Decreasing of Oxidative Stress of Red Tamarillo

(Solanum Betaceum Cav.) Extract in STZ-NA-Induced Diabetic Rats

Gusti Ayu Kadek Diah Puspawati

1,*

, Yustinus Marsono

and Supriyadi

Science and Food Technology Department, Agriculture Technology Faculty, Udayana University,

JL. Kampus Bukit Jimbaran, Badung 80361, Indonesia

Food Science Department, Agriculture Technology Faculty, Gadjah Mada University,

JL. Flora No.1 Bulaksumur, Yogyakarta 55281, Indonesia

Keywords: Oxidative Stress, Red Tamarillo Extract, Diabetic Rats, STZ-NA.

Abstract: The objectivity of the research investigated tamarillo extract to decreasing of oxidative stress in STZ-NA

induced diabetic Sprague Dawley rats including its mechanism. The method used complete random designs

with six groups of male Sprague Dawley rats, every 5 rats. The groups were three groups control such as one

healthy rat as healthy control (COS); two diabetes groups: not treated as a negative control (CON) and given

metformin drug as a positive control (COP); three diabetes groups another with tamarillo extract treatments

such as: given ethanol extract (more anthocyanin) as a DEE; given acetone extract (more carotenoid) as DEE

and given both mixtures as DMEEA. The result showed MDA increased and SOD decreased in diabetes

control rats compared to healthy control rats. Intervention with ethanol extract, acetone extract and its mixture

for 28 days significantly decreased oxidative stress by decreasing of MDA and increasing of SOD. The

mechanism of its pathway was by decreasing of malondialdehyde, increasing of superoxide dismutase so

could be repairing of pancreas Langerhans islet following improving β-cells function, then increasing of

insulin, moreover could decreasing of blood sugar.

1 INTRODUCTION

Oxidative stress implicated an essential in the

pathogenesis of diabetes type 2 and its complications

(Aouacheri et al., 2015). Streptozotocin-nicotinamide

(STZ-NA) induced diabetic rats could rise oxidative

stress conditions that used to model rats of type 2

diabetes (Szkudelski, 2012; Aboonabi et al., 2014).

Oxidative stress is the imbalance between reactive

oxygen species production and breakdown by

endogenous antioxidants. Malondialdehyde (MDA)

and superoxide dismutase (SOD) levels are a

biomarker of oxidative stress (Aouacheri et al.,

2015). Malondialdehyde (MDA) is a marker of

peroxidation lipid and SOD is a marker as antioxidant

status. Type 2 diabetes is the diabetes mellitus that

has characteristic includes hyperglycemia and

disordered metabolism lipid, carbohydrate, and

protein are caused by disturbing of insulin action or

insulin resistance. The prevalence of type 2 diabetes

is the highest of all diabetes prevalence (about 90%

of all diabetes prevalence). The prevalence of

diabetes up to 425 million in 2017, every year always

increases and up to 50% undiagnosed (IDF, 2017).

Red tamarillo is a unique fruit because it has

anthocyanin and carotenoid compounds together in

fruit. The kinds of anthocyanin and carotenoid

compounds in red tamarillo had reported, but its

utilization was still limited compared to tomatoes and

purple eggplants. Red tamarillo fruit had been

reported to be used in extract form as a source of

antioxidants that have health benefits. Previous

research reported the ability of tamarillo extract as a

hypocholesterolemic agent (Idris et al., 2011; Kadir

et al., 2015); and as an antioxidant suppresses

oxidative stress in the in vitro study (Kou et al.,

2009). Asvita & Berawi (2016), reported the extract

of tamarillo capable decreasing of glucose and

cholesterol levels in obese subjects. Puspawati et al.

(2018) reported in the in vitro assay, the tamarillo

extract that focusing to the anthocyanin and

carotenoid compounds having different polarity were

able to inhibit α-glucosidase enzyme, but the in vivo

assay about the potency decreasing of oxidative stress

in type 2 diabetes rats especially in the no obes had

Puspawati, G., Marsono, Y. and Supriyadi, .

