The Antidiabetic Effect of Black Glutinous Tapai Beverage in

Metabolic Syndrome Rats

Rahmi Khoirunnisa

, Wachid Putranto

and Ida Nurwati

Department of Nutrition Sciences, School of Postgraduate, Sebelas Maret University, Surakarta, Indonesia

Department of Internal Medicine, Faculty of Medicine, Sebelas Maret University, Surakarta, Indonesia

Department of Biochemistry, Faculty of Medicine, Sebelas Maret University, Surakarta, Indonesia

Keywords: Black Glutinous Tapai Beverage, Antidiabetic, Blood Glucose, Metabolic Syndrome.

Abstract: Metabolic syndrome (MetS) known as insulin resistance syndrome, is recognized as a risk factor for type 2

diabetes mellitus. Management of MetS involves a combination of lifestyle changes and pharmacological

interventions. Black glutinous tapai beverage (BGTB) as local food contains Lactobacillus spp., which can

be a potential source of probiotics to improve hyperglycemia. This study aimed to determine the efficacy of

BGTB as an antidiabetic in rat models of MetS. This study used 30 male Sprague Dawley rats which were

divided into five groups, one as a normal group (N) given a standard diet, and the other four groups were

given a high-fat diet for 2 weeks and induced by Streptozotocin (STZ) and Nicotinamide (NA), i.e. negative

control (KN) was given a standard diet, positive control (KP) was given metformin 9 mg, treatment 1 (P1)

and treatment 2 (P2) were given BGTB 0,9 ml 200 gr-1 rat BW and 1,8 ml 200 gr-1 rat BW, respectively for

four weeks. The result showed a significant difference (p=0.000) in blood glucose and HbA1c after giving

BGTB. This study showed that BGTB has the potential to be developed as a functional beverage and source

of probiotics for people with MetS.

1 INTRODUCTION

Metabolic syndrome (MetS), known as insulin

resistance syndrome, is recognized as one of the risk

factors for cardiovascular disease (CVD) and type 2

diabetes mellitus (T2DM). Obesity and insulin

resistance are considered significant factors in the

development of MetS (Limanan & Prijanti, 2013;

Rochlani et al., 2017; Srikanthan et al., 2016). The

prevalence of MetS in Indonesia is 28% in men and

46.2% in women. In Indonesia, hyperglycemia (51%)

is the second component of MetS after hypertension

(61,0%) (Sigit et al., 2020).

MetS management involves a dual approach,

combining lifestyle changes and pharmacological

interventions. Emphasis on environmental and

lifestyle factors such as excessive calorie

consumption, lack of fiber intake, and low physical

activity as major contributors to MetS (PERKENI,

2021; Rochlani et al., 2017). There is no single

treatment for MetS, requiring several types of drugs

and a long period to improve each component. The

development of functional and nutraceutical foods

can be used to limit drug use and minimize side

effects (Ayivi et al., 2020; Rochlani et al., 2017).

Functional foods are intended to reduce the risk

of, slow down, or prevent certain diseases and

improve immunity, and are not medicines or dietary

supplements (Goetzke & Spiller, 2014). Black

glutinous tapai is known as a functional food

obtained from the fermentation process of black

glutinous rice. Black glutinous rice contains high

fiber, anthocyanins, phenols, and antioxidant

activity which can be an alternative healthy snack

for people with dyslipidemia, MetS, and

constipation. Consumption of black glutinous tapai

>11.5 grams per day, has a protective benefit against

MetS by 16 times compared to individuals who

consume <11.5 grams (Fauziyah, 2018; Yulianto,

2022).

The International Scientific Association for

Probiotics and Prebiotics (ISAPP) explained that

some types of fermented foods contain probiotics

that can benefit health (Marco et al., 2021).

Probiotics are microorganisms in the form of

bacteria that are given in sufficient doses to provide

health benefits to their hosts (Scavuzzi et al., 2014).

Khoirunnisa, R., Putranto, W. and Nurwati, I.

