Poncirin prevents bone loss in glucocorticoid-induced osteoporosis in vivo and in vitro

Abstract

Poncirin, a flavonoid isolated from the fruit of Poncirus trifoliata, possesses anti-bacterial and anti-inflammatory activities. However, the action of poncirin in bone biology is unclear. In this study, the in vivo and in vitro effects of poncirin in a glucocorticoid-induced osteoporosis (GIO) mouse model were investigated. Seven-month-old male mice were assigned to the following five groups: (1) sham-implantation (sham), (2) prednisolone 2.1 mg/kg/day (GC), (3) GC treated with 10 mg/kg/day of genistein, (4) GC treated with 3 mg/kg/day of poncirin, (5) and GC treated with 10 mg/kg/day of strontium (GC + SrCl(2)). After 8 weeks, bone loss was measured by microcomputed tomography. Osteocalcin (OC) and C-terminal telopeptides of type I collagen (CTX) were evaluated in sera. Runx2 protein, OC and osteoprotegerin (OPG) mRNA expression, alkaline phosphatase (ALP) activity, and mineral nodule assay were performed in C3H10T1/2 or primary bone marrow stromal cells. Poncirin significantly increased the bone mineral density and improved the microarchitecture. Poncirin increased serum OC, Runx2 protein production, expression of OC and OPG mRNA, ALP activity, and mineral nodule formation; and decreased serum CTX. These effects were more prominent in the poncirin group compared to the other positive control groups (genistein and strontium). The poncirin-mediated restoration of biochemical bone markers, increased bone mineral density, and improved trabecular microarchitecture likely reflect increased bone formation and decreased bone resorption in GIO mice.

Poncirin Induces Apoptosis in AGS Human Gastric Cancer Cells through Extrinsic Apoptotic Pathway by up-Regulation of Fas Ligand

“…Citrus fruits contain abundant flavonoids such as Hesperidin, Naringin, Nobiletin, and Poncirin, which exhibit anticancer effect in different cancer cells [ 9 , 10 ]. Poncirin, the 7- O -neohesperidoside of isosakuranetin ( Figure 1 A), is a flavanone glycoside with bitter taste possessing various biological benefits such as antioxidant, anti-microbial, anti-inflammatory, and anti-cancer activities [ 11 , 12 , 13 ]. However, limited reports are available regarding anti-cancer effects of Poncirin and its molecular mechanisms.…”

Supraphysiologic glucocorticoid administration increased biomechanical bone strength of rats' vertebral body

“…However, many studies in vivo have shown GC administration to rats both histologically and histomorphometrically inhibits bone formation in the trabecular bone; particularly in the vertebrae [ 11 12 13 14 15 16 17 18 19 20 21 22 ]. In the other hand, it would reduce bone strength [ 12 15 21 22 ] and bone mineral density (BMD) as shown by BMD and other radiologic imaging techniques [ 11 13 16 19 21 23 24 25 ]. In addition, It would cause a decrease in biomarkers in the serum [ 13 15 16 17 24 25 ].…”

“…In the other hand, it would reduce bone strength [ 12 15 21 22 ] and bone mineral density (BMD) as shown by BMD and other radiologic imaging techniques [ 11 13 16 19 21 23 24 25 ]. In addition, It would cause a decrease in biomarkers in the serum [ 13 15 16 17 24 25 ]. Eventual, GCs cause decrease in the molecular elements of bones as shown by the molecular biology techniques [ 14 17 18 20 22 25 ].…”

“…In addition, It would cause a decrease in biomarkers in the serum [ 13 15 16 17 24 25 ]. Eventual, GCs cause decrease in the molecular elements of bones as shown by the molecular biology techniques [ 14 17 18 20 22 25 ].…”

Aqueous extract of pomegranate seed attenuates glucocorticoid-induced bone loss and hypercalciuria in mice: A comparative study with alendronate

“…Moreover, clinical studies have shown that low-dose GC inhalatory therapy (8) or high-dose oral GC therapy, particularly with dexamethasone (DXM) (9) causes bone loss in humans. Briefly, the underlying molecular mechanisms responsible for GC-induced bone loss involve a decrease in bone formation directly by inhibiting osteoblasts from producing new bone and an increase in bone resorption by increasing osteoclast activity (10,11). In vitro studies demonstrated that GCs are capable of inducing the apoptosis of osteoblasts and osteocytes (3,12).…”