Andrographolide inhibits the upregulation of SLC19A3 to block the adipogenic differentiation of adipose-derived stem cells.

We found that andrographolide (AP), the main active component of medicinal herb Andrographis paniculata, inhibited the differentiation of adipose-derived stem cells (ADSCs) toward adipocytes in culture and in mice fed with high fat diet. RNA-seq analyses revealed that the induction of SLC19A3, a thiamine transporter, was blocked by AP, and knockdown of SLC19A3 abolished the adipogenic differentiation. Further, supplementing thiamine to cultured ADSCs reversed the inhibitory effect of AP dose-dependently, indicating that SLC19A3 mediates the action of AP on adipogenic differentiation. Interestingly, the differentiation of ADSCs was accompanied by the reduction of S9-phosphorylated GSK3β, which was prevented by AP. Subsequent investigation showed that AP and a GSK3β inhibitor upregulated Snail1, a transcriptional repressor influencing cell differentiation. While enforced expression of Snail1 reduced the luciferase activity of the SLC19A3 reporter, siRNA against Snail1 blocked the inhibition of AP on SLC19A3 expression. Thus, the GSK3β-Snail1-SLC19A3 axis mediates the anti-adipogenic action of andrographolide.