C H A P T E R

36
Yacon (Smallanthus sonchifolius) use as an
antioxidant in diabetes
Ana Paula Costa Rodrigues Ferraz1, Jéssica Leite Garcia1, Mariane Róvero
Costa1, Carol Cristina Vágula de Almeida1, Cristina Schimitt Gregolin2,
Pedro Henrique Rizzi Alves3, Fabiana Kurokawa Hasimoto3,
Carolina B. Berchieri-Ronchi1, Klinsmann Carolo dos Santos4 and
Camila Renata Corrêa1
1
Department of Pathology, Medical School, São Paulo State University (UNESP), Botucatu, SP, Brazil,
2
Medical School, Mato Grosso State University (UFMT), Sinop, MT, Brazil, 3Institute of Bioscience, Medical School,
São Paulo State University (UNESP), Botucatu, SP, Brazil, 4Clinical Research Centre (CRC), Lund University
Diabetes Centre, Lund University, Malmö, Sweden

List of abbreviations this pathology, although nutritional and autoimmunity

are the main predictors of its physiopathogenesis.2
AGE advanced glycation end products The major metabolic abnormalities that occur in
CAT catalase
type 1 and 2 diabetes are hyperglycemia, hypertrigly-
eNOS endothelial nitric oxide synthase
FOS fructooligosaccharides
ceridemia, and ketoacidosis, which occur during insu-
GSH-Px glutathione peroxidase lin deprivation and affect the liver, and skeletal muscle
MRSA methicillin-resistant Staphylococcus aureus and adipose tissues.3 Deregulated insulin signaling
PPARS peroxisome proliferator-activated receptors leads to an excessive utilization of free fatty acids as
ROS reactive oxygen species an energy source in cardiac and skeletal muscle tis-
SCFA’s short-chain fatty acids
SLs sesquiterpene lactones sues, which could lead to a process called lipotoxicity
SOD superoxide dismutase and, consequently, oxidative stress.4
T1DM type 1 diabetes mellitus Dysmetabolism may be linked to increased produc-
T2DM type 2 diabetes mellitus tion of free radicals, which could lead to oxidative dam-
age of DNA, proteins, and lipids as well as the
activation of stress-sensitive pathways and the develop-
Introduction: from oxidative stress to ment of stress under the diabetic condition.5 Alternative
antioxidants acting on diabetes therapies based on herbal/medicinal plants have been
shown to possess some contribution toward reducing
Diabetes mellitus is a complex chronic disease char- diabetes-related oxidative stress damages to underlying
acterized by elevated levels of blood glucose and defi- pharmacological and molecular pathways based on their
cient production and/or action of insulin, which is a phytochemical profile by ameliorating the redox state
polypeptide hormone produced by pancreatic β-cells balance.6 Specifically, several studies have shown the
(islets of Langerhans) with anabolic effects in various antioxidant activity of natural compounds suggesting
tissues, participating on glycogen, triacylglycerol, and strong hydrogen- and electron-donating capacities due
protein metabolism.1 Several factors are involved in to their antioxidant potential in combination with

