Abstract:Mulberry has favorable antioxidant ability. Menopause is a major cause of osteoporosis in women, and it is partially associated with oxidative stress. Here, mulberry water extract (MWE) was fed to ovariectomic (OVX) rats to explore the potential effect of MWE on osteoporosis. The results revealed that plasma alkaline phosphatase (ALP) significantly decreased in the OVX rats after MWE administration for 8 weeks. Histological examination showed that the MWE increased the density of trabecular bone in the OVX rat… Show more
“…Among these, RUNX2 is essential for osteoblast differentiation, and is detected in pre-osteoblasts, where its expression increases as the cell develops into an immature osteoblast (7). Some studies have demonstrated that natural extracts can upregulate BMP-2/RUNX2 and promote osteoblast differentiation (30,31). ALP and BSP is involved in early-stage molecular events during osteoblast differentiation and is known to upregulate the initial mineralization stage (32,33).…”
Leonurus sibiricus
L. (LS) is a medicinal plant used in East Asia, Europe and the USA. LS is primarily used in the treatment of gynecological diseases, and recent studies have demonstrated that it exerts anti-inflammatory and antioxidant effects. To the best of our knowledge, the present study demonstrated for the first time that LS may promote osteoblast differentiation and suppress osteoclast differentiation
in vitro
, and that it inhibited lipopolysaccharide (LPS)-induced bone loss in a mouse model. LS was observed to promote the osteoblast differentiation of MC3T3-E1 cells and upregulate the expression of runt-related transcription factor 2 (RUNX2), a key gene involved in osteoblast differentiation. This resulted in the induction of the expression of various osteogenic genes, including alkaline phosphatase (ALP), osteonectin (OSN), osteopontin (OPN), type I collagen (COL1) and bone sialoprotein (BSP). LS was also observed to inhibit osteoclast differentiation and bone resorption. The expression levels of nuclear factor of activated T-cells 1 (NFATc1) and c-Fos were inhibited following LS treatment. NFATc1 and c-Fos are key markers of osteoclast differentiation that inhibit receptor activator of nuclear factor-κB ligand (RANKL)-induced mitogen-activated protein kinase (MAPKs) and nuclear factor (NF)-κB. As a result, LS suppressed the expression of osteoclast-associated genes, such as matrix metallopeptidase-9 (MMP-9), cathepsin K (Ctsk), tartrate-resistant acid phosphatase (TRAP), osteoclast-associated immunoglobulin-like receptor (OSCAR), c-src, c-myc, osteoclast stimulatory transmembrane protein (OC-STAMP) and ATPase H+ transporting V0 subunit d2 (ATP6v0d2). Consistent with the
in vitro
results, LS inhibited the reduction in bone mineral density and the bone volume/total volume ratio in a mouse model of LPS-induced osteoporosis. These results suggest that LS may be a valuable agent for the treatment of osteoporosis and additional bone metabolic diseases.
“…Among these, RUNX2 is essential for osteoblast differentiation, and is detected in pre-osteoblasts, where its expression increases as the cell develops into an immature osteoblast (7). Some studies have demonstrated that natural extracts can upregulate BMP-2/RUNX2 and promote osteoblast differentiation (30,31). ALP and BSP is involved in early-stage molecular events during osteoblast differentiation and is known to upregulate the initial mineralization stage (32,33).…”
Leonurus sibiricus
L. (LS) is a medicinal plant used in East Asia, Europe and the USA. LS is primarily used in the treatment of gynecological diseases, and recent studies have demonstrated that it exerts anti-inflammatory and antioxidant effects. To the best of our knowledge, the present study demonstrated for the first time that LS may promote osteoblast differentiation and suppress osteoclast differentiation
in vitro
, and that it inhibited lipopolysaccharide (LPS)-induced bone loss in a mouse model. LS was observed to promote the osteoblast differentiation of MC3T3-E1 cells and upregulate the expression of runt-related transcription factor 2 (RUNX2), a key gene involved in osteoblast differentiation. This resulted in the induction of the expression of various osteogenic genes, including alkaline phosphatase (ALP), osteonectin (OSN), osteopontin (OPN), type I collagen (COL1) and bone sialoprotein (BSP). LS was also observed to inhibit osteoclast differentiation and bone resorption. The expression levels of nuclear factor of activated T-cells 1 (NFATc1) and c-Fos were inhibited following LS treatment. NFATc1 and c-Fos are key markers of osteoclast differentiation that inhibit receptor activator of nuclear factor-κB ligand (RANKL)-induced mitogen-activated protein kinase (MAPKs) and nuclear factor (NF)-κB. As a result, LS suppressed the expression of osteoclast-associated genes, such as matrix metallopeptidase-9 (MMP-9), cathepsin K (Ctsk), tartrate-resistant acid phosphatase (TRAP), osteoclast-associated immunoglobulin-like receptor (OSCAR), c-src, c-myc, osteoclast stimulatory transmembrane protein (OC-STAMP) and ATPase H+ transporting V0 subunit d2 (ATP6v0d2). Consistent with the
in vitro
results, LS inhibited the reduction in bone mineral density and the bone volume/total volume ratio in a mouse model of LPS-induced osteoporosis. These results suggest that LS may be a valuable agent for the treatment of osteoporosis and additional bone metabolic diseases.
