Reactive oxygen species mediated NF-κB/p38 feedback loop implicated in proliferation inhibition of HFLS-RA cells induced by 1,7-dihydroxy-3,4-dimethoxyxanthone

Zuo, Jian; Dou, De-Yu; Wang, Hui‐Fang; Zhu, Yanhong; Li, Yan; Luan, Jiajie

doi:10.1016/j.biopha.2017.07.164

Cited by 27 publications

(17 citation statements)

References 26 publications

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“…It seems to be contrary to our observation and similar reports, and the subtle effect of MAN on redox status should be further characterized. Previously, we found the exact outcomes from xanthones treatments were concentration-and time-dependent (Zuo et al 2017). In other words, MAN usually acts as an antioxidant in most cases, while intense stimulus will result in ROS accumulation and cytotoxicity.…”

Section: Discussionmentioning

confidence: 93%

α-Mangostin reduced the viability of A594 cells in vitro by provoking ROS production through downregulation of NAMPT/NAD

Ding

Luan

Fan

et al. 2020

Cell Stress and Chaperones

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α-Mangostin (MAN) is a bioactive compound isolated from the inedible pericarp of a tropical fruit mangosteen (Garcinia mangostana Linn). It exhibits notable therapeutic potentials on lung cancers, but the underlying mechanisms are still largely unknown. This study was designed to further explore the mechanisms involved in cytotoxicity of MAN on A549 cells. Apoptosis and cell cycle distribution were analyzed by flow cytometry methods. The fluorescent probes DCFH-DA and JC-1 were used to assess the intracellular reactive oxidative species (ROS) and mitochondrial membrane potential statuses, respectively. The regulation of MAN on relevant pathways was investigated by immunoblotting assays. The results obtained indicated that MAN caused significant apoptosis and cell cycle arrest in A549 cells, which eventually resulted in inhibition on cell proliferation in vitro. All these phenomena were synchronized with escalated oxidative stress and downregulation of nicotinamide phosphoribosyltransferase/nicotinamide adenine dinucleotide (NAMPT/NAD). Supplementation with nicotinamide mononucleotide (NMN) and N-acetylcysteine (NAC) efficiently eased MAN-induced ROS accumulation, and potently antagonized MANelicited apoptosis and cell cycle arrest. The pro-apoptotic effect of MAN was further confirmed by increased expressions of cleaved caspase 3, 6, 7, and 9, and its effect on cell cycle progression was validated by the altered expressions of p-p38, p-p53, CDK4, and cyclin D1. The immunoblotting assays also demonstrated that NAC/NMN effectively restored these molecular changes elicited by MAN treatment. Collectively, this study revealed a unique anti-tumor mechanism of MAN by provoking ROS production through downregulation of NAMPT/NAD signaling and further validated MAN as a potential therapeutic reagent for lung cancer treatment.

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Section: Discussionmentioning

confidence: 93%

α-Mangostin reduced the viability of A594 cells in vitro by provoking ROS production through downregulation of NAMPT/NAD

Ding

Luan

Fan

et al. 2020

Cell Stress and Chaperones

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“…The monomer of 1,7-Dihydroxy-3,4-dimethoxyxanthone (XAN, 20) is isolated from Securidaca inappendiculata Hassk, and can induce apoptosis in RA-FLS by inhibiting the activities of NF-κB and p38. It is worth noting that XAN can also regulate the transcription of X-linked inhibitor of apoptosis protein (XIAP), mediate the occurrence of Caspase cascade reaction, and induce cell apoptosis [87,88]. Furthermore, previous research in 2017 also found that Jinwu-Jiangu decoction (JJD) could reduce inflammatory symptoms of CIA rats and inhibit tumor like hyperplasia of FLS, and the in-depth study found that JJD medicated serum could promote FLS apoptosis by interfering with the expressions of NF-κB p65, IKK-α, and IKK-β [89,90].…”

Section: Nf-κb Mediated Apoptotic Pathwaysmentioning

confidence: 99%

Apoptosis Induction of Fibroblast-Like Synoviocytes Is an Important Molecular-Mechanism for Herbal Medicine along with its Active Components in Treating Rheumatoid Arthritis