The Antidiabetic Effect of Black Glutinous Tapai Beverage in Metabolic Syndrome Rats.

DOI: 10.5220/0012900900004564

Paper published under CC license (CC BY-NC-ND 4.0)

In Proceedings of the 5th International Conference on Social Determinants of Health (ICSDH 2023), pages 75-81

ISBN: 978-989-758-727-6; ISSN: 2975-8297

Black glutinous tapai, in previous studies, was

studied to have several lactic acid bacteria, such as

Lactobacillus fermentum 1 BK 2-5 which have the

potential to become probiotic candidates in black

glutinous tapai (Panjaitan, 2018).

It was mentioned that the water content formed

from the fermentation of black sticky rice reached

55.18% on the 3rd day of fermentation (Fauziyah,

2018). This water content is referred to as black

glutinous tapai beverage. Research on utilizing

black glutinous rice juice against MetS conditions

currently does not exist.

In previous studies, BGTB contained 3x10

Lactobacillus spp.,. Some types of Lactobacillus can

suppress fasting and postprandial blood glucose. In

addition, it can help activate insulin signaling for

glucose absorption (Bobga et al., 2022; Choi et al.,

2020; Yadav et al., 2018). Black glutinous rice is a

good probiotic carrier because it does not need to go

through another processing process that can reduce

the amount of probiotics before consumption

(Nuraida, 2015). In addition, the deep purple color of

BGTB indicates the presence of anthocyanins have

function as a prebiotic. Black sticky rice contains 257

ppm of anthocyanins (Fauziyah & Pardina, 2020).

Anthocyanins can function as a prebiotic which can

significantly increase the number of Lactobacillus

spp., (Wang et al., 2020; Zhu, 2018).

This study aims to see if black glutinous tapai

beverage can be an alternative functional food for

antidiabetics and patients with MetS.

2 MATERIAL AND METHOD

2.1 Production of BGTB

Making BGTB begins with separating black

glutinous rice from foreign objects and washing it.

Black glutinous rice is then soaked overnight or for

approximately 8 hours. Subsequently, black glutinous

rice is steamed for 1 hour. After that, prepare hot

water that has just been brought to a boil in a ratio of

1:1.2, then put the steamed black glutinous rice into

the boiling water and stir again until evenly

distributed. Cover the pot, and let stand for 30

minutes. Prepare the steaming pot again, then steam

the black sticky rice for ± 1 hour until cooked.

Remove and cool the black glutinous rice. After

cooling, mix the sticky rice with the mashed yeast,

then stir until smooth. Store the tapai in a closed

container and let it sit for ± 3 days. After standing for

3 days at room temperature, the black glutinous rice

is squeezed and the black glutinous rice liquid is

taken, which we call BGTB, and stored in a sterilized

glass bottle.

2.2 Induction of Test Animal

Thirty male Sprague Dawley rats were weighed with

an average weight of 200 grams. For 2 weeks, rats

were given HFD and distilled water ad libitum.

After that, rats will be induced using STZ + NA. The

STZ dose was dissolved in citrate buffer (pH 4.5)

and nicotinamide was dissolved in normal

physiological saline. Rats were induced with

nicotinamide (110 mg/kg bw) in the intraperitoneal

section and 15 minutes later induced with STZ (45

mg/kg bw).

Samples that met the criteria for metabolic

syndrome based on NCEP-ATP III (FBG (>250

mg/dL), triglyceride (≥150 mg/dL), and HDL (<40

mg/dL) levels) were considered to have metabolic

syndrome and were used as experimental animals

(Aydin et al., 2014). This research has received

ethical clearance approval from KEPK FK UNS

(61/UN27.06.11/KEP/EC/2023).

2.3 Testing the Antidiabetic Activity of

Black Glutinous Tapai Beverage

This study was a laboratory experimental study,

using a randomized pretest and posttest-controlled

group design. Divided into five groups of 6 rats, one

group as a normal group and four MetS groups:

● KN: Normal (without treatment)

● K-: MetS (without treatment)

● K+: Administration of metformin 9 mg/kg BW

● P1: Administration of 0.9 mL BGTB

● P2: Administration of 1.8 mL BGTB

2.4 Measurement of Blood Glucose

Levels by GOD-PAP

Blood glucose measurements (FBG and PBG) were

conducted before and after treatment for 28 days.

