In a preclinical study, mice received hydroxynaphthoic acid sodium salt (150 mg/kg/day) twice a day for 2 weeks by gavage.

The stable HEK 293 cell line harboring a reporter gene expressed by human grp78 promoter was treated with PA media containing 300 uM of palmitate to induce ER stress and then serial dilutions of hydroxynaphthoic acid were applied (from 0.01 to 1 mM) for 22 h. The drug inhibited ER stress with IC50 value of 44.9 uM. It also reduced PA-induced p-JNK and p-IRS-1(S307) levels in dose-dependent manners in HepG2 cells when incubated for 2 h at concentrations 0.1, 0.3, 0.5 mM. At 0.3 mM hydroxynaphthoic acid restored insulin sensitivity suppressed by PA. When fully differentiated 3T3-L1 cells were co-incubated with or without thapsigargin (Tg) and hydroxynaphthoic acid (30, 100, 300 uM) for 18 h, the acid augmented GLUT4 translocation by sensitizing insulin and PPARgamma signaling and showed 100-fold activation at 300 uM. The drug (0.1 and 0.3 mM) protected INS-1 cells from cell death after the incubation with 300 uM PA in combination with 25 mM glucose for 18 h.