Study of effects of Fructus Ligustri Lucidi on calcium balance and vitamin D metabolism

xxv, 272 leaves : ill. ; 30 cm.PolyU Library Call No.: [THS] LG51 .H577P ABCT 2009 DongOsteoporosis is a worldwide public health problem that poses significant economic burden on society as well as on families of patients that suffer reduced functional independence as a result of osteoporosis related fractures. In most frequently affected postmenopausal women, vertebral and hip fractures are often attributed to low estrogen production and secondary hyperparathyroidism as a result of age-related decline in calcium (Ca) intake and 1,25-dihydroxyvitamin D₃(1,25(OH)₂D₃)-mediated Ca absorption. In the present study, the effects of estrogen deficiency on intestinal Ca absorption and renal Ca reabsorption in aged ovariectomized (OVX) female rats fed different levels of dietary Ca for 3 months were characterized. The results indicated that intestinal Ca absorption and renal Ca reabsorption were reduced in response to long-term estrogen deficiency in aged female rats. The blunted Ca absorption during estrogen deficiency in aged female rats was associated with the alterations of expression of epithelial Ca transporting proteins in intestine and kidney. However, 1,25(OH)₂D₃ dependent Ca transport protein expressions were upregulated in aged normal and OVX female rats fed low Ca diet, suggesting that the blunted Ca transport associated with estrogen deficiency is not due to alteration in l,25(OH)₂D₃-mediated Ca absorption. Previous studies in our laboratories demonstrated that the ethanol extract of Fructus Ligustri Lucidi (Nuzhenzi, FLL), a Chinese Medicinal herb, plays an active role in modulating Ca homeostasis, not only in OVX rats but also in aged female rats with intact ovaries. In order to identify the active fractions which are responsible for the positive actions of FLL on Ca homeostasis, ethyl acetate soluble (lipophilic) fraction (EAF) and water layer (hydrophilic) fraction (WF) were prepared from the ethanol extract (EE) of FLL and administered to young female rats. The effects of different FLL fractions on Ca balance were evaluated. Our results showed that WF fraction of FLL exerted positive effects on Ca balance in rats fed a diet containing adequate Ca. The positive actions of FLL fractions on Ca balance might relate to their abilities to modulate the expression of epithelial Ca transporting proteins.Our previous study also showed that the ethanol extract of FLL increased serum 1,25(OH)₂D₃ levels in aged female rats. Thus, the mechanism by which the ethanol extract of FLL modulates vitamin D₃ metabolism was also investigated. The results indicated that the ethanol extract of FLL could raise the production of serum 1,25(OH)₂D₃ levels in both aged normal and OVX female rats via the induction of the expression and activity of renal 25-hydroxy-lα-hydroxylase (1-OHase) directly. To identify the active fraction that accounts for the positive effects of FLL on renal 1-OHase, human proximal tubule HKC-8 cells were established as an in vitro screening platform. The results indicated that the EA fraction of FLL was the active fraction that contributed to its modulatory action on renal 1-OHase. In conclusion, the results of the study show that FLL ethanol extract is effective in improving Ca balance in both young and aging animals by inducing the expression of epithelial Ca transport protein as well as the activity and expression of renal 1-OHase. The hydrophilic fraction of the FLL ethanol extract is responsible for its stimulatory actions on Ca transport and the lipophilic fraction of the FLL ethanol extract is responsible for its stimulatory actions on renal 1-OHase. The study suggests that FLL ethanol extract might be a useful agent for prevention of postmenopausal osteoporosis by improving disturbances in Ca balance associated with estrogen deficiency.Department of Applied Biology and Chemical TechnologyPh.D., Dept. of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, 200