Decreasing of Oxidative Stress of Red Tamarillo (Solanum Betaceum Cav.) Extract in STZ-NA-Induced Diabetic Rats.

DOI: 10.5220/0010016601730180

In Proceedings of the 16th ASEAN Food Conference (16th AFC 2019) - Outlook and Opportunities of Food Technology and Culinary for Tourism Industry, pages 173-180

ISBN: 978-989-758-467-1

173

been not reported, so the aim of research was to

determine the ability of the dominant compounds

tamarillo extract (anthocyanin and carotenoid) in

decreasing of oxidative stress in type 2 diabetes rat

induced STZ-NA including its mechanism.

2 MATERIALS AND METHODS

2.1 Tamarillo Extract Preparation

Red tamarillos were collected from farmers in the

Dieng Plateau, Wonosobo District, Central Java

Province, Indonesia. Tamarillo fruit was 6 months old

from flowering (anthesis). The tamarillo extraction

was distinguished into two including ethanol

extraction and acetone extraction. The ethanol

extraction was using mesocarp, endocarp, and seed of

tamarillo. The acetone extraction using the mesocarp

of tamarillo. The ethanol extraction was using ethanol

solvent that made a sour condition with adding citric

acid of 3%, so bioactive compounds extracted more

anthocyanin. The acetone extract was using acetone

solvent and not added citric acid, so be extracted more

carotenoid. The methods of ethanol extraction and

acetone extraction were using sonication extraction

with ultrasonic bath (40 kHz frequency, 100% power,

the initial temperature of 27 , end 29 ). Ethanol

extraction was done for 20 minutes, while acetone

extraction was about for 30 minutes. Evaporation

solvent used a rotary evaporator. The ethanol extract

was as the EE, acetone extract was as the AE. The

mixture extract included ethanol extract and acetone

extract with a ratio 1:1 as MEEA.

2.2 In vivo Assay

In vivo assay of tamarillo extract was including of

ethanol extract, acetone extract and its mixture using

Sprague Dawley (SD) males rats, weight: 150-200 g.

Diabetes rats induced STZ-NA (Szkudelski, 2012).

The rats were distinguished into six groups (every 5

rats). They were one as the healthy control (standard

feed diet without treatment) as COS, two groups

diabetes rats, standard feed without treatment as a

negative control (CON) and given the drug metformin

as a positive control (COP). Three other groups were

diabetes groups, standard feed, given (force-feeding)

of ethanol extract (19.3 mg anthocyanin/kg BW) as

DEE, given (force-feeding) acetone extract (2.5 mg

carotenoid/kg BW) as DEA, and given (force-

feeding) its mixture (9.65 mg anthocyanin/kg BW

and 1.25 mg carotenoid/kg BW), as DMEEA. The

intervention was done for 28 days. The MDA and

SOD level of serum and pancreas, histopathology of

the pancreas were analyzed. All procedures related to

experimental animals were approved by the ethical

clearance commission from the LPPT-UGM,

Indonesia (Approval No: 00067/04/LPPT/IX/2016).

2.3 Malondialdehyde (MDA) Assay

Malondialdehyde (MDA) is a secondary product that

used to estimate indirect lipid peroxidation. This

assay employs the quantitative sandwich enzyme

immunoassay technique by the ELISA kit. Antibody

specific for MDA has been pre-coated into a micro-

plate. The MDA kits used Fine Test (Wuhan Fine

Biological Technology Co., Ltd., Hubei-China). The

test sample was supernatant from serum and

pancreas. The sample was diluted with a dilution

factor of 50 times. The standard concentration: (2000;

1000; 500; 250; 125; 62.5; 31.25, 0) pg/mL. The

absorbance test was on the λ450.

2.4 Superoxide Dismutase (SOD)

Enzyme Assay

SOD employs the quantitative sandwich enzyme

immunoassay technique by ELISA kit. Antibody

specific for SOD has been pre-coated into a micro-

plate. The SOD kits used Fine Test (ER1347, Wuhan

Fine Biological Technology Co., Ltd., Hubei-China).

