Protective effect of naringin against ankylosing spondylitis via ossification, inflammation and oxidative stress in mice

Liu,Kang; Wu,Lianguo; Shi,Xiaolin; Wu,Fengqing

doi:10.3892/etm.2016.3410

Protective effect of naringin against ankylosing spondylitis via ossification, inflammation and oxidative stress in mice

Authors:
- Kang Liu
- Lianguo Wu
- Xiaolin Shi
- Fengqing Wu
View Affiliations

Affiliations: Department of Orthopedics, The Second Hospital Affiliated to Zhejiang University of Chinese Medicine, Hangzhou, Zhejiang 310005, P.R. China
Published online on: May 31, 2016 https://doi.org/10.3892/etm.2016.3410
Pages: 1153-1158

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

Naringin is an abundant flavanone in pomelo, grapefruit as well as lime and its variants, has been shown to exhibit certain antioxidative, anti‑inflammatory, anti‑cancer and hypoglycemic effects. The aim of the current study was to evaluate the protective effects of naringin against ankylosing spondylitis (AS) and to elucidate the potential underlying mechanism. Firstly, a mouse model of ankylosing spondylitis (AS) was established. Next, osteocalcin (OC), alkaline phosphatase (ALP) and triglyceride (TG) activity values, inflammatory factor and oxidative stress were evaluated in the AS mice. Then, the Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) protein expression levels in the AS mice were investigated using western blot analysis. The results showed that naringin increased OC, ALP and TG activity values in the AS mouse model. Furthermore, inflammatory factor and oxidative stress levels in the AS mice were restrained by treatment with naringin. Furthermore, JAK2 and STAT3 protein expression levels were reduced by treatment with naringin. In conclusion, the present results indicated that the protective effects of naringin against AS are exerted via the induction of ossification, suppression of inflammation and oxidative stress and the downregulation of JAK2/STAT3 in mice.

