Pages Menu
ISSN (Online): 0975-8232,
ISSN (Print): 2320-5148

International Journal Of
Pharmaceutical Sciences And Research

IJPSR is indexed with Embase

An International Journal published monthly
An Official Publication of Society of Pharmaceutical Sciences and Research

Categories Menu

THE POTENTIAL OF INDONESIAN TRADITIONAL HERBAL MEDICINE AS IMMUNOMODULATORY AGENTS: A REVIEW

HTML Full Text

THE POTENTIAL OF INDONESIAN TRADITIONAL HERBAL MEDICINE AS IMMUNOMODULATORY AGENTS: A REVIEW

Erlia Anggrainy Sianipar

Department of Pharmacy, School of Medicine and Health Science, Atma Jaya Catholic University of Indonesia.

ABSTRACT: The prevalence of infectious diseases in the world, including in Indonesia, has increased significantly. One of the factors of death due to infectious disease is decreasing the human body's immune system. Therefore, studies on immunomodulatory agents need further investigation. Many studies have shown that secondary metabolite compounds contained in plants have immunomodulatory properties. These compounds are flavonoids, alkaloids, polysaccharides, phenols, terpenoids, tannins, glycosides, saponins, and sterols. In Indonesia, there are many types of medicinal plants containing secondary metabolite compounds. Besides, Indonesian people usually consume Jamu for immune-boosting. Jamu is made from Indonesian traditional herbal medicine such as ginger, turmeric, galangal, Curcuma, cinnamon, sand ginger, lemongrass, cardamom, tamarind, lime and cloves. The most frequently used Indonesian traditional herbal medicine investigated regarding their constituents and immunomodulatory effect should be explored. Although, more research is needed to prove efficacy and assure safety scientifically. This paper aims to give comprehensive views useful for future development and further improve its utility as immunomodulatory agents.

Keywords: Immunomodulatory, Indonesia, Jamu, Traditional Herbal Medicines

INTRODUCTION: Immunomodulators are substances that can stimulate or suppress the immune system, both the adaptive and innate immune systems. Nowadays, immunomodulators are very important to study because of the increasing prevalence of infectious diseases worldwide, including in Indonesia. Some infectious diseases are HIV/AIDS, sexually transmitted diseases, diarrhea and other abdominal infections, acute respiratory infections, leprosy, frambusia, hepatitis, meningitis, herpes, HPV, tuberculosis, malaria 1.

In 2019, malaria, tuberculosis, and HIV/AIDS all remained in the top 10 leading causes of death in low-income countries in the world. HIV, TB and malaria accounted for 0.8, 1.2 and 0.4 million deaths, respectively, in 2018 2.

In 2016, there were 28 million cases of malaria in Southeast Asia, with 38 thousand deaths 3. Besides that, infectious diseases also killed 3, 5 million peoples in developing countries like Indonesia. In 2018, Indonesia had several cases, such as AIDS with 641.675 patients and tuberculosis with 316 cases per 100.000 populations. The prevalence of tuberculosis in Indonesia is the second-largest in the world 4. Decreasing of immune system response is usually associated with the number of death due to infectious diseases. The immune system is essential to protect the human body against pathogens.

When the immune system decrease, pathogens will attack our body quickly and our health becomes worse. One of the preventive efforts to increase the immune system is using herbal concoctions or traditional medicines, especially those with an immunomodulatory effect.

Many immunomodulators study had been done. Some researchers explained that the active secondary metabolites compounds containing in herbal plants have an immunomodulatory effect. These compounds are flavonoids, phenols, alkaloids, terpenoids, polysaccharides, glycosides, saponins, tannins, and sterols 5, 6.

According to WHO, 88% of the world's population uses traditional medicine, and 90% of developing countries use traditional herbs as primary healthcare 7. Indonesian people used to consume Indonesian traditional herbal medicines called “jamu”, a hereditary alternative medicine. Jamu is still very popular for maintaining health and treating diseases. The Indonesian tropical climate also supports this, so it makes Indonesia rich in natural resources. More than 30.000 species of plants grow in Indonesia, and around 9.600 species are known to have pharmacological activities.

METHODS: This review article was conducted in 2021 by reviewing all full-text articles published in English and the Indonesian language. Articles were collected from international and national search websites of Google scholar, Pub Med, and Scopus. The search keywords are immunomodulatory activity, herbal medicines, jamu, Indonesian traditional herbal medicine, and immunomodulator.

RESULTS: Based on the results search, 130 articles were identifier. Sixty articles in Google Scholar, 43 articles in Pub Med, and 27 articles in Scopus. After removing the same articles, I finally reviewed 80 articles, such as 70 English-language articles and 10 Indonesian language articles.

Immunomodulatory Activity of Secondary Metabolites in Plants: Types of Immuno-modulators consist of three categories: immuno-adjuvants, immunostimulants and immuno-suppressants. Immunoadjuvants use for increasing the response to a vaccine while not having any specific antigenic effect. Immunostimulants are agents that increase the body's resistance against infections, can act by the stimulated nonspecific immune system. Then, immunosuppressant could be used to control the pathological immune response in autoimmune diseases, hypersensitivity, and immune pathology associated with infections 8.

Secondary metabolite compounds with immuno-modulatory activities are alkaloids, flavonoids, glycosides, polysaccharides, polyphenols, tannins, terpenoids, saponins and sterols. The mode of action of these compounds had been studied in many research studies Fig. 1.

