Planta Med 2013; 79(09): 782-787
DOI: 10.1055/s-0032-1328550
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Inhibition of Lipopolysaccharide-Induced iNOS and COX-2 Expression by Indole Alkaloid, 3-(Hydroxymethyl)-6,7-Dihydroindolo[2,3-a]Quinolizin-(12H)-one, via NF-κB Inactivation in RAW 264.7 Macrophages

Feng Zhao
1   School of Pharmacy, Yantai University, Yantai, PR China
,
Lei Chen
1   School of Pharmacy, Yantai University, Yantai, PR China
,
Menglin Zhang
1   School of Pharmacy, Yantai University, Yantai, PR China
,
Chenchen Bi
1   School of Pharmacy, Yantai University, Yantai, PR China
,
Lichun Li
1   School of Pharmacy, Yantai University, Yantai, PR China
,
Qingzhen Zhang
1   School of Pharmacy, Yantai University, Yantai, PR China
,
Cuicui Shi
1   School of Pharmacy, Yantai University, Yantai, PR China
,
Miao Li
1   School of Pharmacy, Yantai University, Yantai, PR China
,
Songsong Zhou
1   School of Pharmacy, Yantai University, Yantai, PR China
,
Linghua Kong
1   School of Pharmacy, Yantai University, Yantai, PR China
› Author Affiliations
Further Information

Publication History

received 25 February 2013
revised 06 April 2013

accepted 09 April 2013

Publication Date:
13 May 2013 (online)

Abstract

3-(Hydroxymethyl)-6,7-dihydroindolo[2,3-a]quinolizin-(12H)-one is a bioactive indole alkaloid isolated from Nauclea officinalis, a plant species which is used as a traditional Chinese medicine. We investigated the anti-inflammatory properties of 3-(hydroxymethyl)-6,7-dihydroindolo[2,3-a]quinolizin-(12H)-one in RAW 264.7 murine macrophages. The results indicated that it inhibited the overproduction of NO and the release of TNF-α. Furthermore, this compound inhibited the expression of iNOS and COX-2 proteins, the enzymatic activity of iNOS, and the translocation of NF-κB to the nucleus induced by LPS. Therefore, we suggested that the effect of 3-(hydroxymethyl)-6,7-dihydroindolo[2,3-a]quinolizin-(12H)-one-mediated inhibition of the expression of LPS-induced iNOS and COX-2 genes is due to the suppression of NF-κB activation in the transcriptional level.

 
  • References

  • 1 Gidado A, Ameh DA, Atawodi SE, Ibrahim S. A preliminary study of the mechanism of hypoglycaemic activity of Nauclea latifolia leaf ethanolic extract. J Complement Integr Med 2012; 1: 16
  • 2 Mesia K, Tona L, Mampunza MM, Ntamabyaliro N, Muanda T, Muyembe T, Musuamba T, Mets T, Cimanga K, Totté J, Pieters L, Vlietinck AJ. Antimalarial efficacy of a quantified extract of Nauclea pobeguinii stem bark in human adult volunteers with diagnosed uncomplicated falciparum malaria. Part 2: a clinical phase IIB trial. Planta Med 2012; 9: 853-860
  • 3 Mesia K, Tona L, Mampunza MM, Ntamabyaliro N, Muanda T, Muyembe T, Cimanga K, Totté J, Mets T, Pieters L, Vlietinck AJ. Antimalarial efficacy of a quantified extract of Nauclea pobeguinii stem bark in human adult volunteers with diagnosed uncomplicated falciparum malaria. Part 1: a clinical phase IIA trial. Planta Med 2012; 3: 211-218
  • 4 Raghavamma ST, Rao NR. In vitro evaluation of anthelmintic activity of Nauclea orientalis leaves. Indian J Pharm Sci 2010; 4: 520-521
  • 5 Owolabi OJ, Nworgu ZA, Odushu K. Antidiarrheal evaluation of the ethanol extract of Nauclea latifolia root bark. Methods Find Exp Clin Pharmacol 2010; 8: 551-555
  • 6 Sun J, Lou H, Dai S, Xu H, Zhao F, Liu K. Indole alkoloids from Nauclea officinalis with weak antimalarial activity. Phytochemistry 2008; 6: 1405-1410
  • 7 Tao JY, Dai SJ, Zhao F, Liu JF, Fang WS, Liu K. New ursane-type triterpene with NO production suppressing activity from Nauclea officinalis . J Asian Nat Prod Res 2012; 2: 97-104
  • 8 Denizot F, Lang R. Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol 1986; 89: 271-277
  • 9 Zhao F, Wang L, Liu K. In vitro anti-inflammatory effects of arctigenin, a lignan from Arctium lappa L., through inhibition on iNOS pathway. J Ethnopharmacol 2009; 3: 457-462
  • 10 Zhao F, Xu H, Wang L, Jiang YT, Liu K. Inhibitory effects of sesquiterpenes from Saussurea lappa on the overproduction of nitric oxide and TNF-α release in LPS-activated macrophages. J Asian Nat Prod Res 2008; 11: 1045-1053
  • 11 Zhao F, Gao ZT, Jiao WH, Chen LL, Chen L, Yao XS. In vitro anti-inflammatory effects of beta-carboline alkaloids, isolated from Picrasma quassioides, through inhibition of the iNOS pathway. Planta Med 2012; 18: 1906-1911
  • 12 Michel T, Feron O. Nitric oxide synthases: which, where, how, and why?. J Clin Invest 1997; 100: 2146-2152
  • 13 West NE, Qian H, Guzik TJ, Black E, Cai S, George SE, Channon KM. Nitric oxide synthase (nNOS) gene transfer modifies venous bypass graft remodeling; effects in vascular smooth muscle cell differentiation and superoxide production. Circulation 2001; 104: 1526-1532
  • 14 Funk CD, Funk LB, Kennedy ME, Pong AS, Fitzgerald GA. Human platelet/erythroleukemia cell prostaglandin G/H synthase; cDNA cloning, expression and gene chromosomal assignment. FASEB J 1991; 5: 2304-2312
  • 15 Hinz B, Brune K. Cyclooxygenase-2 – 10 years later. J Pharmacol Exp Ther 2002; 300: 367-375
  • 16 Prescott SM, Fitzpatrick FA. Cyclooxygenase-2 and carcinogenesis. Biochim Biophys Acta 2000; 1470: 69-78
  • 17 Bogdan C. Nitric oxide and the regulation of gene expression. Trends Cell Biol 2001; 2: 66-75
  • 18 Baeuerle PA, Baltimore D. IκB: a specific inhibitor of the NF-κB transcription factor. Science 1988; 242: 540-546
  • 19 Beg AA, Baldwin Jr. AS. The IκB proteins: multifunctional regulators of Rel/NF-κB transcription factors. Genes Dev 1993; 7: 2064-2070