So it seems to be the most selective at PDE4 accumulation, but it seems to lower the actual ERK dendritic extension mechanism? Well forskolin at least counter-acts some of this effect, but I dont know if its a good thing.
After researching a bit into it, I see that the ERK protein can also be known as a MAP kinase. That said, researching into the MAPK signal transduction pathway, it seems that it has direct effects on the proliferation of cells, the differentiation of individual cells, transcription and general cellular development? I haven't seen anything on direct MAPK involvement in dendritic extension, but I'm curious to know if I'm just wrong. I suppose if MAPK if is involved in the differentiation of cells and cellular development, dendritic extension would be considered a part of that. This all said, interestingly enough I also found that the development of cancer has been linked to malfunctioning MAP/ERK kinases, and that inhibitors of MAPK/ERK were theorized to help substantially in slowing the development of cancer. So hooray for hesperidin being another element of cancer fighting?
I'm still not quite excited about the idea of slowed cellular development in regular, healthy cells due to inhibition of MAPK/ERK though. I'm curious to know if this was found to be substantial. On this note, hesperidin actually seems to be counter-productive to the facilitation of neuronal growth and therefore counter-productive to the goal of increasing one's intelligence. Seems like something one would certainly want to avoid during a cerebrolysin regimen.
EDIT:
http://www.ncbi.nlm....pubmed/20678535 Protective effects of hesperidin against oxidative stress of tert-butyl hydroperoxide in human hepatocytes.
Chen M, Gu H, Ye Y, Lin B, Sun L, Deng W, Zhang J, Liu J.
Source
State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, China.
Abstract
Increasing evidence regarding free radical generating agents and the inflammatory process suggest that accumulation of reactive oxygen species (ROS) could involve hepatotoxicity. Hesperidin, a naturally occurring flavonoid presents in fruits and vegetables, has been reported to exert a wide range of pharmacological effects that include antioxidant, anti-inflammatory, antihypercholesterolemic, and anticarcinogenic actions. However, the cytoprotection and mechanism of hesperidin to neutralize oxidative stress in human hepatic L02 cells remain unclear. In this work, we assessed the capability of hesperidin to prevent tert-butyl hydroperoxide (t-BuOOH)-induced cell damage by augmenting cellular antioxidant defense. Hesperidin significantly protected hepatocytes against t-BuOOH-induced cell cytotoxicity, such as mitochondrial membrane potential (MMP) deplete and lactate dehydrogenase (LDH) release. Hesperidin also remarkably prevented indicators of oxidative stress, such as the ROS and lipid peroxidation level in a dose-dependent manner. Western blot showed that hesperidin facilitated ERK/MAPK phosphorylation which appeared to be responsible for nuclear translocation of Nrf2, thereby inducing cytoprotective heme oxygenase-1 (HO-1) expression. Based on the results described above, it suggested that hesperidin has potential as a therapeutic agent in the treatment of oxidative stress-related hepatocytes injury and liver dysfunctions.
Copyright © 2010 Elsevier Ltd. All rights reserved.
And here I've found another study that seems to contradict the first study in regards to the phosphorylation of ERK/MAPK. I believe it shouldn't be possible for hesperidin to facilitate the phosphorylation of ERK/MAPK and still have anti-carcinogenic effects though, due to the previously understood mechanism of said effects. The other studies I find seem to agree that hesperidin is involved in inhibiting phosphorylation of ERK/MAPK, I wonder how this study came up with the opposite.
Going off of this study for other reasons though, it's great to see how powerful the antioxidant capabilities of hesperidin seem to be.
Edited by Izat04, 02 July 2012 - 04:33 PM.