Abstract

Materials and Methods Forty-eight male Wistar rats were divided into anti-inflammatory mechanism study (n = 18) and acute toxicity study (n = 30). The anti-inflammatory mechanism study employed six groups (n = 3), e.g., the normal control, negative control, positive control (quercetin 20 mg/kg BW), and three doses of BREE (250 mg/kg BW; 500 mg/kg BW; 1000 mg/kg BW). All groups (except the normal control) were inflammatory-induced i.p. using 0.1 mL of 1% of acetic acid. The expression of Akt and NF-kappaB p65 in the stomach and intestine of the rats was examined using Western blot analysis. The acute toxicity study (21 days) was conducted by following the Regulation of Indonesia National Agency of Drug and Food Control No. 7/2014 about In Vivo Nonclinical Toxicity Study using 5 doses of BREE (250 mg/kg BW; 500 mg/kg BW; 1000 mg/kg BW; 2000 mg/kg BW; 4000 mg/kg BW). Results BREE reduces the infiltration of inflammatory cells in both the stomach and the intestine of acetic acid-induced rats. BREE also alters the expression of Akt and NF-kappaB p65 in the rat's stomach and intestine (p=0.005). The acute toxicity study reveals no lethal effects and behavioral signs of toxicity at all tested doses, which indicates that the LD50 is greater than 4000 mg/kg BW. Conclusion Taken together, BREE could inhibit the expression of Akt and NF-kappaB p65 in the stomach and intestine of acetic acid-induced Wistar rats. This plant could be further explored for its potential as plant-based antistomach ulceration.

Highlights

  • Cornelius Celsus’ four cardinal signs of inflammation, rubor et tumor cum calore et dolore, have attracted increasing attention [1, 2]

  • We investigated the mechanism of B. rotunda rhizome in modulating Akt and NF-kappaB p65 in the stomach and intestine of acetic acid-induced Wistar rats

  • A family survey in Indonesia, which was carried out during 2014-2015, reported that a high prevalence of indigenous medicine was used in children and several social factors and poor health status of its use were identified [41]

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Summary

Introduction

Cornelius Celsus’ four cardinal signs of inflammation, rubor et tumor cum calore et dolore, have attracted increasing attention [1, 2]. Inflammation responses play an important role in multiple diseases with a high prevalence among the population, such as hepatitis [3], lung disease [4], and Alzheimer’s disease [5] They are centrally related to the pathogenesis of a large number of acute and chronic diseases, i.e., colonic inflammatory response [6] and periodontitis [7]. NF-kappaB is a family of transcription factors that regulates diverse cellular activities related to inflammation and innate and adaptive immune responses [8]. Akt activation mediates downstream responses, including cell survival, growth, proliferation, cell migration, and angiogenesis by phosphorylation of various intracellular proteins [13]. We investigated the mechanism of B. rotunda rhizome in modulating Akt and NF-kappaB p65 in the stomach and intestine of acetic acid-induced Wistar rats. It was reported that mucosal surface damage had occurred at 30 minutes postinjection of a single dose of acetic acid solution into the gastric mucosal layer of rats [27]

Materials and Methods
Histopathology Analysis
Findings
Discussion
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