Article Sidebar

Submitted
April 12, 2022
Accepted
September 30, 2022
Published
December 30, 2022
Download
PDF (Bahasa Indonesia)
Statistic
Read Counter : 961 Download : 2327

Downloads

Download data is not yet available.

Main Article Content

Abstract

Background: Phyllanthus niruri (meniran) is a medicinal plant with antimicrobial, antioxidant, anticancer, anti-inflammatory, antiplasmodial, antiviral, hepatoprotective diuretic, and immunomodulator properties.


Objective: This review examined the activity, mode of action, and active compounds of P. niruri as an immunomodulator in various preclinical and clinical studies, along with the bioactive compounds and their mechanism.


Results: Flavonoids, lignans, terpenoids, and alkaloids, among other phytochemicals found in P. niruri, play an essential part in the pharmacological activity of the plant. The immunomodulation activity of P. niruri has been extensively researched in preclinical (in silico, in vitro, and in vivo) and clinical trials. A study in silico revealed the potential of P. niruri as an immunomodulator in Covid-19 infection by inhibiting the COVID-19 target receptors spike glycoprotein (6LZG) and major protease (5R7Y and Mpro). In addition, P. niruri boosted macrophage phagocytic activity, increased antibody total, and reduced inflammation in vitro and in vivo experiments. P. niruri also showed immunomodulatory effects in both healthy subjects and patients. 


Conclusion: P. niruri exhibits pharmacological potential as an immunomodulator in preclinical and clinical trials, according to the findings of various investigations.


Keywords: Phyllanthus niruri, immunomodulator, immunostimulant


Intisari 


Latar belakang: Phyllanthus niruri merupakan tanaman obat yang memiliki beberapa aktivitas farmakologi seperti antimikroba, antioksidan, antikanker, antiinflamasi, antiplasmodium, antivirus, diuretik, hepatoprotektif, dan sebagai imunomodulator. 


Tujuan: Melakukan tinjauan analisis mengenai aktivitas, mekanisme, dan senyawa aktif P. niruri sebagai imunomodulator pada uji preklinis maupun uji klinis.


Hasil: Kandungan kimia P. niruri seperti flavonoid, lignan, terpenoid, dan alkaloid berperan penting pada aktivitas farmakologi P. niruri sebagai imunomodulator.  Uji in silico menunjukkan potensi P. niruri sebagai imunomodulator pada infeksi Covid-19 dengan berikatan pada protein spike dan protease yang bertanggungjawab pada replikasi dan pematangan virus. Uji in vitro dan in vivo menunjukkan bahwa P. niruri mampu meningkatkan aktivitas fagositosis dari makrofag, meningkatkan antibodi serum total, dan mengurangi inflamasi. Pengujian klinis membuktikan bahwa P. niruri memiliki aktivitas imunomodulator baik pada subjek uji sehat maupun pada pasien. 


Kesimpulan: P. niruri memiliki aktivitas sebagai imunomodulator baik pada pengujian preklinis maupun klinis. 


Kata kunci : P. niruri, imunomodulator, imunostimulan

Keywords

Phyllanthus niruri immunomodulator immunostimulant

Article Details

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Crossref
Scopus
Google Scholar
Europe PMC

