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Polyherbal Effect Between Phyllanthus Urinaria and Curcuma Longa as an Anticancer and Antioxidant


Affiliations
1 Doctoral Program, Biology Department, Science and Mathematics Faculty, Brawijaya University, Malang,, Indonesia
2 Biology Department, Science and Mathematics Faculty, Brawijaya University, Malang,, Indonesia
     

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A combination of herbals medicines is an alternative treatment choice for developing anticancer therapy because of its benefits, active compounds, and non-toxic side effect. This study investigates the anticancer and antioxidant activity of Phyllanthus urinaria and Curcuma longa water extract combination. The analysis of their bio-active components was done using LC-HRMS. The biological activity prediction was made using PassOnline and Cytoscape. Anticancer activity, apoptosis, and cell cycle assay were tested on treated T47D breast cancer cells line with the combination herbal extract and individual herbal extract compare to the untreated and cisplatin-treated control cells. This study also determined the antioxidant activity and phenolic and flavonoid total assay. The result showed that these herbs' compounds were predicted to have a biological function in cancer treatment. The herbal combination has efficiency inducing apoptosis with more than 50% compared to the individual herbal treatment and untreated control cells. Cell cycle analysis shows these herbals affect cell cycle arrest at G2/M phase compared to the control cells. The antioxidant activity and total phenol and flavonoid of P. urinaria and C. longa combination positively correlate with the anticancer activity result. Compusyn test results on cell toxicity parameters showed that the combination of both herbs had an additive effect (C = 1). Although this combination has no synergism effect, the water extract of P. urinaria and C. longa combination can be an anticancer agent.

Keywords

Additive effect; Anticancer; Antioxidant activity; Curcuma longa; Herbal formulation; In silico; In vitro; Phyllanthus urinaria.
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  • Elfahmi, Woerdenbag HJ and Kayser O. Jamu: Indonesian traditional herbal medicine towards rational phytopharmacological use. Journal of Herbal Medicine. 2014;4(2):51-73.

  • Sumarni W, Sudarmin S and Sumarti SS. The scientification of jamu: a study of Indonesian's traditional medicine. Journal Physic: Conference Series. 2019;1321:032057.

  • Tao L, Zhu F, Qin C, et al. Nature's contribution to today's pharmacopeia. Nature Biotechnology. 2014;32(10):979-980.

  • Rajendran R, Hemachander R, Ezhilarasan T, et al. Phytochemical analysis and in-vitro antioxidant activity of Mimosa pudica Lin., leaves. Research Journal of Pharmacy and Technology. 2010;3(2):551-555.

  • Harvey AL, Edrada-Ebel R and Quinn RJ. The re-emergence of natural products for drug discovery in the genomics era. Nature Review Drug Discovercy. 2015;14(2):111-129.

  • Mukesh KDJ, Sonia K, Madhan R, et al. Antiyeast, Antioxidant and anticancer activity of Tribulus terrestris Linn and Bougainvillea spectabilis Linn. Research Journal of Pharmacy and Technology. 2011;4(9):1483-1489.

  • Geethangili M and Ding S-T. A review of the phytochemistry and pharmacology of Phyllanthus urinaria L. Front Pharmacology. 2018;9:1109.

  • Mao X, Wu L-F, Guo H-L, et al. The genus phyllanthus: An ethnopharmacological, phytochemical, and pharmacological review. Evidence-Based Complementary and Alternative Medicine.

  • Tanvir EM, Hossen MS, Hossain MF, et al. Antioxidant properties of popular turmeric (Curcuma longa) varieties from bangladesh. Journal of Food Quality. https://doi.org/10.1155/2017/8471785

  • Omosa LK, Midiwo JO, Kuete V. Chapter 19 - Curcuma longa. In: Kuete V. Medicinal spices and vegetables from Africa. Academic Press; 2017:425-435.

  • Gupta SC, Sung B, Kim JH, et al. Multitargeting by turmeric, the golden spice: From kitchen to clinic. Molecular Nutrition and Food Research. 2013;57(9):1510-1528.

