Pegylation enhances the anti-osteoporosis activity of acacetin in both ovariectomized and LPS-stimulated mice.

Osteoporosis is a condition of progressive bone loss attributable to excessive osteoclastic activity. Acacetin is a potential candidate for osteoporosis therapy because it specifically suppressing osteoclastic function. However, the application of acacetin was limited by its poor solubility and bad pharmacokinetic behavior. In current work, we examined whether PEGylation of acacetin enhances its anti-osteoporosis activity in ovariectomy-induced osteoporosis and LPS-induced osteolysis. In the current study, three types of PEGylated acacetin (PEG3-A, PEG4-A, PEG5-A) were tested for their effects on the solubility and anti-inflammatory activity of acacetin in vitro. PEG5-Acacetin was selected for further investigation as it demonstrated the strongest anti-inflammatory activity comparable to that of naked acacetin and other two PEGylated acacetin. PEGylation in PEG5-Acacetin increased maximum plasma concentration of acacetin by 620.77% in mice. Furthermore, PEG5-A showed a higher anti-osteoclastogenic capacity in vitro than that of naked acacetin. It was found that PEG5-A treatment in vivo mitigated lipopolysaccharide (LPS)- and ovariectomy (OVX)-induced bone loss in mice. More importantly, the in vivo efficiency of PEG5-Acacetin was significantly better than that of naked acacetin. In summary, PEGylated acacetin possesses a clean advantage over the naked acacetin and would be a potential candidate for the osteoporosis therapy.