Article | . 2019 Vol. 37, Issue. 1
Evaluation of Cytotoxicity on Human Cancer Cells and Antioxidant and Immune Cell Activities of Codonopsis lanceolata Root Extracts Stored at Different Temperatures and for Different Durations

WELLPHYTO Co. Ltd., BI Center, GIST1
Seoul Center, Korea Basic Science Institute2
Faculty of Food Nutrition and Cookery, Woosong Information College3
Department of Industrial Plant Science & Technology, Chungbuk National University4
Department Horticulture Industry, College of Agriculture and Food Sciences, Wonkwang University5

2019.. 130:139


Codonopsis lanceolata is widely consumed in South Korea; however, its medicinal applications have not been explored in detail. The present study aimed to evaluate the xanthine oxidase (XO) inhibitory activity, reducing power, immune activity, and cytotoxicity of 30% ethanolic extracts of C. lanceolata roots stored at different temperatures (5, 15, 25, 35, and 45°C) and for different storage periods (0, 15, 30, 45, 60, 75, and 90 days). The growth of human T and B cells increased when treated with the root extracts stored at low temperatures for a short period, in a concentration-dependent manner. The XO inhibitory activity of the C. lanceolata roots stored at 5°C and 15°C was higher than for those stored at 45°C. The XO inhibitory activity of the C. lanceolata roots gradually deceased with increasing storage period. The reducing power of the extracts increased significantly in a concentration-dependent manner. Reducing power of the root storage temperature for all temperatures and storage periods using 5 mg·mL-1 extract was higher than that for the other extract concentrations. Cytotoxic activity of C. lanceolata roots on human cancer cell lines (e.g., HeLa, Calu-6, and MCF-7) decreased as storage temperatures decreased from 45°C to 5°C. The cytotoxic effect on the MCF-7 cell line was relatively higher than that on the HeLa and Calu-6 cell lines. The results suggest that the root extract of C. lanceolata can be used to modulate immune response and is also a natural food additive with excellent physiological functionality.

1. Boo HO, Park JH, Kim HG, Kim HY, Kwon SJ, Seo DY, Lee MS (2016) Immune cells activity, nitrite scanvenging and ABTS radical scavenging activities of Codonopsis lanceolata ethanol extracts from districts in Korea. Korean J Plant Res 29:289-296. doi:10.7732/kjpr.2016.29.3.289  

2. Cimanga K, Ying L, De Bruyne T, Apers S, Cos P, Hermans N, Bakana P, Tona L, Kambu K, et al (2001) Radical scavenging and xanthine oxidase inhibitory activity of phenolic compounds from Bridelia ferruginea stem bark. J Pharm Pharmacol 53:757-761. doi:10.1211/0022357011775893  

3. Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, et al (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10:942-949. doi:10.1038/nm1093  

4. Curiel TJ, Wei S, Dong H, Alvarez X, Cheng P, Mottram P, Krzysiek R, Knutson KL, Daniel B, et al (2003) Blockade of B7-H1 improves myeloid dendritic cell–mediated antitumor immunity. Nat Med 9:562–567. doi:10.1038/nm863  

5. Cuyacot AR, Mahilum JJM, Madamba MRSB (2014) Cytotoxicity potentials of some medicinal plants in Mindanao, Philippines. Pelagia Res Libr 4:81-89. doi:10.13140/2.1.3165.4404  

6. Da-Silva JFM, De-Souza MC, Matta SR, De-Andrade MR, Vidal FVN (2006) Correlation analysis between phenolic levels of brazilian propolis extracts and their antimicrobial and antioxidant activities. Food Chem 99:431-435. doi:10.1016/j.foodchem.2005.07.055  

7. Gordon MH (1990) The mechanism of the antioxidant action in vitro. In BJF Hudson, ed, Food Antioxidants. Elsevier, London, UK pp 1–18. doi:10.1007/978-94-009-0753-9_1  