The test sample was supernatant from serum and

pancreas. The sample was diluted with a dilution

factor of 50 times. The standard concentration: (2000;

1000; 500; 250; 125; 62.5; 31.25; 0) ρg/mL

Absorbance test was on λ450.

2.5 Histopathology Study

The pancreas samples fixed in the 10% formalin

which were sliced about 1 cm thick, and placed into

the cassettes, then the cassettes were put into tissue

processor machine, which comprises of dehydration

with alcohol, clearing with xylene and wax, following

with impregnating process automatically for

overnight (14 h). The cassettes were embedded in

molten paraffin, which later cooled down and formed

blocks paraffin. Each block was trimmed then

sectioned about 5 mm by using a microtome. Then

thin sections were put in the water bath at 45  few

seconds, fished out, and set on a microscopic glass

slide, proceed with hematoxylin and eosin (H&E)

staining, and observed under a light microscope for

evaluation. (Tatar et al., 2012).

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2.6 Statistical Analysis

Statistical analysis was performed using SPSS

software for windows, version 21 (SPSS, Inc.,

Chicago, USA). The data were presented as the mean

± S.E.M. (standard error of the mean). The statistical

significance of data analysis has been assessed by

one-way analysis of variance (ANOVA) and a

significant difference among treatment groups was

evaluated by Duncan’s multiple range test. The

results were considered statistically significant at the

p-value of less than 0.05 (p<0.05).

3 RESULTS

3.1 Malondialdehyde (MDA)

Malondialdehyde (MDA) concentration was

measured as a marker of lipid peroxidation, as

markers of oxidative DNA damage. Serum and

pancreatic MDA levels are highest in diabetes control

rats (CON), the lowest in diabetes given a mixture of

ethanol and acetone extract of tamarillo (DMEEA).

Diet of ethanol extract (EE), acetone extract (EA) and

its mixture (MEEA) for 28 days could reduce

malondialdehyde (MDA) in the serum and pancreas

compare to diabetes control rats (p<0.05). All of the

extract tamarillo diets showed similar (no significant

difference) with the diabetes rats, given metformin or

positive control (COP) and healthy control rats

(COS). Malondialdehyde (MDA) levels in serum and

pancreas of Sprague Dawley rats after intervention 28

were shown in Table 1.

Table 1: Malondialdehyde (MDA) levels in serum and

pancreas of Sprague Dawley rats after intervention for 28

days.

Treatments

MDA serum

(µmol/L)

MDA pancreas

(µmol/L)

COS 5.58 ± 0.47 bc 3.18 ± 0.24 cd

CON 7.95 ± 0.92 a 7.62 ± 0.71 a

COP 5.86 ± 0.57 bc 3.32 ± 0.59 cd

DEE 6.48 ± 2.32 b 3.46 ± 0.62 c

DEA 6.60 ± 0.34 b 3.92 ± 0.77 b

DMEEA 5.29 ± 0.68 c 2.65 ± 0.10 d

COS=healty control; CON= negative control (diabetes); COP=

positive control (diabetes, given metformin drugs); DEE=

diabetes, given ethanol extract; DEA=diabetes, given acetone

extract; DMEEA= diabetes, given its mixture of ethanol and

acetone extract; different alphabet in the back column that

similar showed significant difference (p<0,05)

3.2 Superoxide Dismutase (SOD)

Superoxide dismutase (SOD) level in the serum and

pancreatic of diabetes rats as a negative control

showed the lowest levels (p <0.05), while the highest

in diabetes, given the mixture of ethanol extract and

acetone extract (DMEEA). The diet of tamarillo

extract (ethanol extract/EE, acetone extract/EA and

its mixture/MEEA) for 28 days could increase the

SOD level in the serum and pancreatic of diabetic

rats. The decreasing was the highest in diabetes, given

a mixture of tamarillo extract (DMEEA) and all of the

tamarillo extract showed similar to diabetes, given

metformin drugs (COP) and healthy rats (COS).

Superoxide dismutase (SOD) level in the serum and

pancreatic of Sprague Dawley rats after 28 days of

intervention showed in Table 2.

Table 2: Superoxide dismutase (SOD) levels in the serum

and pancreatic of Sprague Dawley rats after 28 days of

intervention.

