Effects of Tripterygium glycoside treatment on experimental autoimmune encephalomyelitis

Qiu,Jianmin; You,Xuelian; Wu,Gang

doi:10.3892/mmr.2017.7627

Effects of Tripterygium glycoside treatment on experimental autoimmune encephalomyelitis

Authors:
- Jianmin Qiu
- Xuelian You
- Gang Wu
View Affiliations

Affiliations: Department of Internal Medicine Neurology, Fujian Putian First Hospital, Putian, Fujian 351100, P.R. China, Department of Internal Medicine Neurology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350004, P.R. China
Published online on: September 26, 2017 https://doi.org/10.3892/mmr.2017.7627
Pages: 8283-8288

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease mediated by CD4+ T cells. It is characterized by mononuclear cell infiltration around the small blood vessels in the central nervous system (CNS). Previous investigations have found that apoptosis is associated with the occurrence and development of autoimmune disease, and that mononuclear cell apoptosis and clearance from the CNS is one of the repair mechanisms of EAE. Tripterygium wilfordii glycoside (TWP) is an organic matter isolated from Tripterygium wilfordii, which has anti‑inflammatory and immunosuppressive effects. In the present study, male Lewis rats were randomly divided into a normal control, EAE and TWP groups. Rats in EAE and TWP groups received injections of emulsified EAE antigen (myelin protein) at two points on the footpad while control group received PBS. The TWP group was then treated with TWP daily for 21 days. Symptoms and nerve function scores were observed and evaluated. Specimens of blood, brain and spinal cord were collected for further pathological examination, Tunel assay, ELISA and immunohistochemistry were performed to examine the effect of TWP on the onset of EAE, and changes in CNS inflammatory infiltration, cell apoptosis, and the expression of nuclear factor (NF)‑κB P65 and interleukin (IL)‑2. The results showed that the TWP treatment group exhibited decreased EAE and delayed onset, compared with the control. The clinical symptoms were significantly reduced and alleviation of inflammatory cell infiltration was observed. Compared with the EAE group, a higher inflammatory cell apoptotic rate, and reduced serum levels of IL‑2 and NF‑κB p65‑positive cells were observed in the TWP treatment group. Therefore, TWP effectively inhibited EAE via the inhibition of CNS inflammatory cell infiltration, enhancement of inflammatory cell apoptosis, and downregulation of the expression of NF‑κB and IL‑2.

