scholarly journals Inhibitory Effect of a Rosmarinic Acid-Enriched Fraction Prepared from Nga-Mon (Perilla frutescens) Seed Meal on Osteoclastogenesis through the RANK Signaling Pathway

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 307
Author(s):  
Kanokkarn Phromnoi ◽  
Maitree Suttajit ◽  
Chalermpong Saenjum ◽  
Pornngarm Limtrakul (Dejkriengkraikul)

The aim of this study is to determine antioxidant and anti-inflammatory activities relating to the antiosteoporosis effects of various perilla seed meal (PSM) fractions. The remaining waste of perilla seed obtained from cold oil compression was extracted with 70% ethanol and sequentially fractionated according to solvent polarity with hexane, dichloromethane, ethyl acetate, and water. The results indicated that the seed-meal ethyl acetate fraction (SMEF) exhibited the highest antioxidant and anti-inflammatory activities, and rosmarinic acid (RA) content. The signaling pathways induced by the receptor activator of the nuclear factor kappa B (NF-κB) ligand (RANKL) that trigger reactive oxygen species (ROS) and several transcription factors, leading to the induction of osteoclastogenesis, were also investigated. The SMEF clearly showed attenuated RANKL-induced tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts and TRAP activity. A Western blot analysis showed that the SMEF significantly downregulated RANKL-induced NF-κB, AP-1 activation, and the nuclear factor of activated T-cell 1 (NFATc1) expression. SMEF also suppressed RANKL-induced osteoclast-specific marker gene-like MMP-9 using zymography. Furthermore, the SMEF showed inhibition of RANKL-induced ROS production in RAW 264.7 cells. The results suggest that the SMEF, which contained high quantities of RA, could be developed as a natural active pharmaceutical ingredient for osteoclastogenic protection and health promotion.

2004 ◽  
Vol 142 (7) ◽  
pp. 1191-1199 ◽  
Author(s):  
María José Alcaraz ◽  
Ana María Vicente ◽  
Amparo Araico ◽  
José N Dominguez ◽  
María Carmen Terencio ◽  
...  

2019 ◽  
Vol 8 (4) ◽  
pp. 431 ◽  
Author(s):  
Mi Kim ◽  
Won Kim ◽  
Jae-Eun Byun ◽  
Jung Choi ◽  
Suk Yoon ◽  
...  

Overactivated osteoclasts lead to many bone diseases, including osteoporosis and rheumatoid arthritis. The p38 MAPK (p38) is an essential regulator of the receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclastogenesis and bone loss. We previously reported TAT conjugated thioredoxin-interacting protein-derived peptide (TAT-TN13) as an inhibitor of p38 in hematopoietic stem cells (HSCs). Here, we examined the role of TAT-TN13 in the differentiation and function of osteoclasts. TAT-TN13 significantly suppressed RANKL-mediated differentiation of RAW 264.7 cells and bone marrow macrophages (BMMs) into osteoclasts. TAT-TN13 also inhibited the RANKL-induced activation of NF-κB and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), leading to the decreased expression of osteoclast-specific genes, including tartrate-resistant acid phosphatase (TRAP) and Cathepsin K. Additionally, TAT-TN13 treatment protected bone loss in ovariectomized (OVX) mice. Taken together, these results suggest that TAT-TN13 inhibits osteoclast differentiation by regulating the p38 and NF-κB signaling pathway; thus, it may be a useful agent for preventing or treating osteoporosis.


2020 ◽  
Vol 21 (10) ◽  
pp. 3439 ◽  
Author(s):  
Thanh Q. C. Nguyen ◽  
Tran Duy Binh ◽  
Tuan L. A. Pham ◽  
Yen D. H. Nguyen ◽  
Dai Thi Xuan Trang ◽  
...  

Lasia spinosa (L.) Thwaites was used as a traditional medicine to treat many inflammatory diseases for centuries. However, its effects on the inflammatory response are not yet characterized. In this study, we investigated the anti-inflammatory activities of L. spinosa leaf extract in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. We found that ethanol extracts of L. spinosa leaves showed anti-oxidant activity due to the presence of high levels of polyphenolic compounds. Treatment with the leaf extract significantly repressed the production of inflammatory mediators such as nitric oxide and reactive oxygen species and the expression of pro-inflammatory cytokines in the LPS-stimulated RAW 264.7 cells. Moreover, L. spinosa leaf extract treatment prevented activation of the nuclear factor-kappa B pathway by inhibiting nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) degradation. Furthermore, the mitogen-activated kinase and phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathways were suppressed upon treatment with the leaf extract. In addition to suppressing inflammatory factors, the extract also activated the nuclear factor erythroid 2-related factor 2/heme-oxygenase-1 pathway. We propose that L. spinosa leaf extract has the potential as an effective therapeutic agent for alleviating oxidative stress and excessive inflammation.


