In vitro inhibitory effects of cirsiliol on IL-6-induced STAT3 activation through anti-inflammatory activity

Lim, Hyung Jin; Jang, Hyun Jae; Bak, Seon Gyeong; Lee, So-Young; Lee, Seung Woong; Lee, Kangmin; Lee, Seung-Jae; Rho, Mun‐Chual

doi:10.1016/j.bmcl.2019.04.053

Cited by 21 publications

(16 citation statements)

References 26 publications

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“…Briefly, RAW 264.7 cells were plated at 1 × 10 5 cell density in a 96-well microplate and cultured for 24 h. Compounds ( 1 – 22 ) were pretreated with increasing dose concentrations (0.5, 1, 5, 10, 25, 50, and 100 μM), and then stimulated with LPS (1 μg/mL, Sigma–Aldrich, St. Louis, MO, USA) for 18 h. The mixture of cell supernatant (100 μL) and Griess reagent [1% sulfanilamide + 0.1% N -(1-naphthyl)ethylenediamine (Sigma–Aldrich)] in 5% phosphoric acid was recorded at 550 nm using a microplate reader (Varioskan LUX, Thermo Fisher Scientific Inc., Waltham, MA, USA). RAW 264.7 cell cytotoxicity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay [47].…”

Section: Methodsmentioning

confidence: 99%

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1-Carbomethoxy-β-Carboline, Derived from Portulaca oleracea L., Ameliorates LPS-Mediated Inflammatory Response Associated with MAPK Signaling and Nuclear Translocation of NF-κB

Kim¹,

Park

Jang³

et al. 2019

Molecules

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Portulaca oleracea is as a medicinal plant known for its neuroprotective, hepatoprotective, antidiabetic, antioxidant, anticancer, antimicrobial, antiulcerogenic, and anti-inflammatory activities. However, the specific active compounds responsible for the individual pharmacological effects of P. oleracea extract (95% EtOH) remain unknown. Here, we hypothesized that alkaloids, the most abundant constituents in P. oleracea extract, are responsible for its anti-inflammatory activity. We investigated the phytochemical substituents (compounds 1–22) using nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESI-MS) and screened their effects on NO production in lipopolysaccharide (LPS)-induced macrophages. Compound 20, 1-carbomethoxy-β-carboline, as an alkaloid structure, ameliorated nitric oxide (NO) production, inducible nitric oxide synthase (iNOS), and proinflammatory cytokines associated with the mitogen-activated protein kinase (MAPK) pathways, p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). Subsequently, we observed that compound 20 suppressed nuclear translocation of nuclear factor κB (NF-κB) using immunocytochemistry. Moreover, we recently reported that compound 8, trans-N-feruloyl-3’, 7’-dimethoxytyramine, was originally purified from P. oleracea extracts. Our results suggest that 1-carbomethoxy-β-carboline, the most effective anti-inflammatory agent among alkaloids in the 95% EtOH extract of P. oleracea, was suppressing the MAPK pathway and nuclear translocation of NF-κB. Therefore, P. oleracea extracts and specifically 1-carbomethoxy-β-carboline may be novel therapeutic candidates for the treatment of inflammatory diseases associated with the activation of MAPKs and NF-κB.

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Section: Methodsmentioning

confidence: 99%

“…The coverslips were sealed and stained with DAPI by using ProLong Gold antifade reagent with DAPI (Thermo Fisher Scientific, Waltham, MA, USA). Immunofluorescence images were obtained using an Olympus IX73 microscope with cellSens software (Olympus, Center Valley, PA, USA) [47].…”

Section: Methodsmentioning

confidence: 99%

1-Carbomethoxy-β-Carboline, Derived from Portulaca oleracea L., Ameliorates LPS-Mediated Inflammatory Response Associated with MAPK Signaling and Nuclear Translocation of NF-κB

Kim¹,

Park

Jang³

et al. 2019

Molecules

View full text Add to dashboard Cite

show abstract

“…The coverslips were sealed and stained with DAPI by using ProLong Gold antifade reagent with DAPI (Thermo Fisher Scientific, Waltham, MA). Immunofluorescence images were obtained using an Olympus IX73 microscope with cellSens software (Olympus, Center Valley, PA) (Lim et al, 2019).…”

Section: Methodsmentioning

confidence: 99%

“…Compounds (1-13) were pretreated with increasing dose concentrations (-10 and 30 μM), and then stimu-lated with LPS (1 μg/mL, Sigma-Aldrich, St. Louis, MO) for 18hr. The mixture of cell supernatant (100 μL) and Griess reagent [1% sulfanilamide +0.1% N-(1-naphthyl)ethylenediamine (Sigma-Aldrich, St. Louis, MO)] in 5% phosphoric acid was recorded at 550 nm using a microplate reader (Varioskan LUX, Thermo Fisher Scientific Inc., Waltham, MA).RAW 264.7 cell cytotoxicity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay(Lim et al, 2019).…”

mentioning

confidence: 99%

Rugosic acid A, derived from Rosa rugosa Thunb., is novel inhibitory agent for NF‐κB and IL‐6/STAT3 axis in acute lung injury model

