Abstract

Lepidium sativum seeds are used traditionally to accelerate healing of bone fracture in addition to its culinary uses. This study aimed to characterize the osteoprotective effect of L. sativum in an ovariectomized rat model at two dose levels (50 and 100 mg/kg) using 17β-estradiol as a positive reference standard. Moreover, a complete metabolite profile of L. sativum via UHPLC/PDA/ESI–MS, as well as headspace solid-phase microextraction (SPME)-GC/MS is presented. Results revealed that L. sativum extract exhibited significant anti-osteoporotic actions as evidenced by mitigating the decrease in relative bone weight concurrent with improved longitudinal and perpendicular femur compression strength. Further, the extract enhanced the serum bone formation biomarkers lactate dehydrogenase (LDH) activity and osteocalcin levels. The extract also inhibited exhaustion of superoxide dismutase (SOD) as well as glutathione peroxidase (GPx) activities and accumulation of lipid peroxides in bone tissues. This is in addition to ameliorating the rise in the markers of bone resorption carboxyterminal telopeptide, type I (CTXI) and tartrate-resistant acid phosphatase (TRAP) and modulating receptor activator of nuclear factor kappa-Β ligand (RANKL)/ osteoprotegerin (OPG) expression. Metabolite characterization suggests that glucosinolates, lignans, coumarins, phenolic acids, and alkaloids mediate these anti-osteoporotic effects in a synergistic manner.

Highlights

  • Osteoporosis is a bone disorder, which is a consequence of imbalance in the formation and resorption of bone tissues in favor of bone loss, with elevated fracture risk

  • This study aimed to evaluate the osteoprotective effects of L. sativum seed extract in ovariectomized rats and characterize the metabolite composition of the extract by large-scale chemical profiling using UHPLC/PDA/ESI-MS and GC/MS

  • Osteoporosis is caused by different risk factors, including estrogen hormone deficiency after menopause, consumption of corticosteroids, aging, malabsorption of calcium, or immune-related factors

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Summary

Introduction

Osteoporosis is a bone disorder, which is a consequence of imbalance in the formation and resorption of bone tissues in favor of bone loss, with elevated fracture risk. Current therapy suffers from various adverse effects; from gastrointestinal disturbances to cancer [6,7] This necessitates the search for new effective and safe therapies. Different plant secondary metabolites impact bone remodeling, for example, isoflavonoids (daidzein, genistein, cajanin, and formononetin due to their estrogenic properties), lignans (secoisolariciresinol and matairesinol, which are converted by gut microflora to mammalian lignans, enterodiol and enterolactone that are estrogenic). Flavonoids such as quercetin, kaempferol, or hesperidin and carotenoids have all shown preservation of bone mineral density following ovariectomy-induced bone loss in female rodents [8,9]

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