•  
  •  
 

Abstract

Clinacanthus nutans (Acanthaceae), locally known as Sabah snake grass, is popularly taken as prevention as well as treatment for cancer in Malaysia, despite lack of concrete clinical evidence. However, it is crucial to evaluate potential antagonistic, additive, or synergistic interactions that may result from the co-treatment of this plant in chemotherapy. In this study, we demonstrate the drug-herb interaction using combination treatment of C. nutans extracts and cyclophosphamide on the WRL 68 cell line. Materials and Methods: Aqueous and 70% ethanol extract of C. nutans leaves were prepared using decoction and maceration methods. MTT assay was used to test single treatment as well as the combination of C. nutans extract and cyclophosphamide. Phytochemical profiling and flavonoid were identified using HPLC. Results: C. nutans ethanolic extract exhibits low antiproliferative activity. A combination of ethanolic extract of C. nutans and cyclophosphamide at various concentrations resulted in antagonism with combination index values of 1.413, 1.482, and 1.525. Flavonoids identified in the phytochemical profile of both extracts were schaftoside, isoorientin, orientin, and vitexin. High flavonoids level in C. nutans ethanolic extract could potentially interact with metabolic enzymes of the cell line, which might have affected metabolism and activated the cyclophosphamide. The in vitro data suggested that there was a potential for drug-herb interactions, which could negatively affect the chemotherapeutic outcomes. Further investigation should be done in vivo and clinical research model.

References

Alam, A., Ferdosh, S., Ghafoor, K., Hakim, A., Juraimi, A. S., Khatib, A., & Sarker, Z. I. (2016). Clinacanthus nutans : A review of the medicinal uses, pharmacology and phytochemistry. Asian Pacific Journal of Tropical Medicine, 9(4), 402-409.

Al-Manhel, A. J., & Niamah, A. K. (2015). Effect of aqueous and alcoholic plant extracts on inhibition of some types of microbes and causing spoilage of food. Journal of Nutrition & Food Sciences, S5.

Annegowda, H. V., Bhat, R., Min-Tze, L., Karim, A. A., & Mansor, S. M. (2011). Influence of sonication treatments and extraction solvents on the phenolics and antioxidants in star fruits. Journal of Food Science and Technology, 49(4), 510-514.

Aziz, A. & Jack, R. (2015). Total phenolic content and antioxidant activity in Nypa fruticans extracts. Journal of Sustainability Science and Management, 10(1), 87- 91.

Bohlooli, S., Jafari, N., & Jahed, S. (2012). Cytotoxic Effect of freeze-dried extract of Ecballium elaterium fruit on gastric adenocarcinoma (AGS) and esophageal squamous cell carcinoma (KYSE30) cell lines. Journal of Gastrointestinal Cancer,43(4), 579-583.

Cadena-Herrera, D., Lara, J. E., Ramírez-Ibañez, N. D., López-Morales, C. A., Pérez, N. O., Flores-Ortiz, L. F., & Medina-Rivero, E. (2015). Validation of three viable- cell counting methods: Manual, semi-automated, and automated. Biotechnology Reports,7, 9-16.

Chelyn, J. L., Omar, M. H., Yousof, S. A. M., Ranggasamy, R., Wasiman, M. I., and Ismail, Z. (2014). Analysis of flavone C-glycosides in the leaves of Clinacanthus nutans (Burm. f.) Lindau by HPTLC and HPLC-UV/DAD. The Scientific World Journal, 1-6.

Chen, C. S., Lin, J. T., Goss, K. A., He, Y. A., Halpert, J. R., & Waxman, D. J. (2004). Activation of the anticancer prodrugs cyclophosphamide and ifosfamide: identification of cytochrome P450 2B enzymes and site-specific mutants with improved enzyme kinetics. Molecular Pharmacology, 65(5), 1278-1285.

Chikezie, P. C., & Ojiako, O. A. (2015). Herbal Medicine: Yesterday, Today and Tomorrow. Alternative & Integrative Medicine, 04(03).

Chin, J. H., Akowuah, G. A., Sabu, M. C., & Khalivulla, S. I. (2014). Sub-Acute (28 days) toxicity study of methanol leaves extract of Clinacanthus nutans in rats.International Journal of Pharmacy, 4(2), 61-69.

Desai, A., Qazi, G., Ganju, R., El-Tamer, M., Singh, J., Saxena, A., Bedi, Y. S., Taneja, S. & Bhat, H. (2008). Medicinal plants and cancer chemoprevention. Current Drug Metabolism, 9, 581-91.

Emadi, A., Jones, R. J., & Brodsky, R. A. (2009). Cyclophosphamide and cancer: golden anniversary. Nature Reviews Clinical Oncology, 6(11), 638–647.

Fasinu, P. S., Bouic, P. J., & Rosenkranz, B. (2012). An overview of the evidence and mechanisms of herb– drug interactions. Frontiers in Pharmacology, 3, 1-19.