Qualitative measurements used the Enzymatic

calorimetric Test GOD-PAP method. Glucose in the

sample was oxidized to form gluconic acid and

hydrogen peroxide. Hydrogen peroxide 4-

Aminoatypirene with phenol indicator was

catalyzed with POD to form quinonimine and water.

Serum (sample) was obtained from blood

centrifuged at 3000 rpm for 10 minutes, 10 µl of

serum was taken and mixed with 1000 µl of standard

sugar, then incubated at 37 C or 10 minutes.

Absorbance was measured by comparing the results

ICSDH 2023 - The International Conference on Social Determinants of Health

of the test solution with standard glucose levels at a

wavelength of 500 nm with a UV-Vis

spectrophotometer (Subiyono et al., 2016). Blood

glucose measurements (FBG and PBG) were

conducted before and after treatment for 28 days.

Qualitative measurements used the Enzymatic

calorimetric Test GOD-PAP method. Glucose in the

sample was oxidized to form gluconic acid and

hydrogen peroxide. Hydrogen peroxide 4-

Aminoatypirene with phenol indicator was

catalyzed with POD to form quinonimine and water.

Serum (sample) was obtained from blood

centrifuged at 3000 rpm for 10 minutes, 10 µl of

serum was taken and mixed with 1000 µl of standard

sugar, then incubated at 37

C or 10 minutes.

Absorbance was measured by comparing the results

of the test solution with standard glucose levels at a

wavelength of 500 nm with a UV-Vis

spectrophotometer (Subiyono et al., 2016).

2.5 Measurement of HbA1c by Elisa

Method

Measurement of HbA1c levels was carried out after

28 days of treatment, using the sandwich enzyme

immunoassay technique. First, the plate was washed

with wash buffer 2 times. Then 100 μl of standard,

sample, and control were added into each well,

sealed, and incubated for 90 minutes at 37oC. The

plate was washed with wash buffer 2 times without

soaking. 100 μl biotin solution was added into each

well and incubated for 60 minutes at 37oC. Washed

the plate with wash buffer 3 times soaking for 1

minute each time. Then, 100 μl of SABC solution was

added into the wells and incubated for 30 minutes at

370. After that, wash the plate again by using wash

buffer 5 times and soak it for 1 minute for each wash.

add 90 μl TMB substrate in each well and incubate

for 10-20 minutes at 37

C. Added 50 μl stop solution

in each well. Read the absorption with a microplate

reader at a wavelength of 450 nm and calculated the

levels (Triyono, 2016).

2.6 Data Analyze

Data were analyzed using the One-way ANOVA test

and continued using the Post Hoc Tukey HSD test.

This test is used to determine the impact of giving

black glutinous rice juice on FBG, PBG, and HbA1c

levels. If the data is not normally distributed, it will

be continued with the Kruskal Wallis non-parametric

test and then continued using the Games-Howell test.

3 RESULT

As the result shown in Table 1, both FBG and PBG in

the K+, P1, and P2 groups decreased, with the highest

decrease in the P2 group. Based on the

Figure 1: Standard Curve HbA1c.

Kruskall-Walis statistical test, there were differences

in each group (p < 0.05). Followed by Games-Howell

post hoc test shows no difference in influence

between groups K+ and P2.

The HbA1C level was calculated by substituting

the absorbance value (y) of the sample at 450 nm

wavelength into the logarithm regression equation y

= (equals to) ax + b, which was obtained from the

standard HbA1C curve so that the HbA1C

concentration value (x) was obtained. Based on the

Kruskal Walis test, black glutinous rice juice had a

significant effect on HbA1c levels between groups.

Post Hoc Tukey HSD test showed a significant

difference (P < 0.05) between doses of intervention

groups. From the difference in comparison with the

K- group in the intervention group, the P2 group had

a better effect of 55.28%.