Treatments

SOD serum

(ng/mL)

SOD pancreas

(ng/mL)

COS 5.57 ± 0.07 ab 0.47 ± 0.07 c

CON 3.00 ± 0.03 c 0.19 ± 0.03 d

COP 5.15 ± 0.11 b 0.61 ± 0.11 bc

DEE 5.45 ± 0.08 ab 0.64 ± 0.08 b

DEA 4.63 ± 0.13 b 0.63 ± 0.13 b

DMEEA

6.67 ± 0.17 a 0.81 ± 0.17 a

COH=healty control; CON= negative control (diabetes); COP=

positive control (diabetes, given metformin drugs); DEE=

diabetes, given ethanol extract; DEA=diabetes, given acetone

extract; DMEEA= diabetes, given its mixture of etanol and

acetone extract; different alfabet in the back coloum that

similar showed significant difference (p<0,05)

3.3 Histopathology

Pancreas histopathology was to determine the change

of morphology of pancreas tissue, especially in the

Langerhans islet. The pancreas of diabetes Sprague

Dawley rats induced STZ-NA could cause the

damage of pancreatic β cell especially in the

Langerhans islet, but not all, so implicated as insulin

resistance. The illustration in Langerhans islet in

diabetes, given ethanol extract (DEE), diabetes, given

acetone extract (DEA), diabetes, given mixture of

ethanol and acetone extract and diabetes given

metformin drugs (COP) after 28 day intervention

showed differences in the shape and structure of the

with the diabetes control (CON) and approaching

healthy control. The Langerhans islet on healthy

control sho

Decreasing of Oxidative Stress of Red Tamarillo (Solanum Betaceum Cav.) Extract in STZ-NA-Induced Diabetic Rats

175

wed that the endocrine arrangement spreads on the

Langerhans islet with a uniform cell shape, bluish-

purple endocrine cell nucleus round, nucleoli visible,

pink cytoplasm, whole, and normal endocrine cells.

The tamarillo ethanol extract diet in diabetes group

(DEE) showed endocrine cell repair on the

Langerhans islet, normal endocrine cells appear more

and empty cytoplasm without nuclei decreases

(Kanter et al., 2003). The same was shown in

diabetes, given acetone extract (DEA) and diabetes,

given a mixture of ethanol and acetone extract

(DMEEA). Improvements in the DEA group were

seen to be less compared to the DEE and DCEEA

groups. This was seen from the lower cell nucleus and

the smallest Langerhan islet size among the other

groups. Endocrine cell conditions in DEE, DEA and

DMEEA were no different from diabetes given

metformin (COP). The illustration of Langerhan islet

in pancreas after intervention 28 days showed in

Figure 1 (A-F) with 400 times

Figure 1: Illustration Langerhans islet in pancreas of

Sprague Dawley rats (400 x): (A) healthy rat (COS); (B)

diabetes (CON); (C) diabetes, given metformin drugs

(COP); (D) diabetes, given ethanol extract (DEE); (E)

diabetes, given acetone extract (DEA); (F) diabetes, given

mixture of ethanol and acetone extract (DCEEA).

Decreasing oxidative stress by reducing MDA

levels and increasing SOD levels which causes an

improvement of pancreas Langerhans islet,

increasing β cell function, further increases insulin

production thereby reducing blood sugar. Decreasing

oxidative stress can also reduce stress signals that will

reduce insulin resistance. Decreasing insulin

resistance will increase insulin sensitivity and

increase GLUT4 thereby increasing glucose uptake,

then lowering blood sugar. The description of the

proposed mechanism for reducing blood sugar by the

anthocyanin of tamarillo ethanol extract or the

carotenoid of tamarillo acetone extract in STZ-NA

induced diabetes Sprague Dawley rats was shown in

the form of a scheme in Figure 2.

