Chlojaponilactone B from <i>Chloranthus japonicus</i>: Suppression of Inflammatory Responses via Inhibition of the NF-κB Signaling Pathway

Zhao, Jingjun; Guo, Yingjie; Yang, Dan; Xue, Xue; Liu, Qin; Zhu, Long‐Ping; Yin, Sheng; Zhao, Zhimin

doi:10.1021/acs.jnatprod.6b00355

Cited by 35 publications

(16 citation statements)

References 38 publications

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“…It was reported that the NF-κB signaling is a classic pathway involved in inflammatory response [ 23 ]. Therefore, further study was conducted to investigate whether OA pathogenesis and the mechanism of VIP plasmid related to NF-κB signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Vasoactive intestinal peptide alleviates osteoarthritis effectively via inhibiting NF-κB signaling pathway

et al. 2018

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BackgroundTo investigate the treatment effect of vasoactive intestinal peptide (VIP) on osteoarthritis (OA) and the relative mechanism.MethodThe OA model on the SD rat knee was established using the modified Hulth method, and the recombinant pcDNA3.1+/VIP plasmid was constructed. One month after the plasmids VIP were injected intra-articularly into the right knee joint of OA and sham-operated rats, the pathological changes of the OA knee joint were observed by Hematoxylin-eosin (HE) and Safranin O/fast green staining. The levels of VIP and serum inflammatory cytokines (TNF-α, IL-2 and IL-4) were measured by ELISA kits. Meanwhile, synoviocytes isolated from OA rat and sham-operated rat were cultured in vitro, and transfected with the VIP plasmid. The proliferation of synoviocytes was determined using BrdU kits. The protein expressions of TNF-α, IL-2, CollagenII, osteoprotegerin (OPG), matrix-degrading enzymes (MMP-13, ADAMTS-5), and the related protein of NF-κB signaling pathway (phosphorylated p65, phosphorylated IκBα) were evaluated by western blot.ResultsThe VIP plasmid could effectively improve the pathological state of the OA rats knee joint, significantly decrease the levels of serum TNF-α and IL-2, and clearly increase the levels of VIP and serum IL-4. At the same time, after the OA synoviocytes were treated with the VIP plasmid, the proliferation ability of OA synoviocytes was reduced, the protein expressions of Collagen II and OPG were remarkably up-regulated, and the protein expressions of TNF-α, IL-2, MMP-13 and ADAMTS-5 were significantly down-regulated. In addition, the p-p65 expression decreased and p-IκBα expression increased.ConclusionOsteoarthritis was effectively treated by VIP via inhibiting the NF-κB signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Vasoactive intestinal peptide alleviates osteoarthritis effectively via inhibiting NF-κB signaling pathway

et al. 2018

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“…NF-κB pathway has long been considered as a prototypical pro-inflammatory signaling pathway, largely based on its role in upregulating the expression of pro-inflammatory genes [31]. The most common NF-κB dimer is the p65/p50 heterodimer, which is bound to an inhibitor of NF-κB (IκBα) and is inactive in the cytoplasm [1]. After LPS stimulation, the phosphorylation of p65 and IκBα enhances NF-κB activation during inflammatory processes [1,32].…”

Section: Discussionmentioning

confidence: 99%

“…The most common NF-κB dimer is the p65/p50 heterodimer, which is bound to an inhibitor of NF-κB (IκBα) and is inactive in the cytoplasm [1]. After LPS stimulation, the phosphorylation of p65 and IκBα enhances NF-κB activation during inflammatory processes [1,32]. TLR4 activates the downstream NF-κB signaling pathway and upregulates pro-inflammatory cytokines expression after recognizing LPS [33].…”

Section: Discussionmentioning

confidence: 99%

“…Inflammation is a first defense initiated by the immune system to noxious stimuli, infections and tissue injury [1]. Appropriate inflammatory responses are protective for the body, but excessive responses lead to inflammation related diseases such as cancer, cardiovascular diseases and rheumatoid arthritis [2,3].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, C. japonicus was used for the treatment of boils, dermatological issues and enteric fever in South Korea [16]. In our previous study, we reported that 1 has anti-inflammatory properties [1]. However, the detailed mechanism of the anti-inflammatory effect of 1 remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Chlojaponilactone B Attenuates Lipopolysaccharide-Induced Inflammatory Responses by Suppressing TLR4-Mediated ROS Generation and NF-κB Signaling Pathway

Zheng

Zhou

et al. 2019

Molecules

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The lindenane-type sesquiterpenoid chlojaponilactone B (1), isolated from Chloranthus japonicus, has been reported to possess anti-inflammatory properties. The present study aimed to further explore the molecular mechanisms underlying the anti-inflammatory activity of 1. RNA-seq analyses revealed the significant changes in the expression levels of genes related to multiple inflammatory pathways upon treatment of lipopolysaccharide (LPS)-induced RAW 264.7 murine macrophages with 1. Real time PCR (RT-PCR) and Western blotting were used to confirm the modulations in the expression of essential molecules related to inflammatory responses. Compound 1 inhibited toll like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) activation upon LPS stimulation, influencing the expression of NF-κB and pro-inflammatory mediators. Molecular docking studies showed that 1 bound to TLR4 in a manner similar to that of TAK-242, a TLR4 inhibitor. Moreover, our results showed that 1 suppressed inflammatory responses by inhibiting TLR4 and subsequently decreasing reactive oxygen species (ROS) generation, downregulating the NF-κB, thus reducing the expression of the pro-inflammatory cytokines iNOS, NO, COX-2, IL-6 and TNF-α; these effects were similar to those of TAK-242. We proposed that 1 should be considered as a potential anti-inflammatory compound in future research.

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Sesquiterpenoids from the Whole Plants of Chloranthus holostegius and Their Anti‐inflammatory Activities

Zhan

Tang

et al. 2021

Chin. J. Chem.

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Chloranthus holostegius | Sesquiterpenoids | NMR spectroscopy | X-ray diffraction | InflammationFive new sesquiterpenoids (1-5), chloranholides A-E, along with three known compounds (6-8), were isolated from the whole plants of Chloranthus holostegius. Their structures were elucidated using the spectroscopic methods (IR, UV, HR-ESI-MS, 1D and 2D NMR), and their absolute configurations were determined by the X-ray crystallography and ECD calculation. Compounds 1-8 were evaluated for their anti-inflammatory effects on LPS-induced RAW 264.7 macrophage cells. Especially, compound 4 exhibited the most significant anti-inflammatory activity with the secretion levels of TNF-α and IL-6 at 15.52% and 5.98%, respectively, better than that of dexamethasone.

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Chlojaponilactone B from Chloranthus japonicus: Suppression of Inflammatory Responses via Inhibition of the NF-κB Signaling Pathway

Cited by 35 publications

References 38 publications

Vasoactive intestinal peptide alleviates osteoarthritis effectively via inhibiting NF-κB signaling pathway

Vasoactive intestinal peptide alleviates osteoarthritis effectively via inhibiting NF-κB signaling pathway

Chlojaponilactone B Attenuates Lipopolysaccharide-Induced Inflammatory Responses by Suppressing TLR4-Mediated ROS Generation and NF-κB Signaling Pathway

Sesquiterpenoids from the Whole Plants of Chloranthus holostegius and Their Anti‐inflammatory Activities

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