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Anti-inflammatory effects of secondary metabolites isolated from the marine-derived fungal strain Penicillium sp. SF-5629

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Abstract

After the chemical investigation of the ethyl acetate extract of the marine-derived fungal strain Penicillium sp. SF-5629, the isolation and structural elucidation of eight secondary metabolites, including (3R,4S)-6,8-dihydroxy-3,4,7-trimethylisocoumarin (1), (3S,4S)-sclerotinin A (2), penicitrinone A (3), citrinin H1 (4), emodin (5), ω-hydroxyemodin (6), 8-hydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylate (7), and 3,8-dihydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylate (8) were carried out. Evaluation of the anti-inflammatory activity of these metabolites showed that 4 inhibited nitric oxide and prostaglandin E2 production in lipopolysaccharide-stimulated BV2 microglia, with IC50 values of 8.1 ± 1.9 and 8.0 ± 2.8 μM, respectively. The inhibitory function of 4 was confirmed based on decreases in inducible nitric oxide synthesis and cyclooxygenase-2 gene expression. In addition, 4 was found to suppress the phosphorylation of inhibitor kappa B-α, interrupt the nuclear translocation of nuclear factor kappa B, and decrease the activation of p38 mitogen-activated protein kinase.

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References

  • Bae U-J, Song M-Y, Jang H-Y, Lim JM, Lee SY, Ryu J-H, Park B-H (2015) Emodin isolated from Rheum palmatum prevents cytokine-induced β-cell damage and the development of type 1 diabetes. J Funct Foods 16:9–19

    Article  CAS  Google Scholar 

  • Baeuerle PA, Henkel T (1994) Function and activation of NF-kappa B in the immune system. Annu Rev Immunol 12:141–179

    Article  CAS  PubMed  Google Scholar 

  • Baldwin ASJ (1996) The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol 14:649–683

    Article  CAS  PubMed  Google Scholar 

  • Blunt JW, Copp BR, Keyzers RA, Munro MH, Prinsep MR (2014) Marine natural products. Nat Prod Rep 31:160–258

    Article  CAS  PubMed  Google Scholar 

  • Blunt JW, Copp BR, Keyzers RA, Munro MH, Prinsep MR (2016) Marine natural products. Nat Prod Rep 33:382–431

    Article  CAS  PubMed  Google Scholar 

  • Bondeson J (1997) The mechanisms of action of disease-modifying antirheumatic drugs: a review with emphasis on macrophage signal transduction and the induction of proinflammatory cytokines. Gen Pharmacol 29:127–150

    Article  CAS  PubMed  Google Scholar 

  • Bonizzi G, Karin M (2004) The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol 25:280–288

    Article  CAS  PubMed  Google Scholar 

  • Ci X, Ren R, Xu K, Li H, Yu Q, Song Y, Wang D, Li R, Deng X (2010) Schisantherin A exhibits anti-inflammatory properties by down-regulating NF-kappaB and MAPK signaling pathways in lipopolysaccharide-treated RAW 264.7 cells. Inflammation 33:126–136

    Article  CAS  PubMed  Google Scholar 

  • Clark BR, Capon RJ, Lacey E, Tennant S, Gill JH (2006) Citrinin revisited: from monomers to dimers and beyond. Org Biomol Chem 4:1520–1528

    Article  CAS  PubMed  Google Scholar 

  • Dheen ST, Kaur C, Ling EA (2007) Microglial activation and its implications in the brain diseases. Curr Med Chem 14:1189–1197

    Article  CAS  PubMed  Google Scholar 

  • Du L, Liu HC, Fu W, Li DH, Pan QM, Zhu TJ, Geng MY, Gu QQ (2011) Unprecedented citrinin trimer tricitinol B functions as a novel topoisomerase IIalpha inhibitor. J Med Chem 54:5796–5810

