Panduratin A, an activator of PPAR-α/δ, suppresses the development of oxazolone-induced atopic dermatitis-like symptoms in hairless mice

Kim, Myung Suk; Pyun, Hee Bong; Hwang, Jae Kwan

doi:10.1016/j.lfs.2014.01.076

Cited by 23 publications

(12 citation statements)

References 35 publications

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“…54,55 Moreover, panduratin A can stimulate AMPK signaling leading to the activation of PPARα and PPARδ. 56,57 The induction of these transcription factor machinery can, in turn, promote autophagy. 58,59 Consistently, it was reported that MERS-CoV blocked the fusion of autophagosomes and lysosomes.…”

Section: Discussionmentioning

confidence: 99%

High-Content Screening of Thai Medicinal Plants Reveals Boesenbergia rotunda Extract and its Component Panduratin A as Anti-SARS-CoV-2 Agents

Kanjanasirirat

Suksatu

Manopwisedjaroen

et al. 2020

Preprint

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Since December 2019, the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused severe pneumonia, a disease named COVID-19, that became pandemic and created an acute threat to public health. The effective therapeutics are in urgent need. Here, we developed a high-content screening for the antiviral candidates using fluorescence-based SARS-CoV-2 nucleoprotein detection in Vero E6 cells coupled with plaque reduction assay. Among 122 Thai natural products, we found that Boesenbergia rotunda extract and its phytochemical compound, panduratin A, exhibited the potent anti-SARS-CoV-2 activity. Treatment with B. rotunda extract and panduratin A after viral infection drastically suppressed SARS-CoV-2 infectivity in Vero E6 cells with IC50 of 3.62 μg/mL (CC50 = 28.06 µg/mL) and 0.81 μΜ (CC50=14.71 µM), respectively. Also, the treatment of panduratin A at the pre-entry phase inhibited SARS-CoV-2 infection with IC50 of 5.30 µM (CC50=43.47 µM). Our study demonstrated, for the first time, that panduratin A exerts the inhibitory effect against SARS-CoV-2 infection at both pre-entry and post-infection phases. Since B. rotunda is a culinary herb generally grown in China and Southeast Asia, its extract and the purified panduratin A may serve as the promising candidates for therapeutic purposes with economic advantage during COVID-19 situation.

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Section: Discussionmentioning

confidence: 99%

High-Content Screening of Thai Medicinal Plants Reveals Boesenbergia rotunda Extract and its Component Panduratin A as Anti-SARS-CoV-2 Agents

Kanjanasirirat

Suksatu

Manopwisedjaroen

et al. 2020

Preprint

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“…Inhibition of fatty acid oxidation with the cPT1 inhibitor etomoxir abrogates differentiation of naïve cd4+ T-cells to Tregs (12). Notably, activation of AhR promotes Treg differentiation (6), activation of PPAR-α ameliorates the course of autoimmune diseases (34)(35)(36)(37), and PPAR-α activity is required for Treg differentiation and suppressive function (38)(39)(40). Finally, it is possible that a portion of free fatty acids is consumed by the expanded cd4+ T-cells as building blocks, since IdO by activating GcN2K decreases fatty acid synthesis (4), which is required for T-cell proliferation (41).…”

Section: Discussionmentioning

confidence: 99%

IDO decreases glycolysis and glutaminolysis by activating GCN2K, while it increases fatty acid oxidation by activating AhR, thus preserving CD4+ T‑cell survival and proliferation

