KnE Life Sciences | The 3rd International Meeting of Public Health and the 1st Young Scholar Symposium on Public Health | pages: 193–202

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1. Introduction

Hypertension is a public health problem in Indonesia by the data of the Health Research (Riskesdas) in 2013 which showed that 25.8% of adults had hypertension [1]. Based on data from SIRS (Hospital Information System) Special Region of Yogyakarta in 2011, the disease is among the ten largest disease cause of death in hospitals. The happens due to hypertension initiate degenerative and cardiovascular diseases. This disease can progress to stroke, heart disease, heart failure, and kidney failure [2].

This disease prevention should have started from prehypertension state. Prehypertension diagnosed to people with 120-139 mmHg for systolic or 80-89 mmHg for diastolic blood pressure. People with prehypertension had a cardiovascular risk two times greater than normal blood pressure [3].

Secang drink is a purplish red traditional drink that commonly consumed in Indonesia. The benefits of secang known as an antioxidant, antibacterial, anti-inflammatory, hypoglycemic activity, vasorelaxant, hepatoprotective, and others. The active polyphenols compound of secang (xanthones, coumarins, chalcones, flavonoids, homoisoflavonoid, and brazilin) can also provide blood pressure lowering effects [4]. Secang can increase the synthesis of endothelial NO (nitric oxide) to activate guanylate cyclase and increase cGMP (cyclic guanosine 3', 5' monophosphate) which serves to give vasorelaxation effect of human vascular smooth muscle [5].

In this study, secang drink give to Balaikota Yogyakarta officers with prehypertension based on data which showed that 32.53% of officers at Balaikota had prehypertension. This study aims to know the effect of secang drink to blood plasma NO level, and blood pressure then compared that effect to the control group not give secang drink.

2. Methods

The was an experimental study with a pre-post test with control group design. Subjects were chosen based on inclusion criteria and exclusion criteria. The inclusion criteria were prehypertension diagnosed by a doctor (120-139 mmHg for systolic blood pressure or 80-89 mmHg for diastolic blood pressure), 25-45 years old, BMI was between 18.5 to 27 kg/m 2 and willing to sign an informed consent, while the exclusion criteria were subjects with diagnosed of kidney disease, heart disease, adrenal tumor, coarctation aorta, diabetes mellitus, antihypertensive drugs, and corticosteroids consumption, alcohol consumption, smoking, and pregnancy or breastfeeding. Meanwhile, the criteria drop out were not drinking secang > 1 week and the use of vitamin supplements, minerals, herbs or herbal tea more than two times/glasses a day during the study. A total of 36 subjects were divided into two groups by a simple random allocation using a computer program.

The intervention group was given a secang drink once a day for four weeks while the control group does not provide a secang drink. Secang that given for one package as much as 3.8 g per 200 mL was calculated based on the study [6,7] and added Diabetasol sugar as non-caloric sugar that did not influence total caloric and phenolic intake. Secang that used was taken from the Regional Forest Mangunan Bantul Yogyakarta then processed and packaged by CV Dewie Makmur in Yogyakarta that has production permit. The subjects in the intervention group were asked to make a secang drink every morning in water with a temperature of 70-90 0 C for 20 minutes to get the most optimal active compounds [7].

Characteristic data of respondents, nutrient intake, physical activity, and stress level measured by interview using a validated questionnaire. Nutritional intake was measured three times before the study and three times during the investigation that includes two days of work and one day off. Subjects were asked to fast for 10-12 hours at night before the day of blood sampling to measure the plasma NO level. Blood specimens were taken from the cubital vein as much as 2 ml in the morning and carried out by a health analyst who has license practice. Measurement of plasma NO level used the Griess method in LPPT UGM unit I. Blood pressure was measured using a calibrated mercury sphygmomanometer at 2:00 p.m. to 16:00 pm. Blood pressure was measured three times by a nurse with ± 5 minutes interval and then averaged.

The data was processed using EXCEL program and analyzed using STATA 12 program. The normality of data was tested using the Shapiro-Wilk test then univariate analyzed. Comparisons between groups were tested using an independent t-test for standard data and Mann-Whitney for abnormal data. The Chi-Square analysis used for categorical data. The data presented in mean and deviation standard for average and median and a minimum-maximum value for anomalous data. The effect of secang drink to plasma NO level analyzed by Wilcoxon Signed-Rank test and outcome of secang drink to blood pressure was examined using repeated ANOVA The significance of the difference are presented by the value of p < 0.05.

