Abstract
The present study aimed to investigate the potential anti-inflammatory and anti-nociceptive activities of glycyrrhizin (GL) in mice and to explore the possible related mechanisms. Xylene-induced ear edema, carrageenan-induced paw edema and acetic acid-induced vascular permeability test were used to investigate the anti-inflammatory activities of GL in mice. Anti-nociceptive effects of GL were assessed by using acetic acid-induced writhing, hot plate test and formalin test, as well as evaluation of spontaneous locomotor activity and motor performance. The mRNA expression of pro-inflammatory cytokines (such as TNF-α, IL-6 and iNOS) and the protein expression of cyclooxygenase-2 (COX-2) were explored by using real-time fluorogenic PCR and Western blot, respectively. The results showed that GL significantly reduced xylene-induced ear edema, carrageenan-induced paw edema, and acetic acid-induced vascular permeation. Additionally, GL significantly inhibited the nociceptions induced by acetic acid and formalin. However, the nociceptions could not be decreased by GL in the hot plate test, and GL did not affect spontaneous locomotor activity and motor performance. The expression levels of TNF-α, IL-6, iNOS and COX-2 were significantly downregulated by GL. In conclusion, GL exerts significant anti-inflammatory and analgesic activities by attenuating the expression levels of TNF-α, IL-6, iNOS and COX-2.
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References
Julius, D., and A.I. Basbaum. 2001. Molecular mechanisms of nociception. Nature 413: 203–210.
Chiu, Y.J., T.H. Huang, C.S. Chiu, T.C. Lu, and W.H. Peng. 2012. Analgesic and anti-inflammatory activities of the aqueous extract from Plectranthus amboinicus (Lour.) Spreng. Both in vitro and in vivo. Evidence-Based Complementary and Alternative Medicine 2012: 508137.
Huang, G.J., B.S. Wang, W.C. Lin, S.S. Huang, and C.Y. Lee. 2012. Antioxidant and anti-inflammatory properties of Longan (Dimocarpus longan Lour.) Pericarp. Evidence-Based Complementary and Alternative Medicine 2012: 709483.
Bogdan, C. 2001. Nitric oxide and the immune response. Nature Immunology 2: 907–916.
Niu, X., H. Zhang, W. Li, Q. Mu, H. Yao, and Y. Wang. 2015. Anti-inflammatory effects of cavidine in vitro and in vivo, a selective COX-2 inhibitor in LPS-induced peritoneal macrophages of mouse. Inflammation 38(2): 923–933.
Utsunomiya, T., M. Kobayashi, R.B. Pollard, and F. Suzuki. 1997. Glycyrrhizin, an active component of licorice roots, reduces morbidity and mortality of mice infected with lethal dose of influenza virus. Antimicrobial Agents and Chemotherapy 41: 551–556.
Okamoto, T. 2000. The protective effect of glycyrrhizin on anti-Fas antibody-induced hepatitis in mice. European Journal of Pharmacology 387: 229–232.
Ohuchi, K., Y. Kamada, S. Tsurufuji, and S. Tsurufuji. 1981. Glycyrrhizin inhibits prostaglandin E2 production by activated peritoneal macrophages from rats. Prostaglandins and Medicine 7: 457–463.
Van Rossum, T.G., A.G. Vulto, W.C. Hop, and S.W. Schalm. 2001. Glycyrrhizin-induced reduction of ALT in European patients with chronic hepatitis C. American Journal of Gastroenterology 96: 2432–2437.
He, X.Y., Q.C. Liu, W. Peng, Y.L. Huang, Y.L. Huang, and C.J. Wu. 2013. Bioactivities and serum pharmacochemistry of Qi-Wei-Xiao-Yan-Tang. Pharmaceutical Biology 51: 629–634.
Li, C.Q., L.C. He, H.Y. Dong, and J.Q. Jin. 2007. Screening for the anti-inflammatory activity of fractions and compounds from Atractylodes macrocephala koidz. Journal of Ethnopharmacology 114: 212–217.
Wang, J.P., Y.M. Zhou, Y.J. Ye, X.M. Shang, and Y.L. Cai. 2011. Topical anti-inflammatory and analgesic activity of kirenol isolated from Siegesbeckia orientalis. Journal of Ethnopharmacology 137: 1089–1094.
