الفهرس 
TitleOnly 14 pages are availabe for public view
 |  | from | 131 |  |  |
| | | from | 131 | | |
Abstract
Osteoporosis (OP) is the most common metabolic bone disorder affecting up to 40% of postmenopausal women, characterized by a reduction in bone mass and strength leading to bone fragility and fractures. The prevalence of OP in Egypt was 21.9% in men and 28.4% in women. Furthermore, 26% men and 53.9% women had osteopenia. The prevalence of OP in postmenopausal women in rural areas of Upper Egypt was higher reaching 47.8%. Despite the available tools for diagnosis and stratification of a fracture risk, bone loss occurs insidiously and osteoporosis is often diagnosed after the first fracture has occurred, with important health-related outcomes. Therefore, the need of biochemical markers that could efficiently diagnose bone fragility and osteoporosis is still necessary.
Conventional therapies commonly used for the treatment of bone disorders include bisphosphates and estrogen hormonal therapy. But the adverse effects like burning sensation and gastrointestinal tract disturbances associated with these therapies limit their use. Thus the herbal medication has been and remains commonly used instead of chemical drugs because of its minor side effects. Lepidium sativum L. (LS), or what is called locally “hab arachad”, is a native shrub belonging to Brassicaceae family, wildly grown in the Middle East where LS is largely recommended by traditional herbal healers for hypertension, diabetes control, renal disease and phytotherapy. The LS seeds are well known in Saudi Arabia and some other Arab countries as a good alternative medication for fracture healing. This property has attracted our interest to study its ability to treat osteoporosis induced by glucocorticoids in rats.
Chitosan has been used as a carrier in polymeric nanoparticles for drug delivery through various routes of administration. Nanoparticles (NP) prepared with chitosan and chitosan derivatives typically possess a positive surface charge and mucoadhesive properties such that can adhere to mucus membranes and release the drug payload in a sustained release manner.
The aim of this study is to evaluate the effect of Lepidium sativum L. extract loaded on chitosan nanoparticles on gene expression of miR-142-3p and miR-23a in experimental rat model of osteoporosis.
This study was conducted on 50 male Wistar rats weighing from 200 to 250 grams. Osteoporosis was induced in rats by subcutaneous injection with methylprednisolone (3.5 mg/kg b.wt / day) for 4 weeks. Rats were divided into 2 groups: group I (control): 10 Healthy male rats. group II: 40 Untreated osteoporotic rats which was subdivided into 4 subgroups: (each group 10 rats) group IIA: Untreated osteoporotic rats. group IIB: osteoporotic rats were orally treated with 400 mg/kg b.wt /day LS extract for 12 weeks. group IIC: osteoporotic rats were orally treated with chitosan nanoparticles (CN) for 12 weeks. group IID: osteoporotic rats were treated with 400 mg/kg b.wt /day LS extract loaded on chitosan nanoparticles for 12 weeks.
Summary, Conclusion and Recommendations
80
At the end of treatment period, all rats were sacrificed under carbon dioxide then blood samples were collected and centrifuged at 3,000 rpm for 10 min to obtain serum samples for biochemical analysis of calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP), tumor necrosis factor alpha (TNF-α) and IL-1. Meanwhile plasma samples were collected for assessment of miR-23a and miR-142-3p. Also the femur tissues of the rats were collected for histopathological examination. The right tibia was dissected, weighed, fixed in 10% (v/v) formaline and embedded in paraffin wax for cross sectioning. Five micron sections were stained with haematoxylin and eosin (H&E) and alzarin red s then examined under light microscope.
The untreated osteoporotic rats showed marked impairment in bone minearalization emphasized by significant decrease in calcium and relative decrease in phosphorus. The rats suffered from severe inflammation confirmed by a significant increase in (TRAP), (TNF-α) and IL-1. The rats suffered from severe osteoporosis emphasized by significant elevation in the expression of miR-23a and a significant decrease in the expression of miR-142-3p. These findings suggests an increased in the bone loss which was supported by the osteoporotic changes that was found by histological examination of tibia bones.
Treatment with either LS, LS loaded on CN and CN ameliorated the above mentioned changes with variable degrees, with a net results of enhanced serum calcium and phosphorus. Treated rats showed a significant decrease in the expression of miR-23a and a significant increase in the expression of miR-142-3p which emphasized treatment of osteoporosis. The effect of treatment was confirmed by histopathological observations.
6.2. Conclusion
from this study we concluded that:
Lepidium sativum L. ethanolic extract has powerful therapeutic effects in the osteoporotic rat model.
Treatment with LS loaded on CN, through a long duration (12 weeks), has significantly improved the biochemical bone indices and restored microarchitecture of femurs and vertebral bones of the glucocorticoid induced osteoporotic rats compared to LS and CN treatment groups. The loading of LS on CN may be a new treatment strategy for preventing bone loss and reversing bone mass and quality in osteoporotic disorders.
All of these effects together with the safety and no adverse effects of LS make it a promising therapeutic agent for management of osteoporosis.
6.3. Recommendations
Further investigation is required to elucidate the particular component of LS that is responsible for the anti-osteoporotic effect documented with the treatment.
MicroRNAs are stable with great potential as biomarkers for several diseases, including osteoporosis.