Nitric oxide production inhibition and mechanism of phenanthrene analogs in lipopolysaccharide-stimulated RAW264.7 macrophages

Chen, Lianqi; Shen, Xiaofei; Hu, Boyang; Lin, Yuan; Igbe, Ighodaro; Zhang, Chenggang; Zhang, Guolin; Yuan, Xin; Wang, Fei

doi:10.1016/j.bmcl.2016.03.088

Cited by 7 publications

(3 citation statements)

References 25 publications

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“…In this study, we found that phomopsinin A acetate (1a), a new polyketide, is a potent anti-inflammatory compound. The substitution of an acetyl group (-COOMe) within the phenanthrene analogues was previously reported to enhance the anti-inflammatory activity [20]. It therefore suggested that the replacement of the hydroxyl group at C-9 by the acetyl group yielded a more potent compound, thereby pointing its importance in the anti-inflammatory activity of phomopsinin A acetate (1a).…”

Section: Resultsmentioning

confidence: 98%

“…7 c). Some phenanthrene derivatives and other compounds such as emodin, aloe-emodin, and lambertellin were found to exert their anti-inflammatory activity by downregulating the expression of the ERK/JNK/p38 MAPK proteins [20,24,25]. We found, in this study, that only ERK1/2 was suppressed after treatment with 1a, which suggests that the activation of these MAPKs proteins may be independent of each other, and the inhibition of one of these proteins may be sufficient for a compound to exhibit its anti-inflammatory potential.…”

Section: Resultsmentioning

confidence: 99%

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Natural Polyketides Isolated from the Endophytic Fungus Phomopsis sp. CAM212 with a Semisynthetic Derivative Downregulating the ERK/IκBα Signaling Pathways

et al. 2020

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Three previously undescribed natural products, phomopsinin A – C (1 – 3), together with three known compounds, namely, cis-hydroxymellein (4), phomoxanthone A (5) and cytochalasin L-696,474 (6), were isolated from the solid culture of Phomopsis sp. CAM212, an endophytic fungus obtained from Garcinia xanthochymus. Their structures were determined on the basis of spectroscopic data, including IR, NMR, and MS. The absolute configurations of 1 and 2 were assigned by comparing their experimental and calculated ECD spectra. Acetylation of compound 1 yielded 1a, a new natural product derivative that was tested together with other isolated compounds on lipopolysaccharide-stimulated RAW 264.7 cells. Cytochalasin L-696,474 (6) was found to significantly inhibit nitric oxide production, but was highly cytotoxic to the treated cells, whereas compound 1 slightly inhibited nitric oxide production, which was not significantly different compared to lipopolysaccharide-treated cells. Remarkably, the acetylated derivative of 1, compound 1a, significantly inhibited nitric oxide production with an IC50 value of 14.8 µM and no cytotoxic effect on treated cells, thereby showing the importance of the acetyl group in the anti-inflammatory activity of 1a. The study of the mechanism of action revealed that 1a decreases the expression of inducible nitric oxide synthase, cyclooxygenase 2, and proinflammatory cytokine IL-6 without an effect on IL-1β expression. Moreover, it was found that 1a exerts its anti-inflammatory activity in lipopolysaccharide-stimulated RAW 264.7 macrophage cells by downregulating the activation of ERK1/2 and by preventing the translocation of nuclear factor κB. Thus, derivatives of phomopsinin A (1), such as compound 1a, could provide new anti-inflammatory leads.

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Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

Natural Polyketides Isolated from the Endophytic Fungus Phomopsis sp. CAM212 with a Semisynthetic Derivative Downregulating the ERK/IκBα Signaling Pathways

et al. 2020

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“…To our knowledge, this is the first study to report this outcome. The only other study related to this effect was that of Chen et al (2016) who reported that certain phenanthrene derivatives inhibited reactive nitrogen species production in a murine macrophage cell line.…”

Section: Compounds Both Developmentally Toxic and Immunotoxicmentioning

confidence: 99%

In vivoassessment of respiratory burst inhibition by xenobiotic exposure using larval zebrafish

Phelps

Fletcher

Rodríguez-Nunez

et al. 2020

Journal of Immunotoxicology

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Currently, assessment of the potential immunotoxicity of a given agent involves a tiered approach for hazard identification and mechanistic studies, including observational studies, evaluation of immune function, and measurement of susceptibility to infectious and neoplastic diseases. These studies generally use costly low-throughput mammalian models. Zebrafish, however, offer an excellent alternative due to their rapid development, ease of maintenance, and homology to mammalian immune system function and development. Larval zebrafish also are a convenient model to study the innate immune system with no interference from the adaptive immune system. In this study, a respiratory burst assay (RBA) was utilized to measure reactive oxygen species (ROS) production after developmental xenobiotic exposure. Embryos were exposed to non-teratogenic doses of chemicals and at 96 h post-fertilization, the ability to produce ROS was measured. Using the RBA, 12 compounds with varying immune-suppressive properties were screened. Seven compounds neither suppressed nor enhanced the respiratory burst; five reproducibly suppressed global ROS production, but with varying potencies: benzo[a]pyrene, 17b-estradiol, lead acetate, methoxychlor, and phenanthrene. These five compounds have all previously been reported as immunosuppressive in mammalian innate immunity assays. To evaluate whether the suppression of ROS by these compounds was a result of decreased immune cell numbers, flow cytometry with transgenic zebrafish larvae was used to count the numbers of neutrophils and macrophages after chemical exposure. With this assay, benzo[a]pyrene was found to be the only chemical that induced a change in the number of immune cells by increasing macrophage but not neutrophil numbers. Taken together, this work demonstrates the utility of zebrafish larvae as a vertebrate model for identifying compounds that impact innate immune function at non-teratogenic levels and validates measuring ROS production and phagocyte numbers as metrics for monitoring how xenobiotic exposure alters the innate immune system.

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Phytochemicals from the rhizome of Bletilla formosana and their antioxidant, cytoprotective and anti-inflammatory activities

Li,

Qiu,

Wang

et al. 2024

Food Bioscience

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Nitric oxide production inhibition and mechanism of phenanthrene analogs in lipopolysaccharide-stimulated RAW264.7 macrophages

Cited by 7 publications

References 25 publications

Natural Polyketides Isolated from the Endophytic Fungus Phomopsis sp. CAM212 with a Semisynthetic Derivative Downregulating the ERK/IκBα Signaling Pathways

Natural Polyketides Isolated from the Endophytic Fungus Phomopsis sp. CAM212 with a Semisynthetic Derivative Downregulating the ERK/IκBα Signaling Pathways

In vivoassessment of respiratory burst inhibition by xenobiotic exposure using larval zebrafish

Phytochemicals from the rhizome of Bletilla formosana and their antioxidant, cytoprotective and anti-inflammatory activities

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