Acitretin is a second-generation aromatic retinoid drug. Acitretin binds to Retinoic Acid Receptor (RAR) α/β/γ and retinoid X receptor (RXR) to regulate gene transcription. Acitretin reduces inflammation by downregulating the expression of inflammatory factors such as IL-6, MRP-8, and IFN-γ and inhibiting neutrophil chemotaxis. Acitretin can be used for research on keratinization disorders including severe plaque psoriasis, pustular psoriasis, erythrodermic psoriasis, Darier disease, pityriasis rubra pilaris, and congenital ichthyosis, as well as chemoprevention of non-melanoma skin cancer after organ transplantation[1-4].
In vitro, SH-SY5Y cells were treated with 10μM Acitretin for 4 days. Acitretin promoted cell differentiation into neuron-like cells with discharge function. Acitretin upregulated the expression of β-tubulin III and NFH[5]. HaCaT cells were treated with 5μM Acitretin for 12-72 hours. Acitretin inhibited cell proliferation, downregulated STAT1, STAT3, SOCS1, and SOCS3 mRNA and protein expression[6]. SCL-1 cells were treated with 10μM Acitretin. Acitretin inhibited cell proliferation, induced cell apoptosis[7].
In vivo, a psoriasis BALB/c mouse model received 400μL 0.3mg/mL Acitretin by gavage once daily for 7 days. Acitretin improved the psoriasiform dermatitis phenotype, reduced the total Psoriasis Area and Severity Index score, reduced IL-23a, IL-6, and Ki67 expression in skin lesions, increased Involucrin expression[8]. A sepsis C57BL/6J mouse model received intraperitoneal injection of 10mg/kg Acitretin for 3 days. Acitretin reduced total cell counts and protein levels in bronchoalveolar lavage fluid, reduced the lung wet-to-dry weight ratio, attenuated alveolar wall thickening and immune cell infiltration, improved the survival rate, improved dynamic lung compliance and airway resistance[9]. C57BL6/J OlaHsd mice received intraperitoneal injection of 10mg/kg Acitretin for 7 days. Acitretin increased liver triglyceride, total cholesterol, and free cholesterol content[10].
References:[1] Sarkar R, Chugh S, Garg VK. Acitretin in dermatology. Indian J Dermatol Venereol Leprol. 2013 Nov-Dec;79(6):759-71.
[2] Tan MG, Shear NH, Walsh S,et al. Acitretin. J Cutan Med Surg. 2017 Jan/Feb;21(1):48-53.
[3] Ling MR. Acitretin: optimal dosing strategies. J Am Acad Dermatol. 1999 Sep;41(3 Pt 2):S13-7.
[4] Sauder MB, Cheung L, Beecker J. Acitretin-induced hepatitis: when to monitor cholestatic enzymes. J Cutan Med Surg. 2015 Mar-Apr;19(2):115-20.
[5] Cai A, Liu N, Lin Z, et al. In Vitro Effects of Acitretin on Human Neuronal SH-SY5Y Cells. Neurochemical Research. 2023;48(1):72-81.
[6] Qin X, Chen C, Zhang Y, et al. Acitretin modulates HaCaT cells proliferation through STAT1- and STAT3-dependent signaling. Saudi Pharm J. 2017;25(4):620-624.
[7] Lin X, He C, Xiao T, et al. Acitretin induces apoptosis through CD95 signalling pathway in human cutaneous squamous cell carcinoma cell line SCL-1. J Cell Mol Med. 2009;13(9A):2888-2898.
[8] Long K, Chen W, Mao M, et al. Role of acitretin in regulating glucose and lipid homeostasis in an imiquimod-induced psoriasis model mouse. J Cent South Univ(Med Sci). 2025;50(3):344-357.
[9] Xu H, Xu H, Li W, et al. Modulating the NLRP3 Inflammasome: Acitretin as a potential treatment for Sepsis-induced acute lung injury. Int Immunopharmacol. 2025;153:114504.
[10] Lauer A.A., Nguyen V.T.T., Janitschke D, et al. The Influence of Acitretin on Brain Lipidomics in Adolescent Mice-Implications for Pediatric and Adolescent Dermatological Therapy. Int. J. Mol. Sci. 2022, 23, 15535.