Acute toxicity of chitosan nanoparticles containing mahkota dewa (Phaleria Macrocarpa) leaf extract and anti-inflammatory effects in a dextran sodium sulfate-induced mouse model of ulcerative colitis

Abstract

Objective: The plant mahkota dewa (Phaleria macrocarpa) is known to have anti-inflammatory effects. This study aimed to determine whether chitosan nanoparticles containing mahkota dewa leaf extract would yield superior anti-inflammatory effects in the colon of a mouse model of dextran sodium sulfate (DSS)-induced ulcerative colitis, compared with ethanol extract alone after testing the acute toxicities (lethal dose) of both preparations. Methods: For acute toxicity testing, 10 Sprague-Dawley rats were administered 6000 mg/kg body weight (BW) of leaf extract alone or with nanoparticles. Subsequently, mice were divided into the following six groups to determine the anti-inflammatory effects: Untreated, negative control (DSS 2% w/v), leaf extract at 12.5 or 25 mg/kg BW, and leaf extract in chitosan nanoparticles at 6.25 or 12.5 mg/kg BW. To induce colitis, DSS (2% w/v) was administered through drinking water for 6 weeks. The anti-inflammatory effect was observed histopathologically by imaging the inflammatory cells of the mice colon with hematoxylin-eosin (HE) staining. Results: For acute toxicity testing, 10 Sprague-Dawley rats were administered 6000 mg/kg BW of leaf extract alone or with nanoparticles. Subsequently, mice were divided into the following six groups to determine the anti-inflammatory effects: Untreated, negative control (DSS 2% w/v), leaf extract at 12.5 or 25 mg/kg BW, and leaf extract in chitosan nanoparticles at 6.25 or 12.5 mg/kg BW. To induce colitis, DSS (1% w/v) was administered through drinking water for 6 weeks. The anti-inflammatory effect was observed histopathologically by imaging the inflammatory cells of the mice colon with HE staining. Conclusion: Chitosan nanoparticles containing mahkota dewa leaf extract can be included in the practically non-toxic class of materials. However, an ethanol extract of mahkota dewa leaf effectively inhibited DSS-induced inflammation in the mouse colon, regardless of delivery vehicle.