A Metabolomics Study on the Bone Protective Effects of a Lignan-Rich Fraction From Sambucus Williamsii Ramulus in Aged Rats

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.

Tilapia nilotica Head Lipids Improved Bone Loss by Regulating Inflammation and Serum Metabolism Through Gut Microbiota in Ovariectomized Rats

“…Xiao et al (50) proved that the bone mineral density of ovariectomized rats continues to decline, and the trabecular bone microstructure deteriorates, which was consistent with the Micro-CT results of the OVX group in this experiment. This experiment compared the Micro-CT data of THLs-treated rats and OVX group rats.…”

Metabolomics in Bone Research

“…The results proved that SWR administration leads to bone recovery by restoring the levels of 26 metabolites corresponding to estrogen deficiency which are involved in lipids, amino acids, tryptophan metabolisms, and anti-oxidative systems. In particular, upon SWR treatment, upregulation of superoxide dismutase and catalase was observed while serotonin was downregulated [ 70 , 114 ]. Additionally, metabolomics can provide valuable data to determine bone tissue treatment a gents’ side effect.…”

Metabolic Alterations in Older Women With Low Bone Mineral Density Supplemented With Lactobacillus reuteri

“…Untargeted metabolomics have provided an opportunity to investigate the global metabolic changes in human populations. (11,12) Although the existing metabolomic studies related to osteoporosis had been performed in rats and human populations, (13)(14)(15)(16) the effects of probiotic supplementation on human bone metabolism have not been explored. Therefore, we investigated the effect of daily supplementation with L. reuteri or placebo on serum metabolomic profiles in older women included in a one-year randomized controlled trial (RCT), in a non-predefined post hoc analysis.…”