Dried Plum Polyphenolic Extract Combined with Vitamin K and Potassium Restores Trabecular and Cortical Bone in Osteopenic Model of Postmenopausal Bone Loss.

Dried plum has unique anabolic effects on bone, but the responsible bioactive components have remained unclear. This study investigated components of dried plum with potential osteoprotective activity utilizing aged, osteopenic Sprague Dawley rats fed diets supplemented with a crude polyphenol extract, potassium, vitamin K or their combination. Whole body and femoral bone mineral density were restored with the polyphenol and combination treatments to a similar extent as the dried fruit. The combination treatment reversed trabecular bone loss in the spine and cortical bone in the femur mid-diaphysis in a similar manner. Biomarkers of bone resorption were reduced by the polyphenol and combination treatments. The polyphenol extract accounted for most of the anabolic effect of dried plum on bone. This study is the first to show the bioactive components in dried plum responsible for restoring bone in vivo.

A comparative study of the bone metabolic response to dried plum supplementation and PTH treatment in adult, osteopenic ovariectomized rat.

Dried plum has been reported to have potent effects on bone in osteopenic animal models, but the mechanisms through which bone metabolism is altered in vivo remain unclear. To address this issue, a study comparing the metabolic response of dried plum to the anabolic agent, parathyroid hormone (PTH), was undertaken. Six month-old female Sprague Dawley rats (n=84) were sham-operated (SHAM) or ovariectomized (OVX) and maintained on a control diet for 6wks until osteopenia was confirmed. Treatments were initiated consisting of a control diet (AIN-93M) supplemented with dried plum (0, 5, 15 or 25%; w/w) or a positive control group receiving PTH. At the end of 6wks of treatment, whole body and femoral bone mineral density (BMD) were restored by the two higher doses of dried plum to the level of the SHAM group. Trabecular bone volume and cortical thickness were also improved with these two doses of dried plum. Dried plum suppressed the OVX-induced increase in bone turnover as indicated by systemic biomarkers of bone metabolism, N-terminal procollagen type 1 (P1NP) and deoxypyridinoline (DPD). Dynamic bone histomorphometric analysis of the tibial metaphysis revealed that dried plum restored the OVX-induced increase in cancellous bone formation rate (BFR) and mineralizing surface (MS/BS) to the SHAM group, but some doses of dried plum increased endocortical mineral apposition rate (MAR). As expected, PTH significantly increased endocortical MAR and BFR, periosteal BFR, and trabecular MAR and BFR beyond that of the OVX and maintained the accelerated rate of bone resorption associated with OVX. Dried plum up-regulated bone morphogenetic protein 4 (Bmp4) and insulin-like growth factor 1 (Igf1) while down-regulating nuclear factor T cell activator 1 (Nfatc1). These findings demonstrate that in the adult osteopenic OVX animal, the effects of dried plum differ from that of PTH in that dried plum primarily suppressed bone turnover with the exception of the indices of bone formation at the endocortical surface.

White button, portabella, and shiitake mushroom supplementation up-regulates interleukin-23 secretion in acute dextran sodium sulfate colitis C57BL/6 mice and murine macrophage J.744.1 cell line.

Interleukin-23 (IL-23), a cytokine produced primarily by dendritic cells, is involved in host defense against gut pathogens and promotes innate immunity and inflammatory responses through the IL-23/interleukin-17 axis. We previously reported that extracts from edible mushrooms enhanced antimicrobial α-defensin production n HL60 cells. Because IL-23 is involved in defensin production, we hypothesized that edible mushrooms may modulate its secretion and gut inflammation. Eight-week-old C57BL/6 mice were fed the AIN76 diet or the same diet supplemented with 5% white button (WBM), portabella, or shiitake mushrooms. To assess in vivo and in vitro cytokine secretion, 7 to 8 mice per group received 3% dextran sodium sulfate (DSS) in drinking water during the last 5 days of the 6-week feeding period. To delineate the mechanisms by which mushrooms alter IL-23 secretion, J.744.1 cells were incubated with (100 µg/mL) WBM, portabella, and shiitake extracts without and with 100 µg/mL curdlan (a dectin-1 agonist) or 1 mg/mL laminarin (a dectin-1 antagonist). The dectin-1 receptor is a pattern-recognition receptor found in phagocytes, and its activation promotes antimicrobial innate immunity and inflammatory responses. In DSS-untreated mice, mushrooms significantly increased IL-23 plasma levels but decreased those of interleukin-6 (IL-6) (P < .05). In DSS-treated mice, mushroom-supplemented diets increased IL-6 and IL-23 levels (P < .05). Mushroom extracts potentiated curdlan-induced IL-23 secretion, and mushroom-induced IL-23 secretion was not blocked by laminarin in vitro, suggesting the involvement of both dectin-1-dependent and dectin-1-independent pathways. Although all mushrooms tended to increase IL-6 in the colon, only WBM and shiitake tended to increase IL-23 levels. These data suggest that edible mushrooms may enhance gut immunity through IL-23.

