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Molecules 2019, 24(2), 253; https://doi.org/10.3390/molecules24020253

Metabolomics Profiling Reveals Rehmanniae Radix Preparata Extract Protects against Glucocorticoid-Induced Osteoporosis Mainly via Intervening Steroid Hormone Biosynthesis

1
Department of Pharmacognosy, Second Military Medical University School of Pharmacy, Shanghai 200433, China
2
Zhejiang Chinese Medical University School of Pharmacy, Hangzhou 310053, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 4 December 2018 / Revised: 2 January 2019 / Accepted: 5 January 2019 / Published: 11 January 2019
(This article belongs to the Special Issue Plant Extracts: Biological and Pharmacological Activity)
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Abstract

Rehmanniae Radix Preparata (RR), the dry rhizome of Rehmannia glutinosa Libosch., is a traditional herbal medicine for improving the liver and kidney function. Ample clinical and pharmacological experiments show that RR can prevent post-menopausal osteoporosis and senile osteoporosis. In the present study, in vivo and in vitro experiments, as well as a UHPLC-Q/TOF-MS-based metabolomics study, were used to explore the preventing effect of RR on glucocorticoid-induced osteoporosis (GIOP) and its underlying mechanisms. As a result, RR significantly enhanced bone mineral density (BMD), improved the micro-architecture of trabecular bone, and intervened in biochemical markers of bone metabolism in dexamethasone (DEX)-treated rats. For the in vitro experiment, RR increased the cell proliferation and alkaline phosphatase (ALP) activity, enhanced the extracellular matrix mineralization level, and improved the expression of runt-related transcription factor 2 (RUNX2) and osteopontin (OPN) in DEX-injured osteoblasts. For the metabolomics study, a total of 27 differential metabolites were detected in the DEX group vs. the control group, of which 10 were significantly reversed after RR treatment. These metabolites were majorly involved in steroid hormone biosynthesis, sex steroids regulation, and amino acid metabolism. By metabolic pathway and Western blotting analysis, it was further ascertained that RR protected against DEX-induced bone loss, mainly via interfering steroid hormone biosynthesis, as evidenced by the up-regulation of cytochrome P450 17A1 (CYP17A1) and aromatase (CYP19A1), and the down-regulation of 11β-hydroxysteroid dehydrogenase (HSD11B1). Collectively, these results indicated that RR had a notable preventing effect on GIOP, and the action mechanism might be related to steroid hormone biosynthesis. View Full-Text
Keywords: Rehmanniae Radix Preparata; glucocorticoid-induced osteoporosis; metabolomics; osteoblast; steroid hormone biosynthesis Rehmanniae Radix Preparata; glucocorticoid-induced osteoporosis; metabolomics; osteoblast; steroid hormone biosynthesis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Xia, T.; Dong, X.; Jiang, Y.; Lin, L.; Dong, Z.; Shen, Y.; Xin, H.; Zhang, Q.; Qin, L. Metabolomics Profiling Reveals Rehmanniae Radix Preparata Extract Protects against Glucocorticoid-Induced Osteoporosis Mainly via Intervening Steroid Hormone Biosynthesis. Molecules 2019, 24, 253.

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