Nutrition Research and Practice

The Korean Nutrition Society (한국영양학회)
권호 표지
DOI QR코드

DOI QR Code

Aqueous extract of Petasites japonicus leaves promotes osteoblast differentiation via up-regulation of Runx2 and Osterix in MC3T3-E1 cells

  • Kim, Eun Ji (Regional Strategic Industry Innovation Center, Hallym University) ;
  • Jung, Jae In (Regional Strategic Industry Innovation Center, Hallym University) ;
  • Jeon, Young Eun (Regional Strategic Industry Innovation Center, Hallym University) ;
  • Lee, Hyun Sook (Department of Food Science & Nutrition, Dongseo University)
  • Received : 2021.03.30
  • Accepted : 2021.04.09
  • Published : 2021.10.01
Download PDF
⟨ Previous Next ⟩

Abstract

BACKGROUND/OBJECTIVES: Petasites japonicus Maxim (P. japonicus) has been used as an edible and medicinal plant and contains many bioactive compounds. The purpose of this study is to investigate the effect of P. japonicus on osteogenesis. MATERIALS/METHODS: The leaves and stems of P. japonicus were separated and extracted with hot water or ethanol, respectively. The total phenolic compound and total polyphenol contents of each extract were measured, and alkaline phosphatase (ALP) activity of each extract was evaluated to determine their effect on bone metabolism. To investigate the effect on osteoblast differentiation of the aqueous extract of P. japonicus leaves (AL), which produced the highest ALP activity among the tested extracts, collagen content was measured using the Sirius Red staining method, mineralization using the Alizarin Red S staining method, and osteocalcin production through enzyme-linked immunosorbent assay analysis. Also, real-time reverse transcription polymerase chain reaction was performed to investigate the mRNA expression levels of Runt-related transcriptional factor 2 (Runx2) and Osterix. RESULTS: Among the 4 P. japonicus extracts, AL had the highest values in all of the following measures: total phenolic compounds, total polyphenols, and ALP activity, which is a major biomarker of osteoblast differentiation. The AL-treated MC3T3-E1 cells showed significant increases in induced osteoblast differentiation, collagen synthesis, mineralization, and osteocalcin production. In addition, mRNA expressions of Runx2 and Osterix, transcription factors that regulate osteoblast differentiation, were significantly increased. CONCLUSIONS: These results suggest that AL can regulate osteoblasts differentiation, at least in part through Runx2 and Osterix. Therefore, it is highly likely that P. japonicus will be useful as an alternate therapeutic for the prevention and treatment of osteoporosis.

Keywords

Acknowledgement

This work was supported by a National Research Foundation of Korea grant funded by the Korean government (No. 2020R1F1A104956711).

