, Port Arthur, Itaya
River, La Campuya; San Martin:
Tarapoto; in Ayacucho:
Chocmacota Valley; in Cusco:
Cosnipata; Madre de Dios:
Manu
Uncaria tomentosa (Willd.) DC. (1830)
Uncaria guianensis (Aubl.) J. F. Gmel. (1796)
SYNONYM [63]
1. Uncaria tomentosa (Willd.) DC. (1830)
- Nauclea aculeata (HBK) (Nov. Gen & sp 3: 382. 1819 no Willd.)
- N. tomentosa Willd. ex R. & S. (Syst Veg 5: 221. 1819)
- Orouparia tomentosa (Willd Ex R. & S.) Schumi (Fl Mart Bras 6
PT 6: 132, 1889)
2. Uncaria guianensis (Aubl.) Gmel. (1796)
- Oruparia guianensis Aublet in 1775
- Uncaria guianensis Schreber in 1789
COMMON NAMES [35,64]
1. Uncaria tomentosa (Willd.) DC. (1830)
- Garabato: (Huallaga) (Forest) Peru
- Unganangui: Peruvian Forest
- Yellow Doodle: Peruvian Forest
- Samento: Ashaninka, Peru
- Kug kukjaqui: Aguaruna, Huambisa, Jibaro (Marañón)
- Paotati - Mosha: Shipibo-Conibo ethnic group
- Misho - mentis: Shipibo-Conibo ethnic group
2. Uncaria guianensis (Aubl.) Gmel. (1796)
- Cat's claw
- Claw hawk
- Garabato Colorado
- Unganangui

- Tambor huasca: natives of the stream of Momón River - Iquitos
- Garabato casha
- Ancayacu
- Paraguayan
- Ancay sillo
ETHNOMEDICINE
In the population, this plant has been used for various therapeutic
purposes [7]. The Ashaninka priests used it for its life-giving
properties and prevention of diseases; however, its effects depend
on the plant part used. Bark: as contraceptive, anticancer, for
rheumatic diseases, as a diuretic, aphrodisiac, prostate
inflammation, as an antihypertensive, antiviral, in women
discharges, respiratory and digestive diseases; fresh bark is used in
snakebites [34,66a,b]. Leaves: for the treatment of measles, in
inflammations, allergies [67a]. Root: for rheumatic diseases, cancer,
gastric ulcers, immunomodulation and prevention of cancer. It is
also used commonly in maceration for wine or pisco, taken as
preventive and to enhance immunity [67a,b].
Phytochemical investigations on Uncaria tomentosa and U.
guianensis revealed the presence of mainly three types of secondary
metabolites: indole and oxindole alkaloids, triterpenes as quinovic
acid glycosides and polyphenols. Both species are found in Peru
and have long been used as part of traditional medicine.
Amongst the alkaloid compounds, the following have been
identified: pentacyclic oxindole, AOP (pterodine, isopteropodine,
speciophylline, uncarine F, mitraphylline, and isomitraphylline: 19-
24, respectively); and tetracyclic, AOT (rhynchophylline,
isorhynchophylline, corynoxeine, isocorynoxeine: 25-28,
respectively). Also, some of their corresponding N-oxides and its
indole precursors (akuammigine, tetrahydroalstonine, isoajmalicine,
hirsutine, dihydrocorynantheine, hirsuteine, and corynantheine)
[68a-e] have been reported, as well presence of harmane, 5α-
carboxystrictosidine [68f].
The following is noteworthy: (a) the concentration of alkaloids is
lower in the U. guianensis and that some of them have not been
found in this species, maybe due to the lack of sufficient studies; (b)
different samples analyzed show variation of the total content of
alkaloids, as well as the individual alkaloids. In addition, it has
been determined that there are two chemical-types for the U.
tomentosa, one that mainly (or only) contains AOP and a second
one with AOT. Also, it is important to mention that no significant
difference has been found in the ratio of oxindole alkaloids between
leaves and roots [69].
Two groups should be considered in the triterpene compounds: the
quinovic acid and its glycosides, and the polyhydroxylated
triterpenes. In the first group, 16 other structures of the glycosylated
quinovic acid have been found, for example: quinovic acid 3β-O-β-
D- quinovopyranoside, quinovic acid 3β-O-β-D-fucopyranosyl-
(27→1)-D-glucopyranoylester, quinovic acid 3β-O-[β-D-
glucopyranosil-(1→3)-β-D-fucopyranosyl]-(27→1)-β-D-
glucopyranosylester (29-31), and 32, 33 [70a-f]. From these, four
are common for both species, two have been reported only on U.
guianensis, and the other 11 only on U. tomentosa. On the other
hand, the sugar units from glycosides are: glucose, fucose,
quinovose, rhamnose, and galactose, which can be in positions C-3,
C-27, C-28, C-3, 27 or C-3, 28. These sugar units are repeated 16
times in glucose, 7 in fucose, 4 in quinovose, 3 in rhamnose, and 1
in galactose [71].
Other polyhydroxylated triterpenes from U. tomentosa have been
isolated. These are derived from ursolic acid, quinovic acid, and
glycosides of nortriterpenes [70f, 72a-d].
Also, other compounds isolated include triterpenes: lupeol, ursolic
and oleanolic acids, and sterols like β-sitosterol, campesterol and
stigmasterol [70f, 72a,b]. Likewise, the presence of the iridoid, 7-
deoxyloganic acid [72e] has been described.
Some phenolic compounds were reported as cinchonains Ia and Ib
(34, 35) [73a] and quinic acid derivatives, amongst these, 3, 4-O-
dicaffeoylquinic acid, 3-O-feruloylquinic acid and the 3-O-
caffeoylquinic acid, known as carboxylalkyl esters [73b] (Figure 3).
Figure 3: Some chemical compounds isolated from Uncaria tomentosa/U.guianesis.
PHARMACOLOGY
Ethanolic and aqueous extracts of Uncaria tomentosa (UT) showed
promising antioxidant activities measured through TEAC (Trolox
equivalent antioxidant capacity), PRTC (Peroxyl radical-trapping
capacity) and SOD (Superoxide radical scavenging activity) tests
[74a].
High antioxidant activities were also detected in DPPH, SOD and
PRTC tests and by inhibition of lipid peroxidation. According to
Gonçalves et al, these activities could be explained by the high
content of proanthocyanidins and phenolic acids, mainly caffeic
acid, in the extract [74b].
Methanol extracts of stem-bark and roots of UT showed antioxidant
activity in rat liver homogenates, by preventing thiobarbituric acid
reactive substances production and free radical-mediated DNA-
sugar damage [74c,d].
Antimicrobial properties have been reported for cat´s claw. Ethanol
bark extracts of Uncaria guianensis (UG) was active against
multidrug-resistant Staphylococcus aureus and Pseudomonas
aeruginosa [75a]. UT showed activity against oral human

pathogens Streptococcus mutans, Staphylococcus spp. and
Enterobacteriaceae [75b]. A bioassay-guided fractionation of UT
led to the isolation of isopteropodine as an antibacterial active
principle against Gram positive bacteria [75c].
Pheophorbide A ethyl ester was isolated from UG leaves. This
compound showed antibacterial activity against Staphylococcus
aureus, Enterococcus faecalis, Escherichia coli and Salmonella
typhimurium [75d].
Caon et al. demonstrated an antiherpetic activity for the
hydroethanolic extract from bark of UT. However, purified
fractions of quinovic acid glycosides and oxindole alkaloids were
less active, suggesting a synergetic effect. The probable mechanism
of action is the inhibition of viral attachment in the host cell [75e].