4 DISCUSSION

The ability to reduce MDA levels from ethanol

extract diets could be caused by antioxidant of

anthocyanin compounds, while in acetone extract

diets because of the antioxidant carotenoid

compounds and in a mixture of ethanol and acetone

extract diets because there are antioxidants i.e:

anthocyanin and carotenoid together which were like

to fresh tamarillo fruit. Puspawati et al. (2018),

reported the anthocyanin extract of red tamarillo

consisted of anthocyanin total of 386.48 ± 19.82

mg/100 g extract and carotenoid extract of tamarillo

consisted of a carotenoid total of 50.80 ± 3.02 mg/100

g extract.

The higher pigment concentrations such as

anthocyanin and carotenoid went along with higher

antioxidant capacities (Stintzing et al., 2002).

Prabowa (2019) reported MDA level decreased in rats

that oxidative stress condition was due to the presence

of antioxidants such as carotenoid and flavonoid.

Anthocyanin belongs to flavonoid groups.

The lowest of MDA levels in serum and tissue

pancreas of diabetes rats, given the mixture of ethanol

and acetone extract indicating that antioxidants of

anthocyanin and carotenoid were not contradicting

synergism. This phenomenon because the antioxidant

could suppress lipid oxidation and free radicals

including MDA, so decreasing oxidative status with

different functions (Koo & Vaziri, 2003;

Tangvarasittichai, 2015; Kim et al., 2018).

Carotenoid available as antioxidant potency

associated with quenching response on oxidative

stress. While there was anthocyanin which presented

with scavenging pathway (Tangvarasittichai, 2015).

The ability of anthocyanin and carotenoid as

antioxidants are influenced by the types of

anthocyanins or anthocyanidin and carotenoids.

Puspawati et al. (2018), reporting the major

anthocyanin types in the tamarillo ethanol extract

were pelargonidin 3-rutinoside, delphinidin 3–

rutinoside and cyanidin 3-rutinoside, while acetone

extract found the major carotenoid types were β-

carotene, β-cryptoxanthin, zeaxanthin and lutein.

The structure of type anthocyanin/anthocyanidin

could reduce the potency of scavenging free radical

due to low bioavailability, so low absorption in the

circulating system and high excretion rate in urine

and feces, but opposite with high bioavailability.

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Tamarillo

Figure 2: Mechanism of decreasing blood sugar by decreasing oxidative stress of anthocyanin or carotenoid of tamarillo in

Sprague Dawley rats.

Anthocyanin with a high bioavailability

efficiently reduces cellular lipid peroxidation, hence

reducing the risk of many diseases (Khoo et al.,

2017). Matsumoto et al. (2001) and reported

delphinidin 3-rutinoside and cyanidin 3-rutinoside

from blackcurrant belongs high bioavailability. They

could be directly absorbed into the circulating system

after 30 minutes of consumption of anthocyanin

mixture from red fruit, the absorbed anthocyanins

were not metabolized into the aglycones or any other

metabolite forms in the human body, but not overall.

There are their glycosylated forms are excreted into

urine and feces (Miyazawa et al., 1994; Matsumoto et

al. 2001). Stintzing et al. (2002) reported the

glycosylated B-ring structure of anthocyanin

contributes to the high antioxidant activity, where

ortho hydroxylation and methoxylation substantially

increase the antioxidant activity. The Anthocyanidins

had higher antioxidant activity than their glycosides,

which are to be expected because the aglycons are

very unstable and highly reactive. Tangvarasittichai

(2015) reported anthocyanidin type was like in

tamarillo extract such as pelargonidin, delphinidin

and cyanidin have antioxidant functions by

scavenging free radicals.

The carotenoid including β-carotene, β-

cryptoxanthin, zeaxanthin and lutein types are

reported to suppress lipid oxidation so that they can

reduce MDA (Murillo & Fernandez, 2016). The β-

cryptoxanthin work by quenching free radicals

decreases MDA levels (Adela & Momeu, 2008).

Table 1 also showed a decrease in serum MDA

levels in diabetes rats, given mixture of ethanol and

acetone extract (DMEEA) lower than in the pancreas

MDA could be caused the anthocyanin or carotenoid

in the serum more in their original form, while the

pancreas has undergone metabolism into their

aglycone (Fernandes et al., 2014).

