scholarly journals Petunidin, a B-ring 5′-O-Methylated Derivative of Delphinidin, Stimulates Osteoblastogenesis and Reduces sRANKL-Induced Bone Loss

2019 ◽  
Vol 20 (11) ◽  
pp. 2795 ◽  
Author(s):  
Masahiro Nagaoka ◽  
Toyonobu Maeda ◽  
Sawako Moriwaki ◽  
Atsushi Nomura ◽  
Yasumasa Kato ◽  
...  

Several lines of evidence suggest that oxidative stress is one of the key pathogenic mechanisms of osteoporosis. We aimed to elucidate the bone protective effects of petunidin, one of the most common anthocyanidins, considering its potent antioxidative activity. Petunidin (>5 μg/mL) significantly inhibited osteoclastogenesis and downregulated c-fos, Nfatc1, Mmp9, Ctsk, and Dc-stamp mRNA expression in RAW264.7 cells. Conversely, petunidin (>16 μg/mL) stimulated mineralized matrix formation and gene expression of Bmp2 and Ocn, whereas it suppressed Mmp13, Mmp2, and Mmp9 mRNA expression and proteolytic activities of MMP13 and MMP9 in MC3T3-E1 cells. Micro-CT and bone histomorphometry analyses of sRANKL-induced osteopenic C57BL/6J mice showed that daily oral administration of petunidin (7.5 mg/kg/day) increased bone volume to tissue volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), the ratio of osteoid volume to tissue volume (OV/TV), osteoid thickness (O.Th), the ratio of osteoid surface to bone surface (OS/BS), the ratio of osteoblast surface to bone surface (Ob.S/BS), and the number of osteoblast per unit of bone surface (N.Ob/BS), and decreased trabecular separation (Tb.Sp), the ratio of eroded surface to bone surface (ES/BS), the ratio of osteoclast surface to bone surface (Oc.S/BS), and number of osteoclast per unit of bone surface (N.Oc/BS), compared to untreated mice. Furthermore, histological sections of the femurs showed that oral administration of petunidin to sRANKL-induced osteopenic mice increased the size of osteoblasts located along the bone surface and the volume of osteoid was consistent with the in vitro osteoblast differentiation and MMP inhibition. These results suggest that petunidin is a promising natural agent to improve sRANKL-induced osteopenia in mice through increased osteoid formation, reflecting accelerated osteoblastogenesis, concomitant with suppressed bone resorption.

2020 ◽  
Vol 18 ◽  
Author(s):  
Zirui Zhang ◽  
Shangcong Han ◽  
Panpan Liu ◽  
Xu Yang ◽  
Jing Han ◽  
...  

Background: Chronic inflammation and lack of angiogenesis are the important pathological mechanisms in deep tissue injury (DTI). Curcumin is a well-known anti-inflammatory and antioxidant agent. However, curcumin is unstable under acidic and alkaline conditions, and can be rapidly metabolized and excreted in the bile, which shortens its bioactivity and efficacy. Objective: This study aimed to prepare curcumin-loaded poly (lactic-co-glycolic acid) nanoparticles (CPNPs) and to elucidate the protective effects and underlying mechanisms of wound healing in DTI models. Methods: CPNPs were evaluated for particle size, biocompatibility, in vitro drug release and their effect on in vivo wound healing. Results : The results of in vivo wound closure analysis revealed that CPNP treatments significantly improved wound contraction rates (p<0.01) at a faster rate than other three treatment groups. H&E staining revealed that CPNP treatments resulted in complete epithelialization and thick granulation tissue formation, whereas control groups resulted in a lack of compact epithelialization and persistence of inflammatory cells within the wound sites. Quantitative real-time PCR analysis showed that treatment with CPNPs suppressed IL-6 and TNF-α mRNA expression, and up-regulated TGF-β, VEGF-A and IL-10 mRNA expression. Western blot analysis showed up-regulated protein expression of TGF-β, VEGF-A and phosphorylatedSTAT3. Conclusion: Our results showed that CPNPs enhanced wound healing in DTI models, through modulation of the JAK2/STAT3 signalling pathway and subsequent upregulation of pro-healing factors.


Antioxidants ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 386 ◽  
Author(s):  
Masahiro Nagaoka ◽  
Toyonobu Maeda ◽  
Masahiro Chatani ◽  
Kazuaki Handa ◽  
Tomoyuki Yamakawa ◽  
...  

