Tectorigenin inhibits inflammation in keratinocytes by inhibition of NLRP3 inflammasome regulated by the TLR4/NF-κB pathway

Main Article Content

Jin Li
Wenliang Yan
Fang Ren
Hong Sang


autophagy, NLRP3 inflammasome, psoriasis, tectorigenin, TLR4/NF-κb


Background: Psoriasis is a prevalent inflammatory skin disease characterized by excessive proliferation and abnormal differentiation of keratinocytes, and infiltration of inflammatory cells into the epidermis. However, the underlying mechanisms remain unclear. Tectorigenin is an active ingredient in traditional medicines and has anti-inflammatory activity. This research explored the effects of tectorigenin on the anti-inflammatory property, autophagy, and the underlying mechanisms in M5 ([IL-22, IL-17A, oncostatin M, IL-1α, and TNF-α])–stimulated HaCaT cells.

Methods: The in vitro model of mixed M5 cytokines–stimulated HaCaT keratinocytes was established to investigate the phenotypic features in psoriasis. Cell viability was assessed by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay, cell proliferative rate by EdU (5-ethynyl-2'-deoxyuridine) assay, and autophagy was detected by immunofluorescence staining. After M5 exposure, the proliferative rate, protein expression of autophagy, and signaling activities of NLR family pyrin domain containing 3 (NLRP3) inflammasome and toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) were measured. The latter were quantitated using quantitative PCR and western blot, respectively. The inflammatory response was detected by enzyme-linked immunosorbent assay (ELISA).

Results: Tectorigenin exerted a protective effect in ameliorating the hyperproliferation and inflammation of HaCaT keratinocytes induced by M5 cytokines. Furthermore, tectorigenin on keratinocytes seemed to inactivate NLRP3 inflammasome and inhibit cell proliferation and inflammation response via suppression of TLR4/NF-κB pathway.

Conclusion: This study proves that tectorigenin may be a potential therapeutic candidate for psoriasis treatment in future.

Abstract 125 | PDF Downloads 202 HTML Downloads 10 XML Downloads 3


1. Nestle FO. Psoriasis mechanisms of disease. N Engl J Med. 2009;361:496–509. 10.1056/NEJMra0804595

2. Boehncke W, Schön M. Psoriasis. Lancet. 2015;386(9997):983–94. 10.1016/S0140-6736(14)61909-7

3. Hawkes JE, Chan TC, Krueger JG. Psoriasis pathogenesis and the development of novel targeted immune therapies. J Allergy Clin Immunol. 2017;140(3):645–53. 10.1016/j.jaci.2017.07.004

4. Albanesi C, De Pità O, Girolomoni G. Resident skin cells in psoriasis: A special look at the pathogenetic functions of keratinocytes. Clin Dermatol. 2007;25(6):581–8. 10.1016/j.clindermatol.2007.08.013

5. Lowes MA, Russell CB, Martin DA, Towne JE, Krueger JG. The IL-23/T17 pathogenic axis in psoriasis is amplified by keratinocyte responses. Trends Immunol. 2013;34(4):174–81. 10.1016/j.it.2012.11.005

6. Yue L, Ailin W, Jinwei Z, Leng L, Jianan W, Li L, et al. PSORI-CM02 ameliorates psoriasis in vivo and in vitro by inducing autophagy via inhibition of the PI3K/Akt/mTOR pathway. Phytomedicine. 2019;64:153054. 10.1016/j.phymed.2019.153054

7. Feng L, Song P, Xu F, Xu L, Shao F, Guo M, et al. cis--Khellactone inhibited the proinflammatory macrophages via promoting autophagy to ameliorate imiquimod-induced psoriasis. J Investig Dermatol. 2019;139(9):1946–56. 10.1016/j.jid.2019.02.021

8. Qu R, Chen X, Hu J, Fu Y, Peng J, Li Y, et al. Ghrelin protects against contact dermatitis and psoriasiform skin inflammation by antagonizing TNF-α/NF-κB signaling pathways. Sci Rep. 2019;9(1):1–14. 10.1038/s41598-018-38174-2

9. Gao J, Chen F, Fang H, Mi J, Qi Q, Yang M. Daphnetin inhibits proliferation and inflammatory response in human HaCaT keratinocytes and ameliorates imiquimod-induced-psoriasis-like skin lesion in mice. Biol Res. 2020;53(1):48. 10.1186/s40659-020-00316-0

10. Zhang L, Zhao Y, Fan L, Xu K, Ji F, Xie Z, et al. Tectorigenin protects against experimental fulminant hepatic failure by regulating the TLR4/mitogen-activated protein kinase and TLR4/nuclear factor-κB pathways and autophagy. Phytother Res. 2019;33(4):1055–64. 10.1002/ptr.6299

11. Yeh L-T, Hsu L-S, Chung Y-H, Chen C-J. Tectorigenin inhibits glioblastoma proliferation by G0/G1 cell cycle arrest. Medicina. 2020;56(12):681. 10.3390/medicina56120681

12. Oh K-B, Kang H, Matsuoka H. Detection of antifungal activity in Belamcanda chinensis by a single-cell bioassay method and isolation of its active compound, tectorigenin. Biosci Biotechnol Biochem. 2001;65(4):939–42. 10.1271/bbb.65.939

