scholarly journals Artocarpus tonkinensis Extract Inhibits LPS-Triggered Inflammation Markers and Suppresses RANKL-Induced Osteoclastogenesis in RAW264.7

2021 ◽  
Vol 11 ◽  
Author(s):  
Elena Orecchini ◽  
Giada Mondanelli ◽  
Ciriana Orabona ◽  
Claudia Volpi ◽  
Sabrina Adorisio ◽  
...  

Artocarpus tonkinensis (At) leaf decoction, a traditional remedy prepared in North Vietnam by the Hmong ethnic group, is a tea extract rich in bioactive compounds that may have therapeutic effects in arthritis and backache. Indeed, it has been demonstrated that At is able to inhibit Th17 lymphocytes development and to protect mice in an experimental model of collagen-induced arthritis. By resorting to macrophage in vitro models of inflammation and osteoclastogenesis, we showed that At extract significantly reduced nitric oxide synthase 2 (NOS2) activity and IL-6 production by RAW 264.7 murine cells. Moreover, At demonstrated an anti-osteoclastogenic effect, as revealed by complete inhibition of TRAP-positive osteoclast formation and decreased expression of key osteoclast-related genes. This At activity likely relies on the inhibition of RANK downstream signaling pathway, as the activation of non-receptor tyrosine kinase Src is reduced upon RANKL-At exposure. Protective effect of At against bone loss was also enlightened in vivo by collagen-induced arthritis (CIA) experiment demonstrating that, although paw edema was only weakly opposed by drinking At decoction, bone and cartilage were well preserved in CIA+At mice and joint tissue expressed decreased levels of osteoclast marker genes respect to CIA control group. Maesopsin 4-O-β-D-glucoside (i.e., TAT-2, one of the main decoction bioactive components) was capable to contrast NOS2 activity, IL-6 expression and osteoclast formation, too, albeit to a lesser extent when compared to At decoction. Overall, this study enlightens another At cell target, macrophages, beside Th17 lymphocytes, and suggests that the anti-arthritic beneficial effects of At decoction largely derives from its ability to counteract not only inflammation, but also osteoclastogenesis.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ruijie Zeng ◽  
Jinghua Wang ◽  
Zewei Zhuo ◽  
Yujun Luo ◽  
Weihong Sha ◽  
...  

AbstractNecrotizing enterocolitis (NEC) is a devastating disease predominately affecting neonates. Despite therapeutic advances, NEC remains the leading cause of mortality due to gastrointestinal conditions in neonates. Stem cells have been exploited in various diseases, and the application of different types of stem cells in the NEC therapy is explored in the past decade. However, stem cell transplantation possesses several deficiencies, and exosomes are considered potent alternatives. Exosomes, especially those derived from stem cells and breast milk, demonstrate beneficial effects for NEC both in vivo and in vitro and emerge as promising options for clinical practice. In this review, the function and therapeutic effects of stem cells and exosomes for NEC are investigated and summarized, which provide insights for the development and application of novel therapeutic strategies in pediatric diseases. Further elucidation of mechanisms, improvement in preparation, bioengineering, and administration, as well as rigorous clinical trials are warranted.


2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Jie Yang ◽  
Yiming Yang ◽  
Huahua Fan ◽  
Hejian Zou

TGF-β-induced regulatory T cells (iTregs) retain Foxp3 expression and immune-suppressive activity in collagen-induced arthritis (CIA). However, the mechanisms whereby transferred iTregs suppress immune responses, particularly the interplay between iTregs and dendritic cells (DCs)in vivo, remain incompletely understood. In this study, we found that after treatment with iTregs, splenic CD11c+DCs, termed “DCiTreg,” expressed tolerogenic phenotypes, secreted high levels of IL-10, TGF-β, and IDO, and showed potent immunosuppressive activityin vitro. After reinfusion with DCiTreg, marked antiarthritic activity improved clinical scores and histological end-points were observed. The serological levels of inflammatory cytokines and anti-CII antibodies were low and TGF-βproduction was high in the DCiTreg-treated group. DCiTregalso induced new iTregsin vivo. Moreover, the inhibitory activity of DCiTregon CIA was lost following pretreatment with the inhibitor of indoleamine 2,3-dioxygenase (IDO). Collectively, these findings suggest that transferred iTregs could induce tolerogenic characteristics in splenic DCs and these cells could effectively dampen CIA in an IDO-dependent manner. Thus, the potential therapeutic effects of iTregs in CIA are likely maintained through the generation of tolerogenic DCsin vivo.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Zhihua Sun ◽  
Peiyi Li ◽  
Xiao Wang ◽  
Shuchang Lai ◽  
Hong Qiu ◽  
...  

