Skip to main content
Erschienen in: Inflammopharmacology 2/2018

22.07.2017 | Original Article

Inhibitory effects of andrographolide on activated macrophages and adjuvant-induced arthritis

verfasst von: Swati Gupta, Kamla Prasad Mishra, Shashi Bala Singh, Lilly Ganju

Erschienen in: Inflammopharmacology | Ausgabe 2/2018

Einloggen, um Zugang zu erhalten

Abstract

Andrographolide, a diterpenoid lactone obtained from plant Andrographis paniculata, is used in South Asian countries to relieve various inflammatory symptoms. To study the effects of this agent, the impact of andrographolide on production of inflammatory mediators were delineated in mouse peritoneal macrophages (PMϕ). Inflammatory mediators like nitric oxide (NO), tumor necrosis factor (TNF)-α, interleukin-6 and related molecular mechanisms of andrographolide-mediated inhibition of enzymes/transcription factors were studied. In addition, the in vivo anti-inflammatory activity of andrographolide was evaluated in an adjuvant-induced arthritis rat model. The results indicated that andrographolide clearly inhibited the production of NO and TNF-α in lipopolysaccharide-activated PMϕ in a dose-related manner. Immunoblot analyses revealed that andrographolide suppressed activation of both inducible NO synthase and cyclo-oxygenase-2 by directly targeting nuclear transcription factor (NF)-κB. Complete Freund’s Adjuvant-induced paw edema in rats was also significantly inhibited by andrographolide treatment. From the data, we concluded that andrographolide imparted anti-inflammatory effects by suppressing two key inflammatory enzymes and a signaling pathway that mediates expression of variety of inflammatory cytokines/agents in situ. It is plausible that eventually, after further toxicologic characterization, andrographolide might be useful as a drug for the clinical treatment of various inflammatory diseases like rheumatoid arthritis or diseases associated with joint pain.
Literatur
Zurück zum Zitat Akagi K et al (2014) A case of macrophage activation syndrome developing in a patient with chronic granulomatous disease-associated colitis. J Pediatr Hematol Oncol 36(3):e169–e172CrossRefPubMed Akagi K et al (2014) A case of macrophage activation syndrome developing in a patient with chronic granulomatous disease-associated colitis. J Pediatr Hematol Oncol 36(3):e169–e172CrossRefPubMed
Zurück zum Zitat Arifullah M et al (2013) Evaluation of anti-bacterial and anti-oxidant potential of andrographolide and echiodinin isolated from callus culture of Andrographis paniculata Nees. Asian Pac J Trop Biomed 3(8):604–610CrossRefPubMedPubMedCentral Arifullah M et al (2013) Evaluation of anti-bacterial and anti-oxidant potential of andrographolide and echiodinin isolated from callus culture of Andrographis paniculata Nees. Asian Pac J Trop Biomed 3(8):604–610CrossRefPubMedPubMedCentral
Zurück zum Zitat Burgos RA et al (2009) Efficacy of an Andrographis paniculata composition for the relief of rheumatoid arthritis symptoms: a prospective randomized placebo-controlled trial. Clin Rheumatol 28(8):931–946CrossRefPubMed Burgos RA et al (2009) Efficacy of an Andrographis paniculata composition for the relief of rheumatoid arthritis symptoms: a prospective randomized placebo-controlled trial. Clin Rheumatol 28(8):931–946CrossRefPubMed
Zurück zum Zitat Chang YW et al (2000) Cyclooxygenase 2 promotes cell survival by stimulation of dynein light chain expression and inhibition of neuronal nitric oxide synthase activity. Mol Cell Biol 20(22):8571–8579CrossRefPubMedPubMedCentral Chang YW et al (2000) Cyclooxygenase 2 promotes cell survival by stimulation of dynein light chain expression and inhibition of neuronal nitric oxide synthase activity. Mol Cell Biol 20(22):8571–8579CrossRefPubMedPubMedCentral
Zurück zum Zitat Chang CC et al (2014) Andrographolide, a novel NF-κB inhibitor, inhibits vascular smooth muscle cell proliferation and cerebral endothelial cell inflammation. Acta Cardiol Sinica 30(4):308–315 Chang CC et al (2014) Andrographolide, a novel NF-κB inhibitor, inhibits vascular smooth muscle cell proliferation and cerebral endothelial cell inflammation. Acta Cardiol Sinica 30(4):308–315
Zurück zum Zitat Das S et al (2009) Oxidative stress in the brain of nicotine-induced toxicity: protective role of Andrographis paniculata Nees and vitamin E. Appl Physiol Nutr Metab 34(2):124–135CrossRefPubMed Das S et al (2009) Oxidative stress in the brain of nicotine-induced toxicity: protective role of Andrographis paniculata Nees and vitamin E. Appl Physiol Nutr Metab 34(2):124–135CrossRefPubMed
