Potential benefits of dihydroartemisinin in suppression of dexamethasone induced osteoporosis, osteoclast formation and RANKL induced signaling pathways in adult female albino rat

Abstract

Osteoporosis is a musculoskeletal disorder characterized by reduced bone density and increased susceptibility to fractures. Fractures cause a considerable increase in mortality, disability, and morbidity incidence. Artemisia annua is a medicinal plant, used for long time in Asian countries and its active metabolite is Dihydroartemisinin (DHA). It is proven to possess anti-inflammatory and antioxidant effects. The present study is the first to investigate the role of different doses of DHA in treatment of Dexamethasone (Dexa)-induced osteoporosis. Thirty female Wister adult rats were divided into three groups for three months. Control and Dexa groups were both six in number. Dihydroartemisinin treated groups, eighteen in number, received intramuscular injection of Dexamethasone and intraperitoneal injection of DHA, then subdivided in three different groups according to DHA doses (10, 20 and 30 mg/kg body wight). Blood level of Ca, P, calcitonin, alkaline and acid phosphatase, and Tissue MDA, GSH were estimated. Tibiae were stained with H&E, Masson- Goldner, and immunological examination of β catenin and RANKL was done. Then, one-way ANOVA test, followed by Tukey’s post-hoc test, was used in order to compare groups, and P value <0.05 was considered statistically significant. A highest dose of DHA showed normalization of blood parameter and oxidative stress markers. Also, bone histology improvement, reduced RANKL and increased β catenin expression were recorded. Treatment with DHA has significantly improved the oxidative stress, biochemical parameters, and bone histology. Dihydroartemisinin might represent a novel approach for modulation of osteoporosis induced by glucocorticoid.