Pentacyclic oxindole alkaloid-enriched fraction was the most
effective in reducing monocyte infection with dengue virus-2
(DENV-2) [75f]. This same alkaloidal fraction showed antiviral
activity, as well as reduction of endotelial permeability, on human
dermal microvascular endotelial cells infected with DENV-2 [75g].
Riva et al. found that UT bark extracts and fractions exert an
antiproliferative activity on MCF7 [76a]. UT extracts, with different
concentrations of alkaloid contents had antiproliferative effects on
HL-60 acute promyelocytic human cells [76b].
Cytotoxic activities of UT extracts have been related to the
alkaloids. Uncarine D exhibited weak cytotoxic activity against SK-
MEL, KB, BT-549 and SK-OV-3 cell lines, while uncarine C
showed low cytotoxicity only against ovarian carcinoma [72e].
Mitraphylline inhibited the growth of human Ewing's sarcoma
MHHES1 and breast cancer MT-3 cell lines, with IC50 values of
17.15 ± 0.82 and 11.80 ± 1.03 μM, respectively. Both IC50 values
were smaller than those obtained for the reference compounds
cyclophosphamide and vincristine [76c]. Micromolar concentrations
of mitraphylline inhibited the growth of glioma and neuroblastoma
cell lines [76d].
Pteropodine exhibited good antioxidant activity in the DPPH test,
increased the production of lymphocytes and decreased bone
marrow cytotoxicity induced by doxorubicin [76e]. Pteropodine and
uncarine F induce apoptosis on acute leukaemic lymphoblasts [76f].
UT has also anticancer activity in vivo. A hydroethanolic extract of
UT inhibited B16/BL6 melanoma cell growth and metastasis in
mice. UT decreased TNF-α, IL-6 and NO production in vitro. NF-
κB activity was also inhibited in LPS-stimulated HeLa cells [77a].
Dreifuss et al. suggested that the anticancer activity in vivo
(Walker-256 tumour) shown by UT extracts may be a result of a
synergic combination of substances, most of them antioxidant
compounds [77b].
C-Med-100®, an aqueous extract of UT, inhibits the growth of
HL60 and Raji cells by producing DNA strand breaks coupled to
selective apoptosis [78a].
However, in an in vivo model, the extract inhibits proliferation of
normal mouse T and B lymphocytes; this inhibition was not caused
by induction of apoptosis [78b].
According to Åkesson et al., the extract induces cell proliferation
arrest and inhibits activation of the transcriptional regulator (NF-κB
in vitro. This effect may be due to the presence of quinic acid in the
extract [73b,78c].
Co-incubation with C-Med-100 with skin cell protected them from
UV exposure; this protection occurred with a concomitant increase
in DNA repair [78d].
The hydroalcoholic extract of UT showed anti-inflammatory
activity in the carrageenan-induced paw edema model in mice. It
also showed little inhibitory activity on cyclooxygenase-1 and -2
[79a].
According to Aquino et al, a bioassay-directed fractionation of UT
extract showed that one of the active antiinflammatory principles is
a quinovic acid glycoside [70c].
Oral pretreatment of mice with an ethanolic extract of UG leaves
decreased paw oedema and pleural exudation induced by zymosan
or ovoalbumin [79b].
A subfraction of a hydroethanolic extract of UG bark inhibited NO,
TNF-α, IL-6 and PGE2 production by macrophages in vitro and in
the serum of LPS-challenged mice. Macrophage expression of IκB
degradation was completely inhibited, while NF-κB activation was
inhibited by 70%. UG subfraction also decreased serum NO, TNF-
α, paw oedema induced by carrageenan and mammary tumour
growth by 91% [80].
Wagner et al. reported that four out of six oxindole alkaloids
present UT caused a pronounced enhancement of phagocytosis,
both in vitro and in vivo [68d].
UG and UT showed antioxidant activity (DPPH test) and strong
ability to inhibit TNF-α production in RAW 264.7 cells [81a,b]. In
THP-1 cells, UT also decreases TNF-α and has a opposite effect on
IL-1β and IL-6 [81c,d].
UG was more active than UT in scavenging DPPH and hydroxyl
radicals, and in inhibiting lipid peroxidation. The inhibition of TNF-
α production was significantly higher for UT.
Non-alkaloid HPLC fractions from UT decreased LPS-induced
TNF-α production. Thus, the presence of oxindolic alkaloids did not
influence the antioxidant and antiinflammatory properties of UT.
Oral pretreatment with UT protected against indomethacin-induced
gastritis in rats [81e].
In mice subjected to bacterial lipopolysaccharide endotoxin,
Mitraphylline inhibited around 50% of the release of interleukins
1α, 1β, 4, 17 and TNF-α. This activity was very similar to that of
dexamethasone [81f].
UG extract decreased peroxynitrite-induced apoptosis in HT29 and
RAW 264.7 cells. It also inhibited lipopolysaccharide-induced
iNOS gene expression, nitrite formation, cell death and inhibited the
activation of NF-κB. Moreover, it attenuated indomethacin-enteritis
[82a].
According to Allen-Hall et al., UT inhibits NF-κB pathway
activation, leading to a decrease in TNF- production and low cell
proliferation. Thus, UT has a potential therapeutic use as anticancer
or anti-inflammatory agent [82b].
An alkaloid-enriched preparation from UT inhibits NF-κB in
promyelocytic leukemia HL-60 cells. Pentacyclic oxindole
alkaloids may be the active compounds responsible for this effect
[82c].

Quinovic acid glycosides purified fraction of U. tomentosa
decreased the growth and viability of human bladder cancer cell
lines by inducing apoptosis through modulation of NF-κB [82d].
Quinic acid enhances DNA repair and has a neuroprotective effect
in neurons. It can improve Caenorhabidits elegans survival under
oxidative stress by upregulating the expression of the small heat
shock protein hsp-16.2 gene. Quinic acid may have potential as a
rejuvenating agent [83].
According to Uchida et al., UG slightly inhibited the progression of
the atherosclerosis in Watanabe heritable hyperlipidemic rabbits.
UG inhibited oxidation of LDL, decreased total cholesterol,
triglycerides, and the percent of plaque area formation [84].
CLINICAL ASPECTS
Concerning the antiinflammatory activity, there are three clinical
studies which evaluated the effect of U. tomentosa (Willd) DC; in
osteoarthritis and in rheumatoid arthritis [81b, 85a,b]. The quality of
these studies was evaluated as poor, according to Natural Standard
database; however, they performed well on reducing pain,
improving joint range and decreasing PGE2 and TNF- levels. The
conclusions were that both uncarias are effective for the treatment
of osteoarthritis; these results are reinforced by the systematic
review prepared by Rosenbaum [85c].
In 2008, a clinical trial conducted in patients with rheumatoid
arthritis showed that the treatment with U. tomentosa (Willd)
inhibits the activation of NF-kB, the expression of COX enzyme
and accelerates the maturation/activation of the subpopulation of
dendritic cells [85d,e]. All these mechanisms are important in the
pathogenesis of rheumatoid arthritis, so it is justified to continue
with larger trials in order to verify UT efficacy. Natural Standard
evaluated a clinical study to verify the immuno-stimulatory activity
of UT. This study [86] was classified as poor quality; however, it
was able to demonstrate the stimulating effect on the immune
system. All these studies suggest that U. tomentosa is able to boost
immune function.
