Deoxyelephantopin from Elephantopus scaber modulates neuroinflammatory response through MAPKs and PI3K/Akt-dependent NF-κB signaling pathways in LPS-stimulated BV-2 microglial cells

Andy, Shathiswaran N.; Chan, Chim Kei; Kadir, Habsah Abdul

doi:10.1016/j.jff.2017.09.017

Cited by 9 publications

(3 citation statements)

References 58 publications

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“…26 Deoxyelephantopin reduced lipopolysaccharide-induced neuroinflammatory response through inactivation of NF-κB signaling. 27 Deoxyelephantopin also reduced expression of pSTAT3-Tyr705 to inhibit cell growth of cervical carcinoma. 28 Here, deoxyelephantopin reduced the expression of p-p65 and p-STAT3 in lipopolysaccharide-treated BEAS-2B and HPAEC, suggesting that inhibition of NF-κB/ STAT3 signaling was involved in the protective effect of deoxyelephantopin in septic lung injury.…”

Section: Discussionmentioning

confidence: 97%

Deoxyelephantopin alleviates lipopolysaccharide-induced septic lung injury through inhibiting NF-ĸB/STAT3 axis

Wang

Chen

2022

Allergol Immunopathol

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Sepsis induces multiple organ dysfunction syndromes, such as acute kidney, liver, or lung injury. Septic lung injury is associated with excessive apoptosis and inflammatory responses in hepatocytes. Deoxyelephantopin is a sesquiterpene lactone found in Elephantopus scaber L, and has immunomodulatory, antibacterial, anti-inflammatory, and antifungal properties. The role of deoxyelephantopin in sepsis-associated lung injury was investigated. First, human bronchial epithelial cells (BEAS-2B) and human pulmonary artery endothelial cells (HPAEC) were treated with lipopolysaccharide to induce cytotoxicity. Treatment with lipopolysac-charide reduced cell viability of BEAS-2B and HPAEC, and promoted cell apoptosis through down-regulation of poly (ADP-ribose) polymerase (PARP) and B-cell lymphoma 2 (Bcl-2), and up-regulation of cleaved PARP and B-cell lymphoma-associated X protein (Bax). Second, lipo-polysaccharide-treated BEAS-2B and HPAEC were incubated with increasing concentrations of deoxyelephantopin, that is, 1, 5, or 10 μM. Deoxyelephantopin enhanced cell viability and reduced cell apoptosis of lipopolysaccharide-treated BEAS-2B and HPAEC. Third, deoxyele-phantopin attenuated lipopolysaccharide-induced decrease of superoxide dismutase and glutathione, and increase of malondialdehyde and myeloperoxidase in BEAS-2B and HPAEC. Moreover, deoxyelephantopin also weakened lipopolysaccharide-induced increase of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. Finally, deoxyelephantopin decreased protein expression of p-p65 and p-signal transducer and activator of transcription 3 (STAT3) in lipopolysaccharide-treated BEAS-2B and HPAEC. In conclusion, deoxyelephantopin exhibited anti-oxidative and anti-inflammatory effects against lipopolysaccharide-treated BEAS-2B and HPAEC through inactivation of nuclear factor kappa B/STAT3 signaling.

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Section: Discussionmentioning

confidence: 97%

Deoxyelephantopin alleviates lipopolysaccharide-induced septic lung injury through inhibiting NF-ĸB/STAT3 axis

Wang

Chen

2022

Allergol Immunopathol

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“…Because Akt is activated by PI3K to inhibit apoptosis, 29 our results suggest that D scandens causes cytotoxicity by direct Akt1 downregulation. Existing literature also demonstrates the targeting of Akt by a compound found in E scaber, deoxy-elephantopin, to induce apoptosis or autophagy in many cell types, including microglia, 46 SiHa (cervical carcinoma) cells, 47 and HCT116 (colorectal cancer) cells. 48 Our results show phosphorylation of Erk1/2 after treatment with E scaber.…”

Section: Discussionmentioning

confidence: 99%

Induction of Human Oral Squamous Carcinoma Apoptosis by Derris scandens Benth and Elephantopus scaber Linn Extracts

