The phenolic acids of Agen prunes (dried plums) or Agen prune juice concentrates do not account for the protective action on bone in a rat model of postmenopausal osteoporosis.

Dietary supplementation with dried plum (DP) has been shown to protect against and reverse established osteopenia in ovariectomized rodents. Based on in vitro studies, we hypothesized that DP polyphenols may be responsible for that bone-sparing effect. This study was designed to (1) analyze whether the main phenolic acids of DP control preosteoblast proliferation and activity in vitro; (2) determine if the polyphenolic content of DP or DP juice concentrate is the main component improving bone health in vivo; and (3) analyze whether DP metabolites directly modulate preosteoblast physiology ex vivo. In vitro, we found that neochlorogenic, chlorogenic, and caffeic acids induce the proliferation and repress the alkaline phosphatase activity of primary preosteoblasts in a dose-dependent manner. In vivo, low-chlorogenic acid Agen prunes (AP) enriched with a high-fiber diet and low-chlorogenic acid AP juice concentrate prevented the decrease of total femoral bone mineral density induced by estrogen deficiency in 5-month-old female rats and positively restored the variations of the bone markers osteocalcin and deoxypyridinoline. Ex vivo, we demonstrated that serum from rats fed with low-chlorogenic acid AP enriched with a high-fiber diet showed repressed proliferation and stimulated alkaline phosphatase activity of primary preosteoblasts. Overall, the beneficial action of AP on bone health was not dependent on its polyphenolic content.

Pomegranate Peel Extract Prevents Bone Loss in a Preclinical Model of Osteoporosis and Stimulates Osteoblastic Differentiation in Vitro.

The nutritional benefits of pomegranate have attracted great scientific interest. The pomegranate, including the pomegranate peel, has been used worldwide for many years as a fruit with medicinal activity, mostly antioxidant properties. Among chronic diseases, osteoporosis, which is associated with bone remodelling impairment leading to progressive bone loss, could eventually benefit from antioxidant compounds because of the involvement of oxidative stress in the pathogenesis of osteopenia. In this study, with in vivo and ex vivo experiments, we investigated whether the consumption of pomegranate peel extract (PGPE) could limit the process of osteopenia. We demonstrated that in ovariectomized (OVX) C57BL/6J mice, PGPE consumption was able to significantly prevent the decrease in bone mineral density (-31.9%; p < 0.001 vs. OVX mice) and bone microarchitecture impairment. Moreover, the exposure of RAW264.7 cells to serum harvested from mice that had been given a PGPE-enriched diet elicited reduced osteoclast differentiation and bone resorption, as shown by the inhibition of the major osteoclast markers. In addition, PGPE appeared to substantially stimulate osteoblastic MC3T3-E1 alkaline phosphatase (ALP) activity at day 7, mineralization at day 21 and the transcription level of osteogenic markers. PGPE may be effective in preventing the bone loss associated with ovariectomy in mice, and offers a promising alternative for the nutritional management of this disease.

Pomegranate and its derivatives can improve bone health through decreased inflammation and oxidative stress in an animal model of postmenopausal osteoporosis.

PURPOSE: Recently, nutritional and pharmaceutical benefits of pomegranate (PG) have raised a growing scientific interest. Since PG is endowed with anti-inflammatory and antioxidant activities, we hypothesized that it may have beneficial effects on osteoporosis. METHODS: We used ovariectomized (OVX) mice as a well-described model of postmenopausal osteoporosis to study the influence of PG consumption on bone health. Mice were divided into five groups as following: two control groups sham-operated and ovariectomized (OVX CT) mice fed a standard diet, versus three treated groups OVX mice given a modified diet from the AIN-93G diet, containing 5.7% of PG lyophilized mashed totum (OVX PGt), or 9.6% of PG fresh juice (OVX PGj) or 2.9% of PG lyophilized mashed peel (OVX PGp). RESULTS: As expected, ovariectomy was associated with a decreased femoral bone mineral density (BMD) and impaired bone micro-architecture parameters. Consumption of PGj, PGp, or PGt induced bone-sparing effects in those OVX mice, both on femoral BMD and bone micro-architecture parameters. In addition, PG (whatever the part) up-regulated osteoblast activity and decreased the expression of osteoclast markers, when compared to what was observed in OVX CT animals. Consistent with the data related to bone parameters, PG consumption elicited a lower expression of pro-inflammatory makers and of enzymes involved in ROS generation, whereas the expression of anti-inflammatory markers and anti-oxidant actors was enhanced. CONCLUSION: These results indicate that all PG parts are effective in preventing the development of bone loss induced by ovariectomy in mice. Such an effect could be partially explained by an improved inflammatory and oxidative status.

