The Immunomodulatory Activity of Pirdot Leaf Extract (Sauraia

Vulcani korth.) on the Immune System of Male Rats

Romauli Anna Teresia Marbun

, Saadah Siregar

, Ahmad Syukur Hasibuan

, Jon Sinurat

, Aminah

Syarifudin

, Debi Dinha Octora

, Vincentia Ade Rizky

, Rahmad Gurusinga

Faculty of Pharmacy, Institut Kesehatan Medistra Lubuk Pakam, Sumatera Utara, Indonesia,

Faculty of Nursing, Institut Kesehatan Medistra Lubuk Pakam, Sumatera Utara, Indonesia.

Keywords: Immunomodulators, Sauraia vulcani Korth, Carbon clerance

Abstract: Immune-mediated diseases are a significant problem in developing countries such as infectious diseases,

cancer, and autoimmune disorders. The Sauraia vulcani Korth was studied has flavonoid compounds that

have the potential as immunostimulants. The purpose of this study was to prove the immunomodulatory

effect on phagocytic activity of phagocytic cells in male rats. The treatment group for carbon clearance test

was divided into 6 groups with each consisting of 5 male rats including 0.5% CMC-Na group, Imboost®

32.5 mg / kgBB, ethanol extract of Sauraia vulcani Korth. doses of 50, 100, 200 and 400 mg / kgBB orally

for 7 days and 8th day given carbon suspension i.v. Taking blood was carried out at a certain time and then

measured the absorbance using a UV-Vis spectrophotometer. The rat's liver and spleen were taken and

weighed.The results showed that the administration with doses of 50, 100, 200 and 400 mg / kgBB of

ethanol extract of Sauraia vulcani Korthsignificantly increased phagocytic activity compared to 0.5% CMC-

Na (p <0.05).This study proves that the ethanol extract of Sauraia vulcani Korth has an immunostimulatory

effect on phagocytic activity which can be seen through phagocytic index parameters, stimulation index,

and carbon clearance value.

1 INTRODUCTION

The environment around us has various types of

pathogenic microorganisms, such as bacteria,

viruses, fungus, protozoa and parasites that can

cause infections in humans. Infections that occur in

normal people are generally brief and rarely leave

permanent damage. Human immunodeficiency virus

(HIV) and Mycobacterium TB (Mtb) have a

synergistic relationship. In coinfected people,

tuberculosis (TB) causes cell activation and

excessive production of cytokines and chemokines.

Later stimulates (Carla et al., 2017).

Human immunodeficiency virus infection results

in early disruption of anthropometric indicators in

children and adolescents. However, combination

antiretroviral therapy has increased safety with the

immune response and viral infection, the severity

and the increase in the severity of the infection in

previously infected (Golluci et al., 2019). The

maintenance of immune homeostasis is essential for

regulation of healthy physiological function and

prevention of disease. Immune dysregulation can

lead to opportunistic infection or, on the other

extreme, self-targeted autoimmune diseases.

Secreted proteins such as cytokines and antibodies

serve as essential messengers and regulators of the

immune system, which has motivated extensive

efforts to use them as therapeutics Despite

significant advancements in protein drug

development, the field is still hampered by

challenges in expression, stability, specificity, and

activity. New platforms and methodologies in

protein engineering have revolutionized drug

development by pioneering novel strategies to

enhance the behavior of natural proteins and

engineer new molecules customized for specific

disease applications (Kureshi et al., 2018).

Oxidative stress is considered to be critically

involved in the normal aging process but also in the

develop-ment and progression of various human

pathologies like cardiovascular and

neurodegenerative diseases,as well as of infections

and malignant tumors. These pathological conditions

involve an overwhelm-ing production of reactive

oxygen species (ROS), which are released as part of

an anti-proliferativestrategy during pro-

Marbun, R., Siregar, S., Hasibuan, A., Sinurat, J., Syarifuddin, A., Octora, D., Rizky, V. and Gurusinga, R.

The Immunomodulatory Activity of Pirdot Leaf Extract (Sauraia Vulcani korth.) on the Immune System of Male Rats.

DOI: 10.5220/0009973805150520

In Proceedings of the International Conference on Health Informatics and Medical Application Technology (ICHIMAT 2019), pages 515-520

ISBN: 978-989-758-460-2

515

inflammatory immune responses. Moreover, ROS

themselves are autocrine forwardregulators of the

immune response. Most of the beneficial effects of

antioxidants are considered to derive from their

influence on theimmune system. Due to their

antioxidant and/or radical scavenging nature,

phytochemicals, botanicalsand herbal preparations

can be of great importance to prevent oxidation

processes and to counteractthe activation of redox-

regulated signaling pathways. Antioxidants can

antagonize the activation ofT-cells and macrophages

during the immune response and this anti-

inflammatory activity could beof utmost importance

for the treatment of above- mentioned disorders and

for the development of immunotolerance (Becker et

al., 2014).

