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Title: A metabolomics study on the bone protective effects of a lignan-rich fraction from Sambucus Williamsii Ramulus in aged rats
Authors: Xiao HH 
Sham, TT 
Chan CO 
Li MH 
Chen, X
Wu, QC
Mok, DKW 
Yao, XS
Wong, MS 
Keywords: Amino acid metabolism
Anti-oxidative action
Sambucus williamsii ramulus
Issue Date: 2018
Publisher: Frontiers Research Foundation
Source: Frontiers in pharmacology, 21 Aug 2018, v. 9, 932, p. 1-16 How to cite?
Journal: Frontiers in pharmacology 
Abstract: The lignan-rich fraction (SWR) of Sambucus Williamsii Ramulus, a folk herbal medicine in China for treatment of bone diseases, has previously reported to exert protective effects on bone without exerting uterotrophic effects in ovariectomized (OVX) mice. The aim of the present study was to identify the potential metabolites and the associated metabolic pathways that contribute to the beneficial effects of SWR on bone in vivo. Aged female Sprague Dawley rats (9 months old) were either sham-operated or ovariectomized for 12 weeks, before receiving treatment for another 12 weeks with the following treatment groups (n = 12 each): vehicle (Sham), vehicle (OVX), Premarin (130 μg/kg) or low (57 mg/kg), medium (114 mg/kg), and high (228 mg/kg) doses of SWR. The results showed that SWRH significantly suppressed bone loss, improved bone micro-architecture and increased bone strength on tibia without stimulating uterus weight gain in OVX rats. Premarin exerted similar bone protective effects as SWRH but elicited uterotrophic effects in OVX rats. The metabolic profiles of serum samples were analyzed by using ultra-performance liquid chromatography quadrupole time-of flight mass spectrometry and gas chromatography time-of flight mass spectrometry, and the metabolites that were significantly altered were identified by multivariate statistical analysis. Our study indicated that SWRH effectively restored the changes of 26 metabolites induced by estrogen-deficiency in OVX rats, which related to lipids, amino acids, tryptophan metabolisms, and anti-oxidative system. A subsequent validation showed that the serum level of superoxide dismutase and catalase were indeed up-regulated, while the serotonin level in a tryptophan hydroxylase 1 (TPH1) high expressing cells (rats RBL-2H3 cells) was down regulated after treatment with SWR. The results also suggested that the gut-microbiota may play an important role on the bone protective effects of SWR. The current study provides insight for understanding the unique mechanism of actions of SWR that might be involved in achieving bone protective effects in vivo.
EISSN: 1663-9812
DOI: 10.3389/fphar.2018.00932
Rights: Copyright © 2018 Xiao, Sham, Chan, Li, Chen,Wu, Mok, Yao andWong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) ( The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
The following publication Xiao, H. -., Sham, T. -., Chan, C. -., Li, M. -., Chen, X., Wu, Q. -., . . . Wong, M. -. (2018). A metabolomics study on the bone protective effects of a lignan-rich fraction from Sambucus Williamsii ramulus in aged rats. Frontiers in Pharmacology, 9, 932, 1-16 is available at
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