Nitric Oxide and cGMP Induce COX-2 Expression and PGE2Production in Human Granulosa Cells Through CREB Signaling Pathway

Abstract Background: Natural small molecules have become more attractive as alternatives to non-steroidal anti-inflammatory drugs in osteoarthritis (OA) treatments. This study aims to investigate the effects of Asiatic acid (AA) on OA in chondrocytes and the surgery-induced OA animal model. Methods: Cytotoxicity of AA in primary rat articular chondrocytes was determined. Chondrocytes were pretreated with AA at the safe concentrations and subsequently treated with IL-1β. The production of inflammatory mediators including nitric oxide (NO), nitric oxide synthase (iNOS), as well as cyclooxygenase (COX)-2, and the expression of chondrogenic and hypertrophic markers including Sox 9, Aggrecan, Col 2a1, and matrix metalloproteinase-13 (MMP13) in the cells were measured. The effect of AA on nuclear factor-kappa B (NF-κB) signaling pathway was further determined by dual luciferase assay and western blot. The surgery-induced OA animals were treated with AA or saline for 6 weeks. The pathological changes in the affected joints were measured by micro-CT and histological analysis. Results: We found a broad safety spectrum of AA from 0 to 25 μM. A dose-dependent inhibitory effect of AA on NO production, as well as iNOS and COX-2 expression were found. Meanwhile, AA promoted chondrogenesis and inhibited hypertrophy in chondrocyte treated with IL-1β. In addition, AA inhibited NF-κB signaling pathway with a dose-dependent manner. Furthermore, results from animal study revealed that AA prevented articular cartilage damage as well as subchondral bone remodeling in the surgery-induced OA animal.

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Sphingosine-1-phosphate induces COX-2 expression and PGE2 production in human granulosa cells through a S1P1/3-mediated YAP signaling

Cellular Signalling ◽

10.1016/j.cellsig.2016.03.006 ◽

2016 ◽

Vol 28 (6) ◽

pp. 643-651 ◽

Cited By ~ 17

Author(s):

Jung-Chien Cheng ◽

Hsun-Ming Chang ◽

Pang-Pin Liu ◽

Peter C.K. Leung

Keyword(s):

Granulosa Cells ◽

Pge2 Production ◽

Human Granulosa Cells ◽

Sphingosine 1 Phosphate ◽

Cox 2

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Piperine, a functional food alkaloid, exhibits inhibitory potential against TNBS-induced colitis via the inhibition of IκB-α/NF-κB and induces tight junction protein (claudin-1, occludin, and ZO-1) signaling pathway in experimental mice

Human & Experimental Toxicology ◽

10.1177/0960327119892042 ◽

2019 ◽

Vol 39 (4) ◽

pp. 477-491 ◽

Cited By ~ 3

Author(s):

G Guo ◽

F Shi ◽

J Zhu ◽

Y Shao ◽

W Gong ◽

...

Keyword(s):

Nitric Oxide ◽

Tight Junction ◽

Signaling Pathway ◽

Nitrosative Stress ◽

Nuclear Factor ◽

Ultrastructural Studies ◽

Caspase 1 ◽

Tnf Α ◽

Junction Protein ◽

Cox 2

Background: Inflammatory bowel disease is a chronic immunoinflammatory disease of the gastrointestinal tract. Piperine, an alkaloid, has been reported to possess antioxidant, anti-inflammatory, antiapoptotic, and antiulcer potential. Aim: To elucidate the plausible mechanisms of action of piperine on experimental trinitrobenzenesufonic acid (TNBS)-induced colitis by assessing various biochemical, molecular, histological, and ultrastructural modifications. Methods: Colitis was induced in male Sprague–Dawley rats via intrarectal instillation of TNBS. Then, the rats were treated with piperine (10, 20, and 40 mg/kg, p.o.) for 14 days. Results: TNBS induced significant ( p < 0.05) colonic damage, which was assessed by disease activity index, macroscopic score, and stool consistency. The administration of piperine (20 and 40 mg/kg) significantly inhibited ( p < 0.05) these damages. Treatments with piperine (20 and 40 mg/kg) notably inhibited ( p < 0.05) the TNBS-induced elevation of oxido-nitrosative stress (superoxide dismutase, glutathione, malondialdehyde, and nitric oxide), 5-hydroxytryptamine, and hydroxyproline content in the colon. Furthermore, colonic inducible nitric oxide synthase (iNOs), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, interferon-gamma, and cyclooxygenase-2 (COX-2) messenger RNA (mRNA) expressions were upregulated after TNBS instillation and piperine (20 and 40 mg/kg) significantly attenuated ( p < 0.05) these elevated mRNA expressions. TNBS decreased the expressions of tight junction (TJ) protein (claudin-1, occludin, and zonula occludens-1 (ZO-1)) and increased the expressions of proapoptotic (caspase-1) protein. These expressions were markedly inhibited ( p < 0.05) by piperine treatment. Histological and ultrastructural studies of transmission electron microscopy suggested that piperine significantly ameliorated ( p < 0.05) TNBS-induced colonic aberrations. Conclusion: Piperine ameliorated the progression of TNBS-induced colitis by modulating the nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha/nuclear factor-kappa B signaling pathway, thus inhibiting the overexpression of proinflammatory cytokines (TNF-α and IL’s), COX-2, iNOs, oxido-nitrosative stress, and proapoptotic proteins (caspase-1) that may improve the expression of TJ protein (claudin-1, occludin, and ZO-1).

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