Development of herbal molecules in treating autoimmune uveitis: a narrative review

Authors

  • Chak Yin Justin Leung The Chinese University of Hong Kong
  • Zheng Xi Austin Tang The Chinese University of Hong Kong
  • Chun Bon Wong The Chinese University of Hong Kong
  • Hei Nga Wong The Chinese University of Hong Kong
  • Wai Kit Chu The Chinese University of Hong Kong

DOI:

https://doi.org/10.12809/hkjo-v25n2-307

Keywords:

Caffeic acid phenethyl ester, Curcumin, Epigallocatechin gallate, Longdan Xiegan Tang, Peony root extract, Triptolide, Uveitis

Abstract

Current treatments for autoimmune uveitis involve the use of corticosteroids topically, locally (including subconjunctival, subtenon, orbital floor, and intraouclar injection), and systemically to attenuate the T cell–mediated response by impairing cell trafficking and activation to the uvea and dampening cell response to ocular antigens. However, long-term local injection of corticosteroids may result in raised intraocular pressure, cataracts, and glaucoma. Systemic use of steroids may result in severe morbidity. Immunomodulatory agents and biologics can circumvent some of these issues but may result in other adverse effects. Herbal molecules are potentially useful in treatment of autoimmune uveitis. We review the literature about the pathogenesis of autoimmune uveitis and the mechanisms, efficacy, and safety of herbal molecules (curcumin, green tea, triptolide, caffeic acid phenethyl ester, total glucosides of peony, and Longdan Xiegan Tang) as a therapeutic option or supplement for autoimmune uveitis.

References

Nussenblatt RB. The natural history of uveitis. Int Ophthalmol 1990;14:303-8. DOI: https://doi.org/10.1007/BF00163549

Bodaghi B, Cassoux N, Wechsler B, et al. Chronic severe uveitis: etiology and visual outcome in 927 patients from a single center. Medicine (Baltimore) 2001;80:263-70. DOI: https://doi.org/10.1097/00005792-200107000-00005

Miserocchi E, Fogliato G, Modorati G, Bandello F. Review on the worldwide epidemiology of uveitis. Eur J Ophthalmol 2013;23:705-17. DOI: https://doi.org/10.5301/ejo.5000278

Tsirouki T, Dastiridou A, Symeonidis C, et al. A focus on the epidemiology of uveitis. Ocul Immunol Inflamm 2018;26:2-16. DOI: https://doi.org/10.1080/09273948.2016.1196713

Bloch-Michel E, Nussenblatt RB. International Uveitis Study Group recommendations for the evaluation of intraocular inflammatory disease. Am J Ophthalmol 1987;103:234-5. DOI: https://doi.org/10.1016/S0002-9394(14)74235-7

Jabs DA, Nussenblatt RB, Rosenbaum JT, Standardization of Uveitis Nomenclature Working G. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol 2005;140:509-16. DOI: https://doi.org/10.1016/j.ajo.2005.03.057

Hwang DK, Chou YJ, Pu CY, Chou P. Epidemiology of uveitis among the Chinese population in Taiwan: a population-based study. Ophthalmology 2012;119:2371-6. DOI: https://doi.org/10.1016/j.ophtha.2012.05.026

Yang P, Zhang Z, Zhou H, et al. Clinical patterns and characteristics of uveitis in a tertiary center for uveitis in China. Curr Eye Res 2005;30:943-8. DOI: https://doi.org/10.1080/02713680500263606

McCannel CA, Holland GN, Helm CJ, Cornell PJ, Winston JV, Rimmer TG. Causes of uveitis in the general practice of ophthalmology. UCLA Community-Based Uveitis Study Group. Am J Ophthalmol 1996;121:35-46. DOI: https://doi.org/10.1016/S0002-9394(14)70532-X

Shafran SD, Deschenes J, Miller M, Phillips P, Toma E. Uveitis and pseudojaundice during a regimen of clarithromycin, rifabutin, and ethambutol. MAC Study Group of the Canadian HIV Trials Network. N Engl J Med 1994;330:438-9. DOI: https://doi.org/10.1056/NEJM199402103300616

