Amurensin H, a Derivative From Resveratrol, Ameliorates Lipopolysaccharide/Cigarette Smoke–Induced Airway Inflammation by Blocking the Syk/NF-κB Pathway

Fan, Yannan; Zhang, Ziqian; Yao, Chun‐Suo; Bai, Jinye; Yang, Hui; Ma, Pei; Fan, Yiyao; Li, Shuyi; Yuan, Jing; Lin, Mingbao; Hou, Qi

doi:10.3389/fphar.2019.01157

Cited by 17 publications

(16 citation statements)

References 31 publications

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“…16,17 Amurensin H is an ATP-competitive inhibitor of Syk due to the interaction between its ring-C/D and Syk, 18 and also, inhibits inflammation via NF-κB signalling. 19 Further, we previously have shown that amurensin H inhibits the sodium nitroprusside-induced chondrocyte apoptosis. 20 However, for amurensin H, the possible relationship between its chondroprotective and anti-inflammatory effects, and possible link between its effects on chronic inflammation and TLR4 signals have not been explored in detail.…”

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confidence: 95%

Chondroprotective and anti‐inflammatory effects of amurensin H by regulating TLR4/Syk/NF‐κB signals

Yue

Yang

et al. 2019

J Cellular Molecular Medi

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The low‐grade, chronic inflammation initiated by TLR4‐triggered innate immune responses has a central role on early osteoarthritis. Amurensin H is a resveratrol dimer with anti‐inflammatory and anti‐apoptotic effects, while its effects on TLR‐4 signals to inhibit osteoarthritis are still unclear. In the present study, treatment with amurensin H for 2 weeks in monosodium iodoacetate‐induced mice significantly slows down cartilage degeneration and inflammation using macroscopic evaluation, haematoxylin and eosin (HE) staining and micro‐magnetic resonance imaging. In IL‐1β‐stimulated rat chondrocytes, amurensin H suppresses the production of inflammatory mediators including nitric oxide, IL‐6, IL‐17, PGE2 and TNF‐α using Greiss and ELISA assay. Amurensin H inhibits matrix degradation via decreasing levels of MMP‐9 and MMP‐13 using Western blot assay, promotes synthesis of type II collagen and glycosaminoglycan using immunostaining and safranin O staining, respectively. Amurensin H inhibits intracellular and mitochondrial reactive oxygen species (ROS) generation, and mitochondrial membrane depolarization using DCFH‐DA, MitoSOX Red and JC‐1 assay as well. IL‐1β stimulates TLR4 activation and Syk phosphorylation in chondrocytes, while amurensin H inhibits TLR4/Syk signals and downstream p65 phosphorylation and translocation in a time and dose‐dependent manner. Together, these results suggest that amurensin H exerts chondroprotective effects by attenuating oxidative stress, inflammation and matrix degradation via the TLR4/Syk/NF‐κB pathway.

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confidence: 95%

Chondroprotective and anti‐inflammatory effects of amurensin H by regulating TLR4/Syk/NF‐κB signals

Yue

Yang

et al. 2019

J Cellular Molecular Medi

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“…Furthermore, administration of BAY to IRI‐induced AKI mouse model significantly inhibited the inflammation in kidney, thereby reducing the serum creatinine and BUN levels as well as kidney injury. Although previous studies have reported the role of Syk in regulating inflammation in macrophage, 49‐54 the specific mechanism is still unclear, and whether it is related to the regulation of Mincle signaling pathway has not been reported. On the contrary, there are many kinds of Syk inhibitors, our research may provide a positive reference for the selection of Syk inhibitor on suppression of inflammation in macrophage or disease.…”

Section: Discussionmentioning

confidence: 97%

BAY61‐3606 protects kidney from acute ischemia/reperfusion injury through inhibiting spleen tyrosine kinase and suppressing inflammatory macrophage response