Flavonoids: Many types of flavonoids have immunomodulatory activity, such as centaurein, apigenin 7-o-β-Dneohesperidoside, orientin, Apigenin 7-O-β-D-galactoside, Vitexin, Silymarin, Naringenin, Dihydroquercetin, Genistein, and Hesperidin. The immunomodulatory effects of naringenin derived from citrus fruits due to down-regulated chemokine expression (CXCL1, CCL4, CCL5, CXCL5, CXCL10) and cytokines (IL-6, IL-10, IL-1β, IL-12p70, TNF, IL-1α) 9. Flavonoids showed immunostimulants activity by stimulated mononuclear cells to secretion cytokine IL-1β, IFN-γ, and TNF-α 10.

Polyphenols: Some polyphenols impact immune cell populations, modulate cytokine production and pro-inflammatory gene expression. They inactivate NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and modulate mitogen-activated protein Kinase (MAPk) and arachidonic acids pathways 11. One example of polyphenols is curcumin, an active compound in Curcuma longa. Curcumin enhances bone marrow cellularity, α esterase positive cells, phagocytic activity. It inhibits IL-2 expression and NF‑κB 12. The extract of Allium carolinianum and Pedicularis longiflora significantly decreased TGF-β1, NF-κB, and TNF-αlevels 13.

Alkaloids: Alkaloids are the primary source of performance enhancement and improving immune functions. Some alkaloids that have been investigated due to their immunomodulatory activities are piperine, berberine, tetrandrine, sinomenine, punarnavine, papaverine 14. Piperine analog augmented the levels of Th1 lymphocytes mediated TNF-α, IL-12, IL-1β and decreased the expressions of Th2 mediated IL-4, IL-10 and cell viability in invitro study 15. Papaverine modulated the activity of Th17 by reducing the expression of NF-κB, p38MAPK, RANKL, and IL-23 16. The tetrandrine in Stephania tetrandra can suppress antibody synthesis by B cells and the mitogen-induced lymphoproliferative response, inhibiting activation of human peripheral blood T-cells 17.

Terpenoids: The favourable effects of terpenoids on the immune system are mainly occurred either production of antibodies or improving T-cell response suppression 18. An example of the terpenoids group is andrographolide, containing in Andrographis paniculata. It enhances the expression of IL-2, inhibits NO in endotoxin to stimulates macrophages. Boswelic acid containing in Bowella serrata can increase the number of peritoneal macrophages significantly 19. Ursolic acid activates the phagocytosis process in human monocyte cells and THP-1 cells, suggesting the intracellular killing effect of macrophages during Mycobacterium tuberculosis infection 20.

Polysaccharide: The mechanism of poly-saccharides as immunomodulators is due to innate immunity modulation, especially in macrophage function. Generally, polysaccharide binds cell membrane receptors and stimulates immuno-modulator response in macrophage cells.

In one study, a polysaccharide from Cipango paludina chinensis could significantly increase the spleen and thymus signals and enhance the macrophage function 21.

Glycosides: Mangiferinis one of the examples of glycoside containing in Mangifera indica Linn. Mangiferin decreased the expression of Th2-mediated TNF-α, IL-3, IL-4, IL-5, IL-9, IL-13, IL-17 and concurrently enhanced the expression of Th1mediated IL-2, IL-12, IL-10, IL-γ in serum. Thus, mangiferin exerts potential immuno-regulatory activity by ameliorating the imbalance between the Th1/Th2 cytokines 22.

FIG. 1: CHEMICAL STRUCTURE OF SECONDARY METABOLITES SUBSTANCES THAT HAVE IMMUNO-MODULATORY EFFECT

Tannins: Tannins have some immunosuppressive activity such as suppressed the expression of IL-2, leukocyte reaction as well as CD3+ T cell infiltration, attenuated the expression of IL-2, TNFα and ROS production, inhibition of NF-κB activation, p38, JNK and ERK ½ phosphorylation, improve the WBC, platelets and DLC counts 14.

Corilagin, hypophyllanthin, geraniin, phyllanthin, which contain in Phyllanthus amarus extract, inhibit the production of NO and myeloperoxidase activity and improved both cellular and humoral immune responses 23.

Saponins: An experimental vaccine study has shown that Quillaja brasiliensis has immuno-stimulatory activity by improving the immune responses and protect lethal challenges in mice 24. Ilexsaponin I derived from Ilex pubescen restricted PGE2 and NO formation by downregulating the expression of cyclooxygenase-2 and iNOS. Davidianoside F saponin also exhibits anti-inflammatory activity in human tumor cell lines by suppressing the IL-1β 25.

Sterols: The phytosterols (stigmasterol, shaftoside, β-sitosterol) extracted from Clinacanthus nutans significantly decreased the T-cell proliferation and improved the Th1 and Th2 mediated cytokines expression 26. The β-sitosterol and daucosterol isolated from Dioscoreabatatas have immuno-modulatory effects. The β-sitosterol showed the immune-boosting effects by enhancing the expressions of iNOS and TNF-α and has immunosuppressive activity by lowering the expression of TNF-α. Besides, the daucosterol showed immunosuppressive effects by inhibiting the expressions of IL-6, iNOS, and TNF-α 27.

The Pharmacological Activity of Indonesian Plant Medicine as Immunomodulators:  Several Indonesian plant medicine with their active compound and their modes of action as immuno-modulators showed in Table 1.

TABLE 1: LIST OF INDONESIAN PLANT MEDICINES HAVING IMMUNOMODULATORY ACTIVITIES

Plant name Partsused Active compounds Immunomodulatory activities
Temulawak

(Curcuma xanthorriza Roxb.)

