Category Archives: Oleuropein

Olive Oleuropein and Hydroxytyrosol Prevents Bone Loss in Mice


Olive polyphenol hydroxytyrosol prevents bone loss.

Polyphenols reportedly exert physiological effects against diseases such as cancer, arteriosclerosis, hyperlipidemia and osteoporosis. The present study was designed to evaluate the effects of oleuropein, hydroxytyrosol and tyrosol, the major polyphenols in olives, on bone formation using cultured osteoblasts and osteoclasts, and on bone loss in ovariectomized mice. No polyphenols markedly affected the proliferation of osteoblastic MC3T3-E1 cells at concentrations up to 10μM. Oleuropein and hydroxytyrosol at 10 to 100μM had no effect on the production of type I collagen and the activity of alkaline phosphatase in MC3T3-E1 cells, but stimulated the deposition of calcium in a dose-dependent manner. In contrast, oleuropein at 10 to 100μM and hydroxytyrosol at 50 to 100μM inhibited the formation of multinucleated osteoclasts in a dose-dependent manner. Furthermore, both compounds suppressed the bone loss of trabecular bone in femurs of ovariectomized mice (6-week-old BALB/c female mice), while hydroxytyrosol attenuated H(2)O(2) levels in MC3T3-E1 cells. Our findings indicate that the olive polyphenols oleuropein and hydroxytyrosol may have critical effects on the formation and maintenance of bone, and can be used as effective remedies in the treatment of osteoporosis symptoms.

Hagiwara K, Goto T, Araki M, Miyazaki H…
Eur. J. Pharmacol. Jul 2011
PMID: 21539839

Oleuropein (from Olives) Increases Osteoblasts In Vitro


Oleuropein enhances osteoblastogenesis and inhibits adipogenesis: the effect on differentiation in stem cells derived from bone marrow.

The effects of oleuropein on the processes of osteoblastogenesis and adipogenesis in mesenchymal stem cells (MSCs) from human bone marrow have been studied. We report that oleuropein, a polyphenol abundant in olive tree products, reduces the expression of peroxisome proliferator-activated receptor gamma (PPARγ), inhibits adipocyte differentiation, and enhances differentiation into osteoblast.
Age-related bone loss is associated with osteoblast insufficiency during continuous bone remodeling. It has been suggested that the formation of osteoblasts in bone marrow is closely associated with adipogenesis, and age-related changes in this relationship could be responsible for the progressive adiposity of bone marrow which occurs with osteoporosis. In addition, the consumption of oleuropein, a major polyphenol in olive leaves and olive oil, has been associated with a reduction in bone loss.
We have analyzed the effects of oleuropein-at concentrations between 10(-6) and 10(-4) M-on the processes of osteoblastogenesis and adipogenesis in MSCs from human bone marrow.
The results show an increase in osteoblast differentiation and a decrease in adipocyte differentiation when there is oleuropein in the culture media. The gene expression of osteoblastogenesis markers, RUNXII, osterix, collagen type I, osteocalcin, or alkaline phosphatase (ALP), was higher in osteoblast-induced oleuropein-treated cells. Also, the ALP activity and extracellular matrix mineralization were higher when oleuropein was present in the media. Oleuropein in MSCs induced adipocytes to produce a decrease in the expression of the genes involved in adipogenesis, the PPARγ, lipoprotein lipase, or fatty acid-binding protein 4, and minor fat accumulation.
Our data suggest that oleuropein, highly abundant in olive tree products included in the traditional Mediterranean diet, could prevent age-related bone loss and osteoporosis.

Santiago-Mora R, Casado-Díaz A, De Castro MD, Quesada-Gómez JM
Osteoporos Int Feb 2011
PMID: 20495905

Every Dose of Oleuropein Protective in Rats


Dose-response study of effect of oleuropein, an olive oil polyphenol, in an ovariectomy/inflammation experimental model of bone loss in the rat.

This study was carried out to assess the dose-dependent bone-sparing effect of oleuropein, an olive oil phenolic compound with anti-inflammatory and anti-oxidative properties, on bone loss induced by talc granulomatosis in oestrogen-deficient rat.
Among 98 rats, 20 were sham-operated (SH) while the others (78) were ovariectomised (OVX). The SH and 26 OVX rats (controls) were given a standard diet for 100 days. The 52 remaining OVX rats were allocated to 4 groups that received oleuropein at 2.5, 5, 10 or 15 mg/kg body weight per day for 100 days. Three weeks before necropsy, an inflammation was induced by subcutaneous injections of talc in half of the SH and OVX rats and in all oleuropein-treated animals.
Castration was associated with a decreased bone mineral density (BMD). In OVX rats, inflammation, characterised by an increase of the spleen weight and plasma fibrinogen levels, exacerbated this bone loss, as shown by values of BMD of the total femur metaphyseal and diaphyseal subregions. The 4 doses of oleuropein reduced bone loss and improved inflammatory biomarkers excepted for 5mg/kg BW.
Every dose of oleuropein elicited protective effects on bone mass in this model of ovariectomy associated with inflammation, probably by modulating inflammatory parameters.

Puel C, Mathey J, Agalias A, Kati-Coulibaly S…
Clin Nutr Oct 2006
PMID: 16740345

Olive Oil and Oleuropein in Rats


Olive oil and its main phenolic micronutrient (oleuropein) prevent inflammation-induced bone loss in the ovariectomised rat.

The present study was designed to evaluate the effect of olive oil and its main polyphenol (oleuropein) in ovariectomised rats with or without inflammation. Rats (6 months old) were ovariectomised or sham-operated as control. Ovariectomised rats were separated into three groups receiving different diets for 3 months: a control diet with 25 g peanut oil and 25 g rapeseed oil/kg (OVX), the control diet with 50 g olive oil/kg or the control diet with 0.15 g oleuropein/kg. The sham-operated group was given the same control diet as OVX. Inflammation was induced 3 weeks before the end of the experiment by subcutaneous injections of talc (magnesium silicate) in one-half of each group. The success of ovariectomy was verified at necropsy by the atrophy of uterine horns. Inflammation, oleuropein or olive oil intakes did not have any uterotrophic activity, as they had had no effect on uterus weight. The plasma concentration of alpha-1-acid glycoprotein (an indicator of inflammation) was increased in OVX rats with inflammation. With regard to bone variables, osteopenia in OVX was exacerbated by inflammation, as shown by a decrease in metaphyseal and total femoral mineral density. Both oleuropein and olive oil prevented this bone loss in OVX rats with inflammation. At necropsy, oleuropein and olive oil consumption had had no effect on plasma osteocalcin concentrations (marker of bone formation) or on urinary deoxypyridinoline excretion (marker of bone resorption). In conclusion, oleuropein and olive-oil feeding can prevent inflammation-induced osteopenia in OVX rats.

Puel C, Quintin A, Agalias A, Mathey J…
Br. J. Nutr. Jul 2004
PMID: 15230995