Pathology.
DOI: https://doi.org/10.1016/B978-0-12-815972-9.00036-6 379 © 2020 Elsevier Inc. All rights reserved.
380 36. Yacon (Smallanthus sonchifolius) use as an antioxidant in diabetes
reactive species scavenging, enzymatic activation, or
inhibition of diabetic conditions.7
Among these medicinal plants, yacon or Smallanthus
sonchifolius is considered a functional food due to the
bioactive compounds present in its roots and antioxi-
dants in its leaves.8 Based on this information, this
chapter aims to elucidate the effects of S. sonchifolius
on diabetic-related complications based on its phyto-
chemical profile.
Antioxidants and diabetes mellitus
Scientific evidence shows around 800 medicinal
plants and more than 200 bioactive compounds identi-
fied as therapeutic alternatives for diabetes treatment.9
Medicinal/herbal plants and diet-based polyphenol-rich
foods play a vital role in the production of the antioxi-
dant defense system by providing essential antioxidant
compounds such as vitamin E, C, and β-carotene, phe-
nols including flavonoids, and essential minerals that
form important antioxidant enzymes. Diet also has an
important effect in the oxidation process by affecting the
substrates that are subject to oxidation.10 Studies in
humans have demonstrated the beneficial effects of vari-
ous antioxidants in diabetic-related complications.
Several antioxidant compounds from herbal medicine
are involved in various diabetic pathological processes6
such as hyperglycemia,11 inflammation,12 insulin deple-
tion,13 and vascular damages.14
Antioxidant activity in hyperglycemia
and cardiomyopathy
Hyperglycemia occurring in diabetes mellitus is
caused by increased levels of glucose hepatic produc-
tion and diminished peripheral glucose utilization by
peripheral tissues (muscle and adipose tissue), which
in turn lead to increased breakdown of structural pro-
teins and lipolysis, leading to weight loss and higher
circulating lipid levels.15
Due to diminished glucose uptake, fatty acids are
used as the major energy source. The lipolysis process
involves the hydrolysis of triacylglycerol stored in adi-
pose tissue to glycerol and fatty acids. As a result, fatty
acids are released into the circulation, thus, increasing
their availability as an energy source and resulting in
their excessive oxidation in cardiac tissue and skeletal
muscle.16 Additionally, the increased oxidation of fatty
acid leads to decreased ATP production in the mitochon-
dria since this kind of energy is mainly provided from
glucose oxidation. Moreover, this process is an initial
unfavorable energetic state associated with the overpro-
duction of reactive oxygen species (ROS). Lipid energy
II. Antioxidants and Pathology
metabolism is activated by a superfamily of nuclear
ligand-activated transcription factors known as peroxi-
some proliferator-activated receptors (PPARs), which reg-
ulate the genes commonly involved in lipid utilization,
lipoprotein metabolism, and insulin action.17
Antioxidants can act as PPAR-α and PPAR-γ agonists,
providing lower fatty acids oxidation and ROS produc-
tion.18 Kaviarasan and Pugalendi19 showed that the
flavonoid-rich fraction from Spermacoce hispida seed pro-
moted the upregulation of PPARα gene expression,
which results in fatty acid catabolism and alleviates liver
and kidney damages. Also, Zheng et al.20 demonstrated
the antidiabetic activity of flavonoids present in
Selaginella tamariscina (Beauv.) through increased PPAR-γ
expression in adipose tissue and increased protein
expression of IRS-1 in hepatic and skeletal muscle tissues.
Oxidative stress, among other mechanisms, is
shown as an onset to diabetes complications. It is
known that in cardiovascular conditions excessive
reactive species such as hydroxyl radicals (•OH),
superoxide radicals (•O22 ), and peroxides (H2O2) are
produced continuously by NADPH oxidases, xanthine
oxidases, mitochondrial enzymes, and dysfunctional
endothelial nitric oxide synthase (eNOS).21 To counter-
act these free radicals and to avoid these reactions,
endogenous antioxidant enzymes (e.g., superoxide dis-
mutase (SOD), catalase (CAT), glutathione peroxidase
(GPx)) are activated, which in diabetic patients is
clearly reduced.22 Maritim et al.23 demonstrated that
antioxidant compounds such α-lipoic acid and vitamin
C and E have the capability to increase intracellular