 Rhizome Curcuminoid, volatile oil As an immunostimulant by elevating B cells and T cells response for antibody production; It regulates the NF-κB pathwayof various immune cells such as dendritic cells, macrophages and NK cells 28
Sambiloto (Andrographis paniculata) Leaves Terpenoid lactone such as deoxy-andrographolide, andrographolide, 14-deoxy-11, neoandrographolide, 12didehydroandrographolid, homoandrographolide, diterpenoid and flavonoids, alkaloids, steroids, glycoside and tannins As an immunostimulator and immunosupressor 29. Stabilize the number of lymphocytes, NK Cells, CD 4+ expression and secretion of IFNγ 30, 31 increasing the levels of total leucocyte counts, along with the phagocytic index 32 Enhance the IgG 33 Andrographolide attenuate innate immune responses by through NF-κB signaling pathway 34
Kayumanis (Cinnamomum verum (L.) Stem Polyphenols, alkaloids, triterpen, Cynamaldehide and volatile oil. Volatile oil from Cinnamomum verum can enhance the immune response in Rheumatoid Arthritis (RA) Cynamaldehide also inhibits the proteinsin RA progression and potentiation 35
Cengkeh (Syzygium aromaticum) Flower Eugenol, eugenol acetate, tannins, tymol and  β-caryophyllene The eugenol compound increases the release of IL-6 and TNF36
Sereh (Cymbopogon flexuosus) Stem Polysaccharides Activates T and B lymphocytes and stimulates secretions from several cytokines. Polysaccharides can inhibit immunopotentiation such as increasing thymus and spleen, stimulating ConA- and inducing LSP splenocyte proliferation and increasing secretion of IL-2, IL-6, IL-12 and TNF-a in mice induced by tumors 37
Jahe (Zingiber officinale Roscoe) Rhizome Gingerol, shogoal, volatile oil Ginger inhibits lymphocyte proliferation, which is mediated by decreased IL-2 and IL-10 production. Ginger water extract significantly increases IL-1β, IL-6 and TNF-α production in rat macrophages and splenocyte proliferation and cytokine production 38. Essential oils in ginger can increase the humoral immune response that involves the interaction between B cells and antigens resulting in proliferation and differentiation into plasma cells that secrete antibodies 39
Kunyit (Curcuma longa L.) Rhizome Curcuminoid, volatile oil Inhibits NO production to activate macrophages 40. Increase white blood cell production and weight of lymphoid organs41increased serum levels of IgG and IgM 42, inhibits the immunostimulatory function of dendritic cells (DCs and  interfere in the myeloid DC maturation 43
Meniran (Phyllanthus niruri) Roots and leaves The flavonoid, consist of Phyllantine, hypophyllantine, quercetin, quercitrine, isoquercitrine, astragaline, tannin, damar, kalium, lignan Water extract from Phyllanthus niruri leaves increases PBMC cell proliferation, improves phagocytic activity and increases the release of NO macrophages 44, 45. As an immunostimulant by increasing neutrophil activity and antibody response significantly 46
Jambubiji (Psidium guajava L.) Leaves Flavonoid, quercetin, guajaverine, gallocatechine, tannin elegat acidandguavin A, C and D, triterpene, volatile oil Immunostimulant  47, stimulates humoral and cellular immunity in mice 48, increases the expression of IL8 gene, which shows potential defense in the immune system 49
Kedondonglaut (Polyscia sobtusa) Leaves Saponins, tannins, flavonoids P. obtuse inhibits the immunomodulating effect 50. Simplesia leaves from P. obtuse have immunostimulants activity in S. typhimurium infections. The administration of P. obtusa leaves increases the levels of CD4+, CD8+ and B220 + cells in S. typhi infection significantly 51, 52
Kemukus (Piper cubeba) Fruit Piperine, piperidine, chavicine, protein, cineol,

p-cymen, lignins, sesquiterpenespiperlotin, schimiditin andcarvon.

 P. cubeba has immuno suppressants activity and decreases peripheral blood neutrophil levels. Another study show that P. cubeba effect on downregulation of cytokines, such as TNF-α and IL-6 so that can reduce the inflammatory reaction in experimental animals 53
Kiseureuh (Piper aduncum), Fruit Piperine, piperidine, chavicine, protein, cineol,

p-cymen, lignins, sesquiterpene, piperlotine, schimiditineandcarvon.

 At low doses,P.aduncumacts as an immunosuppressant by reducing cell phagocytosis by 50% of the normal response. At high doses, hasimmunostimulants effect 53
Cabejawa (Piper retrofractum) Fruit Piperine, piperidine, chavicine, protein, cineol,

p-cymen, lignin, sesquiterpenes, piperlotine, schimiditineandcarvon.

 P. retrofractum acts as an immunostimulant also increase peripheral blood neutrophil levels, which play essential role in the phagocytosis process 53
Sirih (Piper betle) Leaves piperine, piperidine, chavicine, protein, cineol,

p-cymen, lignin, sesquiterpenes, piperlotine, schimiditine and carvon.

 Immunosuppressant, suppressing cellular and humoral immune activity, which indicates the potential of plants in autoimmune diseases 54
Piper longum Fruit and Leaves piperine, piperidine, chavicine, protein, cineol,

p-cymen, lignin, sesquiterpenes, piperlotin, schimiditine and carvon.

