Anti-inflammatory effects of embelin in A549 cells and human asthmatic airway epithelial tissues

Lee, In-Seung; Cho, Dong‐Hyuk; Kim, Ki‐Suk; Kim, Kang-Hoon; Park, Jiyoung; Kim, Yumi; Jung, Ji Hoon; Kim, Kwanil; Jung, Hee-Jae; Jang, Hyeung-Jin

doi:10.1080/08923973.2017.1414836

Cited by 29 publications

(25 citation statements)

References 47 publications

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“…Interestingly, EMB treatment reduces the expression level of CCL2 as compared to the PTZ treated group. These findings are in agreement with the earlier findings reporting anti-inflammatory activities of EMB (Lee et al., 2018). These results are in line with the recent finding of anti-inflammatory activity of EMB in A549 cells and epithelial cell line (Ahmed, 2017).…”

Section: Discussionsupporting

confidence: 94%

Embelin Prevents Seizure and Associated Cognitive Impairments in a Pentylenetetrazole-Induced Kindling Zebrafish Model

et al. 2019

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Epilepsy is a neuronal disorder associated with several neurological and behavioral alterations characterized by recurrent spontaneous epileptic seizures. Despite having more than 20 anti-epileptic drugs (AEDs), they only provide a symptomatic treatment. As well as, currently available AEDs also displayed cognitive alterations in addition to retarding seizure. This leads to the need for exploring new molecules that not only retard seizure but also improve cognitive impairment. Embelin (EMB) is a benzoquinone derivative which has already demonstrated its pharmacological potentials against arrays of neurological conditions. The current study developed a chronic kindling model in adult zebrafish by using repeated administration of small doses of pentylenetetrazole (PTZ) and a single dose of Kainic acid (KA) to investigate the associated memory impairment. This has been done by using the three-axis maze which is a conventional method to test the learning ability and egocentric memory in zebrafish. As well as, the ameliorative potential of EMB has been evaluated against chronic epilepsy-related memory alterations. Moreover the expression level of pro-inflammatory genes such as C-C motif ligand 2 (CCL2), toll-like receptor-4 (TLR4), tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interferon-γ (IFN-γ) were evaluated. The level of several neurotransmitters such as γ-aminobutyric acid (GABA), acetylcholine (Ach) and glutamate (Glu) was evaluated by liquid chromatography-mass spectrometry (LC-MS). The results showed that daily dose of PTZ 80 mg/kg for 10 days successfully induces a kindling effect in zebrafish, whereas the single dose of KA did not. As compared to control, the PTZ and KA group demonstrates impairment in memory as demonstrated by the three-axis maze. The PTZ group treated with a series of EMB doses (ranging from 0.156 to 0.625 mg/kg) was found to have retarded seizure as well as significantly reduces epilepsy-induced memory alteration. In addition, EMB treatment reduces the expression of inflammatory markers implicating its anti-inflammatory potential. Moreover, levels of GABA, Ach, and glutamate are increased in EMB administered group as compared to the PTZ administered group. Overall, findings demonstrate that EMB might be a potential candidate against chronic epilepsy-related cognitive dysfunction as EMB prevents the seizures, so we expect it to prevent the associated neuroinflammation and learning deficit.

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Section: Discussionsupporting

confidence: 94%

Embelin Prevents Seizure and Associated Cognitive Impairments in a Pentylenetetrazole-Induced Kindling Zebrafish Model

et al. 2019

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“…IL-1β also induces the expression of TNF-α [59], which is an important cytokine for systemic inflammation and for acute phase reaction. Both TNF-α and IL-6 signal the immune cells to induce inflammation [60]. TNF-α is a key cytokine in viral diseases and various chronic inflammatory and autoimmune diseases [61].…”

