The Effect of Moringa Leaf (Moringa oleifera Lam.), Pandan Wangi (Pandanus amaryllifolius Roxb.) and Red Ginger (Zingiber officinale Rosc.Var) Extract Supplement Intervention on Uric Acid, Kidney, Liver Function and Perceptions of Hyperuricemia patients on health benefit

 

Tri D. Widyaningsih*, Rinten A. Sari, Widya D. Rukmi , Syavira A. Dahniar

Department of Food Science and Technology, Faculty of Agricultural Technology,

Brawijaya University, Malang, Indonesia.

*Corresponding Author E-mail: tridewantiw@ub.ac.id

 

ABSTRACT:

Giving herbal supplements made from moringa leaf extract 70%, fragrant pandanus 20% and red ginger 10% (KPJ) can lower uric acid levels of rat hyperuricemia significantly. To know the industrial scale production process and its influence on the chemical parameters of capsules extract formula KPJ extract conducted analysis of moisture content, total phenols, flavonoids and antioxidant activity (DPPH, FRAP and ABTS). Meanwhile, knowing the effect of herbal supplements formula moringa leaf extract, pandan fragrance, and red ginger to hyperuricemia sufferers, clinical trials conducted phase I on 40 people with hyperuricemia who consume herbal supplements formula moringa leaf extract, pandan leafe, and red ginger for 14 days. Furthermore, checks on uric acid levels, kidney function, and liver function before and after the intervention of herbal supplements formula moringa leaf extract, pandanus, and red ginger to find out the effectiveness of clinical trials phase I. The results showed that the best supplements are produced from the formula of thick extract KPJ as much as 60% and filler ingredients as much as 40%. The supplement has a water content of 5.49%, phenol 10.67mg GAE/g, flavonoids 4.37mg QE/g, DPPH 7.19mg TE/g, FRAP 12.82mg TE/g, ABTS 29.04mg TE/g, IC50 545.57ppm. Phase II research is a clinical trial phase I. This stage aims to determine the influence of KPJ supplements on uric acid levels, kidney function, and liver function before and after intervention and perception of hyperuricemia sufferers after intervention The perception results of hyperuricemia sufferers showed 65% of sufferers experienced a decrease in uric acid levels and 57.5% of sufferers were satisfied with the benefits and results of KPJ herbal supplements in lowering uric acid levels

 

KEYWORDS: Hyperuricemia, Moringa leaves, Pandan wangi leaves, Red ginger, Supplement KPJ.

 

 


INTRODUCTION:

Hyperuricemia is a condition of a person experiencing excess uric acid in the blood influenced by environmental and genetic factors1,2. A person is said to be hyperuricemia if his uric acid levels reach 357μmol/l (6mg/dL) for women and 416μmol/l (7.0mg/dL) for men3. The condition hyperuricemia can cause inhibition of the secretion and excretion system of renal function as well as causing injury to liver cells4,5.

 

 

Uric acid is a heterocyclic organic compound with the chemical formula C5H4N4O3(7,9-dihydro-1H-purine-2,6,8 (3H) -trione) with a molecular weight of 168 kDa. The main causes of hyperurism are an imbalance between the production of uric acid obtained from food, purin high drinks, the use of diuretic drugs, diabetes, obesity, and genetic factors with excretion and synthesis of uric acid through urine, kidneys, or gastrointestinal tract6-12.

 

An early clinical sign if a person experiences hyperuricemia is spontaneous pain in the joints and the pain disappears suddenly within a few days or a few weeks in the absence of interventions such as the consumption of anti-inflammatory drugs (steroids, NSAIDs, kotikoids, and colchicine) that can help to improve pain inflicted in a short period accompanied by slightly decreased uric acid levels13, but the use of such drugs if consumed over a long time can cause side effects such as indigestion, vertigo, eosinophilia, nephropathy (pain caused by nerve damage), allergic reactions, increased toxicity of 6-mercaptopurine and hepatitis14,15. So more effective and efficient strategies are needed to help lower uric acid levels and prevent the risk of hyperuricemia but remain safe if consumed long term. In addition to regulating lifestyle and consumption patterns, the provision of additional nutrients such as the consumption of supplements derived from natural ingredients can and prevent the onion of hyperuricemia. Plant derived bioactive compounds are referred to as phytochemicals. A wide range of phytochemicals have been studied in humans for their clinical benefits. Among the clinically useful phytochemicals are phenolic compound. Due to the large number of phenolic phytochemicals found in plants, as well as the fact that they are already available as dietary supplements16.

 

One of the formulas of herbal supplements that have the potential to be anti-hyperuricemia is moringa leaf simplicia, pandan wangi, and red ginger (KPJ). based on pre-clinical test results, it was proven that administering herbal supplement extract formula KPJ dose 45mg/kg BB mice that had potassium oxonate induced as much as 300mg/kg BB/day can significantly lower uric acid levels for 3 days17. HPLC-MS (High-Performance Liquid Chromatography With a Mass Spectrometer) analysis of KPJ extract formula supplements shows that there is a content of flavonoid compounds namely quercetin in KPJ extract formula supplements, quercetin contained in the herbal supplement extract formula KPJ is 4.23μg/g (Water extract) and 114.71μg/g (extra ethanol). Quercetin has the ability as an antioxidant, as it has the speed in transferring hydrogen atoms into free radical atoms and binding to transition metal ions so that free radicals become inactive. Free radicals/the oxidant are fundamental to any biochemical process and are required for aerobic life and metabolism. However, the majority of diseases and disorders are caused by oxidative stress due to free radicals16,17.