In our previous investigation, delphinidin, one of the most abundant anthocyanins found in vegetables and berry fruits, had been shown to inhibit osteoclasts and prevent bone loss in mouse models of osteoporosis. In the present study, we investigated whether a delphinidin glycoside-enriched maqui berry extract (MBE, Delphinol®) exhibits beneficial effects on bone metabolism both in vitro and in vivo. MBE stimulated the osteoblastic differentiation of MC3T3-E1 cells, as indicated by enhanced mineralized nodule formation, and increased alkaline phosphatase activity, through the upregulation of bone morphogenetic protein 2 (Bmp2), runt-related transcription factor 2 (Runx2), Osterix (Osx), osteocalcin (Ocn), and matrix extracellular phosphoglycoprotein (Mepe) mRNA expression. Immunostaining and immunoprecipitation assays demonstrated that MBE suppressed NF-κB transnucleation through acting as a superoxide anion/peroxynitrite scavenger in MC3T3-E1 cells. Simultaneously, MBE inhibited both osteoclastogenesis in primary bone marrow macrophages and pit formation by maturated osteoclasts on dentine slices. Microcomputed tomography (micro-CT) and bone histomorphometry analyses of femurs demonstrated that the daily ingestion of MBE significantly increased BV/TV (ratio of bone volume to tissue volume), Tb.Th (trabecular thickness), Tb.N (trabecular number), N.Nd/N.Tm (node to terminus ratio), OV/TV (ratio of osteoid volume to tissue volume), BFR/TV (bone formation rate per tissue volume), and significantly decreased Tb.Sp (trabecular separation), ES/BS (ratio of eroded surface to bone surface) and N.Oc/BS (number of osteoclast per unit of bone surface), compared to vehicle controls in osteopenic mouse models. These findings suggest that MBE can be a promising natural agent for the prevention of bone loss in osteopenic conditions by not only inhibiting bone resorption, but also stimulating bone formation.


Author(s):  
Seema Singh ◽  
Santosh Kumar ◽  
Sunita Singh ◽  
Chetna Mishra ◽  
Dinesh Tripathi ◽  
...  

Postmenopausal osteoporosis, a quiet plague, has become a significant wellbeing danger, harassing about half of postmenopausal ladies around the world, and is accepted to be a malady that is one of the most well-known face to face who is encountering dementia achieved by mature age. It is a constant, dynamic condition, related with infinitesimal weakening of bone tissue, bringing about diminished bone mass, diminished bone quality which builds the danger of break. Ladies are bound to create osteoporosis than men because of decrease in estrogen during menopause which prompts decrease in bone-development and increment in bone-resorption action. Estrogen can stifle creation of proinflammatory cytokines like IL-1, IL-6, IL-7 and TNF-α. This is the reason these cytokines are raised in postmenopausal ladies. This paper manages the different techniques and parameters most every now and again utilized for screening of antiosteoporotic movement in post-menopausal osteoporesis. The ovariectomized creature model is the most proper model for considering the adequacy of various medications to forestall bone misfortune in postmenopausal osteoporosis. Different parameters dissected are: Biomechanical parameters as Three point bowing of tibia, Compression IV lumbar vertebra, Loading trial of femoral neck, Bone mineral thickness estimation; Biochemical parameters viz. serum calcium and inorganic phosphorus, serum basic phosphatase (ALP), Tartrate safe corrosive phosphatase (TRAP), protein profile, serum ACTH, corticosterone, IL-6, TNF-α, osteoprotegerin (OPG) and deoxypyridinoline crosslinks to creatinine proportion (DPD/Cr); Physical parameters like thickness and the length of the femur, weight of femur, Femur bone volume, bone thickness and so forth; Histopathology of femur to watch histopathological changes like size, shape and bone design; problematic and lytic changes, and fibrocartilageneous lattice with osteodystrophy; therapeutic advancement with mineralization alongside genuinely very much dispersed osteocytes; trabeculae and grid, and shaft size and so on; Histopathology of tibia to watch bone zone, bone volume per tissue volume, bone edge, outright number of dynamic osteoblasts, the proportion of indisputably the quantity of dynamic cuboid osteoblasts per bone border, the proportion of without a doubt the quantity of osteoclasts per osteoclast edge which speak to part of the trabeculae that are secured with osteoclasts, trabecular thickness, trabecular partition, trabecular number, mineralized bone volume per tissue volume, the osteoid volume per bone volume, the osteoid surface per bone surface, the osteoblast surface per bone surface, the disintegrated surface per bone surface. Different parameters as histopathology of uterus and mammary organ tissue, immunohistochemical recoloring to quantify ER level, pee examinations, body weight, organ weight, nourishment utilization, estrogen receptor ligand restricting test (ER-LBA), assurance of oxidative pressure, social test by constrained swimming test, neonatal mouse parietal bone resorption measure and so forth can likewise be completed.


