A 1HNMR-Based Metabonomics Study of Postmenopausal Osteoporosis and Intervention Effects of Er-Xian Decoction in Ovariectomized Rats

Abstract

A metabonomics method using 1H nuclear magnetic resonance spectroscopy (1HNMR) was applied to obtain a systematic view of the development and progression of postmenopausal osteoporosis. Using partial least squares discriminant analysis (PLS-DA), 26 and 34 characteristic resonances were found respectively in urine and plasma of ovariectomized rats (Variable importance, VIP value ≥1.0), and the significant altered metabolites identified in the plasma and urine were 10 and 9, respectively. Changes in these metabolites were related to the pathways of lipid, energy and amino acid metabolism, some of which involved the oxidative system. The described method was also used to analyze the therapeutic effects of Er-Xian Decoction (EXD), a traditional Chinese medicine widely used in the clinical treatment of osteoporosis in China. The results showed that EXD administration could provide satisfactory effects on osteoporosis through partially regulating the perturbed pathways of lipid, energy and amino acid metabolism and improving the anti-oxidative ability.

Metabolomics and Its Application in the Development of Discovering Biomarkers for Osteoporosis Research

“…Er-Xian decoction, a popular Chinese medicinal formula comprised of Epimedium brevicornum Maxim, Curculigo orchioides Gaertn, Anemarrhena asphodeloides Bge, Phellodendron chinense Schneid, Morinda officinalis How, and Angelica sinensis Diels in a compositional ratio of 9:9:6:6:9:9, has been widely used for treating osteoporosis and relieving menopausal syndrome [59,60,61,62]. Xue et al demonstrated that the administration of Er-Xian extracts could provide satisfactory effects on OVX rats through the metabolomics analysis [51]. Gushudan, which consists of Herba Epimedii , Fructus Cnidii , Rhizoma Drynariae , and Radix Miltiorrhizae at a ratio of 2:1:1:1, has been accepted as a traditional formula for kidney-tonifying and bone-strengthening [63].…”

“…Ma et al found that the level of glucose was significantly elevated in rats six weeks after OVX removal surgery [52]. Likewise, Xue et al found the increased level of glucose and lactate in the OVX mice, and the results implied that ovariectomy can affect the energy metabolism and utilization [51]. Estrogen-deficiency induced obesity is associated with fat accumulation and excessive intake of energy that break down the balance of energy metabolism.…”

“…Qi et al found that postmenopausal women with osteopenia and osteoporosis had lower concentration of high-density lipoprotein cholesterol (HDL-C) and higher concentrations of low-density lipoprotein cholesterol (LDL-C), triglycerides and total cholesterol [22]. The result from Xue et al showed that ovariectomy induced an increase of plasma levels of low-density lipoprotein (LDL), choline, glycerophosphatide and lipid in mice, which indicated that the biological mechanism of osteoporosis is associated with lipid metabolism [51]. In Lee’s study, the levels of lysoPC 14:0, lysoPC 16:0, lysoPC 16:1, lysoPC 18:0, lysoPC 18:3, lysoPC 20:4, and lysoPC 20:5 increased in the OVX rats.…”

1H-NMR and HPLC–MS/MS-based global/targeted metabolomic evaluation of Hypericum perforatum L. intervention for menopause

“…Simultaneously, global metabolomics using the HPLC-MS/MS method provides corroborative evidence for targeted metabolomics studies. This study attempts to offer metabolomic evidence to explain the fine-tuned systems and complex metabolic networks in bio-systems and to provide a basis for updating and improving the mechanistic study of HPL function in menopausal syndromes (Xue et al, 2011;You et al, 2014;Zhu et al, 2010).…”

Serum Metabolomic Characteristics of Patients with Liver Cirrhotic Ascites

“…It is a powerful analytical platform that allows for the assessment of global metabolic profiles in easily accessible biofluids and biomarker discovery in order to distinguish between diseased and non-diseased status information [8] as well as for the evaluation of drug toxicity and gene function [9]. A number of new analytical technologies have been employed for metabolomics analysis, including 1 H-NMR [10], ultra-high-performance liquid chromatography quadrupole-time-of-flight/high-sensitivity mass spectrometry (UPLC-Q-TOF/HSMS) [11], UPLC-electrospray ionization/MS (UPLC-ESI/MS) [12], gas chromatography/MS [13] and others.…”