 Immunostimulant, enhancestotal leukocytes by increasing stem cell proliferation in the hematopoiesis process in the bone marrow. Enhance antibody titers which play a role in humoral immunity 55, 56
Bawang Dayak (Eleutherine palmifolia (L) Merr) Leaves and roots Alkaloids, glycosides, flavonoids, phenols, quinones, steroids, tannins, and essential oil. Flavonoids stimulate the immune system by increasing the activity of macrophages and T lymphocytes. Ethanol extract have immunomodulators effect in mice and produce immunoglobulin G (IgG) and immunoglobulin M (IgM) 57
Kelakai (Stenochlaena palustris (Burm.f) Bedd) Quercetin, flavonoids

alkaloids and steroids

 Enhances the production of cytoticIL-10in P. berghei infections. IL-10 responds to T-helper cells in malaria to prevent the proliferation of Th1 cells, inhibitsthe production of IFN-γ, IL-6, TNF-α by T cells, by neutralizing the pathology of macrophages by inhibiting the secretion of IFN-γ and TNF-α in cerebral malaria 58
Pasak Bumi (Eurycoma longifolia) Roots Quassinoids, flavonoids, and alkaloids (9-metoksisantin-6- alkaloidsandkantinon alkaloid). Quassinoids increase in-vitro IL-12 secretion. IL-12 is an innate immune response booster that can activate macrophages against microbes by modulating the effector function of NK cells 59

Quassinoids enhance mRNA TNF-α expression, which is an inflammatory cytokine that can kill the Leishmania parasite 60
Akar Kuning (Fibraurea chloroleuca) Stem roots and leaves Alkaloids, terpenoids, berberine Berberine has immunostimulant activity by increasing the ability of macrophages to kill bacteria in the body 61. Berberine can also increase the production of interleukin-12, which stimulates immunoregulatory activity by inhibiting T helper-2 cytokine cells in CD4+ cells 62
Lidahbuaya

(Aloe vera)

 Leaves carotenoids, steroids, terpenes and phytosterols Stimulate T and B cell proliferation, promote the production of IL-1β, TNF-α, IL-2, IL-6 and IFN-γ 63, 64
Mangga

(Mangifera indica L.)

 Fruits Mangiferin Increase in humoral antibody (HA) titer and DTH Modulating the humoral response. Inhibit reactive intermediate-induced oxidative stress in lymphocytes, neutrophils, and macrophages65
Jintanhitam

(Nigella sativa L.)

 Seeds Nigellone, thymohydroquinone, and thymol Release mediators (IL-2, IL-6, PGE2) from human immune cells (including T-lymphocytes and monocytes) 66.
Pepaya

(Carica papaya L.)

 Leaves, pulp and seeds α-tocopherol, ascorbic acid, phenolic acids (trans-ferulic acid, para-coumaric acid, caffeic acid, vanillic acid), flavonoids (myricetin, kaempferol, quercetin), cyanogenic glycosides and glucosinolates Decrease IgM and Nitric oxide levels. Increase IgG levels and phagocytosis. Decrease the proinflammatory cytokines (IL‐10, IL‐12, IL‐1β, IL‐6 and TGF‐β1) 67
Bawangputih (Allium sativum) Fruits Allicin, organosulfur Enhancement in lymphocyte proliferation and cells account in the bone marrow. Allicin inhibits Th1 pro-inflammatory cytokines and activation of NF-Kb 68. antibody secretion,  phagocytosis promotion, and by creating a shift in cytokine production pattern from TH2 to TH1, leads to expansion of a strong cell-mediated immunity 69
Pegagan (Centella asiatica (L.)) Leaves Saponins, triterpenoids It increases IgG levels and activation of macrophages 70
Teh (Camellia sinensis (L.)) Leaves epicatechin (EC), epigallocatechin (EGC), EC gallate and EGC gallate (EGCG) increasing the expression of IL-8, IL-17A and HBD-271
Mengkudu (Morinda citrifolia L) Fruits polysaccharide increased the humoral and cell-mediated immune response 72
Jeruknipis (Citrus aurantiifolia) Fruit and leaves Vitamin C Inhibits proliferation of phytohaemaglutinin activated mononuclear cells73
Asamjawa (Tamarindus indica L.) Fruits polysaccharide Enhancement of phagocytic, inhibition of cell proliferation and leukocyte migration inhibition 74, 75
Brotowali (Tinospora cordifolia) Stem and roots alkaloids, steroids, glycosides, diterpenois lactones, sesquiterenoid and polysaccharides Stimulate the macrophage activation, increase phagocytosis and antibody production, reduce eosinophil count 76
Lengkuas (Alpinia galangal) Rhizomes Polysaccharide It has a stimulating effect on reticulo-endothelial system (RES) and increased the number of peritoneal exudate cells and spleen cells of mice, which may relate to the immunomodulating effect 77
Kencur (Kaemferia galangal) Rhizomes Polysaccharide Effectively protect the thymus and spleen of tumor-bearing mice from solid tumors and enhance the immunoregulatory ability of CD4+ T cells, the cytotoxic effects of CD8+ T cells and NK cells 78

The Immunomodulatory Effect of Jamu, Indonesian Traditional Herbal Medicine: Jamu, the famous traditional herbal elixir from Indonesia have been developed before the 18th century. Based on the results of Riset Kesehatan Dasar in 2018 showed that Indonesian people had used jamu for more than 50% 79. Jamu is a traditional Indonesian medicine derived from ingredients or herb ingredients that are in the form of plant material, veterinary material, mineral material, Sarian preparations, or a mixture of such substances that are hereditary used for treatment and can be applied in accordance with the prevailing norms in the community 80. The plant parts using for Jamu are roots, stems, leaves, fruit, flowers, seeds, rhizomes, or whole plant 81.

