Salidroside from "Golden Roots" : Extending the Life Span of C. elegans by Activating AMPK and Inactivating PAK1.

An old traditional Chinese herb called "Golden Root" (Rhodiola Rosea) from
Tibet Highland or Siberia Taiga contains an anti-cancer sugar called "Salidroside"
. In 2008 a Chinese group found that this sugar activates AMPK and stimulates
glucose uptake by muscle cells, probably by activating the glucose transporter
GLUT-4, thereby would be useful for therapy of type 2 (insulin-resistant
) diabetes. A year later a Dutch group led by Fred Wiegant at Utrecht University
found that Salidroside-based extract of Golden Root extends the life span
of C. elegans by activating FOXO. Since AMPK is known to activate FOXO,
this wouldn't be a big surprise.

However, in 2008 a Polish group led by Eva Skopinska-Rozewska at Warsaw
Medical University discovered that Salidroside suppresses the tumor-
induced angiogenesis, suggesting that this sugar might inactivate
PAK1 somehow, which is required for the angiogenesis. Well, as
previously mentioned, AMPK is mainly activated by LKB1, the kinase which
inactivates PAK1 simultaneously. Thus, it would be quite reasonable to assume
that this AMPK-activating sugar would inactivate PAK1 as well. In 2010
Xiaolan Hu' s group at Zhejiang Medical School in China found that Salidroside
suppresses the PAK1-dependent growth of human breast cancer cells, and up-regulates
a CDK inhibitor called p21, clearly indicating that this sugar is indeed
involved in the inactivation of PAK1, in addition to the activation of AMPK.
However, it still remains to be clarified if this sugar inactivates PAK1
only through LKB1 or other pathways as well.

As mentioned earlier, like this sugar, a dozen of other compounds activate
AMPK and inactivate PAK, simultaneously: CAPE, curcumin, capsaicin/capsiate,
resveratrol, berberine, metformin, emodin, AG 879/GL2003, GW2974 and OSU-03012.
It would be reasonable to assume that these compounds also extend the life
span of C. elegans and human beings, by activating FOXO.