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

Ari Estuningtyas,Santi Widiasari,Kusmardi Kusmardi

doi:10.22159/ijap.2018.v10s1.02

Ari Estuningtyas, Santi Widiasari + Show 1 more

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https://doi.org/10.22159/ijap.2018.v10s1.02

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Abstract

Objective: The plant mahkota dewa (Phaleria macrocarpa) is known to have anti-inflammatory effects. This study aimed to determine whetherchitosan nanoparticles containing mahkota dewa leaf extract would yield superior anti-inflammatory effects in the colon of a mouse model of dextransodium 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), leafextract 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 administeredthrough drinking water for 6 weeks. The anti-inflammatory effect was observed histopathologically by imaging the inflammatory cells of the mice colonwith 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 at12.5 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 throughdrinking water for 6 weeks. The anti-inflammatory effect was observed histopathologically by imaging the inflammatory cells of the mice colon withHE staining.Conclusion: Chitosan nanoparticles containing mahkota dewa leaf extract can be included in the practically non-toxic class of materials. However, anethanol extract of mahkota dewa leaf effectively inhibited DSS-induced inflammation in the mouse colon, regardless of delivery vehicle.

Highlights

Ulcerative colitis (UC) is a subtype of inflammatory bowel disease (IBD) characterized by chronic inflammation of the large intestinal mucosal layer
In a study by Suprapti et al, a 25 mg dose of mahkota dewa leaf extract was shown to reduce the levels of inducible nitric oxide synthase (iNOS), β-catenin, and COX-2, a high-dose extract was fatal to some animals; the survival rate was
The ethanol extract was obtained from the Laboratory of IPB Biopharmaceutical Study Center (Bogor), and the nanoparticles were produced at PT Nanotech Indonesia (Puspiptek-Tangerang)

Summary

Introduction

Ulcerative colitis (UC) is a subtype of inflammatory bowel disease (IBD) characterized by chronic inflammation of the large intestinal mucosal layer. Drug therapy may reduce inflammation, the effect may be short-lived and the patient can experience a relapse. Several studies have investigated the use of natural and apparently safe ingredients for the prevention and treatment of UC. One such ingredient, the plant mahkota dewa (Phaleria macrocarpa) [5,6], contains flavonoid compounds such as kaempferol and quercetin, and an extract of the leaves has been shown to exert anti-inflammatory effects by suppressing the activity of nuclear factor kappa beta (NF-κB), cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) [7,8,9]. This mortality was attributed to the lethal effects of extract components on other organs [10]

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