3. Results

The subjects in this study were officers of the Balaikota Yogyakarta. At least 300 screened into 60 people who met the criteria for inclusion and exclusion, but only 42 peoples who were willing to become respondents. During the pre-test, three respondents were drop out. There were 39 respondents, grouped into two of 20 respondents in the control group and 19 in the intervention group. During for four weeks, there was monitoring of food intake, physical activity, general health, and blood pressure. There was no significant health problem due to secang drink that given. Three respondents met the exclusion criteria (smoking and taking supplements that affect blood pressure) and one subject whose lisis blood.

Figure 1

Consort Diagram Flow.

fig-1.jpg

Based on the results, the intervention group did not differ significantly compared with the control group. The evidence by the characteristics of the subjects in the two groups did not change at baseline and during the intervention.

In this study, subjects were asked not to change their usual consumption. The compliance of Secang drink consumption in this study monitor by food intake and collected the former “secang celup” each week. Average consumption of secang drinks by subjects in the intervention group for 28 days was 91% or 25 packages. It was still relatively good because of more than 80%.

Table 1

Characteristics of Subjects.


Variable Group Sig (p)
Intervension (n=18) Control (n=18)
Age 37.94 ± 4.11 35.89 ± 5.04 0.188 a
Gender
Male 9 (50%) 9 (50%) 1.000 a
Female 9 (50%) 9 (50%)
Education
High School 2 (11%) 7 (39%) 0.126 b
Diploma 2 (11%) 4 (22%)
Bachelor 11 (61%) 5 (28%)
Postgraduate 3 (17%) 2 (11%)
Systolic blood pressure (mmHg) 117.28 ± 9.19 122.56 ± 7.88 0.070 a
Diastolic blood pressure (mmHg) 79.83 ± 6.17 78.83 ± 5.09 0.599 a
Body weight (kg) 58.72 ± 9.54 62.77 ± 7.83 0.172 a
Height (m) 1.58 ± 0.09 1.62 ± 0.06 0.110 a
Body Mass Index (BMI)
Overweight (≥25 kg/m 2 ) 7 (39%) 6 (33%) 0,729 b
Normal (18.5-24.99 kg/m 2 ) 11 (61%) 12 (67%)
Exercise (x/week) 1.28 ± 0.57 1.28 ± 0.57 1.000 a
Hypertension family history
Yes 11 (61%) 10 (56 %) 0.735 c
No 7 (39%) 8 (44 %)
Note: Data presented in mean ± SD for standard data and the median (Min-Max) for abnormal data, the significant value of p < 0.05. An Independent t-test, b Fisher's exact test, and c hi-square test.
Table 2

Stress Level, Activity Level and Nutritional Intake Before the Study.


Variable Group Sig (p)
Intervension (n=18) Control (n=18)
Stress Level
Stress 1 (6%) 2 (11%) 0.500 c
No Stress 17 (94%) 16 (89 %)
Activity level
High activity 7 (39%) 10 (56%) 0.317 d
Low activity 11 (61%) 8 (44%)
Nutrition intake
Energy (kkal) 1454.27 ± 378.70 1452.56 ± 441.53 0.990 a
Fat (gram) 44.59 ± 20.91 56.92 ± 27.55 0.139 a
Protein (gram) 51.14 ± 24.25 52.36 ± 15.87 0.859 a
Karbohidrat (gram) 209.44 ± 70.91 198.76 ± 62.92 0.636 a
Vitamin A (ug) 306.35 (97.57-1069.97) 385.28 (126.87-3067) 0.506 b
Vitamin C (mg) 25.88 (8.23-199.17) 36.78 (13-135.97) 0.429 b
Natrium (mg) 391.4 (34-1271.33) 442.68 ± 251.68 0.506 b
Tea consumption (x/hari) 1.11 ± 0.51 0.88 ± 0.55 0.201 a
Note: Data presented in mean ± SD for standard data and the median (Min-Max) for abnormal data, the significant value of p < 0.05. An Independent t-test, b Mann-Whitney test, c chi-square, and d Fisher's exact test.
Table 3

Stress Level, Activity Level and Nutrition Intake During The Study.


