Planta Med 2016; 82(14): 1246-1251
DOI: 10.1055/s-0042-104417
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Inhibition of Nitric Oxide Production in LPS-Stimulated RAW 264.7 Macrophages and 15-LOX Activity by Anthraquinones from Pentas schimperi

Jean Paul Dzoyem
1   Phytomedicine Programme, Department of Paraclinical Sciences, Faculty of Veterinary Science, University of Pretoria, Pretoria, South Africa
2   Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon
,
Arno R. N. Donfack
3   Department of Chemistry, Faculty of Science, University of Dschang, Dschang, Cameroon
,
Pierre Tane
3   Department of Chemistry, Faculty of Science, University of Dschang, Dschang, Cameroon
,
Lyndy J. McGaw
1   Phytomedicine Programme, Department of Paraclinical Sciences, Faculty of Veterinary Science, University of Pretoria, Pretoria, South Africa
,
Jacobus N. Eloff
1   Phytomedicine Programme, Department of Paraclinical Sciences, Faculty of Veterinary Science, University of Pretoria, Pretoria, South Africa
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Publikationsverlauf

received 12. September 2015
revised 18. Februar 2016

accepted 29. Februar 2016

Publikationsdatum:
19. April 2016 (online)

Abstract

The anti-inflammatory activity of a coumarin and nine anthraquinone derivatives, 3-hydroxy-1-methoxy-2-methylanthraquinone (1), 2-hydroxymethyl anthraquinone (2), schimperiquinone B (3), cleomiscosin A (4), damnacanthal (5), 1,2-dihydroxy anthraquinone (6), damnacanthol (7), 3-hydroxy-2-hydroxymethyl anthraquinone (8), 1-hydroxy-2-methoxyanthraquinone (9), and 2-hydroxymethyl-3-O-prenylanthraquinone (10), isolated from the roots of Pentas schimperi were determined. The anti-15-lipoxygenase activity and nitric oxide production inhibition on lipopolysaccharide-activated macrophages RAW 264.7 cells were determined as indicators of anti-inflammatory activity. The Griess assay was used to measure nitric oxide production and the ferrous oxidation-xylenol orange assay was used to determine the 15-lipoxygenase inhibitory activity. All the compounds significantly decreased nitrite + nitrate accumulation in lipopolysaccharide-stimulated RAW 264.7 cells in a concentration-dependent manner with 85.67 % to 119.75 % inhibition of nitrite + nitrate production at 20 µg/mL. Most of the compounds had a moderate inhibitory effect on 15-lipoxygenase activity. Compounds 8 and 10 were the most potent inhibitor both in nitrite + nitrate production with respective IC50 values of 1.56 µM and 6.80 µM. Compounds 2, 7, and 8 had good anti-15-lipoxygenase activity with respective IC50 values of 13.80 µM, 14.80 µM, and 15.80 µM compared to quercetin, which was used as a standard lipoxygenase inhibitor (IC50 of 16.80 µM). Our study revealed 3-hydroxy-2-hydroxymethyl anthraquinone and damnacanthol as potent inhibitors of both 15-lipoxygenase activity and nitric oxide production. Further studies are needed in order to envisage its possible future use as a therapeutic alternative against inflammatory diseases.

