Podocarpic acid is a natural product, which has the best all-round positive effect and acts as a novel TRPA1 activator.
Podocarpic acid anhydride acts as a 1 nM agonist of LXRalpha and beta receptors. It shows over 8-10-fold better activator of LXR receptors compared to one of the natural ligands, 22-(R)-hydroxy cholesterol, in HEK-293 cells[2].
Podocarpic acid activates SKN-1 in C. elegans, similar to known Nrf2 activators such as α-lipoic acid (LA). Podocarpic acid- or LA-induced SKN-1 activation also requires TRPodocarpic acid-1: trPodocarpic acid-1 knockdown in glod-4;gst-4p::gfp animals reduces expression of gst-4 to wild-type levels. A and LA supplementation results in a robust Ca2+ flux, which is significantly reduces when the Ca2+-impermeable TRPodocarpic acid-1E1018A channel is present, suggesting that TRPodocarpic acid-1 activation is key for these drugs' function. Finally, Podocarpic acid and LA alleviate the Podocarpic acidthogenic phenotypes of glod-4 animals by reverting the high endogenous MGO and GO to almost wild-type-like levels[1].
[1]. Baraka HN. Microbial transformation of podocarpic acid and evaluation of transformation products for antioxidant activity. Planta Med. 2010 May;76(8):815-7. [2]. Singh S, et al. Discovery and development of dimeric podocarpic acid leads as potent agonists of liver X receptor with HDL cholesterol raising activity in mice and hamsters. Bioorg Med Chem Lett. 2005 Jun 2;15(11):2824-8.