Abstract
The present study was aimed to determine the therapeutic effects of Swertia chirayita leaves against oxidative and inflammatory injuries in Freund’s complete adjuvant (FCA) induced arthritic rats. The extract was evaluated for its phytoconstituents and various invitro antioxidant properties followed by its in vivo effects. The hydroethanolic extract of S. chirayita leaves (SCE) was orally administered (200 mg/kg body weight, per day, p.o.) and the effect on the liver lipid peroxidation (LPO), antioxidant status, protein carbonyl formation along with the histopathology of liver were evaluated after induction of adjuvant arthritis. The markers of inflammation and arthritis, such as tumor necrosis factor—α (TNF-α), interleukin 1α (IL-1α), inhibition of paw edema, along with the histological and radiographic changes in the arthritic ankle joint were studied with and without SCE administration. The result showed the presence of major phytoconstituents, such as phenolic, flavonoid and terpenoid content in SCE. HPLC analysis revealed the presence of swertiamarin and amarogentin in high concentration. The extract also showed in vitro antioxidant potential which has positive correlation with the phytoconstituents. The result of in vivo study showed elevated malondialdehyde (MDA) and carbonyl content indicative of LPO and protein oxidation, respectively, with compromised intracellular antioxidant defense system in arthritic rats, which were significantly normalized after SCE treatment. The increase in serum proinflammatory cytokines (TNF- α and IL-1α) and paw edema of arthritic rats was significantly suppressed by SCE. Histology and radiographic analysis of arthritic ankle joints indicated abnormal changes. Marked reduction in inflammation and arthritic changes were observed after treatment with SCE. The present investigation suggests that hydroethanolic extract of S. chirayita leaves exhibit potential immunomodulatory effects, which may possibly be due to boosting the intracellular antioxidant defense.
Similar content being viewed by others
References
Banerjee S, Sur TK, Mandal S, Das PK, Sikdar S (2000) Assessment of anti-inflammatory effects of Swertia chirata in acute and chronic experimental models in male albino rats. Ind J Pharmacol 32:21–24
Berlett BS, Levine RL, Stadtman ER (1998) Carbon dioxide stimulates peroxynitrite-mediated nitration of tyrosine residues and inhibits oxidation of methionine residues of glutamine synthetase: both modifications mimic effects of adenylylation. Proc Nat Acad Sci (USA) 95:2784–2789
Bray TM, Taylor CG (1993) Tissue glutathione, nutrition and oxidative stress. Can J Physiol Pharmacol 71:746–751
Cai Y, Luo Q, Sun M, Corke H (2004) Antioxidant activity and phenolic compounds of 112 traditional Chinese medicinal plants associated with anticancer. Life Sci 74:2157–2184
Caparroz-Assef SM, Bersani-Amado CA, Nascimento EA, Kelmer-Bracht AM, Ishii-Iwamoto EL (1998) Effects of the nonsteroidal anti-inflammatory drug nimesulide on energy metabolism in livers from adjuvant-induced arthritic rats. Res Commun Mol Pathol Pharmacol 99:93–116
Carteron NL (2000) Cytokines in rheumatoid arthritis: trials and tribulations. Mol Med Today 6:315–323
Chapple IL (1997) Reactive oxygen species and antioxidants in inflammatory diseases. J Clin Periodontol 24:287–296
Chou CT (1997) The anti-inflammatory effect of Tripterygium wilfordii Hook F on adjuvant-induced paw edema in rats and inflammatory mediators release. Phytother Res 11:152–154
Comar JF, Nakanishi AB, de Oliveira AL, Wendt MMN, Amado CAB, Iwamoto ELI, Peralta RM, Bracht AA (2013) Oxidative state of the liver of rats with adjuvant-induced arthritis. Free Radic Biol Med 58:144–153
Das SC, Bhadra S, Roy S, Saha SK, Md Islam S, Bachar SC (2012) Analgesic and anti-inflammatory activities of ethanolic root extract of Swertia chirata (Gentianaceae). Jordan J Biol Sci 5:31–36