Caspi RR. Understanding autoimmune uveitis through animal models. The Friedenwald Lecture. Invest Ophthalmol Vis Sci 2011;52:1872-9. DOI: https://doi.org/10.1167/iovs.10-6909

Rothova A, Buitenhuis HJ, Meenken C, et al. Uveitis and systemic disease. Br J Ophthalmol 1992;76:137-41. DOI: https://doi.org/10.1136/bjo.76.3.137

Edmunds L, Elswood J, Calin A. New light on uveitis in ankylosing spondylitis. J Rheumatol 1991;18:50-2.

Banares A, Hernandez-Garcia C, Fernandez-Gutierrez B, Jover JA. Eye involvement in the spondyloarthropathies. Rheum Dis Clin North Am 1998;24:771-84. DOI: https://doi.org/10.1016/S0889-857X(05)70041-7

Lee RW, Nicholson LB, Sen HN, et al. Autoimmune and autoinflammatory mechanisms in uveitis. Semin Immunopathol 2014;36:581-94. DOI: https://doi.org/10.1007/s00281-014-0433-9

Rosenbaum JT, Bodaghi B, Couto C, et al. New observations and emerging ideas in diagnosis and management of non-infectious uveitis: a review. Semin Arthritis Rheum 2019;49:438-45. DOI: https://doi.org/10.1016/j.semarthrit.2019.06.004

Kiss S, Anzaar F, Stephen Foster C. Birdshot retinochoroidopathy. Int Ophthalmol Clin 2006;46:39-55. DOI: https://doi.org/10.1097/00004397-200604620-00006

Chen J, Xie H, Wang Z, et al. Mooren's ulcer in China: a study of clinical characteristics and treatment. Br J Ophthalmol 2000;84:1244-9. DOI: https://doi.org/10.1136/bjo.84.11.1244

Chung YM, Yeh TS, Liu JH. Endogenous uveitis in Chinese: an analysis of 240 cases in a uveitis clinic. Jpn J Ophthalmol 1988;32:64-9.

Ng D, Mohamed S, Chu WK, Luk FO, Brelen M, Chan CKM. Update on uveitis management. Hong Kong J Ophthalmol 2016;20:95.

Bansal S, Barathi VA, Iwata D, Agrawal R. Experimental autoimmune uveitis and other animal models of uveitis: An update. Indian J Ophthalmol 2015;63:211-8. DOI: https://doi.org/10.4103/0301-4738.156914

Namba K, Ogasawara K, Kitaichi N, et al. Identification of a peptide inducing experimental autoimmune uveoretinitis (EAU) in H-2Ak-carrying mice. Clin Exp Immunol 1998;111:442-9. DOI: https://doi.org/10.1046/j.1365-2249.1998.00514.x

Silver PB, Rizzo LV, Chan CC, Donoso LA, Wiggert B, Caspi RR. Identification of a major pathogenic epitope in the human IRBP molecule recognized by mice of the H-2r haplotype. Invest Ophthalmol Vis Sci 1995;36:946-54.

Silver PB, Chan CC, Wiggert B, Caspi RR. The requirement for pertussis to induce EAU is strain-dependent: B10.RIII, but not B10.A mice, develop EAU and Th1 responses to IRBP without pertussis treatment. Invest Ophthalmol Vis Sci 1999;40:2898-905.