  • Chou TC. Drug Combination studies and their synergy quantification using the Chou-Talalay Method. Cancer Reserach. 2010;70(2):440-446.

  • Zhou X, Seto SW, Chang D, et al. Synergistic Effects of chinese herbal medicine: a comprehensive review of methodology and current research. Front Pharmacology. 2016;7.

  • Raju DC, Victoria TD, Biji N, et al. Evaluation of antioxidant potential of ethanolic extract of Centella asiatica L. Research Journal of Pharmacy and Technology. 2015;8(9):1289-1293.

  • Kirtawade R, Salve P, Kulkarni A, et al. Herbal antioxidant: Vitamin C. Research Journal of Pharmacy and Technology. 2010;3(1):58-61.

  • Kanagavalli M and Anuradha R. A study on phytochemical constituents and in vitro antioxidant activity of Carica papaya. Research Journal of Pharmacy and Technology. 2012;5(1):119-120.

  • Gahlot K, Lal VK and Jha S. Total phenolic content, flavonoid content and In vitro antioxidant activities of Flemingia species (Flemingia chappar, Flemingia macrophylla and Flemingia strobilifera). Research Journal of Pharmacy and Technology. 2013;6(5):516-523.

  • Kumar T and Jain V. Phytochemical Screening, Phenolic, Flavonoids, Carotenoids contents and antioxidant activity of Folkloric Memecylon edule roxb. Research Journal of Pharmacy and Technology. 2016;9(10):1547-1551.

  • Pagare MS, Joshi H, Patil L, et al. Human milk: excellent anticancer alternative. Research Journal of Pharmacy and Technology. 2012;5(1):14-19.

  • Saha D, Mridha D, Mondal S, et al. Organoselenium as a cancer chemopreventive agent against carcinogenesis. Research Journal of Pharmacy and Technology. 2011;4(3):367-368.

  • Vemuri SK, Banala RR, Subbaiah GPV, et al. Anticancer potential of a mix of natural extracts of turmeric, ginger and garlic: A cell-based study. Egyptian Journal of Basic and Applied Sciences. 2017;4(4):332-344.

  • Filimonov DA, Rudik AV, Dmitriev AV, et al. Computer-aided estimation of biological activity profiles of drug-like compounds taking into account their metabolism in human body. International Journal of Molecular Sciences. 2020;21(20):7492.

  • Doncheva NT, Morris JH, Gorodkin J, et al. Cytoscape stringapp: network analysis and visualization of proteomics data. Journal of Proteome Research. 2019;18(2):623-632.

  • Melakhessou MA, Benkiki N and Marref SE. Determination of antioxidant capacity, flavonoids and total phenolic content of extracts from Atractylis flava Desf. Research Journal of Pharmacy and Technology. 2018;11(12):5221-5228.

  • Du G, Xiao M, Yu S, et al. Phyllanthus urinaria: a potential phytopharmacological source of natural medicine. International Journal of Clinical Experimental Medicine 2018;11(7):6509-6520

  • Deepika MS, Thangam R, Sheena TS, et al. A novel rutin-fucoidan complex based phytotherapy for cervical cancer through achieving enhanced bioavailability and cancer cell apoptosis. Biomedicine and Pharmacotherapy. 2019;109:1181-1195.

  • Yan X, Hao Y, Chen S, et al. Rutin induces apoptosis via P53 up-regulation in human glioma CHME cells. Translational Cancer Research. 2019;8(5):2005-2013-2013.

  • Fang S-H, Rao YK and Tzeng Y-M. Antioxidant and inflammatory mediator's growth inhibitory effects of compounds isolated from Phyllanthus urinaria. Journal of Ethnopharmacology. 2008;116(2):333-340.

  • Jeong J-H, An JY, Kwon YT, et al. Effects of low dose quercetin: Cancer cell-specific inhibition of cell cycle progression. Journal of Cell Biochemistry. 2009 Jan 1; 106(1): 73–82.

  • Gibellini L, Pinti M, Nasi M, et al. Quercetin and cancer chemoprevention. Evidence-Based Complementary and Alternative Medicine. 2011;2011:1-15.