4 DISCUSSION

The high-fat diet (HFD) formula adds a fat

component of up to 40%-50% of total calories for 4-

8 weeks (Gao & Zheng, 2014). The HFD is made by

the modern human diet which is currently found to be

higher in fat than the recommended diet (20%-25%)

(KEMENKES RI, 2019). The characteristics

obtained from HFD are obesity, impaired glucose

tolerance, and insulin resistance (Husna et al., 2019).

High levels of fat in the blood affect the ability of

insulin receptors and cause the expression of glucose

transporter type 4 (GLUT 4) to decrease. The

The Antidiabetic Effect of Black Glutinous Tapai Beverage in Metabolic Syndrome Rats

decrease in GLUT 4 expression causes glucose

transportation into the cell membrane to be disrupted,

decreasing glucose transport activity. Therefore,

HFD can cause high blood glucose levels (Rahmawati

et al., 2017).

Blood glucose levels after intervention in KN and

K-groups increased by 1.89% and 0.4%, respectively.

The increase in FBG in the normal group can be

caused by the age of the rats entering early adulthood

(Nurmawati, 2017), which was 14 weeks old at the

end of the intervention. Physiologically, increasing

age causes a decrease in the function of pancreatic β-

cells (Setiyorini & Wulandari, 2017). Along with age,

the ability of pancreatic β-cells will weaken until they

are damaged, which triggers hyperglycemia

(Rahmawati et al., 2017).

The increase in FBG in the K- group may be due

to the administration of HFD for two weeks and

STZ+NA induction without BGTB administration.

Furthermore, the results of this study showed that the

average FBG levels in K+, P1, and P2 experienced a

significant decrease after the administration of BGTB

(p<0.05). For the FBG pre-test and post-test from the

analysis results using paired t-test, treatment groups

K +, P1, and P2 showed the effect of BGTB

administration. Similar results of research on rice

bran fermented using Lactobacillus fermentum

MF423, it is known to improve hyperglycemia

conditions in vitro and in vivo and increase the

antioxidant capacity of diabetic rats (Ai et al., 2021).

In addition, it was found that L. rhamnosus BSL and

L. rhamnosus R23 have potential as probiotic foods

and are promising agents for managing T2DM (Eko

Farida et al., 2020). The Lactobacillus bacteria in

BGTB can help maintain the gut microbiota. This

effect inhibits the transfer of bacterial endotoxins into

the bloodstream and reduces circulating

lipopolysaccharides and proinflammatory cytokines,

which in turn decreases inflammation resulting in

decreased insulin resistance and controlled blood

glucose levels (Hindri et al., 2020).

Some LAB strains were reported to inhibit the

enzyme α-glucosidase and have antioxidant activity.

Inhibition of this enzyme will reduce glucose

absorption and thus reduce blood glucose levels. α-

glucosidase is an enzyme in the filamentous

peripheral membrane that catalyzes the process of

carbohydrate digestion, and inhibiting the activity of

α-glucosidase has been demonstrated to decrease

glucose absorption and reduce blood glucose levels

(E. Farida & Jennie, 2019). Inhibition of the enzyme

α-glucosidase is one of the therapeutic approaches to

reduce PBG levels because by inhibiting the enzyme

α-glucosidase, it can delay the breakdown of

oligosaccharides and disaccharides into

monosaccharides so that compounds that can inhibit

the work of the enzyme α-glucosidase can be used as

oral drugs for patients with type 2 diabetes (Febrinda

et al., 2013).

Table 1: Blood Glucose on rats with different treatments.

