INTRODUCTION:

The immune system contributes significantly to human health¹. The immune system (IS) is an intricately interconnected network of cells, tissues, organs and soluble mediators that has evolved to protect the organism from external intrusions that compromise the integrity of the organism^2,3. A decrease in the immune system can be caused by bacteria, viruses, other microbes, and other pathogens. In fact, it produces antibodies (immunoglobulins) to combat the foreign bacteria and viruses in the body^3,4. The human body contains organs of the immune system that protect against disease. The immune system plays a key role in maintaining health and pathogenesis. The immune system also protects the body from harmful substances, such as viruses, bacteria, and disease-causing microbes⁵^,6.

Some diseases associated with a lack of immunity include tuberculosis, HIV, and the most-discussed topic today, the COVID 19^7,8.

Immunity can be maintained and increased by consuming vitamins and herbs from nature that are efficacious as immunomodulators. Immunomodulators are part of immunotherapy that can stimulate the immune system so as to increase the activity of the immune system in fighting infection or disease^9,10. Strong immunity is needed to avoid and cure the above disease. One of the cells that play an important role in the immune system, commonly called immunity, is lymphocyte cells. The B lymphocyte cells come from bone marrow cells and have an important role in forming humoral antibodies in the blood. Meanwhile, the T lymphocyte cells come from the thymus (thymus gland) and are responsible for forming cellular antibodies. The normal value of lymphocyte cells in humans is 25-40% of the total number of leukocyte cells ¹¹.

A number of synthetic and natural immunomodulators have recently been introduced to modulate nonspecific and specific immune responses. Natural products and traditional medicines are major contributors in the design and development of therapeutic agents¹². Currently available therapeutic drugs have immunosuppressive activity and most are cytotoxic, causing various side effects. Isolates with immunomodulatory potential are gaining importance to find alternative immunomodulatory agents^13,14. Alternative immunomodulators that can balance the body's immune function can be obtained from natural materials such as plants and marine biota¹⁵. Some medicinal plants that have immunomodulatory potential have been reported by several researchers. Such medicine uses natural ingredients that serve as immunomodulators or commonly known as herbal medicine. In Indonesia, it has been used by our ancestors for centuries. It was proven from the existence of old manuscripts on the leaves of lontar Husodo (Java), Usada (Bali), Lontarak pabbura (South Sulawesi), and Primbon Jampi Fiber document. It has also been widely used in almost all countries globally³. Some of the traditional medicines are Tamarindus indica L. and Curcuma domestica. These plants are usually used as a traditional medicinal ingredient in the world¹⁶. Tamarindus indica L. plant parts are commonly used for treatment, including the leaves, bark, fruit flesh, and seeds^17-20. Tamarindus indica L. and Curcuma domestica plants are medicinal plants that have been clinically tested to cure or prevent various diseases²¹.

Recently, Tamarindus indica L. and Curcuma domestica have been added to nutraceuticals, beverages, and processed foods. Curcuma domestica belongs to the Zingiberaceae family. Three curcuminoids (curcumin, dimethoxy curcumin, and bisdemethoxy curcumin) are the most common bioactive ingredients in homemade turmeric. Pigmented curcumin or diferuloyl methane accounts for 60% to 70% of raw turmeric extract and is the primary curcuminoid evaluated for its health-enhancing activity^22,23.

Tamarindus indica L is used to lower cholesterol and is one of the herbal remedies that has been clinically proven to treat or prevent various diseases⁸. Homemade Curcuma domestica can stimulate the immune system and increase the number of leukocytes in the blood. Curcumin content in homemade turmeric can increase the number of leukocytes because it consists of lymphocyte cells that act as an antigen against a disease^11,24. Curcumin is also a group of polyphenol compounds that may cause protein denaturation and damage cell membranes. Phenolic compounds in Curcuma domestica can damage and penetrate bacterial cell walls so as to precipitate microbial cell proteins²⁵. Previous research conducted by Hartati et al. showed that the administration of curcumin in laying hens could stimulate lymphocyte activity. In the histopathological picture of the bursa of Fabricius, there was an increase in the number of lymphocytes in the lymphoid follicles and the thymus was also seen in the widening of the cortex compared to the medulla. Curcumin has been shown to enhance adaptive immunity, both humoral and cellular immunity. Therefore, based on this background, researchers aimed to investigate the potential of Tamarindus indica L and Curcuma domestica as immunomodulators in increasing the number of lymphocyte cells.

MATERIALS AND METHODS:

Place and time of research.:

This research was conducted in several locations. The treatment and intervention sites for animal experiments were carried out at Pusvetma Surabaya. Meanwhile, observations of blood removal were performed in the Clinical Pathology Laboratory at the Faculty of Health Sciences, the Muhammadiyah University of Surabaya. The research was conducted from October to November 2021.

