Alpha7 NAChR Expression Is Correlated with Arthritis Development and Inhibited by Sinomenine in Adjuvant-Induced Arthritic Rats

Overview

Journal Evid Based Complement Alternat Med

Specialty Rehabilitation Medicine

Date 2019 Jun 13

PMID 31186658

Citations 6

Authors

Chong Peng

Qing-Ping Shi

Jia-Yan Liu

Yan-Jun Lv

Jing Li

Lang Yi

Sha-Sha Bai

Liang Liu

Pei-Xun Wang

Hua Zhou

Ke-Er Huang

Yan Dong

Affiliations

Soon will be listed here.

Abstract

Sinomenine (SIN) is the active ingredient of the Chinese herb that has been used to treat rheumatoid arthritis (RA) for about 30 years in China. Marked expression of the alpha7 nicotinic acetylcholine receptor (7nAChR) in the joint synovium of RA patients suggested a relationship between 7nAChR and RA. This study investigated the relationship between 7nAChR and RA development and the effects of SIN on 7nAChR expression and . Sprague-Dawley rats were injected with complete Freund's adjuvant to induce arthritis and then treated with SIN or methotrexate (MTX) from day 0 to day 30. Four clinical parameters-paw volume, arthritic index (AI), serum TNF- concentration, and erythrocyte sedimentation rate (ESR)-were measured. Splenic lymphocytes were isolated for Bacille Calmette Guerin (BCG) stimulation. 7nAChR expression in tissues and cells was examined by RT-PCR, western blot, immunofluorescence, flow cytometry, and immunohistochemistry. Cell proliferation was evaluated by the CCK-8 assay. The relationship between 7nAChR expression and the four clinical parameters was analyzed by single-factor correlation analysis. Our results showed that the paw volume, AI, TNF- concentration, and ESR in adjuvant-induced arthritic (AIA) rats were reduced by SIN or MTX treatment. SIN decreased 7nAChR expression in tissues and cells compared to the model group, while MTX had no significant effect on 7nAChR expression. Moreover, there was a positive relationship between 7nAChR expression and paw swelling, AI, and TNF- concentration. Splenic lymphocyte activation was accompanied by increased 7nAChR expression, while SIN treatment inhibited cell activation and downregulated 7nAChR expression. 7nAChR expression showed a positive correlation with the progression of RA in AIA rats that may involve lymphocyte activation. Different from MTX, the inhibition of SIN on 7nAChR expression might contribute to its antiarthritic effect, suggesting that SIN could be an important supplement to the treatment strategy for RA.

Citing Articles

Sinomenine treats rheumatoid arthritis by inhibiting MMP9 and inflammatory cytokines expression: bioinformatics analysis and experimental validation.

Luo J, Zhu Y, Yu Y, Chen Y, He K, Liu J Sci Rep. 2024; 14(1):12786.

PMID: 38834626 PMC: 11151427. DOI: 10.1038/s41598-024-61769-x.

Bioactivities and Mechanisms of Action of Sinomenine and Its Derivatives: A Comprehensive Review.

Hou W, Huang L, Huang H, Liu S, Dai W, Tang J Molecules. 2024; 29(2).

PMID: 38276618 PMC: 10818773. DOI: 10.3390/molecules29020540.

Recent Advancements in Drug Delivery of Sinomenine, A Disease-Modifying Anti-Rheumatic Drug.

Chen X, Lu C, Duan Y, Huang Y Pharmaceutics. 2022; 14(12).

PMID: 36559313 PMC: 9781253. DOI: 10.3390/pharmaceutics14122820.

Natural medicines of targeted rheumatoid arthritis and its action mechanism.

Liu X, Wang Z, Qian H, Tao W, Zhang Y, Hu C Front Immunol. 2022; 13:945129.

PMID: 35979373 PMC: 9376257. DOI: 10.3389/fimmu.2022.945129.

α-Mangostin Treats Early-Stage Adjuvant-Induced Arthritis of Rat by Regulating the CAP-SIRT1 Pathway in Macrophages.

Chen W, Zhang S, Pan S, Wang Z, Xu J, Sheng X Drug Des Devel Ther. 2022; 16:509-520.

PMID: 35250263 PMC: 8893152. DOI: 10.2147/DDDT.S348836.

References

Lee R, Vazquez G . Reduced size and macrophage content of advanced atherosclerotic lesions in mice with bone marrow specific deficiency of alpha 7 nicotinic acetylcholine receptor. PLoS One. 2015; 10(3):e0124584. PMC: 4380454. DOI: 10.1371/journal.pone.0124584. View

Skok M, Grailhe R, Changeux J . Nicotinic receptors regulate B lymphocyte activation and immune response. Eur J Pharmacol. 2005; 517(3):246-51. DOI: 10.1016/j.ejphar.2005.05.011. View

Yang X, Fraser M, Moll U, Basak A, Tsang B . Akt-mediated cisplatin resistance in ovarian cancer: modulation of p53 action on caspase-dependent mitochondrial death pathway. Cancer Res. 2006; 66(6):3126-36. DOI: 10.1158/0008-5472.CAN-05-0425. View

Wang H, Liao H, Ochani M, Justiniani M, Lin X, Yang L . Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med. 2004; 10(11):1216-21. DOI: 10.1038/nm1124. View