Blood

Glucose

Treatment Group

- K+ P1 P2

Fasting (mg/dL)

Pre-test

69.08±1.77

270.66

±2.18

269.70

±2.37

269.76

±4.11

267.39

±2.16

Post-test

70.39±1.52

271.79

±2.39

96.82

±4.04

126.37

±5.13

88.46

±2.97

Δ Mean±SD*

1.31±-0.25

1.13±0.21

-172.88

±1.67

-143.39

±1.02

-178.93

±0.81

pre-

ost** 0.000 0.001 0.262 0.782 0.462

Postprandial (mg/dL)

Pre-test

88.23±1.37

285.30

±1.98

284.06

±2.54

284.06

±3.49

283.84

±2.72

Post-test

92.49±2.12

293.65

±2.43

117.15

±3.85

142.41

±5.13

117.27

±13.02

Δ Mean±SD*

4.26±0.75

8.35±0,45

-166.9

1±1.31

-141.65

±1,64

-166,57

±10,3

re-

ost** 0.000 0.028 0.028 0.000 0.028

*Delta value (different mean between pre and post-test): positive

number indicated an increase and negative indicated a decrease.

**p<0.05 in each column indicated a significant difference

between pre and post-test.

a,b,c,d

)Numbers followed by the same letter indicate no significant

difference

Probiotics produce short-chain fatty acid (SCFA),

namely propionic acid, which can inhibit

gluconeogenesis in the liver to suppress glucose

production and reduce insulin resistance (Bishehsari

et al., 2018). Probiotics can act as inhibitors of the

enzyme α-glucosidase found in intestinal microfili so

that they can cause a decrease in blood glucose levels

(Gomes et al., 2014). A meta-analysis showed that

consuming probiotics can improve glucose

metabolism at a modest level (Zhang et al., 2016).

From the results of Hindri's research, it is stated that

the administration of Lactobacillus fermentum can

reduce blood glucose levels, and HbA1c (Hartini,

2016).

HbA1c levels were compared in each group, from

the results of Kruskal Walis there were differences in

each treatment group (p<0.05). Followed by the

Howell games test, there was an effect of BGTB

administration on HbA1c. In both FBG and PBG,

there was no difference in the K+ and P2 groups,

where 1.8 ml BGTB had similarities with metformin

in reducing blood glucose levels. The improvement

of MetS conditions by metformin is associated with

increased GLP-1 expression, AMPK activation, and

improved gut microbiota composition so it will have

an impact on increasing insulin sensitivity and

decreasing the process of lipolysis (Wang et al.,

2020).

ICSDH 2023 - The International Conference on Social Determinants of Health

The administration of BGTB was more effective

in reducing blood glucose levels presumably due to

the role of anthocyanins as antioxidants. Antioxidants

capture free radicals and reduce inflammation by

suppressing TNF-α production. Decreased TNF-α

production can improve insulin sensitivity through

increased autophosphorylation of insulin receptors,

increased tyrosine kinase activity on insulin

receptors, and increased GLUT-4 expression.

Increased GLUT-4 expression causes the

transportation of blood glucose to the cell membrane

to increase and blood glucose levels to decrease.

Anthocyanins as antidiabetics are also able to activate

AMPK in adipose tissue, muscle, and liver. Tasked

with maintaining energy balance in cells, AMPK will

suppress glyconeogenesis and lipolysis by

phosphorylating acetyl-CoA carboxylase and

AcetylCoA Oxidase, thus preventing glucose

formation in the liver and FFA formation and

increasing insulin sensitivity (Herrera-balandrano et

al., 2021; Takikawa et al., 2010). In addition, it can

also increase GLUT-4 (Glucose Transporter type 4),

so that glucose uptake into cells will increase (Ifadah

et al., 2021).

5 CONCLUSION

Black glutinous tapai beverage contains

Lactobacillus sp., and anthocyanins, which had been

demonstrated to have an antidiabetic effect. Our study

showed that BGTB could improve blood glucose

(FBG and PBG) and HbA1c of metabolic syndrome

rats. These effects might be beneficial to further

extend the application of BGTB as a potential

probiotic and prebiotic for metabolic syndrome.

ACKNOWLEDGEMENTS

The authors would like to thank everyone who

accompanied the steps in writing this article. Also,

they highly appreciate the Department of Nutrition

Science at Sebelas Maret University and the UGM

PSPG Laboratory staff for assisting the authors in

completing this research.

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