An additional immune system is needed to

maintain a balanced immune system. Artificial

immunity can be given by immunization. The

immune response will increase with the

administration of immunostimulant compounds

(Trivedi et al., 2016).

Diseases mediated by the immune system are

significant problems. Such as: treatment for HIV and

Ebola Virus which requires an aggressive and

innovative approach to the development of new

treatments. Therefore, it is necessary to add immune

enhancers Among the many herbs used one of them

is Sauraia vulcani Korth L. which is a family of

Sauraia plants (Sharma et al., 2015).

Natural herbal products are used in the

prevention or treatment of cancer in many countries.

Althoughless antitumor effect than chemotherapy

drugs, it can producemore immune enhancement and

less toxicity (Jeong, Koh, Kim, &Kim, 2011; Kim,

Moon, Choi, Kim, & Lee, 2013; Li et al., 2012;

Wang et al., 2012).

Along with the development of increasingly

sophisticated technology, the use and utilization of

traditional medicines in Indonesia has increased

dramatically. Traditional medicines are re-used by

people who believe in the principle of back to nature

as an alternative treatment, in addition to synthetic

medicines that are developing in the market.

Traditional medicines derived from plants and pure

natural ingredients have side effects, danger levels

and risks that are much lower compared to chemical

drugs (Sharma et al., 2015).

Medicinal plants have the potential to be used as

natural fungicides. This is because medicinal plants

contain secondary metabolites which can act as

antifungal agents. Secondary metabolites such as

saponins, alkaloids, coumarin, xanton, flavonoids,

fatty acids, phenol compounds, terpenes, essential

oils, lectins and polypeptides have been reported to

have antifungal activity.

Synthetic drugs for infections have been widely

marketed. However, resistance related to synthetic

drugs has been widely discussed.Treatment of

infections with multidrug shows the effects of HIV

treatment too early and the delay in co-infected

patients receiving treatment for TB. This study

shows that the burden of coinfection is highly

dependent on when antiretroviral therapy (ART) is

started (Mallela et al., 2016; Spangler et al., 2015).

Previous research (Sitorus, 2015), pirdot leaves

(Saurauia vulcani Korth.) Had an antidiabetic effect

on mice. Previous research related to the genus

Sauraia has potential as an antioxidant and

antidiabetic. Previous research on the leaves of the

pirdot plant, said that this plant has been used by the

people of North Sumatra for a long time to treat

wounds and prevent bacterial infections (Farid et al,

2012).

Pirdot leaves contain compounds in the form of

steroids, flavonoids, saponins, tannins, triterpenes,

and also have antioxidant power. Secondary

metabolites found in pirdot leaves are thought to

have potential as antifungal so testing is needed to

update the potential of these pirdot leaves.

Based on previous research reports, pirdot leaves

(Sauraia vulcani Korth.) contain essential oils,

saponins, flavonoids, tannins and triterpenoids.

Previous research also stated that the pirdot leaf

(Sauraia vulcani Korth.) Contains constituents such

as saponins, flavonoids, tannins and triterpenoids

(Setyowati dkk., 2014). The ethanol extract of the

pirdot leaf (Saurauia vulcani Korth) studied has

potential as an antibacterial and high antioxidant

activity.

Immunotherapy strategies to date have used

antibodies to block inhibitory receptors (also called

"checkpoints") that are regulated on T cells capable

of entering tumor cells (Golluci et al., 2019; Adel et

al., 2016; Moon et al., 2017). Immune system

activity testing can be done by various methods,

namely hemagglutination antibody titer, slow type

hypersensitivity response, and phagocytosis activity

test using carbon cleansing method (Carbon

Clearance) (Shukla et al., 2009).

Phagocytosis activity test uses the carbon

clearance method to determine the picture of a

nonspecific immune system. Carbon clearance

method is usedto measure the activity of phagocytic

cells killing pathogenic organisms that enter the

body and count the number of leukocyte cells

(Marbun et al., 2018).

ICHIMAT 2019 - International Conference on Health Informatics and Medical Application Technology

516

2 METHOD

Place of research

The extract making is carried out in Chemical

laboratory, at Pharmacy Faculty, Institut Kesehatan

Medistra Lubuk Pakam

Research time

This research is carried out on the month (January

2019 to August 2019).