References

  1. Wong SK, Chin KY, Ima-Nirwana S. The osteoprotective effects of kaempferol: the evidence from in vivo and in vitro studies. Drug Des Devel Ther 2019;13:3497-514. https://doi.org/10.2147/DDDT.S227738
  2. He JB, Chen MH, Lin DK. New insights into the tonifying kidney-yin herbs and formulas for the treatment of osteoporosis. Arch Osteoporos 2017;12:14. https://doi.org/10.1007/s11657-016-0301-4
  3. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J; Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002;288:321-33. https://doi.org/10.1001/jama.288.3.321
  4. O'Ryan FS, Lo JC. Bisphosphonate-related osteonecrosis of the jaw in patients with oral bisphosphonate exposure: clinical course and outcomes. J Oral Maxillofac Surg 2012;70:1844-53. https://doi.org/10.1016/j.joms.2011.08.033
  5. Wang S, Jin DQ, Xie C, Wang H, Wang M, Xu J, Guo Y. Isolation, characterization, and neuroprotective activities of sesquiterpenes from Petasites japonicus. Food Chem 2013;141:2075-82. https://doi.org/10.1016/j.foodchem.2013.04.116
  6. Sun ZL, Gao GL, Luo JY, Zhang XL, Zhang M, Feng J. A new neuroprotective bakkenolide from the rhizome of Peatasites tatewakianus. Fitoterapia 2011;82:410-4.
  7. Hiemori-Kondo M. Antioxidant compounds of Petasites japonicus and their preventive effects in chronic diseases: a review. J Clin Biochem Nutr 2020;67:10-8. https://doi.org/10.3164/jcbn.20-58
  8. Ahn EM, Asamenew G, Kim HW, Lee SH, Yoo SM, Cho SM, Cha YS, Kang MS. Anti-obesity effects of Petasites japonicus (Meowi) ethanol extract on RAW 264.7 macrophages and 3T3-L1 adipocytes and its characterization of polyphenolic compounds. Nutrients 2020;12:1261. https://doi.org/10.3390/nu12051261
  9. Kang HG, Jeong SH, Cho JH. Antimutagenic and anticarcinogenic effect of methanol extracts of Petasites japonicus Maxim leaves. J Vet Sci 2010;11:51-8. https://doi.org/10.4142/jvs.2010.11.1.51
  10. Kim HJ, Park SY, Lee HM, Seo DI, Kim YM. Antiproliferative effect of the methanol extract from the roots of Petasites japonicus on Hep3B hepatocellular carcinoma cells in vitro and in vivo. Exp Ther Med 2015;9:1791-6. https://doi.org/10.3892/etm.2015.2296
  11. Kim KM, Im AR, Lee S, Chae S. Dual protective effects of flavonoids from Petasites japonicus against UVB-induced apoptosis mediated via HSF-1 activated heat shock proteins and Nrf2-activated heme oxygenase-1 pathways. Biol Pharm Bull 2017;40:765-73. https://doi.org/10.1248/bpb.b16-00691
  12. Kim N, Choi JG, Park S, Lee JK, Oh MS. Butterbur leaves attenuate memory impairment and neuronal cell damage in amyloid beta-induced Alzheimer's disease models. Int J Mol Sci 2018;19:1644. https://doi.org/10.3390/ijms19061644
  13. Matsumoto T, Imahori D, Saito Y, Zhang W, Ohta T, Yoshida T, Nakayama Y, Ashihara E, Watanabe T. Cytotoxic activities of sesquiterpenoids from the aerial parts of Petasites japonicus against cancer stem cells. J Nat Med 2020;74:689-701. https://doi.org/10.1007/s11418-020-01420-x
  14. Shimoda H, Tanaka J, Yamada E, Morikawa T, Kasajima N, Yoshikawa M. Anti type I allergic property of Japanese butterbur extract and its mast cell degranulation inhibitory ingredients. J Agric Food Chem 2006;54:2915-20. https://doi.org/10.1021/jf052994o
  15. Lee KP, Kang S, Park SJ, Choi YW, Lee YG, Im DS. Anti-allergic and anti-inflammatory effects of bakkenolide B isolated from Petasites japonicus leaves. J Ethnopharmacol 2013;148:890-4. https://doi.org/10.1016/j.jep.2013.05.037
  16. Choi JY, Desta KT, Saralamma VVG, Lee SJ, Lee SJ, Kim SM, Paramanantham A, Lee HJ, Kim YH, Shin HC, Shim JH, Warda M, Hacimuftuoglu A, Jeong JH, Shin SC, Kim GS, Abd El-Aty AM. LC-MS/MS characterization, anti-inflammatory effects and antioxidant activities of polyphenols from different tissues of Korean Petasites japonicus (Meowi). Biomed Chromatogr 2017;31:e4033. https://doi.org/10.1002/bmc.4033
