scholarly journals The natural compound Notopterol targets JAK2/3 to ameliorate macrophage-induced inflammation and arthritis

2019 ◽  
Author(s):  
Qiong Wang ◽  
Xin Zhou ◽  
Long Yang ◽  
Yongjian Zhao ◽  
Jun Xiao ◽  
...  
Keyword(s):  
Natural Compound ◽  
Intraperitoneal Administration ◽  
Inhibitory Effect ◽  
Therapeutic Effects ◽  
Treatment Combination ◽  
Collagen Induced Arthritis ◽  
Chinese Medicinal Herb ◽  
Cytokines And Chemokines

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.

scholarly journals Synthesis and Characterization of Polyvinylpyrrolidone-Modified ZnO Quantum Dots and Their In Vitro Photodynamic Tumor Suppressive Action

2021 ◽  
Vol 22 (15) ◽  
pp. 8106
Author(s):  
Tianming Song ◽  
Yawei Qu ◽  
Zhe Ren ◽  
Shuang Yu ◽  
Mingjian Sun ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Photodynamic Therapy ◽  
Inhibitory Effect ◽  
Therapeutic Effects ◽  
In Vivo Experiments ◽  
Potential Applications ◽  
Zno Quantum Dots ◽  
Zno Qds

Despite the numerous available treatments for cancer, many patients succumb to side effects and reoccurrence. Zinc oxide (ZnO) quantum dots (QDs) are inexpensive inorganic nanomaterials with potential applications in photodynamic therapy. To verify the photoluminescence of ZnO QDs and determine their inhibitory effect on tumors, we synthesized and characterized ZnO QDs modified with polyvinylpyrrolidone. The photoluminescent properties and reactive oxygen species levels of these ZnO/PVP QDs were also measured. Finally, in vitro and in vivo experiments were performed to test their photodynamic therapeutic effects in SW480 cancer cells and female nude mice. Our results indicate that the ZnO QDs had good photoluminescence and exerted an obvious inhibitory effect on SW480 tumor cells. These findings illustrate the potential applications of ZnO QDs in the fields of photoluminescence and photodynamic therapy.

scholarly journals Tolerogenic Splenic IDO+Dendritic Cells from the Mice Treated with Induced-Treg Cells Suppress Collagen-Induced Arthritis

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Jie Yang ◽  
Yiming Yang ◽  
Huahua Fan ◽  
Hejian Zou
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Foxp3 Expression ◽  
Treated Group ◽  
Treg Cells ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Collagen Induced Arthritis

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.

Effects of maleic acid on renal phosphorus transport: role of dietary phosphorus

1991 ◽  
Vol 261 (2) ◽  
pp. F227-F237
Author(s):  
J. Guntupalli ◽  
V. Delaney ◽  
E. J. Weinman ◽  
D. Lyle ◽  
M. Allon ◽  
...  
Keyword(s):  
Maleic Acid ◽  
Competitive Inhibition ◽  
Membrane Vesicle ◽  
Intraperitoneal Administration ◽  
Inhibitory Effect ◽  
Phosphorus Transport ◽  
Dietary Phosphorus ◽  
Pi Transport

The effects of maleic acid on renal phosphate (Pi) transport were examined by clearance and brush-border membrane vesicle (BBMV) transport studies. In normal rats, maleic acid 50 mg.kg body wt-1.h-1 increased the phosphaturia (P less than 0.001). Intraperitoneal administration of a similar dose of maleic acid decreased the BBMV uptake of Pi but not glucose. In rats fed a low-phosphate diet (0.03%), the maleic acid-induced phosphaturia was blunted, but the inhibitory effect on the BBMV transport of Pi persisted. In chronic parathyroidectomized rats fed a low-phosphate diet, where the filtered load of Pi was higher than in the previous groups, the phosphaturia was abolished, but the inhibition of the BBMV transport of Pi was sustained. Both the in vitro incubation of BBMVV and in vivo administration of maleic acid were associated with a competitive inhibition of Pi transport. These studies indicate that the maleic acid-induced phosphaturia is expressed at the apical membrane entry step of Pi, and the enhanced distal tubular reabsorption accounts for the lack of phosphaturia in dietary Pi deprivation.