ECONOMIC IMPORTANCE
The two known species of cat’s claw are used traditionally. They
are commonly found in supplements and have numerous medicinal
demands. Extracts of cat’s claw bark are utilized mainly as dietary
supplements for supporting or improving immune system functions,
as well as in medicinal products for arthritic conditions, and to a
lesser extent in liquid preparations for topical application,
sometimes in combination with other Andean botanicals such as
dragon’s blood croton (Croton lechleri Muell. Arg.); both of them
are regionally and globally marketed [60, 87]
According to the United States Pharmacopeia, cat's claw consists of
the inner bark of the stems of Uncaria tomentosa which contains no
less than 0.3 percent of pentacyclic oxindole alkaloids, calculated
on the dried basis, as the sum of speciophylline, uncarine F,
mitraphylline, isomitraphylline, pteropodine and isopteropodine.
On the other hand ITC listed the most important medicinal and
aromatic plants that are produced in one or more South American
countries, some of them are:
a) Uncaria tomentosa: standardized botanical extract (1.0-1.5%
total alkaloids by HPLC) from Brazil [88a].
b) Uncaria tomentosa: standardized botanical extract (2% total
alcaloids by HPLC) from Peru [88b].
Cat’s claw has been promoted under national policies and has a
significant international market. Patents on the chemicals derived
from cat’s claw (UT) failed to acknowledge or compensate the
source countries and indigenous cultures that held the knowledge of
the plants’ healing qualities. At the moment, there are 555
applications detected by National Biopiracy Commision. Peru
prohibits exports of certain specimens of Cat's Claw (Uncaria
tomentosa and Uncaria guianensis) that are "either unprocessed or
subject to mechanical processing", unless they come from specific
areas [89,90].
Lepidium meyenii Walpers
INTRODUCTION
Lepidium meyenii Walp Class Dicot, Order Brassicales, Family
Brassicaceae. There is evidence that in Peru for over 10,000 years
ago, there were human groups inhabiting the highlands and
mountain ranges, occupying caves and feeding camels and deers,
gathering roots and some fruits and seeds and among these maca,
which has been domesticated by Pumpush culture, established on
the plateau of Bombon in Junín. According to oral histories this
species was cultivated over large areas and the harvest was sent to
Cuzco to feed the Inka´s royal family [91].
Lepidium meyenii Walp. (1843). Nov. Actorum Acad. You fall.
Leop.-Carol. Nat. Cur. 19 (1): 249,249.
SYNONYM [92-93]
- Lepidium affine Wedd.
- Lepidium gelidum Wedd.
- Lepidium marginatum Griseb.
- Lepidium meyenii var. affine (Wedd.) Thell.
- Lepidium meyenii subsp. gelidum (Wedd.) Thell.
- Lepidium meyenii subsp. marginatum (Griseb.) Thell.
- Lepidium orbignyanum Wedd.
- Lepidium peruvianum G. Chacon de Popovici
- Lepidium weddellii O.E. Schulz
COMMON NAMES [35]
Maca, maka, maino, ayak chichita, ayak willku: Quechua
Maca, Andean viagra: Spanish
Maca, Peruvian ginseng: English
PLANT MORPHOLOGY [94]
General: herbaceous, biennial, rarely annual, with underground
storage organ
Root: taproot, the main thickened napiforme 4 to 5 cm in diameter
and 5-8 cm long.
Stem: the main compressed from which arise several leaves,
glabrous, prostrate, decumbent
Leaves: basal rosette, petiolate, bladed petioles 2-3 cm long, with
scarious margin; blade outline oblong, pinnatifid of 7-12 cm in
length and 1.5 to 2.5 cm wide, segments with apex acute.
Inflorescence and flowers: racemose in the end of the branches
(compound panicles). Flowers hermaphrodite, actinomorphic,
pedicellate, 4 free green sepals persistent, 4 free white petals,
alternating with the sepals. Androecium with 4 small staminodes
and 2 fertile stamens with filaments thickened. Gynoecium with

superior ovary, bilocular, bicarpelar, with one ovule per locule and
axillary placentation, short style and slightly globular stigma.
Fruit: Dry silicua, longer than wide (4-5 mm long by 2 -3 mm
wide), longitudinal dehiscence.
Habitat: the cultivation of maca is restricted to non-forested areas of
the highlands vegetation, between 3700-4500 m in height. This
zone corresponds to relatively infertile high Andean floors, which
are characterized by strong winds, high UV radiation and low
temperatures (may reach -10 ° C).
ETHNOMEDICINE
Maca is traditionally used as an energizer, to improve mental ability
and to strengthen the immune system. The part that is consumed is
the plant hypocotyl, which grows in the ground. The smallest maca
hypcotyls are selected for tea because they are sweeter and more
flavourful than the larger ones. Dried maca is mashed to a pulp and
then mixed with milk until reaching a gruel-like consistency
[7,93,95]. It is used to enhance fertility, vitality and mental ability;
to reduce depression, to strengthen bones and protect the skin [96].
The following have been identified as chemical constituents for
maca: glucosinolates (main components), macamides (benzyl
alkamides), macaenes (unsaturated fatty acids), sterols, phenolics,
and essential oil.
Glucosinates are characteristic components of the Brassicaceae,
which undergo enzymatic hydrolysis in damaged tissues releasing
isothiocianates. The latter are responsible for the pungent smell and
peculiar taste of this family.
The following glucosinolates have been reported: benzylglucosino-
late (glucotropaoelin) (36) [97a], 5-methyl-sulfinylpentylglucosino-
late (glucoalisin), p-hydroxybenzylglucosinolate (glucosinalbin),
pent-4-enylglucosinolate (glucobrassicanapin), indolyl-3-methyl-
glucosinolate (glucobrassicin), 4-methoxyindolyl-3-methylgluco-
sinolate (4-methoxy-glucobrassicin) [97b] and m-methoxybenzyl-
glucosinolate (37) [97c].
The following macamides have been found in maca: N-benzyl-
hexadecanamide (38), N-benzyloctadecanamide, N-benzyl-16-
hydroxy-9-oxo-10E, 12E, 14E-octadecatrienamide, N-benzyl-9,16-
dioxo-10E, 12E, 14E-octadecatrienamide [98a]; as well as N-
benzyl-5-oxo-6E,8E-octadecadienamide (39) [98b], N-benzyl-(9Z)-
octadecenamide, N-benzyl-(9Z,12Z)-octadecadienamide, N-benzyl-
(9Z, 12Z, 15Z)-octadecatrienamide [98c], N-benzyl-9-oxo-12Z-
octadecenamide (40),N-benzyl-9-oxo-12Z,15Z-octadecadienamide,
N-benzyl-13-oxo-9E,11E-octadecadienamide,N-benzyl-15Z-
tetracosenamide and N-(m-methoxybenzyl)-hexadecanamide (41)
[98d]. Macamides 38 to 41 are considered the most prominent in
maca [98e].
The fatty acids reported for maca are linoleic, oleic, 7-tridecenoic,
7-pentadecenoic, 9-heptadecenoic, 11-nonadecenoic, 15-eicosenoic,
and 15-tetracosenoic acids [99a]. The unsaturated fatty acids are
known as macaenes due to their presence in maca. Other isolated
compounds are sterols: β-sitosterol (main component), campesterol,
ergosterol, brassicasterol [99a]; phenolics: catechins and
gallocatechins [99b]; flavonoids and anthocyanins [98e] and amino
acids [99a].
Some alkaloids have been found: (1R, 3S)-1-methyltetrahydro-β-
carboline-3-carboxylic acid (42) [97c], macaridine (43) (which
corresponds to the benzylated derivative of 1,2-dihydro-N-
hydroxypyridine [98b] and two imidazole-type, lepidiline A and B
[100] (Fgure 4).
All the polysaccharides reported for maca are composed of
rhamnose, arabinose, glucose and galactose [101].