glutathione levels and restore SOD contents in cardiac
tissue after 14 days of treatment.
ROS production can also mediate several molecular
pathways such as NF-κB activation, which increases
inflammatory mediators and stimulates other free radi-
cals production.24 In hyperglycemia, free radicals over-
production can activate polyol, hexosamine, protein
kinase C, and AGE pathways, which are involved in
structural damage.25 In general terms, antioxidants
prevent oxidant-induced cell damages by reducing
ROS generation via several mechanisms.26
Smallanthus sonchifolius: origins and
ethnobotanical characteristics
Yacon or S. sonchifolius of the Asteraceae family has
some common names in the Andean, Aymara, and
Quechua languages (Yacu and Unu meaning “water” as
well as Yakku meaning “watery,” Llaqon, Llacum,
Llacuma, or Yacumpi, the Quechua words that evolved
into “Yacon,” Aricoma, Aricuma, Jicama, Chicama, Shicama,
Jiquima, Jiquimilla (Ecuador), Poirre De Terre (French),
and Yacon Strawberry (English)). It is an indigean
 The nutritional characteristics and phytochemical profile of Smallanthus sonchifolius
perennial herbaceous plant native to the Andes moun-
tains27 with botanical expansion in regions of Venezuela
to the northwest of Argentina as well as western
Europe, New Zealand, Japan, the United States, the
Czech Republic, and the State of São Paulo.28
In 1845, it was described for the first time as
Polymnia sonchifolia Poepp. by Eduard Friedrich
Poeppig. Thereafter in 1978, Harold Ernest Robinson
established the Smallanthus genre by separating
Polymnia into two different species, namely
Smallanthus and Polymnia, which presents the name
Polymnia edulis Wedd. as its botanical synonym pub-
lished in 1857.29
This plant is a perennial herb (Fig. 36.1), 1.5 3 m
tall that is composed of an aerial system with lower
ovate and hastate leaves, upper ovate-lanceolate
leaves, and connate and auriculate leaves at the base
(Fig. 36.1A). The flower of the yacon plant is yellow to
bright orange and inflorescences that are terminal with
1 5 axes, each one with 3 capitula (Fig. 36.1B), and,
finally, with tuberous roots and short rhizomes system
composed of 4 20 tuberous storage brown, pink, pur-
plish, or cream or ivory white roots (growing
50 100 cm in height) (Fig. 36.1C).28
The organization of the vascular system of the
yacon is typical of roots since they are subterranean
bodies of caulinar nature, formed by short, thick sym-
podial rhizomes or “corona.” It adapts to a wide range
of soils, although it grows better in rich, moderately-
deep to deep soils that are well-structured and
drained, most composed in lateritic soils adjusted by
dolomitic limestone and can tolerate a wide pH range
from acid to weak alkaline.30
FIGURE 36.1 Smallanthus sonchifolious. Botanical specimens of yacon. (A) Yacon leaves; (B) yacon flowers; (C) yacon root system.
II. Antioxidants and Pathology
381
The S. sonchifolius cultivate has several advantages
in that it presents a defense system in its leaves
and glands, making insect attacks and access to
the plant difficult and contributing to cultivations
without the use of pesticides and with lower chemistry
contaminations.31
The nutritional characteristics and
phytochemical profile of Smallanthus
sonchifolius
The S. sonchifolius cultivation has nutritional pur-
poses due to its consumption as tea of its leaves, raw
and organic extracts, and its in -peeled and fresh in
natura or cooked roots, crisp form and juicer32 with
lower energy content (619 937 kJ/kg of fresh matter)
provided by its 70% water’s composition.33
It has a sweet taste due to the presence of
fructose.32 Fructose is derived from fructan, which
consists of any carbohydrate with one or more
fructosyl-fructose linked with osidic bonds; it could
be linear or branched fructose (oligo) polymers such
inulins or fructooligosaccharides.34 The higher pro-
portion of nutrients in the tuberous roots of S. sonchi-
folius regards in the special attention to inulin and
fructooligosaccharides (FOS) mentioned previously.35
The main fructooligosaccharides including kestose
and nystose present in S. sonchifolius are represented
in Fig. 36.2.
Inulin-type fructans are found in garlic, leek,
bananas,36 and in some Northeast Brazilian species.37
These show around 1 4 g (US) and 3 11 g (Europe)
382 36. Yacon (Smallanthus sonchifolius) use as an antioxidant in diabetes