8. Guizani N, Waly MI, Singh V, Rahman MS (2013) Nabag (Zizyphus spina-christi) extract prevents aberrant crypt foci development in colons of azoxymethane-treated rats by abrogating oxidative stress and inducing apoptosis. Asian Pac J Cancer Prev 14:5031-5035. doi:10.7314/APJCP.2013.14.9.5031  

9. Isaykina N, Perevozchicova T, Kalinkina G (2008) Immunotropic activity of plant extract echinosol. Bull Exp Biol. Med 146:223-225. doi:10.1007/s10517-008-0257-5  

10. Janeway CA, Travers P, Walport M, Capra JD (1999) Immunobiology: the immune system in health and disease. Current Biology Publications New York, NY, USA  

11. Joh EH, Lee IA, Han SJ, Chae SJ, Kim DH (2010) Lancemaside A ameliorates colitis by inhibiting NF-kB activation in TNBS-induced colitis mice. Int J Colorectal Dis 25:545–551. doi:10.1007/s00384-009-0858-0  

12. Kintzios E (2006) Terrestrial plant-derived anticancer agents and plant species used in anticancer research. Crit Rev Plant Sci 25:79-113. doi:10.1080/07352680500348824  

13. Lee JY, Hwang WI, Lim ST (2004) Antioxidant and anticancer activities of organic extracts from platycodon grandiflorum De candolle roots. J Ethnopharmacol 93:409-415. doi:10.1016/j.jep.2004.04.017  

14. Li JP, Liang ZM, Yuan Z (2007) Triterpenoid saponins and anti-inflammatory activity of Codonopsis lanceolata. Pharmazie 62:463-466. doi:10.1691/ph.2007.6.6672  

15. Lobo R, Prabhu KS, Shirwaikar A (2009) Curcuma zedoaria Rosc. (white turmeric): a review of its chemical, pharmacological and ethnomedicinal properties. J Pharm Pharmacol 61:13-21. doi:10.1211/jpp.61.01.0003  

16. Majhenic L, Skerget M, Knez Z (2007) Antioxidant and antimicrobial activity of guarana seed extracts. Food Chem 104:1258-1268. doi:10.1016/j.foodchem.2007.01.074  

17. Marja PK, Anu IH, Heikki JV, Jussi-Pekka R, Kalevi P, Tytti SK, Marina H (1999) Antioxidant activity of plant extracts containing phenolic compounds. J Agric Food Chem 47:3954–3962. doi:10.1021/jf990146l  

18. Moon KG, Kim SU, Um IS, Nam JH, Cho YS, Kim YG, Rho IR (2018) Influence of Mulching Materials on Growth and Saponin Content in Codonopsis lanceolate. Hortic Sci Technol 36:1-9. doi:10.12972/kjhst.20180001  

19. Nguten MT, Awale S, Tezuka Y, Tran QL, Watanabe H, Kadota S (2004) Xanthine oxidase inhibitory activity of vietnamese medicinal plants. Biol Pharm Bull 27:1414-1421. doi:10.1248/bpb.27.1414  

20. Noro T, Oda Y, Miyase T, Ueno A, Fukushima S (1983) Inhibitors of xanthine oxidase from the flowers and buds of Daphne genkwa. Chem Pharm Bull 31:3984-3987. doi:10.1248/cpb.31.3984  

21. Oyaizu M (1986) Studies on products of browning reactions: antioxidative activities of products of browning reaction prepared from glucosamine. Jpn J Nutr 44:307–315. doi:10.5264/eiyogakuzashi.44.307   

22. Park HJ, Kim MJ, Ha E, Chung JH (2008) Apoptotic effect of hesperidin through caspase 3 activation in human colon cancer cells, SNU-C4. Phytomedicine 15:147-151. doi:10.1016/j.phymed.2007.07.061  

23. Paul DJ, Laure NB, Guru SK, Khan IA, Ajit SK, Vishwakarma RA, Pierre T (2014) Antiproliferative and antimicrobial activities of alkylbenzoquinone derivatives from Ardisia kivuensis. Pharm Biol 52:392-397. doi:10.3109/13880209.2013.837076.  

