Abstract
Postmenopausal osteoporosis (PMOP) is the most common metabolic bone illness among the elderly especially in postmenopausal women resulting from a reduction in bone mineral density, but there is no effective drug at present. The study was aimed at evaluating efficacy of osthole against osteoporosis using high-throughput metabolomics method. The blood samples for illustrating the pathological mechanism of PMOP and exploring the efficacy of osthole treatment (ST) were collected to perform metabolites and metabolic profiles and pathways analysis using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and pattern recognition methods. In addition, backbone weight, the bone density, and some vital biochemical indexes were also detected. A total of 28 metabolites were identified as biomarkers for ovariectomized-osteoporosis model, and ST could significantly regulate 19 of them including lysine, linoleic acid, 3-hydroxybutyric acid, prostaglandin F2a, taurocholic acid, LysoPC(15:0), l-carnitine, glucose, arginine, citric acid, corticosterone, ornithine, tryptophan, arachidonic acid, Cer(d18:0/18:0), glutamine, uric acid, 8-HETE, estriol, which mainly related with 13 metabolic pathways, such as linoleic acid metabolism, starch, and sucrose metabolism, arachidonic acid metabolism, alanine, aspartate and glutamate metabolism, arginine and proline metabolism, citrate cycle (TCA cycle), and arginine biosynthesis. The ovariectomized model (OVX) rats display a significant decrease bone density, TGF-β1, NO, and NOS level, and a significant increase bone weight, IL-6, TNF-α, and Ca 2+ level. These parameters in the ST rats were evidently improved as compared to the OVX group. ST effectively mitigated ovariectomy-induced osteoporosis in rats by affecting endogenous metabolite-related metabolic mechanism and showed the natural alternative with potential for the treatment of PMOP.
Highlights
Osteoporosis is a progressive bone illness characterized by reduced bone mass and density, microarchitectural deterioration of tissue and proteins expression alteration in bones (Sun et al, 2013a; Aujla and Majithia, 2016; Qiu et al, 2019)
In the light of the position and function of the double bond, polyunsaturated fatty acids (PUFA) are divided into omega-6 series and omega-3 series, which linoleic acid and arachidonic acid belong to the omega-6 series, linoleic acid can be converted into arachidonic acid in the body
This study found that serum linoleic acid, prostaglandin F2a, and arachidonic acid were abnormally elevated in ovariectomized osteoporotic rats
Summary
Osteoporosis is a progressive bone illness characterized by reduced bone mass and density, microarchitectural deterioration of tissue and proteins expression alteration in bones (Sun et al, 2013a; Aujla and Majithia, 2016; Qiu et al, 2019). Women with all ages resulting from physiological structure of bone as well as gradually reducing levels of estrogen and progesterone, which is related with higher rate of bone resorption in osteoclasts are approximately five times possibility to suffer from osteoporosis than men (Srivastava and Deal, 2002; Adler, 2014). It was reported that about 200 million women aged between 45 and 55 years are affected by postmenopausal osteoporosis (Hromadnikova et al, 2020). There is an urgent need to discover and develop emerging methods containing natural products with minimal side effects and strong activity for prevention and treatment of osteoporosis in early stage
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