The Korean Journal of Mycology (한국균학회지)

The Korean Society of Mycology (한국균학회)
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Intracellular Lipid Accumulation Inhibition, Anticancer Activity, and Single Oral Dose Toxicity of Ethanolic Wolfiporia cocos Extracts

에탄올 복령추출물의 지방축적 억제활성, 항암활성 및 단회 경구 독성시험

  • Park, Na-Hye (Laboratory of Veterinary Pharmacokinetics & Pharmacodynamics, College of Veterinary Medicine, Kyungpook National University) ;
  • Lee, Hwa-Yong (EnpuTech) ;
  • Choi, Jong-Woon (Gangwon-do Forest Science Institute) ;
  • Park, Seung-Chun (Laboratory of Veterinary Pharmacokinetics & Pharmacodynamics, College of Veterinary Medicine, Kyungpook National University)
  • 박나혜 (경북대학교 수의과대학 약리독성학연구실) ;
  • 이화용 ((주)엔퓨텍) ;
  • 최종운 (강원도산림과학연구원) ;
  • 박승춘 (경북대학교 수의과대학 약리독성학연구실)
  • Received : 2018.05.11
  • Accepted : 2018.06.10
  • Published : 2018.09.01
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Abstract

In the present study, we compared the effects of 50% ethanolic extracts of Chinese and Korean Wolfiporia cocos (CPE and KPE) on in vitro lipid accumulation in 3T3-L1 cells and their anticancer activities in Sarcoma 180 cells. We further compared the anticancer activities and the 50% inhibitory concentrations ($IC_{50}$) of CPE with KPE with cultivated for one and two years in a landfill and a facility (LPE and FPE), respectively. In addition, the single oral dose toxicities of CPE and KPE were evaluated in mice. Lipid accumulation was inhibited after 48 hours, in CPE and KPE treated 3T3-L1 cells; however, no significant difference was observed between CPE and KPE in their lipid accumulation inhibitory activities. The anticancer activity of KPE was higher than that of CPE at $300{\mu}g/mL$ (p<0.05), revealing the possibility of an auxiliary biological means for origin identification. The anticancer activities of LPE and FPE were significantly stronger than that of CPE (p<0.05) but there was no difference between extracts from one- and two-year-old W. cocos, irrespective of the cultivation method. In single oral dose toxicity tests, CPE and KPE did not induce mortality during the 14-day observation. Thus, the 50% of lethal dose ($LD_{50}$) of CPE and KPE were estimated to be higher than 2,000 mg/kg. Taken together, our results indicate that the anticancer assay could be an auxiliary means of identifying the origin of W. cocos. In addition, artificial cultivation could be an alternative way to reduce the import of W. cocos. Lastly, 50% ethanolic W. cocos extracts could be potential candidates for obesity and cancer managements.

본 연구에서는 국내산 50% 에탄올 복령추출물(KPE)과 중국산 50% 에탄올 복령추출물(CPE)의 약리활성 비교를 위하여 전 지방세포주인 3T3-L1 세포주와 암세포주인 Sarcoma 180 세포주를 이용하여 지방축적 억제활성과 항암활성을 비교하였다. 또한 노지재배 및 시설재배의 1년산 복령과 2년산 복령의 50% 에탄올 복령추출물(LPE, FPE)에 대해서도 50% 항암억제활성($IC_{50}$)로 중국산 복령과 비교하였다. 추가적으로 현재 시중에서 유통되고 CPE와 KPE의 안전성 자료를 획득하고자 단회 경구 독성시험을 실시하였다. CPE와 KPE를 3T3-L1 세포에 처리 후 48시간 이후에 대조군과 비교 시 지방축적 억제를 보였으나(p< 0.05), CPE와 KPE 사이에서는 지방축적 억제활성의 차이가 없었다. Sarcoma 180에 대한 CPE와 KPE의 항암활성을 비교할 때 시험한 농도에서 유사한 활성을 보였지만 $300{\mu}g/mL$의 고농도에서는 KPE가 CPE보다 높은 항암활성을 보였다(p < 0.05). 중국산 복령을 대체하고자 인공재배에서 생산된 노지재배 복령(LPE)과 시설재배 복령(FPE)의 항암활성 비교에서 CPE의 항암활성보다 높게 나타났다(p < 0.05). 단회 독성시험에서 CPE와 KPE의 $LD_{50}$(반수치사량)은 2,000 mg/kg 이상으로 추정되었다. 위의 결과를 종합 시 암세포주인 Sarcoma 180 세포주를 이용한 항암활성측정법은 중국산과 국내산의 원산지 검증의 생물활성검증의 보조수단으로 활용이 가능할 것으로 기대되었다. 국내에서 인공재배 되는 노지재배 복령 및 시설재배 복령은 중국산 복령을 대체하여 수입 감소의 효과를 기대할 수 있으며 지방축적 억제활성 및 항암활성의 기능성 원료로 활용이 가능할 것으로 생각되었다.