Zurück zum Zitat De Castro Costa M et al. (1981) Adjuvant-induced arthritis in rats: a possible animal model of chronic pain. Pain 10(2):173–185CrossRef De Castro Costa M et al. (1981) Adjuvant-induced arthritis in rats: a possible animal model of chronic pain. Pain 10(2):173–185CrossRef
Zurück zum Zitat Duque GA, Descoteaux A (2014) Macrophage cytokines: involvement in immunity and infectious diseases. Front Immunol 5:491–503 Duque GA, Descoteaux A (2014) Macrophage cytokines: involvement in immunity and infectious diseases. Front Immunol 5:491–503
Zurück zum Zitat Fries W, Cottone M, Cascio A (2013) Systematic review: macrophage activation syndrome in inflammatory bowel disease. Aliment Pharmacol Ther 37(11):1033–1045CrossRefPubMed Fries W, Cottone M, Cascio A (2013) Systematic review: macrophage activation syndrome in inflammatory bowel disease. Aliment Pharmacol Ther 37(11):1033–1045CrossRefPubMed
Zurück zum Zitat Hsieh CY et al (2011) Andrographolide enhances nuclear factor-kappaB subunit p65 Ser536 dephosphorylation through activation of protein phosphatase 2A in vascular smooth muscle cells. J Biol Chem 286(8):5942–5955CrossRefPubMed Hsieh CY et al (2011) Andrographolide enhances nuclear factor-kappaB subunit p65 Ser536 dephosphorylation through activation of protein phosphatase 2A in vascular smooth muscle cells. J Biol Chem 286(8):5942–5955CrossRefPubMed
Zurück zum Zitat Jayashankar B et al (2012) A supercritical CO2 extract from seabuckthorn leaves inhibits pro-inflammatory mediators via inhibition of mitogen activated protein kinase p38 and transcription factor nuclear factor-κB. Int Immunopharmacol 13(4):461–467CrossRefPubMed Jayashankar B et al (2012) A supercritical CO2 extract from seabuckthorn leaves inhibits pro-inflammatory mediators via inhibition of mitogen activated protein kinase p38 and transcription factor nuclear factor-κB. Int Immunopharmacol 13(4):461–467CrossRefPubMed
Zurück zum Zitat Lagha A et al (2015) Interleukin-1β, Interleukin1-Ra, Interleukin-10, and tumor necrosis factor-α polymorphisms in Tunisian patients with rheumatoid arthritis. Pathol Biol 63(4–5):179–184CrossRefPubMed Lagha A et al (2015) Interleukin-1β, Interleukin1-Ra, Interleukin-10, and tumor necrosis factor-α polymorphisms in Tunisian patients with rheumatoid arthritis. Pathol Biol 63(4–5):179–184CrossRefPubMed
Zurück zum Zitat Lim JCW et al (2012) Andrographolide and its analogues: versatile bioactive molecules for combating inflammation and cancer. Clin Exp Pharmacol Physiol 39(3):300–310CrossRefPubMed Lim JCW et al (2012) Andrographolide and its analogues: versatile bioactive molecules for combating inflammation and cancer. Clin Exp Pharmacol Physiol 39(3):300–310CrossRefPubMed
Zurück zum Zitat Mishra KP et al (2006) Aqueous extract of Rhodiola imbricata rhizome stimulates proinflammatory mediators via phosphorylated IkappaB and transcription factor nuclear factor-kappaB. Immunopharmacol Immunotoxicol 28(2):201–212CrossRefPubMed Mishra KP et al (2006) Aqueous extract of Rhodiola imbricata rhizome stimulates proinflammatory mediators via phosphorylated IkappaB and transcription factor nuclear factor-kappaB. Immunopharmacol Immunotoxicol 28(2):201–212CrossRefPubMed
Zurück zum Zitat Morgan MJ, Liu ZG (2011) Crosstalk of reactive oxygen species and NF-kappaB signaling. Cell Res 21(1):103–115CrossRefPubMed Morgan MJ, Liu ZG (2011) Crosstalk of reactive oxygen species and NF-kappaB signaling. Cell Res 21(1):103–115CrossRefPubMed
Zurück zum Zitat Poolsup N et al (2004) Andrographis paniculata in the symptomatic treatment of uncomplicated upper respiratory tract infection: systematic review of randomized controlled trials. J Clin Pharm Ther 29(1):37–45CrossRefPubMed Poolsup N et al (2004) Andrographis paniculata in the symptomatic treatment of uncomplicated upper respiratory tract infection: systematic review of randomized controlled trials. J Clin Pharm Ther 29(1):37–45CrossRefPubMed
Zurück zum Zitat Ren J et al (2016) Andrographolide ameliorates abdominal aortic aneurysm progression by inhibiting inflammatory cell infiltration through downregulation of cytokine and integrin expression. J Pharmacol Exp Ther 356(1):137–147CrossRefPubMedPubMedCentral Ren J et al (2016) Andrographolide ameliorates abdominal aortic aneurysm progression by inhibiting inflammatory cell infiltration through downregulation of cytokine and integrin expression. J Pharmacol Exp Ther 356(1):137–147CrossRefPubMedPubMedCentral
