Nrf2,Antifeedant,SREBP1c,NF-κB,p53,Liver protection,Anticancer / Asthma,Ischemic stroke,Acute myocardial infarction,Ischemia-reperfusion injury,BaP-induced skin damage,Convulsions,Vascular endothelium
(E)-1-[2,4-dihydroxy-6-methoxy-3-(3-methylbut-2-enyl)phenyl]-3-(4-hydroxyphenyl)prop-2-en-1-one/(2E)-1-[2,4-Dihydroxy-6-methoxy-3-(3-methylbut-2-en-1-yl)phenyl]-3-(4-hydroxyphenyl)prop-2-en-1-one/Xanthohumol/2-propen-1-one, 1-[2,4-dihydroxy-6-methoxy-3-(3-methyl-2-butenyl)phenyl]-3-(4-hydroxyphenyl)-, (2E)-/2-Propen-1-one, 1-[2,4-dihydroxy-6-methoxy-3-(3-methyl-2-buten-1-yl)phenyl]-3-(4-hydroxyphenyl)-, (2E)-QR D1U1VR BQ DQ FO1 C2UY1&1/(2E)-1-[2,4-Dihydroxy-6-methoxy-3-(3-methyl-2-buten-1-yl)phenyl]-3-(4-hydroxyphenyl)-2-propen-1-one
576.5±50.0 °C at 760 mmHg
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The infection by porcine reproductive and respiratory syndrome virus (PRRSV) has a severe impact on the world swine industry. However, commercially available vaccines provide only incomplete protection against this disease. Thus, novel approaches to control PRRSV infection are essential for the robust and sustainable swine industry. In our previous study, Xanthohumol (Xn), a prenylated flavonoid extracted for hops (Humulus lupulus L), was screened from 386 natural products to inhibit PRRSV proliferation and alleviate oxidative stress induced by PRRSV via the Nrf2-HMOX1 axis in Marc-145 cells. In this study, we furtherly found that Xn could inhibit PRRSV different sub-genotype strains infection with a low IC50 value in porcine primary alveolar macrophages (PAMs). In addition, it caused decreased expression of interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor-α in PAMs infected with PRRSV or treated with lipopolysaccharide. Animal challenge experiments showed that Xn effectively alleviated clinical signs, lung pathology, and inflammatory responses in lung tissues of pigs induced by highly pathogenic PRRSV infection. The results demonstrate that Xn is a promising therapeutic agent to combat PRRSV infections.
Copyright © 2019 Elsevier B.V. All rights reserved.
Antiviral activity; PRRSV; Xanthohumol
Therapeutic effect of Xanthohumol against highly pathogenic porcine reproductive and respiratory syndrome viruses.
Liu X1, Bai J1, Jiang C1, Song Z1, Zhao Y1, Nauwynck H2, Jiang P3.
Xanthohumol (Xan) is a prenylated chalcone mainly found in hops; it has been demonstrated to function against hypercholesterolemia, hyperlipidemia, and atherosclerosis. In this study, we focused on the hypocholesterolemic effect of Xan on cholesterol uptake and the underlying molecular mechanisms of Xan in human intestinal Caco-2 cells. The microarray data showed that Niemann-Pick C1-like 1 (NPC1L1), an essential transporter for dietary cholesterol absorption, was significantly downregulated in Xan-treated Caco-2 cells. We demonstrated that Xan (10 and 20 μM) suppressed the mRNA and protein expression of NPC1L1 by 0.65 ± 0.12-fold and 0.54 ± 0.15-fold and 0.72 ± 0.04-fold and 0.44 ± 0.12-fold, respectively, compared to that of the vehicle-treated Caco-2 cells. Moreover, Xan (10 and 20 μM) significantly inhibited cholesterol uptake by approximately 12 and 32% in Caco-2 cells. NPC1L1 promoter activity was significantly suppressed by Xan, and a DNA element within the NPC1L1 promoter involved in Xan-mediated NPC1L1 reduction located between the -120 and -20 positions was identified. Moreover, Xan markedly decreased the mRNA and protein levels of hepatocyte nuclear factor 4α (HNF-4α), a critical activator of NPC1L1 transcription, and subsequently attenuated HNF-4α/NPC1L1 promoter complex formation, resulting in the suppression of NPC1L1 gene expression. Finally, we demonstrated that Xan markedly abolished lovastatin-induced NPC1L1 overexpression in Caco-2 cells. These findings reveal that Xan suppresses NPC1L1 expression via downregulation of HNF-4α and exerts inhibitory effects on cholesterol uptake in the intestinal Caco-2 cells. Our findings suggest Xan could serve as a potential cholesterol-lowering agent and supplement for statin therapy.
HNF-4α; NPC1L1; cholesterol absorption; statin; xanthohumol
Xanthohumol Suppresses NPC1L1 Gene Expression through Downregulation of HNF-4α and Inhibits Cholesterol Uptake in Caco-2 Cells.
Thang SK1, Chen PY2, Gao WY3, Wu MJ4, Pan MH5, Yen JH1,3.
2019 Oct 9
Porcine reproductive and respiratory syndrome virus (PRRSV) is a prevalent and endemic swine pathogen that causes significant economic losses in the global swine industry. Commercial vaccines provide limited protection against this virus, and no highly effective therapeutic drugs are yet available. In this study, we first screened a library of 386 natural products and found that xanthohumol (Xn), a prenylated flavonoid found in hops, displayed high anti-PRRSV activity by inhibiting PRRSV adsorption onto and internalization into cells. Transcriptome sequencing revealed that Xn treatment stimulates genes associated with the antioxidant response in the nuclear factor-erythroid 2-related factor 2 (Nrf2) signalling pathway. Xn causes increased expression of Nrf2, HMOX1, GCLC, GCLM, and NQO1 in Marc-145 cells. The action of Xn against PRRSV proliferation depends on Nrf2 in Marc-145 cells and porcine alveolar macrophages (PAMs). This finding suggests that Xn significantly inhibits PRRSV proliferation and decreases viral-induced oxidative stress by activating the Nrf2-HMOX1 pathway. This information should be helpful for developing a novel prophylactic and therapeutic strategy against PRRSV infection.
Xanthohumol inhibits PRRSV proliferation and alleviates oxidative stress induced by PRRSV via the Nrf2-HMOX1 axis.
Liu X1, Song Z1, Bai J1, Nauwynck H2, Zhao Y1, Jiang P3,4.
2019 Sep 11