  • Hashemzaei M, Far AD, Yari A, et al. Anticancer and apoptosis-inducing effects of Quercetin in vitro and in vivo. Oncology Reports. 2017;38(2):819-828.

  • Jantan I, Haque MdA, Ilangkovan M, et al. An insight into the modulatory effects and mechanisms of action of phyllanthus species and their bioactive metabolites on the immune system. Front Pharmacology. 2019;10:878.

  • Gupta A, Singh AK, Kumar R, et al. Corilagin in cancer: a critical evaluation of anticancer activities and molecular mechanisms. Molecules. 2019;24(18): 3399.

  • Chen Q, Li P, Li P, et al. Isoquercitrin inhibits the progression of pancreatic cancer in vivo and in vitro by regulating opioid receptors and the mitogen-activated protein kinase signalling pathway. Oncology Reports. 2015;33(2):840-848.

  • Lee W-H, Loo C-Y, Bebawy M, et al. Curcumin and its derivatives: their application in neuropharmacology and neuroscience in the 21st century. Current Neuropharmacology. 2013;11(4):338-378.

  • Abdel-Lateef E, Mahmoud F, Hammam O, et al. Bioactive chemical constituents of Curcuma longa L. rhizomes extract inhibit the growth of human hepatoma cell line (HepG2). Acta Pharmaceutica. 2016;66(3):387-398.

  • Ji M, Choi J, Lee J, et al. Induction of apoptosis by ar-turmerone on various cell lines. International Journal of Molecular Medicine. 2004;14(2):253-256.

  • Gao J, Yu H, Guo W, et al. The anticancer effects of ferulic acid is associated with induction of cell cycle arrest and autophagy in cervical cancer cells. Cancer Cell International. 2018;18(1):102.

  • Naz H, Tarique M, Khan P, et al. Evidence of vanillin binding to CAMKIV explains the anticancer mechanism in human hepatic carcinoma and neuroblastoma cells. Molecular Cell Biochemistry. 2018;438(1):35-45.

  • Kuhn M, von Mering C, Campillos M, et al. STITCH: interaction networks of chemicals and proteins. Nucleic Acids Research. 2007;36:D684-D688.

  • Wang D, Xia D, DuBois RN. The crosstalk of PTGS2 and EGF signaling pathways in colorectal cancer. Cancers (Basel). 2011;3(4):3894–3908.

  • Perk AA, Shatynska-Mytsyk I, Gerçek YC, et al. Rutin mediated targeting of signaling machinery in cancer cells. Cancer Cell International. 2014;14(1):124.

  • Starok M, Preira P, Vayssade M, et al. EGFR inhibition by curcumin in cancer cells: a dual mode of action. Biomacromolecules. 2015;16(5):1634-1642.

  • Jung JH, Lee JO, Kim JH, et al. Quercetin suppresses HeLa cell viability via AMPK-induced HSP70 and EGFR down-regulation. Journal of Cellular Physiology. 2010;223(2):408-414.

  • Podkalicka P, Mucha O, Józkowicz A, et al. Heme oxygenase inhibition in cancers: possible tools and targets. Contemp Oncol (Pozn). 2018;2018(1):23-32.

  • Shan Y-S, Hsu H-P, Lai M-D, et al. Cyclin D1 overexpression correlates with poor tumor differentiation and prognosis in gastric cancer. Oncology Letters. 2017;14(4):4517-4526.

  • Zhang Q, Lei L and Jing D. Knockdown of SERPINE1 reverses resistance of triple‑negative breast cancer to paclitaxel via suppression of VEGFA. Oncology Reports. 2020;44(5):1875-1884.

  • Slattery ML, Lundgreen A and Wolff RK. Dietary influence on MAPK-signaling pathways and risk of colon and rectal cancer. Nutrition Cancer. 2013;65(5):729-738.

  • Ma J, Qin L and Li X. Role of STAT3 signaling pathway in breast cancer. Cell Communication Signal. 2020;18(1):33.

  • Baity M, Wang L, Correa AM, et al. Glutathione reductase (GSR) gene deletion and chromosome 8 aneuploidy in primary lung cancers detected by fluorescence in situ hybridization. American Journal of Cancer Reserach. 2019;9(6):1201–1211.