2020 ◽  
Vol 19 (4) ◽  
pp. 715-720
Author(s):  
XiaoBo Wang ◽  
JianHua Wu ◽  
BuKao Ni

Purpose: To investigate the protective effects of 4, 5-O-dicaffeoylquinic acid (DCQA) isolated from Xanthium sibiricum Patr. against mouse sepsis caused by cecal ligation/puncture (CLP) in vivo, as well as the molecular mechanisms of action involved.Methods: DCQA (7.5, 15, and 30 mg/kg/day) were administered to the mice with sepsis and the survival rate was obtained. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 were examined by enzyme-linked immunosorbent assay (ELISA). Subsequently, the lipopolysaccharide (LPS) neutralizing ability of DCQA (2, 4, and 8 μg/mL) was measured using limulus amebocyte lysate (LAL) test in vitro. Furthermore, the effect of DCQA (10, 20, and 40 μg/mL) on mRNA expression of TNF-α, IL-6, and IL-8 in LPS (100 ng/mL)-treated RAW 264.7 cells was assessed using quantitative real time-polymerase chain reaction (RT-qPCR) assay.Results: DCQA significantly improved the survival rate of mice with sepsis caused by CLP (35, 50, and 65 %, respectively vs. 15 % for control, p < 0.05). LPS levels fell on co-incubation with DCQA in vitro. Moreover, ELISA and RT-qPCR results revealed that DCQA treatment lowered tendency in the mRNA expression of TNF-α, IL-6, and IL-8 (p < 0.01).Conclusion: DCQA exhibits protective effects against sepsis in mice mediated by downregulating TNF-α, IL-6, and IL-8. Further studies, in animals and humans are requied to determine the safety and efficacy of DCQA in both animal and clinical management of sepsis. Keywords: Xanthium sibiricum, 4,5-O-Dicaffeoylquinic acid, Sepsis, Cecal ligation and puncture, Lipopolysaccharide, TNF-α, IL-6, IL-8


2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Jun Qin ◽  
Yan-song Liu ◽  
Jun Liu ◽  
Jing Li ◽  
Yang Tan ◽  
...  

This study investigated the effect ofAngelica sinensispolysaccharides (APS-3c) on rat osteoarthritis (OA) modelin vivoand rat interleukin-1-beta- (IL-1β-) stimulated chondrocytesin vitro. APS-3c was administrated into rat OA knee joints and had protective effects on rat OA cartilagein vivo. Primary rat articular chondrocytes were cotreated with APS-3c and IL-1β  in vitro. 2~50 μg/mL APS-3c had no effect on chondrocytes viability, whereas it increased the proteoglycans (PGs) synthesis inhibited by IL-1β. Microarray analysis showed that the significant changes were concentrated in the genes which were involved in PGs synthesis. RT-PCR confirmed that treatment with APS-3c increased the mRNA expression of aggrecan and glycosyltransferases (GTs) inhibited by IL-1βbut did not affect the mRNA expression of matrix-degrading enzymes. These results indicate that APS-3c can improve PGs synthesis of chondrocytes on rat OA modelin vivoand IL-1β-stimulated chondrocytesin vitro, which is due to the promotion of the expression of aggrecan and GTs involved in PGs synthesis but not the inhibition of the expression of matrix-degrading enzymes. Our findings suggest the clinical relevance of APS-3c in the prospective of future alternative medical treatment for OA.


2021 ◽  
Author(s):  
Masaya Kotsuka ◽  
Yuki Hashimoto ◽  
Richi Nakatake ◽  
Tetsuya Okuyama ◽  
Masahiko Hatta ◽  
...  

