Alpinone

Alpinone: A positive regulator molecule of immune antiviral response in Atlantic salmon kidney cells.[Pubmed:34543663]

Dev Comp Immunol. 2022 Jan;126:104262.

Alpinone is a flavonoid obtained from the resinous exudate of Heliotropium huascoense. This flavonoid shows antiviral activity against the infectious salmon anemia virus (ISAV), which causes severe disease in farmed Atlantic salmon. Here, we aim to elucidate mechanisms underlying the antiviral effects of the flavonoid. In this regard, we evaluated whether Alpinone can act upregulating the pattern-recognition receptor genes, i.e., the RIG-I-like, TLR3, and TLR9 genes, and the genes of the downstream signaling pathways. Transcriptional expression of the genes was analyzed using real-time PCR after 8, 24, and 48 h treatment of salmon kidney adherent cells with 15 mug/mL of Alpinone. First, we showed that Alpinone induced IFNa expression in the kidney adherent cells, indicating that this type of salmon cells is in part responsible for the effects previously reported in vivo. Upregulation of the IFN-induced myxovirus resistance (Mx) gene was also observed in the head kidney cells in response to the treatment. Overexpression reached a maximum level at 24 h post-treatment. Interestingly, Alpinone also induced upregulation of the cytosolic receptors of ssRNA, named Retinoic acid-inducible gene I (RIG-I) and Melanoma Differentiation-Associated protein 5 (MDA5), but there were no effects on the transcriptional expression of the TLR3 and TLR9 endosomal receptors. In addition, Alpinone upregulated the expression of genes encoding the main components of the RIG-I/MDA5 signaling pathways, such as the mitochondrial antiviral-signaling protein (MAVS), TNF Receptor Associated Factor 3 (TRAF3), TANK-binding kinase 1 (TBK1), I-kappaB kinase epsilon (IKKepsilon), the transcription factors IRF-3, and IRF7. The increased expression of all these genes is consistent with the upregulation of IFNa and Mx mRNAs. Because BX795 completely prevents Alpinone-dependent upregulation of IFNa and IRF3, the flavonoid targets seem to be upstream of the kinases TBK1 and IKKepsilon. Altogether, this study contributes to elucidating the mechanisms involved in Alpinone antiviral activity in fish. Alpinone can be used to counteract virus mechanisms of evasion where the onset of interferon-mediated response is prevented or delayed.

Alpinone exhibited immunomodulatory and antiviral activities in Atlantic salmon.[Pubmed:29292197]

Fish Shellfish Immunol. 2018 Mar;74:76-83.

In this study, we seek to identify flavonoids able to regulate the gene expression of a group of cytokines important for the control of infections in Atlantic salmon (Salmo salar). Particularly, we studied the potential immunomodulatory effects of two flavonoids, Alpinone and Pinocembrine, which were isolated and purified from resinous exudates of Heliotropium huascoense and Heliotropium sinuatum, respectively. The transcript levels of TNF-alpha and IL-1 (inflammatory cytokines), IFN-gamma and IL-12 (T helper 1 type cytokines), IL4/13A (Th2-type cytokine), IL-17 (Th17 type cytokine) TGF-beta1 (regulatory cytokine) and IFN-alpha (antiviral cytokine) were quantified by qRT-PCR in kidneys of flavonoid-treated and control fish. We demonstrated that the administration of a single intramuscular dose of purified Alpinone increased the transcriptional expression of five cytokines, named TNF-alpha, IL-1, IFN-alpha, IFN-gamma and TGF-beta1 in treated fish compared to untreated fish. Conversely, administration of purified Pinocembrine reduced the transcriptional expression of TNF-alpha, IL-1 and IL-12 in the kidney of treated fish. No other changes were observed. Interestingly, Alpinone also induced in vitro antiviral effects against Infectious Salmon Anaemia virus. Results showed that Alpinone but not Pinocembrine induces the expression of cytokines, which in vertebrates are essential to control viral infections while Pinocembrine reduces pro-inflammatory cytokines. Altogether results suggest that Alpinone is a good candidate to be further tested as immunostimulant and antiviral drug.

Anti-inflammatory effects of alpinone 3-acetate from Alpinia japonica seeds.[Pubmed:27137785]

J Nat Med. 2016 Jul;70(3):653-60.

We aimed to investigate the bioactive components of Alpinia japonica as anti-inflammatory compounds using searches of the Alpinia genus, and subsequently demonstrated that Alpinone 3-acetate markedly inhibits 12-O-tetradecanoyiphorbol 13-acetate-induced inflammation in a mouse model of ear edema. To assess other bioactivities of Alpinone 3-acetate, we performed translatome analyses and compared them with those of hydrocortisone. Polysome-associated mRNAs were prepared from Alpinone 3-acetate- or hydrocortisone-treated and control cells from 12-O-tetradecanoyiphorbol 13-acetate-induced THP-1-derived macrophages cultured in the presence of Escherichia coli O-111 lipopolysaccharide. Subsequent microarray analysis revealed that Alpinone 3-acetate and hydrocortisone upregulated and downregulated the same 155 and 41 genes, respectively. Moreover, direct comparisons of translationally regulated genes indicated 5 and 10 gene probes that were upregulated and downregulated by Alpinone 3-acetate and hydrocortisone, respectively. In conclusion, assays of 12-O-tetradecanoyiphorbol 13-acetate-induced inflammation ear edema in mice and polysome profiling of Alpinone 3-acetate bioactivities indicated similar medicinal possibilities to those of hydrocortisone.

A benzil and isoflavone from Iris tenuifolia.[Pubmed:18472117]

Phytochemistry. 2008 Jun;69(9):1880-5.

Two compounds, tenuifodione (1) and tenuifone (2), and 12 known compounds, izalpinin (3), Alpinone (4), arborinone (5), irilin B (6), irisone A (7), irisone B (8), betavulgarin (9), beta-sitosterol (10), 5,7-dihydroxy-2',6-dimethoxyisoflavone (11), 2',5-dihdroxy-6,7-methylenedioxy flavanone (12), irisoid A (13) and ethyl-beta-d-glucopyranoside (14) were isolated from the whole plant of Iris tenuifolia Pall. All compounds, except 12, were isolated for the first time from this plant. Compounds 2, 3 and 11 have shown a considerable DPPH radical scavenging activity. Structures of these compounds were identified on the basis of spectroscopic techniques, including 2D NMR. Compounds 3, 5 and 7 were also subjected to single-crystal X-ray diffraction analysis and their structures were unambiguously deduced.

Heliotropium huascoense resin exudate: chemical constituents and defensive properties.[Pubmed:11575941]

J Nat Prod. 2001 Sep;64(9):1123-6.

From the resinous exudate of Heliotropium huascoense a new compound, rel-(8R,9R)-carrizaloic acid, (1) (3-[rel-(8R,9R-9-hydroxy-9,13,13-trimethyl-12-oxo-10-cyclohexenyl)methyl]-4-methoxybenzoic acid), and three known flavonoids, [3-methylgalangin, 3,7-dimethylgalangin, and (-)-Alpinone] have been isolated. The structure of 1 was determined by spectral and chemical methods. Several plant defensive properties of 1 (insecticidal and antifungal) have been evaluated.

Alpinone (CAS 480-13-7) is a natural product offered by BioCrick for research applications. Customers can buy or order Alpinone from BioCrick, a supplier and manufacturer of research chemicals, with product specifications, purity, packaging, and pricing information available upon request.