  17. Lee JS, Jeong M, Park S, Ryu SM, Lee J, Song Z, Guo Y, Choi JH, Lee D, Jang DS. Chemical constituents of the leaves of butterbur (Petasites japonicus) and their anti-inflammatory effects. Biomolecules 2019;9:806. https://doi.org/10.3390/biom9120806
  18. Guo L, Li K, Cui ZW, Kang JS, Son BG, Choi YW. S-Petasin isolated from Petasites japonicus exerts anti-adipogenic activity in the 3T3-L1 cell line by inhibiting PPAR-γ pathway signaling. Food Funct 2019;10:4396-406. https://doi.org/10.1039/C9FO00549H
  19. Lee JS, Yang EJ, Yun CY, Kim DH, Kim IS. Suppressive effect of Petasites japonicus extract on ovalbumininduced airway inflammation in an asthmatic mouse model. J Ethnopharmacol 2011;133:551-7. https://doi.org/10.1016/j.jep.2010.10.038
  20. Singleton VL, Rossi TA. Colorimetry of total phenolics with phosphomolybdic-phosphotungstic acid reagents. Am J Enol Vitic 1965;16:144-58.
  21. Moreno MI, Isla MI, Sampietro AR, Vattuone MA. Comparison of the free radical-scavenging activity of propolis from several regions of Argentina. J Ethnopharmacol 2000;71:109-14. https://doi.org/10.1016/S0378-8741(99)00189-0
  22. Kim EJ, Holthuizen PE, Park HS, Ha YL, Jung KC, Park JH. Trans-10,cis-12-conjugated linoleic acid inhibits Caco-2 colon cancer cell growth. Am J Physiol Gastrointest Liver Physiol 2002;283:G357-67. https://doi.org/10.1152/ajpgi.00495.2001
  23. Sakamura S, Yoshihara T, Toyoda K. The constituents of Petasites japonicas: structures of fukiic acid and fukinolic acid. Agric Biol Chem 1973;37:1915-21. https://doi.org/10.1080/00021369.1973.10860912
  24. Calderon-Montano JM, Burgos-Moron E, Perez-Guerrero C, Lopez-Lazaro M. A review on the dietary flavonoid kaempferol. Mini Rev Med Chem 2011;11:298-344. https://doi.org/10.2174/138955711795305335
  25. Imran M, Rauf A, Shah ZA, Saeed F, Imran A, Arshad MU, Ahmad B, Bawazeer S, Atif M, Peters DG, Mubarak MS. Chemo-preventive and therapeutic effect of the dietary flavonoid kaempferol: a comprehensive review. Phytother Res 2019;33:263-75. https://doi.org/10.1002/ptr.6227
  26. Heino TJ, Hentunen TA. Differentiation of osteoblasts and osteocytes from mesenchymal stem cells. Curr Stem Cell Res Ther 2008;3:131-45. https://doi.org/10.2174/157488808784223032
  27. Vimalraj S, Arumugam B, Miranda PJ, Selvamurugan N. Runx2: Structure, function, and phosphorylation in osteoblast differentiation. Int J Biol Macromol 2015;78:202-8. https://doi.org/10.1016/j.ijbiomac.2015.04.008
  28. Komori T. Signaling networks in RUNX2-dependent bone development. J Cell Biochem 2011;112:750-5. https://doi.org/10.1002/jcb.22994
  29. Kawane T, Qin X, Jiang Q, Miyazaki T, Komori H, Yoshida CA, Matsuura-Kawata VK, Sakane C, Matsuo Y, Nagai K, Maeno T, Date Y, Nishimura R, Komori T. Runx2 is required for the proliferation of osteoblast progenitors and induces proliferation by regulating Fgfr2 and Fgfr3. Sci Rep 2018;8:13551. https://doi.org/10.1038/s41598-018-31853-0
  30. Bruderer M, Richards RG, Alini M, Stoddart MJ. Role and regulation of RUNX2 in osteogenesis. Eur Cell Mater 2014;28:269-86. https://doi.org/10.22203/eCM.v028a19
  31. Fu H, Doll B, McNelis T, Hollinger JO. Osteoblast differentiation in vitro and in vivo promoted by Osterix. J Biomed Mater Res A 2007;83:770-8.
  32. Zhang C. Transcriptional regulation of bone formation by the osteoblast-specific transcription factor Osx. J Orthop Surg 2010;5:37. https://doi.org/10.1186/1749-799X-5-37
  33. Pokrovskaya LA, Nadezhdin SV, Zubareva EV, Burda YE, Gnezdyukova ES. Expression of RUNX2 and Osterix in rat mesenchymal stem cells during culturing in osteogenic-conditioned medium. Bull Exp Biol Med 2020;169:571-5. https://doi.org/10.1007/s10517-020-04931-5