As the major cause of female anovulatory infertility, polycystic ovary syndrome (PCOS) affects a great proportion of women at childbearing age. Although glucagon-like peptide 1 receptor agonists (GLP-IRAs) show therapeutic effects for PCOS, its target and underlying mechanism remains elusive. In the present study, we identified that, both in vivo and in vitro, GLP-1 functioned as the regulator of proliferation and antiapoptosis of MGCs of follicle in PCOS mouse ovary. Furthermore, forkhead box protein O1 (FoxO1) plays an important role in the courses. Regarding the importance of granulosa cells (GCs) in oocyte development and function, the results from the current study could provide a more detailed illustration on the already known beneficial effects of GLP-1RAs on PCOS and support the future efforts to develop more efficient GLP-1RAs for PCOS treatment.


2019 ◽  
Author(s):  
Qiong Wang ◽  
Xin Zhou ◽  
Long Yang ◽  
Yongjian Zhao ◽  
Jun Xiao ◽  
...  

Abstract:Notopterol (NOT) is one of the main constituents of the traditional Chinese medicinal herb Notopterygium incisum Ting ex H.T. Chang has anti-rheumatism activity, but the target of NOT remains unknown. Here we have demonstrated that orally or intraperitoneal administration of NOT exhibits significant therapeutic effects on the collagen-induced arthritis (CIA) model in both DBA/1J and C57/BL6 mice. NOT treatment in vivo and in vitro reduces production of inflammatory cytokines and chemokines in TNFα- or LPS/IFNγ-stimulated macrophages via blocking the JAK2/3-STAT3/5 activation. Mechanistically, NOT directly binds JAK2 to inhibit its activity via Arg980, Asn981, and Leu932 in the JH1 domain. Importantly, expression of the L938A/R980A/N981A mutant in zebrafish significantly inhibited the in vivo inflammatory response after LPS injection, which showed no further inhibitory effect upon NOT treatment. Combination of NOT and an anti-TNFα antibodies could achieve a better therapeutic effect than anti-TNFα alone in the CIA model. We therefore suggest that as a specific JAK2/3 inhibitor, the natural compound NOT ameliorates pathology of RA, which might be useful to treat other JAK2/3-related diseases.


2020 ◽  
pp. S555-S571
Author(s):  
Z Paluch ◽  
L Biriczová ◽  
G Pallag ◽  
E Carvalheiro Marques ◽  
N Vargová ◽  
...  

Agrimonia eupatoria L. is an herb of the Rosaceae family, widely used in traditional (folk) medicine for its beneficial effects. Its water extracts (infusions and decoctions) are used in the treatment of airway and urinary system diseases, digestive tract diseases, and chronic wounds. Phytochemical analyses of Agrimonia eupatoria L. identified a variety of bioactive compounds including tannins, flavonoids, phenolic acids, triterpenoids and volatile oils possessing antioxidant, immunomodulatory and antimicrobial activities. The authors review the available literature sources examining and discussing the therapeutic and pharmacological effects of Agrimonia eupatoria L. at the molecular level in vitro and in vivo.


