Enhancement of Anticancer Activities of Ephedra sinica Stapf Extracts by Nano-encapsulation

마황 추출물의 나노 입자화를 통한 항암 활성 증진

  • Received : 2010.04.03
  • Accepted : 2010.05.26
  • Published : 2010.06.30

Abstract

This study showed the increase of antitumor activities of water soluble E. sinica extract by nano-encapsulation process with lecithin. Five groups of lecithin only group (LO), lecithin nano-encapsulated E. sinica group (LE), E. sinica only group (EO), one negative control group (NCO) and positive control group (PCO) were set for several anticancer experiment and fed into Sarcoma-180 injected mice. The cytotoxicity of LE on the human normal kidney cell (HEK293) showed 14.8% lower than 19.2% of EO and 18.4% of LO. Growth of human liver carcinoma cell and human stomach carcinoma cell as representative of digestive system in vitro was inhibited up to about 85.1% and 87.3%, in adding 1.0 mg/$m{\ell}$ of LE, which values 15% higher than that from conventional EO. The survival rates of each mice group were 40%, 63%, 48%, 33% and 100%, respectively after 40 days of injecting Sarcoma-180. The increment of their body weights of the extract feeding groups was suppressed down to 10~15%, compared to the negative control. The nano-particles also reduced the hypertrophy of the internal organs such as spleen and liver down to 15~20%, compared to those as the other groups. Among them, LE effectively reduced the size of tumor form to 20%. From these results, in vitro and in vivo antitumor activities of E. sinica could be enhanced by using nano-encapsulation process with lecithin because of better permeation into the cancer cells by confocal observations.