Caspi RR, Chan CC, Leake WC, Higuchi M, Wiggert B, Chader GJ. Experimental autoimmune uveoretinitis in mice. Induction by a single eliciting event and dependence on quantitative parameters of immunization. J Autoimmun 1990;3:237-46. DOI: https://doi.org/10.1016/0896-8411(90)90143-G

Caspi R. Autoimmunity in the immune privileged eye: pathogenic and regulatory T cells. Immunol Res 2008;42:41-50. DOI: https://doi.org/10.1007/s12026-008-8031-3

Agarwal RK, Silver PB, Caspi RR. Rodent models of experimental autoimmune uveitis. Methods Mol Biol 2012;900:443-69. DOI: https://doi.org/10.1007/978-1-60761-720-4_22

Chen J, Caspi RR. Clinical and functional evaluation of ocular inflammatory disease using the model of experimental autoimmune uveitis. Methods Mol Biol 2019;1899:211-27. DOI: https://doi.org/10.1007/978-1-4939-8938-6_15

Hayden MS, Ghosh S. NF-kappaB in immunobiology. Cell Res 2011;21:223-44. DOI: https://doi.org/10.1038/cr.2011.13

Dick AD, Forrester JV, Liversidge J, Cope AP. The role of tumour necrosis factor (TNF-alpha) in experimental autoimmune uveoretinitis (EAU). Prog Retin Eye Res 2004;23:617-37. DOI: https://doi.org/10.1016/j.preteyeres.2004.06.005

Okada AA, Keino H, Fukai T, Sakai J, Usui M, Mizuguchi J. Effect of type I interferon on experimental autoimmune uveoretinitis in rats. Ocul Immunol Inflamm 1998;6:215-26. DOI: https://doi.org/10.1076/ocii.6.4.215.4024

Croxford AL, Kulig P, Becher B. IL-12-and IL-23 in health and disease. Cytokine Growth Factor Rev 2014;25:415-21. DOI: https://doi.org/10.1016/j.cytogfr.2014.07.017

Taniguchi K, Karin M. NF-kappaB, inflammation, immunity and cancer: coming of age. Nat Rev Immunol 2018;18:309-24. DOI: https://doi.org/10.1038/nri.2017.142

Sugita S, Kawazoe Y, Imai A, Yamada Y, Horie S, Mochizuki M. Inhibition of Th17 differentiation by anti-TNF-alpha therapy in uveitis patients with Behcet's disease. Arthritis Res Ther 2012;14:R99. DOI: https://doi.org/10.1186/ar3824

Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 1989;7:145-73. DOI: https://doi.org/10.1146/annurev.iy.07.040189.001045

Morinobu A, Gadina M, Strober W, et al. STAT4 serine phosphorylation is critical for IL-12-induced IFN-gamma production but not for cell proliferation. Proc Natl Acad Sci U S A 2002;99:12281-6. DOI: https://doi.org/10.1073/pnas.182618999

Caspi RR, Silver PB, Chan CC, et al. Genetic susceptibility to experimental autoimmune uveoretinitis in the rat is associated with an elevated Th1 response. J Immunol 1996;157:2668-75. DOI: https://doi.org/10.4049/jimmunol.157.6.2668

Egwuagu CE, Mahdi RM, Chan CC, et al. Expression of interferon-gamma in the lens exacerbates anterior uveitis and induces retinal degenerative changes in transgenic Lewis rats. Clin Immunol 1999;91:196-205. DOI: https://doi.org/10.1006/clim.1999.4701

Forrester JV, Huitinga I, Lumsden L, Dijkstra CD. Marrow-derived activated macrophages are required during the effector phase of experimental autoimmune uveoretinitis in rats. Curr Eye Res 1998;17:426-37. DOI: https://doi.org/10.1080/02713689808951224

Barnes PJ. How corticosteroids control inflammation: Quintiles Prize Lecture 2005. Br J Pharmacol 2006;148:245-54. DOI: https://doi.org/10.1038/sj.bjp.0706736

Sen HN, Vitale S, Gangaputra SS, et al. Periocular corticosteroid injections in uveitis: effects and complications. Ophthalmology 2014;121:2275-86. DOI: https://doi.org/10.1016/j.ophtha.2014.05.021

Nussenblatt RB, Dinning WJ, Fujikawa LS, Chan CC, Palestine AG. Local cyclosporine therapy for experimental autoimmune uveitis in rats. Arch Ophthalmol 1985;103:1559-62. DOI: https://doi.org/10.1001/archopht.1985.01050100135035