View Figures

View References

1	Liu YF, Dong H, Tu SH, Zheng CH, Liu PL and Hu YH: Etanercept in the treatment of ankylosing spondylitis: A systematic review and meta-analysis. Exp Ther Med. 8:1585–1592. 2014.PubMed/NCBI
2	Chou CT, Huo AP, Chang HN, Tsai CY, Chen WS and Wang HP: Cytokine production from peripheral blood mononuclear cells in patients with ankylosing spondylitis and their first-degree relatives. Arch Med Res. 38:190–195. 2007. View Article : Google Scholar : PubMed/NCBI
3	Zhou L, Zhang Y, Xu H, et al: Decreased programmed death-1 expression on the T cells of patients with ankylosing spondylitis. Am J Med Sci. 349:488–492. 2015. View Article : Google Scholar : PubMed/NCBI
4	Rednic S, Marinescu C, Chira R, Rogojan L and Rednic N: Treatment with infliximab in a patient with ankylosing spondylitis and Crohn's disease. J Gastrointestin Liver Dis. 15:379–382. 2006.PubMed/NCBI
5	Mielants H, Veys EM, Cuvelier C, et al: Gut inflammation in children with late onset pauciarticular juvenile chronic arthritis and evolution to adult spondyloarthropathy––a prospective study. J Rheumatol. 20:1567–1572. 1993.PubMed/NCBI
6	Weber U, Hodler J, Kubik RA, Rufibach K, Lambert RG, Kissling RO, Pfirrmann CW and Maksymowych WP: Sensitivity and specificity of spinal inflammatory lesions assessed by whole-body magnetic resonance imaging in patients with ankylosing spondylitis or recent-onset inflammatory back pain. Arthritis Rheum. 61:900–908. 2009. View Article : Google Scholar : PubMed/NCBI
7	Maksymowych WP, Chiowchanwisawakit P, Clare T, Pedersen SJ, Østergaard M and Lambert RG: Inflammatory lesions of the spine on magnetic resonance imaging predict the development of new syndesmophytes in ankylosing spondylitis: Evidence of a relationship between inflammation and new bone formation. Arthritis Rheum. 60:93–102. 2009. View Article : Google Scholar : PubMed/NCBI
8	Okano K, Kimura K, Tanaka Y, Tsuchiya K, Akiba T and Nitta K: Direct measurement of reactive oxygen species in leukocytes during hemodialysis therapy. Int J Clin Exp Med. 8:20959–20964. 2015.PubMed/NCBI
9	Kozaci LD, Sari I, Alacacioglu A, Akar S and Akkoc N: Evaluation of inflammation and oxidative stress in ankylosing spondylitis: A role for macrophage migration inhibitory factor. Mod Rheumatol. 20:34–39. 2010. View Article : Google Scholar : PubMed/NCBI
10	Jagetia GC, Reddy TK, Venkatesha VA and Kedlaya R: Influence of naringin on ferric iron induced oxidative damage in vitro. Clin Chim Acta. 347:189–197. 2004. View Article : Google Scholar : PubMed/NCBI
11	Zhou X, Zhang P, Zhang C and Zhu Z: Promotion of bone formation by naringin in a titanium particle-induced diabetic murine calvarial osteolysis model. J Orthop Res. 28:451–456. 2010.PubMed/NCBI
12	Kim SY, Kim HJ, Lee MK, Jeon SM, Do GM, Kwon EY, Cho YY, Kim DJ, Jeong KS, Park YB, et al: Naringin time-dependently lowers hepatic cholesterol biosynthesis and plasma cholesterol in rats fed high-fat and high-cholesterol diet. J Med Food. 9:582–586. 2006. View Article : Google Scholar : PubMed/NCBI
13	Choe SC, Kim HS, Jeong TS, Bok SH and Park YB: Naringin has an antiatherogenic effect with the inhibition of intercellular adhesion molecule-1 in hypercholesterolemic rabbits. J Cardiovasc Pharmacol. 38:947–955. 2001. View Article : Google Scholar : PubMed/NCBI
14	Fernandez SP, Nguyen M, Yow TT, Chu C, Johnston GA, Hanrahan JR and Chebib M: The flavonoid glycosides, myricitrin, gossypin and naringin exert anxiolytic action in mice. Neurochem Res. 34:1867–1875. 2009. View Article : Google Scholar : PubMed/NCBI
15	Camargo CA, Gomes-Marcondes MC, Wutzki NC and Aoyama H: Naringin inhibits tumor growth and reduces interleukin-6 and tumor necrosis factor alpha levels in rats with Walker 256 carcinosarcoma. Anticancer Res. 32:129–133. 2012.PubMed/NCBI
16	Liu Q, Lu L and Xiao M: Cell surface engineering of α-l-rhamnosidase for naringin hydrolysis. Bioresour Technol. 123:144–149. 2012. View Article : Google Scholar : PubMed/NCBI
17	Gu X, Wu H and Fu P: Allicin attenuates inflammation and suppresses HLA-B27 protein expression in ankylosing spondylitis mice. Biomed Res Int. 2013:1715732013. View Article : Google Scholar : PubMed/NCBI
18	Kumar VS, Rajmane AR, Adil M, Kandhare AD, Ghosh P and Bodhankar SL: Naringin ameliorates acetic acid induced colitis through modulation of endogenous oxido-nitrosative balance and DNA damage in rats. J Biomed Res. 28:132–145. 2014.PubMed/NCBI
19	Shiau MY, Lo MK, Chang CP, Yang TP, Ho KT and Chang YH: Association of tumour necrosis factor alpha promoter polymorphisms with ankylosing spondylitis in Taiwan. Ann Rheum Dis. 66:562–563. 2007. View Article : Google Scholar : PubMed/NCBI
20	Tam LS, Chan KY and Li EK: The influence of illness and variables associated with functional limitations in Chinese patients with ankylosing spondylitis. J Rheumatol. 34:1032–1039. 2007.PubMed/NCBI