Keywords

References

  1. Dai YC, Yang ZL, Cui BK, Yu CJ, Zhou LW. Species diversity and utilization of medicinal mushrooms and fungi in China (review). Int J Med Mushrooms 2009;11:287-302. https://doi.org/10.1615/IntJMedMushr.v11.i3.80
  2. Esteban CI. Medicinal interest of Poria cocos (Wolfiporia extensa). Rev Iberoam Micol 2009;26:103-7. https://doi.org/10.1016/S1130-1406(09)70019-1
  3. Wang YZ, Zhang J, Zhao YL, Li T, Shen T, Li JQ, Li WY, Liu HG. Mycology, cultivation, traditional uses, phytochemistry and pharmacology of Wolfiporia cocos (Schwein.) Ryvarden et Gilb.: a review. J Ethnopharmacol 2013;147:265-76. https://doi.org/10.1016/j.jep.2013.03.027
  4. Gao Y, Yan H, Jin R, Lei P. Antiepileptic activity of total triterpenes isolated from Poria cocos is mediated by suppression of aspartic and glutamic acids in the brain. Pharm Biol 2016;54:2528-35. https://doi.org/10.3109/13880209.2016.1168853
  5. Smriga M, Saito H, Nishiyama N. Hoelen (Poria cocos Wolf) and ginseng (Panax ginseng C. A. Meyer), the ingredients of a Chinese prescription DX-9386, individually promote hippocampal long-term potentiation in vivo. Biol Pharm Bull 1995;18:518-22. https://doi.org/10.1248/bpb.18.518
  6. Wang Q, Chen S, Han L, Lian M, Wen Z, Jiayinaguli T, Liu L, Sun R, Cao Y. Antioxidant activity of carboxymethyl ($1{\rightarrow}3$)-${\beta}$-d-glucan (from the sclerotium of Poria cocos) sulfate (in vitro). Int J Biol Macromol 2014;69:229-35. https://doi.org/10.1016/j.ijbiomac.2014.05.038
  7. Zhou L, Zhang Y, Gapter LA, Ling H, Agarwal R, Ng KY. Cytotoxic and anti-oxidant activities of lanostane-type triterpenes isolated from Poria cocos. Chem Pharm Bull (Tokyo) 2008;56:1459-62. https://doi.org/10.1248/cpb.56.1459
  8. Jeong JW, Lee HH, Han MH, Kim GY, Hong SH, Park C, Choi YH. Ethanol extract of Poria cocos reduces the production of inflammatory mediators by suppressing the NF-kappaB signaling pathway in lipopolysaccharide-stimulated RAW 264.7 macrophages. BMC Complement Altern Med 2014;14:101. https://doi.org/10.1186/1472-6882-14-101
  9. Kim SJ, Shin HJ, Lee BJ, Kim DS, Lee JH, Jeong MY, Kim HL, Park J, Lim H, Kim SH, et al. The antiinflammatory mechanism of Igongsan in mouse peritoneal macrophages via suppression of NF-${\kappa}B$/Caspase-1 activation. Phytother Res 2014;28:736-44. https://doi.org/10.1002/ptr.5058
  10. Cheng S, Eliaz I, Lin J, Thyagarajan-Sahu A, Sliva D. Triterpenes from Poria cocos suppress growth and invasiveness of pancreatic cancer cells through the downregulation of MMP-7. Int J Oncol 2013;42:1869-74. https://doi.org/10.3892/ijo.2013.1902
  11. Park NH, Jo WS, Park SC. Comparison of mineral contents and antioxidant activities of domestic and Chinese Wolfiporia extensa for origin identification. J Mushrooms 2016;14:232-6. https://doi.org/10.14480/JM.2016.14.4.232
  12. Scudiero DA, Shoemaker RH, Paull KD, Monks A, Tierney S, Nofziger TH, Currens MJ, Seniff D, Boyd MR. Evaluation of a soluble tetrazolium/formazan assay for cell growth and drug sensitivity in culture using human and other tumor cell lines. Cancer Res 1988;48:4827-33.
  13. Zhang L, Chen L, Xu X, Zeng F, Cheung PC. Effect of molecular mass on antitumor activity of heteropolysaccharide from Poria cocos. Biosci Biotechnol Biochem 2005;69:631-4. https://doi.org/10.1271/bbb.69.631
  14. Reza MA, Hossain MA, Damte D, Jo WS, Hsu WH, Park SC. Hypolipidemic and hepatic steatosis preventing activities of the wood ear medicinal mushroom Auricularia auriculajudae (Higher Basidiomycetes) ethanol extract in vivo and in vitro. Int J Med Mushrooms 2015;17:723-34. https://doi.org/10.1615/IntJMedMushrooms.v17.i8.30
  15. Li TH, Hou CC, Chang CL, Yang WC. Anti-hyperglycemic properties of crude extract and triterpenes from Poria cocos. Evid Based Complement Alternat Med 2011;2011:Article ID 128402.
  16. Park E, Song JH, Kim GN, Kim HO. Anti-oxidant and anti-obese effects of mulberry (Morus alba L.) leaf extract in 3T3-L1 cells. Korean J Aesthet Cosmetol 2015;13:19-26.
  17. Akihisa T, Uchiyama E, Kikuchi T, Tokuda H, Suzuki T, Kimura Y. Anti-tumor-promoting effects of 25-methoxyporicoic acid A and other triterpene acids from Poria cocos. J Nat Prod 2009;72:1786-92. https://doi.org/10.1021/np9003239
  18. Akihisa T, Nakamura Y, Tokuda H, Uchiyama E, Suzuki T, Kimura Y, Uchikura K, Nishino H. Triterpene acid from Poria cocos and their anti-tumor-promoting effects. J Nat Prod 2007;70:948-53. https://doi.org/10.1021/np0780001
  19. Lee BI, Hong IP, Kim DW, Lee MW. Effects of Poria cocos and Panax ginseng extracts on hemogram of sarcoma-180 mouse. Kor J Mycol 1990;18:218-24.