Kim

Park

Jang

et al. 2020

Phytotherapy Research

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Rosa rugosa Thunb., is as a medicinal plant known for anti‐diabetic, and anti‐inflammatory activities. However, the specific active compounds responsible for the individual pharmacological effects of in R. rugosa extract (95% EtOH) remain unknown. Here, we hypothesized that terpenoid structure, the most abundant constituents in R. rugosa extract, are responsible for its anti‐inflammatory activity. We investigated the phytochemical substituents (compounds 1–13 ) and newly purified 11‐methoxy polisin A, and 13‐methoxy bisaborosaol F using NMR and ESI‐MS and to screened their effects on NO production in LPS‐induced macrophages. Rugosic acid A (RA) induced to ameliorate NO production, iNOS, and pro‐inflammatory cytokines associated with the NF‐κB. And, RA suppressed IL‐6 secretion and IL‐6‐mediated STAT3 activation in LPS‐mediated inflammation. In addition, RA was evaluated in LPS‐mediated acute lung injury (ALI) model similar to acute pneumonia. Our results suggested that RA was suppressed to translocate nuclear NF‐κB and IL‐6‐mediated STAT3 activation. Finally, RA led to amelioration of ALI by decreasing myeloperoxidase (MPO) and inhibiting phosphorylation of NF‐κB and STAT3. Our group originally found that R. rugosa extract had new methoxy compounds and RA may be alternative natural agent for acute pneumonia similar to severe acute respiratory syndrome by coronavirus.

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“…Total cell lysates were extracted using cell lysis buffer (Cell Signaling Technology, Beverly, MA, USA) containing a protease and phosphatase inhibitor cocktail (Thermo Scientific, Rockford, IL, USA). Western blotting was performed as described previously [14]. Monocyte nuclear extracts were prepared with NE-PER Nuclear Extraction Reagents according to the manufacturer’s instructions (Thermo Scientific, Waltham, MA, USA).…”

Section: Methodsmentioning

confidence: 99%

Oleanolic Acid Acetate Exerts Anti-Inflammatory Activity via IKKα/β Suppression in TLR3-Mediated NF-κB Activation

et al. 2019

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Oleanolic acid acetate (OAA), a major triterpenoid compound of Vigna angularis (azuki bean, V. angularis), has been shown to downregulate inflammatory responses in macrophages. Here, we show the molecular basis for the effect of OAA on Toll-like receptor (TLR) downstream signaling. OAA treatment significantly inhibited the secretion of embryonic alkaline phosphatase (SEAP) induced by polyinosinic acid (poly(I), TLR3 ligand) in a dose-dependent manner and without cytotoxicity in THP1-XBlue cells. In addition, OAA downregulated the gene expression of poly(I) induced pro-inflammatory cytokines and chemokines genes such as MCP-1, IL-1β, IL-8, VCAM-1 and ICAM-1. Furthermore, we found that the inhibition activity of OAA was accompanied by decreased activation of not only nuclear factor-kappa B (NF-κB) signaling but also mitogen-activated protein kinase (MAPK) signaling upon stimulation with the TLR3 agonist. Interestingly, the interaction of OAA with IκB kinase α/β (IKKα/β) strongly attenuated the production of certain proteins and inflammatory cytokines in the TLR3 signaling pathway, such as nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IkBα), extracellular regulated kinases (ERK), and p38, in an in vitro model. The action of OAA was regulated by TLR3, demonstrating that TLR3 plays a critical role in mediating the physiologically-relevant anti-inflammatory action of OAA and that the interaction with IKKα/β is modulated through TLR3. These results reveal new insight into the understanding of the regulatory mechanisms of the downstream TLR3 signaling pathway and consequent inflammatory responses that are involved in the development and progression of inflammatory diseases.

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In vitro inhibitory effects of cirsiliol on IL-6-induced STAT3 activation through anti-inflammatory activity

Cited by 21 publications

References 26 publications

1-Carbomethoxy-β-Carboline, Derived from Portulaca oleracea L., Ameliorates LPS-Mediated Inflammatory Response Associated with MAPK Signaling and Nuclear Translocation of NF-κB

1-Carbomethoxy-β-Carboline, Derived from Portulaca oleracea L., Ameliorates LPS-Mediated Inflammatory Response Associated with MAPK Signaling and Nuclear Translocation of NF-κB

Rugosic acid A, derived from Rosa rugosa Thunb., is novel inhibitory agent for NF‐κB and IL‐6/STAT3 axis in acute lung injury model

Oleanolic Acid Acetate Exerts Anti-Inflammatory Activity via IKKα/β Suppression in TLR3-Mediated NF-κB Activation

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