    Article  CAS  PubMed  Google Scholar 

  • Feng GJ, Goodridge HS, Harnett MM, Wei XQ, Nikolaev AV, Higson AP, Liew FY (1999) Extracellular signal-related kinase (ERK) and p38 mitogen-activated protein (MAP) kinases differentially regulate the lipopolysaccharide-mediated induction of inducible nitric oxide synthase and IL-12 in macrophages: Leishmania phosphoglycans subvert macrophage IL-12 production by targeting ERK MAP kinase. J Immunol 163:6403–6412

    CAS  PubMed  Google Scholar 

  • Francis GW, Aksnes DW, Holt Ø (1998) Assignment of the 1H and 13C NMR spectra of anthraquinone glycosides from Rhamnus frangula. Magn Reson Chem 36:769–772

    Article  CAS  Google Scholar 

  • Fujimoto H, Nakamura E, Okuyama E, Ishibashi M (2004) Six immunosuppressive features from an ascomycete, Zopfiella longicaudata, found in a screening study monitored by immunomodulatory activity. Chem Pharm Bull 52:1005–1008

    Article  CAS  PubMed  Google Scholar 

  • Gomez PF, Pillinger MH, Attur M, Marjanovic N, Dave M, Park J, Bingham CO 3rd, Al-Mussawir H, Abramson SB (2005) Resolution of inflammation: prostaglandin E2 dissociates nuclear trafficking of individual NF-kappaB subunits (p65, p50) in stimulated rheumatoid synovial fibroblasts. J Immunol 175:6924–6930

    Article  CAS  PubMed  Google Scholar 

  • Gonzalez-Scarano F, Baltuch G (1999) Microglia as mediators of inflammatory and degenerative diseases. Annu Rev Neurosci 22:219–240

    Article  CAS  PubMed  Google Scholar 

  • Guha M, Mackman N (2001) LPS induction of gene expression in human monocytes. Cell Signal 13:85–94

    Article  CAS  PubMed  Google Scholar 

  • Guo W, Kong X, Zhu T, Gu Q, Li D (2015) Penipyrols A-B and peniamidones A-D from the mangrove derived Penicillium solitum GWQ-143. Arch Pharm Res 38:1449–1454

    Article  CAS  PubMed  Google Scholar 

  • Han Z, Mei W, Zhao Y, Deng Y, Dai H (2009) A new cytotoxic isocoumarin from endophytic fungus Penicillium sp. 091402 of the mangrove plant Bruguiera sexangula. Chem Nat Compd 45:805–807

    Article  CAS  Google Scholar 

  • Harhaji L, Mijatovic S, Maksimovic-Ivanic D, Popadic D, Isakovic A, Todorovic-Markovic B, Trajkovic V (2007) Aloe emodin inhibits the cytotoxic action of tumor necrosis factor. Eur J Pharmacol 568:248–259

    Article  CAS  PubMed  Google Scholar 

  • Hwang JK, Noh EM, Moon SJ, Kim JM, Kwon KB, Park BH, You YO, Hwang BM, Kim HJ, Kim BS, Lee SJ, Kim JS, Lee YR (2013) Emodin suppresses inflammatory responses and joint destruction in collagen-induced arthritic mice. Rheumatology 52:1583–1591

    Article  CAS  PubMed  Google Scholar 

  • Khan S, Shehzad O, Lee KJ, Tosun A, Kim YS (2014) Anti-inflammatory properties of samidin from Seseli resinosum through suppression of NF-kappa B and AP-1-mediated-genes in LPS-stimulated RAW 264.7 cells. Arch Pharm Res 37:1496–1503

    Article  CAS  PubMed  Google Scholar 

  • Kim DC, Quang TH, Ngan NT, Yoon CS, Sohn JH, Yim JH, Feng Y, Che Y, Kim YC, Oh H (2015) Dihydroisocoumarin derivatives from marine-derived fungal isolates and their anti-inflammatory effects in lipopolysaccharide-induced BV2 microglia. J Nat Prod 78:2948–2955

    Article  CAS  PubMed  Google Scholar 

  • Kirk PM, Cannon PF, Minter DW, Stalpers JA (2008) Dictionary of the fungi. CABI, Wallingford

