Drynaria fortunei-derived total flavonoid fraction and isolated compounds exert oestrogen-like protective effects in bone

Drynaria fortunei (Kunze) J. Sm. (DF), a Chinese herb commonly used for the treatment of bone fracture, was previously shown to exert anabolic effects on bone. However, its active ingredients as well as the mechanisms of action are far from clear. The present study aimed to characterise the bone anabolic effects of DF flavonoid fraction (DFTF) in ovariectomised (OVX) mice and to determine if DFTF and its isolated compounds exert oestrogen-like effects in rat osteoblast-like UMR-106 cells. Young OVX C57/BL6J mice were treated orally with DFTF (0·087, 0·173 or 0·346 mg/g per d), 17β-oestradiol (2 μg/g per d) or its vehicle for 6 weeks. Serum and urine samples were collected for biochemical marker analysis. Bones were collected for computed tomography analysis. UMR-106 cells were treated with DFTF and isolated compounds naringin, (2S)-5,7,3′,5′-tetrahydroxy-flavonone 7-O-neohesperidoside (compound 1) and 5,7-dihydroxychromone 7-O-neohesperidoside (compound 2). DFTF exerted dose-dependent effects in improving bone mineral densities as well as bone strength at the femur, tibia and lumbar spine L1 in OVX mice. DFTF and the three isolated compounds stimulated osteoblastic cell proliferation and alkaline phosphatase activities in a dose-dependent manner. In addition, they stimulated the ratio of osteoprotegrin and receptor-activator NF-κB ligand mRNA expression, suggesting their involvement in inhibiting osteoclastogenesis. These stimulatory effects on osteoblastic functions were abolished in the presence of oestrogen receptor (ER) antagonist, ICI 182780. The present results suggested that DFTF is effective in protecting against OVX-induced bone loss in mice, and its actions in regulating osteoblastic activities appear to be mediated by ER.

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Tetramethylpyrazine protects Schwann cells from ischemia-like injury and increases cell survival in cold ischemic rat nerves

Brazilian Journal of Pharmaceutical Sciences ◽

10.1590/s1984-82502015000100014 ◽

2015 ◽

Vol 51 (1) ◽

pp. 127-141

Author(s):

Ming-Ming Yang ◽

Wei Huang ◽

Dian-Ming Jiang

Keyword(s):

Cell Viability ◽

Cell Survival ◽

Schwann Cells ◽

Caspase 3 ◽

Chinese Herb ◽

Dependent Manner ◽

Protective Effects ◽

Injury Model ◽

Nerve Model ◽

Dose Dependent

Tetramethylpyrazine (TMP), a major active ingredient of Ligusticum wallichi Franchat extract (a Chinese herb), exhibits neuroprotective properties in ischemia. In this study, we assessed its protective effects on Schwann cells (SCs) by culturing them in the presence of oxygen glucose deprivation (OGD) conditions and measuring cell survival in cold ischemic rat nerves. In the OGD-induced ischemic injury model of SCs, we demonstrated that TMP treatment not only reduced OGD-induced cell viability losses, cell death, and apoptosis of SCs in a dose-dependent manner, and inhibited LDH release, but also suppressed OGD-induced downregulation of Bcl-2 and upregulation of Bax and caspase-3, as well as inhibited the consequent activation of caspase-3. In the cold ischemic nerve model, we found that prolonged cold ischemic exposure for four weeks was markedly associated with the absence of SCs, a decrease in cell viability, and apoptosis in preserved nerve segments incubated in University of Wisconsin solution (UWS) alone. However, TMP attenuated nerve segment damage by preserving SCs and antagonizing the decrease in nerve fiber viability and increase in TUNEL-positive cells in a dose-dependent manner. Collectively, our results indicate that TMP not only provides protective effects in an ischemia-like injury model of cultured rat SCs by regulating Bcl-2, Bax, and caspase-3, but also increases cell survival and suppresses apoptosis in the cold ischemic nerve model after prolonged ischemic exposure for four weeks. Therefore, TMP may be a novel and effective therapeutic strategy for preventing peripheral nervous system ischemic diseases and improving peripheral nerve storage.

