Planta Med 2016; 82(16): 1403-1409
DOI: 10.1055/s-0042-106304
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Anti-inflammatory Effect of Picrorhiza kurroa in Experimental Models of Inflammation

Rohit Kumar
1   Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), New Delhi, India
,
Yogendra Kumar Gupta
1   Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), New Delhi, India
,
Surender Singh
1   Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), New Delhi, India
,
Arun Raj
2   Research officer, Natural Remedies Pvt. Ltd., Bangalore, India
› Author Affiliations
Further Information

Publication History

received 01 April 2015
revised 22 March 2016

accepted 30 March 2016

Publication Date:
10 May 2016 (online)

Abstract

Picrorhiza kurroa is an important medicinal plant in the Ayurvedic system of medicine. The root and rhizome of this plant are used for the treatment of various liver and inflammatory conditions. In the present study, we sought to investigate the anti-inflammatory activity of P. kurroa rhizome extract against carrageenan-induced paw edema and cotton pellet implantation-induced granuloma formation in rats. In addition, its immunomodulatory activity was evaluated in Complete Freundʼs Adjuvant-induced stimulation of a peritoneal macrophage model and lipopolysaccharide-stimulated RAW 264.7 murine macrophages. Pretreatment with P. kurroa rhizome extract inhibited carrageenan-induced paw edema and cotton pellet-induced granuloma formation in a dose-dependent manner. This was associated with reduced levels of inflammatory cytokines (TNF-α, IL-1β, IL-6) accompanied with increased anti-inflammatory cytokine (IL-10) in the serum and peritoneal macrophages. Additionally, P. kurroa rhizome extract inhibited inflammatory TNF-receptor 1 and cyclooxygenase-2 in Complete Freundʼs Adjuvant-induced activated peritoneal macrophages. Furthermore, P. kurroa rhizome extract treatment significantly inhibited iNOS and suppressed the activation of NF-κB through inhibition of its phosphorylation and by blocking the activation of IκB kinase alpha in lipopolysaccharide-stimulated RAW264.7 macrophages. Taken together, these results suggest that P. kurroa has anti-inflammatory activity that is mediated through the suppression of macrophage-derived cytokine and mediators via suppression of NF-κB signaling.