The essential oil found in the aerial portions of maca (0.06%)
includes 53 components; the most abundant are phenylacetonitrile
(85.9%), benzaldehyde (3.1%) and 3-methoxy-phenylacetonitrile
(2.1%) [102].
Figure 4: Some chemical compounds isolated from Lepidium meyenii.
PHARMACOLOGY
The aqueous extract of L. meyenii (maca) was able to scavenge
DPPH and peroxyl radicals (IC50=0.61 and 0.43 mg/ml,
respectively) and to protect deoxyribose against hydroxyl radicals
(74% at 3 mg/ml). It also protects macrophages RAW 264.7 against
peroxynitrite-induced apoptosis. However, maca was comparatively
less active than green tea or cat´s claw [103a]. Similarly, Valentová
et al. [103b] found weak antioxidant activity in the DPPH test for
methanolic and aqueous extracts of maca. They were not cytotoxic
against rat hepatocytes and exhibited estrogenic activity in MCF-7
breast cancer cell line.
Some polysaccharides from maca can be partly responsible for its
antioxidant activity, as they were able to scavenge hydroxyl and
superoxide radicals [101].
Methanol extract of maca was tested in Madin-Darby canine kidney
cells infected with influenza type A and B viruses. In this model,
maca extract showed good antiviral activity against both viruses
with selectivity indices of 157.4 and 110.5, respectively [104].
L. meyenii also has an influence on rat lipid and glucose
metabolism. Maca treatment decreased the levels of glucose,
VLDL, LDL, total cholesterol and triacylglycerols in hereditary
hypertriglyceridemic rats [105].
A pentane extract of maca has a neuroprotective effect on crayfish
neurons. This effect was also observed on rats receiving the extract
intravenously, but only at the lowest dose [106a].
Neuroprotective action of maca might be due to the presence of
macamides, especially N-3-methoxybenzyl-linoleamide, a strong
fatty acid amide hydrolase inhibitor. In vivo experiments are needed

to prove macamides´ action on the fatty acid amide hydrolase and to
evaluate their potential applications as analgesic or neuroprotective
agents [106b].
An aqueous extract of maca hypocotyls protects rat skins from UV
irradiation [107a]. Similar activity was found for the leaves; maca
leaves extracts, especially from the red variety, applied on mice
dorsal skins have photoprotective effect against UV-B irradiation
[107b].
The administration of an aqueous extract of yellow maca reversed
the immunosuppressive effect of cyclophosphamide by increasing
gene expression of three hematopoietic cytokines and augmenting
cell counts in bone marrow [108].
Using ethanol in rats as a model of memory impairment, a 28-days
treatment with a hydroalcoholic extract of black maca showed a
dose-response improvement in spatial memory [109a].
Similarly, rats treated with an aqueous extract of black maca
showed improvement on learning and memory impairment induced
by ovariectomy [109b] or by esccopolamine [109c].
Treatment of mice with black maca improved latent learning in
ovariectomized mice, while the three varieties (black, yellow and
red) exhibited antidepressant activity. Learning was assessed using
the water finding task and the antidepressant activity was evaluated
by the forced swimming test [109d].
In the chronic mild stress model of depression in mice, a petroleum
ether extract from maca showed antidepressant-like effects.
According to Cheng et al. [109e], they were related to the activation
of noradrenergic and dopaminergic systems, as well as reduction of
oxidative stress in the mouse brain.
Mice treated with benzylglucosinolate showed increased endurance
exercise capacity, probably related to a higher utilization of non-
esterified fatty acids as energy source [109f].
Treatment with red maca extract decreased prostate size of normal
rats and also of rats with prostatic hyperplasia induced by
testosterone enanthate [110a,b].
An ethanol extract of maca prevented bone loss on ovariectomized
rats with postmenopausal osteoporosis [111a]. In this model, red
and black maca varieties showed the highest protective effects
[111b].
The fertility enhancing properties of maca have been studied in
several models in vivo. An aqueous extract of yellow maca
increases litter size in normal female size; it also increased uterine
weights in ovariectomized mice compared to the control group
[112a].
An alcoholic extract of maca activates onset and progression of
spermatogenesis at 48 mg/day or 96 mg/day in rats [112b].
Spermatogenesis was better activated by black variety of maca.
Treatment with black maca increased daily sperm production and
epididymal sperm motility in rats [112c,d]. Similarly,
administration of yellow or black maca to male rats for 84 days
enhanced epididymal sperm count and sperm count in vas deferens
without affecting daily sperm production [112e]. The partition of a
hydroalcoholic extract of black maca with solvents of different
polarities led to the ethylacetate fraction, which was the one that
showed the highest sperm production [112f].
Co-administration of maca with lead acetate to male rats prevents
reduction of daily sperm production caused by the latter [112g].
Treatment of rats with maca also prevents spermatogenic disruption
induced by high altitude [112h] and by the organophosphorous
pesticide malathion [112i].
Maca has also an effect on serum hormone levels. Female rats fed
with maca powder ad libitum for 7 weeks showed an increase of
serum luteinizing hormone during the pro-oestrus, supporting this
result the traditional use of maca for enhancement of fertility
[113a].
On the other hand, Gasco et al. reported that adult female rats
treated with aqueous extract of maca during 28 days showed no
changes in the number of ova, serum estradiol levels, wet uterine
and body weights compared to vehicle [113b].
However, according to Zhang et al. [113c], ovariectomized rats
treated orally for 28 weeks with maca ethanol extract showed a
serum estradiol level similar to sham control, while follicle-
stimulating hormone did not increase as in the ovariectomized
group. In another similar experiment, the ethanol extract of maca
decreased cholesterol and serum follicle-stimulating hormone level,
while estradiol level increased compared to the control [113d].
Oshima et al. found that treatment with maca increased
progesterone and testosterone levels in mice, with no changes in
estradiol-17β blood levels or the rate of embryo implantation
[113e].
The effect of maca on sexual behavior has been evaluated on mice,
rats, sheeps and bulls. The number of mounts and ejaculations were
increased in hair sheep rams (Ovis aries) after 8 weeks of
supplementation with maca. No changes in semen characteristics
were observed [114a].
Maca oral administration improved sexual performance parameters
(decreased first mount, first intromission, ejaculation and
postejaculatory latencies) in male rats [114b].
On the other hand, in a 23-week cross-over design study maca
supplementation seemed to improve sperm quantity and quality of
peripubertal breeding bulls, but had no effect on mating behavior,
and ejaculate volume [114c]. Similarly, maca treatment did not
produce large changes in male rats ejaculation and mounting
behaviors [114d].
CLINICAL ASPECTS
In 2008 a randomized, double-blind, placebo controlled,
crossoverstudy was conducted in 14 postmenopausal women, who
received 3.5 grams per day of maca for a total of 12 weeks. All
patients were evaluated at baseline, 6th week and at the end of the
study. The assessment included measurement of estradiol, follicle
stimulating hormone, luteinizing hormone and sex hormone binding
globulin, as well as completing the Greene Climacteric Scale. The
results showed that maca (3.5 g/day) reduces psychological
symptoms such as anxiety and depression, and reduces the measures
of sexual dysfunction in postmenopausal women regardless of
estrogenic and androgenic activity [115a].
In 2008 a pilot randomized double-blind dose-finding study was
published by comparing a low dose (1.5 g/day) to a high dose (3.0
g/day) of maca in 17 women and 3 men presenting sexual
dysfunction induced by different antidepressants (sertraline,

venlafaxine, fluoxetine, paroxetine, citalopram and fluvoxamine).