The antioxidant function of anthocyanin is

influenced by the type of aglycone associated with

β cell function/

HOMA β

Repaired of

Langerhans islet

Anthocyanin

Cy3R, Dp3R, Pg3R

β-carotene, β-cryptoxanthin,

eaxanthin

Blood su

carotenoid

Insulin sensitivity

GLUT4

3 R

-Cr

toxanthin

MDA

SOD

Uptake

glucose

Oxidative

stress

Insulin

resistance/HOMA-IR

acetone extraction

by a sonicator

Ethanol extraction

by sonicator

Decreasing of Oxidative Stress of Red Tamarillo (Solanum Betaceum Cav.) Extract in STZ-NA-Induced Diabetic Rats

177

their hydroxyl group. Tangvarasittichai, (2015)

reported the cyanidin, pelargonidin, and delphinidin

have the ability to scavenging free radicals better than

their original forms. The ability of anthocyanin is due

to the presence of hydroxyl groups in C3’, C4'-ortho-

dihydroxyl and 3 hydroxyl. Pelargonidin aglycone

could reduce MDA levels in STZ-NA induced rats to

normal conditions (Lucioli, 2012). This was similar

to Puspawati et al. (2018), who reported tamarillo had

the highest type of pelargonidin between cyanidin and

delphinidin. So, the pelargonidin in tamarillo had

potent to reduce MDA levels in type 2 diabetes.

Suzuki et al. (2011) reported that β-cryptoxanthin

was the highest type of carotenoid in tamarillo that

reduces oxidative stress with high levels of

hyperglycemia. This shows that tamarillo extract,

especially a mixture of ethanol and acetone extract of

tamarillo can reduce MDA levels better than the

individual form.

The superoxide dismutase (SOD) enzyme is one

of the antioxidant enzymes that are responsible for

neutralizing superoxide radicals (O2*) to be more

stable hydrogen peroxide (H

). The role of SOD is

the most critical role among antioxidant enzymes in

reducing the effects of oxidative stress (Sari et al.,

2005). Low serum and pancreatic SOD levels in

diabetes no treatment (CON) were associated with

high levels of MDA. High levels of MDA could cause

the body's antioxidant system such as SOD would

increase but following to decrease. This condition

was caused by oxidative stress which leads to

oxidative damage such as interference or damage to

the SOD enzyme.

Szkudelski (2001) reported induction STZ-NA in

rats could free radical cause oxidative stress which

leads to damage to β cells, but not overall. Kamble et

al. (2015), reported type 2 diabetes characterized by

oxidative stress could lead to oxidative damage such

as protein damage and could reduce the expression of

antioxidant enzymes such as SOD.

The ability of tamarillo ethanol extract can be

caused by the type of anthocyanin belonging to the

flavonoid group. Magalingam et al. (2013) reported

the flavonoid compounds to have the ability to

activate the antioxidant enzyme gene so that it can

increase its activity. The activation mechanism by

maintaining the bioavailability of NO, so that it does

not change into NOO- so that it can induce

antioxidant transcription factors, namely nuclear

factor E2-related factor-2 (Nrf-2) binds to ARE

(antioxidant response element) which will regulate

antioxidant gene formation such as SOD. This

enzyme in the production process is triggered by

levels of endothelial NO synthetase (eNOs) which is

positive regulators of mRNA to produce

SOD(Levonen et al., 2007). Stimulation of the

Nrf2/ARE pathway is fundamental for the induction

of antioxidant defense enzymes and the modulation

of the intracellular GSH in response to stress (Liu et

al., 2018). Flavonoid bound with the antioxidant

enzymes and caused direct activation of these

enzymes, where any of these mechanisms will result

in increased activity of the antioxidant enzyme

(Magalingam et al., 2013). Other mechanisms can be

through abilities as antioxidants that directly suppress

free radicals thereby suppressing the occurrence of

oxidative stress and oxidative damage (Kamble et al.,

2015). These compounds help in scavenging the

species that initiate the peroxidation, breaking the

autoxidative chain reaction, quenching •O2-, and

preventing the formation of peroxides (Gaschler &

Stockwell, 2017) The most effective antioxidants are

those possessing the ability to interfere with the free

radical chain reaction (Wojtunik-kulesza, et al. 2016)

The ability of tamarillo acetone extract can be

caused by the presence of carotenoid compounds that

function as antioxidants. The antioxidant function

directly suppresses free radicals by breaking chain

reactions into more stable products, which can reduce

oxidative stress levels and oxidative damage as in the

SOD enzyme (Kamble et al., 2015).

