Literature‐Based Drug Repurposing in Traditional Chinese Medicine: Reduced Inflammatory M1 Macrophage Polarization by Jisil Haebaek Gyeji‐Tang Alleviates Cardiovascular Disease In Vitro and Ex Vivo

Yu, Ga‐Ram; Lee, Seungjun; Kim, Da-Hoon; Lim, Dong‐Woo; Kim, Hyuck; Park, Won‐Hwan; Kim, Jai‐Eun

doi:10.1155/2020/8881683

Cited by 6 publications

(6 citation statements)

References 55 publications

(24 reference statements)

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“…In addition to NF-κB and JNK signaling, the activation of p44/42 MAPK and Akt signaling was observed to regulate the transcription of pro-inflammatory cytokines in macrophages. Indeed, it has been reported that a wide variety of herbal extracts and herbderived natural compounds exert anti-inflammatory effects on LPS-stimulated macrophage cell lines, such as RAW264.7 and U937, by suppressing either p44/42 MAPK signaling [37][38][39][40] or Akt signaling [41][42][43]. In this regard, we found that ETAS®50 co-treatment suppressed S1-induced phosphorylation of p44/42 MAPK and Akt after 6 h of culture.…”

Section: Discussionmentioning

confidence: 49%

ETAS®50 Attenuates SARS-CoV-2 Spike Protein-Induced IL-6 and IL-1β Production by Suppressing p44/42 MAPK and Akt Phosphorylation in Murine Primary Macrophages

Shirato

Takanari

Kizaki

2021

Preprint

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Excessive host inflammation following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with severity and mortality in coronavirus disease 2019 (COVID-19). We recently reported that the SARS-CoV-2 spike protein S1 subunit (S1) induces pro-inflammatory responses by activating toll-like receptor 4 (TLR4) signaling in macrophages. ETAS®50, a standardized extract of Asparagus officinalis stem, is a unique functional food that elicits anti-photoaging effects by suppressing pro-inflammatory signaling in hydrogen peroxide- and ultraviolet B-exposed skin fibroblasts. To elucidate its potential in preventing excessive inflammation in COVID-19, we examined the effects of ETAS®50 on pro-inflammatory responses in S1-stimulated murine peritoneal exudate macrophages. Co-treatment of the cells with ETAS®50 significantly attenuated S1-induced secretion of interleukin (IL)-6 in a concentration-dependent manner without reducing cell viability. ETAS®50 also markedly suppressed the S1-induced transcription of IL-6 and IL-1β. However, among the TLR4 signaling proteins, ETAS®50 did not affect the degradation of inhibitor κBα, nuclear translocation of nuclear factor-κB p65 subunit, and phosphorylation of c-Jun N-terminal kinase p54 subunit after S1 exposure. In contrast, ETAS®50 significantly suppressed S1-induced phosphorylation of p44/42 mitogen-activated protein kinase (MAPK) and Akt. Attenuation of S1-induced transcription of IL-6 and IL-1β by the MAPK kinase inhibitor U0126 was greater than that by the Akt inhibitor perifosine, and the effects were potentiated by simultaneous treatment with both inhibitors. These results suggest that ETAS®50 attenuates S1-induced IL-6 and IL-1β production by suppressing p44/42 MAPK and Akt signaling in macrophages. Therefore, ETAS®50 may be beneficial in regulating excessive inflammation in patients with COVID-19.

show abstract

Section: Discussionmentioning

confidence: 49%

ETAS®50 Attenuates SARS-CoV-2 Spike Protein-Induced IL-6 and IL-1β Production by Suppressing p44/42 MAPK and Akt Phosphorylation in Murine Primary Macrophages

Shirato

Takanari

Kizaki

2021

Preprint

View full text Add to dashboard Cite

show abstract

“…In addition to NF-κB and JNK signaling, the activation of p44/42 MAPK and Akt signaling was observed to regulate the transcription of pro-inflammatory cytokines in macrophages. Indeed, it has been reported that a wide variety of herbal extracts and herb-derived natural compounds exert anti-inflammatory effects on LPS-stimulated macrophage cell lines, such as RAW264.7 and U937, by suppressing either p44/42 MAPK signaling [ 35 , 36 , 37 , 38 ] or Akt signaling [ 39 , 40 , 41 ]. In this regard, we found that EAS co-treatment suppressed S1-induced phosphorylation of p44/42 MAPK and Akt after 6 h of culture without affecting the degradation of IκBα degradation and nuclear translocation of NF-κB p65 subunit.…”

Section: Discussionmentioning

confidence: 99%

Standardized Extract of Asparagus officinalis Stem Attenuates SARS-CoV-2 Spike Protein-Induced IL-6 and IL-1β Production by Suppressing p44/42 MAPK and Akt Phosphorylation in Murine Primary Macrophages