References

  1. Agrawal, P. K., Agrawal, C., & Blunden, G. (2020). Quercetin: Antiviral Significance and Possible COVID-19 Integrative Considerations. Natural Product Communications, 15(12), 1934578X20976293. https://doi.org/10.1177/1934578X20976293
  2. Bagalkotkar, G., Sagineedu, S. R., Saad, M. S., & Stanslas, J. (2006). Phytochemicals from Phyllanthus niruri Linn. and their pharmacological properties: a review. J Pharm Pharmacol, 58(12), 1559-1570. https://doi.org/10.1211/jpp.58.12.0001
  3. Balahbib, A., El Omari, N., Hachlafi, N. E., Lakhdar, F., El Menyiy, N., Salhi, N., Mrabti, H. N., Bakrim, S., Zengin, G., & Bouyahya, A. (2021). Health beneficial and pharmacological properties of p-cymene. Food Chem Toxicol, 153, 112259. https://doi.org/10.1016/j.fct.2021.112259
  4. Baranowska, M., Koziara, Z., Suliborska, K., Chrzanowski, W., Wormstone, I., Namieśnik, J., & Bartoszek, A. (2021). Interactions between polyphenolic antioxidants quercetin and naringenin dictate the distinctive redox-related chemical and biological behaviour of their mixtures. Scientific Reports, 11, 12282. https://doi.org/10.1038/s41598-021-89314-0
  5. Bascones-Martinez, A., Mattila, R., Gomez-Font, R., & Meurman, J. H. (2014). Immunomodulatory drugs: oral and systemic adverse effects. Med Oral Patol Oral Cir Bucal, 19(1), e24-31. https://doi.org/10.4317/medoral.19087
  6. Cealan, A., Coman, R. T., Simon, V., Andras, I., Telecan, T., Coman, I., & Crisan, N. (2019). Evaluation of the efficacy of Phyllanthus niruri standardized extract combined with magnesium and vitamin B6 for the treatment of patients with uncomplicated nephrolithiasis. Med Pharm Rep, 92(2), 153-157. https://doi.org/10.15386/mpr-1246
  7. Comalada, M., Camuesco, D., Sierra, S., Ballester, I., Xaus, J., Gálvez, J., & Zarzuelo, A. (2005). In vivo quercitrin anti-inflammatory effect involves release of quercetin, which inhibits inflammation through down-regulation of the NF-kappaB pathway. Eur J Immunol, 35(2), 584-592. https://doi.org/10.1002/eji.200425778
  8. Das, A., Jawed, J. J., Das, M. C., Parveen, S., Ghosh, C., Majumdar, S., Saha, B., & Bhattacharjee, S. (2021). Lupeol and amphotericin B mediate synergistic anti-leishmanial immunomodulatory effects in Leishmania donovani-infected BALB/c mice. Cytokine, 137, 155319. https://doi.org/10.1016/j.cyto.2020.155319
  9. Del Toro-Arreola, S., Flores-Torales, E., Torres-Lozano, C., Del Toro-Arreola, A., Tostado-Pelayo, K., Guadalupe Ramirez-Dueñas, M., & Daneri-Navarro, A. (2005). Effect of D-limonene on immune response in BALB/c mice with lymphoma. Int Immunopharmacol, 5(5), 829-838. https://doi.org/10.1016/j.intimp.2004.12.012
  10. Eze, C. O., Nworu, C. S., Esimone, C. O., & Okore, V. C. (2014). Immunomodulatory activities of methanol extract of the whole aerial part of Phyllantus niruri L. Journal of Pharmacognosy and Phytotherapy, 6, 41-46.
  11. Formiga, R. D., Alves Júnior, E. B., Vasconcelos, R. C., Guerra, G. C., Antunes de Araújo, A., Carvalho, T. G., Garcia, V. B., de Araújo Junior, R. F., Gadelha, F. A., Vieira, G. C., Sobral, M. V., Barbosa Filho, J. M., Spiller, F., & Batista, L. M. (2020). p-Cymene and Rosmarinic Acid Ameliorate TNBS-Induced Intestinal Inflammation Upkeeping ZO-1 and MUC-2: Role of Antioxidant System and Immunomodulation. International Journal of Molecular Sciences, 21(16). https://doi.org/10.3390/ijms21165870
  12. Han, L., Fu, Q., Deng, C., Luo, L., Xiang, T., & Zhao, H. (2022). Immunomodulatory potential of flavonoids for the treatment of autoimmune diseases and tumour. Scandinavian Journal of Immunology, 95(1), e13106. https://doi.org/https://doi.org/10.1111/sji.13106
  13. Harikrishnan, H., Jantan, I., Haque, M. A., & Kumolosasi, E. (2018). Anti-inflammatory effects of Phyllanthus amarus Schum. & Thonn. through inhibition of NF-κB, MAPK, and PI3K-Akt signaling pathways in LPS-induced human macrophages. BMC Complement Altern Med, 18(1), 224. https://doi.org/10.1186/s12906-018-2289-3