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Necroptosis protects against exacerbation of acute pancreatitis

Cell Death and Disease ◽

10.1038/s41419-021-03847-w ◽

2021 ◽

Vol 12 (6) ◽

Author(s):

Michittra Boonchan ◽

Hideki Arimochi ◽

Kunihiro Otsuka ◽

Tomoko Kobayashi ◽

Hisanori Uehara ◽

...

Keyword(s):

Acute Pancreatitis ◽

Necrotizing Pancreatitis ◽

Neutrophil Infiltration ◽

Dependent Manner ◽

Protective Effects ◽

Interacting Protein ◽

Inflammatory Conditions ◽

Edematous Pancreatitis ◽

Genetic Deletion ◽

Dose Dependent

AbstractThe sensing of various extrinsic stimuli triggers the receptor-interacting protein kinase-3 (RIPK3)-mediated signaling pathway, which leads to mixed-lineage kinase-like (MLKL) phosphorylation followed by necroptosis. Although necroptosis is a form of cell death and is involved in inflammatory conditions, the roles of necroptosis in acute pancreatitis (AP) remain unclear. In the current study, we administered caerulein to Ripk3- or Mlkl-deficient mice (Ripk3−/− or Mlkl−/− mice, respectively) and assessed the roles of necroptosis in AP. We found that Ripk3−/− mice had significantly more severe pancreatic edema and inflammation associated with macrophage and neutrophil infiltration than control mice. Consistently, Mlkl−/− mice were more susceptible to caerulein-induced AP, which occurred in a time- and dose-dependent manner, than control mice. Mlkl−/− mice exhibit weight loss, edematous pancreatitis, necrotizing pancreatitis, and acinar cell dedifferentiation in response to tissue damage. Genetic deletion of Mlkl resulted in downregulation of the antiapoptotic genes Bclxl and Cflar in association with increases in the numbers of apoptotic cells, as detected by TUNEL assay. These findings suggest that RIPK3 and MLKL-mediated necroptosis exerts protective effects in AP and caution against the use of necroptosis inhibitors for AP treatment.

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Effects of Propentofylline on Hypoxia—Hypoglycemia-Induced Calcium Accumulation in Gerbil Hippocampal Slices

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1992.41 ◽

1992 ◽

Vol 12 (2) ◽

pp. 301-305 ◽

Cited By ~ 12

Author(s):

Fumito Kadoya ◽

Akira Mitani ◽

Tatsuru Arai ◽

Kiyoshi Kataoka

Keyword(s):

Cerebral Ischemia ◽

Intracellular Calcium ◽

Neuronal Damage ◽

Hippocampal Slices ◽

Dependent Manner ◽

Protective Effects ◽

Calcium Accumulation ◽

Xanthine Derivative ◽

Acute Increase ◽

Dose Dependent

The xanthine derivative propentofylline (HWA 285) has been reported to show protective effects against neuronal damage induced by cerebral ischemia. In the present study, microfluorometry was used to investigate the effect of propentofylline on the hypoxia–hypoglycemia-induced intracellular calcium accumulation in gerbil hippocampal slices. When slices were superfused with hypoxic–hypoglycemic medium that did not contain propentofylline, an acute increase in calcium accumulation was detected 75–200 s (mean latency of 123 s) after the beginning of hypoxia–hypoglycemia. When slices were superfused with hypoxic–hypoglycemic mediums that contained 10 μ M, 100 μ M, and 1 m M propentofylline, the latency of the acute increase in calcium accumulation was prolonged in all subregions of the hippocampus in a dose-dependent manner: mean latencies in field CA1 were 146, 168, and 197 s after hypoxia–hypoglycemia, respectively. This retardation in calcium accumulation may be involved in the mechanisms by which propentofylline diminishes ischemic injury.

