20‐O‐β‐d‐Glucopyranosyl‐20(S)‐Protopanaxadiol Suppresses UV‐Induced MMP‐1 Expression Through AMPK‐Mediated mTOR Inhibition as a Downstream of the PKA‐LKB1 Pathway

Abstract

Various health effects have been attributed to the ginsenoside metabolite 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol (GPD); however, its effect on ultraviolet (UV)-induced matrix metalloproteinase (MMP)-1 expression and the mechanism underlying this effect are unknown. We examined the inhibitory effect of GPD on UV-induced MMP-1 expression and its mechanisms in human dermal fibroblasts (HDFs). GPD attenuated UV-induced MMP-1 expression in HDFs and suppressed the UV-induced phosphorylation of mammalian target of rapamycin (mTOR) and p70(S6K) without inhibiting the activity of phosphatidylinositol 3-kinase and Akt, which are well-known upstream kinases of mTOR. GPD augmented the phosphorylation of liver kinase B1 (LKB1) and adenosine monophosphate-activated protein kinase (AMPK), which are inhibitors of mTOR, to a greater extent than UV treatment alone. Similar to GPD, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranosyl 5'-monophosphate (AICAR), an activator of AMPK, augmented UV-induced AMPK phosphorylation to a greater extent than UV treatment alone, resulting in the inhibition of MMP-1 expression. AICAR also decreased the phosphorylation of mTOR and p70(S6K). However, compound C, an antagonist of AMPK, increased MMP-1 expression. In HDF cells with AMPK knock-down using shRNA, MMP-1 expression was increased. These results indicate that AMPK activation plays a key role in MMP-1 suppression. Additionally, the cAMP-dependent protein kinase (PKA) inhibitor, H-89, antagonized GPD-mediated MMP-1 suppression via the inhibition of LKB1. Our results suggest that the suppressive activity of GPD on UV-induced MMP-1 expression is due to the activation of AMPK as a downstream of the PKA-LKB1 pathway.

Nuclear factor kappa-B- and activator protein-1-mediated immunostimulatory activity of compound K in monocytes and macrophages

“…Ginseng researchers have recently focused on CK because of its antidisease activity such as hepatoprotective activity [24], inhibition of tumor invasion [20], induction of tumor cell apoptosis [25], and protection from wrinkle and skin damage [26], [27]. Despite these previous studies focusing on the regulatory activities of CK in various diseases, its immunomodulatory role in innate immunity mediated by monocytes and macrophages has been poorly explored.…”

Youngiasides A and C Isolated from Youngia denticulatum Inhibit UVB-Induced MMP Expression and Promote Type I Procollagen Production via Repression of MAPK/AP-1/NF-κB and Activation of AMPK/Nrf2 in HaCaT Cells and Human Dermal Fibroblasts

“…9 Recently, it was reported that AMPK activation plays an important role in MMP-1 expression in human dermal fibroblasts (HDFs) by regulating the upstream and downstream signaling of AMPK. 10 Thus, AMPK activators could be used to prevent UV-induced skin photoaging.…”

20 S -Protopanaxadiol, an aglycosylated ginsenoside metabolite, induces hepatic stellate cell apoptosis through liver kinase B1–AMP-activated protein kinase activation

“…It has been reported that the fully aglycosylated metabolite, PPD, can be produced from ginseng extract, Rb1, Rg3, or Comp. K by intestinal microflora [16], [18], [19], [29], and that aglycosylated metabolites are more potent than their parent compounds [26], [29], [30]. Studies have shown that 20 S -PPD inhibits the growth of Helicobacter pylori [29], attenuates the progression and growth of castration-resistant prostate cancer [31], enhances the sensitivity of chemotherapy against colorectal cancer [16], and protects neurons from permanent focal cerebral ischemic damage [32].…”