n vivo Antidiarrheal and Molecular Docking Studies of a Coumarin from the Root Extract of Impatiens ethiopica Grey-Wilson (Balsaminaceae)
No Thumbnail Available
Date
2023-11
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Addis Ababa University
Abstract
Diarrhea continues to be a major health problem worldwide, particularly in developing countries
like Ethiopia. In Ethiopia, as in many other developing nations, traditional medicine plays a
significant role in healthcare, with people relying on the therapeutic properties of plants to treat
various infectious diseases. One such plant is Impatiens ethiopica, a member of the Impatiens
genus traditionally used for the treatment of diarrhea. Thus, the present study was aimed to
investigate the potential antidiarrheal effects of 80% hydroalcoholic root extract of I. ethiopica
and its major constituents using both in vivo models integrated with molecular docking studies.
Three experimental models, such as intestinal transit, intestinal secretion and castor oil-induced
mice models, were employed to determine the effects of the root extract, fractions, and the
isolated compound. The findings of the study revealed that the root extract significantly reduced
the frequency of defecation, the weight of feces, and the onset of diarrhea at 100 mg/kg, 200
mg/kg, and 400 mg/kg. Additionally, the root extract exhibited significant reduction in intestinal
fluid accumulation and gastrointestinal (GI) motility. The active root extract was then divided
into four fractions based on solubility-based fractionations, utilizing successively petroleum
ether, chloroform, methanol, and water solubility as the basis for separation. Of these fractions,
the methanol and water fractions demonstrated a dose-dependent antidiarrheal effect, with the
methanol fraction exhibiting the highest activity at a dose of 400 mg/kg. Further fractionation of
ii
the active methanol fraction by normal-phase column chromatography led to the isolation a
coumarin, coded as SY-1. The structure of SY-1 was identified as 7-hydroxy-6-
methoxycoumarin (7-hydroxy-6-methoxy-2H-chromen-2-one), commonly known as scopoletin,
on the basis of various spectroscopic techniques (ESI-MS, 1H-NMR, 13C-NMR and DEPT-135
spectral data). The antidiarrheal effects of scopoletin were also evaluated, demonstrating a
significant reduction in intestinal fluid accumulation and gastrointestinal (GI) motility at the
doses of 10 mg/kg, 20 mg/kg and 40 mg/kg. In this study, prostaglandin synthase (PGS) was
chosen as a target for molecular docking analysis. Assessing scopoletin interaction with
prostaglandin synthase (PGS) (COX-2; PDB ID: 4COX) revealed a promising docking score of
−7.941 kcal/mol. Scopoletin demonstrated a strong binding affinity, engaging in hydrogen
bonding with SER530 and pi-pi stacking interactions with TYR385 and TRP387, at specific
COX-2 binding sites. These findings highlight that the antidiarrheal-like activity of I. ethiopica
was partly attributed due to the presence of scopoletin. Overall, these results provide validation
for the traditional use of I. ethiopica roots in the treatment of diarrhea and highlight the potential
of scopoletin as antidiarrheal compound.
Description
Keywords
In vivo Antidiarrheal, Impatiens ethiopica, coumarin, castor oil, intestinal secretion, gastrointestinal motility, molecular docking, 7-hydroxy-6-methoxycoumarin, scopoletin