Wang, Q.S., L. Yang, W.Y. Cui, L. Chen, and Y.H. Jiang. 2014. Anti-Inflammatory and anti-nociceptive activities of methanol extract from aerial part of Phlomis younghusbandii Mukerjee. Plos One 9(3), e89149.
Li, M.X., X.F. Shang, Z.P. Jia, and R.X. Zhang. 2010. Phytochemical and biological studies of plants from the genus Phlomis. Chemistry & Biodiversity 7: 283–301.
Ribeiro, N.A., T.M. Abreu, H.V. Chaves, M.M. Bezerra, H.S. Monteiro, and R.J. Jorge. 2014. Sulfated polysaccharides isolated from the green seaweed Caulerpa racemosa plays antinociceptive and anti-inflammatory activities in a way dependent on HO-1 pathway activation. Inflammation Research 63: 569–580.
Carballo-Villalobos, A.I., M.E. González-Trujano, and F.J. López-Muñoz. 2014. Evidence of mechanism of action of anti-inflammatory/antinociceptive activities of acacetin. European Journal of Pain 18: 396–405.
Khatun, A., M.Z. Imam, and M.S. Rana. 2015. Antinociceptive effect of methanol extract of leaves of Persicaria hydropiper in mice. BMC Complementary and Alternative Medicine 15: 63–71.
Chen, Y.F., Y. Haung, W.Z. Tang, L.P. Qin, and H.C. Zheng. 2009. Antinociceptive activity of Paederosidic Acid Methyl Ester (PAME) from the n-butanol fraction of Paederia scandens in mice. Pharmacology Biochemistry and Behavior 93: 97–104.
Wang, H.Y., Y.X. Li, L.L. Dun, and T.T. Xu. 2013. Antinociceptive effects of matrine on neuropathic pain induced by chronic constriction injury. Pharmaceutical Biology 7: 844–850.
Soares, D.G., A.M. Godin, R.R. Menezes, R.D. Nogueira, and A.M. Brito. 2014. Anti-inflammatory and antinociceptive activities of Azadirachtin in mice. Planta Medica 80: 630–636.
de Oliveira, A.M., A.F. de Araújo, R.P. Lyra Lemos, L.M. Conserva, J.N. de Souza Ferro, and E. Barreto. 2015. Antinociceptive and anti-inflammatory activity of the siaresinolic acid, a triterpene isolated from the leaves of Sabicea grisea Cham. & Schltdl. var. grisea. Journal of Natural Medicines 69: 232–240.
Fang, J.Q., J.Y. Du, Y. Liang, and J.F. Fang. 2013. Intervention of electroacupuncture on spinal p38 MAPK/ATF-2/VR-1 pathway in treating inflammatory pain induced by CFA in rats. Molecular Pain 9: 1–14.
da Silva, K.A., M.N. Manjavachi, A.F. Paszcuk, M. Pivatto, and C. Viegas Jr. 2012. Plant derived alkaloid (-)-cassine induces anti-inflammatory and anti-hyperalgesics effects in both acute and chronic inflammatory and neuropathic pain models. Neuropharmacology 62: 967–977.
Khor, Y.H., A.K. Teoh, S.M. Lam, D.C. Mo, and S. Weston. 2009. Increased vascular permeability precedes cellular inflammation as asthma control deteriorates. Clinical and Experimental Allergy 39: 1659–1667.
Wilhelm, D.L., and B. Mason. 1960. Vascular permeability changes in inflammation: the role of endogenous permeability factors in mild thermal injury. British Journal of Experimental Pathology 41: 487–506.
Chang, T.N., J.S. Deng, Y.C. Chang, C.Y. Lee, and L. Jung-Chun. 2012. Ameliorative effects of Scopoletin from Crossostephium chinensis against inflammation pain and its mechanisms in mice. Evidence-Based Complementary and Alternative Medicine 2012: 595603.
Vinegar, R., W. Schreiber, and R. Hugo. 1969. Biphasic development of carrageenan oedema in rats. Journal of Pharmacology and Experimental Therapeutics 166: 96–103.
Niu, X., Y. Li, W. Li, H. Hu, H. Yao, and H. Li. 2014. The anti-inflammatory effects of Caragana tangutica ethyl acetate extract. Journal of Ethnopharmacology 152: 99–105.