  14. Hosseinzade, A., Sadeghi, O., Naghdipour Biregani, A., Soukhtehzari, S., Brandt, G. S., & Esmaillzadeh, A. (2019). Immunomodulatory Effects of Flavonoids: Possible Induction of T CD4+ Regulatory Cells Through Suppression of mTOR Pathway Signaling Activity. Front Immunol, 10, 51. https://doi.org/10.3389/fimmu.2019.00051
  15. Ilangkovan, M., Jantan, I., Mesaik, M. A., & Bukhari, S. N. (2016). Inhibitory Effects of the Standardized Extract of Phyllanthus amarus on Cellular and Humoral Immune Responses in Balb/C Mice. Phytother Res, 30(8), 1330-1338. https://doi.org/10.1002/ptr.5633
  16. Jantan, I., Haque, M. A., Ilangkovan, M., & Arshad, L. (2019). An Insight Into the Modulatory Effects and Mechanisms of Action of Phyllanthus Species and Their Bioactive Metabolites on the Immune System. Front Pharmacol, 10, 878. https://doi.org/10.3389/fphar.2019.00878
  17. Jeon, J. H., Lee, B. C., Kim, D., Cho, D., & Kim, T. S. (2018). Hydrophilic Astragalin Galactoside Induces T Helper Type 1-Mediated Immune Responses via Dendritic Cells. Int J Mol Sci, 19(10). https://doi.org/10.3390/ijms19103120
  18. Jia, Q., Wang, T., Wang, X., Xu, H., Liu, Y., Wang, Y., Shi, Q., & Liang, Q. (2019). Astragalin Suppresses Inflammatory Responses and Bone Destruction in Mice With Collagen-Induced Arthritis and in Human Fibroblast-Like Synoviocytes. Front Pharmacol, 10, 94. https://doi.org/10.3389/fphar.2019.00094
  19. Kajaria, D., Tripathi, J. S., Tiwari, S. K., & Pandey, B. L. (2013). Immunomodulatory effect of ethanolic extract of Shirishadi compound. Ayu, 34(3), 322-326. https://doi.org/10.4103/0974-8520.123136
  20. Kaur, N., Kaur, B., & Sirhindi, G. (2017). Phytochemistry and Pharmacology of Phyllanthus niruri L.: A Review. Phytother Res, 31(7), 980-1004. https://doi.org/10.1002/ptr.5825
  21. Kim, C. H., Kim, J. E., & Song, Y. J. (2020). Antiviral Activities of Quercetin and Isoquercitrin Against Human Herpesviruses. Molecules, 25(10). https://doi.org/10.3390/molecules25102379
  22. Lappas, C. M., & Lappas, N. T. (2012). d-Limonene modulates T lymphocyte activity and viability. Cellular Immunology, 279(1), 30-41. https://doi.org/https://doi.org/10.1016/j.cellimm.2012.09.002
  23. Lin, Y., Wu, X., Feng, S., Jiang, G., Zhou, S., Vrijmoed, L. L. P., & Jones, E. B. G. (2001). A novel N-cinnamoylcyclopeptide containing an allenic ether from the fungus Xylaria sp. (strain #2508) from the South China Sea. Tetrahedron Letters, 42(3), 449-451. https://doi.org/https://doi.org/10.1016/S0040-4039(00)01948-1
  24. Mao, X., Wu, L. F., Guo, H. L., Chen, W. J., Cui, Y. P., Qi, Q., Li, S., Liang, W. Y., Yang, G. H., Shao, Y. Y., Zhu, D., She, G. M., You, Y., & Zhang, L. Z. (2016). The Genus Phyllanthus: An Ethnopharmacological, Phytochemical, and Pharmacological Review. Evid Based Complement Alternat Med, 2016, 7584952. https://doi.org/10.1155/2016/7584952
  25. Marhaeny, H. D., Widyawaruyanti, A., Widiandani, T., Fuad Hafid, A., & Wahyuni, T. S. (2021). Phyllanthin and hypophyllanthin, the isolated compounds of Phyllanthus niruri inhibit protein receptor of corona virus (COVID-19) through in silico approach. J Basic Clin Physiol Pharmacol, 32(4), 809-815. https://doi.org/10.1515/jbcpp-2020-0473
  26. Mittal, L., Kumari, A., Srivastava, M., Singh, M., & Asthana, S. (2021). Identification of potential molecules against COVID-19 main protease through structure-guided virtual screening approach. J Biomol Struct Dyn, 39(10), 3662-3680. https://doi.org/10.1080/07391102.2020.1768151
  27. Mohan, M., James, P., Valsalan, R., & Nazeem, P. A. (2015). Molecular docking studies of phytochemicals from Phyllanthus niruri against Hepatitis B DNA Polymerase. Bioinformation, 11(9), 426-431. https://doi.org/10.6026/97320630011426
  28. Mulchandani, N. B., & Hassarajani, S. A. (1984). 4-Methoxy-nor-Securinine, a New Alkaloid from Phyllanthus niruri. Planta Med, 50(1), 104-105. https://doi.org/10.1055/s-2007-969635