The assessmentof sexual dysfunction was made by Arizona Sexual
Experience Scale (ASEX) and Massachusetts General Hospital
Sexual Functioning Questionnaire (MGH-SFQ). The results showed
that maca can relieve SSRI antidepressant-induced sexual
dysfunction andhas a beneficial effect on libido enhancement
[115b].
In 2005 and 2006 Meissner in its various studies concluded that
maca in a notorious way relieve the severity of symptoms of
menopause, according to results of evaluation with Kupperman
index and Greene scale. Significant improvement from hot flashes,
night sweats, sleep disorders, nervousness, fatigue, loss of energy,
interest in sexual life and increased libido were evident. The results
explain maca´s widespread use among women living in the central
Andes to relieve symptoms of menopause [115c-f].
ECONOMIC IMPORTANCE
In 1994 maca was considered as a neglected crop by FAO, in spite
of its high calcium and iron contents [116]. Maca has been used for
years as a “super food” and as a sexual health enhancer in the North
American [117] and Canadian markets [60]. Maca has high content
of nutritious elements making it an effective revitalizer and an
invigorating food. The United States Pharmacopeia (USP) began to
develop a quality standards monograph for 'Lepidium meyenii
Tuber' with the English common names 'Maca' and 'Peruvian
Ginseng' (proposed for development in the USP Herbal Medicines
Compendium (HMC) [118].
At the international market, L. meyenii is avaible as maca root
(powder), maca root (dry extract), roasted maca, maca fluid extracts
or powder (certified organic), among others. They are promoted as
nutraceuticals, herbal dietary supplements, functional foods, food
supplements and cosmetics.
Based on USA - Peru Free Trade Agreement (2009) the HS code in
Peru is 1106.20.10.00 (maca flour) and in USA HS Code is
1106.20.90.00 Flour, meal and powder of sago, or of roots or tubers
of heading 0714 (excluding Chinese water chesnuts) [117].
The Peruvian Anti-Biopiracy Commission has rejected the request
of 12 attempts to patent maca, from a group of 550 applications
coming mainly from Japan, United States and France. Peru is still
the major global producer and exporter of maca; however, during
2013 -2014, maca plantations are scaling up in China and Japan
[119].
Physalis peruvianus Linnaeus
INTRODUCTION
Physalis peruviana L., Class Dicot, Order Solanales, Family
Solanaceae. It is native from the South American Andes [120], plant
with high nutritional content and antioxidant compounds.
Physalis peruviana L. (1753). Sp. Pl., Ed. 2. 2: 1670 1753 [Aug
1763]
SYNONYM [121,122]
- Alkekengi pubescens Moench
- Boberella peruviana (L.) E.H.L.Krause
- Physalis esculenta Salisb.
- Physalis latifolia Lam.
- Physalis peruviana var. latifolia (Lam.) Dunal
- Physalis tomentosa Medik.
COMMON NAMES [121,122]
Uchuva: Colombia, Costa Rica, Mexico
Capulí: Mexico, Peru
Aguaymanto: Peru
"Guchuba" (Boyaca), "hierbabuena", "uchuva" y "uchuvo"
(Cundinamarca), "uvilla" (Huila), "vejigón" (Huila, Tolima),
"tomato" (Magdalena): Colombia
PLANT MORPHOLOGY [121-124]
Habit: Herbaceous perennial between 1 to 1.5 m high.
Root: the main root can grow to 80 cm, the ramifications are
abundant and shallow only deepened to 15 cm.
Stem: is aerial, erect, slightly branched, densely pubescent.
Leaf: petiolate, alternate, hairy, ovate limbo, subcordate base,
apiculate apex, margin entire or with small teeth.
Inflorescence and flowers: solitary flowers are axillary, erect or
inclined, pedicellate, pentamer. Calyx campanulate, pubescent,
accrescent during fruiting. Corolla with yellow petals, fusioned,
with purple macules on the throat of the corolla tube. Stamens with
anthers oblong, biloculate and lateral dehiscence, basifixed.
Gynoecium consists of superior ovary, greenish yellow to green.
Fruit: berries when ripe are yellow to orange.
Habitat: P. peruviana is found wild or semiwild on altitudinal
intermediate floors of the Andes, between 1500 and 3000 m, from
Venezuela to Chile.
ETHNOMEDICINE
The ripe fruit of yacon is edible, sweet and rich in vitamin C. It is
used for kidney [125] diseases, so as to prevent scurvy, pharyngitis,
stomatitis; the infusion is used as an ocular decongestant, diuretic
and for colds and jaundice [7, 126]. The juice from fresh fruits is
used traditionally as an antitussive and to treat malaria, asthma and
dermatitis. The ethanol extract of stems and leaves is used to inhibit
tumor growth. Its external use is as infusion or decoction of the
leaves, for the relief of oro-pharyngeal affections and to purify
blood. It is recommended for people with diabetes and prostate
problems [127].
The fruits contain an oil that is composed of unsaturated fatty acids
(mainly linoleic acid, followed by oleic acid, and linolenic acid in
much lower concentrations), phytosterols (δ-5-avenasterol,
campesterol, ergosterol, lanosterol, stigmasterol, β-sitosterol, δ-7-
avenasterol), vitamins (A, C, K, E: tocopherols), carotenes
(provitamin A) [128], flavonols (rutin and myricetin), and other
volatile components responsible for the characteristic taste and
scent [129a,b]. Cape gooseberry´s high level of fructose makes it
valuable for diabetics.
Steroidal lactones are found in leaves and roots, they are known as
withanolides, which are part of a group of steroids that occur
naturally with a skeleton of ergostane, in which carbons 22 and 26
are oxidized to form a lactone ring, hence been known as steroidal
lactones. These withanolides and others formed by modifications of
the cyclic skeleton and/or lateral chain are present in Physalys
genus. P. peruviana is very rich in whitanolides, which are
especially found in the leaves and roots [130].
The first research regarding components responsible for the typical
taste and scent of the fruits, reported 40 volatile components. From
these, 34.5% have an aromatic structure, 31.5% are acids, 19%

aliphatic alcohols, 6.5% hydroxyesters and 3.2% terpenoids [129a].
Later, 83 total volatile components were identified and quantified in
the fruit pulp. They included 23 esters, 21 alcohols, 11 terpenes, 8
ketones, 8 acids, 6 lactones, 4 aldehydes and 2 miscellaneous. The
main aroma components of the cape gooseberry were γ-
hexalactone, benzyl alcohol, dimethylvinylcarbinol, 1-butanol, 2-
methyl-1-butanol, cuminol, γ-octalactone and 1-hexanol. The
calculated odor activity values suggest that γ-octalactone, γ-
hexalactone, ethyl octanoate, 2-heptanone, nonanal, hexanal,
citronellol, 2-methyl-1-butanol, benzyl alcohol, phenethyl alcohol,
1-heptanol, ethyl decanoate and 1-butanol are the compounds
responsible for the aroma of cape gooseberry. Within these, γ-
octalactone was the most powerful contributor to the fruit aroma. It
was concluded that cape gooseberry has characteristic indicator
odorants that contribute to the overall aroma, which also can be
used as quality-freshness markers of this fruit [131a]. Lastly, using
headspace solid-phase microextraction, a total of 133 volatile
compounds were identified in fruit pulp; among them 1-hexanol,
eucalyptol, ethyl butanoate, ethyl octanoate, ethyl decanoate, 4-
terpineol, and 2-methyl-1-butanol were the major components in the
sample extracts [131b].
Figure 5: Some chemical compounds isolated from Physalis peruvianus.