Ishola, I.O., E.O. Agbaje, O.O. Adeyemi, and R. Shukla. 2014. Analgesic and anti-inflammatory effects of the methanol root extracts of some selected Nigerian medicinal plants. Pharmaceutical Biology 52: 1208–1216.
Cunha, T.M., G.R. Souza, A.C. Domingues, E.U. Carreira, and C.M. Lotufo. 2012. Stimulation of peripheral Kappa opioid receptors inhibits inflammatory hyperalgesia via activation of the PI3Kγ/AKT/nNOS/NO signaling pathway. Molecular Pain 8: 1–10.
Wang, J., X.W. Wang, Y. Zhang, C.P. Yin, and S.W. Yue. 2011. Nuclear factor-κB mediates TRPV4-NO pathway involved in thermal hyperalgesia following chronic compression of the dorsal root ganglion in rats. Behavioural Brain Research 221: 19–24.
Xu, Y.Q., S.J. Jin, N. Liu, Y.X. Li, and J. Zheng. 2014. Aloperine attenuated neuropathic pain induced by chronic constriction injury via anti-oxidation activity and suppression of the nuclear factor kappa B pathway. Biochemical and Biophysical Research Communications 451: 568–573.
Erchler, W.B., and E.T. Keller. 2000. Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty. Annual Review of Medicine 51: 245–270.
Khan, S., O. Shehzad, J. Chun, and Y.S. Kim. 2013. Mechanism underlying anti-hyperalgesic and anti-allodynic properties of anomalin in both acute and chronic inflammatory pain models in mice through inhibition of NF-κB, MAPKs and CREB signaling cascades. European Journal of Pharmacology 718: 448–458.
Smith, W.L., D.L. DeWitt, and R.M. Garavito. 2000. Cyclooxygenases: structural, cellular and molecular biology. Annual Review of Biochemistry 69: 145–182.
Collier, H.O.J., L.C. Dinneen, C.A. Johnson, and C. Schneider. 1968. The abdominal constriction response and its suppression by analgesic drugs in the mouse. British Journal of Pharmacology 32: 295–310.
Damasceno, S.R., F.R. Oliveira, N.S. Carvalho, C.F. Brito, and I.S. Silva. 2014. Carvacryl acetate, a derivative of carvacrol, reduces nociceptive and inflammatory response in mice. Life Sciences 94: 58–66.
Afsar, T., M.R. Khan, S. Razak, S. Ullah, and B. Mirza. 2015. Antipyretic, anti-inflammatory and analgesic activity of Acacia hydaspica R. Parker and its phytochemical analysis. BMC Complementary and Alternative Medicine 15: 136–148.
Xu, Q., Y. Wang, S. Guo, Z. Shen, Y. Wang, and L. Yang. 2014. Anti-inflammatory and analgesic activity of aqueous extract of Flos populi. Journal of Ethnopharmacology 152: 540–545.
Devaraj, S., A.S. Esfahani, S. Ismail, S. Ramanathan, and M.F. Yam. 2010. Evaluation of the anti-nociceptive activity and acute oral toxicity of standardized ethanolic extract of the rhizome of Curcuma xanthorrhiza Roxb. Molecules 15: 2925–2934.
Sani, M.H., Z.A. Zakaria, T. Balan, L.K. Teh, and M.Z. Salleh. 2012. Antinociceptive activity of methanol extract of Muntingia calabura leaves and the mechanisms of action involved. Evidence-Based Complementary and Alternative Medicine 2012: 89361.
Tsai, D.S., M.H. Huang, J.C. Tsai, Y.S. Chang, and Y.J. Chiu. 2015. Analgesic and anti-inflammatory activities of Rosa taiwanensis nakai in mice. Journal of Medicinal Food 18: 592–600.
Acknowledgments
This research was supported by Natural Science Foundation of Ningxia (Grant No. Nz13227). We thank Dr. Margaret for editing our manuscript.
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The authors declare that they have no competing interests.
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Hong-Ling Wang and Yu-Xiang Li contributed equally to this work.
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Wang, HL., Li, YX., Niu, YT. et al. Observing Anti-inflammatory and Anti-nociceptive Activities of Glycyrrhizin Through Regulating COX-2 and Pro-inflammatory Cytokines Expressions in Mice. Inflammation 38, 2269–2278 (2015). https://doi.org/10.1007/s10753-015-0212-3
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DOI: https://doi.org/10.1007/s10753-015-0212-3