Nowadays, many jamu variants have been introduced to the Indonesian public. Each contains different ingredients due to the rich diversity of spices and herbs available in Indonesia that have many different benefits. Generally, jamu is used to maintain good health. It consists of turmeric, ginger, galangal, curcuma, cinnamon, lemongrass, cardamom, tamarind and cloves. Most of these ingredients work greatly for immune-boosting 82.

CONCLUSION: Based on the results of studies, some Indonesian traditional plant medicines including in Jamu can potentially be immunomodulatory agents. Because of their secondary metabolites content, which has pharmacological activities as immunoadjuvant, immunostimulants, and immunosuppressants?

The study of Indonesian herbal medicines needs further investigation to determine their specific mechanisms and prove efficacy and assure safety scientifically. The improvement of its utility as immunomodulatory agents should be developed in the future. Hopefully, Indonesian traditional herbal medicine will be used by Indonesian people to prevent various infectious diseases.

Financial Support and Sponsorship: Nil

ACKNOWLEDGMENT: Nil

CONFLICTS OF INTEREST: There is no conflict of interest.

REFERENCES:

  1. Wulan IGAK and Agusni I: Immunomodulators for a variety of viral infections of the skin. BerkalaIlmu Kesehatan KulitdanKelamin- Periodical of Dermatology and Venereology 2015; 27(1): 63-9.
  2. World health statistics 2020: Monitoring health for the SDGs, Sustainable Development Goals. 2020 [Available from: https://www.who.int/gho/publications/ world_health_statistics/2018/en/]
  3. Margono DPNH, Suhartono E and Arwati H: Potentiality of kelakai (Stenochlaena palustris (Burm.f) Bedd) extract against the level of tumor necrosis factor-alfa (TNF-α) in the BALB/c mice infected with Plasmodium Berghe Anka. Berkala Kedokteran 2016; 12(1): 77-85.
  4. Ministry of Health of Republic of Indonesia: Profil Kesehatan Indonesia 2019. 2020 [available from: https://pusdatin.kemkes.go.id/resources/download/pusdatin/profil-kesehatan-indonesia/Profil-Kesehatan-Indonesia-2019.pdf]
  5. Sharma P, Kumar P, Sharma R, Gupta G and Chaudhary A: Immunomodulators: Role of medicinal plants in immune system. Nat J of Physio, Pharmacy and Pharmacology 2017; 7(6): 552-6.
  6. Utami YP, Aliyah andSyukur R: Immunostimulant effect combination syrup of Carthamus tinctorius and Eleutherine palmifolia extracts on mice (Mus musculus). JST Kesehatan 2016; 6: 179-84.
  7. World Health Organization. Who Global Report On Traditional And Complementary Medicine 2019. Geneva: World Health Organization, 2019.
  8. Venkatalakshmi1 P, Vadivel V and Brindha P: Role of phytochemicals as immunomodulatory agents: A review. Intern J of Green Pharm 2016; 10 (1): 1-18.
  9. W Zeng, L Jin, F Zhang, C Zhang and W Liang: Naringenin as a potential immunomodulator in therapeutics. Pharmacol Res 2018; 135: 122–6.
  10. Liao DY, Chai YC, Wang SH, Chen CW and Tsai MS: Antioxidant activities and contents of flavonoids and phenolic acids of Talinum triangulare extracts and their immunomodulatory effects. J Food Drug Anal 2015; 23: 294-302.
  11. Yahfoufi N, Alsadi N, Jambi M and Matar C: The Immunomodulatory and Anti-Inflammatory Role of Polyphenols. Nutrients 2018; 10(1618): 1-23.
  12. Boroumand N, Samarghandian S and Hashemy S I: Immunomodulatory, anti-inflamatory and antioxidant effects of curcumin. J Herbmed Pharmac 2018; 7(4):211-9.
  13. Yatoo M, Dimri U, Gopalakrishnan A, Saxena A, Wani S and Dhama K: In-vitro and in-vivo immuno-modulatory potential of Pedicularislongiflora and Allium carolinianum in alloxan-induced diabetes in rats. Biomed. Pharmacother 2018; 97: 375-84
  14. Cell T, Kumar K, Brisc C, Rus M, Cseppento DCN, Bustea C: Exploring the multifocal role of phytochemicals as immunomodulators. Biomedicine & pharmacotherapy 2021; 133: 110959.
  15. Santos J, Brito M, Ferreira R, Moura A, Sousa T and Batista T: Th1-biased immunomodulation and in-vivo antitumor effect of a novel piperine analogue. Int J Mol Sci 2018; 19: 2594.
  16. Guan S, Liu Q, Gu H, Zhang Y, Wei P and Qi Y: Pluripotent antiinflammatory immunomodulatory effects of papaverine against cerebral ischemic-reperfusion injury; J Pharmacol Sci 2020; 144: 69-75.
  17. Jiang Y, Liu M, Liu H and Liu S: A critical review: traditional uses, phytochemistry, pharmacology and toxicology of Stephania tetrandra Moore (Fen Fang Ji). Acta Pharmacol Sin 2020; 19: 449-89.
  18. Ludwiczuk A, Skalicka-Wo´zniak K, Georgiev M: Terpenoids. Pharmacognosy Fundamentals, Application and Strategies. Academic Press, 2017: 233–66.