New withanolides have been found in this last decade. In 2012, ten
new withanolides were reported, including four perulactone-type
withanolides; perulactones E, F, G (44), H; three 28-hydroxy-
withanolides, withaperuvins I, J, K; and three other new
withanolides, withaperuvines L, M (45) N; together with other
known withanolides such as withanolide S 5–methylether,
withanolide C, withanolide S and physalactone from the aerial parts
of Physalis peruviana [132a]. Before that, two new perulactone-
type withanolides, perulactones C and D and a novel 1,10-seco
withaperuvin C have been isolated [132b,c]; as well as six new
phyperunolides A (46), B (47), C-F and a peruvianoxide [132d].
Previously, during the two last decades of the last century other
withanolides have been isolated: withaperuvines D, E (48), F, G and
H [133a,b,c]; withanolide E (49) and its 4β-hydroxylated (50)
[133d]; withaphysanolide [133e], physalactones B and C [133f],
witha-5,24-dienolide derivatives, i.e. (20R, 22R)-14α,20,27-
trihydroxy-1-oxowitha-5,24-dienolide-3β-(O-β-D-glucopyranoside)
(51) [133g], among others (Figure 5).
PHARMACOLOGY
In rat liver homogenates, the ethanol extract of the whole plant of P.
peruviana possesses good antioxidant activity on the FeCl2-ascorbic
acid induced lipid peroxidation. It also has better antioxidant
activity than -tocopherol in the thiobarbituric acid assay, in
cytochrome C test and in xanthine oxidase inhibition test
[134a].The methanol extract of the fruits also had good activity in
the lipid peroxidation inhibition test [134b].
In this test, whitaperuvin E isolated from the fruits showed an
antioxidant activity comparable to the synthetic antioxidant
parabenzoquinone [134c]. According to Licodiedidoff et al., the
antioxidant activity of the fruits is also correlated to the content of
the flavonols rutin and myricetin [134d].
An extract of the leaves of P. peruviana obtained by CO2-
supercritical fluid extraction showed higher antioxidant and
antiinflammatory activities than extracts prepared by solvent
extractions [134e].
Using the 12-O-tetradecanoylphorbol-13-acetate-induced mouse
model of ear edema, Franco et al. found a good anti-inflammatory
activity in an extract of P. peruviana calyces [135a]. According to
Toro et al., the anti-inflammatory activity of this extract and its
butanolic fraction is mainly due to the presence of rutin [135b].
In a rabbit eye inflammation model, the fruit juice of P. peruviana
showed a mild antiinflammatory activity compared with
methylprednisolone [135c].
The ethanol extract of the whole plant possess antibacterial activity
against Bacillus subtilis, Sarcinia lutea, Neisseriasp. and
Mycobacterium phlei; while an ethanol extract of the leaves was
even active against Escherechia coli and Candida albicans[136a].
The chloroform fraction of P. peruviana calyces showed potent
activity (MIC≤ 0.256 mg/mL) against Staphylococcus aureus,
Klebsiella pneumoniae and Pseudomonas aeruginosa [136b].
Several compounds with insecticidal activity have been isolated
from the leaves of P. peruviana. Compound (20R,22R)-14,20,27-
trihydroxy-1-oxowitha-5,24-dienolide-3β-(O-β-D-glucopyranoside)
showed good activity against Helicoverpa zea larvae, a pest that
affects tobacco and tomato crops [137a]. Another less active
compound against H. zea was perulactone 3-O-β-D-glucopyranoside
[137b]. Whitanolide E was active against the insect Spodoptera
littoralis [137c].
P. peruviana aqueous extract showed a dose-dependent protective
effect against acetaminophen-induced hepatotoxicity in rats. A pre-
treatment with P. peruviana extract prevented the increase of
hepatic enzymes glutamic pyruvic transaminase, glutamic
oxaloacetic transaminase and alkaline phosphatase, which are high
during liver hepatitis. According to Chang et al., ellagic acid could
be the compound responsible for the hepatoprotective activity of P.
peruviana [138a].
Water extract of P. peruviana fruits showed a protective effect
against hepatic cell damage in rats treated with CCl4. Rats treated
only with this toxin had a marked increase in several liver enzymes
and biochemical parameters as a result of liver injury. Treatment
with P. peruviana decreased the levels of alanine transaminase,
aspartate transaminase, alkaline phosphatase, lactate
dehydrogenase, creatinine, urea and bilirubin in CCl4-intoxicated
rats [138b].
Water extract of the leaves [138c] and the fruit juice [138d] of P.
peruviana showed similar antihepatotoxic activities against CCl4
induced hepatotoxicity. The juice was able to improve liver enzyme
concentrations and to restore the activities of superoxide dismutase,
catalase, glutathione-S-transferase, glutathione peroxidase, and

glutathione reductase. The hepatoprotective effect of the juice may
be due to the presence of quercetin and kaempferol, both strong
antioxidants [138d]. P. peruviana fruits also protects from hepatic
and renal fibrosis induced by CCl4 [138e,f].
Lyophilized fruit juice of P. peruviana does not induce genetic
damage. The LD50 value was found to be high (>5 g/Kg). No
hepatic, renal or hematological toxic effects were observed in
subchronic toxicity studies. However, the juice at high dose (>5
g/Kg) induced cardiac toxicity in male rats [139].
The oral administration of Physalis peruviana fruit extract during
15 days reduced the blood glucose levels in more than 30% in
streptozotocin-diabetic rats [140a]. An aqueous decoctions of leaves
of P. peruviana at a dose of 100 mg/kg had a hypoglycemic effect
on guinea pigs. The LD50 in these animals was 1.2 g/kg [140b].
P. peruviana fruit juice was able to lower levels of total cholesterol,
total triacylglycerol and LDL-cholesterol, as well as to increase
levels of HDL-cholesterol in high-cholesterol diet fed rats [140c].
Ethanol extract of P. peruviana leaves and stems were more
cytotoxic than cisplatin and 5-fluorouracil against HT-29, PC-3 and
K562 cancer cell lines [141a]. Similarly, the ethanol extract of P.
peruviana whole plant inhibits growth and induce apoptosis of
human Hep G2 cells. Apoptosis is probably mediated through the
CD95/CD95L system and mitochondrial signaling transduction
pathway [141b,c].
Compounds phyperunolide A, 4β-hydroxywithanolide E,
hydroxywithanolide E, withanolide E and withanolide C showed
cytotoxicity against lung cancer (A549), breast cancer (MDA-MB-
231 and MCF7), and liver cancer (Hep G2 and Hep 3B) cancer cell
lines [132d].
The compound 4β-hydroxywithanolide (4βHWE), isolated from the
fruits of P. peruviana caused inhibition of proliferation of human
lung cancer cell line H1299 by DNA damage and a mechanism of
apoptosis and G2/M arrest [141d]. Compound 4βHWE also
selectively killed oral cancer Ca9-22 cell line by causing DNA
damage and apoptosis, with a minimal effect on normal fibroblasts
[141e].
CLINICAL ASPECTS
At present there are no reports of clinical trials of high statistical
significance; however, we discuss here a clinical study performed
with the fruits of Physalis peruviana that can guide future trials.
The clinical trial was undertaken to determine the effect of the
intake of P. peruviana (aguaymanto) on postprandial glycemia in
young adults. It involved 26 volunteer subjects (mean age 25.03 ±
2.74 years, mean BMI 22.76 ± 1.48 kg/m2) who were randomly
divided into two groups: group I ingested first 25 g of P. peruviana
fruist and after 40 minutes received a glucose overload; group II
was given only the latter. Blood samples were collected after 30, 60,
90 and 120 minutes in both groups. After three days, the treatments
were exchanged. There was a significant difference at 90 (p < 0.01)
and at 120 (p < 0.05) minutes postprandial between glycemia values
in both groups [142]. However, it is still necessary to continue the
research in order to validate important effects from this medicinal
plant.