Abstract Omeprazole (OMZ) is a proton pump inhibitor (PPI) that is used to reduce gastric acid secretion, but little is known about its possible liver protective effects. This study investigated whether OMZ has beneficial effects in rat septic models of lipopolysaccharide (LPS)-induced liver injury after D-galactosamine (GalN) treatment and 70% hepatectomy (PH), and to determine the mechanisms of OMZ in an in vitro model of liver injury. In the in vivo models, the effects of OMZ were examined 1 h before treatment. OMZ increased survival and decreased tumor necrosis factor-alpha, inducible nitric oxide synthase, cytokine-induced neutrophil chemoattractant 1, interleukin (IL)-6, and IL-1β mRNA expression, and increased IL-10 mRNA expression in the livers of both GaIN/LPS- and PH/LPS-treated rats. Necrosis and apoptosis were inhibited by OMZ in GaIN/LPS rats, but OMZ had no effects on necrosis in PH/LPS rats. Primary rat hepatocytes were treated with IL1-β in the presence or absence of OMZ (in vitro model). OMZ inhibited iNOS induction partially through suppression of NF-κB signaling in hepatocytes. Furthermore, OMZ inhibited the induction of several inflammatory mediators, resulting in the prevention of LPS-induced liver injury after GalN liver failure and PH, although OMZ showed different doses and mechanisms in the two models.


Planta Medica ◽  
2015 ◽  
Vol 81 (16) ◽  
Author(s):  
T Ratanavalachai ◽  
S Thitiorul ◽  
A Itharat ◽  
N Runraksa ◽  
S Ruangnoo

2019 ◽  
Author(s):  
C. Tigrine ◽  
A. Kameli

In this study a polyphenolic extract from Cleome arabica leaves (CALE) was investigated for its antioxidant activity in vitro using DPPH•, metal chelating and reducing power methods and for its protective effects against AraC-induced hematological toxicity in vivo using Balb C mice. Results indicated that CALE exhibited a strong and dose-dependent scavenging activity against the DPPH• free radical (IC50 = 4.88 μg/ml) and a high reducing power activity (EC50 = 4.85 μg/ml). Furthermore, it showed a good chelating effects against ferrous ions (IC50 = 377.75 μg/ml). The analysis of blood showed that subcutaneous injection of AraC (50 mg/kg) to mice during three consecutive days caused a significant myelosupression (P < 0.05). The combination of CALE and AraC protected blood cells from a veritable toxicity. Where, the number of the red cells, the amount of hemoglobin and the percentage of the hematocrite were significantly high. On the other hand, AraC cause an elevation of body temperature (39 °C) in mice. However, the temperature of the group treated with CALE and AraC remained normal and did not exceed 37.5 °C. The observed biological effects of CALE, in vitro as well as in vivo, could be due to the high polyphenol and flavonoid contents. In addition, the antioxidant activity of CALE suggested to be responsible for its hematoprotective effect.


2013 ◽  
Vol 9 (2) ◽  
pp. 202-210
Author(s):  
Pradum Pundlikrao Ige ◽  
Nilesh Ashok Bachhav ◽  
Hitendra Shaligram Mahajan ◽  
Pankaj Padmakar Nerkar ◽  
Surendra Ganeshlal Gattani

Author(s):  
Thea Magrone ◽  
Emilio Jirillo ◽  
Manrico Magrone ◽  
Matteo Antonio Russo ◽  
Paolo Romita ◽  
...  

Background: Our previous findings demonstrated that in vitro supplementation of polyphenols, extracted from seeds of red grape (Nero di Troia cultivar), to peripheral lymphomonocytes from patients affected by allergic contact dermatitis (ACD) to nickel (Ni) could reduce release of pro-inflammatory cytokines and nitric oxide (NO), while increasing levels of interleukin (IL)-10, an anti-inflammatory cytokine. Objective: To assess whether an intervention with oral administration of polyphenols leads to a reduction of peripheral biomarkers in ACD patients. Method: At T0, 25 patients affected by ACD to Ni were orally administered with 300 mg polyphenols prodie extracted from seeds of red grape (Nero di Troia cultivar) (NATUR-OX®) for 3 months (T1). Other 25 patients affected by ACD to Ni received placebo only for the same period of time. Serum biomarkers were analyzed at T0 and T1. In both groups seven drop outs were recorded. Result: At T1 in comparison to T0, in treated patients, values of IFN-γ, IL-4, IL-17, PTX3 and NO decreased, while IL-10 levels increased when compared with T0 values. Conversely, in placebo-treated patients no modifications of biomarkers were evaluated at T1. Conclusion: Present laboratory data rely on the anti-oxidant, anti-inflammatory and anti-allergic properties of polyphenols.


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