Tan

Liu

et al. 2020

The FASEB Journal

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Acute kidney injury (AKI) is a highly prevalent clinical syndrome with high mortality and morbidity. Previous studies indicated that inflammation promotes tubular damage and plays a key role in AKI progress. Spleen tyrosine kinase (Syk) has been linked to macrophage-related inflammation in AKI. Up to date, however, no Syk-targeted therapy for AKI has been reported. In this study, we employed both cell model of LPS-induced bone marrow-derived macrophage (BMDM) and mouse model of ischemia/reperfusion injury (IRI)-induced AKI to evaluate the effects of a Syk inhibitor, BAY61-3606 (BAY), on macrophage inflammation in vitro and protection of kidney from AKI in vivo. The expression and secretion of inflammatory cytokines, both in vitro and in vivo, were significantly inhibited even back to normal levels by BAY. The upregulated serum creatinine and blood urea nitrogen levels in the AKI mice were significantly reduced after administration of BAY, implicating a protective effect of BAY on kidneys against IRI. Further analyses from Western blot, immunofluorescence staining and flow cytometry revealed that BAY inhibited the Mincle/Syk/NF-κB signaling circuit and reduced the inflammatory response. BAY also inhibited the reactive oxygen species (ROS), which further decreased the Talents, Grant/Award Number: Lan HuiYao Team formation of inflammasome and suppressed the mature of IL-1β and IL-18. Notably, these inhibitory effects of BAY on inflammation and inflammasome in BMDM were significantly reversed by Mincle ligand, trehalose-6,6-dibehenate. In summary, these findings provided compelling evidence that BAY may be an efficient inhibitor of the Mincle/Syk/NF-κB signaling circuit and ROS-induced inflammasome, which may help to develop Syk-inhibitors as novel therapeutic agents for AKI.

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“…The morphometric analysis of inflammatory cell infiltration was performed under light microscopy (100×), selecting venules with diameter of 100–200 μm and bronchi with 150–300 μm of diameter, five blood vessels or bronchi from four lung sections for each experimental group. The results were expressed as average on a four-point scale ( Fan et al, 2019 ). The observer who performed the evaluation was blind to the group.…”

Section: Methodsmentioning

confidence: 99%

Brusatol Derivative–34 Attenuates Allergic Airway Inflammation Via Inhibition of the Spleen Tyrosine Kinase Pathway

et al. 2021

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Brusatol derivative-34 (Bru-34), a derivative of brusatol, has been shown significantly anti-inflammatory activity in mice in our previously work. However, to our knowledge, there were very limited studies on how Bru-34 affected airway inflammation. Thus, in this present study, the effects and potential mechanisms of Bru-34 on allergic airway inflammation were examined both in vivo and in vitro. The results showed that Bru-34 attenuated the allergic airway inflammation in mice, with significant decreasing of the inflammatory cells and mediators in bronchoalveolar lavage fluids and attenuation of the histopathological alterations in the lung tissues. In addition, Bru-34 significantly inhibited the release of inflammatory cytokines in antigen induced rat basophilic leukemia -2H3 (RBL-2H3) cells. What’s more, Bru-34 significantly decreased the expression of spleen tyrosine kinase (Syk), p-Syk, cytoplasmic phospholipase A2 (cPLA2), p-cPLA2, nuclear factor-κB (NF-κB) and p-NF-κB both in allergic mice lung tissue and antigen induced RBL-2H3 cells. Furthermore, the collaborative effects of Bru-34 with inhibitors against Syk, cPLA2, and NF-κB, showed that Syk was an important target of Bru-34, and cPLA2 and NF-κB played important roles in the coordinated inflammatory response. In conclusion, Bru-34 could significantly modulate the allergic airway inflammation, and its potential mechanism was revealed at least partially via down-regulating of Syk-cPLA2 -NF-κB signaling.

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Amurensin H, a Derivative From Resveratrol, Ameliorates Lipopolysaccharide/Cigarette Smoke–Induced Airway Inflammation by Blocking the Syk/NF-κB Pathway

Cited by 17 publications

References 31 publications

Chondroprotective and anti‐inflammatory effects of amurensin H by regulating TLR4/Syk/NF‐κB signals

Chondroprotective and anti‐inflammatory effects of amurensin H by regulating TLR4/Syk/NF‐κB signals

BAY61‐3606 protects kidney from acute ischemia/reperfusion injury through inhibiting spleen tyrosine kinase and suppressing inflammatory macrophage response

Brusatol Derivative–34 Attenuates Allergic Airway Inflammation Via Inhibition of the Spleen Tyrosine Kinase Pathway

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