 

Also, KPJ extract herbal supplement contains flavonoids compounds 32943.33±709.46μg QE/g and phenols amounting to 7557.26±85.36μg GAE/g18. Both compounds also have activity as antioxidants that can inhibit the work of xanthine oxidase enzymes so that the formation of uric acid is inhibited, and can capture free radicals by donating hydrogen atoms or electrons to free radicals19,20.

 

 

The herbal supplement extract formula KPJ is further developed from laboratory scale to industrial scale. Products produced on a factory scale are expected to have good functional value at an affordable price. The development of new herbal supplements needs to go through several stages before marketing to the public which aims to provide safety guarantees and benefits as well as verify the results of in vivo and in vitro testing if the new supplement has the same effect when applied to humans.

 

The purpose of this study is to know the effect of herbal supplements on moringa leaf extract, pandan wangi leaves, and red ginger on uric acid levels, kidney function, and liver function before and after intervention in hyperuricemia sufferers. As well as knowing the perception of hyperuricemia sufferers after the intervention of herbal supplements formula of moringa leaf extract, pandan wangi leaves, and red ginger.

 

MATERIALS AND METHODS:

Material and Tools:

Simplicia moringa leaves, pandan wangi, and red ginger from Magelang City, Central Java, Indonesia. MCC 101 (Microcrystalline Cellulose), corn starch, silica dioxide, and colorless capsules measuring 0 (fill size 500mg). Chemicals used for analysis include ethanol 96%, Na2CO3, aluminum chloride, acid error, quercetin, NaNO2, AlCl3, NaOH, trolox, TPTZ (Tris Pyridyl Triazine), FeCl3, HCl, FeCl3 6H2O, DPPH, FRAP, ABTS, and folin ciocalteau. While the ingredients used for steering hyperuricemia patients includekapas, alcohol swab, and alcohol 70%.

 

Tools used include Vacuum Extractor, Hydraulic Press, Evaporator, Mixer "Wet Mixing Add Granulating Machine", Electric Oven, Moisturizer Analyzer, BJ-2 Disintegration Tester, WF 30 Electric Grinding Machine and NJP-800C Encapsulation Machine. Tools used for chemical and physical analysis are measuring pipettes, bulbs, analytical balance sheets, filter paper, buncher funnels, Petri dish, ovens, glass watches, pH-Meters, glassware, UV-Vis spectrophotometers, desiccators, and vortex-mixers. The tool used for screening hyperuricemia sufferers is Nesco Multi check, Test Strips Easy Touch Blood Uric Acid. While the tools used for health checking and blood sampling of sufferers include a tourniquet, split, GEA ZT-120 body scales, sphygmomanometer, and blood tubes.

 

Methods:

The research design uses descriptive methods on raw material analysis and perception testing as well as one group pre-test and post-test in phase I clinical testing.

 

 

Analysis of ingredients and herbal supplements of KPJ extract formula tested includes moisture content, total phenols, total flavonoids, antioxidant activity methods FRAP, ABTS, DPPH, and IC50 as well as levels of uric acid, urea, creatinine, BUN, SGOT, SGPT, and perception in hyperuricemia sufferers.

 

Procedure:

Making Herbal Supplement extract formula KPJ industrial scale:

As much as 70% simplicia of moringa leaves, 20% pandan wangi, and 10% red ginger extracted with water (1:10) using vacuum extractor for 8 hours at 50°C temperature to obtain the liquid extract. The liquid extract obtained is then evaporated for 24 hours using a temperature of 60°C and obtained a viscous extract as much as 6% of the initial material. Viscous extract mixed with filler 23% MCC, 15.6% corn starch, and 1% silica dioxide then mixed for 1 minute at a speed of 20 rpm. The material has been mixed with a temperature of 60°C to LOD <5%, if the material has met the standard and formed granules then the material is ready to be milled with a size of 22 mesh and sifted using a 24 mesh. Granules that have passed in the measurement of flow rate and silent angle are filled using the NJP800 machine and done packaging.

 

Population Study:

All prospective subjects who had met inclusion criteria such as aged 20-70 years, male uric acid levels >7.2 mg/dL and women >6mg/dL as well as exclusionary criteria namely: prospective participants took uric acid-lowering drugs, prospective participants had Berta complications (chronic and advanced kidney failure) interviewed for demographic information, food, and health checks. After a detailed interview at each participant's house, participants were invited to conduct an examination session related to the collection of blood specimens to measure uric acid levels, kidney function, and liver function at Laboratoium Klinik Prisma Husada, Ngunut-Tulungagung.

