Herbal Formula Science (대한한의학방제학회지)

The Korean Medicine Society for the Herbal Formula Study (대한한의학방제학회)
권호 표지
DOI QR코드

DOI QR Code

Safety Verification through Repeated Dose 90-Day Oral Toxicity Test of Schisandra Fruit Extract Powder(SFEP)

오미자추출물(SFEP)의 90일 반복경구투여 독성 시험을 통한 안전성 검증

  • Received : 2023.11.01
  • Accepted : 2023.11.15
  • Published : 2023.11.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives : This study conducted a repeated dose 90-day oral toxicity test in order to up-cycling Schisandra fruit extract powder(SFEP) using discarded Schisandra chinensis by-products and evaluated the NOAEL of SFEP. Methods : SD-rats were orally administered SFEP at concentrations of 0, 62.5, 125, and 250 mg/kg once daily for 90 days. Body weights and clinical signs were observed during the administration period. After completion of the experiment, the experimental animals were autopsied to observe necropsy findings and organ weights changes, and hematological parameters and blood chemistry values were measured. Results : During the SFEP administration period, clinical signs such as salivation, wounds, and erosion were sporadically observed in 1 to 2 animals. In the SFEP 250 mg/kg administered group, weights of the liver and thyroid gland significantly increased compared to the control group, but no significant changes were observed in organ weights according to body weights. As a result of measuring hematological parameters and blood chemistry values, a decrease in RDW, T-BIL, and TBA, and an increase in TP, ALB, and Ca were observed due to SFEP administration. However, these changes following SFEP administration were accidental and not dose-dependent. Additionally, no correlation was found between gender and other parameters. Conclusions : Therefore, the NOAEL of SFEP was confirmed to be 250 mg/kg.

Keywords

Acknowledgement

본 결과물은 환경부의 재원으로 한국환경산업기술원의 야생생물 유래 친환경 신소재 및 공정기술개발사업(과제번호 : 2021003270008)의 지원을 받아 연구되었습니다.