    Google Scholar 

  • Kong FD, Zhou LM, Ma QY, Huang SZ, Wang P, Dai HF, Zhao YX (2016) Metabolites with Gram-negative bacteria quorum sensing inhibitory activity from the marine animal endogenic fungus Penicillium sp. SCS-KFD08. Arch Pharm. doi:10.1007/s1227201608443

    Google Scholar 

  • Korhonen R, Lahti A, Kankaanranta H, Moilanen E (2005) Nitric oxide production and signaling in inflammation. Curr Drug Targets Inflamm Allergy 4:471–479

    Article  CAS  PubMed  Google Scholar 

  • Kozlovskii AG, Zhelifonova VP, Antipova TV (2013) Fungi of the genus Penicillium as producers of physiologically active compounds (review). Appl Biochem Microbiol 49:1–10

    Article  CAS  Google Scholar 

  • Lai D, Brötz-Oesterhelt H, Müller WEG, Wray V, Proksch P (2013) Bioactive polyketides and alkaloids from Penicillium citrinum, a fungal endophyte isolated from Ocimum tenuiflorum. Fitoterapia 91:100–106

    Article  CAS  PubMed  Google Scholar 

  • Lee CH, Kim SI, Lee KB, Yoo YC, Ryu SY, Song KS (2003) Neuraminidase inhibitors from Reynoutria elliptica. Arch Pharm Res 26:367–374

    Article  CAS  PubMed  Google Scholar 

  • Lee DS, Ko W, Quang TH, Kim KS, Sohn JH, Jang JH, Ahn JS, Kim YC, Oh H (2013) Penicillinolide A: a new anti-inflammatory metabolite from the marine fungus Penicillium sp. SF-5292. Mar Drugs 11:4510–4526

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee DS, Keo S, Ko W, Kim KS, Ivanova E, Yim JH, Kim YC, Oh H (2014) Secondary metabolites isolated from Castilleja rubra exert anti-inflammatory effects through NF-kappa B inactivation on lipopolysaccharide-induced RAW264.7 macrophages. Arch Pharm Res 37:947–954

    Article  CAS  PubMed  Google Scholar 

  • Li Q, Verma IM (2002) NF-kappaB regulation in the immune system. Nat Rev Immunol 2:725–734

    Article  CAS  PubMed  Google Scholar 

  • Liu Y-H, Feng Z-W, Luo W, Guo Z-Y, Deng Z-S, Tu X, Chen J-F, Zou K (2013) The secondary metabolites from endophytic fungus Penicillium sp. of Paris polyphylla Sm. Tianran Chanwu Yanjiu Yu Kaifa 25:585–589

    Google Scholar 

  • Lu Z-Y, Lin Z-J, Wang W-L, Du L, Zhu T-J, Fang Y-C, Gu Q-Q, Zhu W-M (2008) Citrinin dimers from the halotolerant fungus Penicillium citrinum B-57. J Nat Prod 71:543–546

    Article  CAS  PubMed  Google Scholar 

  • Lull ME, Block ML (2010) Microglial activation & chronic neurodegeneration. Neurotherapeutics 7:354–365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Quang TH, Lee D-S, Sohn JH, Kim Y-C, Oh H (2013) A new deoxyisoaustamide derivative from the marine-derived fungus Penicillium sp. JF-72. Bull Korean Chem Soc 34:3109–3112

    Article  CAS  Google Scholar 

  • Quang TH, Ngan NT, Ko W, Kim DC, Yoon CS, Sohn JH, Yim JH, Kim YC, Oh H (2014) Tanzawaic acid derivatives from a marine isolate of Penicillium sp. (SF-6013) with anti-inflammatory and PTP1B inhibitory activities. Bioorg Med Chem Lett 24:5787–5791

    Article  CAS  PubMed  Google Scholar 

  • Shao C, Wang C, Wei M, Gu Y, Xia X, She Z, Lin Y (2008) Structure elucidation of two new xanthone derivatives from the marine fungus Penicillium sp. (ZZF 32#) from the South China Sea. Magn Reson Chem 46:1066–1069