View Figures

View References

1	Diab A, Deng C, Smith JD, Hussain RZ, Phanavanh B, Lovett-Racke AE, Drew PD and Racke MK: Peroxisome proliferator-activated receptor-gamma agonist 15-deoxy-Delta(12,14)-prostaglandin J(2) ameliorates experimental autoimmune encephalomyelitis. J Immunol. 168:2508–2515. 2002. View Article : Google Scholar : PubMed/NCBI
2	Magnus T, Chan A, Linker RA, Toyka KV and Gold R: Astrocytes are less efficient in the removal of apoptotic lymphocytes than microglia cells: Implications for the role of glial cells in the inflamed central nervous system. J Neuropathol Exp Neurol. 61:760–766. 2002. View Article : Google Scholar : PubMed/NCBI
3	Hao L, Pan MS, Zheng Y and Wang RF: Effect of cordyceps sinensis and Tripterygium wilfordii polyglycosidium on podocytes in rats with diabetic nephropathy. Exp Ther Med. 7:1465–1470. 2014.PubMed/NCBI
4	Zhu J, Cui K, Kou J, Wang S, Xu Y, Ding Z, Han R and Qin Z: Naja naja atra venom protects against manifestations of systemic lupus erythematosus in MRL/lpr mice. Evid Based Complement Alternat Med. 2014:9694822014. View Article : Google Scholar : PubMed/NCBI
5	Ho LJ, Chang DM, Chang ML, Kuo SY and Lai JH: Mechanism of immunosuppression of the antirheumatic herb TWHf in human T cells. J Rheumatol. 26:14–24. 1999.PubMed/NCBI
6	Seger J, Zorzella-Pezavento SF, Pelizon AC, Martins DR, Domingues A and Sartori A: Decreased production of TNF-alpha by lymph node cells indicates experimental autoimmune encephalomyelitis remission in Lewis rats. Mem Inst Oswaldo Cruz. 105:263–268. 2010. View Article : Google Scholar : PubMed/NCBI
7	Steen K, Narang P and Lippmann S: Electroconvulsive therapy in multiple sclerosis. Innov Clin Neurosci. 12:28–30. 2015.PubMed/NCBI
8	Halmer R, Davies L, Liu Y, Fassbender K and Walter S: The innate immune receptor CD14 mediates lymphocyte migration in EAE. Cell Physiol Biochem. 37:269–275. 2015. View Article : Google Scholar : PubMed/NCBI
9	Fisher JD, Acharya AP and Little SR: Micro and nanoparticle drug delivery systems for preventing allotransplant rejection. Clin Immunol. 160:24–35. 2015. View Article : Google Scholar : PubMed/NCBI
10	Kodela R, Nath N, Chattopadhyay M, Nesbitt DE, Velázquez-Martinez CA and Kashfi K: Hydrogen sulfide-releasing naproxen suppresses colon cancer cell growth and inhibits NF-κB signaling. Drug Des Devel Ther. 9:4873–4882. 2015.PubMed/NCBI
11	Nakajima S, Chi Y, Gao K, Kono K and Yao J: eIF2α-independent inhibition of TNF-α-triggered NF-κB activation by salubrinal. Biol Pharm Bull. 38:1368–1374. 2015. View Article : Google Scholar : PubMed/NCBI
12	Ni L, Zhou X, Ma J, Zhang XM, Li CJ, Li L, Yang DJ, Shao YY, Zhou SB, Zhang TT and Zhang DM: Wilfordonols A-D: Four new norsesquiterpenes from the leaves of Tripterygium wilfordii. J Asian Nat Prod Res. 17:615–624. 2015. View Article : Google Scholar : PubMed/NCBI
13	Schmied M, Breitschopf H, Gold R, Zischler H, Rothe G, Wekerle H and Lassmann H: Apoptosis of T lymphocytes in experimental autoimmune encephalomyelitis. Evidence for programmed cell death as a mechanism to control inflammation in the brain. Am J Pathol. 143:446–452. 1993.
14	Lai JH, Ho LJ, Lu KC, Chang DM, Shaio MF and Han SH: Western and Chinese antirheumatic drug-induced T cell apoptotic DNA damage uses different caspase cascades and is independent of Fas/Fas ligand interaction. J Immunol. 166:6914–6924. 2001. View Article : Google Scholar : PubMed/NCBI
15	Suvannavejh GC, Dal Canto MC, Matis LA and Miller SD: Fas-mediated apoptosis in clinical remissions of relapsing experimental autoimmune encephalomyelitis. J Clin Invest. 105:223–231. 2000. View Article : Google Scholar : PubMed/NCBI
16	Zhu B, Luo L, Chen Y, Paty DW and Cynader MS: Intrathecal Fas ligand infusion strengthens immunoprivilege of central nervous system and suppresses experimental autoimmune encephalomyelitis. J Immunol. 169:1561–1569. 2002. View Article : Google Scholar : PubMed/NCBI
17	McCombe PA, Nickson I, Tabi Z and Pender MP: Apoptosis of V beta 8.2⁺ T lymphocytes in the spinal cord during recovery from experimental autoimmune encephalomyelitis induced in Lewis rats by inoculation with myelin basic protein. J Neurol Sci. 139:1–6. 1996. View Article : Google Scholar : PubMed/NCBI
18	Behan PO and Chaudhuri A: EAE is not a useful model for demyelinating disease. Mult Scler Relat Disord. 3:565–574. 2014. View Article : Google Scholar : PubMed/NCBI
19	D'Acquisto F, May MJ and Ghosh S: Inhibition of nuclear factor kappa B (NF-B): An emerging theme in anti-inflammatory therapies. Mol Interv. 2:22–35. 2002. View Article : Google Scholar : PubMed/NCBI
20	He JK, Yu SD, Zhu HJ, Wu JC and Qin ZH: Triptolide inhibits NF-kappaB activation and reduces injury of donor lung induced by ischemia/reperfusion. Acta Pharmacol Sin. 28:1919–1923. 2007. View Article : Google Scholar : PubMed/NCBI
21	Noor NA, Fahmy HM, Mohammed FF, Elsayed AA and Radwan NM: Nigella sativa amliorates inflammation and demyelination in the experimental autoimmune encephalomyelitis-induced Wistar rats. Int J Clin Exp Pathol. 8:6269–6286. 2015.PubMed/NCBI