 
  • References

  • 1 Laskin DL, Sunil VR, Gardner CR, Laskin JD. Macrophages and tissue injury: agents of defence or destruction?. Annu Rev Pharmacol Toxicol 2011; 51: 267-288
  • 2 Kinne RW, Stuhlmüller B, Burmester GR. Cells of the synovium in rheumatoid arthritis. Macrophages. Arthritis Res Ther 2007; 9: 224-240
  • 3 Ulfgren AK, Lindblad S, Klareskog S, Anderson J, Anderson U. Detection of cytokine producing cells in the synovial membrane from patients with rheumatoid arthritis. Ann Rheum Dis 1995; 54: 654-661
  • 4 Kang RY, Freire-Moar J, Sigal E, Chu CQ. Expression of cyclooxygenase-2 in human and an animal model of rheumatoid arthritis. Br J Rheumatol 1996; 35: 711-718
  • 5 Kumar R, Gupta YK, Singh S, Arunraja S. Picrorhiza kurroa inhibits experimental arthritis through inhibition of pro-inflammatory cytokines, angiogenesis and MMPs. Phytother Res 2016; 30: 112-119
  • 6 Umar S, Umar K, Hasnath A, Sarwar G, Khan A, Ahmad N, Ahmad S, Katiyar CK, Husain SA, Khan HA. Boswellia serrata extract attenuates inflammatory mediators and oxidative stress in collagen induced arthritis. Phytomedicine 2014; 21: 847-856
  • 7 Efthimiou P, Kukar M. Complementary and alternative medicine use in rheumatoid arthritis: proposed mechanism of action and efficacy of commonly used modalities. Rheumatol Int 2010; 30: 571-586
  • 8 Atal CK, Sharma ML, Kaul A, Khajuria A. Immunomodulating agents of plant origin. I: Preliminary screening. J Ethnopharmacol 1986; 18: 133-141
  • 9 Subedi BP. Plant profile: Kutki (Picrorhiza scrophulariiflora). Himalayan Bioresources 2000; 4: 14-15
  • 10 Singh GB, Bani S, Singh S, Khajuria A, Sharma ML, Gupta BD, Banerjee SK. Anti inflammatory activity of the iridoids kutkin, picroside-1 and kutkoside from Picrorhiza kurroa . Phytother Res 1993; 7: 402-407
  • 11 Langer JG, Gupta OP, Atal CK. Clinical trials on Picrorhiza kurroa . Ind J Pharmacol 1981; 13: 98-103
  • 12 Vinger R, Truax JF, Selph JL, Johnston PR, Venable AL, McKenzie KK. Pathway to carrageenan-induced inflammation in the hind limb of the rat. Fed Proc 1987; 46: 118-126
  • 13 Nair V, Kumar R, Singh S, Gupta YK. Investigation into the anti-inflammatory and antigranuloma activity of Colchicum luteum Baker in experimental models. Inflammation 2012; 35: 881-888
  • 14 Meier R, Schuler W, Desaulles P. Zur Frage des Mechanismus der Hemmung des Bindegewebswachstums durch Cortisone. Experientia 1950; 6: 469-471
  • 15 Swingle KF, Shideman FE. Phases of the inflammatory response to subcutaneous implantation of a cotton pellet and their modification by certain anti inflammatory agents. J Pharmacol Exp Ther 1972; 183: 1226-1234
  • 16 Mosser DM. The many faces of macrophage activation. J Leukoc Biol 2003; 73: 209-212
  • 17 Brennan FM, McInnes IB. Evidence that cytokines play a role in rheumatoid arthritis. J Clin Invest 2008; 118: 3537-3545
  • 18 Shibata H, Yoshioka Y, Abe Y, Ohkawa A, Nomura T, Minowa K. The treatment of established murine collagen-induced arthritis with a TNFR1-selective antagonistic mutant TNF. Biomaterials 2009; 30: 6638-6647
  • 19 Kinne RW, Bräuer R, Stuhlmüller B, Palombo-Kinne E, Burmester GR. Macrophages in rheumatoid arthritis. Arthritis Res 2000; 2: 189-202
  • 20 Giroux M, Descoteaux A. Cyclooxygenase-2 expression in macrophages: modulation by protein kinase C-α . J Immunol 2000; 165: 3985-3991
  • 21 Sacerdote P, Carrabba M, Galante A, Pisati R, Manfredi B, Panerai AE. Plasma and synovial fluid interleukin-1, interleukin-6 and substance P concentrations in rheumatoid arthritis patients: effect of the nonsteroidal anti inflammatory drugs indomethacin, diclofenac and naproxen. Inflamm Res 1995; 44: 486-490
  • 22 Yang Z, Nandi J, Wang J, Bosco G, Gregory M, Chung C, Xie Y, Yang X, Camporesi EM. Hyperbaric oxygenation ameliorates indomethacin induced enteropathy in rats by modulating TNF-α and IL-1β production. Dig Dis Sci 2006; 51: 1426-1433
  • 23 Albina JE, Cui S, Mateo RB, Reichner JS. Nitric oxide-mediated apoptosis in murine peritoneal macrophages. J Immunol 1993; 150: 5080-5085
  • 24 Sarih M, Souvannavong V, Adam A. Nitric oxide synthase induces macrophage death by apoptosis. Biochem Biophys Res Commun 1993; 191: 503-508
  • 25 Lorsbach RB, Murphy WJ, Lowenstein CJ, Snyder SH, Russell SW. Expression of the nitric oxide synthase gene in mouse macrophages activated for tumor cell killing. Molecular basis for the synergy between interferon-gamma and lipopolysaccharide. J Biol Chem 1993; 25: 1908-1913
  • 26 Kumar KJS, Li J, Vani MG, Hsieh YH, Kuo YH, Wang SY. Bornyl cinnamate inhibits inflammation-associated gene expression in macrophage cells through suppression of nuclear factor-κB signaling pathway. Planta Med 2015; 81: 39-45
  • 27 Tak PP, Firestein GS. NF-kappaB: a key role in inflammatory diseases. J Clin Invest 2001; 107: 7-11
  • 28 Hambleton J, Weinstein SL, Lem L, DeFranco AL. Activation of c-Jun N terminal kinase in bacterial lipopolysaccharide-stimulated macrophages. Proc Natl Acad Sci USA 1996; 93: 2774-2778
  • 29 Zhang Y, DeWitt DL, Murugesan S, Nair MG. Cyclooxygenase-2 enzyme inhibitory triterpenoids from Picrorhiza kurroa seeds. Life Sci 2005; 77: 3222-3230
  • 30 Guo Y, Xu X, Li Q, Li Z, Du F. Anti-inflammation effects of Picroside 2 in cerebral ischemic injury rats. Behav Brain Funct 2010; 6: 43-50
  • 31 Singh N, Gupta AP, Singh B, Kaul VK. Quantification of Picroside-I and Picroside-II in Picrorhiza kurroa by HPTLC. J Liq Chromatogr Relat Technol 2005; 28: 1679-1691
  • 32 U.S. Pharmacopeial Convention (Herbal Medicines Compendium). Picrorhiza kurroa root and rhizome dry extract. Available at. https://hmc.usp.org/monographs/picrorhiza-kurrooa-root-and-rhizome-dry-extract-0-2 Accessed February 24, 2015
  • 33 Kumar R, Nair V, Gupta YK, Singh S. Anti-inflammatory and anti-arthritic activity of aqueous extract of Rosa centifolia in experimental models in rats. Int J Rheum Dis DOI: 10.1111/1756-185X.12625. advance online publication 27.07.2015;
  • 34 Kumar R, Gupta YK, Singh S. Anti-inflammatory and anti-granuloma activity of Berberis aristata DC. In experimental models of inflammation. Indian J Pharmacol 2016; 48: 155-161
  • 35 Nair V, Kumar R, Singh S, Gupta YK. Anti-granuloma activity of Terminalia chebula retz. in Wistar rats. Eur J Inflamm 2012; 10: 185-191
  • 36 Billiau A, Matthys P. Modes of action of Freundʼs adjuvants in experimental models of autoimmune diseases. J Leukoc Biol 2001; 70: 849-860
  • 37 Kumar R, Gupta YK, Singh S, Arunraja S. Cissus quadrangularis attenuates the adjuvant induced arthritis by down regulating pro-inflammatory cytokine and inhibiting angiogenesis. J Ethnopharmacol 2015; 175: 346-355
  • 38 Griet M, Zelaya H, Mateos MV, Salva S, Juarez GE, de Valdez GF, Villena J, Salvador GA, Rodriguez AV. Soluble factors from Lactobacillus reuteri CRL1098 have anti-inflammatory effects in acute lung injury induced by lipopolysaccharide in Mice. PLoS One 2014; 9: e110027