  • Zhang J, Guo S, Wu Y, et al. P4HB, a novel hypoxia target gene related to gastric. BioMed Research International. 2019. https://doi.org/10.1155/2019/9749751

  • Alsubait A, Aldossary W, Rashid M, et al. CYP1B1 gene: Implications in glaucoma and cancer. Journal of Cancer. 2020;11(16):4652-4661.

  • Dozmorov MG, Azzarello JT, Wren JD, et al. Elevated AKR1C3 expression promotes prostate cancer cell survival and prostate cell-mediated endothelial cell tube formation: implications for prostate cancer progressioan. BMC Cancer. 2010;10(1):672.

  • Poh AR, O'Donoghue RJJ, Ernst M. Hematopoietic cell kinase (HCK) as a therapeutic target in immune and cancer cells. Oncotarget. 2015;6(18):15752-15771.

  • Xiang W, Yang C-Y and Bai L. MCL-1 inhibition in cancer treatment. Oncology Targets Therapy. 2018;11:7301-7314.

  • Frank AK, Pietsch EC, Dumont P, et al. Wild-type and mutant p53 proteins interact with mitochondrial caspase-3. Cancer Biology Therapy. 2011;11(8):740–745.

  • Grigalius I and Petrikaite V. Relationship between antioxidant and anticancer activity of trihydroxyflavones. Molecules. 2017;22(12).

  • Florea AM and Büsselberg D. Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects. Cancers. 2011;3(1):1351.

  • Hu S, Xu Y, Meng L, et al. curcumin inhibits proliferation and promotes apoptosis of breast cancer cells. Experimental Therapy Medicine. 2018;16(2):1266-1272

  • Foucquier J and Guedj M. Analysis of drug combinations: current methodological landscape. Pharmacology Research and Perspectives. 2015;3(3):e00149.


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  • Polyherbal Effect Between Phyllanthus Urinaria and Curcuma Longa as an Anticancer and Antioxidant

Abstract Views: 156  |  PDF Views: 0

Authors

Sapti Puspitarini
Doctoral Program, Biology Department, Science and Mathematics Faculty, Brawijaya University, Malang,, Indonesia
Nashi Widodo
Biology Department, Science and Mathematics Faculty, Brawijaya University, Malang,, Indonesia
Sri Widyarti
Biology Department, Science and Mathematics Faculty, Brawijaya University, Malang,, Indonesia
Yoga Dwi Jatmiko
Biology Department, Science and Mathematics Faculty, Brawijaya University, Malang,, Indonesia
Muhaimin Rifa’i
Biology Department, Science and Mathematics Faculty, Brawijaya University, Malang,, Indonesia

Abstract


A combination of herbals medicines is an alternative treatment choice for developing anticancer therapy because of its benefits, active compounds, and non-toxic side effect. This study investigates the anticancer and antioxidant activity of Phyllanthus urinaria and Curcuma longa water extract combination. The analysis of their bio-active components was done using LC-HRMS. The biological activity prediction was made using PassOnline and Cytoscape. Anticancer activity, apoptosis, and cell cycle assay were tested on treated T47D breast cancer cells line with the combination herbal extract and individual herbal extract compare to the untreated and cisplatin-treated control cells. This study also determined the antioxidant activity and phenolic and flavonoid total assay. The result showed that these herbs' compounds were predicted to have a biological function in cancer treatment. The herbal combination has efficiency inducing apoptosis with more than 50% compared to the individual herbal treatment and untreated control cells. Cell cycle analysis shows these herbals affect cell cycle arrest at G2/M phase compared to the control cells. The antioxidant activity and total phenol and flavonoid of P. urinaria and C. longa combination positively correlate with the anticancer activity result. Compusyn test results on cell toxicity parameters showed that the combination of both herbs had an additive effect (C = 1). Although this combination has no synergism effect, the water extract of P. urinaria and C. longa combination can be an anticancer agent.

Keywords


Additive effect; Anticancer; Antioxidant activity; Curcuma longa; Herbal formulation; In silico; In vitro; Phyllanthus urinaria.

References