TABLE 36.1 Yacon roots and its nutritional composition.

Fresh weight basis Dry weight basis

Water (%) 93 70
Ash (%) 0.3 2.0 1.1 6.7
Protein (%) 0.4 2.0 1.3 7.3
Fat (%) 0.1 0.3 0.4 1.0
Fiber (%) 0.3 1.7 1.0 5.7
Calcium (mg/g) 23

Phosphorus (mg/g) 21
Iron (mg/g) 0.3
Retinol (mg/g) 10
Carotene (mg/g) 0.08
Thiamin (mg/g) 0.01
Riboflavin (mg/g) 0.1

Niacin (mg/g) 0.33

FIGURE 36.2 Fructooligosaccharides. Kestose and nystose.
Ascorbic acid (mg/g) 13
Nutritional composition of Yacon roots.

(158 mg/g DW), sucrose (74 mg/g DW), and low-

FIGURE 36.3 Inulin structure in yacon. Inulin’ structure repre-
sentation. N 5 B35.
average daily consumptions and are used as sugar
substitutes in miscellaneous products.38 The S. sonchifo-
lius roots accumulate around 60% (on dry basis) of
insulin type β (2-1) fructans, mainly oligomers
(GF2 GF16) (Fig. 36.3).32
The main contents of carbohydrates in S. sonchifo-
lius roots are fructose (350 mg/g DW), glucose
polymerization degree (DP) oligosaccharides (GF2 9
around 201 mg/g),39 which oscillate during the grow-
ing cycle and harvest.40 Additionally, S. sonchifolius
holds other types of nutrients such proteins (1.3%
7.3% DW), fat (0.4% 1.0% DW), and fiber (1.0% 5.7%
DW), which are represented in Table 36.1.
The large dark green leaves and tubers of S. sonchi-
folius include the polyphenols group demonstrated
in Fig. 36.4A F including chlorogenic acid, caffeic
acid, quercetin, protocatechuic acid, p-coumaric acid,
and ferulic acid as major antioxidant compounds
(Fig. 36.4).41 Other polyphenols from S. sonchifolius
leaves that are bioactive compounds are in the form of
polyphenol ions of saturated and polyunsaturated
fatty acids such as dihexose and derivatives of palmi-
tic, oleic, and linoleic acids34 together with sesquiter-
pene lactones42 and essential oils such as β-pinene,
β-caryophyllene, and γ-cadinene.43
The different techniques as well as types of solvents
used in S. sonchifolius extract preparation are divergent
in literature. For instance, Dos Santos et al.44 show
quercetin as a major compound found in S. sonchifolius
leaves using 70% ethanol as a solvent.44 Genta et al.45
formulated a butanolic S. sonchifolius extract that
demonstrated the presence of caffeic acid and chloro-
genic acid. These report data may explain how the
preparation of the extract can affect the concentration
and biologically active principle of the polyphenolics
profile.