 

Furthermore, participants who had already performed the examination and retrieval of the initial blood specimen were asked to consume the herbal supplement extract formula KPJ for 14 days consumed daily as much as 2 capsules (1000mg/day). After 7 and 14 days of consuming herbal supplement extract formula, KPJ carried out examination and retrieval of blood specimens to find out the levels of uric acid, kidney function, and liver function of hyperuricemia sufferers who followed this study. Also, participants were interviewed about health and emotional perception after consuming the herbal supplement extract formula KPJ for 2 weeks.

 

 

Measurement of Uric Acid Levels, Kidney Function, and Liver Function:

Analysis of uric acid, urea, creatinine, BUN, SGOT, and SGPT in hyperuricemia patients was conducted by Husada Prism Clinical Laboratory in Ngunut District of Tulungagung Regency of East Java Province-Indonesia.

 

Data Analysis:

The data analysis used in univariate analysis to describe the characteristics of the variables studied namely gender, age, occupation, weight, and height as well as bivariate analysis to explain the influence between the two variables (independent variables and dependent variables) using the help of the Minitab statistics application version 17.0 for Windows Another test is described using descriptive analysis.

 

RESULT AND DISCUSSION:

Characteristics of Raw Materials Herbal Supplements Extract Formula KPJ:

Based on Table 1, it can be seen that the average moisture content of the three simplicia has met bpom standard No. 12 of 2014 which is <10%. The low water content will inhibit the growth of microbes, especially mycotoxins in simplicia20. Moringa leaves have a higher total phenol and flavonoids compared to other simplicia, it is shown that moringa leaves have non-nutritive antioxidant properties influenced by their hydroxyl groups21. Plants produce a large amount of antioxidants in order to control the oxidative stress caused by free radicals. For spesific metabolic requirements, free radicals of various type are constantly generated and quenched by an effective antioxidant network in the body. When the production of these species exceeds the capacity of the antioxidant system, oxidative damage to tissues and biomolecules occurs, eventually leading to disease conditions22.

 

The results of the antioxidant activity test of the third DPPH method of simplicia showed that moringa leaf simplicia has higher antioxidant activity compared to other simplicia, this is because moringa leaves contain active compounds namely flavonoids which are one of the secondary antioxidants or non-enzymatic antioxidants that can inhibit the formation of reactive oxygen compounds by binding to an atom or its forming is tampered with and capture free radicals so that free radicals (DPPH) do not react with cellular components or lose the properties of free radicals23. Flavonoids are hydoxylated phenolic substances that plants produce in response to microbial infections and have been shown to be antimicrobial agents against a variety of microorganism in vitro. Their activity could be attributed to their ability to complex with extracellular and soluble proteins, as well as bacterial cell walls. They are also powerful antioxidants with anticancer properties24. Antioxidants are substances that significantly delay or inhibit the oxidation of an oxidisable substrate when present in low concentrations compared to those of the oxidisable substrate. Antioxidants play an important role in preventing free radical mediated oxidation by scavenging radicals and inhibiting their formation. The antioxidant’s reactivity and concentration affect its ability to scavenge free radicals25.

 

The results of the frap method antioxidant activity test showed that moringa leaves simplicia also had higher antioxidant activity against Fe compared to other simplicia. This is because the flavonoid compounds found in simplicia can break the free radical chain so that it can stabilize free radicals by donating electrons or hydrogen atoms and radical compounds (Fe) so that they turn more stable26,27.

 

The results of the abts method's antioxidant activity test also showed that moringa leaf simplicia has higher antioxidant activity against ABTS free radicals compared to other simplicia. This is influenced by the absence of flavonoid compounds that have secondary antioxidant activity successfully donating 1 hydrogen atom to ABTS cation radicals so that free radicals become more stable26.

 

Based on the results of measuring antioxidant activity using 3 different methods show different results in each method. The ABTS method leads to a higher value of antioxidant activity when compared to the other two methods, this is because the ABTS method provides more specific absorbance at visible wavelengths and faster retention times. Also, ABTS can be dissolved in organic solvents and aquades so that it can detect hydrophilic and lipophilic compounds such as flavonoid compounds contained in moringa leaf simplicia, pandan wangi leaves, and red ginger. But the ABTS method cannot describe the body's defense system against free radicals so ABTS can only be used as a comparative method because it does not represent the body's biological systems27.

 

The method that can describe the body's defense system against free radicals is DPPH because the DPPH method provides information on the antioxidant activity of a bioactive compound in countering free radicals seen based on the value of IC5027. The low value of antioxidant activity in the DPPH method is influenced by DPPH which can only be dissolved in organic media and not in water media so that the ability to determine antioxidant activity in this type of hydrophilic compound becomes limited. DPPH and FRAP methods have something in common: both transfer electron and hydrogen atoms to disconnect and capture free radicals. In contrast to the FRAP method that is based only on electron transfer reaction28.

 

The value of  IC50 indicates that moringa leaf simplicia has higher free radical damping activity with other simplicia of 251.85±2.81ppm. It is affected due to the presence of flavonoid compounds that act as reducers, hydrogen donors, free radical catchers, singlet-forming reducers, and metal chelates29. These results show that moringa leaves have the potential as antioxidants.