  19. Chahal K and Jha M: In-vivo study of Boswellia serrata for modulating immune system and quenching free radicals. Adv in Zoology and Botany 2020; 8(4):358-68.
  20. Podder B, Jang WS, Nam KW, Lee BE and Song HY: Ursolic acid activates intracellular killing effect of macrophages during Mycobacterium tuberculosis infection. J Microbiol Biotechnol 2015; 25: 738-44.
  21. Abood WM: Immunomodulatory and Natural Immuno-modulators. J of allergy and inflame 2017; 1 ( 2) : 1-3
  22. Guo H, Yun C, Hou G, Du J, Huang X and Lu Y: Mangiferin attenuates Th1/ Th2 cytokine imbalance in an ovalbumin-induced asthmatic mouse model. PLoS One 2014; e100394.
  23. Ilangkovan M, Jantan I, Mesaik M and Bukhari S: Inhibitory effects of the standardized extract of Phyllanthusam aruson cellular and humoral immune response in Balb/C mice. Phytother Res 2016; 30: 1330-38.
  24. Yendo A, de Costa F, Cibulski S, Teixeira T, Colling L and Mastrogiovanni M: A rabies vaccine adjuvanted with saponins from leaves of the soap tree (Quillaja brasiliensis) induces specific immune responses and protects against lethal challenge. Vacci 34 2016; 2305-11.
  25. Zhou M, Huang L, Li L, Wei Y, Shu J and Liu X: New furostanolsaponins with anti-inflammatory and cytotoxic activities from the rhizomes of Smilax davidiana. Steroids 2017; 127: 62–8.
  26. Le C, Kailaivasan K, Chow S, Abdullah Z, Ling S and Fang C: Phytosterols isolated from Clinacanthus nutans induce immunosuppressive activity in murine cells. Int Immunopharmacol 2017; 44: 203-10.
  27. Park M, Cho S, Ahn T, Kim D, Kim S, Lee J, Kim J, Seo E, Son K and Lim J: Immunomodulatory effects of β -sitosterol and Daucosterol isolated from Dioscorea batatas on LPS-stimulated RAW 264.7 and TK-1 cells. J Life Sci 2020; 30: 359-69.
  28. Kim DH, Lee HG and Choi JM: Curcumin elevates Tfh cells and germinal center b cell response for antibody production in mice. Immune Netw2019; 19(5): 1-8.
  29. Wuelina, Meles DK, Mustofa I, Zakaria S and Adnyana DPA: Alkaloid immunomodulatory effects of sambiloto (Andrographis paniculate) On the response of gamma interferon and thelper cell (cd4+). Advances in Natural and Aapplied Sciences 2017; 11(9): 154-8.
  30. Mustofa I, Wurlina, Meles D K, Utama S, susilowati S: Immunostumulator effect of Sambiloto (Andrographis paniculata L) Alkaloid in Rat (Rattus norvegicus). Biotechn Strengthen on Biomedical Science and Veterinary Medicine 2017; 1-8.
  31. Azimah D, Yuswanto, Wahyono, Santosa D and Setyowati EP: Immunomodulator effect of combination of Andrographis paniculata (Burn f.) Nees Herb and Ginger Rhizome (Curcuma xanthorrhiza) Etanolic extract on cell proliferation of Balb/c Mice lymphocytes in-vitro. Trad Med J 2016; 21(3): 157-68.
  32. Palanikani R, Chanthini KMP, Soranam R, Thanigaivel A, Karthi S, Nathan SS and Murugesan AG: Efficacy of Andrographis paniculata supplements induce a non-specific immune system against the pathogenicityof Aeromonas hydrophila infection in Indian major carp (Labeorohita). Environ SciPollut Res 2020; 27: 23420-36.
  33. Alkandahri MY, Subarnas A and Berbudi A: Review: Aktivitas Immunomodulator TanamanS ambiloto (Andrographis paniculata Nees). Farmaka 2018; 16(3): 16-9.
  34. Nie X, Chen SR, Wang K, Peng Y, Wang YT and Wang D: Attenuation of innate immunity by Andrographolide derivatives through NF-kB signaling pathway. Scientific Eeports 2017; 7: 4738.
  35. Qadir MMF, Bhatti A, Ashraf MU, Sandhu MA, Anjum S and John P: Immunomodulatory and therapeutic role of Cinnamomum verum extracts in collagen-induced arthritic BALB/c mice. Inflammopharmacol2017;
  36. Dibazar SP, Fateh S and Daneshmandi S: Immuno-modulatory effects of clove (Syzygium aromaticum) constituents on macrophages: In-vitro evaluations of aqueous and ethanolic components. J Immunotoxicol 2015; 12(2): 124–3.
  37. Bao XL: Polysaccharides from Cymbopogon citratus with antitumor and immunomodulatory activity. Pharm Biol 2015; 53(1): 117-24.
  38. Singh R and Singh K: Zingiber officinale: A Spice With Multiple Roles. RJLBPCS 2019; 5(2): 117.
  39. Peterfalvi A, Miko E, Nagy T, Reger B, Simon D and Miseta A: Much more than a pleasant scent: A review on essential oils supporting the immune system. Molecules 2019; 24(4530): 1-16.
  40. Thangadurai K, Savitha R, Rengasundari S, Suresh K and Banumathi: Immunomodulatory action of traditional herbs for the management of acquired immunodeficiency syndrome: A review. Internat J of Herb Med 2018; 6(6): 10-4.