Variable Group Sig (p)
Intervension (n=18) Control (n=18)
Stress Level
Stress 2 (11%) 0 (0%) 0.486 c
Not Stress 16 (89%) 18 (100%)
Activity level
High activity 10 (56%) 10 (56%) 1.000 d
Low activity 8 (44%) 8 (44%)
Nutrition intake
Energy (kkal) 1450.05 ± 409.69 1512.13 ± 479.59 0.678 a
Fat (gram) 51.12 ± 16.52 59.39 ± 21.22 0.200 a
Protein (gram) 50.93 ± 15.87 55.00 ± 20.54 0.509 a
Karbohidrat (gram) 202.85 ± 72.63 195.93 ± 60.55 0.758 a
Vitamin A (ug) 489.92 (84.23-1828.1) 285.2 (12-1286.93) 0.055 b
Vitamin C (mg) 51.68 (18.2-155.83) 30.53 (5-118.07) 0.376 b
Natrium (mg) 538.11 ± 236.33 552.4 ± 304.05 0.875 b
Tea consumption (x/hari) 1 ± 0.65 1.09 ± 0.67 0.676 a
Note: Data presented in mean ± SD for normal data and the median (Min-Max) for abnormal data, the significant value of p < 0.05. An Independent test t-test, b Mann-Whitney test, c Fisher's exact test, and d chi-square test.
Table 4

Changes of plasma NO levels after study


Variable Group Sig (p) b
Intervension (n=17) Control (n=18)
NO level (µmol/L)
Before 30.44 (20.95-52.21) 30.44 (22.96-53.32) 0.855
After 33.14 (19.57-56.89) 34.81(25.35-47.14) 0.923
Δ 2.69 (-10.69-25.29) 2.32 (-7.65-18.48) 0.775
Sig (p) a 0.047 0.044
Note: Data presented in median (Min-Max), the significance value of p < 0.05. A Wilcoxon test and b Mann-Whitney.
Figure 2

Changes in Blood Pressure during the study (Note: (I) = Intervention and (C) = Control).

fig-2.jpg
Table 5

Changes of blood pressure after the study.


Variable Group Sig (p)
Intervention (n=18) Control (n=18)
Systolic blood pressure (mmHg) Before 120.65 ± 5.78 119.78 ± 7.58 0.704 b
After 116.44 ± 7.78 115.833 ± 7.89 0.816 b
Δ -4.20 ± 7.27 -3.95 ± 7.08 0.639 a
Sig (p) 0.016 a 0.310 a
Diastolic blood pressure (mmHg) Before 83.38 ± 7.35 80.76 ± 8.57 0.333 b
After 78.38 ± 4.25 76,31 ± 7,47 0.311 b
Δ -4.99 ± 9,12 -4.46 ± 8.62 0.478 a
Sig (p) 0.000 a 0.084 a
Note: Data presented in mean ± SD, significance value of p < 0.05. a Repeated ANOVA Test and b Independent t-test
Table 6

Classification of blood pressure after study.


Blood pressure classification Intervention Control Sig (p)
n % n %
Prehypertension 7 38.89 11 61.11 0.182 a
Normal 11 61.11 7 38.89
Total 18 100 18 100
Note: the significance value of p < 0,05 a chi-square test
Table 7

The Relationship of the Plasma NO Level and Blood Pressure Changes.


Variable Plasma NO Level
R p-value
Systolic blood pressure -0.0562 0.748 a
Diastolic blood pressure 0.0619 0.724 a
Note: the signifikansi value p < 0,05. a n Independent t-test

The data analysis showed there increased plasma NO levels not only in the intervention group but also the control group. There were no significant differences plasma NO level between the intervention and control group (p > 0.05). Meanwhile, the effect of secang drink had been found to lower systolic and diastolic blood pressure in the intervention group significantly. Based on the results, there was a decline when compared between groups was not significant (p > 0.05). There were 11 of 18 (61%) who initially had prehypertension become normal blood pressure after being given a cup of drinks for four weeks. This proportion was more than the healthy subjects without being given any treatment (7 out of 18 people or 39%) in the control group.