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Dual effect of polyphosphate on mineralization of rat osteoblast ROS17/2.8 cells in a dose-dependent manner

Journal of Pharmacological Sciences ◽

10.1016/j.jphs.2018.10.002 ◽

2018 ◽

Vol 138 (3) ◽

pp. 209-213 ◽

Cited By ~ 1

Author(s):

Yoshikazu Mikami ◽

Daisuke Omagari ◽

Yusuke Mizutani ◽

Manabu Hayatsu ◽

Tatsuo Ushiki ◽

...

Keyword(s):

Dependent Manner ◽

Dual Effect ◽

Rat Osteoblast ◽

Dose Dependent

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Hepatoprotective effects of Sapium sebiferum in paracetamol-induced liver injury

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v10i2.22576 ◽

2015 ◽

Vol 10 (2) ◽

pp. 393 ◽

Cited By ~ 3

Author(s):

Liaqat Hussain ◽

Muhammad Sajid Hamid Akash ◽

Madeha Tahir ◽

Kanwal Rehman

Keyword(s):

Liver Injury ◽

Serum Levels ◽

Therapeutic Effects ◽

Sapium Sebiferum ◽

Dependent Manner ◽

Protective Effects ◽

Drug Induced ◽

Standard Drug ◽

Hepatoprotective Effects ◽

Dose Dependent

Sapium sebiferum leaves were used to determine its hepatoprotective effects against paracetamol-induced hepatotoxicity in mice. A dose dependent study was conducted using two different doses (200 mg/kg and 400 mg/kg) of the extract of S. sebiferum against toxic effects of paracetamol (500 mg/kg) in experimental animal model. Silymarin (50 mg/kg) was used as standard drug to compare therapeutic effects of S. sebiferum with control and paracetamol-treated groups. Paracetamol significantly increased the serum levels of liver enzyme markers like alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and direct bilirubin. The extract showed protective effects by normalizing the liver enzymes markers in a dose dependent manner. Histopathological results confirmed the hepatoprotective effects of leaves of S. sebiferum. We conclude that leaves of S. sebiferum have strong hepatoprotective effects against paracetamol-induced liver injury and can be used in liver injuries caused by drug-induced toxicity.

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α-Lipoic acid suppresses osteoclastogenesis despite increasing the receptor activator of nuclear factor κB ligand/osteoprotegerin ratio in human bone marrow stromal cells

Journal of Endocrinology ◽

10.1677/joe.1.05995 ◽

2005 ◽

Vol 185 (3) ◽

pp. 401-413 ◽

Cited By ~ 18

Author(s):

Jung-Min Koh ◽

Young-Sun Lee ◽

Chang-Hyun Byun ◽

Eun-Ju Chang ◽

Hyunsoo Kim ◽

...

Keyword(s):

Bone Marrow ◽

Lipoic Acid ◽

Nuclear Factor Κb ◽

Human Bone ◽

Human Bone Marrow ◽

Mouse Bone Marrow ◽

Dependent Manner ◽

Nuclear Factor ◽

Receptor Activator ◽

Dose Dependent

Growing evidence has shown a biochemical link between increased oxidative stress and reduced bone density. Although α-lipoic acid (α-LA) has been shown to act as a thiol antioxidant, its effect on bone cells has not been determined. Using proteomic analysis, we identified six differentially expressed proteins in the conditioned media of α-LA-treated human bone marrow stromal cell line (HS-5). One of these proteins, receptor activator of nuclear factor κB ligand (RANKL), was significantly up-regulated, as confirmed by immunoblotting with anti-RANKL antibody. ELISA showed that α-LA stimulated RANKL production in cellular extracts (membranous RANKL) about 5-fold and in conditioned medium (soluble RANKL) about 23-fold, but had no effect on osteoprotegerin (OPG) secretion. Despite increasing the RANKL/OPG ratio, α-LA showed a dose-dependent suppression of osteoclastogenesis, both in a coculture system of mouse bone marrow cells and osteoblasts and in a mouse bone marrow cell culture system, and reduced bone resorption in a dose-dependent manner. In addition, α-LA-induced soluble RANKL was not inhibited by matrix metalloprotease inhibitors, indicating that soluble RANKL is produced by α-LA without any posttranslational processing. In contrast, α-LA had no significant effect on the proliferation and differentiation of HS-5 cells. These results suggest that α-LA suppresses osteoclastogenesis by directly inhibiting RANKL–RANK mediated signals, not by mediating cellular RANKL production. In addition, our findings indicate that α-LA-induced soluble RANKL is not produced by shedding of membranous RANKL.

