Indonesian Ciplukan Extract Inhibited TGF-β1/NF-κB Pathway in Experimental Psoriasis Mouse Models

Abstract

Background:The global prevalence of psoriasis, a chronic inflammatory skin disease, has substantially increased in the last decade. The increase activity of Transforming Growth Factor ß1 (TGFß1)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway which cause inflammation, is the major pathological mechanism in psoriasis. Current psoriasis treatment using chemical agents is hampered by the side-effects when used long-term, which underlines the need for alternative, low side-effect anti-psoriatic agents. The extract of Physalis angulata L., also known as Ciplukan in Indonesia, contains Physalins, compounds known for their anti-inflammatory effects, but whose effect on psoriasis has not been studied.
 Objective: This study aimed to investigate the effect of Ciplukan extract (CE) to TGFß1/NF-κB pathway in psoriasis mouse models.
 Methods: This was experimental study with posttest-only control group design. The CE active ingredients were identified using Liquid chromatography-tandem mass spectrometry (LC-MS/MS). Twenty-five female imiquimod (IMQ) induced psoriasis-like dermatitis mice were allocated into five groups, with three groups receiving 7 days of 400, 800, and 1200 mg/kg bodyweight doses of CE, respectively, and two groups serving as control and IMQ groups. The NF-κB and TGFß1 expressions were evaluated using Allred score based on immunohistochemistry (IHC) staining. Histopathology and clinical psoriasis manifestations were assessed using Baker’s from Hematoxylin Eosin (HE) staining and Psoriasis Area Severity Index (PASI) scores. The Kruskal-Wallis followed by Mann Whitney tests were conducted for data analysis. The p-value < 0.05 was considered to be statistically different. 
 Results: Based on LC-MS/MS test, Physalin B, D, and F were active ingredients from CE in ethyl acetate solution. An improvement in psoriasis inflammation was observed in 400 and 800 mg/kg bodyweight doses of CE, but only the dosage of 800 mg/kg BW significantly decreased of Allred scores from NF-κB and TGFß1 expressions; Baker’s and PASI scores compared to IMQ group (p<0.05). The 1200 mg/kg bodyweight doses of CE associated with acute toxicity signs and mortality, meanwhile dosage of 800 mg/kg BW showed the highest efficacy with lowest toxicity effect.
 Conclusions: Ciplukan extract improved psoriasis manifestations via inhibition effect to TGFß1/NF-κB pathway and the extract might be developed as an alternative anti-psoriasis agent