| Description: |
Geraniin is a TNF-α releasing inhibitor with numerous activities including anticancer, anti-inflammatory, has anti-oxidant , and anti-hyperglycemic activities, with an IC50 of 43 μM. Geraniin presents radioprotective effects by regulating DNA damage on splenocytes, exerting immunostimulatory capacities and inhibiting apoptosis of radiosensitive immune cells and jejunal crypt cells. Geraniin induces 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.
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| Targets: |
NF-kB | ERK | Nrf2 | PI3K | Akt | NADPH-oxidase | HO-1 | ROS | MMP(e.g.TIMP) | p53 | NQO1 | TNF-α |
| In vitro: |
| Exp Cell Res. 2015 Jan 1;330(1):91-101. | | Geraniin suppresses RANKL-induced osteoclastogenesis in vitro and ameliorates wear particle-induced osteolysis in mouse model.[Pubmed: 25016282] |
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. | | Can J Physiol Pharmacol. 2013 Dec;91(12):1016-24. | | Geraniin induces apoptotic cell death in human lung adenocarcinoma A549 cells in vitro and in vivo.[Pubmed: 24289071] | 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. | | J Biochem Mol Toxicol . 2017 Sep;31(9). | | Geraniin suppresses ovarian cancer growth through inhibition of NF-κB activation and downregulation of Mcl-1 expression[Pubmed: 28590547] | | Abstract
This study investigated the anticancer effects of geraniin on ovarian cancer cells and the signaling pathways involved. Ovarian cancer cells were treated with different concentrations of geraniin for 48 h and examined for viability, apoptosis, mitochondrial membrane depolarization, and gene expression. Xenograft tumor studies were performed to determine the anticancer activity of geraniin in vivo. Geraniin significantly decreased cancer cell viability in a concentration-dependent fashion. Geraniin significantly triggered apoptosis, which was accompanied by loss of mitochondrial membrane potential and increased cytochrome c release and caspsase-3 activity. Mechanistically, geraniin significantly downregulated Mcl-1 and impaired NF-κB p65 binding to the mcl-1 promoter. Overexpression of Mcl-1 significantly reversed geraniin-induced apoptosis in OVCAR3 cells. In addition, geraniin retarded ovarian cancer growth and reduced expression of phospho-p65 and Mcl-1. Collectively, geraniin elicits growth suppression in ovarian cancer through inhibition of NF-κB and Mcl-1 and may provide therapeutic benefits for this malignancy.
Keywords: NF-κB; growth suppression; ovarian cancer; phytochemical. |
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| In vivo: |
| Bioorg Med Chem Lett. 2015 Feb 1;25(3):673-9. | | Osteoprotective effect of geraniin against ovariectomy-induced bone loss in rats.[Pubmed: 25532904] | 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. |
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