Pomegranate seed oil prevents bone loss in a mice model of osteoporosis, through osteoblastic stimulation, osteoclastic inhibition and decreased inflammatory status.

In the current context of longer life expectancy, the prevalence of osteoporosis is increasingly important. This is why development of new strategies of prevention is highly suitable. Pomegranate seed oil (PSO) and its major component, punicic acid (a conjugated linolenic acid), have potent anti-inflammatory and anti-oxidative properties both in vitro and in vivo, two processes strongly involved in osteoporosis establishment. In this study, we demonstrated that PSO consumption (5% of the diet) improved significantly bone mineral density (240.24±11.85 vs. 203.04±34.19 mg/cm(3)) and prevented trabecular microarchitecture impairment in ovariectomized (OVX) mice C57BL/6J, compared to OVX control animals. Those findings are associated with transcriptional changes in bone tissue, suggesting involvement of both osteoclastogenesis inhibition and osteoblastogenesis improvement. In addition, thanks to an ex vivo experiment, we provided evidence that serum from mice fed PSO (5% by gavage) had the ability to significantly down-regulate the expression of specific osteoclast differentiation markers and RANK-RANKL downstream signaling targets in osteoclast-like cells (RAW264.7) (RANK: negative 0.49-fold vs. control conditions). Moreover, in osteoblast-like cells (MC3T3-E1), it elicited significant increase in alkaline phosphatase activity (+159% at day 7), matrix mineralization (+271% on day 21) and transcriptional levels of major osteoblast lineage markers involving the Wnt/ß-catenin signaling pathways. Our data also reveal that PSO inhibited pro-inflammatory factors expression while stimulating anti-inflammatory ones. These results demonstrate that PSO is highly relevant regarding osteoporosis. Indeed, it offers promising alternatives in the design of new strategies in nutritional management of age-related bone complications.

Borage and fish oils lifelong supplementation decreases inflammation and improves bone health in a murine model of senile osteoporosis.

Fats are prevalent in western diets; they have known deleterious effects on muscle insulin resistance and may contribute to bone loss. However, relationships between fatty acids and locomotor system dysfunctions in elderly population remain controversial. The aim of this study was to analyze the impact of fatty acid quality on the age related evolution of the locomotor system and to understand which aging mechanisms are involved. In order to analyze age related complications, the SAMP8 mouse strain was chosen as a progeria model as compared to the SAMR1 control strain. Then, two months old mice were divided in different groups and subjected to the following diets : (1) standard "growth" diet - (2) "sunflower" diet (high ω6/ω3 ratio) - (3) "borage" diet (high γ-linolenic acid) - (4) "fish" diet (high in long chain ω3). Mice were fed ad libitum through the whole protocol. At 12 months old, the mice were sacrificed and tissues were harvested for bone studies, fat and muscle mass measures, inflammation parameters and bone cell marker expression. We demonstrated for the first time that borage and fish diets restored inflammation and bone parameters using an original model of senile osteoporosis that mimics clinical features of aging in humans. Therefore, our study strongly encourages nutritional approaches as relevant and promising strategies for preventing aged-related locomotor dysfunctions.