Bioactivity‐guided Isolation of Antiosteoporotic Compounds from Ligustrum lucidum

Abstract

The fruits of Ligustrum lucidum (FLL) has long been used for the treatment of osteoporosis in China, but the antiosteoporotic compounds in FLL are still poorly understood. In this study, the alkaline phosphatase (ALP) activity-guided isolation of osteogenic components from FLL was carried out by using osteoblast-like UMR-106 cells. Eight compounds, namely tyrosol (1), tyrosyl acetate (2), hydroxytyrosol (3), salidroside (4), oleoside dimethyl ester (5), oleoside-7-ethyl-11-methyl ester (6), nuzhenide (7), and G13 (8), were isolated and identified. Further study showed that compounds 3, 4, 7, and 8 increased ALP activity in UMR-106 cells. Compounds 5, 6, and 7 promoted the proliferation of UMR-106 cells. The aqueous extract of FLL-activated ERα/β-mediated gene transcription, whereas the isolated compounds were inactive. All eight isolated compounds also exhibited antioxidative activity, with compounds 1, 2, and 3 being the most potent. These results indicate that the antiosteoporotic effect of FLL is derived from different compounds together with different mechanisms such as ER-dependent or independent pathways and antioxidative effects. Salidroside (4) and nuzhenide (7) warrant further investigation as new pharmaceutical tools for the prevention and treatment of osteoporosis.

Antioxidant Effect of Fructus Ligustri Lucidi Aqueous Extract in Ovariectomized Rats Is Mediated through Nox4-ROS-NF-κB Pathway

“…In addition, Zhang et al (Chen et al, 2013) demonstrated that aqueous extract of FLL and its 20% ethanol fraction exhibited estrogenic activity via ERα and ERβ mediated estrogen response element gene expression in Hela cells. Further, Wang et al (2011) found that the addition of ER antagonist (ICI182780) to aqueous extract of FLL treated UMR-106 osteoblasts effectively inhibited ALP activity.…”

“…In fact, Nox4 is widely expressed in bone (Fu et al, 2015) and uteri (Fletcher et al, 2014). Additionally, FLL has been demonstrated to exhibit antioxidant activity in vitro (Chen et al, 2013). Ovariectomy aggravates bone loss partly through disturbing redox homeostasis (Huang et al, 2014).…”

Icariin from Epimedium brevicornum Maxim promotes the biosynthesis of estrogen by aromatase (CYP19)

“…An ethanolic extract of Cuscuta chinensis and water extract of Ligustrum lucidum were prepared as described in previous studies Chen et al, 2012). Dried leaves of Epimedium brevicornum, dried rhizomes of Rhizoma drynariae, and dried roots of Polygonum multiflorum were purchased from Tongrentang Chinese Medicine (Beijing, China) and voucher specimens were deposited in the herbarium of Herpetology and Herbarium, Chengdu Institute of Biology, Chinese Academy of Sciences (Voucher nos., SC1705, SC1706, and SC1707).…”

Antiosteoporotic and antioxidant activities of diterpenoids from the Vietnamese soft corals Sinularia maxima and Lobophytum crassum

“…Although oxidative stress is believed to be one of the primary contributors to the pathogenesis of osteoporosis via its role in osteoclastic resorption and detrimental effects on bone-forming osteoblasts (which could be prevented by supplementation with antioxidants (Arai et al, 2007;Chen et al, 2013;Muhammad et al, 2012;Rao and Rao, 2013), the detailed mechanism by which oxidative stress leads to osteoporosis through osteoclasts and osteoblasts remains controversial and unclear. Under these conditions, an imbalance between ROS production and antioxidant mechanisms may be disturbed, resulting in oxidative stress that could lead to osteoporosis (Abdollahi et al, 2005).…”