 

Table 1. Preliminary Raw Material Analysis Results

Components

SDK

SDPW

SJM

Moisture Content (%)

9.083

9.911

9.590

Total Phenols (mg GAE/g)

15.027±

0.74

6.908±

0.36

3.942±

0.28

Total Flavonoids (mg QE/g)

8.547±

0,58

5.316±

0.58

2.075±

0.36

Antioxidant Activity Methods:

DPPH

(mg TE/g)

7.44±

0,11

4.723±

0.06

2.165±

0,03

FRAP

(mg TE/g)

21.743±

0.08

11.314±0.32

4.984±

0,03

ABTS

(mg TE/g)

53.636±

0.60

20.276±0.49

16.154±0,17

IC50

251.85±

2.81

719.189±21.94

1037.965±21.70

Description :

SDK         : Simplicia Moringa Leaves

SDPW      : Simplicia Pandan Wangi Levaes

SJM         : Simplicia Red ginger

 

Characteristics of KPJ Herbal Supplement Extract Formula:

The average test result of antioxidant activity of herbal supplement extract formula KPJ using DPPH method is 7.198±0.33mg TE/g, the results show that viscous extract results evaporation formula simplicia has antioxidant activity against free radicals (DPPH). At room temperature, DPPH is a stable free radical that accepts an electron or a hydrogen radical to form a diamagnetic molecule that is stable. The ability of DPPH radicals to be reduced was determined by the reduction in their absorbance at 517nm caused by antioxidants30. This is influenced because the herbal supplement extract formula KPJ contains flavonoids amounting to 4.371±0.63mg QE/g which is a secondary antioxidant by cutting out chain oxidation reactions caused by free radicals or flavonoid compounds catching free radicals so that free radicals (DPPH) do not react with cellular components or lose free radical properties23.

 

The result of measuring the activity of antioxidant herbal supplements in KPJ extract formula with FRAP method is 12.823±0.20mg TE/g. The following results suggest that the herbal supplement extract formula KPJ has antioxidant activity against free radicals (Fe). The flavonoid compounds contained in the herbal supplement extract formula KPJ have redox properties that allow them to act as reducing agents, hydrogen donors, and disconnecting single oxygen. Flavonoid compounds play an important role in determining the potential of a natural ingredient as an antioxidant agent31. Flavonoid have shown to be potent antioxidants capable of protecting the human body from free radicals. An antioxidant’s function is to catch and react with free radicals at a faster rate than the substrate30. Stated that antioxidants are beneficial components which can neutralize free radicals before they attack cell proteins, lipids, carbohydrates, nucleic acid, and connective tissue macromolecules32. The mechanism involves significant inhibition or postponement of oxidative process.

 

The results of testing the activity of antioxidant herbal supplement extract formula KPJ with the ABTS method is 30.064±0.29mg TE/g. It shows that the herbal supplement extract formula KPJ has antioxidant activity against free radicals. This is influenced by flavonoid compounds that successfully contribute one hydrogen atom to the ABTS cation radical so that the free radical becomes stable. The value of IC50 obtained from the herbal supplement extract formula KPJ is 545.578±0.35 ppm.

 

Table 2. Results of Analysis of Herbal Supplements Simplicia KPJ Formula

Components

Percentage

Moisture Content (%)

5.49

Total Phenols (mg GAE/g)

10.672±1.80

Total Flavonoids (mg QE/g)

4.371±0.63

Antioxidant Activity Methods :

DPPH (mg TE/g)

7.198±0.33

FRAP (mg TE/g)

12.823±0.20

ABTS (mg TE/g)

29.048±0.83

IC50

545.578±0.35

 

The results of hygroscopic tests of herbal supplements simplicia KPJ formula stored for 5 weeks remain brownish green and weight changes that occur insignificant in each capsule with a change value of less than 0.005%, this is due to the role of silica dioxide filler (Cab O Sil) which has the properties of being able to absorb water without changing the shape or chemical reaction.

 

Characteristics of Respondent Hyperurisemia Sufferers:

A total of 40 people with hyperuricemia were willing to participate in this study. Demographic characteristics of hyperuricemia sufferers can be seen in Table 3. male hyperuricemia patients are 12 men and 28 females. The majority of people with hyperuricemia who participated in the study were aged 51-60 years old.

 

Table 3. Characteristics of Hyperuricemia Sufferers

Subject characteristics

Total subyek

Gender:

F

%

­     Male

12

30%

­     Female 

28

70%

∑ Respondent

40

100%

Age :

 

 

­     25-39 years old

11

27.50%

­     40-50 years old

12

30.00%

­     51-60 years old

14

35.00%

­     61-70 years old

3

7.50%

∑ Respondent

40

100%

Job :

­     Wiraswasta

11

27.50%

­     Private 

2

5.00%

­     Civil servants

3

7.50%

­     Farmer or laborer

12

32.50%

­     Housewives

10

27.50 %

∑ Respondent

40

100%

Weight :

­     Underweight

1

2.50%

­     Nomoweight

10

25.00%

­     Overweight

9

22.50%

­     Obese I

8

20.00%

­     Obese II

11

27.50%

­     Obese III

1

2.50%

∑ Respondent

40

100%

Food :