Tools and materials.:

The tools used in this research included spuit 1 ml, sonde, Olympus CX 33 microscope, beaker glass, gauze, and digital scales brand Sonde SV-490C. Further, the materials covered DDY Strain male musculus mice aged 1-2 months with a weight of 20-30gr, Tamarindus indica L powder, Curcuma domestica powder, aqua dest, stimuno (manufacturer's immunomodulator), and pH buffer 6.4 -cat wright -oil immersion. Meanwhile, Mus musculus was fed from Pokphand with the code BR1 CP511B.

Data collection techniques.:

The type of this research was experimental design with the Post Test Only Design Control Group. It used mice experiments (Mus musculus) aged 1-2 months as the research object. There were five group treatments used in this study. In group 1 (G1), the treatment was carried out by feeding and aqua dest as much as 0.25ml/BB 20gr (control). While group 2 (G2) treatment was with feeding and stimuno as much as 0.25ml/BB 20gr, group 3 (G3) was treated by feeding and infusing Tamarindus indica L and Curcuma domestica with a 12.5% concentration of as much as 0.25ml/BB 20gr. Group 4 (G4) treatment was undergone by feeding and infusing Tamarindus indica L and Curcuma domestica with a 25% concentration of as much as 0.25ml/BB 20gr. Finally, group 5(G5) treatment was performed by feeding and infusing Tamarindus indica L and Curcuma domestica with a higher concentration of 37.5% as much as 0.25ml/BB 20gr. The treatment was carried out daily for 14 days of observation.

Manufacture of infusa Tamarindus indica L and Curcuma domestica:

Simplisia Tamarindus indica L and Curcuma domestica were infused at 12.5%, 25%, and 37.5% by heating a water bath at 90⁰C for 15 minutes while stirring occasionally. After that, the infuse was filtered using a flannel cloth and placed in a 100mL measuring flask (26).

Observation of the number of lymphocytes.:

Blood sampling was taken from the tail of the mice, after which the edge blood removal was made. If the blood removal is dry, then the coloring process is carried out using the Wright method. After the coloring process was completed, a reading was performed to determine the number of leukocyte cell types using the differential counting method. One of which was lymphocytes in 100 cells using a microscope with an objective lens of 100x, showing markers of an immune response.

Etic Clerence:

The procedure for using experimental animal samples in this study has followed the ethical feasibility test at the Poltekkes Kemenkes Surabaya with number No.EA/1323/KEPK-Poltekkes_Sby/V/2022.

RESULT:

During the study, mice were weighed weekly for four weeks. The weighing was done using a digital scale. The mice weighing and the number of lymphocytes in each group is summarized in Table 1: normally distributed weight and lymphocyte count (p >0.05).

Table 1. Number of lymphocytes in blood removal (N =30)

Group	Weight (gr)	Lymphocytes (%)
G1	20.50±0.548	21.00±1,673
G2	22.00±0.632	30.67±2,503
G3	22.50±0.548	30.33±2,166
G4	23.50±0.548	41.83±3,545
G5	24.50±0.548	41.83±3,545

*Mean±SD

Information:

G1: treatment with feeding and aqua dest as much as 0.25 ml / BB 20gr (control)

G2: treatment with feeding and stimuno as much as 0.25 ml / BB 20gr

G3: treatment by feeding and infusing Tamarindus indica L and Curcuma domestica with a 12.5% concentration of as much as 0.25 ml / BB 20gr

G4: treatment with feeding and infusing Tamarindus indica L and Curcuma domestica with a 25% concentration of as much as 0.25 ml / BB 20gr

G5: treatment with feeding and infusing Tamarindus indica L and Curcuma domestica with a 37.5% concentration of as much as 0.25 ml / BB 20gr

Figure 1. Graph of the increase in the number of lymphocytes

The results showed that the number of lymphocytes increased. It can be seen in the G3, G4, and G5 treatments that have the same value as the comparison of the manufacturer's immunomodulatory supplement (G2), as provided in table 1 and picture 1.

The reading of lymphocyte cells on the blood removal that had been stained with Wright's coloring was then calculated using the differential counting method. It counted as many as 100 leukocyte-type cells. Then, the results were obtained in the form of percentages. The observations found lymphocyte cells and neutrophil cells, while other types of leukocyte cells such as basophils, eosinophils, and monocytes were not found

Microscope observations at 100x objective lens magnification had different results on each treatment. In treatment G1, lymphocyte and erythrocyte cells were seen very rarely in each field of view. Meanwhile, treatments G2 to G4 found that the number of lymphocytes and erythrocyte cells looked almost to fill the field of view. In treatment G5, in addition to lymphocytes and erythrocyte cells that met the field of view, there was also another type of leukocyte cell, namely neutrophil cells indicated on the red arrow.

