Gastrointestinal Motility, Muscle Relaxation, Antipyretic and Acute Toxicity Screening of Amyrin Type Triterpenoid (Daturaolone) Isolated From Datura metel Linnaeus (Angel’s Trumpet) Fruits

Abstract

Datura metel Linn is used traditionally for the treatment of various diseases including relaxation of smooth muscles, relief of fever, as well as gastrointestinal disorder. This study deals with the bio-guided isolation of an active, amyrin-type triterpenoid, namely 3-oxo-6b-hydroxy-b-amyrin (daturaolone; 1), from the chloroform fraction of Datura metel L. (Angel's trumpet) fruits and its gastrointestinal motility, antipyretic, and muscle relaxation effects in animal models. The chemical structure of daturaolone (1) was elucidated by NMR spectroscopy and crystallography techniques. The chloroform fraction and daturaolone (1) were assessed for the GIT motility test. Data exhibited in charcoal meal GI transit test show that chloroform fraction and daturaolone (1) significantly reduce GIT motility and increased intestinal transit time, comparable to the standard (atropine), a muscarinic receptor blocking agent. Muscle relaxant potency of the extract and daturaolone (1) was assessed in various animal paradigms. In the inclined plane screening test, it produced a significant (P < 0.05) muscle relaxation potential in a dose-dependent manner after 30, 60, and 90 min. Likewise, the muscle relaxation potential of the extract and daturaolone (1) was strongly complemented by the chimney and traction test, representing a dominant effect after 60 min of sample administration. The chloroform fraction showed good antipyretic activity, and while daturaolone (1) exhibited significant activity at a higher dose, the maximum effect (84.64%) was at 20 mg/kg i.p. In acute toxicity screening test, the chloroform extract (100, 250, 500, and 1,000 mg/kg) and daturaolone (1) (5, 10, 20, and 50 mg/kg) were found safe. In conclusion, the chloroform extract and daturaolone (1) exhibited strong gastrointestinal motility, muscle relaxation, and antipyretic activity in different animal models and intestinally, was found safe at higher tested doses.

Potential benefits of gallic acid as skeletal muscle relaxant in animal experimental models

“…The inverted screen is a 43-centimetre-square wire mesh ( Vogel and Drug, 2002 , Deacon, 2013 , Bawazeer et al, 2020 ) made up of 12-remillimetre squares of 1 mm-diameter wire. It is surrounded by a 4 cm deep wooden bead (which pre-vents the occasional mouse which attempts to climb onto the other side).…”

Anti-Inflammatory Potential of Daturaolone from Datura innoxia Mill.: In Silico, In Vitro and In Vivo Studies

“…Scientific reports on anti-inflammatory prospects of daturaolone are scarce and earlier study on daturaolone isolated from P. integerrima has reported its in vivo anti-inflammatory and antinociceptive potential, which was further corroborated in silico showing its interactions with the COXs receptors only [5]. Bawazeer et al isolated daturaolone from D. metel, wherein, it was tested in various acute in vivo experiments and its role was found to be in relaxation of muscles, gastrointestinal motility and reduction of fever [6]. Furthermore, daturaolone has shown significant α-glucosidase and β-secretase inhibitory activity and has exhibited a potent antibacterial and antifungal spectrum [7,8].…”

“…[5]. Bawazeer et al isolated daturaolone from D. metel wherein, it was tested in various acute in vivo experiments and its role was found to be in relaxation of muscles, gastrointestinal motility and reduction of fever [6]. Furthermore daturaolone has shown significant α-glucosidase and β-secretase inhibitory activity and has exhibited a potent antibacterial and antifungal spectrum [7,8].…”

Toxicity evaluation induced by single and 28-days repeated exposure of withametelin and daturaolone in Sprague Dawley rats

“…It also shows neuroprotective properties by modulating the oxidative stress by Nrf2/Keap1/HO-1 in the CNS and the neuroinflammatory stress by TLR4/IκB-α/NF-κB/AP-1 in the CNS ( Khan et al, 2021a ). Moreover, daturaolone is an amyrin type triterpenoid affective in fever, muscle relaxation and gastrointestinal problems ( Bawazeer et al, 2020a ). It significantly inhibits inflammation and cancer markers (NF-κB and NO, as shown in silico and in vitro models.…”