  41. Afolayan FID, Erinwusi B and Oyeyemi OT: Immuno-modulatory activity of curcumin-entrapped poly d,l-lactic-co-glycolic acid nanoparticles in mice. Integrative Medicine Research 2018; 7(2): 168-75.
  42. Alagawany M, Ashour EA and Reda FM: Effect of dietary supplementation of garlic (Allium sativum)and turmeric (Curcuma Longa) on growth performance, carcass traits, blood profile and oxidative status in growing rabbits. Ann Anim Sci 2016; 16: 489-05.
  43. Catanzaro M, Corsini E, Rosini M, Racchi M and Lanni C: Immunomodulators Inspired by nature: a Review on Curcumin and Echinacea. Molecules 2018; 23(2778): 1-17.
  44. Putri DU, Rintiswati N, Soesatyo MHNE and Haryana SM: Immune modulation properties of herbal plant leaves: Phyllanthus niruri aqueous extract on immune cells of tuberculosis patient – in-vitro Natural Product Res 2018; 32(4): 463-67.
  45. Hutomo S, Putri DU, Suryanto YI and Susilowati H: Potential immunomodulatory activity of Phyllanthus niruri aqueous extract on macrophage infected with Streptococcus sanguinis. Dent J 2018; 51(3): 124–8.
  46. Muthulakshmi M, Subramani PA and Michael RD: Immunostimulatory effect of the aqueous leaf extract of Phyllanthus niruri on the specific and nonspecific immune responses of Oreochromis mossambicus Iran J Vet Res 2016; 17(3): 200-2.
  47. Laily N, Kusumaningtyas RW, Sukarti L and Rini MRDK: The Potency of Psidium guajava (L.) Leaves as a Functional Immunostimulatory Ingredient. Procedia Chemistry 2015; 14: 301-7.
  48. Shabbir A, Butt HI, Shahzad M, Arshad HM and Waheed I: Immunostimulatory effect o methanolic leaves extract of Psidium guajava (Guava) on humoral and cell-mediated immunity in mice. The J Anim Plant SCi 2016; 26(5): 1492-8.
  49. Hoseinifar SH, Sohrabi A, Paknejad H, Jafari V, Paolucci M and Doan HV: Enrichment of common carp (Cyprinus carpio) fingerlings diet with Psidium guajava: The effects on cutaneous mucosal and serum immune parameters and immune related genes expression. Fish and Shellfish Immunology 2019; 86: 688-94.
  50. Asfi N and Djati MS: Perkembangansel T CD4 dan CD62L pada Organ Spleen Mencit yang diinfeksiSalmonella typhimurium setelah pemberian Ekstrak Ethanol Daun Polyscias obtuse dan Elephantopus scaber. J Biotropika 2014; 2(4): 223-28.
  51. Fadhilah A and Djati MS: Pengaruh Ekstrak Daun Polyscias obtuse dan Elephantopus scaber L TerhadapSel B220+ Dan TER 119+Mencit Balb/C Bunting yang Diinfeksi Bakteri Salmonella thypimurium. Jurnal Biotropika 2014; 2(4): 218-22.
  52. Pradana ARA, Djati MS and Rifai M: Mobilization of CD4+, CD8+, and B220+ on Broiler Chicken Spleen with Feed Contained Polyscias obtusa Post Infection of Salmonella typhimurium. J Exp Life Sci 2013; 3(1):1-5.
  53. Roseno M, Sudaryat Y and Widyastiwi D: Aktivitasimuno modulator ekstraketanol Kemukus (Piper cubeba), Kiseureh (Piper aduncum), dancabejawa (Piper retrofractum) padamencit Jantan Galur Balb/C. JurnalIlmuKefarmasian Indonesia 2019; 17(2): 255-61.
  54. Graidist P, Martla M and Sukpondma Y: Cytotoxic Activity of Piper cubeba Extract in Breast Cancer Cell Lines. Nutrients 2015; 7: 2707–18.
  55. Alsaid M, Mothana R, Raish M, Al-Sohaibani M, Al-Yahya M and Ahmad A: Evaluation of the effectiveness of Piper cubeba extract in the amelioration of CCl4-induced liver injuries and oxidative damage in the rodent model. Biomed Res Int 2015; 1-11.
  56. Nahak G and Sahu RK: Phytochemical Evaluation and Antioxidant activity of Piper cubeba and Piper nigrum. J Appl Pharm Sci 2011; 1(8): 153–7.
  57. Carmelita AB: Effects of orally Bawang Dayak (Eleutherine palmifolia (L.) Merr.) root extract on BALB/c mice against the prevention of the decrease Germinal Center parameters on the lymph gland and IgG serum concentration. J Biosains Pascasarjana 2016; 18: 1-13.
  58. Margono DPNH, Suhartono E and Arwati H. Effects of kelakai (Stenochlaena palustris (Burm.f) Bedd) extract against the level of interleukin-10 (IL10) on mice. Medical Laboratory Technology Journal 2016; 2: 31-6.
  59. Arifah AN and Nurkhasanah: The effect of ethyl acetate fraction of ethanolic extract of pasakbumi (Eurycoma longifolia, Jack) on macrophages phagocytic activity in-vitro, Pharmaciana 2014; 4: 9-14.
  60. Chabib L, Muhtadi WK, Rizki MI, Rahman RA, Suhendri MR and Hidayat A:Potential medicinal plants for improve the immune system from Borneo Island and the prospect to be developed as nanomedicine. MATEC Web of Conferences 2018; 154: 1-6.
  61. Li C, Yan L, Jing Y, Xu L, Liang Y and Wei H: Berberine augments ATP-induced inflammasome activation in macrophages by enhancing AMPK signaling. Oncotarget 2017; 8: 95-109.
