Rutin exhibits an anti-resorptive effect in a medaka fish model of osteoporosis
Author affiliations
DOI:
https://doi.org/10.15625/2525-2518/18785Keywords:
medaka fish, osteoporosis, IM, IP, rutinAbstract
With the increasing prevalence of osteoporosis worldwide due to an aging population, there is a substantial need for the search and development of new anti-osteoporosis substances. Rutin (quercetin-3-O-rhamnosyl glucoside) is a flavonoid glycoside found in many plants and herbal medicines, known for its potent antioxidant and potential osteoprotective properties. In this study we investigated the anti-osteoporotic effects of rutin, for the first time, using a medaka fish (Oryzias latipes) model for osteoporosis. The medaka fish model is a non-mammalian model that is increasingly preferred for drug screening. RANKL-induced osteoporosis fish larvae were treated with rutin at five different doses (10, 25, 50, 100, and 200 µM) for 96 hours starting from 7 days post-fertilization (dpf). The effect of rutin on bone damage was assessed via indexes of mineralization protection (IP) which are based on the index of bone mineralization (IM) of the tested fish. The results showed that rutin significantly reduced the level of RANKL-induced bone damage at concentrations of 10, 25, 50, and 100 µM, with the highest effect observed at a concentration of 10 µM. These findings provide important evidence for further studies on the bone-protective effects of rutin on medaka fish models for the development of anti-osteoporosis drugs.
Downloads
References
1. Al-Bari A. A., Mamun A. A. - Current advances in regulation of bone homeostasis. FASEB BioAdv., 2 (2020) 668-679. https://doi.org/10.1096/fba.2020-00058.
2. International Osteoporosis Foundation - Osteoporosis. https://www.osteoporosis.foundation/educational-hub/topic/osteoporosis (accessed 2023/06/25).
3. Khosla S., Hofbauer L. C. - Osteoporosis treatment: recent developments and ongoing challenges. Lancet Diabetes Endocrinol., 5 (2017) 898-907. https://doi.org/10.1016/S2213-8587(17)30188-2.
4. Hoang D. K., Doan M. C., Mai L. D., Ho-Le T. P., Ho-Pham L. T. - Burden of osteoporosis in Vietnam: An analysis of population risk. PLoS One, 16(6) (2021) e0252592. https://doi.org/10.1371/journal.pone.0252592.
5. Tu K. N., Lie J. D., Wan C. K. V., Cameron M., Austel A. G., Nguyen J. K., Van K., Hyun D. - Osteoporosis: A review of treatment options. Pharm. Ther., 43 (2018) 92-104.
6. Sharpe M., Boble S., Spencer C. M. - Alendronate: an update of its use in osteoporosis. Drugs, 61 (2001) 999-1039. https://doi.org/10.2165/00003495-200161070-00010.
7. Boyce B. F., Xing L. - The RANKL/RANK/OPG pathway. Curr. Osteoporos. Rep., 5 (2007) 98-104. https://doi.org/10.1007/s11914-007-0024-y.
8. Cheng C. H., Chen L. R., Chen K. H. - Osteoporosis due to hormone imbalance: An overview of the effects of estrogen deficiency and glucocorticoid overuse on bone turnover. Int. J. Mol. Sci., 23 (2022) 1376. https://doi.org/10.3390/ijms23031376.
9. Lleras-Forero L., Winkler C., Schulte-Merker S. - Zebrafish and medaka as models for biomedical research of bone diseases. Dev. Biol., 457 (2020) 191-205. https://doi.org/10.1016/j.ydbio.2019.07.009.
10. To T. T., Witten P. E., Renn J., Bhattacharya D., Huysseune A., Winkler C. - Rankl-induced osteoclastogenesis leads to loss of mineralization in a medaka osteoporosis model. Development, 139 (2012) 141-150. https://doi.org/10.1242/dev.071035.
