1. Protective Effects of Ligustroflavone, an Active Compound from Ligustrum lucidum, on Diabetes-Induced Osteoporosis in Mice: A Potential Candidate as Calcium-Sensing Receptor Antagonist.
- Author
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Feng R, Ding F, Mi XH, Liu SF, Jiang AL, Liu BH, Lian Y, Shi Q, Wang YJ, and Zhang Y
- Subjects
- Animals, Apigenin administration & dosage, Apigenin isolation & purification, Bone Density drug effects, Calcium metabolism, Cancellous Bone metabolism, Cells, Cultured, Gene Expression drug effects, Glycosides administration & dosage, Glycosides isolation & purification, HEK293 Cells, Humans, Kidney metabolism, Male, Mice, Inbred C57BL, Parathyroid Glands cytology, Parathyroid Glands metabolism, Parathyroid Hormone metabolism, Receptors, Calcium-Sensing genetics, Receptors, Calcium-Sensing metabolism, Time Factors, Apigenin pharmacology, Diabetes Complications complications, Glycosides pharmacology, Ligustrum chemistry, Osteoporosis etiology, Osteoporosis prevention & control, Receptors, Calcium-Sensing antagonists & inhibitors
- Abstract
Ligustroflavone is one major compound contained in active fraction from Fructus Ligustri Lucidi (the fruit of Ligustrum lucidum), which could regulate parathyroid hormone (PTH) levels and improve calcium balance by acting on calcium-sensing receptors (CaSR). This study aimed to explore the potency of ligustroflavone as a CaSR antagonist and its protective effects against diabetic osteoporosis in mice. LF interacted well with the allosteric site of CaSR shown by molecular docking analysis, increased PTH release of primary parathyroid gland cells and suppressed extracellular calcium influx in HEK-293 cells. The serum level of PTH attained peak value at 2 h and maintained high during the period of 1 h and 3 h than that before treatment in mice after a single dose of LF. Treatment of diabetic mice with LF inhibited the decrease in calcium level of serum and bone and the enhancement in urinary calcium excretion as well as elevated circulating PTH levels. Trabecular bone mineral density and micro-architecture were markedly improved in diabetic mice upon to LF treatment for 8 weeks. LF reduced CaSR mRNA and protein expression in the kidneys of diabetic mice. Taken together, ligustroflavone could transiently increase PTH level and regulate calcium metabolism as well as prevent osteoporosis in diabetic mice, suggesting that ligustroflavone might be an effective antagonist on CaSR.
- Published
- 2019
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