  62. Shen P, jiao Y, Miao L, Chen JH and Borojeni AAM: Immunomodulatory effect of berberine on the inflamed joint reveal new therapeutic targets for rheumatoid arthritis management. J Cell Mol Med 2020; 24: 12234-45.
  63. Yin M, Zhang Y and Li H: Advance in reasearch Immunoregulation of Macrophages by Plant Poly-saccharides. Clin Hemorheol Micro 2019; 10: 145.
  64. Surjushe A, Vasani R and Saple DG: Aloe vera: a short review. Indian J Dermatol Let 2008; 53(4): 163-66.
  65. Du S, Liu H, Lei T, Xie X, Wang H and He X: Mangiferin: an effective therapeutic agent against several disorders (Review). Mole Medi Report 2018; 18: 4775-86.
  66. Koshak AE, Yousif NM, Fiebich BL, Koshak E and Heinrich M: Comparative Immunomodulatory activity ofNigella sativa L. Preparations on Proinflammatory Mediators: A focus on asthma. Front Pharm 2018; 9: 1075.
  67. Amin AH, Bughdadi FA, Zaid MAA, Ismail AH, Agamy SAE and Alqahtani A: Immunomodulatory effect of papaya (Carica papaya) pulp and seed extracts as a potential natural treatment for bacterial stress. J Food Biochem 2019; 1-11.
  68. Moutia m, Habti N and Badou A: In-vitro and in-vivo Immunomodulator activities of Allium sativum. Evidence-Basd Complementary and alternative medicine2018; 1–10.
  69. Rad MF, Tappeh KH and Khademvatan S: Antoleishmanial and immunomodulatory activity of Allium sativum (Garlic): A review. J Evidence Based Complementary & Alternative Medicine 2017; 22: 141-55.
  70. Griana TP:Potential effect of pegagan (Centella asiatica (L).Urban) and Widuri (Clotropis gigantean (L)) as immunomodulator. J Food Pharm Sci 2019; 7(2): 55-72.
  71. Rahayu RP, Prasetyo RA, Purwanto DA, Kresnoadi U, Iskandar RPD and Rubianto M: The immunomodulatory effect of green tea (Camellia sinensis) leves extract on immunocompromised wistar rats infected by Candida albicans. Vaterinary World 2018; 11(6): 765-70.
  72. Nayak S and Mengi S: Immunostimulant activity of noni (Morinda citrifolia) on T and B lymphocyte. Pharmaceutical Biology 2010; 48(7): 724-31.
  73. Enejoh OS, Ogunyemi IO, Bala MS, Oruene IS, Suleiman MM and Ambali SF: Ethnomedical Importance of Citrus aurantifolia (Christm) Swingle. IPIJ 2015; 4(8): 1-6.
  74. Zohrameena S, Mujahid M, Bagga P, Khalid M, Nouru H and Nesar A: Medicinal uses and pharmacology activities of Tamarindus indica. World J Pha Sci 2017; 5(2): 121-33.
  75. Librandi APL, Chrysóstomo TN, Azzolini AECS, Recchia CGV, UyemuraSA and Pandochi AIA: Effect of the extract of the tamarind (Tamarindus indica) fruit on the complement system: Studies in-vitro and in hamsters submitted to a cholesterol-enriched diet. Food Chem Toxicol 2007; 45: 1487-95.
  76. Sibi PI and Rahees T: Tinospora cordifolia: a potential plant with immunomodulatory activity. Iranian J Pharmacology & Therapeutic 2013; 12(1): 30-8.
  77. Chouni A and Paul S: A review on Phytochemical and Pharmacological Potential of Alpinia galangal. Pharmacogn J 2018; 10(1): 9-15.
  78. Yang X, Ji H, Feng Y, Yu J and Liu A: Strustural Characterization and antitumor activity of polysaccharides from Kaemferia galangal Oxidative Medicine and Cellular Longevity 2018; 1- 10.
  79. Riset Kesehatan Dasar (Riskesdas) (2018). Badan Penelitiandan Pengembangan Kesehatan Kementerian RI tahun 2018. [Available from https://kesmas.kemkes.go.id /assets/upload/dir_519d41d8cd98f00/files/Hasil-riskesdas-2018_1274.pdf]
  80. Ministry of Health. Permenkes No.003 Year 2010 tentangsaintifikasi Jamu dalam penelitian berbasis pelayan an kesehatan Jakarta 2010
  81. Purwaningsih EH: Jamu, Obat Tradisional Asli Indonesia Pasang Surut P emanfaatannya di Indonesia. JKI 2013; 1(2): 85-9
  82. CNN Indonesia. Rekomendasi Rempah Tradisional untuk Menjaga Daya TahanTubuh. 2020. [Available from: https://www.cnnindonesia.com/gayahidup/20200302205551-255-479914/rekomendasi-rempah-tradisional-untuk-menjaga-daya-tahan-tubuh].

    How to cite this article:

    Sianipar EA: The potential of Indonesian traditional herbal medicine as immunomodulatory agents: A Review:. Int J Pharm Sci & Res 2021; 12(10): 5229-37. doi: 10.13040/IJPSR.0975-8232.12(10).5229-37.

    All © 2021 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.

Article Information

8

5229-5237

582 KB

746

6

English

IJPSR

Erlia Anggrainy Sianipar

Department of Pharmacy, School of Medicine and Health Science, Atma Jaya Catholic University of Indonesia.

erlia.anggarainy@atmajaya.ac.id

04 August 2020

11 February 2021

24 May 2021

10.13040/IJPSR.0975-8232.12(10).5229-37

01 October 2021

Download