Keywords

References

  1. Antina S, Kumar S, Bohidar HB and Antina KV. (2005). Effect of molecular weight heterogeneity on drug encapsulation efficiency of gelatin nano-particles. Colloids and Surfaces B. 45:42-48. https://doi.org/10.1016/j.colsurfb.2005.07.005
  2. Bárdos G, Móricz K, Jaszlits L, Rabloczky G, Tory K, Rácz I, Bernáth S, Sümegi B, Farkas B, Literáti-Nagy B and Literáti-Nagy P. (2003). BGP-15, a hydroximic acid derivative, protects against cisplatin- or taxol-induced peripheral neuropathy in rats. Toxicology and Applied Pharmacology. 190:9-16. https://doi.org/10.1016/S0041-008X(03)00155-8
  3. Deventer K, Thuyne WV, Mikulcíková P, Eenoo PV and Delbeke FT. (2007). Detection of selected stimulants as contaminants in solid nutritional supplements by liquid chromatography-mass spectrometry. Food Chemistry. 103:1508- 1513. https://doi.org/10.1016/j.foodchem.2006.09.015
  4. Dol R and Peto R. (1981). The causes of cancer; Quantitative estimates of avoidable risks of cancer in the Unitede States today. Journal of the National Cancer Institute. 66:1192-1308. https://doi.org/10.1093/jnci/66.6.1192
  5. Fallouh NA, Treupel LR, Fessi H, Devissaguet J and Puisieux F. (1986). Development of a new process for the manufacture of polyisobutylcyanoacrylate nanocapsules. International Journal of Pharmaceutics. 28:125-132. https://doi.org/10.1016/0378-5173(86)90236-X
  6. Ha JH, Kim Y, Kim SS, Jeong MH, Jeong HS, Jeong JH, Yu KW and Lee HY. (2009). High pressure extraction process of low quality fresh ginseng for enhancing anticancer activities. Korean Journal of Medicinal Crop Science. 17:397-406.
  7. Han JG, Kwon MC, Ha JH, Jeong HS, Kim Y, Jeong MH, Kim JC and Lee HY. (2009). Enhancement of immuno modulatory activities of Rubus coreanus Miquel extracts by nano-encapsulation process. Korean Journal of Medicinal Crop Science. 17:54-60.
  8. Jagetia G.C. and Nayak V. (1996). Treatment of mice with a novel antineoplastic agent taxol before irradiation increases the frequency of micronuclei in the bone marrow. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 349:219-227. https://doi.org/10.1016/0027-5107(95)00181-6
  9. Jeong HS, Han JG, Ha JH, Kim Y, Oh SH, Kim SS, Jeong MH, Choi GP, Park UK and Lee HY. (2009). Enhancement of anticancer activities of Ephedra sinica, Angelica gigas by ultra high pressure extraction. Korean Journal of Medicinal Crop Science. 17:102-108.
  10. Jeong HS, Han JG, Ha JH, Kim Y, Oh SH, Kim SS, Jeong MH, Choi GP, Park UK and Lee HY. (2009). Antioxidant activities and skin-whitening effects of nano-encapsuled water extract from Rubus coreanus Miquel. Korean Journal of Medicinal Crop Science. 17:83-89.
  11. Ji LL, Chen Y and Wang ZT. (2008). The toxic effect of pyrrolizidine alkaloid clivorine on the human embryonic kidney 293 cells and its primary mechanism. Experimental and Toxicologic Pathology. 60:87-93. https://doi.org/10.1016/j.etp.2007.11.010
  12. Jin WY, Bu X, Philips D, Yan H, Liu G, Chen X, Bush JA and Li G. (2008). Antitumor activity of health food-C22. Korean Journal of Pharmacognosy. 39:237-240.
  13. Jung KO, Lee KY, Rhee SK and Park KY. (2002). Effect of various kinds of salt on the tumor formation, NK cell activity and lipid peroxidation in Sarcoma-180 cell transplanted mice. Journal of Korean Association of Cancer Prevention. 7:134-142.
  14. Kim DM and Kwak HS. (2004). Nano food materials and approchable development of nanofunctional dairy products. Korean Journal of Dairy Technology Science. 22:1-12.
  15. Kim HT, Kim JW, Jin TW, Kim JE, Lim MK, Yeo SG, Jang KH, Oh TH and Lee KW. (2007). Effects of blood biochemistry and tumor' weights of Artemisia capollaris methanol extract in mice bearing cancer cells. Journal of Veterinary Clinics. 24:372-378.
  16. Kim IC. (2008). Antioxidative properties and whitening effects of the Polygoni multiflori Radix, Polygonati rhizoma and Ephedrae herba. Journal of the Korean Oil Chemists Society. 25:533-538.
  17. Kim SY and Lee YM. (2001). Taxol-loaded block copolymer nanospheres composed of methoxy poly(ethylene glycol) and poly(-caprolactone) as novel anticancer drug carriers. Biomaterials. 22:1697-1704. https://doi.org/10.1016/S0142-9612(00)00292-1
  18. Lee GY, Kenny PA, Lee EH and Bissell MJ. (2007). Threedimensional culture models of normal and malignant breast epithelial cells. Nature Methods. 4:359-365. https://doi.org/10.1038/nmeth1015
  19. Lee JI and Yoo HS. (2008). Preparation and application of nano drug delivery system. Polymer Science and Technology. 19:146-151.
  20. Lee SC, Park SJ, Seo SW, Hwang SW, Kim YW, Song DS, Chae YS, Shin MK and Song HJ. (2005). Effect of Herba ephedrae on airway hyperreactivity. Korean Journal of Herbology. 20:69-76.
  21. Li DC, Zhong XK, Zeng ZP, Jiang JG, Li L, Zhao MM, Yang XQ, Chen J, Zhang BS, Zhao QZ, Xie MY, Xiong H, Deng ZY, Zhang XM, Xu SY and Gao YX, (2009). Application of targeted drug delivery system in Chinese medicine. Journal of Controlled Release. 138:103-112. https://doi.org/10.1016/j.jconrel.2009.05.008
  22. Lochner N, Pittner F, Wirth M and Gabor F. (2003). Preparation, characterization and application of artificial Caco-2 cell surfaces in the silver nanoparticle enhanced fluorescence technique. Journal of Controlled Release. 89:249-259. https://doi.org/10.1016/S0168-3659(03)00102-0
  23. Ma P, Liu S, Huang Y, Chen X, Zhang L and Jing X. (2010). Lactose mediated liver-targeting effect observed by ex vivo imaging technology. Biomaterials. 31:2646-2654. https://doi.org/10.1016/j.biomaterials.2009.12.019
  24. Marchei E, Pellegrini M, Pacifici R, Zuccaro P and Pichini S. (2006). A rapid and simple procedure for the determination of ephedrine alkaloids in dietary supplements by gas chromatography-mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis. 41:1633-1641. https://doi.org/10.1016/j.jpba.2006.02.043
  25. Mertins O, Sebben M, Pohlmann AR and Silveira NP. (2005). Production of soybean phosphatidylcholine-chitosan nanovesicles by reverse phase evaporation: a step by step study. Chemistry and Physics of Lipids. 138:29-37. https://doi.org/10.1016/j.chemphyslip.2005.07.004
  26. Parag A, Jennifer BH, Christopher BM, Marina AD and Scott EM. (2009). Nanoparticle interaction with plasma proteins as it relates to particle biodistribution, biocompatibility and therapeutic efficacy. Advanced Drug Delivery Reviews. 61:428-437. https://doi.org/10.1016/j.addr.2009.03.009
  27. Park JH, Lee HS, Mun HC, Kim DH, Seong NS, Jung HG, Bang JK and Lee HY. (2004). Improvement of anticancer activation of ultrasonificated extracts from Acanthopanax senticosus Harms, Ephedra sinica Stapf, Rubus coreanus Miq. and Artemisia capillaris Thunb. Korean Journal of Medicinal Crop Science. 12:273-278.
  28. Sandoval M, Okuhama NN, Clark M, Angeles FM, Lao J, Bustamante S and Miller MJS. (2002). Sangre de grado Croton palanostigma induces apoptosis in human gastrointestinal cancer cells. Journal of Ethnopharmacology. 80:121-129. https://doi.org/10.1016/S0378-8741(02)00013-2
  29. Saxena A, Sachin K, Bohidar HB and Verma AK. (2005). Effect of molecular weight heterogeneity on drug encapsulation efficiency of gelatin nano-particles. Colloids and Surfaces B: Biointerfaces. 45:42-48. https://doi.org/10.1016/j.colsurfb.2005.07.005
  30. Shin YW and Kim DH. (2005). The anti-scratching effect of Ephedrae herba and Ephedrae Radix. Bulletin of Kyung Hee Pharmaceutical Science. 33:17-22.
  31. Song HG and Lee H. (2006). The effect of EH-HA(Ephedrae Herba Herbal Acupuncture) at ST36 on OVA-induced Asthma in mice. The Journal of Korean Acupuncture & Moxibustion Society. 23:1-14.
  32. Twan L. (2010). Improving the efficacy of combined modality anticancer therapy using HPMA copolymer-based nanomedicine formulations. Advanced Drug Delivery Reviews. 62:203-230. https://doi.org/10.1016/j.addr.2009.11.028
  33. Youn HW, Kang KW, Chung JK and Lee DS. (2008). Nanomedicine: drug delivery systems and nanoparticle targeting. The Korean Society of Nuclear Medicine. 42:337- 346.