References

  1. Szopa A, Ekiert R, Ekiert H. Current knowledge of Schisandra chinensis (Turcz.) Baill. (Chinese magnolia vine) as a medicinal plant species: a review on the bioactive components, pharmacological properties, analytical and biotechnological studies. Phytochem Rev. 2017;16(2):195-218.  https://doi.org/10.1007/s11101-016-9470-4
  2. Hu G, Qi Z, Wang A, Jia J. Effects of Deacidification on Composition of Schisandra chinensis Ethanolic Extract and Studies on Acute Toxicity in Mice. Molecules. 2020;25(24):6038. 
  3. Kopustinskiene DM, Bernatoniene J. Antioxidant Effects of Schisandra chinensis Fruits and Their Active Constituents. Antioxidants (Basel). 2021;10(4):620. 
  4. Nowak A, Zaklos-Szyda M, Blasiak J, Nowak A, Zhang Z, Zhang B. Potential of Schisandra chinensis (Turcz.) Baill. in Human Health and Nutrition: A Review of Current Knowledge and Therapeutic Perspectives. Nutrients. 2019;11(2):333. 
  5. Jiang Y, Fan X, Wang Y, et al. Hepato-rotective effects of six schisandra lignans on acetaminophen-induced liver injury are partially associated with the inhibition of CYP-mediated bioactivation. Chem Biol Interact. 2015;231:83-89.  https://doi.org/10.1016/j.cbi.2015.02.022
  6. Hu D, Yang Z, Yao X, et al. Dibenzocyclooctadiene lignans from Schisandra chinensis and their inhibitory activity on NO production in lipopolysaccharide-activated microglia cells. Phytochemistry. 2014;104:72-78.  https://doi.org/10.1016/j.phytochem.2014.04.014
  7. Jeong EJ, Lee HK, Lee KY, et al. The effects of lignan-riched extract of Shisandra chinensis on amyloid-β-induced cognitive impairment and neurotoxicity in the cortex and hippocampus of mouse. J Ethnopharmacol. 2013;146(1):347-354.  https://doi.org/10.1016/j.jep.2013.01.003
  8. Park HJ, Cho JY, Kim MK, et al. Anti-obesity effect of Schisandra chinensis in 3T3-L1 cells and high fat diet-induced obese rats. Food Chem. 2012;134:227-234. https://doi.org/10.1016/j.foodchem.2012.02.101
  9. Kim J.W., Ku S.K., Han M.H., Kim K.Y., Kim S.G., Kim G.Y., Hwang H.J., Kim B.W., Kim C.M., Choi Y.H. The administration of Fructus Schisandrae attenuates dexamethasone-induced muscle atrophy in mice. Int. J. Mol. Med. 2015;36:29-42.  https://doi.org/10.3892/ijmm.2015.2200
  10. Ekiert R.J., Szopa A., Ekiert H., Krzek J., Dzik E. Analysis of lignans in Schisandra chinensis fruits, leaves, biomasses from in vitro cultures and food supplements. J. Funct. Foods. 2013;5:1576-1581. https://doi.org/10.1016/j.jff.2013.06.008
  11. Mocan A., Crisan G., Vlase L., Crissan O., Vodnar D.C., Raita O., Gheldiu A.M., Toiu A., Oprean R., Tilea I. Comparative studies on polyphenolic composition, antioxidant and antimicrobial activities of Schisandra chinensis leaves and fruits. Molecules. 2014;19:15162-15179.  https://doi.org/10.3390/molecules190915162
  12. Szopa A., Ekiert H. The importance of applied light quality on the production of lignans and phenolic acids in Schisandra chinensis (Turcz.) Baill. cultures in vitro. Plant Cell Tissue Organ Cult. 2016;127:115-121. https://doi.org/10.1007/s11240-016-1034-1
  13. Korea Food and Drug Administration. Testing Guidelines for Safety Evaluation of Drugs. Notification No. 2009-116. 
  14. OECD Guideline For The Testing Of Chemicals. Test No. 423: Acute Oral toxicity - Acute Toxic Class Method. 
  15. OECD Guideline For The Testing Of Chemicals. Test No. 408: Repeated Dose 90-Day Oral Toxicity Study in Rodents. 
  16. Kim, S., Yoo, B. R., Kim, Y.-S., Lim, J.-M., Ku, B.-H., Kwak, K. T., & Jeon, B. Y. (2022). Evaluation of Acute Toxicity of Pomace Schisandra chinensis Extracts Using SD-rats. Herbal Formula Science, 30(4), 281-291.  https://doi.org/10.14374/HFS.2022.30.4.281
  17. Lu Y, Chen DF. Analysis of Schisandra chinensis and Schisandra sphenanthera. J Chromatogr A. 2009;1216(11):1980-1990.  https://doi.org/10.1016/j.chroma.2008.09.070
  18. Park WS, Koo KA, Bae JY, et al. Dibenzocyclooctadiene Lignans in Plant Parts and Fermented Beverages of Schisandra chinensis. Plants (Basel). 2021;10(2):361. 
  19. Brandli-Baiocco A, Balme E, Bruder M, et al. Nonproliferative and Proliferative Lesions of the Rat and Mouse Endocrine System. J Toxicol Pathol. 2018;31(3 Suppl):1S-95S.  https://doi.org/10.1293/tox.31.1S
  20. Willard-Mack CL, Elmore SA, Hall WC, et al. Nonproliferative and Proliferative Lesions of the Rat and Mouse Hematolymphoid System. Toxicol Pathol. 2019;47(6):665-783.  https://doi.org/10.1177/0192623319867053
  21. Sireeratawong S, Jaijoy K, Panunto W, Nanna U, Lertprasertsuke N, Soonthornchareonnon N. Acute and chronic toxicity studies of the water extract from dried fruits of Terminalia bellerica (Gaertn.) Roxb. In Spargue-Dawley rats. Afr J Tradit Complement Altern Med. 2012;10(2):223-231.  https://doi.org/10.4314/ajtcam.v10i2.6
  22. Hidayat M, Prahastuti S, Rakasiwi AS, Prisilia S, Hasan K. Sub-chronic toxicity study of green peas protein hydrolysate in rats. Toxicol Rep. 2022;9:735-742.  https://doi.org/10.1016/j.toxrep.2022.03.020
  23. Zhong-Ze Han, et al, Reference Data of the Main Physiological Parameters in Control Sprague-Dawley Rats from Pre-clinical Toxicity Studies, Lab Anim Res 2010;26(2), 153-164.  https://doi.org/10.5625/lar.2010.26.2.153
  24. Kyung-ah Kim (2009). Understanding and application of liver function tests. Korean J Med, 76(2), 163-168.