2021

View full text Add to dashboard Cite

Excessive host inflammation following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with severity and mortality in coronavirus disease 2019 (COVID-19). We recently reported that the SARS-CoV-2 spike protein S1 subunit (S1) induces pro-inflammatory responses by activating toll-like receptor 4 (TLR4) signaling in macrophages. A standardized extract of Asparagus officinalis stem (EAS) is a unique functional food that elicits anti-photoaging effects by suppressing pro-inflammatory signaling in hydrogen peroxide and ultraviolet B-exposed skin fibroblasts. To elucidate its potential in preventing excessive inflammation in COVID-19, we examined the effects of EAS on pro-inflammatory responses in S1-stimulated macrophages. Murine peritoneal exudate macrophages were co-treated with EAS and S1. Concentrations and mRNA levels of pro-inflammatory cytokines were assessed using enzyme-linked immunosorbent assay and reverse transcription and real-time polymerase chain reaction, respectively. Expression and phosphorylation levels of signaling proteins were analyzed using western blotting and fluorescence immunomicroscopy. EAS significantly attenuated S1-induced secretion of interleukin (IL)-6 in a concentration-dependent manner without reducing cell viability. EAS also markedly suppressed the S1-induced transcription of IL-6 and IL-1β. However, among the TLR4 signaling proteins, EAS did not affect the degradation of inhibitor κBα, nuclear translocation of nuclear factor-κB p65 subunit, and phosphorylation of c-Jun N-terminal kinase p54 subunit after S1 exposure. In contrast, EAS significantly suppressed S1-induced phosphorylation of p44/42 mitogen-activated protein kinase (MAPK) and Akt. Attenuation of S1-induced transcription of IL-6 and IL-1β by the MAPK kinase inhibitor U0126 was greater than that by the Akt inhibitor perifosine, and the effects were potentiated by simultaneous treatment with both inhibitors. These results suggest that EAS attenuates S1-induced IL-6 and IL-1β production by suppressing p44/42 MAPK and Akt signaling in macrophages. Therefore, EAS may be beneficial in regulating excessive inflammation in patients with COVID-19.

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“…RAW264.7 cells were seeded and grown at 37°C and 5% CO 2 for 24 h. RAW264.7 cells were cultured in 1 μg/mL dexamethasone (Sigma, United States), 10–300 μg/mL PLE and 500 ng/mL lipopolysaccharide (LPS) for 24 h. Then, cell supernatants were mixed with Griess reagent (1:1 ratio), and the NO concentration was measured at 540 nm ( Lee et al, 2019 ; Jo et al, 2020 ). Cell viability was analyzed using Ez-Cytox reagent (DoGenBio, Korea) according to the manufacturer’s protocols ( Yu et al, 2020 ; Jo et al, 2023a ). This experiment was repeated triplicated.…”

Section: Methodsmentioning

confidence: 99%

Network analysis, in vivo, and in vitro experiments identified the mechanisms by which Piper longum L. [Piperaceae] alleviates cartilage destruction, joint inflammation, and arthritic pain

Jo,

Baek,

Kim

et al. 2024

Front. Pharmacol.

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Osteoarthritis (OA) is characterized by irreversible joint destruction, pain, and dysfunction. Piper longum L. [Piperaceae] (PL) is an East Asian herbal medicine with reported anti-inflammatory, analgesic, antioxidant, anti-stress, and anti-osteoporotic effects. This study aimed to evaluate the efficacy of PL in inhibiting pain and progressive joint destruction in OA based on its anti-inflammatory activity, and to explore its potential mechanisms using in vivo and in vitro models of OA. We predicted the potential hub targets and signaling pathways of PL through network analysis and molecular docking. Network analysis results showed that the possible hub targets of PL against OA were F2R, F3, MMP1, MMP2, MMP9, and PTGS2. The molecular docking results predicted strong binding affinities for the core compounds in PL: piperlongumine, piperlonguminine, and piperine. In vitro experiments showed that PL inhibited the expression of LPS-induced pro-inflammatory factors, such as F2R, F3, IL-1β, IL-6, IL-17A, MMP-1, MMP-2, MMP-3, MMP-9, MMP-13, NOS2, PTGS2, PGE2, and TNF-β. These mechanisms and effects were dose-dependent in vivo models. Furthermore, PL inhibited cartilage degradation in an OA-induced rat model. Thus, this study demonstrated that multiple components of PL may inhibit the multilayered pathology of OA by acting on multiple targets and pathways. These findings highlight the potential of PL as a disease-modifying OA drug candidate, which warrants further investigation.

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Literature‐Based Drug Repurposing in Traditional Chinese Medicine: Reduced Inflammatory M1 Macrophage Polarization by Jisil Haebaek Gyeji‐Tang Alleviates Cardiovascular Disease In Vitro and Ex Vivo

Cited by 6 publications

References 55 publications

ETAS®50 Attenuates SARS-CoV-2 Spike Protein-Induced IL-6 and IL-1β Production by Suppressing p44/42 MAPK and Akt Phosphorylation in Murine Primary Macrophages

ETAS®50 Attenuates SARS-CoV-2 Spike Protein-Induced IL-6 and IL-1β Production by Suppressing p44/42 MAPK and Akt Phosphorylation in Murine Primary Macrophages

Standardized Extract of Asparagus officinalis Stem Attenuates SARS-CoV-2 Spike Protein-Induced IL-6 and IL-1β Production by Suppressing p44/42 MAPK and Akt Phosphorylation in Murine Primary Macrophages

Network analysis, in vivo, and in vitro experiments identified the mechanisms by which Piper longum L. [Piperaceae] alleviates cartilage destruction, joint inflammation, and arthritic pain

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