Droge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82:47–95
Dutta AK, Gope PS, Makhnoon S, Md Rahman S, Siddiquee MA, Kabir Y (2012) Effect of Solvent extraction on Phenolic content, Antioxidant and α-Amylase Inhibition activities of Swertia chirata. Int J Drug Dev Res 4:317–325
Ekambaram S, Perumal SS, Subramanian V (2010) Evaluation of antiarthritic activity of Strychnos potatoum Linn seeds in Freund’s adjuvant induced arthritic rat model. Complement Altern Med 10:56
Esterbauer H, Schaur RJ, Zollner H (1991) Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 11:81–128
Fedatto Z Jr, Ishiii-Iwamoto EL, Amado CB, Vicentini G, D’urso-Panerari A, Bracht A, Kelmer-Bracht AM (1999) Gluconeogenesis in the liver of arthritic rats. Cell Biochem Funct 17:271–278
Filippin LI, Vercelino R, Marroni NP, Xavier RM (2008) Redox signaling and the inflammatory response in rheumatoid arthritis. Clin Exp Immunol 152:415–422
Findlay DM, Haynes DR (2005) Mechanisms of bone loss in rheumatoid arthritis. Mod Rheumatol 15:232–240
Hayes ID, Pulford DJ (1995) The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol 30:445–600
Hitchon CA, El-Gabalawy HS (2004) Oxidation in rheumatoid arthritis. Arthritis Res Ther 6:265–278
Huang D, Ou B, Prior RL (2005) The chemistry behind antioxidant capacity assays. J Agric Food Chem 53:1841–1856
Issekutz AC, Meager A, Otternesst I, Issekutz TB (1994) The role of tumor necrosis factor-alpha and IL-1 in polymorphonuclear leucocyte and T lymphocyte recruitment to joint inflammation in adjuvant arthritis. Clin Exp Immunol 97:26–32
Karan M, Vashisht K, Handa SS (1999) Anti-hepatotoxic activity of Swertia chirata on carbon tetrachloride induced hepatotoxicity in rats. Phytother Res 13:24–30
Keisari Y, Braun L, Flescher E (1983) The oxidative burst and related phenomena in mouse macrophages elicited by different sterile inflammatory stimuli. Immunobiology 165:78–89
Kinne RW, Brauer R, Stuhlmuller B, Kinne EP, Burmester GR (2000) Macrophages in rheumatoid arthritis. Arthritis Res 2:189–202
Kitamura T, Hashimoto J, Murase T, Tomita T, Hattori T, Yashikawa H, Sugamoto K (2007) Radiographic study of joint destruction patterns in rheumatoid elbow. Clin Rheumatol 26:515–519
Kono Y, Fridovich I (1982) Superoxide radical inhibits catalase. J Biol Chem 257:5751–5754
Kumar RV, Kumar S, Shashidhara S, Anitha S, Manjula M (2011) Comparison of the antioxidant capacity of an important hepatoprotective plants. Int J Pharm Sci Drug Res 3:48–51
Lad H, Dixit D, Joshi A, Bhatnagar D (2015) Antioxidant and antiinflammatory effects of Vitex negundo on Freund’s complete adjuvant induced arthritis. Int J Pharm Pharm Sci 7:81–85
Lad H, Joshi A, Dixit D, Sharma H, Bhatnagar D (2016) Antioxidant, genoprotective and immunomodulatory potential of Vitex negundo leaves in experimental arthritis. Orient Pharm Exp Med 16:217–224. doi:10.1007/s13596-016-0234-x
Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG, Ahn BW, Shaltiel S, Stadtman ER (1990) Determination of carbonyl content in modified proteins. Method Enzymol 186:464–478
Makinen H, Kautiainen H, Hannonen P, Mottonen T, Leirisalo- Repo M, Laasonen L, Korpela M, Blafield H, Hakola M, Sokka T (2007) Sustained remission and reduced radiographic progression with combination disease modifying anti-rheumatic drugs in early rheumatoid arthritis. J Rheumatol 34:316–321
Mindrescu C, Thorbecke GJ, Klein MJ, Vilcek J, Wisniewski HG (2000) Amelioration of collagen-induced arthritis in DBA/1 J mice by recombinant TSG-6, a tumor necrosis factor/interleukin-1-inducible protein. Arthritis Rheum 43:2668–2677
Moynagh PN (2005) The NF-kappa B pathway. J Cell Sci 118:4589–4592
Mulherin D (1996) Synovial tissue macrophage populations and articular damage in rheumatoid arthritis. Arthritis Rheum 39:115–124