scholarly journals Dopamine D2 Receptor Is Involved in Alleviation of Type II Collagen-Induced Arthritis in Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Jian-Hua Lu ◽  
Yi-Qian Liu ◽  
Qiao-Wen Deng ◽  
Yu-Ping Peng ◽  
Yi-Hua Qiu
Keyword(s):  
Transforming Growth Factor ◽  
Dopamine D2 Receptor ◽  
Intraperitoneal Administration ◽  
Intradermal Injection ◽  
Type Ii ◽  
Wild Type ◽  
Collagen Induced Arthritis ◽  
Igg Level

Human and murine lymphocytes express dopamine (DA) D2-like receptors including DRD2, DRD3, and DRD4. However, their roles in rheumatoid arthritis (RA) are less clear. Here we showed that lymphocyte DRD2 activation alleviates both imbalance of T-helper (Th)17/T-regulatory (Treg) cells and inflamed symptoms in a mouse arthritis model of RA. Collagen-induced arthritis (CIA) was prepared by intradermal injection of chicken collagen type II (CII) in tail base of DBA/1 mice orDrd2−/−C57BL/6 mice. D2-like receptor agonist quinpirole downregulated expression of proinflammatory Th17-related cytokines interleukin- (IL-) 17 and IL-22 but further upregulated expression of anti-inflammatory Treg-related cytokines transforming growth factor- (TGF-)βand IL-10 in lymphocytesin vitroand in ankle jointsin vivoin CIA mice. Quinpirole intraperitoneal administration reduced both clinical arthritis score and serum anti-CII IgG level in CIA mice. However,Drd2−/−CIA mice manifested more severe limb inflammation and higher serum anti-CII IgG level and further upregulated IL-17 and IL-22 expression and downregulated TGF-βand IL-10 expression than wild-type CIA mice. In contrast,Drd1−/−CIA mice did not alter limb inflammation or anti-CII IgG level compared with wild-type CIA mice. These results suggest that DRD2 activation is involved in alleviation of CIA symptoms by amelioration of Th17/Treg imbalance.

Everolimus shows synergistic antimyeloma effects with bortezomib via the AKT/mTOR pathway

2018 ◽  
Vol 67 (1) ◽  
pp. 39-47
Author(s):  
Jing Li ◽  
Zhaoyun Liu ◽  
Yanqi Li ◽  
Qian Jing ◽  
Honglei Wang ◽  
...  
Keyword(s):  
Mtor Inhibitor ◽  
Plasma Cells ◽  
Mammalian Target Of Rapamycin ◽  
Inhibitory Effect ◽  
Mtor Pathway ◽  
Therapeutic Effects ◽  
Mice Model ◽  
Antitumor Effects

Multiple myeloma (MM) is characterized by the proliferation of malignant plasma cells and a subsequent overabundance of monoclonal paraproteins (M proteins). Everolimus works similarly to sirolimus as a mammalian target of rapamycin (mTOR) inhibitor. Bortezomib was the first therapeutic proteasome inhibitor to be tested in humans with MM. However, the combination of these two drugs for the treatment of MM has been rarely reported. In this study, we compared the therapeutic effects of everolimus and bortezomib, as well as those of a combination of everolimus and bortezomib, using an in vitro MM cell line model and in vivo xenograft mouse model. Our results showed that the synergistic antitumor effects of everolimus and bortezomib have significant inhibitory effect through inhibition of the AKT/mTOR pathway in both the MM cell lines and MM-bearing mice model. Our results provided evidence that the mTOR inhibitor, everolimus, will be a potential drug in MM therapy.

scholarly journals Antimicrobial Effects of Minocycline, Tigecycline, Ciprofloxacin, and Levofloxacin against Elizabethkingia anophelis using In Vitro Time-Kill Assays and In Vivo Zebrafish Animal Models

Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 285
Author(s):  
Jiun-Nong Lin ◽  
Chung-Hsu Lai ◽  
Yi-Han Huang ◽  
Chih-Hui Yang
Keyword(s):  
Animal Models ◽  
Antibacterial Activities ◽  
Bactericidal Effect ◽  
Multidrug Resistant ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Therapeutic Effects ◽  
Time Kill

Elizabethkingia anophelis is a multidrug-resistant pathogen. This study evaluated the antimicrobial activity of minocycline, tigecycline, ciprofloxacin, and levofloxacin using in vitro time-kill assays and in vivo zebrafish animal models. The E. anophelis strain ED853-49 was arbitrarily selected from a bacterial collection which was concomitantly susceptible to minocycline, tigecycline, ciprofloxacin, and levofloxacin. The antibacterial activities of single agents at 0.5–4 × minimum inhibitory concentration (MIC) and dual-agent combinations at 2 × MIC using time-kill assays were investigated. The therapeutic effects of antibiotics in E. anophelis-infected zebrafish were examined. Both minocycline and tigecycline demonstrated bacteriostatic effects but no bactericidal effect. Minocycline at concentrations ≥2 × MIC and tigecycline at concentrations ≥3 × MIC exhibited a long-standing inhibitory effect for 48 h. Bactericidal effects were observed at ciprofloxacin and levofloxacin concentrations of ≥3 × MIC within 24 h of initial inoculation. Rapid regrowth of E. anophelis occurred after the initial killing phase when ciprofloxacin was used, regardless of the concentration. Levofloxacin treatment at the concentration of ≥2 × MIC consistently resulted in the long-lasting and sustainable inhibition of bacterial growth for 48 h. The addition of minocycline or tigecycline weakened the killing effect of fluoroquinolones during the first 10 h. The minocycline-ciprofloxacin or minocycline–levofloxacin combinations achieved the lowest colony-forming unit counts at 48 h. Zebrafish treated with minocycline or a combination of minocycline and levofloxacin had the highest survival rate (70%). The results of these in vitro and in vivo studies suggest that the combination of minocycline and levofloxacin is the most effective therapy approach for E. anophelis infection.

scholarly journals Promotion of ubiquitination-dependent survivin destruction contributes to xanthohumol-mediated tumor suppression and overcomes radioresistance in human oral squamous cell carcinoma

2020 ◽  
Author(s):  
ming li ◽  
feng gao ◽  
xinfang yu ◽  
qiung zhao ◽  
li zhou ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Natural Compound ◽  
Gene Knockout ◽  
Inhibitory Effect ◽  
Compound Screening

Abstract Background: Overexpression of survivin plays a crucial role in tumorigenesis and correlates with poor prognosis in human malignancies. Thus, survivin has been proposed as an attractive target for new anti-tumor interventions. Methods: A natural product library was used for natural compound screening through MTS assay. The expression of survivin in oral squamous cell carcinoma (OSCC) and the inhibitory effect of xanthohumol (XN) on OSCC were examined by anchorage-dependent and -independent growth assays, immunoblot, immunofluorescence, immunohistochemical staining, ubiquitination analysis, co-immunoprecipitation assay, CRISPR-Cas9-based gene knockout, and xenograft experiment. Results: Survivin is highly expressed in OSCC patient-derived tissues and cell lines. Knockout of survivin reduced the tumorigenic properties of OSCC cells in vitro and in vivo . With a natural compound screening, we identified that xanthohumol inhibited OSCC cells by reducing survivin protein level and activating mitochondrial apoptotic signaling. Xanthohumol inhibited the Akt-Wee1-CDK1 signaling, which in turn decreased survivin phosphorylation on Thr34, and facilitated E3 ligase Fbxl7-mediated survivin ubiquitination and degradation. Xanthohumol alone or in combination with radiation overcame radioresistance in OSCC xenograft tumors. Conclusion: Our findings indicate that targeting survivin for degradation might a promising strategy for OSCC treatment.

scholarly journals Evaluating the effect of rice (Oryza sativa L.: SRNC05053-6-2) crude extract on psoriasis using in vitro and in vivo models

