Polyguluronic acid alleviates doxorubicin-induced cardiotoxicity by suppressing Peli1-NLRP3 inflammasome-mediated pyroptosis

Polyguluronic acid (PG), a polysaccharide from alginate , possesses excellent bioactivities. We prepared high-purity PG with 10.41 kDa molecular weight (Mw) and a 59 average degree of polymerization (DP) by acid hydrolysis , three pH grades, Q-Sepharose column elution, and Sephadex G-25 column desalination . Then, we evaluated the PG protective effects on doxorubicin-induced cardiotoxicity (DIC) in vitro and in vivo. The nontoxic PG enhanced cellular viability , reduced cell pyroptosis morphology, diminished the LDH and IL-1β release, and downregulated expressions of ASC oligomerization , NLRP3 , cl-CASP1, and GSDMD, by which PG protected the cardiomyocytes from NLRP3 inflammasome-mediated pyroptosis in doxorubicin-stimulated HL-1 cells and C57BL/6J mice. The probable underlying mechanism may be that PG downregulated doxorubicin -induced Peli1, the deficiency of which could inhibit doxorubicin-induced NLRP3 inflammasome-mediated pyroptosis. These results suggested that polysaccharide PG from alginate could prevent DIC and may be a potential therapeutic agent or bioactive material for preventing DIC.