Dried plum's unique capacity to reverse bone loss and alter bone metabolism in postmenopausal osteoporosis model.

Interest in dried plum has increased over the past decade due to its promise in restoring bone and preventing bone loss in animal models of osteoporosis. This study compared the effects of dried plum on bone to other dried fruits and further explored the potential mechanisms of action through which dried plum may exert its osteoprotective effects. Adult osteopenic ovariectomized (OVX) C57BL/6 mice were fed either a control diet or a diet supplemented with 25% (w/w) dried plum, apple, apricot, grape or mango for 8 weeks. Whole body and spine bone mineral density improved in mice consuming the dried plum, apricot and grape diets compared to the OVX control mice, but dried plum was the only fruit to have an anabolic effect on trabecular bone in the vertebra and prevent bone loss in the tibia. Restoration of biomechanical properties occurred in conjunction with the changes in trabecular bone in the spine. Compared to other dried fruits in this study, dried plum was unique in its ability to down-regulate osteoclast differentiation coincident with up-regulating osteoblast and glutathione (GPx) activity. These alterations in bone metabolism and antioxidant status compared to other dried fruits provide insight into dried plum's unique effects on bone.

Dietary supplementation with dried plum prevents ovariectomy-induced bone loss while modulating the immune response in C57BL/6J mice.

This study was designed to investigate the effects of dried plum on the changes in bone metabolism and the immune response associated with ovarian hormone deficiency. Adult female C57BL/6J mice were either sham-operated (Sham) and fed AIN-93 diet (control) or ovariectomized (OVX) and fed a control diet with 0%, 5%, 15% or 25% dried plum (w/w), corresponding to control, low- (LDP), medium- (MDP) and high (HDP)-dose dried plum. Four weeks of HDP supplementation prevented the decrease in spine bone mineral density and content induced by OVX. The OVX compromise in trabecular bone of the vertebra and proximal tibia was prevented by the higher doses of dried plum, and in the vertebra these effects resulted in greater (P<.05) bone strength and stiffness. In the bone marrow, OVX suppressed granulocyte and committed monocyte populations and increased the lymphoblast population, but the MDP and HDP restored these myeloid and lymphoid populations to the level of the Sham. Dried plum also suppressed lymphocyte tumor necrosis factor (TNF)-α production ex vivo by splenocytes, in response to concanavalin (Con) A stimulation. These data indicate that dried plum's positive effects on bone structural and biomechanical properties coincide with the restoration of certain bone marrow myeloid and lymphoid populations, and suppressed splenocyte activation occurring with ovarian hormone deficiency.

Differential effects of shiitake- and white button mushroom-supplemented diets on hepatic steatosis in C57BL/6 mice.

Shiitake mushrooms (SMs) have been used in Asia for treatment and/or prevention of chronic diseases and hypercholesterolemia. Previously, we observed a diet supplemented with 5% SM resulted in a twofold increase in plasma IL-6 levels in DBA arthritic mice. An elevation in plasma IL-6 has also been implicated in the pathogenesis fatty liver disease. Thus, the aim of this study was to investigate the effect of SM supplemented-diet on hepatic steatosis. In study 1, eight-week old female C57BL/6 mice were randomly assigned to the following groups for 6 weeks: the AIN-93 diet; 5% SM, and 5% white button mushroom (WBM) supplemented diets (12/group). In study 2, mice were fed either the AIN-93 diet or SM (20/group). After 6 weeks, 13 mice fed SM diet were given the AIN93 diet for 8 or 15 days. Unlike other groups, all mice fed the SM diet developed fatty liver (mean histopathology score 4.5 vs <1 in the other groups; p<0.001) without fibrosis and inflammation. Fifteen days post withdrawal of SM completely normalized liver histology. To the best of our knowledge, this is the first report that chronic consumption of SM is associated with the development of fatty liver. The mechanism by which SM causes hepatic steatosis warrants further investigation.