DISCUSSION:

The study showed that exposure to Tamarindus indica L and Curcuma domestica infusions increased mice weight compared to the control group. In the treatment of G2 (the manufacturer's immunomodulatory supplement), the value of lymphocytes was almost comparable to that of infusions of Tamarindus indica L and Curcuma domestica. Phyllanthus niruri extract and Xylopia aethiopica report that an increase in white blood cells indicates a high probability that plant extracts contain agents that can stimulate leukocyte production. Immune defense is a complex interaction between nonspecific and specific immune responses, cellular and humoral, stimulation and suppression of immunocompetent cells, as well as endocrine influences. Another mechanism in the immune system is macrophages and granulocytes, which play a central role in immune stimulation. Macrophage activation is important for pathogens to stay in touch with active cells. The second most important function is the stimulation of T lymphocytes, which can be achieved directly or indirectly through macrophages²⁷.

The antioxidant properties of the seeds and leaves of Tamarindus Indica have been shown in many studies^28,29. Not only are the phenolic properties (tannins) of raw seeds, but hot dried seeds also contain antioxidant properties⁹. In addition, phenol-rich foods and drinks such as red wine, seed wine, green tea, and acids have hypolipidemic, anti-atherosclerotic, antioxidant, anti-inflammatory, and immunomodulatory effects. The fruit of Tamarindus indica is rich in organic acids, pectin, vitamins, mineral content, polyphenols, and flavonoids rich polyphenol content present in seeds and fruit shows a regulatory effect on neutrophils³⁰.

In the G5 treatment, there were also neutrophil cells in addition to lymphocyte cells. Neutrophils are a major component in the innate immune system and perform an integral role in normal tissue homeostasis, although neutrophil dysregulation contributes to the pathogenesis of various chronic inflammatory diseases, infectious disorders, and certain autoimmune diseases^31,32. Neutrophils are also professional phagocytes and end effector cells of innate immunity, with a leading role in the clearance of extracellular pathogens. They can also directly interact with macrophages, dendritic cells, natural killer cells, T cells, and B cells to complete innate and adaptive immune responses³³. As a result, the identification of substances can modulate neutrophils. In addition, it has been known that various compounds of plant origin show favorable pharmacological effects through their ability to modulate phagocyte function ^26,34. Indeed, some small plant-derived molecules have been shown to exhibit immunomodulatory activity through the regulation of neutrophil function^31,35-37.

Based on the screening results, Curcuma domestica has the main content, namely curcumin. Additionally, it contains steroids and flavonoids. The main factor contributing to the increase in the number of white blood cells (WBC) may be due to the immune stimulation activity of curcumin. The substance is the active ingredient extracted from Curcuma domestica. A significant increase in mice WBC suggests that the extract may provide immunological properties, thereby improving the defense system against infected antigens from the surrounding environment¹. According to³³ curcuminoids have a dose-dependent inhibitory effect on the production of reactive oxygen species (ROS) and the release of myeloperoxidase by activated neutrophils. Curcumin has been found to activate macrophages differently and increase phagocytosis activity in mice^3,12. Strikingly, prolonged administration of curcumin does not impair the cytotoxic function of natural killer cells, the formation of ROS, and the production of nitric oxide and cytokines³⁸.

From differential counting results, the absence of eosinophil and basophil cells was caused by mice that did not have an infection. This finding is in accordance with the statement ^39,40 that an increase in the number of basophils is an indication of acute inflammation that causes hypersensitivity and the presence of respiratory tract infections and severe tissue damage. Basophils have the same function as mast cells, which evokes an acute bleeding process at the place of antigen deposition.

CONCLUSION:

The results showed that infusing Tamarindus indica L and Curcuma domestica have the potential to be used as immunomodulators at the lowest doses. Therefore, it can serve as an alternative immunomodulator by continuing phytochemical research.

CONFLICT OF INTEREST:

The authors have no conflicts of interest regarding this investigation.

ACKNOWLEDGMENTS:

The author thanked the Muhammadiyah Research Center Assembly, Muhammadiyah University of Surabaya, Pusvetma, and the Clinical Pathology Laboratory of the Muhammadiyah University of Surabaya for providing the necessary facilities to carry out research work.

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Received on 12.12.2023 Modified on 16.04.2024

Research J. Pharm. and Tech 2024; 17(11):5215-5220.

DOI: 10.52711/0974-360X.2024.00798