Geraniin

Geraniin suppresses RANKL-induced osteoclastogenesis in vitro and ameliorates wear particle-induced osteolysis in mouse model.[Pubmed: 25016282]

Exp Cell Res. 2015 Jan 1;330(1):91-101.

Wear particle-induced osteolysis and subsequent aseptic loosening remains the most common complication that limits the longevity of prostheses. Wear particle-induced osteoclastogenesis is known to be responsible for extensive bone erosion that leads to prosthesis failure. Thus, inhibition of osteoclastic bone resorption may serve as a therapeutic strategy for the treatment of wear particle induced osteolysis.
METHODS AND RESULTS:
In this study, we demonstrated for the first time that Geraniin, an active natural compound derived from Geranium thunbergii, ameliorated particle-induced osteolysis in a Ti particle-induced mouse calvaria model in vivo. We also investigated the mechanism by which Geraniin exerts inhibitory effects on osteoclasts. Geraniin inhibited RANKL-induced osteoclastogenesis in a dose-dependent manner, evidenced by reduced osteoclast formation and suppressed osteoclast specific gene expression. Specially, Geraniin inhibited actin ring formation and bone resorption in vitro. Further molecular investigation demonstrated Geraniin impaired osteoclast differentiation via the inhibition of the RANKL-induced NF-κB and ERK signaling pathways, as well as suppressed the expression of key osteoclast transcriptional factors NFATc1 and c-Fos.
CONCLUSIONS:
Collectively, our data suggested that Geraniin exerts inhibitory effects on osteoclast differentiation in vitro and suppresses Ti particle-induced osteolysis in vivo. Geraniin is therefore a potential natural compound for the treatment of wear particle induced osteolysis in prostheses failure.

Geraniin induces apoptotic cell death in human lung adenocarcinoma A549 cells in vitro and in vivo.[Pubmed: 24289071]

Can J Physiol Pharmacol. 2013 Dec;91(12):1016-24.

Geraniin has previously been reported to possess extensive biological activity. In this study, we reported that Geraniin is an inhibitor of tumor activity in vitro and in vivo.
METHODS AND RESULTS:
Geraniin suppressed the proliferation of A549 cells in a dose- and time-dependent manner. Geraniin arrested the cell cycle in the S phase and induced a significant accumulation of reactive oxygen species (ROS), as well as an increased percentage of cells with mitochondrial membrane potential (MMP) disruption. Western blot analysis showed that Geraniin inhibited Bcl-2 expression and induced Bax expression to disintegrate the outer mitochondrial membrane and cause cytochrome c release. Mitochondrial cytochrome c release was associated with the activation of caspase-9 and caspase-3 cascades. Additionally, Geraniin resulted in tumor growth inhibition in A549 xenografts.
CONCLUSIONS:
Our results indicate cytotoxic activity of Geraniin towards cancer cells in vitro and in vivo.

Osteoprotective effect of geraniin against ovariectomy-induced bone loss in rats.[Pubmed: 25532904]

Bioorg Med Chem Lett. 2015 Feb 1;25(3):673-9.

In the present study, we investigated the antiosteoporotic effect of Geraniin on osteoporosis induced by OVX in rats.
METHODS AND RESULTS:
The analysis of biochemical parameters showed that Geraniin could significantly increase serum calcium, estradiol and calcitonin levels, and decrease serum ALP, tartrate-resistant acid phosphatase, serum crosslinked C-terminal telopeptide of type I collagen, and urinary deoxypyridinoline/creatinine ratio levels, respectively. Geraniin was also found to prevent OVX-induced bone loss in bone mineral density and bone mineral content, to elevate femur weight and bone calcium content, and to enhance the bone mechanical properties as compared with OVX group. In addition, Geraniin was demonstrated to improve the histomorphological parameters of OVX-induced bone loss, including bone trabecular number, thickness, and separation.
CONCLUSIONS:
These results indicated that Geraniin have a protective effect against OVX-induced rat osteoporosis.

Geraniin exerts cytoprotective effect against cellular oxidative stress by upregulation of Nrf2-mediated antioxidant enzyme expression via PI3K/AKT and ERK1/2 pathway.[Pubmed: 25917210]

Biochim Biophys Acta. 2015 Apr 23;1850(9):1751-1761.

Geraniin, an active compound with remarkable antioxidant activity, was isolated from Geranium sibiricum. The present study aimed to investigate whether Geraniin has the ability to activate Nrf2, induce antioxidant enzyme expression and protect cells from oxidative damage.
METHODS AND RESULTS:
The cells were pretreated with Geraniin for 24h and exposed to hydrogen peroxide (H2O2) for 4h. Intracellular reactive oxygen species (ROS) levels, mitochondrial membrane potential and apoptosis were measured. We also investigated intracellular glutathione (GSH) levels and changes in nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated signaling cascade in cells treated with Geraniin. We investigated the protective effects of Geraniin against H2O2-induced apoptosis in HepG2 cells. Geraniin significantly reduced H2O2-induced oxidative damage in a dose dependent manner. Further, Geraniin induced the expression of heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase-1 (NQO1) and level of glutathione (GSH) in a concentration- and time-dependent manner, and increased Nrf2 nuclear translocation. The Nrf2-related cytoprotective effects of Geraniin were PI3K/AKT and extracellular signal-regulated protein kinase1/2 (ERK1/2) pathway-dependent. However, inhibitors of PI3K/AKT and ERK1/2 (LY294002 or U0126) not only suppressed Geraniin-induced nuclear translocation of Nrf2 but also abolished the expression of HO-1, NQO1 and GSH.
CONCLUSIONS:
These results demonstrated that Geraniin induced Nrf2-mediated expression of antioxidant enzymes HO-1 and NQO1, presumably via PI3K/AKT and ERK1/2 signaling pathways, thereby protecting cells from H2O2-induced oxidative cell death. GENERAL SIGNIFICANCE: Geraniin, at least in part, offers an antioxidant defense capacity to protect cells from the oxidative stress-related diseases.

Geraniin down regulates gamma radiation-induced apoptosis by suppressing DNA damage.[Pubmed: 23541438]

Food Chem Toxicol. 2013 Jul;57:147-53.

Gamma ray irradiation triggers DNA damage and apoptosis of proliferating stem cells and peripheral immune cells, resulting in the destruction of intestinal crypts and lymphoid system. Geraniin is a natural compound extracts from an aquatic plant Nymphaea tetragona and possesses good antioxidant property.
METHODS AND RESULTS:
In this study, we demonstrate that Geraniin rescues radiosensitive splenocytes and jejunal crypt cells from radiation-induced DNA damage and apoptosis. Isolated splenocytes from C57BL/6 mice treated with Geraniin were protected against radiation injury of 2 Gy irradiation through the enhancement of the proliferation and attenuation of DNA damage. Also, Geraniin inhibited apoptosis in radiosensitive splenocytes by reducing the expression level and immunoreactivity of proapoptotic p53 and Bax and increasing those of anti-apoptotic Bcl-2. In mice exposed to radiation, Geraniin treatment protected splenocytes and intestinal crypt cells from radiation-induced cell death.
CONCLUSIONS:
Our results suggest that Geraniin presents radioprotective effects by regulating DNA damage on splenocytes, exerting immunostimulatory capacities and inhibiting apoptosis of radiosensitive immune cells and jejunal crypt cells. Therefore, Geraniin can be a radioprotective agent against γ-irradiation exposure.