Leenutaphong

Tancharoen

Nararatwanchai

et al. 2022

Natural Product Communications

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D scandens ( Derris scandens Benth.) and E scaber ( Elephantopus scaber Linn.) contain flavonoids and phenolic acids, which have antitumor activity in various cancer cell lines. Oral cancer is among the most common cancers in Southeast Asia, and the survival rate remains low. Thus, this study screened 2 ethanolic plant extracts for cytotoxicity on the oral human squamous carcinoma cell line (HSC-2), and compared the mechanisms of action. Extracts of D scandens and E scaber showed cytotoxicity against HSC-2 cells in a dose-dependent manner. Observation of nuclear morphology by Hoechst 33342 staining revealed chromatin condensation. Apoptosis was confirmed by Annexin V-FITC staining and cell sorting (fluorescence-activated cell sorting) analysis. We demonstrated that cancer apoptosis was accompanied by changes in the expression of procaspase 3 and that D scandens-mediated apoptosis in HSC-2 cells was potentiated by protein kinase B (Akt) and B-cell lymphoma-2 (Bcl-2), while E scaber apoptosis was mediated by mitogen-activated protein kinase (MAPK) pathways, involving stress-activated protein kinases/jun amino-terminal kinase (SAPK/JNK) and p38-MAPK. Further investigation into targets for apoptosis induction by these plant extracts may have potential in oral cancer therapy.

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“…Finally, we investigated whether the neuromodulatory and neuroprotective effects of FAB are associated with changes in expression of regulatory and inflammatory molecules ( Figure 7). Once LPS or IL-1β binds to its specific receptor (Toll-like receptor 4 (TLR4) and IL1R, respectively), several signal transduction pathways are activated, which in turn lead to increased expression of inflammatory molecules [21,22], with important roles for IL-1β, TNF-α, IL-6, NOS2, CCL2, and CCL5 in neuronal death [22][23][24][25][26][27], while IL-10, arginase, and TGF-β are important regulatory molecules involved in the control of the inflammatory response and neuroprotection [11,19,28]. Both LPS and IL-1β induced an increase of mRNA expression of neuroinflammatory molecules IL-1β, TNF, and NOS2, as well as the expression of the chemokine CCL2, and these increases were almost completely blocked by FAB treatment (Figure 7A,B).…”

Section: Agathisflavone (Fab) Positively Impacts Neuroinflammatory Gementioning

confidence: 99%

Phytoestrogen Agathisflavone Ameliorates Neuroinflammation-Induced by LPS and IL-1β and Protects Neurons in Cocultures of Glia/Neurons

et al. 2020

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Inflammation and oxidative stress are common aspects of most neurodegenerative diseases in the central nervous system. In this context, microglia and astrocytes are central to mediating the balance between neuroprotective and neurodestructive mechanisms. Flavonoids have potent anti-inflammatory and antioxidant properties. Here, we have examined the anti-inflammatory and neuroprotective potential of the flavonoid agathisflavone (FAB), which is derived from the Brazilian plant Poincianella pyramidalis, in in vitro models of neuroinflammation. Cocultures of neurons/glial cells were exposed to lipopolysaccharide (LPS, 1 µg/mL) or interleukin (IL)-1β (10 ng/mL) for 24 h and treated with FAB (0.1 and 1 µM, 24 h). FAB displayed a significant neuroprotective effect, as measured by nitric oxide (NO) production, Fluoro-Jade B (FJ-B) staining, and immunocytochemistry (ICC) for the neuronal marker β-tubulin and the cell death marker caspase-3, preserving neuronal soma and increasing neurite outgrowth. FAB significantly decreased the LPS-induced microglial proliferation, identified by ICC for Iba-1/bromodeoxyuridine (BrdU) and CD68 (microglia M1 profile marker). In contrast, FAB had no apparent effect on astrocytes, as determined by ICC for glial fibrillary acidic protein (GFAP). Furthermore, FAB protected against the cytodestructive and proinflammatory effects of IL-1β, a key cytokine that is released by activated microglia and astrocytes, and ICC showed that combined treatment of FAB with α and β estrogen receptor antagonists did not affect NF-κB expression. In addition, qPCR analysis demonstrated that FAB decreased the expression of proinflammatory molecules TNF-α, IL-1β, and connexins CCL5 and CCL2, as well as increased the expression of the regulatory molecule IL-10. Together, these findings indicate that FAB has a significant neuroprotective and anti-inflammatory effect in vitro, which may be considered as an adjuvant for the treatment of neurodegenerative diseases.

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Deoxyelephantopin from Elephantopus scaber modulates neuroinflammatory response through MAPKs and PI3K/Akt-dependent NF-κB signaling pathways in LPS-stimulated BV-2 microglial cells

Cited by 9 publications

References 58 publications

Deoxyelephantopin alleviates lipopolysaccharide-induced septic lung injury through inhibiting NF-ĸB/STAT3 axis

Deoxyelephantopin alleviates lipopolysaccharide-induced septic lung injury through inhibiting NF-ĸB/STAT3 axis

Induction of Human Oral Squamous Carcinoma Apoptosis by Derris scandens Benth and Elephantopus scaber Linn Extracts

Phytoestrogen Agathisflavone Ameliorates Neuroinflammation-Induced by LPS and IL-1β and Protects Neurons in Cocultures of Glia/Neurons

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