ECONOMIC IMPORTANCE
Cape gooseberry is marketed as food product or food supplement
ingredient. It is usually labelled as conventional food product.
In United States according to the tariff schedules of Colombia and
Peru fresh cape gooseberry (Physalis peruviana), also known as
“Uchuva”, has the Harmonized System (HS) code of 0810.90.5000;
while dried cape gooseberry has the HS 081340 code, along with
other dried fruits and nuts. The cape gooseberries from Peru should
qualify as duty free as per United States-Peru Trade Promotion
Agreement Implementation Act PTPA [143,144].
It is used worldwide and is part of several patents of medicinal,
food and/or cosmetic use; such as: Chinese patent for toxicant
elimination medicament for eyes (CN 101869631) B [145]; (CN
101810730 A) use of a extract of golden berry for ulcers and
preparation method thereof [146]; (JP 2011051920) a group of
Physalis peruviana, Physalis pruinosa and Physalis philadelphica
as bleaching agent [147].
OTHER PLANT SPECIES USED IN PERUVIAN
TRADITIONAL MEDICINE
The most important traditional uses, chemical constituents and
biological activities of Minthostachys mollis (muña), Notholaena
nívea (cuti cuti), Maytenus macrocarpa (chuchuhuasi), Dracontium
loretense (jargon sacha), Zea mays (maíz morado), Plukenetia
volubilis (sacha inchi) and Gentianella nítida (hercampuri) are
presented in Table 1.
OTHER PLANT SPECIES USED IN PERUVIAN
TRADITIONAL MEDICINE
The most important traditional uses, chemical constituents and
biological activities of Minthostachys mollis (muña), Notholaena
nívea (cuti cuti), Maytenus macrocarpa (chuchuhuasi), Dracontium
loretense (jargon sacha), Zea mays (maíz morado), Plukenetia
volubilis (sacha inchi) and Gentianella nítida (hercampuri) are
presented in Table 1.
CONCLUSIONS
The botanical, chemical, pharmacological and clinical propierties of
the 12 most representative Peruvian plants have been reviewed.
These plants posses several interesting biological activities and can
be considered an important source for the development of new
drugs or phytomedicines; however, for most of them, more research
work is still needed.
Peru has a great potential to supply food and raw materials derived
from native biodiversity, and linking up to value chains that
guarantee their sustainable use and commercialization. These
products have been identified as a new promising opportunity,
emerging as a solid green economic sector. The demand in the
global market is growing considerably, especially in the United
Sates, the European Union and Japan.
There is still a stable market for certain established herbs, such as
uña de gato, sangre de grado, which are also interesting for the
general well-being and natural personal care markets. Furthermore,
a new trend in ‘superfoods’ derived from plants like maca,
aguaymanto or other health products such as yacon (high fiber) and
maiz morado (antioxidants) is rising. Research and development in
this field should be increased.

Table 1: Other native plants used in Peruvian traditional medicine.
Plant name (Family), common names
Ethnomedical use
Chemical constituents Pharmacology
Minthostachys mollis Griseb. (Lamiaceae), “muña”,
“poleo”,”agamanchano”.
Carminative, colics, flatulence, diarrhoea, cold,
cough, flu; broncodilatador, asthma; local
antisepeptic, antimicrobial, acaricide, parasiticide [3]
Essential oils with variable composition, they contain mainly two
monoterpenes: pulegone and menthone. Samples from Argentina,
Colombia, Ecuador, Peru and Venezuela show different amounts of
these two terpenes. Other components are menthol, limonene,
carvacrol, nerolidol, carvone, caryophyllene, linalool, germacrene,
among others [148a-k].
Muña was used since Inka times to preserve potatoes and avoid its
germination. The essential oil showed a significant inhibitory effect
against Gram-positive and Gram-negative bacteria, especially
Bacillus subtilus and Salmonella typhi [148i].
Notholaena nívea Desv. (Pteridaceae), “cuti cuti”
“doradilla”.
Leaves used for the preparation of infusions of herbal
teas with hypoglycaemic effect [149a]. Also as
emmenagogue, sudorific, depurative and abortive [3].
Benzyl and bibenzyl derivatives compounds:
5-hydroxy-3,12-dimethoxy-6-carboxybibenzyl (notholaenic acid);
3,12-dihydroxy-5-methoxybibenzyl (52) [149a]; 5,12-
dihydroxy-3-methoxy-bibenzyl-6-carboxylic acid (53); 5-acetyloxy-
12-hydroxy-3-methoxybibenzyl-6-carboxylic acid; 12-O-[3’-(5’-
methoxy-12’-hydroxy)-bibenzyl]-hydroxyl-3-methoxybibenzyl-6-
carboxylic acid; 3-O-{12’-[12”-O-(3”,5”-dimethoxy-6”-
carboxybibenzyl)]-5’methoxy-6’-carboxybibenzyl}-12-hydroxy-5-
methoxybibenzyl-6-carboxylic acid [149b]
Compound 52 showed the highest activity in the ABTS free-radical
scavenging test, while in the coupled oxidation of beta-caroteno and
linoleic acid assay; coumpound 53 was the most ac active one. The
investigation on the possible protective effect of each of the isolated
compounds against reactive oxygen species-induced Caco-2-
cytotoxicity shows that 52 is the most active, although all of them
play a protective role against ROM-induced oxidative injury, using a
cell culture model as the experimental system [149b].
Maytenus macrocarpa (Ruiz & Pavon) Briq.
(Celastraceae). “chuchuhuasi”,
“chuchuwasha”,”chocho-huascha”.
Bark extract used as antiarthritic, antirheumatic,
aphrodisiac, antidiarrheic, for upset stomach, to
regulate menstrual periods, insect repellent. The wood
is used for lumber [150], bronchitis, to enhance
immue system, muscle relaxant [3, 4, 35].
Friedelane triterpenoids (i.e. 28-hydroxyfriedelane-1,3-dione (53), 3-
oxo-29-hydroxyfriedelane) [151a]; nor triterpenes (macrocarpins A,
B, C, D) [151b]; sesquiterpene polyol esters (i.e.6β ,8β,15-triacetoxy-
1α,9α-dibenzoyloxy-4β-hydroxy-β-dihydroagarofuran, 1α,6β,8β,15-
tetracetoxy-9α-benzoyloxy-4β-hydroxy-β-dihydroagarofuran,
(1S,4S,6R,7R,8R,9R)-1,6,15-triacetoxy-8,9-dibenzoyl-4-hydroxy-β-
dihydroagarofurane) [151c]; dammarene triterpenes (i.e. 24(Z)-3-
oxodammara-20(21),24-dien-27-oic acid, octa-nor-13-
hydroxydammara-1-en-3,17-diona [151d]; 24-(E)-3-oxo-23-
methylene-dammara-20,24-dien-26-oic acid, 23-(Z)-3,25-dioxo-25-
nor-dammara-20,24-diene [151e]; tingenol derivatives (i.e.22-β-
hydroxy-6-oxo-tingenol, 7,8-dihydro-7-oxo-22-β-hydroxy tingenona
[151f]; coumarin noreugenin [151g].