Smolen J, Aletaha D, McInnes I . Rheumatoid arthritis. Lancet. 2016; 388(10055):2023-2038. DOI: 10.1016/S0140-6736(16)30173-8. View

Nizri E, Irony-Tur-Sinai M, Lory O, Orr-Urtreger A, Lavi E, Brenner T . Activation of the cholinergic anti-inflammatory system by nicotine attenuates neuroinflammation via suppression of Th1 and Th17 responses. J Immunol. 2009; 183(10):6681-8. DOI: 10.4049/jimmunol.0902212. View

van Maanen M, Stoof S, Larosa G, Vervoordeldonk M, Tak P . Role of the cholinergic nervous system in rheumatoid arthritis: aggravation of arthritis in nicotinic acetylcholine receptor α7 subunit gene knockout mice. Ann Rheum Dis. 2010; 69(9):1717-23. DOI: 10.1136/ard.2009.118554. View

Cai Q, Huang H, Qian D, Chen K, Luo J, Tian Y . 13-methyltetradecanoic acid exhibits anti-tumor activity on T-cell lymphomas in vitro and in vivo by down-regulating p-AKT and activating caspase-3. PLoS One. 2013; 8(6):e65308. PMC: 3676434. DOI: 10.1371/journal.pone.0065308. View

Westman M, Saha S, Morshed M, Lampa J . Lack of acetylcholine nicotine alpha 7 receptor suppresses development of collagen-induced arthritis and adaptive immunity. Clin Exp Immunol. 2010; 162(1):62-7. PMC: 2990930. DOI: 10.1111/j.1365-2249.2010.04204.x. View

10.

Shao W, Growney J, Feng Y, OConnor G, Pu M, Zhu W . Activity of deacetylase inhibitor panobinostat (LBH589) in cutaneous T-cell lymphoma models: Defining molecular mechanisms of resistance. Int J Cancer. 2010; 127(9):2199-208. DOI: 10.1002/ijc.25218. View

11.

Cai X, Wong Y, Zhou H, Liu Z, Xie Y, Jiang Z . Manipulation of the induction of adjuvant arthritis in Sprague-Dawley rats. Inflamm Res. 2006; 55(9):368-77. DOI: 10.1007/s00011-006-6026-x. View

12.

Yoshikawa H, Kurokawa M, Ozaki N, Nara K, Atou K, Takada E . Nicotine inhibits the production of proinflammatory mediators in human monocytes by suppression of I-kappaB phosphorylation and nuclear factor-kappaB transcriptional activity through nicotinic acetylcholine receptor alpha7. Clin Exp Immunol. 2006; 146(1):116-23. PMC: 1809735. DOI: 10.1111/j.1365-2249.2006.03169.x. View

13.

Cortes M, Cao M, Liu H, Moore C, Durosier L, Burns P . α7 nicotinic acetylcholine receptor signaling modulates the inflammatory phenotype of fetal brain microglia: first evidence of interference by iron homeostasis. Sci Rep. 2017; 7(1):10645. PMC: 5587535. DOI: 10.1038/s41598-017-09439-z. View

14.

Baez-Pagan C, Delgado-Velez M, Lasalde-Dominicci J . Activation of the Macrophage α7 Nicotinic Acetylcholine Receptor and Control of Inflammation. J Neuroimmune Pharmacol. 2015; 10(3):468-76. PMC: 4546521. DOI: 10.1007/s11481-015-9601-5. View

15.

Khatri V, Chauhan N, Vishnoi K, von Gegerfelt A, Gittens C, Kalyanasundaram R . Prospects of developing a prophylactic vaccine against human lymphatic filariasis - evaluation of protection in non-human primates. Int J Parasitol. 2018; 48(9-10):773-783. PMC: 6054809. DOI: 10.1016/j.ijpara.2018.04.002. View

16.

Gahring L, Rogers S . Neuronal nicotinic acetylcholine receptor expression and function on nonneuronal cells. AAPS J. 2006; 7(4):E885-94. PMC: 2750958. DOI: 10.1208/aapsj070486. View

17.

Yi L, Luo J, Xie B, Liu J, Wang J, Liu L . α7 Nicotinic Acetylcholine Receptor is a Novel Mediator of Sinomenine Anti-Inflammation Effect in Macrophages Stimulated by Lipopolysaccharide. Shock. 2015; 44(2):188-95. DOI: 10.1097/SHK.0000000000000389. View

18.

Fraser M, Leung B, Yan X, Dan H, Cheng J, Tsang B . p53 is a determinant of X-linked inhibitor of apoptosis protein/Akt-mediated chemoresistance in human ovarian cancer cells. Cancer Res. 2003; 63(21):7081-8. View

19.

Liu Y, Lin H, Zou R, Wu J, Han R, Raymond L . Suppression of complete Freund's adjuvant-induced adjuvant arthritis by cobratoxin. Acta Pharmacol Sin. 2009; 30(2):219-27. PMC: 4002463. DOI: 10.1038/aps.2008.20. View

20.

Vivanco I, Sawyers C . The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer. 2002; 2(7):489-501. DOI: 10.1038/nrc839. View