et al. 2018

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It is generally hypothesized in the literature that indoleamine 2,3‑dioxygenase (IDO), by degrading L‑tryptophan along the kynurenine pathway, suppresses CD4+ T‑cell function by inducing apoptosis, inhibiting proliferation and promoting differentiation towards a regulatory phenotype. These effects are either accompanied or directly lead to alterations in cell metabolism. The present study evaluated the pathways that govern the effect of IDO on the utilization of the three main energy sources in CD4+ T‑cells. Two‑way mixed lymphocyte reactions were performed with or without oleate and/or the IDO inhibitor 1‑methyl‑DL‑tryptophan. In addition, isolated CD4+ T‑cells cultured in an oleate‑containing medium were activated in the presence or not of the general control nonderepressible 2 kinase (GCN2K) activator tryptophanol. L‑tryptophan, glucose and free fatty acid consumption, cell proliferation, apoptosis and the levels of key proteins involved in IDO‑mediated signal transduction, and glucose, glutamine and free fatty acid utilization were assessed. The results indicate that IDO decreased glycolysis and glutaminolysis by activating GCN2K, resulting in activation of AMP‑activated protein kinase (AMPK). In parallel with AMPK activation, IDO‑induced activation of aryl hydrocarbon receptor increased the expression of all carnitine palmitoyltransferase I isoenzymes, leading ultimately to increased free fatty acid oxidation and preservation of CD4+ T‑cell survival and proliferation. Thus, contrary to what is generally hypothesized, in a normal environment containing fatty acids, the immunosuppressive effect of IDO may not be due to a decrease in CD4+ T‑cell survival and proliferation, since IDO supplies the required energy for cell survival and proliferation by increasing free fatty acid oxidation.

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“…Although frequently viewed as an anti‐inflammatory transcription factor (Michalik & Wahli, ), PPARβ/δ regulation of inflammation is complex and is context dependent. Previous work has shown that its activation with an agonist decreased inflammatory symptoms in mouse models of contact dermatitis (Plager et al , ; Kim et al , ), and cutaneous inflammatory response after 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) treatment was exacerbated in PPARβ/δ‐deficient mice (Man et al , ). In contrast to these anti‐inflammatory actions, PPARβ/δ increased expression in murine epidermis provoked a psoriasis‐like phenotype, and its expression is elevated in human psoriatic lesions (), where it was proposed to contribute to the persistence of activated T cells (al Yacoub et al , ; Romanowska et al , ).…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel PPAR β/δ/miR‐21‐3p axis in UV ‐induced skin inflammation

et al. 2016

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Although excessive exposure to UV is widely recognized as a major factor leading to skin perturbations and cancer, the complex mechanisms underlying inflammatory skin disorders resulting from UV exposure remain incompletely characterized. The nuclear hormone receptor PPARβ/δ is known to control mouse cutaneous repair and UV‐induced skin cancer development. Here, we describe a novel PPARβ/δ‐dependent molecular cascade involving TGFβ1 and miR‐21‐3p, which is activated in the epidermis in response to UV exposure. We establish that the passenger miRNA miR‐21‐3p, that we identify as a novel UV‐induced miRNA in the epidermis, plays a pro‐inflammatory function in keratinocytes and that its high level of expression in human skin is associated with psoriasis and squamous cell carcinomas. Finally, we provide evidence that inhibition of miR‐21‐3p reduces UV‐induced cutaneous inflammation in ex vivo human skin biopsies, thereby underlining the clinical relevance of miRNA‐based topical therapies for cutaneous disorders.

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Panduratin A, an activator of PPAR-α/δ, suppresses the development of oxazolone-induced atopic dermatitis-like symptoms in hairless mice

Cited by 23 publications

References 35 publications

High-Content Screening of Thai Medicinal Plants Reveals Boesenbergia rotunda Extract and its Component Panduratin A as Anti-SARS-CoV-2 Agents

High-Content Screening of Thai Medicinal Plants Reveals Boesenbergia rotunda Extract and its Component Panduratin A as Anti-SARS-CoV-2 Agents

IDO decreases glycolysis and glutaminolysis by activating GCN2K, while it increases fatty acid oxidation by activating AhR, thus preserving CD4+ T‑cell survival and proliferation

Identification of a novel PPAR β/δ/miR‐21‐3p axis in UV ‐induced skin inflammation

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