4. Conclusions

The increasing plasma NO level in the group given secang drink described in studies on isolated rat aorta cells and human umbilical endothelial vein. Secang extract can give vasorelaxation effects by induces the increasing formation of NO, NOS activity and influx of extracellular Ca 2+ in cells [6] and inhibiting the activity of arginase II of human umbilical endothelial vein [9]. Meanwhile, plasma NO level of the control group was not given secang drink also increased. It relates to the type of NO in the blood consist of three kinds of isoforms (iNOS, nNOS, and eNOS) that cannot measure using Griess Method. The NO level in subcutaneous adipose tissue of human also influenced by gene expression [10], age, sex, smoking behavior, BMI, cholesterol, and triglyceride levels [11]. Gene expression, cholesterol, and triglyceride level not measured in this study. The results are different from the study of chocolate given for 15 days increased the NO level significantly [12]. It is likely due to differences in active substances. The results as same as with spinach juice not given any effect on the NO level in serum of men with prehypertension [13]. High physical activity has a more powerful influence on the NO level [14]. The also may occur because of the proportion of subjects with high activity more than subjects with low action.

The decreasing systolic and diastolic blood pressure in the intervention group describe in previous studies [5]. Secang extract lowered α1-receptor agonist phenylephrine-precontracted aortic ring significantly through increased endogenous NO and cGMP formation. Secang also can reduce blood pressure by inhibits vasoconstriction through norepinephrine, blocking voltage and Ca 2+ receptor that independent from the endothelium [15]. The effect of secang drink on lowering blood pressure also can be through the antioxidant activity of its polyphenols that reduce oxidative stress [16]. The decrease in oxidative stress can affect blood pressure by lowering peroxides nitrite (NOX) from NO [17]. Meanwhile, there was a decrease in blood pressure in the control group that not statistically different compared to the intervention group. The blinding method not used in this study can affect the result.

Secang drink was not strong enough to give a significant effect on the decrease of blood pressure compared with the control group. These results have similarities with the study [18] that consumption of tea for four weeks did not affect blood pressure reduction. Meanwhile, this result is different from the study of chocolate that decreased lower systolic blood pressure significantly [12]. Polyphenols of tea drink can be affected by heating then decrease the antioxidant activity [19]. It may occur that using hot water in the making of drink influenced the polyphenols activity.

The control group had a blood pressure decrease were not statistically different in the intervention group. The decline can be affected by factors that not examined in this study. According to [20], the blood pressure control by hemodynamic hypertension, renin-angiotensin system, autonomic nervous system, endothelial dysfunction, insulin sensitivity, genetic and kidney function. The control mechanism influenced by age, gender, genetics, BMI, stress levels, physical activity, salt intake, and blood lipid levels. In this study, several factors that influence blood pressure has minimized through the inclusion and exclusion criteria. These factors are analyzed using statistical and showed no difference between groups. Meanwhile, lipids and blood cholesterol not studied because of limitation. It may influence the results.

Plasma NO was associated with blood pressure can be caused by the low bioavailability of NO in their function as vasorelaxant [21]. Bioavailability of NO produced by eNOS is influenced by many factors: the expression of protein / mRNA eNOS, the availability of L-arginine as a substrate which is constrained by ADMA, the availability of NO cofactors including BH4 catalyzed by GTP cyclohydrolase, protein interactions such as Caveolin, HSP90, modification posttranslational and the reaction of NO with SOD against peroxynitrite anion.

There was plasma NO level increase and blood pressure decreased significantly in the group that given secang drink, but there was no difference compared to the control group. For further study, it is expected to study the influence of secang drink to blood pressure with the blinded method.

Acknowledgment

The authors would like to thank LPDP (Lembaga Pengelola Dana Pendidikan) for financial support of the study.

Ethical Approval

The study was conducted in June-August 2016 in the Balaikota Yogyakarta and has received permission from the ethics committee of the medical faculty of UGM (KE / FK / 464 / EC / 2016).

Competing Interest

The authors declare they have no conflict of interest. The authors alone are responsible for the content and writing of this article.

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