Section: Discussionmentioning

confidence: 99%

Application of Humanized Zebrafish Model in the Suppression of SARS-CoV-2 Spike Protein Induced Pathology by Tri-Herbal Medicine Coronil via Cytokine Modulation

et al. 2020

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Zebrafish has been a reliable model system for studying human viral pathologies. SARS-CoV-2 viral infection has become a global chaos, affecting millions of people. There is an urgent need to contain the pandemic and develop reliable therapies. We report the use of a humanized zebrafish model, xeno-transplanted with human lung epithelial cells, A549, for studying the protective effects of a tri-herbal medicine Coronil. At human relevant doses of 12 and 58 µg/kg, Coronil inhibited SARS-CoV-2 spike protein, induced humanized zebrafish mortality, and rescued from behavioral fever. Morphological and cellular abnormalities along with granulocyte and macrophage accumulation in the swim bladder were restored to normal. Skin hemorrhage, renal cell degeneration, and necrosis were also significantly attenuated by Coronil treatment. Ultra-high-performance liquid chromatography (UHPLC) analysis identified ursolic acid, betulinic acid, withanone, withaferine A, withanoside IV–V, cordifolioside A, magnoflorine, rosmarinic acid, and palmatine as phyto-metabolites present in Coronil. In A549 cells, Coronil attenuated the IL-1β induced IL-6 and TNF-α cytokine secretions, and decreased TNF-α induced NF-κB/AP-1 transcriptional activity. Taken together, we show the disease modifying immunomodulatory properties of Coronil, at human equivalent doses, in rescuing the pathological features induced by the SARS-CoV-2 spike protein, suggesting its potential use in SARS-CoV-2 infectivity.

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“…Additionally, in epithelial cells, NF-κB is also involved in the activation of cyclooxygenase-2 (COX-2) and consequently prostaglandin E2 (PGE2), two significant factors in the development of inflammatory diseases such as asthma. In this work, inhibition of NF-κB also downregulated the expression of several cytokines such as IL-4, IL-6, and eotaxin involved in asthmatic pathology ( Lee et al, 2018 ).…”

Section: Role Of Nitric Oxide On the Regulation Of Immune Responsesmentioning

confidence: 62%

Nitric Oxide System and Bronchial Epithelium: More Than a Barrier

et al. 2021

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Airway epithelium forms a physical barrier that protects the lung from the entrance of inhaled allergens, irritants, or microorganisms. This epithelial structure is maintained by tight junctions, adherens junctions and desmosomes that prevent the diffusion of soluble mediators or proteins between apical and basolateral cell surfaces. This apical junctional complex also participates in several signaling pathways involved in gene expression, cell proliferation and cell differentiation. In addition, the airway epithelium can produce chemokines and cytokines that trigger the activation of the immune response. Disruption of this complex by some inflammatory, profibrotic, and carcinogens agents can provoke epithelial barrier dysfunction that not only contributes to an increase of viral and bacterial infection, but also alters the normal function of epithelial cells provoking several lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF) or lung cancer, among others. While nitric oxide (NO) molecular pathway has been linked with endothelial function, less is known about the role of the NO system on the bronchial epithelium and airway epithelial cells function in physiological and different pathologic scenarios. Several data indicate that the fraction of exhaled nitric oxide (FENO) is altered in lung diseases such as asthma, COPD, lung fibrosis, and cancer among others, and that reactive oxygen species mediate uncoupling NO to promote the increase of peroxynitrite levels, thus inducing bronchial epithelial barrier dysfunction. Furthermore, iNOS and the intracellular pathway sGC-cGMP-PKG are dysregulated in bronchial epithelial cells from patients with lung inflammation, fibrosis, and malignancies which represents an attractive drug molecular target. In this review we describe in detail current knowledge of the effect of NOS-NO-GC-cGMP-PKG pathway activation and disruption in bronchial epithelial cells barrier integrity and its contribution in different lung diseases, focusing on bronchial epithelial cell permeability, inflammation, transformation, migration, apoptosis/necrosis, and proliferation, as well as the specific NO molecular pathways involved.

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Anti-inflammatory effects of embelin in A549 cells and human asthmatic airway epithelial tissues

Abstract: The results of this study suggest that Emb may be used as an anti-inflammatory agent via inhibition of NF-κB and related cytokines.

Cited by 29 publications

References 47 publications

Embelin Prevents Seizure and Associated Cognitive Impairments in a Pentylenetetrazole-Induced Kindling Zebrafish Model

Embelin Prevents Seizure and Associated Cognitive Impairments in a Pentylenetetrazole-Induced Kindling Zebrafish Model

Application of Humanized Zebrafish Model in the Suppression of SARS-CoV-2 Spike Protein Induced Pathology by Tri-Herbal Medicine Coronil via Cytokine Modulation

Nitric Oxide System and Bronchial Epithelium: More Than a Barrier

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