­     Chicken seasoning

1

2.50%

­     Duck seasoning

1

2.50%

­     Meat (Beef or goat)

1

2.50%

­     Toy, tempeh & nuts

15

37.50%

­     Toy, tempeh & spinach

1

2.50%

­     Spinach, nuts & fish

7

17.50%

­     Toy, tempeh & kale

3

7,.50 %

­     Toy & tempeh

4

10.00%

­     Carrots, cabbage, broccoli, celery & leeks

7

17.50%

∑ Respondent

40

100%

 

Uric Acid Levels, Kidney, Liver Function Measurement:

The results of measuring average levels of uric acid, kidney and liver function in the blood in hyperuricemia sufferers who have consumed the herbal supplement extract formula KPJ for 14 days can be seen in Table 4.

 

Table 4. Average Results of Uric Acid, Kidney and Liver Function Pretest and Post-Test Patients Hyperuricemia

Parameters

Day

H0

H7

H14

P

Uric acid (mg/dL)

8.0±0.8

6.1±1.0

5.7±0.9

0.0

Ureum (mg/dL)

27.8±7,5

23.2±5,3

18.7±3,5

0.0

Bun (mg/dL)

14.3±3,4

11.7±2,2

10.0±2.1

0.0

Creatinin (mg/dL)

0.8±0.1

0.6±0.1

0.6±0.1

0.0

SGOT (U/L)

35.0±9.0

29.6±9.7

26.1±8.8

0.0

SGPT (U/L)

21.9±10.3

17.9±5.6

15.5±5.3

0.0

Description:

Table 4 data is the average uric acid, kidney and liver function ±SD

Normal value of uric acid < 6.8 mg/dL (Yakupova, 2018)

Normal value of ureum 15 mg/dl - 38 mg/dl, BUN: 7 mg/dl - 18 mg/dl, Creatinine : (Male : 0,7 mg/dl - 1,4 mg/dl, Female : 0.6 mg/dl - 1.2 mg/dl)

Normal value of liver function: SGOT : (Male : 6 U/L - 25 U/L, Female : 6 U/L - 21 U/L), SGPT : (Male : 4 U/L - 30 U/L, Female : 4 U/L - 20 U/L)

Based on the average measurement of pretest or H0 uric acid levels is 8.0±0.8mg/dL and post-test or H14 is 5.7±0.9mg/dL with a decreasing percentage of 29%, meaning that this supplement can lower the uric acid levels of hyperuricemia patients well enough.

 

The percentage of decreased normal uric acid levels of hyperuricemia patients who have consumed the herbal supplement extract formula KPJ for 14 days is 82.5% (33People), while as many as 17.5% (7 people) also experience a decrease in uric acid levels but the uric acid levels are not yet under normal conditions meaning this treatment has a positive benefit in lowering the uric acid levels of hyperuricemia sufferers.

 

Statistical test results with paired T-Test to test different values of pre-test and post-test uric acid levels show a value of p=0.000 (α<0.05), meaning that there is a significant difference between pre-test uric acid levels and post-test after administering herbal supplement extract formula KPJ for 14 days in hyperuricemia sufferers. It is affected by the presence of flavonoid compounds amounting to 4,371±0.63mg QE/g in the herbal supplement extract formula KPJ. Flavonoid compounds in this supplement have a role in increasing urination and electrolyte expenditure. Flavonoids function like potassium, which is to electrolyte ion fluid such as sodium in the blood intracellular to go extracellular into the renal tubules31. Flavonoid compounds also affect glomerular filtration speed (GFR) in bowman capsules. The increase in GFR caused the kidneys (in proximal tubules by 65% and ansahenle by 25%) able to remove waste products from the body quickly, also, it can cause all bodily fluids to be filtrated and processed by the kidneys (in tubules kolingetes) at all times and able to regulate the volume and composition of bodily fluids precisely and quickly33. As stated by Shettigar, SR and Vanita GK (2021) that the control of varying electrolyte concentrations in bodily liquids and the maintenance of regular blood potential of hydrogen ions (pH) levels are the primary functions of the excretion cycle. The majority of kidney function is concerned with the ion composition of plasma ions, its osmolarity, and the concentration of plasma hydrogen ions (pH).

 

Also, the content of quercetin, kaempferol, and routine compounds is a group of flavonoid compounds34. These three compounds have mechanisms in lowering uric acid levels by inhibiting the competitive activity of xanthine oxidase through insertion at xo hydrophobic active sites to interfere with the entry of substrates that interact with some amino acid residues so that the production of uric acid can be prevented33,35. The role of xanthine oxidase is a key enzyme that converts hypoxanthine to xanthine and then to uric acid36.

Measurement Of Kidney Function:

The results of pre-test and post-test renal function measurements in people with hyperuricemia can be seen in Table 4.

 

Descriptively seen a decrease in levels of urea, BUN, and creatinine in hyperuricemia sufferers before and after the intervention of herbal supplement formula simplicia extract KPJ. Based on the results of paired sample t-test pre-test and post-test against urea, BUN and creatinine results of hyperuricemia patients obtained a value of p=0.00 (<0.05) meaning there is a significant decrease in levels of urea, BUN, and creatinine hyperuricemia sufferers after the intervention of herbal supplement formula simplicia extract KPJ.