Galanakis, C., Goulas, V., Tsakona, S., Manganaris, G., & Gekas, V. (2013). A knowledge base for the recovery of natural phenols with different solvents. International Journal of Food Properties, 16(2), 382-396.

Hu, Z., Yang, X., Chi, L. H., Yung, C. S.,Wan, W. S. H., Chan, E. & Duan, W. & Koh, H. L., & Zhou, S. (2005). Herb-Drug Interactions: A Literature Review. Drugs. 65. 1239-82.

Kalita, Pallab & Barman, T.K. & Pal, Tapas & Kalita, Ramen. (2013). Estimation of total flavonoids content (TFC) and antioxidant activities of methanolic whole plant extract of Biophytum sensitivum Linn. Journal of Drug Delivery and Therapeutics. 3.

Malta, L. G., Tessaro, E. P., Eberlin, M., Pastore, G. M., & Liu, R. H. (2013). Assessment of antioxidant and antiproliferative activities and the identification of phenolic compounds of exotic Brazilian fruits. Food Research International, 53(1), 417-425.

Meijerman, I., Beijnen, J. H., & Schellens, J. H. (2006). Herb-drug interactions in oncology: focus on mechanisms of induction. The Oncologist, 11(7), 742- 752.

Mokrani, A., & Madani, K. (2016). Effect of solvent, time and temperature on the extraction of phenolic compounds and antioxidant capacity of peach (Prunus persica L.) fruit. Separation and Purification Technology, 162, 68-76.

Ng, C. T., Fong, L. Y., Tan, J. J., Rajab, N. F., Abas, F., Shaari, K., Yong, Y. K. (2018). Water extract of Clinacanthus nutans leaves exhibits in vitro, ex vivo and in vivo anti-angiogenic activities in endothelial cell via suppression of cell proliferation. BMC Complementary and Alternative Medicine, 18(1).

Norfazlina, M. N., Farida Zuraina, M. Y., Rajab, N. F., Mohd Nazip, S., Rumiza, A. R., Suziana Zaila, C. F. & Florinsiah, L. (2014). In vitro cytotoxicity effects of single and combination Nigella sativa and Zingiber zerumbet extracts on human myeloid leukemia (HL60) cells and its mode of cell death. Journal of Applied Pharmaceutical Science, 4(05), 51-55.

Quah, S. Y., Chin, J. H., Akowuah, G. A., Khalivulla, S. I., Yeong, S. W., & Sabu, M. C. (2017). Cytotoxicity and cytochrome P450 inhibitory activities of Clinacanthus nutans. Drug Metabolism and Personalized Therapy, 32(1).

Raja-Lexshimi, R. G., Oranye, N. O., Ho, S. E., Zuraida, J., & Zulkifli, S. Z. (2013). Complementary and alternative medicine use among breast cancer patients in a tertiary hospital in Malaysia. Malaysian Journal of Public Health Medicine, 13(1), 11–19.

Sakdarat, S., Shuyprom, A., Pientong, C., Ekalaksananan, T., & Thongchai, S. (2009). Bioactive constituents from the leaves of Clinacanthus nutans Lindau. Bioorganic & Medicinal Chemistry, 17(5), 1857-1860.

Say, A., Ayar, A., & Çakir, D. (217). Interaction Between Grapefruit Juice and Drugs. Acta Physica Polonica A, 132(3-II), 1030-1031.

Sharma, K., Ko, E. Y., Assefa, A. D., Ha, S., Nile, S. H., Lee, E. T., & Park, S. W. (2015). Temperature-dependent studies on the total phenolics, flavonoids, antioxidant activities, and sugar content in six onion varieties. Journal of Food and Drug Analysis, 23(2), 243–252.

Su, M., Yu, T., Zhang, H., Wu, Y., Wang, X., & Li, G. (2016). The antiapoptosis effect of glycyrrhizate on HepG2 cells induced by hydrogen peroxide. Oxidative Medicine and Cellular Longevity, 1-9.

Tauchen, J., Bortl, L., Huml, L., Miksatkova, P., Doskocil, I., Marsik, P., & Kokoska, L. (2016). Phenolic composition, antioxidant and antiproliferative activities of edible and medicinal plants from the Peruvian Amazon. Revista Brasileira De Farmacognosia, 26(6), 728-737.

Vuong, Q., Hirun, S., Phillips, P., Chuen, T., Bowyer, M., Goldsmith, C., & Scarlett, C. (2014). Fruit- derived phenolic compounds and pancreatic cancer: perspectives from Australian native fruits. Journal of Ethnopharmacology, 152(2), 227-242.

Wargovich, M. J., Hollis, D. M., & Zander, M. E. (2001). Herbals and Cancer Prevention. Functional Foods & Nutraceuticals in Cancer Prevention, 237-262.

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.