Material

Pirdot leaf, carboxy methyl cellulose (CMC),

chloroform, 2 N hydrochloric acid, Mayer reagent

(mercury (II). chloride and potassium iodide),

Dragendorff reagent (bismuth, nitric acid and

potassium iodide), Maych reagent (mercury (II)

chloride and potassium iodide), Dragendorff reagent

(bismuth, nitric acid and potassium iodide),

Bourchardat reagents, mercury (II) chloride and

potassium iodide), Dragendorff reagents (bismuth,

nitric acid and potassium iodide), Bourchardic

reagents, iodine and potassium iodide, Zn powder,

concentrated hydrochloric acid, amyl alcohol,

concentrated sulfuric acid, Molish reagent, iron (III)

chloride, n-hexane, Liebermann Burchat reagent

(anhydrous acetic acid and concentrated sulfuric

acid), chloroform, chlorohydrate, n-hexane, distilled

water, carbon ink (Pelikan B17), Imboost®, sodium

citrate, 1% acetic acid, and 0.9% NaCl and distilled

water.

Sample Processing

Saurauia vulcani Korth. are cleaned of dirt by

washing under running water until clean then

drained to dry after it is sliced into small pieces

dried in a drying cabinet / in the room (aerated).

Saurauia vulcani Korth. that have dried are blended

until they become powder weighed by weight and

are called simplicia. As much as 1 kg of pirdot leaf

simplicia powder (Saurauia vulcani Korth.) Was put

into a closed vessel, added 7.5 liters of 96% ethanol

then the vessel was closed and left for 5 days

protected from light while frequently stirring. Then

filtered and the pulp is rinsed again with 96%

ethanol until 100 parts are obtained. Maserat is

accommodated in a dark bottle, left in a cool place

and protected from light for 2 days then filtered.

Then the extract was concentrated using a rotary

evaporator. Each extract was dried with a freeze

dryer.

Group test

In the test, 4 dosage variations will be used, namely

doses of 50, 100, 200, and 400 mg / kgBW.

Weighed 1 gram of EEDP extract. Put into mortar,

then pour gradually CMC Na 0.5% suspension while

crushed until homogeneous, after homogeneous

poured into a 100 ml flask and filled with 0.5%

CMC Na suspension up to the mark line.

Obtainedpirdot leaf extract concentration of 1%. For

positive control use Imboost®.

3 RESULT AND DISCUSSION

3.1 Test Results Evaluation of Carbon

Elimination Rate

Based on EEDP phytochemical screening, it was

found that all parameters (flavonoids, tannins,

saponins, glycosides, steroids / triterpenoids) except

alkaloids have positive simplicia andextracts.

According to Salihin (2017) that Pirdot Leaf Ethanol

Extract contains saponin compounds which have the

potential as antidiabetic. The chemical content of the

pirdot leaf ethanol extract, namely flavonoids, is

reported to have an effect as oat cancer and as a

chemotherapy companion agent. The active

compound of the flavonoid group is reported as an

inhibitor of the enzyme DNA topoisomerase. This

inhibitor results in damage to the DNA of cancer

cells, further influencing the processes in the cell.

Carbon elimination rate is a method used to

measure phagocytic activity in mice. The amount of

carbon in the blood decreases with time, due to

phagocytic events by leukocyte cells, especially

neutrophils, monocytes, macrophages, and

eosinophil (Bao et al., 2013; Baratawidjaja, 2010).

Data on carbon elimination rates can be seen in the

Table 1 below.

Table 1. Elimination Carbon Clearence

Group

( mg/k

gbb)

Rate of Carbon elimination

Minute 5 Minute -10 Minute -15 Minute -20

CMC

0,5%

1 0,14 0,14 0,14 0,13

2 0,14 0,14 0,13 0,13

3 0,14 0,13 0,13 0,13

4 0,14 0,12 0,13 0,13

5 0,14 0,14 0,13 0,13

Mean

0,14± 0,01 0,14± 0,01 0,12±0,01 0,13±0,01

Imboos

1 0,10 0,08 0,07 0,06

2 0,10 0,09 0,08 0,05

3 0,10 0,08 0,07 0,05

4 0,10 0,08 0,08 0,06

5 0,11 0,08 0,07 0,05

Mean

0,10±0,01 0,08±0,01 0,07±0,01 0,05±0,01

1 0,14 0,13 0,12 0,12

2 0,14 0,13 0,13 0,12

3 0,14 0,13 0,12 0,12

4 0,14 0,13 0,12 0,12

The Immunomodulatory Activity of Pirdot Leaf Extract (Sauraia Vulcani korth.) on the Immune System of Male Rats

