Gastroprotective Efficacy and Safety Evaluation of Scoparone Derivatives on Experimentally Induced Gastric Lesions in Rodents

Abstract

This study investigated the gastroprotective efficacy of synthesized scoparone derivatives on experimentally induced gastritis and their toxicological safety. Six scoparone derivatives were synthesized and screened for gastroprotective activities against HCl/ethanol- and indomethacin-induced gastric ulcers in rats. Among these compounds, 5,6,7-trimethoxycoumarin and 6,7,8-trimethoxycoumarin were found to have gastroprotective activity greater than the standard drug rebamipide; 6-methoxy-7,8-methylenedioxycoumarin, 6-methoxy-7,8-(1-methoxy)-methylenedioxycoumarin, 6,7-methylenedioxycoumarin, and 6,7-(1-methoxy)-methylenedioxycoumarin were found to be equipotent or less potent that of rebamipide. Pharmacological studies suggest that the presence of a methoxy group at position C-5 or C-8 of the scoparone’s phenyl ring significantly improves gastroprotective activity, whereas the presence of a dioxolane ring at C-6, C-7, or C-8 was found to have decreased activity. In order to assess toxicological safety, two of the potent gastroprotective scoparone derivatives—5,6,7-trimethoxycoumarin and 6,7,8-trimethoxycoumarin—were examined for their acute toxicity in mice as well as their effect on cytochrome P450 (CYP) enzyme activity. These two compounds showed low acute oral toxicity in adult male and female mice, and caused minimal changes to CYP3A4 and CYP2C9 enzyme activity. These results indicate that compared to other scoparone derivatives, 5,6,7-trimethoxycoumarin and 6,7,8-trimethoxycoumarin can improve gastroprotective effects, and they have low toxicity and minimal effects on drug-metabolizing enzymes.

Prodigiosins from a marine sponge-associated actinomycete attenuate HCl/ethanol-induced gastric lesion via antioxidant and anti-inflammatory mechanisms

“…Thirty-six rats were randomly assigned to six groups of six rats each, and fasted for 24 h prior to oral dosing with normal saline solution (positive control), omeprazole (OMZ) 20 mg/kg (Borg Pharmaceutical Ind., Egypt; standard treatment control) [17], or PdGs at 100, 200, or 300 mg/kg. At 1 h after treatment, the rats were orally administered using an orogastric tube 5 ml/kg of a mixed solution of 0.15 M HCl (Sigma, St. Louis, MO, USA) and 60% ethanol (Sigma), as described by Son et al [18]. Two additional control groups, the healthy control and PdGs control groups received only vehicle (normal saline solution) and 300 mg/kg PdGs, respectively, without HCl/ethanol induction.…”

Phytochemistry and pharmacological activity of the genus artemisia

“…It was investigated by some researchers about the gastroprotective activity of an isopropanol extract from the aerial segments of A. princeps (IPAP) and designed as a gastroprotective floating tablet of IPAP (IPAP-FR) and obtained gastroprotective results against the excessive gastric mucosa secretion (Kim et al 2017 ). The medicinally active constituent that is scoparone (6,7-dimethoxycoumarin), a coumarin-derived component obtained from Hericium erinaceus with A. capillaries , confirms an efficacious gastroprotective impact on gastric secretion induced by HCl/ethanol in rats (Son et al 2015 ). Aqueous extract of A. capillaris (AEAC) against the gastric mucosal lesion (Yeo et al 2018 ).…”

The Allelopathic Effects of Trewia nudiflora Leaf Extracts and Its Identified Substances

“…On the other hand, 6,7,8-trimethoxycoumarin is a naturally occurring simple coumarin identified in plants, mostly in the Apiaceae family. Coumarin is a large class of lactones produced by the shikimic acid pathway [ 52 , 53 ], and 6,7,8-trimethoxycoumarin is 3,4-unsubstituted coumarins [ 54 ]. In our study, both substances inhibited the growth of lettuce seedlings ( Figure 6 and Figure 7 ).…”

“…Dayan et al [ 68 ] speculate that the structural variations of the substances may be the reason for the disparities in effectiveness between them. The scoparone phenyl ring in 6,7,8-trimethoxycoumarin with the methoxy group at the C-5 or C-8 position was reported to enhance some bioactivity, which might be responsible for the greater inhibitory effectiveness of 6,7,8-trimethoxycoumarin [ 53 ]. In this research, the T. nudiflora extracts and the two substances significantly inhibited the growth of the test plants.…”