Supporting Information

 
  • References

  • 1 Lee J, Sowndhararajan K, Kim M, Kim J, Kim D, Kim S, Kim G, Kim S, Jhoo J. Antioxidant, inhibition of α-glucosidase and suppression of nitric oxide production in LPS-induced murine macrophages by different fractions of Actinidia arguta stem. Saudi J Biol Sci 2014; 21: 532-538
  • 2 Khanapure SP, Garvey DS, Janero DR, Letts LG. Eicosanoids in inflammation: biosynthesis, pharmacology, and therapeutic frontiers. Curr Top Med Chem 2007; 7: 311-340
  • 3 Heller A, Koch T, Schmeck J, van Ackern K. Lipid mediators in inflammatory disorders. Drugs 1998; 55: 487-496
  • 4 Li Y, Yan Z, Brauner A, Tullus K. Activation of macrophage nuclear factor-kappa B and induction of inducible nitric oxide synthase by LPS. Respir Res 2002; 3: 23
  • 5 Lenon GB, Li CG, Xue CC, Thien FCK, Story DF. Inhibition of inducible nitric oxide production and iNOS protein expression in lipopolysaccharide-stimulated rat aorta and Raw 264.7 macrophages by ethanol extract of a Chinese herbal medicine formula (RCM-101) for allergic rhinitis. J Ethnopharmacol 2008; 116: 547-553
  • 6 Laskin JD, Heck DE, Laskin DL. Multifunctional role of nitric oxide in inflammation. Trends Endocrinol Metab 1994; 5: 377-382
  • 7 Joo T, Sowndhararajan K, Hong S, Lee J, Park S, Kim S, Jhoo J. Inhibition of nitric oxide production in LPS-stimulated RAW 264.7 cells by stem bark of Ulmus pumila L. Saudi J Biol Sci 2014; 21: 427-435
  • 8 Ji HF, Li XJ, Zhang HY. Natural products and drug discovery. Can thousands of years of ancient medical knowledge lead us to new and powerful drug combinations in the fight against cancer and dementia?. EMBO Rep 2009; 10: 194-200
  • 9 Bukuru JF, van Nguyen T, van Puyvelde L, Mathenge SG, Mudida FP, de Kimpe N. A benzochromene from the roots of Pentas bussei . J Nat Prod 2002; 65: 783-785
  • 10 Giday M, Asfaw Z, Woldu Z, Teklehaymanot T. Medicinal plant knowledge of the Bench ethnic group of Ethiopia: an ethnobotanical investigation. J Ethnobiol Ethnomed 2009; 5: 34
  • 11 Focho DA, Ndam WT, Fonge BA. Medicinal plants of Aguambu – Bamumbu in the Lebialem highlands, southwest province of Cameroon. Afr J Pharm Pharmacol 2009; 3: 1-13
  • 12 Bukuru J. Isolation and structural elucidation of natural products from Pentas bussei K. Krause, Pentas lanceolata (Forsk.) Deflers and Pentas parvifolia Hiern (Rubiaceae) [dissertation]. Ghent, Belgium: University of Ghent; 2003
  • 13 Donfack ARN, Tala MF, Wabo HK, Jerz G, Zeng GZ, Winterhalter P, Tan NH, Tane P. Two new anthraquinone dimers from the stem bark of Pentas schimperi (Rubiaceae). Phytochem Lett 2014; 8: 55-58
  • 14 Endale M, Ekberg A, Alao JP, Akala HM, Ndakala A, Sunnerhagen P, Erdélyi M, Yenesew A. Anthraquinones of the roots of Pentas micrantha . Molecules 2012; 18: 311-321
  • 15 Muzychkina RA. Natural anthraquinones: biological and physicochemical properties. Moscow: House Phasis; 1998
  • 16 Dave H, Ledwani L. A review on anthraquinones isolated from Cassia species and their applications. Indian J Nat Prod Resour 2012; 3: 291-319
  • 17 Wang CC, Huang YJ, Chen LG, Lee LT, Yang LL. Inducible nitric oxide synthase inhibitors of Chinese herbs III. Rheum palmatum . Planta Med 2002; 68: 869-874
  • 18 Chang P, Lee KH. Cytotoxic antileukemic anthraquinones from Morinda parvifolia . Phytochemistry 1984; 23: 1733-1736
  • 19 Ranjan R, Sahai M. Coumarinolignans from the Seeds of Annona squamosa Linn. E-J Chem 2009; 6: 518-522
  • 20 Li S, Ouyang Q, Tan X, Shi S, Yao Z. [Chemical constituents of Morinda officinalis How]. Zhongguo Zhong Yao Za Zhi 1991; 16: 675-676 703
  • 21 Wu YB, Zheng CJ, Qin LP, Sun LN, Han T, Jiao L, Zhang QY, Wu JZ. Antiosteoporotic activity of anthraquinones from Morinda officinalis on osteoblasts and osteoclasts. Molecules 2009; 14: 573-583
  • 22 Liu Q, Kim SB, Ahn JH, Hwang BY, Kim SY, Lee MK. Anthraquinones from Morinda officinalis roots enhance adipocyte differentiation in 3T3-L1 cells. Nat Prod Res 2012; 26: 1750-1754
  • 23 Yoon W, Kim K, Kim J, Kim H, Park S, Lee WJ, Hyun C. 89 Suppression of pro-inflammatory cytokines and mediators expression by brown algae Sargassum micracanthum extracts in murine macrophages RAW 264.7 cells. Cytokine 2008; 43: 257-257
  • 24 Alves CCS, Da Costa CF, De Castro SBR, Corrêa TA, Santiago GO, Diniz R, Ferreira AP, De Almeida MV. Synthesis and evaluation of cytotoxicity and inhibitory effect on nitric oxide production by J774A.1 macrophages of new anthraquinone derivatives. Med Chem 2013; 9: 812-818
  • 25 Lee HS. Suppression effect of purpurin derivatives on nitric oxide synthase. J Appl Biol Chem 2011; 54: 302-307
  • 26 Pinto Mdel C, Tejeda A, Duque AL, Macias P. Determination of lipoxygenase activity in plant extracts using a modified ferrous oxidation-xylenol orange assay. J Agric Food Chem 2007; 55: 5956-5959
  • 27 Ngoc TM, Minh PTH, Hung TM, Thuong PT, Lee I, Min BS, Bae K. Lipoxygenase inhibitory constituents from rhubarb. Arch Pharm Res 2008; 31: 598-605
  • 28 Mu MM, Chakravortty D, Sugiyama T, Koide N, Takahashi K, Mori I, Yoshida T, Yokochi T. The inhibitory action of quercetin on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophage cells. J Endotoxin Res 2001; 7: 431-438
  • 29 Dzoyem JP, Eloff JN. Anti-inflammatory, anticholinesterase and antioxidant activity of leaf extracts of twelve plants used traditionally to alleviate pain and inflammation in South Africa. J Ethnopharmacol 2015; 160: 194-201