21	Gu X, Wu H and Fu P: Allicin attenuates inflammation and suppresses HLA-B27 protein expression in ankylosing spondylitis mice. Biomed Res Int. 2013:1715732013. View Article : Google Scholar : PubMed/NCBI
22	Liu M, Li Y and Yang ST: Effects of naringin on the proliferation and osteogenic differentiation of human amniotic fluid-derived stem cells. J Tissue Eng Regen Med. 2014.(Epub ahead of print). View Article : Google Scholar
23	Li L, Zeng Z and Cai G: Comparison of neoeriocitrin and naringin on proliferation and osteogenic differentiation in MC3T3-E1. Phytomedicine. 18:985–989. 2011. View Article : Google Scholar : PubMed/NCBI
24	Lange U, Teichmann J and Stracke H: Correlation between plasma TNF-alpha, IGF-1, biochemical markers of bone metabolism, markers of inflammation/disease activity and clinical manifestations in ankylosing spondylitis. Eur J Med Res. 5:507–511. 2000.PubMed/NCBI
25	Schulz M, Dotzlaw H and Neeck G: Ankylosing spondylitis and rheumatoid arthritis: serum levels of TNF-alpha and Its soluble receptors during the course of therapy with etanercept and infliximab. Biomed Res Int. 2014:6751082014. View Article : Google Scholar : PubMed/NCBI
26	Huang WN, Tso TK, Kuo YC and Tsay GJ: Distinct impacts of syndesmophyte formation on male and female patients with ankylosing spondylitis. Int J Rheum Dis. 15:163–168. 2012. View Article : Google Scholar : PubMed/NCBI
27	Liu C, Hong T, Shao M, Chen Z and Wang C: Melatonin synergized with cyclosporine A improves cardiac allograft survival by suppressing inflammation and apoptosis. Mol Med Rep. 10:1323–1328. 2014.PubMed/NCBI
28	Golechha M, Sarangal V, Bhatia J, Chaudhry U, Saluja D and Arya DS: Naringin ameliorates pentylenetetrazol-induced seizures and associated oxidative stress, inflammation, and cognitive impairment in rats: Possible mechanisms of neuroprotection. Epilepsy Behav. 41:98–102. 2014. View Article : Google Scholar : PubMed/NCBI
29	Jung UJ and Kim SR: Effects of naringin, a flavanone glycoside in grapefruits and citrus fruits, on the nigrostriatal dopaminergic projection in the adult brain. Neural Regen Res. 9:1514–1517. 2014. View Article : Google Scholar : PubMed/NCBI
30	Feijoo M, Tunez I, Tasset I, Montilla P, Ruiz A and Collantes E: Infliximab reduces oxidative stress in ankylosing spondylitis. Clin Exp Rheumatol. 27:167–168. 2009.PubMed/NCBI
31	Karakoc M, Altindag O, Keles H, Soran N and Selek S: Serum oxidative-antioxidative status in patients with ankylosing spondilitis. Rheumatol Int. 27:1131–1134. 2007. View Article : Google Scholar : PubMed/NCBI
32	Chen Y, Nie YC, Luo YL, Lin F, Zheng YF, Cheng GH, Wu H, Zhang KJ, Su WW, Shen JG and Li PB: Protective effects of naringin against paraquat-induced acute lung injury and pulmonary fibrosis in mice. Food Chem Toxicol. 58:133–140. 2013. View Article : Google Scholar : PubMed/NCBI
33	Cui QJ, Wang LY, Wei ZX and Qu WS: Continual naringin treatment benefits the recovery of traumatic brain injury in rats through reducing oxidative and inflammatory alterations. Neurochem Res. 39:1254–1262. 2014. View Article : Google Scholar : PubMed/NCBI
34	Kicinska A, Leluk J and Jarmuszkiewicz W: Acanthamoeba castellanii STAT protein. PLoS One. 9:e1113452014. View Article : Google Scholar : PubMed/NCBI
35	Danoy P, Pryce K, Hadler J, Bradbury LA, Farrar C and Pointon J: Australo-Anglo-American Spondyloarthritis Consortium, Ward M, Weisman M, Reveille JD, et al: Association of variants at 1q32 and STAT3 with ankylosing spondylitis suggests genetic overlap with Crohn's disease. PLoS Genet. 6:e10011952010. View Article : Google Scholar : PubMed/NCBI
36	Ahmad SF, Attia SM, Bakheet SA, Zoheir KM, Ansari MA, Korashy HM, Abdel-Hamied HE, Ashour AE and Abd-Allah AR: Naringin attenuates the development of carrageenan-induced acute lung inflammation through inhibition of NF-κb, STAT3 and pro-inflammatory mediators and enhancement of IκBα and anti-inflammatory cytokines. Inflammation. 38:846–857. 2015. View Article : Google Scholar : PubMed/NCBI
37	Davidson SI, Liu Y, Danoy PA, Wu X, Thomas GP, Jiang L, Sun L, Wang N, Han J, Han H, et al: Association of STAT3 and TNFRSF1A with ankylosing spondylitis in Han Chinese. Ann Rheum Dis. 70:289–292. 2011. View Article : Google Scholar : PubMed/NCBI
38	Zimmers TA, Fishel ML and Bonetto A: STAT3 in the Systemic Inflammation of Cancer Cachexia. Semin Cell Dev Biol. 2016. View Article : Google Scholar : PubMed/NCBI
39	Chen C, Zhang X and Wang Y: Analysis of JAK2 and STAT3 polymorphisms in patients with ankylosing spondylitis in Chinese Han population. Clin Immunol. 136:442–446. 2010. View Article : Google Scholar : PubMed/NCBI
40	Liu H, Yang Z, Hu J, et al: Improvement of thoracic aortic vasoreactivity by continuous and intermittent exercise in high-fat diet-induced obese rats. Biomed Rep. 3:527–532. 2015.PubMed/NCBI