الفهرس 
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Abstract
The present work was performed to study the effect of berberine on metabolic and bone changes in ovariectomized rats. The present work was carried out on 60 female Wister rats of local strain. All rats were randomly divided into 6 groups (10 rats in each group) after the acclimatization period as the following: group I : (Normal control group): the animals of this group received 0.5 ml saline by oral gavage for 8 weeks. group II : (Sham operated group): the animals of this group received 0.5 ml saline by oral gavage for 8 weeks, but after underwent sham ovariectomy. group III : (Ovariectomized group): the animals of this group received 0.5 ml saline by oral gavage for 8 weeks, but after underwent bilateral ovariectomy group IV : (50 mg berberine treated ovariectomized group): the animals of this group underwent bilateral ovariectomy then treated with 50 mg BBR /kg dissolved in 0.5 ml saline and given by oral gavage daily for 8 weeks. group V : (100 mg berberine treated ovariectomized group) : the animals of this group underwent bilateral ovariectomy then treated with 100 mg BBR /kg dissolved in 0.5 ml saline and given by oral gavage daily for 8 weeks. group VI : (200 mg berberine treated ovariectomized group): the animals of this group underwent bilateral ovariectomy then treated with 200 mg BBR/kg dissolved in 0.5 ml saline and given by oral gavage daily for 8 weeks. Ovariectomy and sham operation: Bilateral ovariectomy and sham operations were done under general anaesthesia (using 16 mg Xylazine + 60 mg Ketamine I.p.) and under umbrella of broad-spectrum antibiotic (using 7mg/kg amoxicillin subcutaneously). Also, skin was disinfected with povidone iodine solution. Then, animals were kept in safe houses with possible measures of post-operative care. At the end of experimental period, 24 h after last treatment, all animals were anesthetized for blood sampling then decapitated while bone samples were taken for measurement of malondialdehyde (MDA) and reduced glutathione (GSH), detection of DNA damage and for routine histopathological study. Then, the sacrificed rats were packed in special package according to safety precautions and infection control measures and sent with hospital biohazards. For all animals, the following parameters were measured: • Serum estradiol • Serum glucose • Serum insulin • Homeostasis model assessment insulin resistance (HOMA-IR) index. • Serum total cholesterol (TC) • Serum low-density lipoprotein cholesterol (LDL-C) • Serum high-density lipoprotein cholesterol (HDL-C). • Serum malondialdehyde (MDA) • Serum reduced glutathione (GSH) • tumor necrosis factor-α (TNF-α) • Serum osteocalcin (OC) • Serum alkaline phosphatase (ALP) • Serum Cross-linked Carboxy-terminal telopeptide of type I collagen (CTX-I) Summary of results: Biochemical results from the present work revealed that sham operated group showed insignificant change in all studied parameters as compared to control group. These results were confirmed by histopathological findings and DNA examination of femur bone tissue as normal bony tissue formed of anastomosing thick bony trabeculae with normal osteocytes inside their lacunae and smooth endosteal surface lined by osteoblasts with cellular bone marrow spaces containing haemopoietic cells with few adipocytes. However, the ovariectomized group showed significant decrease in serum estradiol, HDL and bone GSH while serum GSH decreased insignificantly. There was significant increase in serum glucose, insulin, HOMA IR , total cholesterol ,LDL , serum MDA ,bone MDA ,TNF α , osteocalcin , ALP and CTX-I. The results of these parameters were confirmed by histopathological findings of femur bone tissue which showed signs indicating osteoporosis as: thin bony trabeculae with irregular endosteal surface , areas of pores and minor fractures , no mature osteocytes in lacunae , wide bone marrow spaces containing less haemopoietic cells and abundant adipocytes. DNA examination of femur bone tissue showed apoptotic DNA fragmentation at approximately 300 bp. However, after administration of BBR with doses 50, 100, 200 mg to ovariectomized rats the biochemical results revealed that there was significant decrease in serum glucose, insulin, HOMA IR, total cholesterol, LDL, serum MDA ,bone MDA ,TNF α , osteocalcin , ALP and CTX-I. While HDL and bone GSH significantly increased. Serum estradiol level remained decreased. Serum LDL was significantly lower in 200 mg BBR treated ovx group as compared to 50 mg BBR treated ovx group. Serum HDL was significantly higher in 200 mg BBR treated ovx group as compared to 50 ,100 mg BBR treated ovx groups. Serum MDA was significantly lower in 200 mg BBR treated ovx group as compared to 50 ,100 mg BBR treated ovx groups. Serum GSH was insignificantly increased in 50 mg BBR treated ovx group while significantly increased in 100, 200 mg BBR treated ovx groups. Serum TNF α was insignificantly decreased in 50 mg BBR treated ovx group while significantly decreased in 100, 200 mg BBR treated ovx groups and significantly lower in 200 mg BBR treated ovx group as compared to 50 mg BBR treated ovx group. Serum osteocalcin was significantly lower in 200 mg BBR treated ovx group as compared to 50 ,100 mg BBR treated ovx groups. Serum ALP and CTX -I were significantly lower in 200 mg BBR treated ovx group as compared to 50 mg BBR treated ovx group. The results of these parameters were confirmed by histopathological findings and DNA analysis of femur bone tissue that showed better improvement especially with higher doses as bony trabeculae became thick and anastomosing with mature osteocytes in their lacunae. More regular endosteal surface was detected. Bone marrow spaces were more cellular containing haemopoietic cells with few adipocytes. Also, reduction of apoptotic DNA fragmentation was detected.