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sumate Ampawong ◽  
Kanchana Kengkoom ◽  
Passanesh Sukphopetch ◽  
Pornanong Aramwit ◽  
Watcharamat Muangkaew ◽  
...  
Keyword(s):  
Oryza Sativa ◽  
Inflammatory Cytokines ◽  
Crude Extract ◽  
Oryza Sativa L ◽  
Therapeutic Effects ◽  
In Vivo Models ◽  
Cytokines And Chemokines ◽  
Anti Inflammatory

Abstract Psoriasis is mainly caused because of inappropriate immune responses in the epidermis. Rice (Oryza sativa L.: SRNC05053-6-2) consists of anthocyanin, which exhibits strong antioxidative and anti-inflammatory properties. This study aimed to evaluate the role of this black-coloured rice crude extract in alleviating the symptoms of psoriasis using human psoriatic artificial skin and an imiquimod-induced rat psoriasis model. Psoriasis-related genes, cytokines and chemokines were examined; in addition, the antioxidative and anti-inflammatory properties and the immunohistopathological features of this condition were studied. The results showed that the rice extract reduced the severity of psoriasis by (1) decreasing the epidermal thickness, acanthosis, hyperkeratosis, epidermal inflammation and degree of apoptosis induction via caspase-3, (2) increasing the expression levels of anti-inflammatory cytokines (IL-10 and TGF-β), (3) reducing the levels of pro-inflammatory cytokines (IL-6, IL-8, IL-20, IL-22 and TNF-α), chemokines (CCL-20) and anti-microbial peptides (psoriasin and β-defensin), (4) enhancing the antioxidative property (Nrf-2), (5) downregulating the levels of psoriasis-associated genes (psoriasin, β-defensin, koebnerisin 15L and koebnerisin 15S) and (6) upregulating the levels of psoriasis-improving genes (caspase-14, involucrin and filaggrin). Thus, the extract appears to exert therapeutic effects on psoriasis through its antioxidative and immunomodulatory properties.

scholarly journals Tomatidine Suppresses the Destructive Behaviors of Fibroblast-Like Synoviocytes and Ameliorates Type II Collagen-Induced Arthritis in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaolu Yu ◽  
Junnan Zhou ◽  
Fuli Zhao ◽  
Xuan Liu ◽  
Yuhang Mao ◽  
...  
Keyword(s):  
Joint Destruction ◽  
Type Ii Collagen ◽  
Inhibitory Effect ◽  
Collagen Induced Arthritis ◽  
Alternative Agent ◽  
And Migration ◽  
Solanaceae Family ◽  
Fibroblast Like Synoviocytes

Fibroblast-like synoviocytes (FLSs) are the prominent non-immune cells in synovium and play a pivotal role in rheumatoid arthritis (RA) pathogenesis. Searching for natural compounds that may suppress the pathological phenotypes of FLSs is important for the development of RA treatment. Tomatidine (Td), a steroidal alkaloid derived from the solanaceae family, has been reported to have anti-inflammatory, anti-tumor and immunomodulatory effects. However, its effect on RA remains unknown. Here, we examined the inhibitory effect of Td on TNFα-induced arthritic FLSs, and subsequently investigated its therapeutic effect on collagen-induced arthritis (CIA) rats. Our results revealed that Td significantly inhibited TNFα-induced proliferation and migration of arthritic FLSs. In addition, we found that Td treatment could efficaciously ameliorate synovial inflammation and joint destruction of rats with CIA. Both in vitro and in vivo studies showed that Td significantly suppressed the production of pro-inflammatory cytokines including IL-1β, IL-6 and TNFα, and downregulated the expression of MMP-9 and RANKL. Further molecular mechanism studies revealed that the inhibitory effect of Td on RA might attribute to the decreased activations of MAPKs (ERK and JNK) and NF-κB. These findings provide evidence that Td has the potential to be developed into a complementary or alternative agent for RA therapy.

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 ◽  
...  
Keyword(s):  
Osteoclast Formation ◽  
Control Group ◽  
Marker Genes ◽  
Therapeutic Effects ◽  
Collagen Induced Arthritis ◽  
Beneficial Effects ◽  
Th17 Lymphocytes ◽  
Tea Extract

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.

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