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TNF-α and IL-6 inhibitory effects of cyclic dipeptides isolated from marine bacteria Streptomyces sp

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Abstract

Inflammation is mediated by a variety of soluble factors, including a group of secreted polypeptides known as cytokines. The anti-inflammatory cytokines are a series of immune regulatory molecules that control the pro inflammatory cytokine response. Cytokines act in concert with specific cytokine inhibitors and soluble cytokine receptors to regulate the human immune response. The aim of the present study is to probe the anti-inflammatory potential of the crude extract and the bioactive metabolite isolated from marine bacteria Streptomyces sp. on key inflammatory mediators like tumor necrosis factor-α and interleukin-6. Here, we isolated ten known pyrazine-1,4-dione substituted cyclic dipeptide by semi-preparative HPLC and studied their anti-inflammatory activities against tumor necrosis factor-α and interleukin-6. Compound 3, 4, 5, 7 and 8 showed good inhibition of the both the cytokines in lipopolysaccharide-stimulated macrophages. The study reveal that compound 7 was to be specific inhibitor for tumor necrosis factor-α which efficiently inhibited tumor necrosis factor-α release in a dose-dependent manner and decreased lipopolysaccharide induced tumor necrosis factor-α production in human peripheral blood mononuclear cells in both the in vitro and in vivo experiments.

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References

  • Akyol S, Tanriverdi T, Hanci M (2012) Do immunologic events in degenerative disc tissue alter the peripheral immune tolerance? World Spinal Column J 3:45–49

    Google Scholar 

  • Ali A et al (2013) Modulation of LPS induced inflammatory response by Lawsonyl monocyclic terpene from the marine derived Streptomyces sp. Immunol Lett 150:79–86

    Article  CAS  PubMed  Google Scholar 

  • Ammon HPT (2010) Modulation of the immune system by Boswellia serrata extracts and boswellic acids. Phytomedicine 17:862–867

    Article  CAS  PubMed  Google Scholar 

  • Cronan JM, Davidson TR, Singleton FL, Colwell RR, Cardellina JH (1998) Plant growth promoters isolated from a marine bacterium associated with Palythoa sp. Nat Prod Lett 11:271–278

    Article  CAS  Google Scholar 

  • De Vries DJ, Beart PM (1995) Fishing for drugs from the sea: status and strategies. Trends Pharmacol Sci 16:275–279

    Article  PubMed  Google Scholar 

  • Debitus C et al (1998) Quinolones from a bacterium and tyrosine metabolites from its host sponge, Suberea creba from the coral sea. J Mar Biotechnol 6:136–141

    CAS  PubMed  Google Scholar 

  • Fdhila F, Vázquez V, Sánchez JL, Riguera R (2003) dd-Diketopiperazines: antibiotics active against vibrio anguillarum isolated from marine bacteria associated with cultures of pecten maximus. J Nat Prod 66:1299–1301

    Article  CAS  PubMed  Google Scholar 

  • Gayathri B, Manjula N, Vinaykumar KS, Lakshmi BS, Balakrishnan A (2007) Pure compound from Boswellia serrata extract exhibits anti-inflammatory property in human PBMCs and mouse macrophages through inhibition of TNF-α, IL-1β, NO and MAP kinases. Int Immunopharmacol 7:473–482

    Article  CAS  PubMed  Google Scholar 

  • Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM (1995) Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 95:2409–2415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jahromi MM, Millward BA, Demaine AG (2000) A polymorphism in the promoter region of the gene for interleukin-6 is associated with susceptibility to type 1 diabetes mellitus. J Interferon Cytokine Res 20:885–888

    Article  CAS  PubMed  Google Scholar 

  • Jayatilake GS, Thornton MP, Leonard AC, Grimwade JE, Baker BJ (1996) Metabolites from an Antarctic sponge-associated bacterium, Pseudomonas aeruginosa. J Nat Prod 59:293–296

    Article  CAS  PubMed  Google Scholar 

  • Lam KS (2006) Discovery of novel metabolites from marine actinomycetes. Curr Opin Microbiol 9:245–251

    Article  CAS  PubMed  Google Scholar 

  • Lin WC, Lin JY (2011) Five bitter compounds display different anti-inflammatory effects through modulating cytokine secretion using mouse primary splenocytes in vitro. J Agric Food Chem 59:184–192

    Article  CAS  PubMed  Google Scholar 

  • Lovering F, Zhang Y (2005) Therapeutic potential of TACE inhibitors in stroke. Curr Drug Targets CNS Neurol Disord 4:161–168

    Article  CAS  PubMed  Google Scholar 

  • Papa Gobbi R et al (2016) A galectin-specific signature in the gut delineates Crohn’s disease and ulcerative colitis from other human inflammatory intestinal disorders. BioFactors 42:93–105

    CAS  PubMed  Google Scholar 

  • Park YC, Gunasekera SP, Lopez JV, Mccarthy PJ, Wright AE (2006) Metabolites from the marine-derived fungus Chromocleista sp. Isolated from a deep-water sediment sample collected in the Gulf of Mexico. J Nat Prod 69:580–584

