Ginsenoside Rb1 does not halt osteoporotic bone loss in ovariectomized rats

Abstract

Osteoporosis (OP) is a systemic skeletal disorder, manifesting with a reduction in bone mass and deterioration of the microarchitecture. Mesenchymal stem cells (MSCs) have an innate ability to differentiate into several cell types, including osteoblasts (OB). Ginsenoside Rb1 (GRb1) is an ethanol extract from ginseng and contains a highly concentrated form of ginsenoside. GRb1 shows extensive beneficial health effects such as anti-oxidative and anti-inflammatory functions, modulating the immune system and inhibiting osteoclastogenesis. We hypothesized that GRb1 can promote MSC differentiation into OBs and inhibit bone loss. In the present study, we aimed to address two questions: (1) Will GRb1 have a positive effect on osteogenic differentiation of MSCs? and (2) Will GRb1 halt bone loss in ovariectomized (OVX) rats? We investigated the effects of GRb1 on viability and osteogenic differentiation of rat mesenchymal stem cells (rMSCs). Our results showed that GRb1 at concentrations of 10−8 M and 10−6 M can increase alkaline phosphatase activity, mineralization and the expression of osteogenic related proteins, such as osteopontin and osteoprotegerin, while incubating rMSCs with osteogenic induction medium and GRb1. Adding GRb1 into the medium can prevent rMSCs from Oxidative damage at the concentration of 25μM H2O2. Furthermore, 40 4-month-old rats were assigned to 5 groups(8 rats per group): the basal group, the sham group, the OVX group, the high dose of GRb1 group (6 mg/kg/day) and the low dose of GRb1 group (3 mg/kg/day). Rats recrived treatment 3days after surgery and last for 14 weeks. Examinations included serum analysis, mechanical testing, Masson-Goldner trichrome staining and bone histomorphometry analysis. The results showed that OVX can lead to dyslipidemia and excessive oxidative stress, whereas GRb1 cannot significantly halt dyslipidemia and excessive oxidative stress in OVX rats. In addition, the bone density of the lumbar vertebra and femur were decreased significantly in the OVX rats, and GRb1 could not inhibit bone loss. Bone histomorphometry analysis showed that the number and width of bone trabecula of the tibia were reduced in OVX rats, and GRb1 could not prevent their occurrence. A bone biomechanics assay showed that GRb1 cannot improve the ability of bone structure to resist fracture of the femur in OVX rats. The current study demonstrated that GRb1 has an obvious effect on osteogenic differentiation in rMSCs but no obvious effect on bone loss in OVX rats. These findings indicate GRb1 has a positive effect on rMSCs but does not have an effect on bone loss in OVX rats at the concentration we used.

Effect of Co-Administration of Panax ginseng and Brassica oleracea on Postmenopausal Osteoporosis in Ovariectomized Mice

“…Moreover, ginsenoside Rg1 countervailed the decreased BMD in OVX rats [ 17 ], ginsenoside Rb2 revealed anti-osteoporosis effect by reducing oxidative damage and bone resorbing cytokines in osteoblast cells [ 19 ]. In contrary, ginsenoside Rb1 increased osteogenic differentiation and osteogenic proteins, however, did not halt osteoporotic bone loss in OVX rats [ 20 ]. However, despite accumulating data on the effect of P. notoginseng on OP in rats, the effect of P. ginseng on postmenopausal OP is not clearly defined; thus, we investigated the effect of P. ginseng on this disorder.…”

Effects of Korean red ginseng on three-dimensional trabecular bone microarchitecture and strength in growing rats: Comparison with changes due to jump exercise

“…Several studies have demonstrated that ginsenosides inhibit osteoclastogenesis and reduce bone resorption [ 15 – 18 ], although this is not uniformly the case [ 36 , 37 ]. The histomorphometric data in the present study showed similar results.…”

Emerging Natural-Product-Based Treatments for the Management of Osteoarthritis

“…Ginsenosides also have osteoprotective properties. Several studies have demonstrated that Rb1, Rh1, Rg3, and Rg5 stimulated osteoblast differentiation in vitro [ 255 , 256 , 257 , 258 ]. Furthermore, Rb1 and Rg3 inhibited osteoclastogenesis by suppressing RANKL-induced activation via modulating MAPKs and NF-κB pathways in vitro, but only Rg3 was able to alleviate bone mineral density loss in vivo [ 259 , 260 ].…”