Chronobiology and Obesity: Interactions between Circadian Rhythms and Energy Regulation

Mice deficient in a circadian gene (Bmal1) had defects in insulin secretion, both at base levels and in response to glucose stimulation. These mice were highly susceptible to diabetes.

Sulforaphane activates heat shock response and enhances proteasome activity through up-regulation of Hsp27.

The major mechanism by which SFN, an electrophile, protects cells is believed to be through induction of direct and indirect antioxidant response, including up-regulation of glutathione and activation of NF-E2-related factor 2 (Nrf2)-mediated phase II enzymes and
antioxidant enzymes that relieve cells from oxidant stress and carcinogenic attacks (11)

. However, its chemopreventive activity also includes other mechanisms, such as induction of cell cycle arrest and apoptotic pathways, inhibition of angiogenesis, and anti-inflammatory activity (9). Recently, SFN has been shown to enhance mammalian proteasome activity through induction of 26 S proteasome subunit PSMB5 (13). Both induction of PSMB5 and proteasome activation have been associated with antioxidant response mediated through the Keap1-Nrf2
pathway (13–16).

Bmal1 and β-cell clock are required for adaptation to circadian disruption, and their loss of function leads to oxidative stress-induced β-cell fai...

Keywords: ARNTL Transcription Factors;Adaptation, Physiological;Animals;Antioxidants;Circadian Rhythm;Diabetes Mellitus, Experimental;Gene Expression Regulation;Glucose;Hyperglycemia;Insulin;Insulin-Secreting Cells;Ion Channels;Male;Mice;Mice, Transgenic;Mitochondrial Proteins;Oxidative Stress;Reactive Oxygen Species;Uncoupling Protein 2

Effect of Nrf2 activators on release of glutathione, cysteinylglycine and homocysteine by human U373 astroglial cells.

«Effect of Nrf2 activators on release of glutathione, cysteinylglycine and homocysteine by human U373 astroglial cells.

GSH levels increased dose-dependently in response to all four drugs.
Sulforaphane produced the most potent effect, increasing GSH by up to 2.4-fold. PC-Res increased GSH up to
1.6-fold, followed by TBHQ (1.5-fold) and LA (1.4-fold).

While the order of drug potency remained almost the same for boosting GSH and CysGly, all drugs were able to increase GSH levels between 1.2 and 1.4 times more than they were able to
increase CysGly (Table 1).»

Fisetin Regulates Nrf2 Expression and the Inflammation-Related Signaling Pathway to Prevent UVB-Induced Skin Damage in Hairless Mice.

«Our results demonstrate that fisetin attenuates UVB-induced damage, oxidative stress,
inflammation, and skin barrier function disruption. Fisetin inhibits the UVB-induced expression of MMP, COX-2, IL-6, and NF-κB, thus protecting the skin from wrinkles and erythema. Fisetin also
increases the expression of Nrf2 in the mice skin. In addition, fisetin effectively inhibits UV-induced aquaporin and filaggrin damage. The present study demonstrates the protective effects of fisetin against UV-induced skin damage.»

Sulforaphane as anticancer agent: A double-edged sword? Tricky balance between effects on tumor cells and immune cells.

«Sulforaphane (SFN) is a naturally occurring isothiocyanate derived from cruciferous vegetables such as broccoli. It has been reported to inhibit the growth of a variety of cancer, such as breast, prostate, colon, skin, lung, gastric or bladder cancer. SFN is supposed to act primarily as an antioxidant due to the activation of the Nrf2-Keap1 signaling pathway. This enhances the activity of phase II detoxifying enzymes and the trapping of free radicals. Finally, SFN induces cell cycle arrest or apoptosis of tumor cells. Here, we discuss effects of SFN on the immune defense system. In contrast to the situation in tumor cells, SFN acts pro-oxidatively in primary human T cells. It increases intracellular ROS levels and decreases GSH, resulting in inhibition of T cell activation and T cell effector functions. Regarding the use of SFN as an "anticancer agent" we conclude that SFN could act as a double-edged sword. On the one hand it reduces carcinogenesis, on the other hand it blocks the T cell-mediated immune response, the latter being important for immune surveillance of tumors. Thus, SFN could also interfere with the successful application of immunotherapy by immune checkpoint inhibitors (e.g. CTLA-4 antibodies and PD-1/PD-L1 antibodies) or CAR T cells. Therefore, a combination of SFN with T cell-mediated cancer immunotherapies does not seem advisable.»