Compound 53 showed weak activity against aldose-reductase assay
[151a]; macrocarpins A, B and D are cytotoxic against four tumoral
cell lines (P-388, A-549, HT29, SK-MEL-28) [151b]. Extracts of
leaves of M. macrcarpa showed bradycardic activity, as well as
depressing effects on respiratory frequency and body temperature
[152a]. Antinocicptive effects, measured by the writhing test in
rodents, were demonstrated for leaves extracts at doses of 2000
mg/kg [152b]. In an in vivo intestinal motility assay, chuchuhuasi
extract showed a synergistic effect with metoclopramide and an
antagonistic effect with loperamide [152c].
Dracontium loretense Engl (Araceae), “jergón
sacha”, “hierba del jergon”,”ronon rao”.
The roots are edible; the branchs are used to repel
snakes and the tubers against snakebites. Other uses
include treatment of gastrointestinal ulcers and tumors
[35, 150]. The infusion obtained from the corms has
been traditionally used as immunomodulator; in
particular, together with Uncaria tomentosa extract, it
is used by AIDS patients to reinforce the immune
system [153a].
Oxylipins: (9S*, 10R*, 11R*, 12Z, 15Z)-9,10,11,-trihydroxyoctadeca-
12,15-dienoic acid; (9S*, 10R*, 7E)-6,9,10- trihydroxyoctadec-7-
enoic acid (1); (9R*, 10R*, 7E) -6,9,10-trihydroxy-octadec-7-enoic
acid; and (8R*, 9R*, 10S, 6Z)- trihydroxyoctadec-6-enoic acid.
[153a]; dracontioside A and B and others; 19 ceramides and
cerebrosides.among which 7 have never been reported before [153b].
The potential immunostimulatory effect of the n-butanol extract, a
fraction of this extract containing the four oxylipins (fraction A), and
isolated oxilypins were used to perform a proliferation assay on
human PBMC by 3H-thymidine incorporation. Significant cell
activation was obtained by fraction A, the n-butanol exract at 10
μg/ml and by compound 1 at 10 μM. On the other hand, the n-
butanol extract and fraction A were shown to also contain ceramides
and cerebrosides, which could also be responsible for the activity
[153a].
Zea mays L. (Poaceae), “purple corn”, “maiz
morado”.
Used as a food colouring and to make a beverage
named “chicha morada” as an antioxidant, antiobesity
and to lower blood pressure [154a,f].
The most prevalent constituents are cyanidin-3-glucoside, cyanidin-3-
succinylglucoside, pelargonidin -3-(6”-malonylglucoside) [154a].
Other anthocyanins are: pelargonidin and peonidin-3-glucoside,
cyanidin and peonidin -3- (6”-malonylglucoside) cyanidin,
pelargonidin and peonidin- 3- (6”-ethylmalonylglucoside). Flavanol-
anthocyanins such as catechin-(4,8)-cyanidin-3-glucoside, catechin
and epicatechin- (4,8)-cyanidin-3-malonylglucoside; catechin and
epicatechin-(4,8)-peonidin-3-glucoside, catechin and epicatechin-
(4,8)-cyanidin-3,5-diglucoside, among others [154a-d]. Phenolic
acids such as p-coumaric acid, vainillic acid, ferulic acid, syringic
and caffeic acids, chorogenic acid. Flavonoids such as derivatives of
hesperitin, rutin, morin, naringenin, quercetin and kaempferol
[154e,f].
Anthocyanin pigments posses various physiological activities, such
as hydroxyl and superoxide radical scavenging and growth inhibition
of colon cancer cell; one of them, C-3-G possesses authentic
antioxidant and anti-inflammatory effects in vivo. There are even
reports that anthocyanins mediate an antiobesity effect when
consumed at high levels [154a]. Purple corn extract was capable of
significantly reducing lipid peroxidation and at the same time
increasing endogenous antioxidant enzyme activities in isolated
mouse kidney, liver and brain [154f].
Plukenetia volubilis L. (Euphorbiaceae), “sacha
inchi”, “mani del monte”.
Seeds are edible when cooked or toasted. Fresh seeds
are mildly laxative; leaves are edible; fresh leaves
used against burns [150].
Sacha inchi seeds contain predominantly unsaturated fatty acids
including oleic, linoleic and α-linolenic acids [155a-i]; and to a lesser
extent, saturated fatty acids including palmitic and stearic
acids.[155a,c,d,f,h]. Other compounds present in the seeds were:
(2R)-2,8-dimethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-3,4-
dihydrochromen-6-ol; (2R)-2,7,8-trimethyl-2-[(4R,8R)-4,8,12-
trimethyltridecyl]-3,4-dihydrochromen-6-ol [155c,d,f,h]. Other
identified compounds are: phenyl alcohols, flavonoids, secoiridoids,
lignans and common sterols such as campesterol, stigmasterol and β-
sitosterol [155f,h,i].
Huaman et al. performed an oral triglyceride tolerance test in 12
healthy young adults, using olive oil (82 g) as the lipid overload.
Sacha inchi seeds (50 g) significantly decreased triglycerides levels
after 1.5 and 4.5 h of ingestion [156a].
Gonzales et al. examined plasma fatty acid responses after a single
dose ingestion of sacha inchi or sunflower oil in 18 healthy
volunteers. Plasma α-linolenic, DHA, lauric, palmitic,
heptadecanoic, linolelaidic, cis-8,11,14-eicosatrienoic and cis-13,16-
docosadienoic acids increased after sacha inchi but not after
sunflower oil ingestion [156b]. In a randomized, double-blind study,
30 healthy adults received either sacha inchi or sunflower oil for 4
months. Sacha inchi oil was found to have unacceptable taste the
first week of the study; however, acceptability increased over time.
Hepatic and renal biochemical markers remained unchanged [156c].
Gentianella nitida (Griseb.) Fabris (Gentianaceae)
“hercampuri”, “hircampuri”, “te amargo”.
It is used as a remedy for hepatitis, diabetes, as a
cholagogue, microbiocide, diuretic, in the treatment of
obesity, among other uses [3].
Secoiridoides: secologanoside, amaroswerin, amarogentin [157a].
Secoiridoide glucoside: amaronitidin [157b]. C-glucosylflavone:
isoorientin. Xanthone glycosides and aglycones: mangiferine,
demethylbellidifoline and its 8-O-glucoside, norswertianine and its 1-
O-glucoside; swertianine and its 8-O-glucoside and 1-O-
primaveroside, gentisine, isoorientine [157a, c]. Sesteterpenoids:
nitidasin [157d] and nitiol [157e].
Extracts of G. nitida exhibited a strong hypoglycemic activity in
normoglycemic rats, as well as in rats with diabetes induced by
streptozotocin or alloxan or in rats receiving an overload of glucose
[157c]. The ethanol extract of G. nitida has potent antifungal activity
against C. albicans, T. mentagrophytes and M. gypseum. The ethyl
acetate fraction, obtained through a partition process of the ethanol
extract, showed an antioxidant activity similar to that of rutin [158].
References
[1] World Health Organization (2002) WHO Traditional Medicine Strategy 2002–2005. Geneva. WHO, p1.
[2] Cabieses F. (1993) Apuntes sobre Medicina Tradicional, la racionalización de lo irracional. Tomo II., Talleres de A&B, S.A. Lima.
[3] Mejía K, Rengifo E. (2000) Plantas Medicinales de Uso Popular en la Amazonía Peruana. (2da. ed.). Agencia Española de Cooperación
Internacional, Lima, 284 pp.
[4] Villar M, Villavicencio O. (2000) Manual de fitoterapia. EsSalud/OPS. Lima, 405 pp.
[5] Busssman RW, Sharon D. (2014) Two decades of ethnobotanical research in Southern Ecuador and Northern Peru. Ethnobiology and Conservation,
3, 1-50.

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