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Open AccessArticle

Cerevisterol Alleviates Inflammation via Suppression of MAPK/NF-κB/AP-1 and Activation of the Nrf2/HO-1 Signaling Cascade

1
Department of Food Science and Biotechnology, Graduate School, Kyungpook National University, Daegu 41566, Korea
2
Food and Bio-Industry Research Institute, Inner Beauty/Anti-Aging Center, Kyungpook National University, Daegu 41566, Korea
3
Department of Pharmacy, Manarat International University, Dhaka 1212, Bangladesh
4
Pharmaceutical Sciences Research Division (PSRD), BCSIR Laboratories, Dhaka 1205, Bangladesh
5
Department of Pharmacy, Jahangirnagar University, Dhaka 1342, Bangladesh
6
Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka 1205, Bangladesh
7
knu BnC, Daegu 41566, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to the study.
Biomolecules 2020, 10(2), 199; https://doi.org/10.3390/biom10020199
Received: 31 December 2019 / Revised: 22 January 2020 / Accepted: 26 January 2020 / Published: 29 January 2020
(This article belongs to the Section Natural and Bio-inspired Molecules)
As part of our continuous effort to find potential anti-inflammatory agents from endophytic fungi, a Fusarium solani strain, isolated from the plant Aponogeton undulatus Roxb., was investigated. Cerevisterol (CRVS) was identified from endophytic fungi, a Fusarium solani strain, and moreover exhibited anti-inflammatory activity. However, the underlying mode of action remains poorly understood. The aim of this study is to reveal the potential mechanisms of CRVS against inflammation on a molecular level in LPS-activated RAW 264.7 peritoneal macrophage cells. CRVS was isolated from F. solani and characterized based on spectral data analysis. The MTT assay was performed to measure cell viability in CRVS-treated macrophages. Anti-inflammatory activity was assessed by measurement of nitric oxide (NO) and prostaglandin E2 (PGE2) levels, as well as the production of various cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and -6 (IL-6) in LPS-stimulated macrophages. RT-PCR and immunoblotting analyses were done to examine the expression of various inflammatory response genes. A reporter gene assay was conducted to measure the level of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activator protein-1 (AP-1) transactivation. CRVS suppresses the LPS-induced production of NO and PGE2, which is a plausible mechanism for this effect is by reducing the expression of iNOS and COX-2. CRVS also decreases the expression of pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-1β. CRVS halted the nuclear translocation of NF-κB by blocking the phosphorylation of inhibitory protein κBα (IκBα) and suppressing NF-κB transactivation. The mitogen-activated protein kinases (MAPK) signaling pathways are also suppressed. CRVS treatment also inhibited the transactivation of AP-1 and the phosphorylation of c-Fos. Furthermore, CRVS could induce the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) by down-regulating Kelch-like ECH-associated protein 1 (Keap-1) and up-regulating hemeoxygenases-1 (HO-1) expression. The results suggest that CRVS acts as a natural agent for treating inflammatory diseases by targeting an MAPK, NF-κB, AP-1, and Nrf2-mediated HO-1 signaling cascade. View Full-Text
Keywords: cerevisterol; Fusarium solani; Aponogeton undulatus Roxb.; NF-κB; Nrf2; HO-1 cerevisterol; Fusarium solani; Aponogeton undulatus Roxb.; NF-κB; Nrf2; HO-1
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MDPI and ACS Style

Alam, M.B.; Chowdhury, N.S.; Sohrab, M.H.; Rana, M.S.; Hasan, C.M.; Lee, S.-H. Cerevisterol Alleviates Inflammation via Suppression of MAPK/NF-κB/AP-1 and Activation of the Nrf2/HO-1 Signaling Cascade. Biomolecules 2020, 10, 199.

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