LaMattina KC, Goldstein DA. Adalimumab for the treatment of uveitis. Expert Rev Clin Immunol 2017;13:181-8. DOI: https://doi.org/10.1080/1744666X.2017.1288097

Khalili H, Lee RW, Khaw PT, Brocchini S, Dick AD, Copland DA. An anti-TNF-alpha antibody mimetic to treat ocular inflammation. Sci Rep 2016;6:36905. DOI: https://doi.org/10.1038/srep36905

Gupta SC, Patchva S, Koh W, Aggarwal BB. Discovery of curcumin, a component of golden spice, and its miraculous biological activities. Clin Exp Pharmacol Physiol 2012;39:283-99. DOI: https://doi.org/10.1111/j.1440-1681.2011.05648.x

Radomska-Lesniewska DM, Osiecka-Iwan A, Hyc A, Gozdz A, Dabrowska AM, Skopinski P. Therapeutic potential of curcumin in eye diseases. Cent Eur J Immunol 2019;44:181-9. DOI: https://doi.org/10.5114/ceji.2019.87070

Mohan R, Sivak J, Ashton P, et al. Curcuminoids inhibit the angiogenic response stimulated by fibroblast growth factor-2, including expression of matrix metalloproteinase gelatinase B. J Biol Chem 2000;275:10405-12. DOI: https://doi.org/10.1074/jbc.275.14.10405

Allegri P, Mastromarino A, Neri P. Management of chronic anterior uveitis relapses: efficacy of oral phospholipidic curcumin treatment. Long-term follow-up. Clin Ophthalmol 2010;4:1201-6. DOI: https://doi.org/10.2147/OPTH.S13271

Lal B, Kapoor AK, Asthana OP, et al. Efficacy of curcumin in the management of chronic anterior uveitis. Phytother Res 1999;13:318-22. DOI: https://doi.org/10.1002/(SICI)1099-1573(199906)13:4<318::AID-PTR445>3.3.CO;2-Z

Liu XF, Hao JL, Xie T, et al. Curcumin, A potential therapeutic candidate for anterior segment eye diseases: a review. Front Pharmacol 2017;8:66. DOI: https://doi.org/10.3389/fphar.2017.00066

Nelson KM, Dahlin JL, Bisson J, Graham J, Pauli GF, Walters MA. The essential medicinal chemistry of curcumin. J Med Chem 2017;60:1620-37. DOI: https://doi.org/10.1021/acs.jmedchem.6b00975

Heger M. Drug screening: Don't discount all curcumin trial data. Nature 2017;543:40. DOI: https://doi.org/10.1038/543040c

Dhillon N, Aggarwal BB, Newman RA, et al. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res 2008;14:4491-9. DOI: https://doi.org/10.1158/1078-0432.CCR-08-0024

DiSilvestro RA, Joseph E, Zhao S, Bomser J. Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people. Nutr J 2012;11:79. DOI: https://doi.org/10.1186/1475-2891-11-79

Sharma RA, Euden SA, Platton SL, et al. Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res 2004;10:6847-54. DOI: https://doi.org/10.1158/1078-0432.CCR-04-0744

Lao CD, Ruffin MTt, Normolle D, et al. Dose escalation of a curcuminoid formulation. BMC Complement Altern Med 2006;6:10. DOI: https://doi.org/10.1186/1472-6882-6-10

Cabrera C, Artacho R, Gimenez R. Beneficial effects of green tea--a review. J Am Coll Nutr 2006;25:79-99. DOI: https://doi.org/10.1080/07315724.2006.10719518

Wu D, Wang J, Pae M, Meydani SN. Green tea EGCG, T cells, and T cell-mediated autoimmune diseases. Mol Aspects Med 2012;33:107-18. DOI: https://doi.org/10.1016/j.mam.2011.10.001

