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PP-12

Zebrafish-based screening for herbal products with therapeutic potential in

osteoporosis

+,2
+,1
Yi-Tzu Lin, Muhammad Shahbaz Shafique, Wen-Ying Lin, Kameshwara Kumar
3
4
Dharini, Cheng-Huan Peng, Chi-Ying Li,* Ming-Der Lin* ,2,3,5
,1
3

1 School of Pharmacy, Tzu Chi University, Hualien, Taiwan
2 Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien, Taiwan
3 Institute of Medical Science, Tzu Chi University, Hualien, Taiwan
4 Department of Orthopedics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation,
Hualien, Taiwan
5 Integration Center of Traditional Chinese and Modern Medicine, Hualien Tzu Chi Hospital,
Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
+ These authors contribute equally
* Email: cyli@gms.tcu.edu.tw (C.-Y. Li); mingder@gms.tcu.edu.tw (M.-D. Lin)

Abstract
Bone homeostasis is maintained by a balance between bone resorption and formation
mediated by osteoblasts, osteoclasts, and osteocytes. Disruption of this equilibrium shifts
remodeling toward resorption, resulting in osteoporosis. Recently, herbal products have gained
considerable attention as promising multi-target therapeutic agents for the prevention and
treatment of osteoporosis. In this study, we employed a zebrafish glucocorticoid-induced
osteoporosis model to screen a collection of herbal products and identified TCU521-1, a
Moraceae species commonly distributed in low-altitude regions of Taiwan, as a potential
candidate for osteoporosis therapy. Water extracts of TCU521-1 significantly reversed
dexamethasone-induced calcification loss by enhancing osteogenesis in zebrafish. To enrich
and characterize the active compounds responsible for bone formation, we performed solvent
partitioning of TCU521-1. The bioactive compounds were found to be enriched in the methanol
and butanol subfractions following ethyl acetate partitioning of the 95% ethanol extract.
Beyond zebrafish, the osteoblast-promoting activity of TCU521-1 was further validated in
primary human osteoblasts. Collectively, these findings highlight the utility of zebrafish larvae
as a platform for screening herbal products that modulate bone homeostasis and underscore the
therapeutic potential of TCU521-1 as a novel agent for osteoporosis management.

Keywords: Bone homeostasis; Osteoporosis; Zebrafish; Moraceae; Osteogenesis