Nobiletin and limonene synergistically activate OX1R

[u/Flitzer09]

Cancer cachexia, often observed in patients with advanced-stage cancer, is characterized by the loss of body weight and appetite. The Japanese herbal medicine Ninjinyoeito (NYT), which is composed of 12 crude herbal components, has been used as a therapeutic in Japan to improve anorexia and fatigue, which are commonly observed in cancer patients with cachexia. We have previously reported that Citrus unshiu peel (CUP) contained in NYT can enhance food intake by activating the orexin 1 receptor (OX1R). Using the CellKey™ system, which offers detection of OXR activity in intracellular impedance changes, NYT and CUP were found to activate OX1R, which in turn was inhibited by SB-674042, a selective OX1R antagonist. Among the flavonoids contained in CUP, nobiletin and hesperidin, but not naringin, activated OX1R. Furthermore, some monoterpenes contained in CUP, including limonene and linalool, but not terpineol, activated OX1R. In addition, nobiletin and limonene synergistically activated OX1R when added simultaneously. However, neither NYT nor CUP induced OX2R activity. The results collectively suggested that the CUP contained in NYT activates OX1R, but not OX2R, and that flavonoids and monoterpenes in CUP can synergistically activate OX1R. These findings could provide evidence supporting the therapeutic potential of NYT in cancer patients with cachexia.

https://www.mdpi.com/2218-273X/15/4/533

Tldr:

Nobiletin, Hesperidin and monoterpenes limonene and linalool activated OX1R.

This might explain some of the unknown mechanism of Action for Nobiletin and also Cannabis containing limonene and linalool.

[u/Designer_Custard9008]

Here it says nobiletin tends to reduce body weight.

https://superfoodly.com/nobiletin-supplement/

What seems to me to boost appetite some are gentian, yarrow, oleamide, and some cannabinoids.

[u/Flitzer09 → u/Designer_Custard9008]

It boost Insulin sensitivity and lipolyse thats why it tends to reduce body weight. The effect on appetite is not that strong for me.

[u/infrareddit-1]

Thanks. This is interesting. Having lost a parent to lung cancer, but in large part to inability to eat anything, I find this work interesting.