Hovenia dulcis Thunb extract and its ingredient methyl vanillate activate Wnt/β-catenin pathway and increase bone mass in growing or ovariectomized mice.
The Wnt/β-catenin pathway is a potential target for development of anabolic agents to treat osteoporosis because of its role in osteoblast differentiation and bone formation. However, there is no clinically available anti-osteoporosis drug that targets this Wnt/β-catenin pathway. In this study, we screened a library of aqueous extracts of 350 plants and identified Hovenia dulcis Thunb (HDT) extract as a Wnt/β-catenin pathway activator. HDT extract induced osteogenic differentiation of calvarial osteoblasts without cytotoxicity. In addition, HDT extract increased femoral bone mass without inducing significant weight changes in normal mice. In addition, thickness and area of femoral cortical bone were also significantly increased by the HDT extract. Methyl vanillate (MV), one of the ingredients in HDT, also activated the Wnt/β-catenin pathway and induced osteoblast differentiation in vitro. MV rescued trabecular or cortical femoral bone loss in the ovariectomized mice without inducing any significant weight changes or abnormality in liver tissue when administrated orally. Thus, natural HDT extract and its ingredient MV are potential anabolic agents for treating osteoporosis.
Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea ; Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
Pu-Hyeon
PH
Cha
Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea ; Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
Wookjin
W
Shin
Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea ; Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
Muhammad
M
Zahoor
Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea ; Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
Hyun-Yi
HY
Kim
Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea ; Department of Molecular Biology, College of Natural Science, Pusan National University, Pusan, Korea.
Do Sik
do S
Min
Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea ; Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
Kang-Yell
KY
Choi
D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D001851:Bone Diseases, Metabolic / Q000209:etiology / Q000517:prevention & control; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D008813:Mice, Inbred ICR; D018613:Microscopy, Confocal; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010052:Ovariectomy / Q000009:adverse effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D034622:RNA Interference; D027823:Rhamnaceae / Q000737:chemistry*; D012886:Skull / Q000166:cytology; D014641:Vanillic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D060449:Wnt Signaling Pathway / Q000187:drug effects* / Q000235:genetics; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D010936:Plant Extracts; D051176:beta Catenin; D014641:Vanillic Acid