Effects and mechanisms of 8‐prenylnaringenin on osteoblast MC3T3‐E1 and osteoclast‐like cells RAW264.7

8‐Prenylnaringenin (8‐PN) is a phytoestrogen with the highest estrogenic activity. The objective of the present study was to confirm the superiority of 8‐PN on bone metabolisms and the estrogen receptor (ER) subtype mediating effects of 8‐PN. The osteoblast MC3T3‐E1 and osteoclast‐like cell line RAW264.7 were treated with 17β‐estradiol (10−8 mol/L), genistein (10−5 mol/L), daidzein (10−5 mol/L), 8‐PN (10−5 mol/L) alone or in the presence of ERα antagonist MPP (10−7 mol/L) and ERβ antagonist PTHPP (1.5 × 10−7 mol/L). It has been found that 8‐PN did not affect osteoblast proliferation, and that 8‐PN increased alkaline phosphatase (ALP) activity, osteocalcin (OCN) concentrations, and the mineralized nodules. 8‐PN inhibited RAW264.7 differentiating into osteoclasts and reduced the pit area of bone resorption. 8‐PN could also inhibit the protein and mRNA expression of receptor activator of nuclear factor‐κB ligand (RANKL) in osteoblasts, and conversely promote the expression of osteoprotegerin (OPG). These effects of 8‐PN were mainly inhibited not by PTHPP but by MPP and they were weaker than estrogen's effects but stronger than those of genistein and daidzein. In conclusion, the effects of 8‐PN on promoting osteoblastic bone formation and inhibiting osteoclastic bone resorption were mediated by ERα instead of ERβ and the efficacy was more potent than that of the two classic phytoestrogens: genistein and daidzein. The effects of 8‐PN on promoting osteoblastic bone formation and inhibiting osteoclastic bone resorption were mediated by ERα but not ERβ and were more potent than those of the two classic phytoestrogens, genistein, and daidzein.