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

## TL;DR

Andrographolide, a compound from a medicinal herb, prevents fat cell development in mice by blocking a specific gene pathway.

## Contribution

Identifies a novel mechanism by which andrographolide inhibits adipogenesis through the GSK3β-Snail1-SLC19A3 axis.

## Key findings

- Andrographolide inhibits adipose-derived stem cell differentiation into adipocytes in culture and in mice.
- SLC19A3 induction is blocked by andrographolide, and its knockdown abolishes adipogenic differentiation.
- The GSK3β-Snail1-SLC19A3 axis mediates the anti-adipogenic action of andrographolide.

## Abstract

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.

•Andrographolide (AP) inhibits the differentiation of ADSCs toward adipocytes•AP prevents the development of obesity in a high-fat diet (HFD)-induced mouse model•The anti-adipogenic and anti-obese effects of AP are dependent on its inhibition of GSK3β•The effects of AP are mediated by Snail1, which downregulates SLC19A3 upon GSK3β inhibition

Andrographolide (AP) inhibits the differentiation of ADSCs toward adipocytes

AP prevents the development of obesity in a high-fat diet (HFD)-induced mouse model

The anti-adipogenic and anti-obese effects of AP are dependent on its inhibition of GSK3β

The effects of AP are mediated by Snail1, which downregulates SLC19A3 upon GSK3β inhibition

Biological sciences; Cell biology; Health sciences; Natural product biochemistry; Natural sciences