24. Pereira JA, Oliveira I, Sousa A, Valentao P, Andrade PB, Ferreira IC, Ferreres F, Bento A, Seabra R, et al (2007) Walnut (Juglans regia L.) leaves: Phenolic compounds, antibacterial activity and antioxidant potential of different cultivars. Food Chem Toxicol 45:2287-2295. doi:10.1016/j.fct.2007.06.004  

25. Pin-Der-Duh X (1998) Antioxidant activity of burdock (Arctium lappa Linne): its scavenging effect on free radical and active oxygen. J Am Oil Chem Soc 75:455–461. doi:10.1007/s11746-998-0248-8  

26. Pulla RK, Kim YJ, Kim MK, Senthil KS, In JG, Yang DC (2008) Isolation of a novel dehydrin gene from Codonopsis lanceolata and analysis of its response to abiotic stresses. BMB Rep 41:338-343. doi:10.5483/BMBRep.2008.41.4.338  

27. Rice-Evans C, Miller NJ, Bolwell GP, Bramley PM, Pridham JB (1995) The relative antioxidant activities of plant-derived polyphenolic flavonoids. Free Radic Res 22:375–383. doi:10.3109/10715769509145649  

28. Sanchez-Moreno C, Larrauri JA, Saura-Calixto F (1999) Free radical scavenging capacity and inhibition of lipid oxidation of wines, grape juices and related polyphenolic constituents. Food Res Int 32:407–412. doi:10.1016/S0963-9969(99)00097-6  

29. Shahidi F, Wanasundara PKJPD (1992) Phenolic antioxidants. Critical Rev Food Sci Nutr 32:67–103. doi:10.1080/10408399209527581  

30. Singleton V, Rossi JA (1965) Colorimetry of total phenolics with phosphomolybdic phosphotungstic acid reagents. Am J Enol Vitic 16:144-158.  

31. Sugihara N, Arakawa T, Ohnishi M, Furuno K (1999) Anti and pro-oxidative effects of flavonoids on metal induced lipid hydroperoxide- dependent lipid peroxidation in cultured hepatocytes loaded with α-linolenic acid. Free Radic Biol Med 27:1313–1323. doi: 10.1016/S0891-5849(99)00167-7  

32. Tilahun S, Park DS, Taye AM, Jeong CS (2017) Effects of storage duration on physicochemical and antioxidant properties of tomato (Lycopersicon esculentum Mill.). Hortic Sci Technol 35:88-97. doi:10.12972/kjhst.20170010  

33. Timmerman JM, Czerwinski DK, Davis TA, Hsu FJ, Benike C, Hao ZM, Taidi B, Rajapaksa R, Caspar CB, et al (2002) Idiotype-pulsed dendritic cell vaccination for B-cell lymphoma: clinical and immune responses in 35 patients. Blood 99:1517-1526. doi:10.1182/ blood.V99.5.1517  

34. Vijayarathna S, Sasidharan S (2012) Cytotoxicity of methanol extracts of Elaeis guineensis on MCF-7 and Vero cell lines. Asian Pac J Trop Biomed 2:826-829. doi:10.1016/S2221-1691(12)60237-8  

35. Wang L, Xu ML, Hu JH, Rasmussen SK, Wang MH (2011) Codonopsis lanceolata extract induces G0/G1 arrest and apoptosis in human colon tumor HT-29 cells – Involvement of ROS generation and polyamine depletion. Food Chem Toxicol 49:149-154. doi:10.1016/ j.fct.2010.10.010  

36. Yan-Wei H, Chun-Yu L, Chong-Min D, Zhang J, Wen-Qian W, Zhen-Lun G (2009) Induction of apoptosis in human hepatocarcinoma SMMC-7721 cells in vitro by flavonoids from Astragalus complanatus. J Ethnopharmacol 123:293-301. doi:10.1016/j.jep.2009.03.016  

37. Zhishen J, Mengcheng T, Jianming W (1999) The determination of flavonoid contents in mulberry and their scavenging effects on superoxide radicals. Food Chem 64:555-559. doi:10.1016/S0308-8146(98)00102-2