“…This can also be partly supported by the evidence that morin has been observed in ethanolic extracts of Mori Ramulus (mulberry twigs) [19], and high glucose induced oxidative stress-mediated apoptosis in primary rat hepatocytes [20]. These findings, that LAMF, LAMR and relevant phytophenols can release the oxidative stress of MSCs, can also explain the latest findings that mulberries have the potential to decelerate osteoporosis that is associated with oxidative stress in an experimental ovariectomic rat model [24]. Fig.…”
Background
Mori Fructus and Mori Ramulus are two traditional Chinese herbal medicines from mulberries. The present work explores their beneficial effects on •OH–treated mesenchymal stem cells (MSCs) and discusses possible mechanisms.MethodsLyophilized aqueous extracts of Mori Fructus (LAMF) and Mori Ramulus (LAMR) were prepared and analyzed using HPLC. LAMF and LAMR (along with morin) were further investigated for their effects on •OH-treated MSCs using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl (MTT) assay. The direct antioxidation mechanisms were studied using 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO•)-scavenging, 2,2′-azino-bis (3-ethylbenzo-thiazoline-6-sulfonic acid (ABTS+•)-scavenging and 1,1-diphenyl-2-picryl-hydrazl (DPPH•)-scavenging, as well as Cu2+-reducing and Fe3+-reducing antioxidant power. Finally, the indirect antioxidant mechanism was investigated based on the UV-vis spectra of Fe2+-chelation.ResultsIn each LAMF and LAMR, seven phytophenols were successfully measured by HPLC, including five flavonoids (morin, rutin, astragalin, isoquercitrin and luteolin) and two non-flavonoids (chlorogenic acid and maclurin). MTT assays revealed that LAMF, LAMR and morin could effectively increase the survival of •OH-treated MSCs at 10–100 μg/mL, and could effectively scavenge PTIO• (IC 50 6609.7 ± 756.6, 4286.9 ± 84.9 and 103.4 ± 0.9 μg/mL, respectively), DPPH• (IC 50 208.7 ± 3.0, 97.3 ± 3.1 and 8.2 ± 0.7 μg/mL, respectively) and ABTS+• (IC 50 73.5 ± 5.8, 34.4 ± 0.1 and 4.2 ± 0.2 μg/mL, respectively), and reduce Cu2+ (IC 50 212.5 ± 7.0, 123.2 ± 0.9 and 14.1 ± 0.04 μg/mL, respectively) & Fe3+ (IC 50 277.0 ± 3.1, 191.9 ± 5.2 and 5.0 ± 0.2 μg/mL, respectively). In the Fe2+-chelating assay, the five flavonoids produced much stronger shoulder-peaks than the two non-flavonoids within 420–850 nm.Conclusion
Mori Fructus and Mori Ramulus, can protect MSCs from •OH-induced damage. Such beneficial effects can mainly be attributed to the antioxidant action of phytophenols, which occurs via direct (ROS-scavenging) and indirect mechanism (Fe2+-chelating). The ROS-scavenging mechanism, however, include at least a H+-transfer and an electron-transfer (ET), and possibly includes a hydrogen-atom-transfer (HAT). In the Fe2+-chelating, flavonoids are more effective than non-flavonoids. This can be attributed to several adjacent planar chelating-sites between the 3-OH and 4-C = O, between the 4-C = O and 5-OH, or between the 3′-OH and 4′-OH in flavonoids. Such multiple-Fe2+-chelating reactions cause overlap in the UV-vis absorptions to deepen the complex color, enhance the peak strength, and form shoulder-peaks. By comparison, two non-flavonoids with catechol moiety produce only a weak single peak.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-017-1730-3) contains supplementary material, which is available to authorized users.
“…The guava fruit was also effective against osteoporosis according to Chinese medicine due to the presence of polyphenolic compounds and increased bone health [31][32][33][34][35]. The results showed similar properties as Rumex crispus extract in osteoblast differentiation through runt related transcription factor 2 and suppress the RANKL induced bone loss through suppressing the RANKL signaling [36,37].…”
Trigonella stellata has used in folk medicine as palatable and nutraceutical herb. It also regulates hypocholesterolemia, hypoglycemia, and has showed anti-inflammatory activities as well as antioxidants efficacy. Osteoporosis is a one of bone metabolic disorders and is continuously increasing worldwide. In the present study, caffeic acid was isolated from Trigonella stellata and identified using 1 D- and 2 D-NMR spectroscopic data. Caffeic acid was investigated on osteoblast and osteoclast in vitro using mice bone marrow-derived mesenchymal cells. Caffeic acid played reciprocal proliferation between osteoblast and osteoclast cells and accelerated the bone mineralization. It was confirmed by cytotoxicity, alkaline phosphatase (ALP), alizarin red S (ARS), and Tartrate resistant acid phosphatase (TRAP) assay. Caffeic acid regulated the osteogenic marker and upregulated the osteopontin, osteocalcin, and bone morphogenic proteins (BMP). Quantitative real time PCR and Western blot were used to quantify the mRNA and protein markers. It also regulated the matrix metalloprotease-2 (MMP-2) and cathepsin-K proteolytic markers in osteoclast cells. In addition, caffeic acid inhibited bone resorption in osteoclast cells. On the other hand, it upregulate osteoblast differentiation through stimulation of extracellular calcium concentrations osteoblast differentiation, respectively. The results also were confirmed through in silico docking of caffeic acid against cathepsin-B and cathepsin-K markers. These findings revealed that caffeic acid has a potential role in bone-metabolic disorder through its multifaceted effects on osteoblast and osteoclast regulations and controls osteoporosis.
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