    Article  CAS  PubMed  Google Scholar 

  • Remsing LL et al (2003) Mithramycin SK, a novel antitumor drug with improved therapeutic index, mithramycin SA, and demycarosyl-mithramycin SK: three new products generated in the mithramycin producer Streptomyces argillaceus through combinatorial biosynthesis. J Am Chem Soc 125:5745–5753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rosler N, Wichart I, Jellinger KA (2001) Intra vitam lumbar and post mortem ventricular cerebrospinal fluid immunoreactive interleukin-6 in Alzheimer’s disease patients. Acta Neurol Scand 103:126–130

    Article  CAS  PubMed  Google Scholar 

  • Rudi A, Kashman Y, Benayahu Y, Schleyer M (1994) Amino acid derivatives from the marine sponge Jaspis digonoxea. J Nat Prod 57:829–832

    Article  CAS  PubMed  Google Scholar 

  • Ruiz-Alcaraz AJ et al. (2011) Peritoneal macrophage priming in cirrhosis is related to ERK phosphorylation and IL-6 secretion. Eur J Clin Invest 41:8–15

    Article  CAS  PubMed  Google Scholar 

  • Selmaj K, Raine CS, Cannella B, Brosnan CF (1991) Identification of lymphotoxin and tumor necrosis factor in multiple sclerosis lesions. J Clin Invest 87:949–954

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smolen JS, Steiner G (2003) Therapeutic strategies for rheumatoid arthritis. Nat Rev Drug Discov 2:473–488

    Article  CAS  PubMed  Google Scholar 

  • Solanki R, Khanna M, Lal R (2008) Bioactive compounds from marine actinomycetes. Indian J Microbiol 48:410–431

    Article  CAS  PubMed  Google Scholar 

  • Such J et al (2001) Tumor necrosis factor-alpha, interleukin-6, and nitric oxide in sterile ascitic fluid and serum from patients with cirrhosis who subsequently develop ascitic fluid infection. Dig Dis Sci 46:2360–2366

    Article  CAS  PubMed  Google Scholar 

  • Sujatha P, Bapi Raju KV, Ramana T (2005) Studies on a new marine streptomycete BT-408 producing polyketide antibiotic SBR-22 effective against methicillin resistant Staphylococcus aureus. Microbiol Res 160:119–126

    Article  CAS  PubMed  Google Scholar 

  • Takaya Y et al (2007) Antioxidant constituents in distillation residue of awamori spirits. J Agric Food Chem 55:75–79

    Article  CAS  PubMed  Google Scholar 

  • Williams PG et al (2007) Saliniketals A and B, bicyclic polyketides from the marine actinomycete Salinispora arenicola. J Nat Prod 70:83–88

    Article  CAS  PubMed  Google Scholar 

  • Wu SJ, Fotso S, Li F, Qin S, Laatsch H (2007) Amorphane sesquiterpenes from a marine Streptomyces sp. J Nat Prod 70:304–306

    Article  CAS  PubMed  Google Scholar 

  • Yuan G, Wahlqvist ML, He G, Yang M, Li D (2006) Natural products and anti-inflammatory activity. Asia Pac J Clin Nutr 15:143–152

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors are grateful to the University grant commission (UGC-New Delhi) and CSIR for providing financial support having the Grant No. ITR-0001 for the work of YN, and SM. YK, SG and VK acknowledge AcSIR for their enrolment in Ph. D program. VK also acknowledge DST for INSPIRE Fellowship. We are also thankful to Deeαpika Singh for recording the NMR experiments.

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Authors and Affiliations

  1. Natural Product Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu- Tawi, J&K, 180001, India

    Yedukondalu Nalli, Mehak Sajgotra & Asif Ali

  2. Academy of Scientific and Innovative Research, CSIR-Indian Institute of Medicine, Canal Road, Jammu-Tawi, J&K, 180001, India

    Yedukondalu Nalli, Shilpa Gupta, Vidushi Khajuria, Mehak Sajgotra, Zabeer Ahmed & Asif Ali

  3. Inflammation Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu-Tawi, J&K, 180001, India

    Shilpa Gupta, Vidushi Khajuria & Zabeer Ahmed

  4. Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, 180 001, India

    Varun P. Singh

  5. Chemical Oceanography Division, CSIR-National Institute of Oceanography, Goa, 403004, India

    Narsinh L. Thakur

Authors
  1. Yedukondalu Nalli
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  2. Shilpa Gupta
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  3. Vidushi Khajuria
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  4. Varun P. Singh
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  5. Mehak Sajgotra
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  6. Zabeer Ahmed
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  7. Narsinh L. Thakur
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  8. Asif Ali
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Correspondence to Asif Ali.

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Nalli, Y., Gupta, S., Khajuria, V. et al. TNF-α and IL-6 inhibitory effects of cyclic dipeptides isolated from marine bacteria Streptomyces sp. Med Chem Res 26, 93–100 (2017). https://doi.org/10.1007/s00044-016-1730-8

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  • DOI: https://doi.org/10.1007/s00044-016-1730-8

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