Comprehensive GC-MS Profiling and Multi-Modal Pharmacological Evaluations of Haloxylon griffithii: In Vitro and In Vivo Approaches

<b>Background/Objectives:</b><i>Haloxylon griffithii</i> is a medicinal plant possessing therapeutic effects in disorders associated with the gastrointestinal (GIT) system. This research aims to study the pharmacological activity of <i>Haloxylon griffithii</i> in a multidimensional manner, involving phytochemistry screening and in vitro and in vivo experiments. <b>Methods:</b> The whole dried plant was extracted with 80% methanol and further fractionation using solvents of increasing polarity. GC-MS analysis was performed on the crude extract to discover volatile compounds. The spasmolytic/spasmogenic effect was assessed in isolated rabbit jejunum using spontaneous and K⁺-induced contractions, as well as contractions induced by increasing concentrations of calcium ions in depolarized tissue. Antidiarrheal activity was evaluated in Swiss albino rats/mice (<i>n</i> = 6/group) using castor oil-induced diarrhea and peristaltic index models. In silico ADMET screening was conducted via SwissADME and pkCSM. <b>Results</b>: The GC-MS profiling of <i>H. griffithii</i> revealed the presence of 59 phytochemicals and a rare azulene derivative and constituents, including α-santonin and hexadecanoic acid esters, with favorable pharmacokinetic profiles, as predicted using SwissADME and pkCSM computational tools. The in vitro and in vivo experiments revealed the significant calcium channel blocking activity in non-polar fractions (<i>n</i>-hexane and ethyl acetate), while the polar extracts (ethanolic, aqueous) exhibited cholinergic effects, indicating a dual mode of action. <b>Conclusions</b>: This was a first-time demonstration of both antidiarrheal and smooth muscle-relaxant activity in <i>H. griffithii</i>, supported by GC-MS profiling and pharmacological assay. The findings lend scientific credibility to the traditional use of the plant in community healthcare, while also reinforcing the need for further pharmacological and clinical studies to explore its potential in drug development.