2016 ◽  
Vol 2016 ◽  
pp. 1-20 ◽  
Author(s):  
Valérie Pireaux ◽  
Aude Sauvage ◽  
Benoît Bihin ◽  
Martine Van Steenbrugge ◽  
Alexandre Rousseau ◽  
...  

Macrophages and oxidized LDLs play a key role in atherogenesis but their heterogeneity has been neglected up to now. Macrophages are prone to polarization and subsets of polarized macrophages have been described in atheromas. LDLs can be oxidized not only chemically by copper (Ox-LDLs) but also enzymatically by myeloperoxidase (MpOx-LDLs) resulting in oxidized LDLs poor in lipid peroxides. The effects of physiologically relevant myeloperoxidase-oxidized LDLs on macrophage polarization or on polarized macrophages remain largely unknown. In this study, the effects of LDLs on macrophage polarization were investigated by monitoring the expression of M1 and M2 genes following stimulation with native LDLs, Ox-LDLs, or MpOx-LDLs in RAW 264.7 cells. Except forMRC1, which is induced only by Ox-LDLs, MpOx-LDLs induced an overexpression of most of the selected marker genes at the mRNA level. MpOx-LDLs also modulate marker gene expression in polarized macrophages favoring notably anti-inflammatoryArg1expression in M2 cells and also in the other phenotypes. Noteworthy, MpOx-LDLs were the most efficient to accumulate lipids intracellularly in (un)polarized macrophages whatever the phenotype. These data were largely confirmed in murine bone marrow-derived macrophages. Our data suggest that MpOx-LDLs were the most efficient to accumulate within cells and to enhance an anti-inflammatory and antioxidant phenotype in M2 cells and also in the other macrophage phenotypes.


Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6757
Author(s):  
Payungsak Tantipaiboonwong ◽  
Wittaya Chaiwangyen ◽  
Maitree Suttajit ◽  
Napapan Kangwan ◽  
Sirichat Kaowinn ◽  
...  

Industrially, after the removal of oil from perilla seeds (PS) by screw-type compression, the large quantities of residual perilla seed meal (PSM) becomes non-valuable waste. Therefore, to increase the health value and price of PS and PSM, we focused on the biological effects of perilla seed oil (PSO) and rosmarinic acid-rich fraction (RA-RF) extracted from PSM for their role in preventing oxidative stress and inflammation caused by TNF-α exposure in an A549 lung adenocarcinoma culture model. The A549 cells were pretreated with PSO or RA-RF and followed by TNF-α treatment. We found that PSO and RA-RF were not toxic to TNF-α-induced A549 cells. Both extracts significantly decreased the generation of reactive oxygen species (ROS) in this cell line. The mRNA expression levels of IL-1β, IL-6, IL-8, TNF-α, and COX-2 were significantly decreased by the treatment of PSO and RA-RF. The Western blot indicated that the expression of MnSOD, FOXO1, and NF-κB and phosphorylation of JNK were also significantly diminished by PSO and RA-RF treatment. The results demonstrated that PSO and RA-RF act as antioxidants to scavenge TNF-α induced ROS levels, resulting in decreased the expression of MnSOD, FOXO1, NF-κB and JNK signaling pathway in a human lung cell culture exposed to TNF-α.


Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 726 ◽  
Author(s):  
Taekil Eom ◽  
Ekyune Kim ◽  
Ju-Sung Kim

Rumex crispus is a perennial plant that grows in humid environments across Korea. Its roots are used in traditional Korean medicine to treat several diseases, including diseases of the spleen and skin and several inflammatory pathologies. In this study, different solvent fractions (n-hexane, dichloromethane, ethyl acetate, n-butanol, and aqueous fractions) from an ethanol extract of R. crispus roots were evaluated for the presence and composition of anthraquinone compounds and antioxidants by checking for such things as free radical scavenging activity, and electron and proton atom donating ability. In addition, anti-inflammatory activity was measured by NO scavenging activity and inflammatory cytokine production; furthermore, anti-cancer activity was measured by apoptosis-inducing ability. Polyphenolic and flavonoid compounds were shown to be abundant in the dichloromethane and ethyl acetate fractions, which also exhibited strong antioxidant activity, including free radical scavenging and positive results in FRAP, TEAC, and ORAC assays. HPLC analysis revealed that the dichloromethane fractions had higher anthraquinone contents than the other fractions; the major anthraquinone compounds included chrysophanol, emodin, and physcione. In addition, results of the anti-inflammatory assays showed that the ethyl acetate fraction showed appreciable reductions in the levels of nitric oxide and inflammatory cytokines (TNF-α, IL-1β, and IL-6) in Raw 264.7 cells. Furthermore, the anthraquinone-rich dichloromethane fraction displayed the highest anticancer activity when evaluated in a human hepatoma cancer cell line (HepG2), in which it induced increased apoptosis mediated by p53 and caspase activation.


2009 ◽  
Vol 123 (1) ◽  
pp. 97-105 ◽  
Author(s):  
Jun-Yan Tao ◽  
Guo-Hua Zheng ◽  
Lei Zhao ◽  
Jian-Guo Wu ◽  
Xiao-Yu Zhang ◽  
...  

Medicina ◽  
2021 ◽  
Vol 57 (7) ◽  
pp. 641
Author(s):  
Seong-Hee Moon ◽  
Ju-Lee Son ◽  
Seong-Jin Shin ◽  
Seung-Han Oh ◽  
Seong-Hwan Kim ◽  
...  

Background and Objectives:Asplenium incisum, a natural plant, is known to possess numerous pharmacological and biochemical properties. However, the inhibitory effect of A. incisum against Porphyromonas gingivalis and other factors related to periodontal disease have not yet been demonstrated. This study aimed to investigate the potential of A. incisum extract as a phytotherapeutic candidate for improving periodontal diseases by assessing its antibacterial, anti-inflammatory, and anti-osteoclastogenic activities. Materials and Methods: The inhibition of proliferation of P. gingivalis by A. incisum and the sustainability of its antibacterial activity were evaluated in this study. The production of inflammatory cytokines (tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)) and nitric oxide (NO) from lipopolysaccharide-stimulated RAW 264.7 cells was assessed using an enzyme-linked immunosorbent assay. To identify the anti-osteoclastogenic activity, tartrate-resistant acid phosphatase (TRAP) staining and TRAP activity analyses were performed on bone marrow macrophages. Results: The proliferation of P. gingivalis was significantly inhibited by A. incisum (p < 0.001), and the antibacterial activity was sustained for up to 3 days. A. incisum showed anti-inflammatory activities by significantly decreasing the release of TNF-α, IL-6 (p < 0.05), and NO (p < 0.01). In addition, A. incisum significantly suppressed TRAP-positive cells and TRAP activity (at 30 μg/mL, p < 0.01) without causing any cytotoxicity (p > 0.05). Conclusions:A. incisum showed antibacterial, anti-inflammatory, and anti-osteoclastogenic activities, suggesting it has strong therapeutic potential against periodontal diseases.


2021 ◽  
Vol 13 ◽  
Author(s):  
Jiandong Ren ◽  
Subhadeep Chakrabarti ◽  
Jianping Wu

Phosvitin (PV) is an egg protein. Our recent study showed both phosvitin and phosvitin hydrolysate (PVH) could promote osteoblast differentiation in osteoblast cells. The objective of the study was to investigate the effects of PV and PVH on osteoclastogenesis and possible signalling pathways in RAW264.7 cells. Both PV and PVH inhibited osteoclastogenesis (fewer tartrate-resistant acid phosphatase (TRAP) positive cells and lower TRAP activity), reduced levels of transcription factors, c-Fos and NFATc1 (nuclear factor of activated T-cells, cytoplasmic 1), and suppressed inflammatory biomarkers TNF-α (tumor necrosis factor alpha), MCP-1 (monocyte chemoattractant protein 1), RANTES (regulated on activation, normal T cell expressed and secreted), and inducible nitric oxide synthase. The inhibitory effects of PV and PVH on RAW264.7 cells differentiation were likely mediated through p38, c-Jun N-terminal kinases (JNK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways. These results indicated that PV and PVH might inhibit bone resorption activities.  


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