Nagalekshmi R, Aditya MA, Chandrasekharan DK, Nair CKK (2011) Hepatoprotective activity of Andrographis paniculata and Swertia chirayita. Food Chem Toxicol 49:3367–3373
Negi JS, Singh P, Rawat B (2011) Chemical constituents and biological importance of Swertia: a review. Curr Res Chem 3:1–15
Obiri DD, Osafo N, Ayande PG, Antwi AO (2014) Xylopia aethiopica (Annonaceae) fruit extract suppresses Freund’s adjuvant-induced arthritis in Sprague-Dawley rats. J Ethnopharmacol 152:522–5231
Ozturk HS, Cimen MY, Cimen OB, Kacmaz M, Durak I (1999) Oxidant/antioxidant status of plasma samples from patients with rheumatoid arthritis. Rheumatol Int 19:35–37
Phoboo S, Pinto MS, Bhowmik PC, Jha PK, Shetty K (2010) Quantification of major phytochemicals of Swertia chirayita, a medicinal plant from nepal. Ecoprint 17:59–68
Ratheesh M, Shyni GL, Helen A (2009) Methanolic extract of Ruta graveolens L inhibits inflammation and oxidative stress in adjuvant induced model of arthritis in rats. Inflammopharmacology 17:100–105
Saha P, Mandal S, Das A, Das PC, Das S (2004) Evaluation of anti-carcinogenic activity of Swertia chirata Buch. Ham, an Indian medicinal plant on DMBA-induced mouse skin carcinogenesis model. Phytother Res 18:373–378
Salvemini D, Mazzon E, Dugo L, Serraino I, De SA, Caputi AP, Cuzzocrea S (2001) Amelioration of joint disease in a rat model of collagen-induced arthritis by M40403, a superoxide dismutase mimetic. Arthritis Rheum 44:2909–2921
Saravanan S, Islam VI, Thirugnanasambantham K, Pazhanivel N, Raghuraman N, Paulraj MG, Ignacimuthu S (2014a) Swertiamarin ameliorates inflammation and osteoclastogenesis intermediates in IL-1β induced rat fibroblast-like synoviocytes. Inflamm Res 63:451–462
Saravanan S, Islam VI, Babu NP, Pandikumar P, Thirugnanasambantham K, Chellappandian M, Raj CS, Paulraj MG, Ignacimuthu S (2014b) Swertiamarin attenuates inflammation mediators via modulating NF-κB/I κB and JAK2/STAT3 transcription factors in adjuvant induced arthritis. Eur J Pharm Sci 2:70–86. doi:10.1016/j.ejps.2014
Scott D, Wolfe F, Huizinga TWJ (2010) Rheumatoid arthritis. Lancet 376:1094–1108
Sharma S, Sahu D, Das HR, Sharma D (2011) Amelioration of collagen-induced arthritis by Salix nigra bark extract via suppression of pro-inflammatory cytokines and oxidative stress. Food Chem Toxicol 49:3395–3406
Summ O, Evers S (2013) Mechanism of action of indomethacin in indomethacin-responsive headaches. Curr Pain Headache Rep 17:327
Taysi S, Polat F, Gul M, Sari RA, Bakan E (2002) Lipid peroxidation, some extracellular antioxidants, and antioxidant enzymes in serum of patients with rheumatoid arthritis. Rheumatol Int 21:200–204
Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39:44–84
Venkatesha SH, Berman BM, Moudgil KD (2011) Herbal medicinal products target defined biochemical and molecular mediators of inflammatory autoimmune arthritis. Bioorg Med Chem 19:21–29
Verma VK, Sarwa KK, Kumar A, Md Zaman K (2013) Comparison of hepatoprotective activity of Swertia chirayita and Andrographis paniculata plant of North East India against CCl4 induced hepatotoxic rats. J Pharm Res 7:647–653
Warren JS (1990) Interleukins and tumor necrosis factor in inflammation. Crit Rev Clin Lab Sci 28:37–59
Yadav AS, Bhatnagar D (2007) Chemo-preventive effect of Star anise in N-nitrosodiethylamine initiated and phenobarbital promoted hepato-carcinogenesis. Chem Biol Interact 169:207–214
Yingyu M, Pope RM (2005) The role of macrophages in rheumatoid arthritis. Curr Pharm Des 11:569–580
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that there are no conflicts of interest.
Rights and permissions
About this article
Cite this article
Lad, H., Bhatnagar, D. Amelioration of oxidative and inflammatory changes by Swertia chirayita leaves in experimental arthritis. Inflammopharmacol 24, 363–375 (2016). https://doi.org/10.1007/s10787-016-0290-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10787-016-0290-3