517

5 0,14 0,13 0,12 0,12

Mean 0,14±0,01 0,13±0,01 0,12±0,01 0,12±0,01

100

1 0,14 0,13 0,12 0,11

2 0,14 0,12 0,10 0,09

3 0,14 0,12 0,11 0,10

4 0,14 0,12 0,12 0,09

5 0,14 0,12 0,12 0,10

Mean 0,14±0,01 0,12±0,01 0,11±0,01 0,10±0,01

200

1 0,13 0,10 0,09 0,07

2 0,13 0,10 0,08 0,07

3 0,13 0,10 0,08 0,07

4 0,12 0,09 0,08 0,07

5 0,12 0,10 0,08 0,07

Mean 0,12±0,01 0,10±0,01 0,08±0,01 0,07±0,01

400

1 0,11 0,09 0,08 0,05

2 0,10 0,09 0,08 0,05

3 0,11 0,10 0,09 0,05

4 0,10 0,09 0,07 0,05

5 0,10 0,09 0,07 0,06

Mean 0,11±0,01 0,09±0,01 0,08±0,01 0,056±0,01

Based on EEDP phytochemical screening, it was

found that all parameters (flavonoids, tannins,

saponins, glycosides, steroids / triterpenoids) except

alkaloids have positive simplicia andextracts.

According to Salihin (2017) that Pirdot Leaf Ethanol

Extract contains saponin compounds which have the

potential as antidiabetic. The chemical content of the

pirdot leaf ethanol extract, namely flavonoids, is

reported to have an effect as oat cancer and as a

chemotherapy companion agent. The active

compound of the flavonoid group is reported as an

inhibitor of the enzyme DNA topoisomerase. This

inhibitor results in damage to the DNA of cancer

cells, further influencing the processes in the cell.

Carbon elimination rate is a method used to

measure phagocytic activity in mice. The amount of

carbon in the blood decreases with time, due to

phagocytic events by leukocyte cells, especially

neutrophils, monocytes, macrophages, and

eosinophil (Bao et al., 2013; Baratawidjaja, 2010).

Data on carbon elimination rates can be seen in the

Table 2 below.

Table 2. Results of value carbon elimination rate,

fagocytic index, and stimulation index

Group

treatment

(mg/

kgBB)

Carbon

elimination

(MEAN±SEM)

Fagocyti

index

Stimulation

index

CMC Na

0,5%

0,0021 ±0,0002

(+)

6,34 1,14

Imboost

32,5

0,0151±0,0039

(*)

9,25 1,41

3 EEDP 50

0,0061±0,0014

(+)

7,68 1,12

4 EEDP 100

0,0083±0,0013

(*,+)

8,15 1,19

5 EEDP 200

0,0110±0,0010

(*,+)

8,45 1,37

6 EEDP 400

0,0176±0,0013

(*,+)

8,92 1,45

Based on the above table, the results of carbon

elimination rate data are used to calculate the value

of carbon elimination constant. The carbon

elimination constant is one of the parameters used to

determine the rate of phagocytosis. The greater the

value of the carbon elimination constant, the higher

the rate of carbon clearance, which means the faster

the phagocytic cells carry out the process of

phagocytosis (Hamdy et al., 2015). Non-specific

immune system is the body's leading defense against

antigens. One of the body's efforts to defend against

antigen entry is to destroy the antigen by the process

of phagocytosis. Phagocytic cells attack through

several processes, namely recognition of foreign

objects to be digested, movements toward objects

(chemotaxis), attachment, ingestion (ingestion), and

digestion (digestion). Phagocytosis is carried out

mainly by mononuclear, neutrophil and eosinophil

phagocytes. Mononuclear phagocytes are produced

by stem cells (steam) cells in the bone marrow. In

the bone marrow it proliferates and is released into

the blood after one period through the monoblast

phase - the promonocyte phase - the monocyte

phase. The monocyte is only briefly in the blood

then the cell moves to the tissue and differentiates

into macrophages (Bao et al., 2013).

Based on the results obtained indicate that the

greater the dose the phagocytic index value

increases. Increasing the phagocyte index indicates

an increase in phagocytic activity of macrophages

and an increase in non-specific immunity.