et al. 2019

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Rheumatoid arthritis (RA) is a known chronic autoimmune disease can cause joint deformity and even loss of joint function. Fibroblast-like synoviocytes (FLS), one of the main cell types in synovial tissues of RA patients, are key effector cells in the development of RA and are considered as promising therapeutic targets for treating RA. Herbal medicines are precious resources for finding novel agents for treating various diseases including RA. It is reported that induction of apoptosis in FLS is an important mechanism for the herbal medicines to treat RA. Consequently, this paper reviewed the current available references on pro-apoptotic effects of herbal medicines on FLS and summarized the related possible signal pathways. Taken together, the main related signal pathways are concluded as death receptors mediated apoptotic pathway, mitochondrial dependent apoptotic pathway, NF-κB mediated apoptotic pathways, mitogen-activated protein kinase (MAPK) mediated apoptotic pathway, endoplasmic reticulum stress (ERS) mediated apoptotic pathway, PI3K-Akt mediated apoptotic pathway, and other reported pathways such as janus kinase/signal transducers and activators of transcription (JAK-STAT) signal pathway. Understanding the apoptosis induction pathways in FLS of these herbal medicines will not only help clear molecular mechanisms of herbal medicines for treating RA but also be beneficial for finding novel candidate therapeutic drugs from natural herbal medicines. Thus, we expect the present review will highlight the importance of herbal medicines and its components for treating RA via induction of apoptosis in FLS, and provide some directions for the future development of these mentioned herbal medicines as anti-RA drugs in clinical.

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“…We have already noticed that the effective protective effect of XANs in experimental arthritis was closely related to their inhibitory effects on RA-FLSs. [9][10][11][12] MG and other XANs are capable of down-regulating the NF-κB pathway in RA-FLSs both in vivo and in vitro, and therefore have great potential in treating synovitisrelated symptoms. [10][11][12] It should be noted that the abnormal functions of RA-FLSs result largely from immune responses of infiltrated immune cells.…”

Section: Discussionmentioning

confidence: 99%

“…Previously, we found that xanthone derivatives (XANs) can restore the cytokine network balance, alleviate oxidative stresses, inhibit hyperproliferation of fibroblast-like synoviocytes (FLSs), and thereby have good therapeutic effects on experimental arthritis. [7][8][9][10][11][12][13] Among investigated compounds, the anti-rheumatic potential of α-mangostin (MG, an isoprenyl-substituted xanthone isolated from mangosteen) is especially notable. It not only significantly improved systematic inflammation but also greatly reduced joint damage in rats with experimental arthritis.…”

Section: Introductionmentioning

confidence: 99%

<p>Activation of Cholinergic Anti-Inflammatory Pathway in Peripheral Immune Cells Involved in Therapeutic Actions of α-Mangostin on Collagen-Induced Arthritis in Rats</p>

Yin¹,

Wu²,

Pan³

et al. 2020

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Background: Studies have shown that α-mangostin (MG) could exert anti-rheumatic effects in vivo by restoring immunity homeostasis, and have indicated that activation of the choline anti-inflammatory pathway (CAP) may contribute to this immunomodulatory property. The current study was designed to further investigate the effects of MG on the CAP in peripheral immune cells and clarify its relevance to the potential anti-rheumatic actions. Methods: The catalytic activity of acetylcholinesterase (AChE) and expression of α7nicotinic cholinergic receptor (α7nAChR) in peripheral blood mononuclear cells (PBMCs) from rats with collagen-induced arthritis (CIA) or human volunteers were evaluated after MG treatment. Consequent influences on the immune environment were assessed by flow cytometry and ELISA analyses. Indirect effects on joints resulting from these immune changes were studied in a co-culture system comprised of fibroblast-like synoviocytes (FLSs) and PBMCs. Results: MG promoted α7nAChR expression in PBMCs both in vivo and in vitro, and inhibited the enzymatic activity of AChE simultaneously. Activation of the CAP was accompanied by a significant decrease in Th17 cells (CD4 + IL-17A +), while no obvious changes concerning the distribution of other T-cell subsets were noticed upon MG treatment. Meanwhile, MG decreased the secretion of TNF-α and IL-1β under inflammatory conditions. PBMCs from MG-treated CIA rats lost the potential to stimulate NF-κB activation and proinflammatory cytokine production of FLSs in the co-culture system. Conclusion: Overall, the evidence suggested that MG can improve the peripheral immune milieu in CIA rats by suppressing Th17-cell differentiation through CAP activation, and achieve remission of inflammation mediated by FLSs.

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Reactive oxygen species mediated NF-κB/p38 feedback loop implicated in proliferation inhibition of HFLS-RA cells induced by 1,7-dihydroxy-3,4-dimethoxyxanthone

Cited by 27 publications

References 26 publications

α-Mangostin reduced the viability of A594 cells in vitro by provoking ROS production through downregulation of NAMPT/NAD

α-Mangostin reduced the viability of A594 cells in vitro by provoking ROS production through downregulation of NAMPT/NAD

Apoptosis Induction of Fibroblast-Like Synoviocytes Is an Important Molecular-Mechanism for Herbal Medicine along with its Active Components in Treating Rheumatoid Arthritis

<p>Activation of Cholinergic Anti-Inflammatory Pathway in Peripheral Immune Cells Involved in Therapeutic Actions of α-Mangostin on Collagen-Induced Arthritis in Rats</p>

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