 

The effect of decreased levels of urea, BUN, and creatinine after the intervention is influenced by herbal supplement extract formula KPJ containing flavonoid compounds such compounds can prevent oxidative stress in the kidneys by increasing the antioxidant activity of glutathione S- transferase (GSH), increasing GSH synthesis, and directly concatenate ROS by donating atom H from hydroxyl groups (OH) to free radical compounds so that free radical compounds formed are not reactive and in the meantime, the donor flavonoid compound turns into a radical flavonoid compound that will bond with other radical flavonoid compounds into an inactive form37.

 

Liver Function Measurement:

The results of pre-test and post-test liver function measurements in hyperuricemia patients can be found in Table 4.

 

Based on the results of paired sample t-test pre-test and post-test against SGOT and SGPT levels of hyperuricemia patients obtained a value of p=0.00 (<0.05) which means there is a significant decrease in SGOT and SGPT levels after the intervention of herbal supplement formula extract simplicia KPJ and can improve liver function of hyperuricemia sufferers.

 

This positive influence is influenced because the herbal supplement extract simplicia extract KPJ contains phenol and flavonoid compounds that serve as antioxidant agents. Flavonoids are antioxidant compounds because they have phenolic hydroxy groups in their molecular structures that have the capture of free radicals and as metal-like. Oh, clusters in flavonoid compounds will replace glutathione that has been oxidized by free radicals as a result of hyperuricemia. The OH group on flavonoids will help conjugate free radicals into mercapturic acid and convert the reactive.

 


 

Table 5. Health and Emotional Perception of Hyperuricemia Sufferers After Intervention of Herbal Supplement Extract KPJ Formula For 14 Days

Questions

Frequency (%)

SS

S

TS

STS

Perception of validity

P1. Has the herbal supplement extract formula KPJ had a reduced effect on uric acid levels after you consumed it for 14 days?

65

35

0

0

P2. Has the herbal supplement extract formula KPJ consumed have a decreased effect on pain in the joints?

70

30

0

0

P3. Whether an herbal supplement to KPJ extract formula can also reduce the impact of hyperuricemia on your body?

72.5

27.5

0

0

P4. Do you feel that the herbal supplement extract formula KPJ provides the appropriate benefits as listed on the packaging?

42.5

57.5

0

0

P5. Do you think taking an herbal supplement to extract KPJ 2 times a day has had an effect on the decrease in uric acid levels in the blood?

40

60

0

0

P6. Do you feel side effects such as bowel care or other digestive problems after consuming herbal supplements extract formula KPJ?

0

0

22.5

77.5

P7. Do you feel side effects such as nausea, dizziness, and heart palpitations after consuming herbal supplement extract formula KPJ?

0

0

40

60

P8. After consuming herbal supplement products KPJ extract formula, would you recommend to others (hyperuricemia sufferers)?

70

30

0

0

P9. Do you agree that this product is safe to consume in the long term?

50

50

0

0

P10. Is after consuming herbal supplement extract formula KPJ occurs increased appetite?

 

 

60

40

Emotional perception

P11. After consuming and benefiting from the herbal supplement extract formula KPJ, do you feel happy?

52.5

47.5

0

0

P12. Do you like the taste of the herbal supplement extract formula KPJ?

62.5

37.5

0

0

P13. After consuming the herbal supplement extract formula KPJ, does your body become healthier and fitter ?

65

35

0

0

P14. Are you satisfied with the benefits provided by the herbal supplement extract formula KPJ?

57.5

42.5

0

0

Description:

SS: Strongly Agree TS : Disagree

S: Agree STS: Strongly Disagree

 


metabolites of free radicals resulting from the metabolism of cytochrome P-450 i.e. N-acetyl p-benzoquinone imine (NAPQI) into hydrophilic non-active metabolites so that it is easily excreted through urine and increased SGOT and SGPT levels can be suppressed38.

 

Measurement of Perception Of Hyperuricemia Sufferers After Intervention of Herbal Supplement Extract Formula KPJ:

Interviews in sufferers can describe health and emotional perceptions after an intervention, as presented in Table 5.

 

Based on the results in Table 5 shows positive health and emotional perceptions of hyperuricemia sufferers who have been in the intervention of herbal supplement extract simplicia KPJ for 14 days. The perception of health is influenced by this KPJ herbal supplement extract formula containing flavonoid compounds (quercetin, kaemferol and routine) that have effects as anti hyperuricemia34. The flavonoid compounds contained in this supplement have such high inhibition power that it can easily capture electrons from the enzyme xanthine oxidase19,39, which causes this compound to potentially be a competitive inhibitor for xanthine oxidase. Flavonoid compounds also have a diuretic mechanism by increasing urination and increasing the production of electrolytes in the body to help lower uric acid levels in the blood of hyperuricemia sufferers. Also, before intervening researchers first provide exposure regarding the content and benefits of herbal supplements of KPJ extract formula to their health conditions, it can have a positive influence on the perception of respondents.