Qin YJ, Chu KO, Yip YW, et al. Green tea extract treatment alleviates ocular inflammation in a rat model of endotoxin-induced uveitis. PLoS One 2014;9:e103995. DOI: https://doi.org/10.1371/journal.pone.0103995

Li J, Yip YWY, Ren J, et al. Green tea catechins alleviate autoimmune symptoms and visual impairment in a murine model for human chronic intraocular inflammation by inhibiting Th17-associated pro-inflammatory gene expression. Sci Rep 2019;9:2301. DOI: https://doi.org/10.1038/s41598-019-38868-1

Wu Y, Wang Y, Zhong C, Li Y, Li X, Sun B. The suppressive effect of triptolide on experimental autoimmune uveoretinitis by down-regulating Th1-type response. Int Immunopharmacol 2003;3:1457-65. DOI: https://doi.org/10.1016/S1567-5769(03)00144-9

Choi JH, Roh KH, Oh H, et al. Caffeic acid phenethyl ester lessens disease symptoms in an experimental autoimmune uveoretinitis mouse model. Exp Eye Res 2015;134:53-62. DOI: https://doi.org/10.1016/j.exer.2015.03.014

Armutcu F, Akyol S, Ustunsoy S, Turan FF. Therapeutic potential of caffeic acid phenethyl ester and its anti-inflammatory and immunomodulatory effects (Review). Exp Ther Med 2015;9:1582-8. DOI: https://doi.org/10.3892/etm.2015.2346

Natarajan K, Singh S, Burke TR Jr, Grunberger D, Aggarwal BB. Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B. Proc Natl Acad Sci U S A 1996;93:9090-5. DOI: https://doi.org/10.1073/pnas.93.17.9090

Crane IJ, Kuppner MC, McKillop-Smith S, Knott RM, Forrester JV. Cytokine regulation of RANTES production by human retinal pigment epithelial cells. Cell Immunol 1998;184:37-44. DOI: https://doi.org/10.1006/cimm.1997.1235

Li H, Wu F, Tan J, et al. Caffeic acid phenethyl ester exhibiting distinctive binding interaction with human serum albumin implies the pharmacokinetic basis of propolis bioactive components. J Pharm Biomed Anal 2016;122:21-8. DOI: https://doi.org/10.1016/j.jpba.2016.01.040

Yordanov Y, Aluani D, Tzankova V, et al. Safety assessment of a newly synthesized copolymer for micellar delivery of hydrophobic caffeic acid phenethyl ester. Pharm Dev Technol 2020;25:1271-80. DOI: https://doi.org/10.1080/10837450.2020.1818259

Huang XT, Wang B, Zhang WH, Peng MQ, Lin D. Total glucosides of paeony suppresses experimental autoimmune uveitis in association with inhibition of Th1 and Th2 cell function in mice. Int J Immunopathol Pharmacol 2018;32:394632017751547. DOI: https://doi.org/10.1177/0394632017751547

Tang K, Guo D, Zhang L, et al. Immunomodulatory effects of Longdan Xiegan Tang on CD4+/CD8+ T cells and associated inflammatory cytokines in rats with experimental autoimmune uveitis. Mol Med Rep 2016;14:2746-54. DOI: https://doi.org/10.3892/mmr.2016.5558

Lee CH, Wang JD, Chen PC. Risk of liver injury associated with Chinese herbal products containing radix bupleuri in 639,779 patients with hepatitis B virus infection. PLoS One 2011;6:e16064. DOI: https://doi.org/10.1371/journal.pone.0016064

Downloads

Published

2021-12-23

Issue

Section

Review Articles

How to Cite

1.
Development of herbal molecules in treating autoimmune uveitis: a narrative review. Hong Kong J Ophthalmol [Internet]. 2021 Dec. 23 [cited 2026 Aug. 14];25(2). Available from: https://www.hkjo.hk/index.php/hkjo/article/view/307

Similar Articles

21-28 of 28

You may also start an advanced similarity search for this article.