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Physicochemical Properties of Collagen from Acaudina Molpadioides and Its Protective Effects against H2O2-Induced Injury in RAW264.7 Cells

Marine Drugs ◽

10.3390/md18070370 ◽

2020 ◽

Vol 18 (7) ◽

pp. 370

Author(s):

Jie Li ◽

Yan Li ◽

Yuyao Li ◽

Zuisu Yang ◽

Huoxi Jin

Keyword(s):

Sulfonic Acid ◽

Antioxidant Activities ◽

Physicochemical Characterization ◽

Raw264.7 Cells ◽

Composition Analysis ◽

Dependent Manner ◽

Protective Effects ◽

Dose Dependent ◽

Zeta Potential Analysis ◽

Improve Cell Viability

Collagen is a promising biomaterial used in the beauty and biomedical industries. In this study, the physicochemical characterization, antioxidant activities, and protective effects against H2O2-induced injury of collagen isolated from Acaudina molpadioides were investigated. The amino acid composition analysis showed that the collagen was rich in glycine (Gly), alanine (Ala), and glutamic acid (Glu), but poor in tyrosine (Tyr) and phenylalanine (Phe). Zeta potential analysis revealed that the isoelectric point (pI) of collagen from Acaudina molpadioides was about 4.25. It possessed moderate scavenging activities of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2’-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radicals in a dose-dependent manner. In addition, the collagen was able to effectively improve cell viability and morphology, inhibit the production of Malondialdehyde (MDA), and increase the activities of Superoxide Dismutase (SOD) and Glutathione Peroxidase (GSH-Px) in cultured RAW264.7 cells, resulting in a protective effect against H2O2-induced injury. Overall, the results showed that collagen extracted from A. molpadioides has promising prospects in the beauty and cosmetics industries.

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Effect of Hydroxyapatite Nanoparticles of Different Concentrations on Rat Osteoblast

Materials Science Forum ◽

10.4028/www.scientific.net/msf.610-613.1364 ◽

2009 ◽

Vol 610-613 ◽

pp. 1364-1369 ◽

Cited By ~ 9

Author(s):

Zheng Li Xu ◽

Jiao Sun ◽

Chang Sheng Liu ◽

Jie Wei

Keyword(s):

Specific Surface ◽

Surface Area ◽

Specific Surface Area ◽

Control Group ◽

Dependent Manner ◽

Hydroxyapatite Nanoparticles ◽

Inhibition Ratio ◽

Rat Osteoblast ◽

Induced Apoptosis ◽

Dose Dependent

Nano-HAP (10-20nm) were obtained from East China University of Science and Technology. The osteoblasts were primary cultured from rat calvaria and then treated with five different concentrations(20，40，60，80，100µg/ml) of nano-HAP, the osteoblasts without nano-HAP was used as control group. Inhibition ratio, apoptotic rate were evaluated by MTT assay and flow cytometry (FCM), respectively. The specific surface area of nano-HAP was detected by BET. All date were expressed as mean ± standard deviation.Statistical analysis was performed by t test using software SPSS11.0 for Windows. The results indicated that the nano-HAP could inhibit the growth of osteoblasts in a dose-dependent manner. When the concentrations of nano-HAP were 20, 40, 60, 80, 100µg/ml, the inhibition ratio were 2.8%, 22.2%, 26.9%, 38% and 47.7%, and the apoptotic rate were 4.63%, 6.75%, 9.47%, 11.49%, 17.22%, respectively, which were obviously higher than that of control group. The nano-HAP significantly induced apoptosis in osteoblasts. There were the same tendency that the apoptotic and inhibition ratio of osteoblasts were rising with the increasing of the concentration of the nano-HAP. The specific surface area of nano-HAP was 148.140m2/g.