II. Antioxidants and Pathology

 Smallanthus sonchifolius nutrients and its interaction in diabetes
FIGURE 36.4 Polyphenols profile in yacon. Polyphenols in Smallanthus sonchifolious. (A) Chlorogenic acid, (B) caffeic acid, (C) quercetin,
(D) protocatechuic acid, (E) p-coumaric acid, and (F) ferulic acid.
Smallanthus sonchifolius nutrients and its
interaction in diabetes
Several studies have evaluated the effect of the crude
extract of S. sonchifolius leaves and roots, obtained in dif-
ferent ways, on the glycemia of diabetic animals.
Important data report that a significant decrease in post-
prandial blood glucose levels can be explained by the
stimulation of pancreatic mechanisms, the regeneration
or protection of β-cells that were partially destroyed
with the use of streptozotocin for the induction of exper-
imental type 1 diabetes mellitus (T1DM), the potentia-
tion of insulin secretion, and the possible increase in
peripheral glucose utilization.46 48
Based on these studies, the antioxidant and antidia-
betogenic effects of S. sonchifolius on β-pancreatic cells
is attributed. In other studies, it was verified that treat-
ment with hydroethanolic extract of S. sonchifolius
leaves promoted an improvement in the glycemic and
lipid profiles, an increase in the activity of antioxidant
enzymes in the skeletal44 and cardiac muscles, and
improvement of the alterations related to diabetic
cardiomyopathy (fibrosis and cellular disorganization)
and of the Langerhans islet architecture and function.49
Additionally, its shows an antioxidant potential in
literature.50
Hydroethanolic extract of S. sonchifolius leaves upre-
gulated the glycemic condition, reducing blood glu-
cose levels and, consequently, insulin resistance.51 The
hypoglycemic effect may be due to its phytochemical
profile, since the caffeic acid is associated with
II. Antioxidants and Pathology
383
reducing blood glucose through glycogenesis modula-
tion.52 Whereas chlorogenic acid (CGA) could modu-
late the antioxidant status and lipid and glucose
metabolism.53 It is known that the number of hydroxyl
groups (OH) present (trihydroxy phenolic acids,
dihydroxy (catechol), and mono-hydroxyl) in phenols
structure comprise the antioxidant properties. Based
on this knowledge, chlorogenic acid and its metabo-
lites present in S. sonchifolius leaves are possibly
associated with catechol groups, which, in turn, can
diminish the production of IL-8 though inhibiting the
activation of this cytokine and PKD-IKK-NFkB signal-
ing. Additionally, this compound could decrease the
mRNA expression of macrophage inflammatory pro-
tein 2 (MIP-2, a mouse homolog of IL-8).54
The main mechanism for the rapid glucose regula-
tion in diabetes as well as the lower levels of triglycer-
ides from chlorogenic acid improvement could be
associated with the prevention of glucose-6-
phosphatase translocase 1 and glucose-6-phosphatase
(provides glucose starvation) activities in the liver and
small intestine. In particular, this compound can
enhance phosphorylation, adiponectin (a glucose
hormone regulator) and adiponectin receptors of
AMP-activated protein kinase (AMPK).55
Therapeutic strategies such as S. sonchifolius use
lead to glycemic homeostasis and reduce the metabolic
shift generated in the diabetic condition, favoring the
use of glucose and decreasing the oxidation of fatty
acids and, consequently, improving the recovery of
cardiac and muscle tissues.
384 36. Yacon (Smallanthus sonchifolius) use as an antioxidant in diabetes
Applications in other areas of pathology
S. sonchifolius could be considered a food with mul-
tiple functions and effects on the human body as well
as a high source of functional ingredients to the food
industry. It has others types of applications due to its
prebiotic,56 antibacterial,57 and antimicrobial58 effects.
The most interesting additional application of
S. sonchifolius is that its prebiotic effect from inulin-
types fructans and FOS has interesting nutritional and
function actions on the gastrointestinal tract as these
substances are resistant to the hydrolytic activity in the
stomach they go through a fermentation process in the
large bowel, thus, increasing bacterial populations and,
consequently, fecal mass, thereby reducing disease risk
development.34 Campos et al.56 reported that an
S. sonchifolius flour diet promoted colon heath benefits
improving short-chain fatty acids (SCFAs) in a male
guinea pigs model. Specifically, a study by Reina
et al.59 showed that S. sonchifolius fermentation
improves a progressive drop in pH, enhancing
Leuconostoc species production in the intestinal tract.59
In other hand, de Andrade et al.60 isolated sesquiter-
pene lactones (SLs) from a dichloromethane extract of
S. sonchifolius and reported antibacterial proprieties
against S. aureus and others Gram-negative populations.60
Corroborating with this study, Joung et al.57 reported var-
ious types of S. sonchifolius leaf extracts against six strains
of methicillin-resistant S. aureus (MRSA).57
For these reasons, S. sonchifolius seems to be a plant
prebiotic through its nondigestible oligosaccharides
and against Staphylococcus aureus as an antimicrobial
effect, promising great perspectives in biotechnology,
clinical trials, and practice.
Summary points
• Deregulated metabolism, also referred as
dysmetabolism, which occurs in diabetes promotes
the overproduction of free radicals as well as the
depletion of the endogenous antioxidant system,
which, in turn, leads to oxidative damage in
different components of cellular and structural
compartments.
• Therapy approaches aiming to attenuate/alleviate
oxidative stress have been shown to be an efficient
strategy in promoting the regulation of metabolism
under the diabetic condition.
• The use of herbal/medicinal plants for the
treatment of many chronic diseases such as diabetes
and its complications has been recognized by a
number of scientists and physicians based on their
therapeutic properties.
II. Antioxidants and Pathology
• Phytochemicals from herbal medicines, specially
antioxidants, play an important role in the
antioxidant/oxidative balance in the diabetic
condition.
• Yacon, a perennial plant, rich in phenolic
compounds, possess antioxidant and
antiinflammatory properties.
• Evidences have emerged regarding hypo- and
antihyperglycemic effects of different yacon leaf and
root extracts.
• The potential therapeutic effects of yacon could
contribute to the detection of new targets and
treatments for diabetes and its complications.
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II. Antioxidants and Pathology