13. Lim H-S, Kim YJ, Kim B-Y, Park G, Jeong S-J. The anti--neuroinflammatory activity of tectorigenin pretreatment via downregulated NF-κB and ERK/JNK pathways in BV-2 microglial and microglia inactivation in mice with lipopolysaccharide. Front Pharmacol. 2018;9:462. 10.3389/fphar.2018.00462

14. Xiang J, Yang G, Ma C, Wei L, Wu H, Zhang W, et al. Tectorigenin alleviates intrahepatic cholestasis by inhibiting hepatic inflammation and bile accumulation via activation of PPARγ. Br J Pharmacol. 2021;178(12):2443–60. 10.1111/bph.15429

15. Feng W. Tectorigenin attenuates cognitive impairments in mice with chronic cerebral ischemia by inhibiting the TLR4/NF-κB signaling pathway. Biosci Biotechnol Biochem. 2021;85(7):1665–74. 10.1093/bbb/zbab086

16. Noh D, Choi JG, Huh E, Oh MS. Tectorigenin, a flavonoid-based compound of leopard lily rhizome, attenuates UV-B-induced apoptosis and collagen degradation by inhibiting oxidative stress in human keratinocytes. Nutrients. 2018;10(12):1998. 10.3390/nu10121998

17. Andreska T, Aufmkolk S, Sauer M, Blum R. High abundance of BDNF within glutamatergic presynapses of cultured hippocampal neurons. Front Cell Neurosci. 2014;8:107. 10.3389/fncel.2014.00107

18. Armstrong AW, Read C. Pathophysiology, clinical presentation, and treatment of psoriasis: A review. JAMA. 2020;323(19):1945–60. 10.1001/jama.2020.4006

19. Kamiya K, Kishimoto M, Sugai J, Komine M, Ohtsuki M. Risk factors for the development of psoriasis. Int J Mol Sci. 2019;20(18):4347. 10.3390/ijms20184347

20. Greb JE, Goldminz AM, Elder JT, Lebwohl MG, Gladman DD, Wu JJ, et al. Psoriasis. Nat Rev Dis Primers. 2016;2:16082. 10.1038/nrdp.2016.82

21. Ni X, Lai Y. Keratinocyte: A trigger or an executor of psoriasis? J Leukoc Biol. 2020;108(2):485-91. 10.1002/JLB.5MR0120-439R

22. Ozawa M, Aiba S. Immunopathogenesis of psoriasis. Curr Drug Targets Inflamm Allergy. 2004;3(2):137–44. 10.2174/1568010043343868

23. Rabeony H, Petit-Paris I, Garnier J, Barrault C, Pedretti N, Guilloteau K, et al. Inhibition of keratinocyte differentiation by the synergistic effect of IL-17A, IL-22, IL-1α, TNFα and oncostatin M. PLoS One. 2014;9(7):e101937. 10.1371/journal.pone.0101937

24. Albanesi C, Madonna S, Gisondi P, Girolomoni G. The interplay between keratinocytes and immune cells in the pathogenesis of psoriasis. Front Immunol. 2018;9:1549. 10.3389/fimmu.2018.01549

25. Kim J, Krueger JG. The immunopathogenesis of psoriasis. Dermatol Clin. 2015;33(1):13–23. 10.1016/j.det.2014.09.002

26. Lee K-T, Sohn I-C, Kim D-H, Choi J-W, Kwon S-H, Park H-J. Hypoglycemic and hypolipidemic effects of tectorigenin and kaikasaponin III in the streptozotocin-induced diabetic rat and their antioxidant activityin vitro. Arch Pharm Res. 2000;23(5):461–6. 10.1007/BF02976573

27. Weng Y, Yu L, Cui J, Zhu Y-R, Guo C, Wei G, et al. Antihyperglycemic, hypolipidemic and antioxidant activities of total saponins extracted from Aralia taibaiensis in experimental type 2 diabetic rats. J Ethnopharmacol. 2014;152(3):553–60. 10.1016/j.jep.2014.02.001

28. Kaur J, Debnath J. Autophagy at the crossroads of catabolism and anabolism. Nat Rev Mol Cell Biol. 2015;16(8):461–72. 10.1038/nrm4024

29. Kim HR, Kang SY, Kim HO, Park CW, Chung BY. Role of aryl hydrocarbon receptor activation and autophagy in-psoriasis-related inflammation. Int J Mol Sci. 2020;21(6):2195. 10.3390/ijms21062195

30. Ciążyńska M, Olejniczak-Staruch I, Sobolewska-Sztychny D, Narbutt J, Skibińska M, Lesiak A. The role of NLRP1, NLRP3, and AIM2 inflammasomes in psoriasis. Int J Mol Sci. 2021;22(11):5898. 10.3390/ijms22115898

31. Sharon C, Jiquan S. Association of NLRP1 and NLRP3 gene polymorphism with psoriasis. Our Dermatol Online. 2020;11:275–83.

32. Franchi L, Eigenbrod T, Núñez G. Cutting edge: TNF-α mediates sensitization to ATP and silica via the NLRP3 inflammasome in the absence of microbial stimulation. J Immunol. 2009;183(2):792–6. 10.4049/jimmunol.0900173

33. Zheng S-C, Zhu X-X, Xue Y, Zhang L-H, Zou H-J, Qiu J-H, et al. Role of the NLRP3 inflammasome in the transient release of IL-1β induced by monosodium urate crystals in human-fibroblast-like synoviocytes. J Inflamm. 2015;12(1):1–9. 10.1186/s12950-015-0070-7