 

While positive emotional perception in hyperuricemia sufferers is influenced by the physical receiving power of the product as well as the physiological aspects they feel. Factors that influence food preference include intrinsic factors, namely appearance, aroma, and biological factors38. Positive emotional perception is also influenced by individual experiences, horizons, and knowledge39. The experience felt by respondents and knowledge of the efficacy of herbal supplement extract formula KPJ will give meaning to the perception conveyed.

 

CONCLUSION:

Based on the results of this it can be concluded that the herbal supplement extract formula KPJ affects the subjects of hyperuricemia:

1.     The average uric acid levels of hyperuricemia subjects before intervention were 8.0mg/dL and after the intervention of herbal supplement extract formula, KPJ for 14 days dropped to 5.7mg/dL Also as much as 82.5% of hyperuricemia patients in this study experienced a decrease in normal uric acid levels. The average value of SGOT levels before intervention is 35 U/L and after the intervention of herbal supplement extract formula KPJ is 26.1 U/L, SGPT levels before intervention were 17.9 U/L, Ureum levels before intervention were 27.8mg/dL and after the intervention was 18.7mg/dL, BUN levels before intervention were 14.3 and after the intervention was 10.0mg/dL and creatinine levels before intervention were 0.8mg/dL and after the intervention was 0.6mg/dL.

2.     Based on the perception of hyperuricemia sufferers to health shows that as many as 65% of subjects strongly agree and 35% agree to experience decreased uric acid levels after consuming the herbal supplement extract formula KPJ and emotionally 57.5% of subjects feel very satisfied and 42.5 express satisfied with the benefits of herbal supplement extract formula KPJ in lowering uric acid levels.

 

CONFLICT OF INTEREST:

The authors have no conflicts of interest regarding this investigation.

 

ACKNOWLEDGMENTS:

The authors would like to thank PT. ASIMAS, Malang and Public Selorejo Village, Pune for their kind support during reasearch and all other lab studies.

 

REFERENCE:

1.      Li L. Zhang Y. Zeng C. Update on the epidemiology, genetics, and therapeutic options of hyperuricemia. 2020;12(7):3167-3181.

3.      Rivera-paredez B. Mac L. Fernandez-lopez JC. et al. Influence of Genetic and Non-Genetic Risk Factors for Serum Uric Acid Levels and Hyperuricemia in Mexicans. 2019;1014290:1-19.

4.      Vedder D. Walrabenstein. Heslinga M. Vries R De. Dietary interventions for gout and effect on cardiovascular risk factors : A systematic review. Nutrients. 2019;11(2955):1-19.

5.      Ramesh S. Vanita G. Evaluation of anti-hyperuricemic activity of the alcoholic extract of dried capparis moonii wight fruits in wistar rats. Res J Pharm Technol. 2021;14(6):3173-3178. doi:10.5958/0974-360X

6.      Huang Q. Yu J. Zhang X. Liu S. Ge Y. Association of the serum uric acid level with liver histology in biopsy-proven non-alcoholic fatty liver disease. Biomed Reports. 2016;5(2):188-192. doi:10.3892/br.2016.698

7.      Roddy E. Choi H. Epidemiology of gout. Natl Intitutes Heal. 2015;40(2):155-175. doi:10.1016/j.rdc.2014.01.001

8.      Robinson PC. Gout – An update of aetiology, genetics, co-morbidities and management. Maturitas. 2018;118:67-73. doi:10.1016/j.maturitas.2018.10.012

9.      Wang H. Zhang H. Sun L. Guo W. Roles of hyperuricemia in metabolic syndrome and cardiac-kidney-vascular system diseases. Am J Transl Res. 2018;10(9):2749-2763.

10.   Ni Q. Lu X. Chen C. Du H. Zhang R. Risk factors for the development of hyperuricemia. Medicine (Baltimore). 2019;98(42):1-6.

11.   Sato Y. Feig DI. Stack AG. et al. The case for uric acid-lowering treatment in patients with hyperuricaemia and CKD. Nat Rev Nephrol. 2019;15(12):767-775. doi:10.1038/s41581-019-0174-z

12.   Chaudhary NS. Jr SLB. Saag KG. et al. Severity of hypertension mediates the association of hyperuricemia with stroke in the Regards Case Cohort Study. Am Hear Assoc. Published online 2019:1-11. doi:10.1161/HYPERTENSIONAHA.119.13580

13.   Steiger S. Ma Q. Anders HJ. The case for evidence-based medicine for the association between hyperuricaemia and CKD. Nat Rev Nephrol. 2020;16(7):422. doi:10.1038/s41581-020-0288-3

14.   Burns CM. Wortmann RL. Latest evidence on gout management: What the clinician needs to know. Ther Adv Chronic Dis. 2012;3(6):271-286. doi:10.1177/2040622312462056

15.   Hendriani R. Sukandar EY. In vitro evaluation of xanthine oxidase inhibitory activity of selected medicinal plants. Int J Pharm Clin Res. 2016;8(4):235-238.