2019 ◽  
Vol 73 ◽  
pp. 182-188
Author(s):  
Sabina Galiniak ◽  
Marek Biesiadecki ◽  
Bożena Czubat ◽  
Dorota Bartusik-Aebisher

Curcumin, a compound belonging to the group of polyphenols with a characteristic yellow-orange color, is the most active ingredient of the long-leaved Curcuma longa L. and the ingredient of seasoning mixes, including curry spices. Due to its antioxidant, anti-inflammatory and anti-cancer properties, it has a wide range of therapeutic effects and has been studied for many years. Curcumin has enormous potential in preventing many diseases due to the widely described benefits of its use, it is non-toxic and additionally. Therapy with curcumin is low cost. Currently, many studies focus on the anti-glycation activity of curcumin, which could be used as an active inhibitor of glycation, i.e. a non-enzymatic process of combining a keto or aldehyde group of sugar with a free amino group of a protein. Finally, heterogeneous end products of advanced glycation are formed in the multistage and complicated glycation reaction. Formation of glycation products is intensified with age, as well as in various disease states, including diabetes or neurodegenerative diseases. Many literature data describe the role of curcumin in the prevention and treatment of diabetes. It is known that polyphenol has beneficial effects on hyperglycemia, insulin resistance and regeneration of secretory cells of pancreatic islets. It seems that addition of curcumin, the main ingredient of curry spice, to food could help people prevent the development of lifestyle diseases, including diabetes and its complications. The article presents the current state of knowledge on the curcumin anti-glycation properties in vitro as well as in vivo.


Author(s):  
Xuan Zhao ◽  
Xin Zuo ◽  
Jing Zhong ◽  
Bowen Wang ◽  
Saiqun Li ◽  
...  

Ocular chemical burns are potentially blinding ocular injuries and require urgent management. Amniotic membrane (AM) transplantation is an effective surgical treatment, one of the reasons is because AM is a rich source of growth factors that can promote epithelialization and wound healing. However, growth factors will be gradually lost and insufficient after preparation process and long-time storage, leading to unsatisfactory therapeutic effects. Herein, we present a modified AM (AM-HEP) for the supplement and sustained release of growth factor by surface grafting heparin for treatment of ocular chemical burns. Heparin grafting rate and stability, microstructure, physical property, and sustained release of epithelial growth factor (EGF) of AM-HEP were characterized. Biocompatibility and ability to promote corneal epithelial cell growth and migration were evaluated and compared with a biological amnion, which is available on the market in vitro. The therapeutic effects of AM-HEP combined with EGF (AM-HEP@EGF) in vivo had been evaluated in a model of mouse corneal alkali burn. The results indicated that heparin was introduced into AM and maintain stability over 3 weeks at 37°C. The modification process of AM-HEP did not affect microstructure and physical property after comparing with non-modified AM. EGF could be combined quickly and effectively with AM-HEP; the sustained release could last for more than 14 days. AM-HEP@EGF could significantly promote corneal epithelial cell growth and migration, compared with non-modified AM and control group. Faster corneal epithelialization was observed with the transplantation of AM-HEP@EGF in vivo, compared with the untreated control group. The corneas in the AM-HEP@EGF group have less inflammation and were more transparent than those in the control group. The results from in vitro and in vivo experiments demonstrated that AM-HEP@EGF could significantly enhance the therapeutic effects. Taken together, AM-HEP@EGF is exhibited to be a potent clinical application in corneal alkali burns through accelerating corneal epithelial wound healing.


2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Jae Gwang Park ◽  
Young-Jin Son ◽  
Tae Ho Lee ◽  
Nam Joon Baek ◽  
Deok Hyo Yoon ◽  
...  

Cordyceps militaris is used widely as a traditional medicine in East Asia. Although a few studies have attempted to elucidate the anticancer activities of C. militaris, the precise mechanism of C. militaris therapeutic effects is not fully understood. We examined the anticancer activities of C. militaris ethanolic extract (Cm-EE) and its cellular and molecular mechanisms. For this purpose, a xenograft mouse model bearing murine T cell lymphoma (RMA) cell-derived cancers was established to investigate in vivo anticancer mechanisms. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, immunoblotting analysis, and flow cytometric assay were employed to check in vitro cytotoxicity, molecular targets, and proapoptotic action of Cm-EE. Interestingly, cancer sizes and mass were reduced in a C. militaris-administered group. Levels of the phosphorylated forms of p85 and AKT were clearly decreased in the group administered with Cm-EE. This result indicated that levels of phosphoglycogen synthase kinase 3β (p-GSK3β) and cleaved caspase-3 were increased with orally administered Cm-EE. In addition, Cm-EE directly inhibited the viability of cultured RMA cells and C6 glioma cells. The number of proapoptotic cells was significantly increased in a Cm-EE treated group compared with a control group. Our results suggested that C. militaris might be able to inhibit cancer growth through regulation of p85/AKT-dependent or GSK3β-related caspase-3-dependent apoptosis.