11. Cuong P. V., Thanh P. T., Hoa N. T., Long T. D., Thuy T. T. - Segregation of rankl:HSE:CFP medaka transgenic fish line for use as osteoporosis models. VNU J. Sci. Nat. Sci. Technol., 31 (2015) 24-34.
12. Thuy L. T., Thanh P. T., Cuong P. V. C., Long T. D. L., Thuy T. T. - Stability of the transgene rankl in the RANKL:HSE:CFP transgenic medaka fish used as a model for osteoporosis. Vietnam J. Physiol., 19 (2015) 10-17.
13. Cuong P. V., Thanh P. T., Thuy L. T., Dat T. C., Huong N. V. M., Tam H. T. T. M., Thuong P. T. T., Long T. D., Winkler C., Thuy T. T. - Icariin reduces bone loss in a Rankl-induced transgenic medaka (Oryzias latipes) model for osteoporosis. J. Fish Biol., 98 (2021) 1039-1048. https://doi.org/10.1111/jfb.14241.
14. Martiniakova M., Babikova M., Mondockova V., Blahova J., Kovacova V., Omelka R. - The role of macronutrients, micronutrients and flavonoid polyphenols in the prevention and treatment of osteoporosis. Nutrients, 14(3) (2022) 523. https://doi.org/10.3390/nu14030523.
15. Paniwnyk L., Beale E., Lorimer J. P., Mason T. J. - The extraction of rutin from flower buds of Sophora japonica. Ultrason. Sonochem., 8 (2001) 299-301. https://doi.org/10.1016/s1350-4177(00)00075-4.
16. Patel K., Patel D. K. - Chapter 26 - The beneficial role of rutin, a naturally occurring flavonoid in health promotion and disease prevention: A systematic review and update. In Bioactive Food as Dietary Interventions for Arthritis and Related Inflammatory Diseases, Academic Press (2019) 457-479.
17. Lee H. H., Jang J. W., Lee J. K., Park C. K. - Rutin improves bone histomorphometric values by reduction of osteoclastic activity in osteoporosis mouse model induced by bilateral ovariectomy. J. Korean Neurosurg. Soc., 63 (2020) 433. https://doi.org/10.3340/jkns.2019.0097.
18. Kyung T. W., Lee J. E., Shin H. H., Choi H. S. - Rutin inhibits osteoclast formation by decreasing reactive oxygen species and TNF-alpha by inhibiting activation of NF-kappaB. Exp. Mol. Med., 40 (2008) 52-58. https://doi.org/10.3858/emm.2008.40.1.52.
19. Xiao Y., Wei R., Zhen Y., Lan X., Kuang J., Hu D., Song Y., Luo J. - Rutin suppresses FNDC1 expression in bone marrow mesenchymal stem cells to inhibit postmenopausal osteoporosis. Am. J. Transl. Res., 11 (2019) 6680-6690.
20. Dung N. T., Long M. T., Cuong B. H. - Flavonoid and lignan compounds isolated from underground parts of the plant Podophylum tonkinense Gagnep. collected in Sapa, Lao Cai. Vietnam Pharm. J., 507 (2018) 48-53.
21. Walker M. B., Kimmel C. B. - A two-color acid-free cartilage and bone stain for zebrafish larvae. Biotech. Histochem., 82 (2007) 23-28. https://doi.org/10.1080/10520290701333558.
22. Chaturvedi P., Binhui Z., Zimmerman D. L., Belmont A. S. - Stable and reproducible transgene expression independent of proliferative or differentiated state using BAC TG-EMBED. Gene Ther., 25 (2018) 376-391. https://doi.org/10.1038/s41434-018-0021-z.
23. Hyun H. H., Park H., Jeong J., Kim J., Kim H., Oh H. I., Hwang H. S., Kim H. H. - Effects of watercress containing rutin and rutin alone on the proliferation and osteogenic differentiation of human osteoblast-like MG-63 cells. Korean J. Physiol. Pharmacol., 18 (2014) 347-352. https://doi.org/10.4196/kjpp.2014.18.4.347.