16.   Ragab G. Elshahaly M. Bardin T. Gout: An old disease in new perspective – A review. J Adv Res. 2017;8(5):495-511. doi:10.1016/j.jare.2017.04.008

17.   Sahu P. Sahu K. Dubey RD. Chatterjee S. Chatterjee T. Herbal Antioxidants: A Review. Res J Pharmacogn Phytochem. 2010;2(6):4427-4434.

18.   Alrawaiq N. A. Review of flavonoid quercetin: Metabolism . Bioactivity and Antioxidant Properties. Int J PharmTech Res. 2019;6(3):933-941.

19.   Widyaningsih TD. Rachmawati M. Prabawati E. Antihyperuricemia of functional products intergrated food therapy formula of moringa leaves, Pandan wangi and red ginger on wistar rat induced by potassium oxonate. Vol 2.; 2017.

20.   Mohamed Isa SSP. Ablat A. Mohamad J. The antioxidant and xanthine oxidase inhibitory activity of plumeria rubra flowers. Molecules. 2018;23(2). doi:10.3390/molecules23020400

21.   Erkmen O. Bozoglu TF. Food Microbiology Principles into Practice.; 2016. doi:10.1002/9781119237860.ch30

22.   Hasanah Q. Andrianto D. Faridah N. Aktivitas antioksidan dan antihiperkolesterolemia in vitro dari campuran ekstrak angkak dan bekatul. 2018;29(2):145-154. doi:10.6066/jtip.2018.29.2.145

23.   Tiwari P. Phenolics and flavonoids and antioxidant potential of balarishta prepared by traditional and modern methods. Asian J Pharm Ana. 2014;4(1):5-10.

24.   Sayuti K. Yenrina R. Antioksidan, alami dan sintetik.; 2015.

25.   Narasimhan R. Sathiyamoorthy. Phytochemical screening and antioxidant studies in the pulp extracts of cucurbita maxima. Asian J Pharm Ana. 2016;6(1):04-04.

26.   Selvakumar K. Madhan R. Srinivasan G. Bakar V. Antioxidants assays in pharmacological research. Asian J Pharm Tech. 2011;1(4):99-103.

27.   Chu YH. Chang CL. Hsu HF. Flavonoid content of several vegetables and their antioxidant activity. J Sci Food Agric. 2000;80(5):561-566.

28.   Karadag A. Ozcelik B. Saner S. Review of methods to determine antioxidant capacities. 2009;(November 2008):41-60. doi:10.1007/s12161-008-9067-7

29.   Prior RL. Wu X. Identification and characterization of anthocyanins by high-performance liquid chromatography − electrospray ionization − tandem mass spectrometry in common foods in the united states: Vegetables, nuts, and grains. J Agric Food Chem. 2005;53:3101-3113.

30.   Huyut Z. Beydemir F. Gülçin E. Antioxidant and antiradical properties of selected flavonoids and phenolic compounds. 2017;2017.

31.   Sushil DP. Masood A. Aher P. Pavin B. Yardi S. Synthesis and evaluation of novel flavonoid derivatives for antibacterial activity. Asian JPharm Res. 2016;6(1):27-30.

32.   Iraz M. Dose. Dependent effects of caffeic acid phenethyl ester on heart rate and blood pressure in rats. Eur J Gen Med. 2005;2(2):69-75.

33.   Septian BA. Widyaningsih TD. The role of black jelly grass drinks (Mesona palustris Bl .) For high blood pressure reduction: a Review. J Pangan dan Agroindustri. 2014;2(3):198-202.

34.   Kusmiyati A. Kadar asam urat serum dan urin tikus putih hiperurikemia setelah pemberian jus kentang (Solanum tuberosum L.). Thesis. Departement Biology. Universitas Negeri Solo. Surakarta

35.   Vermerris W. Nicholson R. Phenolic compound biochemistry.

36.   Dahal A. Mulukuri S. Flavonoids in kidney protection. World J Pharm Sci. 2015;4:362-382.

37.   Buvana C. Sumathy A. Sukumar M. In silico identification of potential xanthine oxidase inhibitors for the treatment of gout and cardiovascular disease. Asian J Res Chem. 2013;6(11):1049-1053.

38.   Aryadi. Uji ekstrak methanol daun kepel (Stelechocarpus burahol (BI.)Hook.F.&Th.) terhadap aktivitas enzim xantin oksidase secara in vitro.Thesis. Departemen Farmasi. Universitas Gadjah Mada. Yogyakarta

39.   Permana P. EB. Sumarni S. Nisa FZ. Faktor yang berhubungan dengan preferensi konsumen street food pada mahasiswa Universitas Gadjah Mada. J Gizi dan Diet Indones (Indonesian J Nutr Diet. 2016;3(3):131. doi:10.21927/ijnd.2015.3(3).131-138

40.   Huda AK. Persepsi direktur dan tenaga medis terhadap layanan bimbingan rohani islam dan relevansinya dalam meningkatkan kualitas layanan di RSUD Ambarawa. Published online 2017.

 

 

 

 

Received on 09.09.2021            Modified on 24.12.2021

Accepted on 03.02.2022           © RJPT All right reserved

Research J. Pharm. and Tech 2022; 15(10):4477-4484.

DOI: 10.52711/0974-360X.2022.00751