  29. Murugesan, S., Kottekad, S., Crasta, I., Sreevathsan, S., Usharani, D., Perumal, M. K., & Mudliar, S. N. (2021). Targeting COVID-19 (SARS-CoV-2) main protease through active phytocompounds of ayurvedic medicinal plants - Emblica officinalis (Amla), Phyllanthus niruri Linn. (Bhumi Amla) and Tinospora cordifolia (Giloy) - A molecular docking and simulation study. Comput Biol Med, 136, 104683. https://doi.org/10.1016/j.compbiomed.2021.104683
  30. Nworu, C. S., Akah, P. A., Okoye, F. B., Proksch, P., & Esimone, C. O. (2010). The effects of Phyllanthus niruri aqueous extract on the activation of murine lymphocytes and bone marrow-derived macrophages. Immunol Invest, 39(3), 245-267. https://doi.org/10.3109/08820131003599585
  31. Porto, C. R. C., Soares, L. A. L., Souza, T. P., Petrovick, P. R., Lyra, I. L., Araújo Júnior, R. F., Zucolotto Langassner, S. M., Ferreira, A. A. A., & Guerra, G. C. B. (2013). Anti-inflammatory and antinociceptive activities of Phyllanthus niruri spray-dried standardized extract. Revista Brasileira de Farmacognosia, 23(1), 138-144. https://doi.org/https://doi.org/10.1590/S0102-695X2013005000004
  32. Putri, D. U., Rintiswati, N., Soesatyo, M. H., & Haryana, S. M. (2018). Immune modulation properties of herbal plant leaves: Phyllanthus niruri aqueous extract on immune cells of tuberculosis patient - in vitro study. Nat Prod Res, 32(4), 463-467. https://doi.org/10.1080/14786419.2017.1311888
  33. Ratty, A. K., & Das, N. P. (1988). Effects of flavonoids on nonenzymatic lipid peroxidation: structure-activity relationship. Biochem Med Metab Biol, 39(1), 69-79. https://doi.org/10.1016/0885-4505(88)90060-6
  34. Riaz, A., Rasul, A., Hussain, G., Zahoor, M. K., Jabeen, F., Subhani, Z., Younis, T., Ali, M., Sarfraz, I., & Selamoglu, Z. (2018). Astragalin: A Bioactive Phytochemical with Potential Therapeutic Activities. Adv Pharmacol Sci, 2018, 9794625. https://doi.org/10.1155/2018/9794625
  35. Shukla, R., Pandey, V., Vadnere, G. P., & Lodhi, S. (2019). Role of Flavonoids in Management of Inflammatory Disorders. Bioactive Food as Dietary Interventions for Arthritis and Related Inflammatory Diseases.
  36. Tjandrawinata, R., Susanto, L., & Nofiarny, D. (2017). The use of Phyllanthus niruri L. as an immunomodulator for the treatment of infectious diseases in clinical settings. Asian Pacific Journal of Tropical Disease, 7, 132-140. https://doi.org/10.12980/apjtd.7.2017D6-287
  37. Wahdaningsih, S., Wahyuono, S., Riyanto, S., & Murwanti, R. (2020). Terpenoid-lupeol of red dragon fruit (Hylocereus polyrhizus) and its immunomodulatory activity. Pak J Pharm Sci, 33(2), 505-510.
  38. Yoon, W. J., Lee, N. H., & Hyun, C. G. (2010). Limonene suppresses lipopolysaccharide-induced production of nitric oxide, prostaglandin E2, and pro-inflammatory cytokines in RAW 264.7 macrophages. J Oleo Sci, 59(8), 415-421. https://doi.org/10.5650/jos.59.415
  39. Yuandani, Y., Ilangkovan, M., Jantan, I., Mohamad, H., Husain, K., & Razak, A. (2013). Inhibitory Effects of Standardized Extracts of Phyllanthus amarus and Phyllanthus urinaria and Their Marker Compounds on Phagocytic Activity of Human Neutrophils. Evidence-based complementary and alternative medicine : eCAM, 2013, 603634. https://doi.org/10.1155/2013/603634
  40. Zhang, W., Li, J.-Y., Lan, P., un, P.-H., Wang, Y., Ye, W.-C., & Chen, W.-M. (2011). Chemical synthesis and biological activities of Securinega alkaloids. Journal of Chinese Pharmaceutical Sciences, 20(3), 203-217. http://www.jcps.ac.cn
  41. Zhen, J., Villani, T. S., Guo, Y., Qi, Y., Chin, K., Pan, M.-H., Ho, C.-T., Simon, J. E., & Wu, Q. (2016). Phytochemistry, antioxidant capacity, total phenolic content and anti-inflammatory activity of Hibiscus sabdariffa leaves. Food Chemistry, 190, 673-680. https://doi.org/https://doi.org/10.1016/j.foodchem.2015.06.006
  42. Zhou, J., Xie, G., & Yan, X. (2011). Encyclopedia of Traditional Chinese Medicines - Molecular Structures, Pharmacological Activities, Natural Sources and Applications

Most read articles by the same author(s)