The highest SOD levels in DMEEA show that

anthocyanin and carotenoid compounds in the extract

can work in synergy to increase antioxidant levels.

This research is in line with that reported by Kadir et

al. (2015), the tamarillo extract diet derived from all

parts of tamarillo fruit given to Sprague Dawley rats

on a high-fat diet can increase SOD.

The illustration in diabetes, not treatment (CON)

was due to too STZ-NA induction, lesion of the

pancreatic tissue, endocrine cell degeneration on the

Langerhans islet, picnosis (endocrine cells

constrict/shrink), then necrosis, disappear, only the

cytoplasm appears empty and contains glycogen

deposits, enlarges without nucleus or vacuolization.

Necrosis is cell death that occurs after the blood

supply is lost or the presence of toxins characterized

by vacuolization (cell swelling), protein denaturation

and organelle damage. Besides necrosis, there is a

pattern of apoptotic cell death. Apoptosis occurs in

undesirable cell conditions eliminated in

physiological conditions and irreparable damage to

mutations (pathological conditions)(Tatar et al.,

2012).

Normal endocrine cell enhancement in diabetes,

given ethanol extract (DEE), diabetes given acetone

extract (DEA) and diabetes given mixture of ethanol

and acetone extract (DMEEA) was caused by the

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antioxidant properties of anthocyanin and carotenoids

which protect cells from oxidative damage due to

oxidative stress and the presence of anthocyanin and

carotenoids will play a role in increasing cell

proliferation. The ability as an antioxidant is also

shown by the results of increased SOD and decreased

MDA. The repairing pancreatic Langerhans islets in

DEE, DEA, and DMEEA were not different from

what happened in diabetes given metformin drug

(COP). Metformin can repair the pancreatic

Langerhans islet, not because of its antioxidant

properties but through its ability to increase insulin

sensitivity, thereby increasing GLUT4 levels and

blood glucose uptake to the tissues causing blood

sugar to decrease. This condition causes endocrine

cells to regenerate by mitosis or proliferation (Song,

2016; Rena et al., 2017).

Figure 2 went through starts from tamarillo in the

form of ethanol extract and acetone extract. Ethanol

extract predominantly contained anthocyanin, while

acetone extract was more dominant containing

carotenoids. From the dominant type of anthocyanin

i.e: pelargonidin 3-rutinoside and the dominant of

carotenoid type i.e: β-cryptoxanthin which were

antioxidant function. They could suppress oxidative

stress by reducing MDA levels, increasing SOD

levels. That condition would cause cell repair such as

β-cells on the pancreas Langerhans islet, so the β cell

could increase to producing insulin which was used

to reduce blood sugar in STZ-NA induced diabetes

rats. Decreasing of oxidative stress also could reduce

insulin resistance, so the insulin sensitivity increased,

further GLUT4 activity increased, followed by the

increase of glucose uptake, then also decreasing of

blood sugar.

5 CONCLUSION

Tamarillo extract that caused synergism of

anthocyanin and carotenoid compounds with

different polarity properties could decrease oxidative

stress in STZ-NA induced diabetes rats by decreasing

malondialdehyde (MDA), increasing the level of

superoxide dismutase (SOD) and repairing of

Langerhans islet of pancreas rats. Its mechanism of

decreasing oxidative stress with decreased MDA,

increased SOD, so impaired of Langerhans islet,

moreover improved function of beta cells/HOMA-β

following improved β-cells function, moreover

increased insulin level than would decrease blood

sugar. Other hand decreasing oxidative stress also

implied decreasing HOMA IR/insulin resistance, so

improved insulin sensitivity, moreover increasing of

GLUT activity, then increasing of uptake glucose

following to decreasing of blood sugar.

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