Icariin inhibits corticosterone-induced apoptosis in hypothalamic neurons via the PI3-K/Akt signaling pathway.
Zhang H, Liu B, Wu J, Xu C, Tao J, Duan X, Cao Y, Dong J.
Laboratory of Lung, Inflammation and Cancers, Huashan Hospital, Fudan University, Shanghai 200040, PR China.
Excessive corticosterone (CORT) is acknowledged to induce neuronal damage in a number of regions of the brain, particularly the hippocampus, the main area implicated in depression. However, little research has been conducted on alterations to hypothalamic neurons in depression and the cellular and molecular basis for these changes. In the present study, we aimed to determine whether CORT causes apoptosis in primary cultured hypothalamic neurons, and to investigate the protective effects of icariin, an active natural ingredient from the Chinese plant, Epimedium sagittatum Maxim. Our study demonstrates that exposure of hypothalamic neurons to CORT causes a significant loss in viability, a significant decrease in mitochondrial membrane potential, an increase in caspase-3 activity, an elevation in intracellular reactive oxygen species elevation and decreased superoxide dismutase activity.
However, pretreatment of cells with icariin prior to CORT exposure was identified to noticeably suppress these CORT-induced events. Furthermore, icariin may prevent CORT-induced cell death via activation of the PI3-K/Akt pathway. In conclusion, icariin is able to prevent CORT-induced hypothalamic cell apoptosis via activation of the PI3-K/Akt pathway.
Icariin delays homocysteine-induced endothelial cellular senescence involving activation of the PI3K/AKT-eNOS signaling pathway.
Institute of Integrated Traditional Chinese and Western Medicine, Huashan Hospital, Fudan University , Shanghai , China.
Context: Homocysteine-induced endothelial cellular senescence may contribute to some cardiovascular disorders. Icariin (ICA), a flavonoid derived from Epimedium sagittatum Maxim. (Berberidaceae), has been reported to increase production of nitric oxide (NO) and reduce reactive oxygen species (ROS) levels in human umbilical vein endothelial cells (HUVECs). Objective: To observe the effects of ICA on homocysteine-induced senescence and the underlying mechanisms in HUVECs. Materials and methods: ICA at concentrations of 0.1, 1, and 5 μM was added into homocysteine pretreated HUVECs. Cellular senescence was assayed by senescence-associated β-galactosidase (SA-β-gal) staining and cumulative population doublings (CPDs). ICA (5 μM) was given orally to homocysteine-treated rats, luminal surface of aortic artery of rats was subjected to SA-β-gal staining. Protein expression was measured by western blot. Results: Homocysteine significantly increased cellular senescence both in vitro and in vivo. After treatment by ICA, the percentage of SA-β-gal-positive cells, and the ROS level significantly decreased. The CPDs were partially restored. ICA also significantly reduced the mean density of SA-β-gal staining in vivo.
found that NO production and phosphorylation of AKT, ERK, and endothelial NO synthase (eNOS) were elevated by ICA in HUVECs. Furthermore, the increased level of NO production was fully abolished by the phosphatidylinositol-3-kinase (PI3K) inhibitor wortmannin. The mitogen-activated protein kinase (MEK) inhibitor PD98059, which can inhibit phosphorylation of ERK, did not show this ability. Discussion and conclusion: Our results indicate that ICA delays homocyteine-induced endothelial senescence in vitro and in vivo.
Activation of PI3K/Akt-eNOS-dependent signaling pathway may be responsible for this efficacy of ICA.
PMID: 23336586 [PubMed - as supplied by publisher
*********This certainly isn't my area of expertise, but anytime you can blunt hemocysteine induced cell-damage, I am a fan. Also, Icariin should confer cardio-protective benefits by way of Akt-eNOS.
Healthy Bones? Icariin and its emerging role in the treatment of osteoporosis.
http://www.cmj.org/Periodical/PDF/201311839338570.pdf
Icariin accentuates osteoblast maturation. Icariin increases the activity of alkaline phosphatase and up regulates receptor activator of nuclear factor κ-B ligand (RANKL) expression thereby enhancing bone formation.2 It also affects the bone morphogenic protein-2 (BMP-2)/Smad4 pathway and thereby up regulates both BMP-2 and Smad4 expression leading to the formation of calcified nodules in bone tissue. In fact, icariin exhibits greater efficacy in increasing osteogenic differentiation in comparison to other natural flavonoids such as genistein.3 Besides the above mentioned effects, up regulation of osteoprogeterin is another of the effects of icariin. Knockout of osteoprogeterin has a negative impact on the anabolic activity of icariin.4 Icariin also has a dose dependent effect on differentiation of bone stem cells.5 Icariin also promotes bone genesis during distraction and can thus decrease the duration of distraction therapy.
Icariin also causes G2/M arrest in osteoclasts thus decreasing bone resoption and attenuates tartrate-resistant acid phosphatase (TRAP) expression by osteoclasts.6 Simultaneously, it has a negative impact on RANKL induced formation of osteoclasts in bone tissue. Icariin also promotes chondro-genesis and may thus have a role in cartilaginous engineering. Icariin up regulates Sox 9 and aggrecan expression and thereby enhances chondro-genesis when administered in high concentrations. It also increases collagen synthesis by chondrocytes and increases glycol-amino-glycan synthesis,7 as a result in promoting extracellular matrix synthesis.
The fact that icariin is not very expensive makes it an ideal candidate in bone regeneration. The above examples clearly illustrate that icariin is a potent drug and the coming few years may see its increased use as a drug to mitigate and treat osteoporosis in humans.
REFERENCES
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