Regulation of bone and fat balance by fructus ligustri lucidi in ovariectomized mice

Abstract

Fructus Ligustri Lucidi, a traditional Chinese medicine, is the fruit of Ligustrum lucidum Ait. (Oleaceae). It has invigorating effects on the liver and kidneys and is a commonly used herb in the treatment of age-related diseases. The ethanol extract of FLL is a potential candidate for the prevention and treatment of postmenopausal osteoporosis. In the present study, we aimed to determine whether the ethanol extract of FLL wields an anti-osteoporotic effect on ovariectomized mice and to explore the relevant underlying mechanisms of action. One week after surgery, animals were randomly assigned to five groups, at 10 per group: a sham group, OVX group, E2 group, and FLL group (2 g/kg and 4 g/kg). Eight weeks after treatment, we harvested the uteri, femurs, tibias, visceral organs, and plasma from the mice. The levels of estradiol, Trap, Trap5b, OPG, and RANKL in plasma were determined by ELISA. We assessed bone mineral density and bone microstructure by X-ray absorptiometry and micro-CT, and the formation of F-actin rings was detected by immunofluorescence staining assay. FLL significantly decreased osteoclast activity, increased bone mineral density, and improved bone microstructure in OVX mice (P < 0.05). The fat content of abdominal fat and bone marrow were also reduced after treatment with FLL (P < 0.01). In addition, FLL (1 μg/mL) suppressed the formation of osteoclasts and F-actin rings in vitro (P < 0.01). FLL inhibited adipocyte differentiation in both fate determination and maturation from monocytes by inhibiting Zfp423 and PPARγ mRNAs (P < 0.01 or P < 0.05). In summary, FLL prevented additional bone loss and improved bone microstructure in OVX mice by suppressing the activity of osteoclasts and reducing the fat content in the abdomen and the bone marrow.