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NEMO-Binding Domain Peptide Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting the NF-κB Signaling Pathway

Mediators of Inflammation ◽

10.1155/2016/7349603 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 6

Author(s):

Jianhua Huang ◽

Li Li ◽

Weifeng Yuan ◽

Linxin Zheng ◽

Zhenhui Guo ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Signaling Pathway ◽

Binding Domain ◽

Dependent Manner ◽

Protective Effects ◽

Lps Challenge ◽

Domain Peptide ◽

Nemo Binding Domain ◽

Dose Dependent

The aim of the present study is to investigate the protective effects and relevant mechanisms exerted by NEMO-binding domain peptide (NBD) against lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice. The ALI model was induced by intratracheally administered atomized LPS (5 mg/kg) to BABL/c mice. Half an hour before LPS administration, we treated the mice with increasing concentrations of intratracheally administered NBD or saline aerosol. Two hours after LPS administration, each group of mice was sacrificed. We observed that NBD pretreatment significantly attenuated LPS-induced lung histopathological injury in a dose-dependent manner. Western blotting established that NBD pretreatment obviously attenuated LPS-induced IκB-αand NF-κBp65 activation and NOX1, NOX2, and NOX4 overexpression. Furthermore, NBD pretreatment increased SOD and T-AOC activity and decreased MDA levels in lung tissue. In addition, NBD also inhibited TNF-αand IL-1βsecretion in BALF after LPS challenge. In conclusion, NBD protects against LPS-induced ALI in mice.

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The osteoprotective effect ofHerba epimedii(HEP) extractin vivoandin vitro

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/neh101 ◽

2005 ◽

Vol 2 (3) ◽

pp. 353-361 ◽

Cited By ~ 70

Author(s):

Fang Xie ◽

Chun-Fu Wu ◽

Wan-Ping Lai ◽

Xu-juan Yang ◽

Pik-Yuan Cheung ◽

...

Keyword(s):

Serum Alkaline Phosphatase ◽

Calcium Excretion ◽

Dependent Manner ◽

Sprague Dawley ◽

Alp Activity ◽

Post Menopausal Osteoporosis ◽

Ovx Rats ◽

Rankl Mrna ◽

Umr 106 ◽

Dose Dependent

Herba epimedii(HEP) is one of the most frequently used herbs prescribed for treatment of osteoporosis in China. In the present study, thein vivoeffects of HEP extract on bone metabolism were evaluated using 4-month-old ovariectomized (OVX) or sham-operated (Sham) female Sprague-Dawley rats orally administered with HEP extract (110 mg kg−1d−1), 17ß-estrogen (2 mg kg−1d−1) or its vehicle for 3 months. HEP extract significantly decreased urinary calcium excretion, suppressed serum alkaline phosphatase (ALP) activity and urinary deoxypyridinoline levels in OVX rats (P< 0.05 versus vehicle-treated OVX rats). Histomorphometric analysis indicated that HEP extract could prevent OVX-induced bone loss by increasing tibial trabecular bone area and decreasing trabecular separation in OVX rats (P< 0.05 versus vehicle-treated OVX group). Thein vitroeffects of HEP extract were also studied using rat osteoblast-like UMR 106 cells. HEP extract significantly stimulated cell proliferation in a dose-dependent manner (P< 0.01 versus vehicle-treated) and increased ALP activity at 200 μgml−1 (P< 0.01 versus vehicle-treated) in UMR 106 cells. It modulated osteoclastogenesis by increasing osteoprotegrin (OPG) mRNA and decreasing receptor activator of NF-κB ligand (RANKL) mRNA expression, resulting in a dose-dependent increase in OPG/RANKL mRNA ratio (P< 0.01 versus vehicle-treated). Taken together, HEP treatment can effectively suppress the OVX-induced increase in bone turnover possibly by both an increase in osteoblastic activities and a decrease in osteoclastogenesis. The present study provides the evidence that HEP can be considered as a complementary and alternative medicine for treatment of post-menopausal osteoporosis.

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