Macrophages are responsible for the process of

elimination, especially in the liver and the rest are in

the spleen. Lymph as a secondary lymphoid organ

contains B lymphocyte cells and T lymphocytes

which play a role in the process of specific immune

responses. In addition, there are also dendritic cells

and macrophages in the lymph that act as APC

(Antigen Presenting Cell) which serves to present

antigens to lymphoid cells. Increased immune cells

are correlated with lymphatic weight. This increase

in relative lymphatic weight indicates the effect of

binara herbaceous ethanol extract on

immunostimulatory activity. Based on the results of

statistical tests, the graph shows that the negative

control group CMC Na 0.5% suspension with

phagocytosis index 6.34 has a significant difference

(p <0.05) with other treatment groups. EEDP 50 mg

/ kg body weight with phagocytosis index of 7.68

had a significant difference (p <0.05) with other

treatment groups. EEDP 100 suspension with

phagocytosis index 8.15 and 200 mg / kgBB with

phagocytosis index 8.45 did not have a significant

difference (p> 0.05) but significantly different from

EEDP 400 mg / kgBB with phagocytosis index 8.92

and Imboost ® with phagocytosis index 9.25. EEDP

ICHIMAT 2019 - International Conference on Health Informatics and Medical Application Technology

518

suspension 400 mg / kgBB and Imboost® did not

have a significant difference (p> 0.05). The main

mission of phagocytic cells is to maintain

(Murray et

al., 2011). In addition, they are also involved in

innate immune cell responses (immune to bacterial,

fungal, parasitic and viral infections).

3.2 Test Results Evaluation of Stimulan

Index

The stimulation index is the result of a comparison

between the test group and the control group.

Previous research stated an immunostimulant

substance if the stimulation index is greater than 1

and immunosuppressant if the stimulation index is

smaller than 1. EEDP suspensions of 50, 100, 200,

400 mg / kgBW indicate that there is a relationship

between the increase in dose and the stimulation

index value, ie the greater the dose increases, the

value of the stimulant index obtained increases. This

shows that EEDP is an immunostimulant substance.

Compounds that may act as immunostimulants are

flavonoids. This is in accordance with the research

of Prastiwi et al. (2015) which states that the saponin

compound, tannins have immunostimulant activity

so that it is suspected that the immunostimulant

activity of pirdot leaves might be caused by

flavonoid content. Compounds that act as

immunostimulants are flavonoids, alkaloids. This is

in accordance with the research of Prastiwi et al.

(2015)

which states that alkaloid compounds,

saponins, tannins have activity as

immunostimulants. so it is suspected that the

immunostimulatory activity of pirdot leaves might

be caused by flavonoid content.

Research Marbun, 2017

also reported that

flavonoid compounds have immunostimulatory

activity by increasing IFN-sel cell stimulation. IFN-γ

produced by NK cells can function as a mediator of

innate immune responses, the main function of IFN-

γ in regulating the immune system is as a potential

activator for mononuclear phagocytes. IFN-mengind

directly induces the synthesis of enzymes that play a

role in respiratory bursts, so macrophages can kill

the microbes that are ingested by the mechanism of

phagocytosis. IFN-γ also activates neutrophils and

increases respiratory bursts. According to Hamdy

(2015), EEDP contains flavonoids, alkaloids, and

saponins which have anti-inflammatory, antioxidant

and can also reduce serum TNF-α levels. EEDP

stimulation index values obtained are still under

positive control (Imboost).

Each imboost tablet contains 250 mg of

Echinacea purpurea. E. Purpurea is reported to have

the ability to increase phagocytosis because of the

content of polysaccharides that can activate

macrophage cells and NK cells and have been tested

preclinically and clinically as immunostimulants

besides Flavonoids are compounds that function as

immunostimulants including triterpenoids and

polysaccharides. Thus, both EEDP and Echinacea

purpurea have activity as immunostimulants but

with different strengths. Leukocytes form the innate

and adaptive immune system and respond, for

example against infection, inflammation and tumor

growth growth (Gajewski et al., 2013).

4 CONCLUSIONS

Conclusion of this study is Ethanol extract of pirdot

leaves (Saurauia vulcani Korth.) can increase

phagocytic activity not significantly different from

Imboost available in the market. Macrophage cells

in male rats injected with carbon suspension. EEDP

doses of 50, 100, 200, and 400 mg / kg body weight

can influence phagocytic activity compared with

negative control CMC-Na 0.5% (p <0.05). EEDP

400 mg / kgBB gives phagocytosis effect which is

almost the same as the positive control of Imboost®

which shows the rate of carbon elimination at a

dose of 400 mg / kgBB 0.0065 ± 0,0005 and

Imboost 32.5 mg / kgBB 0.0041 ± 0,0002. This

shows an insignificant difference between a dose of

400 mg / kgBW and Imboost. Based on the results of

the study, ethanol extract of pirdot leaves increased

the immunostimulatory activity of immune cells of

male rats

ACKNOWLEDGEMENTS

This Research was supported by Institut Kesehatan

MEDISTRA Lubuk Pakam, Indonesia and

Grandmed Hospital, Indonesia

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