    Article  CAS  PubMed  Google Scholar 

  • Siddiqui IN, Zahoor A, Hussain H, Ahmed I, Ahmad VU, Padula D, Draeger S, Schulz B, Meier K, Steinert M, Kurtan T, Florke U, Pescitelli G, Krohn K (2011) Diversonol and blennolide derivatives from the endophytic fungus Microdiplodia sp.: absolute configuration of diversonol. J Nat Prod 74:365–373

    Article  CAS  PubMed  Google Scholar 

  • Strayhorn WD, Wadzinski BE (2002) A novel in vitro assay for deubiquitination of IκBα. Arch Biochem Biophys 400:76–84

    Article  CAS  PubMed  Google Scholar 

  • Trivedi AB, Hirota M, Doi E, Kitabatake N (1993) Formation of a new toxic compound, citrinin H1, from citrinin on mild heating in water. J Chem Soc Perkin Trans 1:2167–2171

    Article  Google Scholar 

  • Verma IM, Stevenson JK, Schwarz EM, Van Antwerp D, Miyamoto S (1995) Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation. Genes Dev 9:2723–2735

    Article  CAS  PubMed  Google Scholar 

  • Wakana D, Hosoe T, Itabashi T, Okada K, de Campos Takaki G, Yaguchi T, Fukushima K, K-i Kawai (2006) New citrinin derivatives isolated from Penicillium citrinum. J Nat Med 60:279–284

    Article  CAS  Google Scholar 

  • Wang N, Cui CB, Li CW (2016) A new cyclic dipeptide penicimutide: the activated production of cyclic dipeptides by introduction of neomycin-resistance in the marine-derived fungus Penicillium purpurogenum G59. Arch Pharm Res 39:762–770

    Article  CAS  PubMed  Google Scholar 

  • Xue J, Chen F, Wang J, Wu S, Zheng M, Zhu H, Liu Y, He J, Chen Z (2015) Emodin protects against concanavalin A-induced hepatitis in mice through inhibiting activation of the p38 MAPK-NF-kappaB signaling pathway. Cell Physiol Biochem 35:1557–1570

    Article  CAS  PubMed  Google Scholar 

  • Zhang X, Zhang R, Lv P, Yang J, Deng Y, Xu J, Zhu R, Zhang D, Yang Y (2015) Emodin up-regulates glucose metabolism, decreases lipolysis, and attenuates inflammation in vitro. J Diabetes 7:360–368

    Article  CAS  PubMed  Google Scholar 

  • Zhou HY, Shin EM, Guo LY, Youn UJ, Bae K, Kang SS, Zou LB, Kim YS (2008) Anti-inflammatory activity of 4-methoxyhonokiol is a function of the inhibition of iNOS and COX-2 expression in RAW 264.7 macrophages via NF-kappaB, JNK and p38 MAPK inactivation. Eur J Pharmacol 586:340–349

    Article  CAS  PubMed  Google Scholar 

  • Zhou SL, Wang M, Zhao HG, Huang YH, Lin YY, Tan GH, Chen SL (2016) Penicilazaphilone C, a new antineoplastic and antibacterial azaphilone from the Marine Fungus Penicillium sclerotiorum. Arch Pharm Res. doi:10.1007/s1227201608283

    Google Scholar 

  • Zhu X, Zeng K, Qiu Y, Yan F, Lin C (2013) Therapeutic effect of emodin on collagen-induced arthritis in mice. Inflammation 36:1253–1259

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We acknowledge the financial support by grants from the Global R&D Center (GRDC, NRF-2010-00719) programs of the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning of Korea (MSIFP). This research was also supported by grants from the National Research Foundation of Korea (NRF) funded by the Korean Government (MSIP) (2008-0062484) (2015M3A9E3051054).

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Correspondence to Hyuncheol Oh.

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Nguyen Thi Thanh Ngan, Tran Hong Quang and Kwan-Woo Kim have contributed equally to this work.

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Ngan, N.T.T., Quang, T.H., Kim, KW. et al. Anti-inflammatory effects of secondary metabolites isolated from the marine-derived fungal strain Penicillium sp. SF-5629. Arch. Pharm. Res. 40, 328–337 (2017). https://doi.org/10.1007/s12272-017-0890-5

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