2021 ◽  
Vol 22 (16) ◽  
pp. 8476
Author(s):  
Chiara Sabbadin ◽  
Alessandra Andrisani ◽  
Gabriella Donà ◽  
Elena Tibaldi ◽  
Anna Maria Brunati ◽  
...  

Endometriosis, an estrogen-dependent chronic gynecological disease, is characterized by a systemic inflammation that affects circulating red blood cells (RBC), by reducing anti-oxidant defenses. The aim of this study was to investigate the potential beneficial effects of licorice intake to protect RBCs from dapsone hydroxylamine (DDS-NHOH), a harmful metabolite of dapsone, commonly used in the treatment of many diseases. A control group (CG, n = 12) and a patient group (PG, n = 18) were treated with licorice extract (25 mg/day), for a week. Blood samples before (T0) and after (T1) treatment were analyzed for: i) band 3 tyrosine phosphorylation and high molecular weight aggregates; and ii) glutathionylation and carbonic anhydrase activity, in the presence or absence of adjunctive oxidative stress induced by DDS-NHOH. Results were correlated with plasma glycyrrhetinic acid (GA) concentrations, measured by HPLC–MS. Results showed that licorice intake decreased the level of DDS-NHOH-related oxidative alterations in RBCs, and the reduction was directly correlated with plasma GA concentration. In conclusion, in PG, the inability to counteract oxidative stress is a serious concern in the evaluation of therapeutic approaches. GA, by protecting RBC from oxidative assault, as in dapsone therapy, might be considered as a new potential tool for preventing further switching into severe endometriosis.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hye Rim Cho ◽  
Nisha Kumari ◽  
Nishant Thakur ◽  
Hien Thi Vu ◽  
Hyeonjin Kim ◽  
...  

Abstract Glioblastoma multiforme (GBM) is one of the most aggressive human tumors with poor survival rates. The current standard treatment includes chemotherapy with temozolomide (TMZ), but acquisition of resistance is a persistent clinical problem limiting the successful treatment of GBM. The purpose of our study was to investigate therapeutic effects of nitroxoline (NTX) against TMZ-resistant GBM in vitro and in vivo in TMZ-resistant GBM-bearing mouse model, which was correlated with diffusion-weighted imaging (DWI). For in vitro study, we used TMZ-resistant GBM cell lines and evaluated therapeutic effects of NTX by clonogenic and migration assays. Quantitative RT-PCR was used to investigate the expression level of TMZ-resistant genes after NTX treatment. For in vivo study, we performed 9.4 T MR imaging to obtain T2WI for tumor volume measurement and DWI for assessment of apparent diffusion coefficient (ADC) changes by NTX in TMZ-resistant GBM mice (n = 8). Moreover, we performed regression analysis for the relationship between ADC and histological findings, which reflects the changes in cellularity and apurinic/apyrimidinic endonuclease-1 (APE-1) expression. We observed the recovery of TMZ-induced morphological changes, a reduced number of colonies and a decreased rate of migration capacity in TMZ-resistant cells after NTX treatment. The expression of APE-1 was significantly decreased in TMZ-resistant cells after NTX treatment compared with those without treatment. In an in vivo study, NTX reduced tumor growth in TMZ-resistant GBM mice (P = 0.0122). Moreover, ADC was increased in the NTX-treated TMZ-resistant GBM mice compared to the control group (P = 0.0079), which was prior to a tumor volume decrease. The cellularity and APE-1 expression by histology were negatively correlated with the ADC value, which in turn resulted in longer survival in NTX group. The decreased expression of APE-1 by NTX leads to therapeutic effects and is inversely correlated with ADC in TMZ-resistant GBM. Therefore, NTX is suggested as potential therapeutic candidate against TMZ-resistant GBM.


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