Notopterol is a naturally occurring
furanocoumarin compound found in the root of Notopterygium incisum.
Hyperuricemia involves the activation of chronic
inflammation and leads to cardiac damage. Whether
notopterol has cardioprotective potential in
hyperuricemia mice remains elusive. The hyperuricemic mouse model was constructed by administration of
potassium oxonate and
adenine every other day for six weeks.
Notopterol (20 mg/kg) and
allopurinol (10 mg/kg) were given daily as treatment, respectively. The results showed that
hyperuricemia dampened heart function and reduced exercise capacity.
Notopterol treatment improved exercise capacity and alleviated cardiac dysfunction in hyperuricemic mice. P2X7R and pyroptosis signals were activated both in hyperuricemic mice and in
uric acid-stimulated H9c2 cells. Additionally, it was verified that inhibition of P2X7R alleviated pyroptosis and inflammatory signals in
uric acid-treated H9c2 cells.
Notopterol administration significantly suppressed expression levels of pyroptosis associated
proteins and P2X7R in vivo and in vitro. P2X7R overexpression abolished the inhibition effect of
notopterol on pyroptosis. Collectively, our findings suggested that P2X7R played a critical role in
uric acid-induced NLRP3 inflammatory signals.
Notopterol inhibited pyroptosis via inhibiting the P2X7R/NLRP3 signaling pathway under
uric acid stimulation.
Notopterol might represent a potential therapeutic strategy against pyroptosis and improve cardiac function in hyperuricemic mice.