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
Article Details
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References
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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.
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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.
- 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
- 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.
- 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
- 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
- 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
- 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
- Zhou, J., Xie, G., & Yan, X. (2011). Encyclopedia of Traditional Chinese Medicines - Molecular Structures, Pharmacological Activities, Natural Sources and Applications
References
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
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
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
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
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
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
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
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
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
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.
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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.
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
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.
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
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
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
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
Zhou, J., Xie, G., & Yan, X. (2011). Encyclopedia of Traditional Chinese Medicines - Molecular Structures, Pharmacological Activities, Natural Sources and Applications