Polyandric Acid A, a Clerodane Diterpenoid from the Australian Medicinal PlantDodonaea polyandra,Attenuates Pro-inflammatory Cytokine Secretion in Vitro and in Vivo

2014 ◽  
Vol 77 (1) ◽  
pp. 85-91 ◽  
Author(s):  
Bradley S. Simpson ◽  
Xianling Luo ◽  
Maurizio Costabile ◽  
Gillian E. Caughey ◽  
Jiping Wang ◽  
...  
2009 ◽  
Vol 15 (3) ◽  
pp. 168-173 ◽  
Author(s):  
Hiromi Ogino ◽  
Miho Fujii ◽  
Mariko Ono ◽  
Kayoko Maezawa ◽  
Junko Kizu ◽  
...  

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Ben J Wu ◽  
Kwok L Ong ◽  
Sudichhya Shrestha ◽  
Kang Chen ◽  
Philip J Barter ◽  
...  

Introduction. Arthritis is a chronic inflammatory disease characterized by joint inflammation and destruction, reduced high-density lipoprotein (HDL) levels, and increased cardiovascular risk. Objective To determine if apolipoprotein (apo) A-I, the main HDL apolipoprotein, prevents joint inflammation in arthritis. Methods and Results In vivo: Arthritis was induced in female Lewis rats with a single 15 mg/kg intraperitoneal streptococcal cell wall peptidoglycan-polysaccharide (PG-PS) injection and quantified as a combined forepaw and hindpaw inflammation score. Arthritis progressed from an initial, acute phase of joint inflammation during the first 4 days post-PG-PS administration to remission by day 8, followed by chronic joint inflammation up to sacrifice at day 21. Two intravenous infusions of lipid-free apoA-I (8 mg/kg) 24 h pre- and 24 h post-PG-PS injection reduced the acute and chronic joint inflammation by 63±9% at day 3 and by 61±8% at day 21. Infusion of apoA-I at days 7, 9 and 11 post-PG-PS injection reduced the chronic response by 43±11% at day 21. ApoA-I infusions at 24 h prior to and at days 1, 7, 9, 11 post-PG-PS injection reduced joint inflammation by 61±5% at day 3 and by 90±5% at day 21 (p<0.05 for all vs saline infusion). These beneficial effects of apoA-I were accompanied by a reduced inflammatory white blood cell count, reduced pro-inflammatory cytokine levels in synovial fluid, and reduced macrophage accumulation, toll-like receptor 2 (TLR2) and inflammatory cytokine expression in synovial tissue. In vitro: Human monocyte-derived macrophages (HMDMs) were pre-incubated with lipid-free apoA-I, then stimulated with PG-PS (20 μg/mL). Pre-incubation with apoA-I inhibited PG-PS-induced TLR2 and MyD88, a TLR2 adapter protein, expression. Nuclear factor-κB activation and pro-inflammatory cytokine production were also attenuated. These anti-inflammatory effects of apoA-I were abolished in HMDMs transfected with ATP-binding cassette transporter 1 (ABCA1) siRNA. Conclusions These findings establish that apoA-I attenuates PG-PS induced arthritis in the rat. These effects may involve ABCA-1 and inhibition of TLR2 expression and activation.


MedChemComm ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 421-430 ◽  
Author(s):  
Priyanka Chandel ◽  
Anoop Kumar ◽  
Nishu Singla ◽  
Anshul Kumar ◽  
Gagandeep Singh ◽  
...  

In the present work, coumarin based pyrazolines (7a–g) have been synthesized and investigated for their in vitro and in vivo anti-inflammatory potential.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Qinjun Zhao ◽  
Leisheng Zhang ◽  
Yimeng Wei ◽  
Hao Yu ◽  
Linglin Zou ◽  
...  

Abstract Background Mesenchymal stem cells are heterogenous populations with hematopoietic supporting and immunomodulating capacities. Enormous studies have focused on their preclinical or clinical therapeutic effects, yet the systematic study of continuous in vitro passages on signatures and functions of UC-MSCs at both the cellular and molecular levels is still lacking. Methods In this study, to systematically evaluate the biological properties of MSCs at various passages, we analyzed biomarker expression, cell proliferation and apoptosis, chromosome karyotype, and tri-lineage differentiation potential. Subsequently, we took advantage of whole-exome sequencing to compare the somatic hypermutation of hUC-MSCs at P3, P6, and P15 including SNV and INDEL mutations. In addition, to explore the safety of the abovementioned hUC-MSCs, we performed metabolic pathway enrichment analysis and in vivo transplantation analysis. Furthermore, we cocultured the abovementioned hUC-MSCs with UCB-CD34+ HSCs to evaluate their hematopoietic supporting capacity in vitro. Finally, we transplanted the cells into acute graft-versus-host disease (aGVHD) mice to further evaluate their therapeutic effect in vivo. Results The hUC-MSCs at P3, P6, and P15 showed similar morphology, biomarker expression, and cytokine secretion. hUC-MSCs at P15 had advantages on adipogenic differentiation and some cytokine secretion such as IL-6 and VEGF, with disadvantages on cell proliferation, apoptosis, and osteogenic and chondrogenic differentiation potential. Based on the SNP data of 334,378 exons and bioinformatic analyses, we found the somatic point mutations could be divided into 96 subsets and formed 30 kinds of signatures but did not show correlation with risk of tumorigenesis, which was confirmed by the in vivo transplantation experiments. However, hUC-MSCs at P15 showed impaired hematologic supporting effect in vitro and declined therapeutic effect on aGVHD in vivo. Conclusions In this study, we systematically evaluated the biological and genetic properties of hUC-MSCs at various passages. Our findings have provided new references for safety and effectiveness assessments, which will provide overwhelming evidence for the safety of hUC-MSCs after continuous in vitro passages both at the cellular and molecular levels for the first time. Taken together, our studies could help understand the controversial effects of disease treatment and benefit the clinical research of UC-MSCs.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Eman Y. Abu-rish ◽  
Ahmad T. Mansour ◽  
Hebah T. Mansour ◽  
Lina A. Dahabiyeh ◽  
Shereen M. Aleidi ◽  
...  

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