Zurück zum Zitat Saranya P, Geetha A (2011) Antiulcer activity of Andrographis paniculata (Burm.F.) Wall. against cysteamine-induced duodenal ulcer in rats. Indian J Exp Biol 49(7):525–533PubMed Saranya P, Geetha A (2011) Antiulcer activity of Andrographis paniculata (Burm.F.) Wall. against cysteamine-induced duodenal ulcer in rats. Indian J Exp Biol 49(7):525–533PubMed
Zurück zum Zitat Suriyo T et al (2014) Andrographis paniculata extracts and major constituent diterpenoids inhibit growth of intrahepatic cholangiocarcinoma cells by inducing cell cycle arrest and apoptosis. Planta Medica 80(7):533–543CrossRefPubMed Suriyo T et al (2014) Andrographis paniculata extracts and major constituent diterpenoids inhibit growth of intrahepatic cholangiocarcinoma cells by inducing cell cycle arrest and apoptosis. Planta Medica 80(7):533–543CrossRefPubMed
Zurück zum Zitat Wagner-Weiner L (2015) Systemic juvenile idiopathic arthritis complicated by macrophage activation syndrome. Pediatr Ann 44(6):e142–e147CrossRefPubMed Wagner-Weiner L (2015) Systemic juvenile idiopathic arthritis complicated by macrophage activation syndrome. Pediatr Ann 44(6):e142–e147CrossRefPubMed
Zurück zum Zitat Wang D et al (2007) Novel dexamethasone-HPMA copolymer conjugate and its potential application in treatment of rheumatoid arthritis. Arthr Res Ther 9(1):R2CrossRef Wang D et al (2007) Novel dexamethasone-HPMA copolymer conjugate and its potential application in treatment of rheumatoid arthritis. Arthr Res Ther 9(1):R2CrossRef
Zurück zum Zitat Wang Q et al (2013) Naturally derived anti-inflammatory compounds from Chinese medicinal plants. J Ethnopharmacol 146(1):9–39CrossRefPubMed Wang Q et al (2013) Naturally derived anti-inflammatory compounds from Chinese medicinal plants. J Ethnopharmacol 146(1):9–39CrossRefPubMed
Zurück zum Zitat Watts AD et al (1999) Soluble TNF-alpha receptors bind and neutralize over-expressed transmembrane TNF-alpha on macrophages, but do not inhibit its processing. J Leukoc Biology 66:1005–1013CrossRef Watts AD et al (1999) Soluble TNF-alpha receptors bind and neutralize over-expressed transmembrane TNF-alpha on macrophages, but do not inhibit its processing. J Leukoc Biology 66:1005–1013CrossRef
Zurück zum Zitat Wen L et al (2014) Activity of antibacterial, antiviral, anti-inflammatory in compounds andrographolide salt. Eur J Pharmacol 740:421–427CrossRefPubMed Wen L et al (2014) Activity of antibacterial, antiviral, anti-inflammatory in compounds andrographolide salt. Eur J Pharmacol 740:421–427CrossRefPubMed
Zurück zum Zitat Yu Z et al (2015) Andrographolide ameliorates diabetic retinopathy by inhibiting retinal angiogenesis and inflammation. Biochim et Biophys Acta 1850(4):824–831CrossRef Yu Z et al (2015) Andrographolide ameliorates diabetic retinopathy by inhibiting retinal angiogenesis and inflammation. Biochim et Biophys Acta 1850(4):824–831CrossRef
Zurück zum Zitat Zamora R, Vodovotz Y, Billiar TR (2000) Inducible nitric oxide synthase and inflammatory diseases. Mol Med 6(5):347–373PubMedPubMedCentral Zamora R, Vodovotz Y, Billiar TR (2000) Inducible nitric oxide synthase and inflammatory diseases. Mol Med 6(5):347–373PubMedPubMedCentral
Zurück zum Zitat Zhang QQ et al (2014) Andrographolide inhibits melanoma tumor growth by inactivating the TLR4/NF-κB signaling pathway. Melanoma Res 24(6):545–555CrossRefPubMed Zhang QQ et al (2014) Andrographolide inhibits melanoma tumor growth by inactivating the TLR4/NF-κB signaling pathway. Melanoma Res 24(6):545–555CrossRefPubMed
Zurück zum Zitat Zündorf I, Fürst R (2014) Plant-derived anti-inflammatory compounds: Hopes and disappointments regarding the translation of preclinical knowledge into clinical progress. Mediat Inflamm 2014:1–9 Zündorf I, Fürst R (2014) Plant-derived anti-inflammatory compounds: Hopes and disappointments regarding the translation of preclinical knowledge into clinical progress. Mediat Inflamm 2014:1–9
Metadaten
Titel
Inhibitory effects of andrographolide on activated macrophages and adjuvant-induced arthritis
verfasst von
Swati Gupta
Kamla Prasad Mishra
Shashi Bala Singh
Lilly Ganju
Publikationsdatum
22.07.2017
Verlag
Springer International Publishing
Erschienen in
Inflammopharmacology / Ausgabe 2/2018
Print ISSN: 0925-4692
Elektronische ISSN: 1568-5608
DOI
https://doi.org/10.1007/s10787-017-0375-7

Weitere Artikel der Ausgabe 2/2018

Inflammopharmacology 2/2018 Zur Ausgabe