PIISVYWK

PIISVYWK is an orally active inhibitor of PPARγ, as well as an activator of heme oxygenase-1 and Nrf2. By acting through the HO-1/Nrf2 pathway, PIISVYWK alleviates oxidative stress, reduces inflammation, and exhibits anti-obesity properties. It is applicable for research related to obesity.

PIISVYWK, at concentrations of 10-100 μM for 48 hours, exhibits no cytotoxic effects on BMMSCs. With treatment over 7 days, PIISVYWK inhibits adipocyte differentiation in BMMSCs by suppressing adipogenic transcription factors and enzymes, and enhancing lipolysis, achieving up to 40.97% inhibition of lipid accumulation at 100 μM. This compound activates the HO-1/Nrf2 signaling pathway within BMMSCs, resulting in increased expression of cytoplasmic HO-1 and nuclear Nrf2 at 100 μM (Nrf2 for 2 days, HO-1 for 3 days). It also reduces oxidative stress during the adipogenic differentiation of BMMSCs by decreasing ROS production and enhancing antioxidant enzyme activity, with significant effects at 100 μM over 7 days. Additionally, PIISVYWK alleviates inflammation in BMMSCs through the inhibition of pro-inflammatory cytokine production and modulation of the MAPK pathway, showing notable impact at 100 μM. When treated with 100 μM for 7 days, preceded by 1-hour incubation with 5 μM ZnPP, PIISVYWK displays anti-adipogenic activity mediated by HO-1, as ZnPP pre-treatment reverses its inhibitory effects on adipocyte differentiation, transcription factor expression, and lipolysis in BMMSCs. Similarly, this pre-treatment reverts PIISVYWK's HO-1 mediated oxidative stress inhibition and anti-inflammatory effects in BMMSCs.

PIISVYWK (1-10 mg/kg; oral administration; daily for 15 weeks) significantly reduces weight gain, fat accumulation, and pro-inflammatory cytokine levels in high-fat diet (HFD) induced obese mice. At a 10 mg/kg dose, it activates anti-obesity and antioxidant pathways, while a 1 mg/kg dose results in only moderate effects.