4-Methylumbelliferone (4MU) is an orally bioavailable bile acid compound that attenuates hyaluronan (HA) synthesis by binding to the UDP-glucuronic acid donor site of HA synthases and depleting their substrate. Preclinical studies have shown that 4mupro online tumor growth and metastasis by inhibiting HA synthesis, and has potent antitumor activities alone and in combination with other agents.

Benefits of 4MU Supplement

In our study, we administered 1.2 g/day of 4MU to TRAMP-positive mice for 10 weeks followed by a 2-month wash-out period. Systemic administration of 4MU was well tolerated and did not result in significant side effects. During the treatment period, we observed downregulation of HA and chondroitin sulfate proteoglycans in blood samples. This was accompanied by increased bile acids and by increased levels of interleukins IL10, IL12p70 and IFN gamma.

We also performed rotarod and forelimb grip strength tests to test motor functions in the treated mice. The results showed that the sensitivity of the forelimbs to mechanical stimuli was significantly lower in 4MU-treated animals compared with controls. However, the rotarod and forelimb grip strengths returned to their baseline values after the 2-month wash-out period.

Besides being effective on its own, 4MU enhances the response of GBM cells to TMZ and VCR. This is likely because it attenuates HA synthesis, which is the first step in this signaling cascade and reduces cell proliferation. Our data further suggest that 4MU could be used to improve GBM therapy even in TMZ-refractory patients. Furthermore, our results indicate that 4MU can be used to regulate plasticity in the central nervous system through perineuronal net (PNN) modulation.