24. Hosseinzadeh H., Nassiri-Asl M. - Review of the protective effects of rutin on the metabolic function as an important dietary flavonoid. J. Endocrinol. Investig., 37 (2014) 783-788. https://doi.org/10.1007/s40618-014-0096-3.
25. Srivastava S., Bankar R., Roy P. - Assessment of the role of flavonoids for inducing osteoblast differentiation in isolated mouse bone marrow derived mesenchymal stem cells. Phytomedicine, 20 (2013) 683-690. https://doi.org/10.1016/j.phymed.2013.03.001.
26. Pickrell J. A. - Chapter 28 - Radiation and Health Effects. In Handbook of Toxicology of Chemical Warfare Agents, Academic Press (2009) 381-392.
27. de Witte W. E. A., Danhof M., van der Graaf P. H. - The implications of target saturation for the use of drug-target residence time. Nat. Rev. Drug Discov., 18 (2019) 84. https://doi.org/10.1038/nrd.2018.234.
28. To T. T., Witten P. E., Huysseune A., Winkler C. - An adult osteopetrosis model in medaka reveals the importance of osteoclast function for bone remodeling in teleost fish. Comp. Biochem. Physiol. C, 178 (2015) 68-75. https://doi.org/10.1016/j.cbpc.2015.08.007.
29. Renn J., Buttner A., To T. T., Chan S. J. H., Winkler C. - A col10a1:nlGFP transgenic line displays putative osteoblast precursors at the medaka notochordal sheath prior to mineralization. Dev. Biol., 381 (2013) 134-143. https://doi.org/10.1016/j.ydbio.2013.05.030.
30. Gera S., Pooladanda V., Godugu C., Swamy-Challa V., Wankar J., Dodoala S., Sampathi S. - Rutin nanosuspension for potential management of osteoporosis: effect of particle size reduction on oral bioavailability, in vitro and in vivo activity. Pharm. Dev. Technol., 25 (2020) 971-988. https://doi.org/10.1080/10837450.2020.1765378.
31. Morikane D., Zang L., Nishimura N. - Evaluation of the percutaneous absorption of drug molecules in zebrafish. Molecules, 25 (2020) 3974. https://doi.org/10.3390/molecules25173974.
32. Zhang F., Qin W., Zhang P., Hu Q. - Antibiotic toxicity and absorption in zebrafish using liquid chromatography-tandem mass spectrometry. PLoS One, 10 (2015) e0124805. https://doi.org/10.1371/journal.pone.0124805.
33. Yang C. Y., Hsiu S. L., Wen K. C., Lin S. P., Tsai S. Y., Hou Y. C., Chao P. D. L. - Bioavailability and metabolic pharmacokinetics of rutin and quercetin in rats. J. Food Drug Anal., 13 (2005) https://doi.org/10.38212/2224-6614.2517.
Downloads
Published
How to Cite
Issue
Section
License

This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Vietnam Journal of Sciences and Technology (VJST) is an open access and peer-reviewed journal. All academic publications could be made free to read and downloaded for everyone. In addition, articles are published under term of the Creative Commons Attribution-ShareAlike 4.0 International (CC BY-SA) Licence which permits use, distribution and reproduction in any medium, provided the original work is properly cited & ShareAlike terms followed.
Copyright on any research article published in VJST is retained by the respective author(s), without restrictions. Authors grant VAST Journals System a license to publish the article and identify itself as the original publisher. Upon author(s) by giving permission to VJST either via VJST journal portal or other channel to publish their research work in VJST agrees to all the terms and conditions of https://creativecommons.org/licenses/by-sa/4.0/ License and terms & condition set by VJST.
Authors have the responsibility of to secure all necessary copyright permissions for the use of 3rd-party materials in their manuscript.
Funding data
-
National Foundation for Science and Technology Development
Grant numbers 106-YS.06-2014.15

