Retinoids: Vertebrae Analouges To Juvenile Hormone Of Insects?

[LeeLemonoil]

Farnesol attenuates lipopolysaccharide-induced neurodegeneration in Swiss albino mice by regulating intrinsic apoptotic cascade. - PubMed - NCBI

Farnesol attenuates lipopolysaccharide-induced neurodegeneration in Swiss albino mice by regulating intrinsic apoptotic cascade.

Abstract
Neuronal apoptosis occurs as a sequel of oxidative stress associated with various neuropathies. In this study, we have investigated the protective effect of farnesol, a sequisterpene on lipopolysaccharide (LPS) induced neurodegeneration through modulation of intrinsic apoptotic cascade in the cortex and hippocampus of Swiss albino mice. Intraperitoneal (i.p.) injection of LPS (250 μg/kg b.wt. for 7 days) resulted in elevated levels of lipid peroxidation, protein carbonyls and 8-Hydroxydeoxyguanosine (8OHdG), with subsequent depletion in the antioxidant status and severe histological aberrations. These anomalies were accompanied by increased expressions of pro-apoptotic Bax, caspase-3 and p53 with decrease in anti-apoptotic Bcl-2. Farnesol treatment (100mg/kg b.wt.) ameliorated LPS-induced oxidative stress by enhancing the antioxidant defense system as evident from the increased levels of SOD, CAT, GSH and GST and exhibited protected cellular morphology manifested from histopathological and nissl staining analyses. Farnesol treatment also reduced the expulsion of cytochrome c from mitochondria and downregulated caspase 3 activation as revealed by immunoblot analysis. Furthermore, farnesol treatment reduced the expression of Bax and antagonized LPS-induced decrease in anti-apoptotic Bcl-2. Results of this study show that farnesol exerts neuroprotective effect by regulating intrinsic apoptotic cascade through its antioxidant effect during LPS-induced neurodegeneration.

 

[LeeLemonoil]

There are a lot of interesting studies and research on Farnesol, including metabolic enhancement, inducing of brow fat tissue, reversing of kidney damage, and especially anti-cancer effects. Farnesylthiosalisylic acid is a derived compound that sees a lot of anti-cancer research. It's a Farnesoid esterified with Salicylic acid.
But I've also come across the study which you can find on the bottom of this post, which sugest Estrogenic, pro-breast cancer action of Farnesol. Among other factors Farnesols agonism and activation of te FxR seem to be responsible. Androsterone is also a FxR-agonist with som similar action as Farnesol, for examle in kidney therapeutic, regenerative acion. And another known compound here, Phytol, is also closely related to Farnesol. I wonder how viable the study above is - given its extremely in vitro and test-tube style.
Maybe @haidut can have a look



Immunomodulatory properties of farnesoids: the new steroids? - PubMed - NCBI

Immunomodulatory properties of farnesoids: the new steroids?

Abstract
Farnesylthiosalisylic acid (FTS) is a potent non-toxic anticancer drug that targets oncogenic and pathologically activated Ras. The mechanism of action of FTS is well understood. It interferes with the binding of activated Ras proteins to their escort chaperons and with Ras tethering to the plasma membrane. This agent has been evaluated successfully in phase II clinical trials of pancreatic and lung cancer patients. It is generally agreed that Ras proteins play an important role in cancer, but they also drive activation of the immune system. Therefore we hypothesized that inhibiting Ras might be beneficial in autoimmune and inflammatory conditions. Over the past decade we have extensively studied the effects of FTS in multiple animal models of such diseases. We were able to show potent anti-inflammatory properties of FTS in autoimmune disease models such as systemic lupus erythematous, antiphospholipd syndrome, Guillain-Barré syndrome, multiple sclerosis, and inflammatory bowel diseases. Its potential was also shown in type I and type II diabetes. Animal models of contact dermatitis, allergic inflammation, and proliferative nephritis were studied as well. We have also investigated the molecular mechanisms, signaling pathways, and inflammatory mediators underlying these conditions. In this review we summarize our (and others) published data, and conclude that FTS has great potential as a safe anti-inflammatory drug.



Farnesol, a mevalonate pathway intermediate, stimulates MCF-7 breast cancer cell growth through farnesoid-X-receptor-mediated estrogen receptor act... - PubMed - NCBI

Farnesol, a mevalonate pathway intermediate, stimulates MCF-7 breast cancer cell growth through farnesoid-X-receptor-mediated estrogen receptor activation.

Abstract
Farnesoid X receptor (FXR) is a metabolic nuclear receptor expressed in the liver and traditionally considered as a bile acid sensor. Yet, FXR has been recently demonstrated in other tissues and cells, such as the kidneys, the adrenals, and arterial smooth muscle cells. Immunohistochemical data reported in this study point to the expression of FXR in human breast cancer. In addition, FXR expression was also found by Western blotting and immunofluorescence microscopy in breast-cancer-derived cell lines MCF-7 (estrogen receptor [ER]-positive) and MDA-MB-231 (ER-negative). The FXR activator farnesol, a mevalonate pathway intermediate, exerts a mitogenic effect on MCF-7 cells. The growth stimulation is completely suppressed by antiestrogens. In contrast, MDA-MB-231 cells appear farnesol-insensitive, suggesting an involvement of ER in farnesol mitogenicity. In accordance with this interpretation, farnesol induces in MCF-7 cells a decrease of ER level, consistent with a phenomenon of receptor downregulation. Farnesol also increases progesterone receptor (PgR) expression in MCF-7 cells and stimulates ER-mediated gene transactivation in MVLN cells (MCF-7 cells stably transfected with an ER reporter gene). Of note, both effects of farnesol on ER expression and activity are completely suppressed by antiestrogens. In addition, farnesol-induced PgR is markedly reduced by FXR gene silencing (siRNA), demonstrating the involvement of FXR in the estrogenic effects of farnesol. Finally, coimmunoprecipitation experiments (FXR immunoprecipitation followed by Western blot analysis of ER in the immunoprecipitate) produced definite evidence that FXR interacts with ER. Altogether, these observations reveal the hitherto unreported presence of FXR in breast cancer and show that the latter receptor functionally interacts with ER. The occurrence of such a crosstalk calls for some caution regarding the pharmacological use of FXR agonists.