Anti‐Allergic and Cytotoxic Properties of <i>Abutilon indicum</i> Linn. Extract and Its Phytochemical Constituents: By Ex Vivo, In Vitro Models, and In Silico Analysis

Abutilon indicum Linn., a shrub belonging to the Malvaceae family, was investigated for its cytotoxicity and anti-allergic properties. This study evaluated the effects of the hydroalcoholic extract of A. indicum (HAEAI) and its phytomolecules using various experimental and computational approaches. The cytotoxicity of the HAEAI and its phytomolecules, namely, syringaldehyde (SYD), methyl coumarate (MC), and methyl-3-indole carboxylate (M3IC), was assessed at different concentrations using the MTT assay on rat basophilic leukemia (RBL-2H3) cells. Ionomycin was employed to stimulate RBL-2H3 cells and mediate allergic responses. Degranulation levels were determined using β-hexosaminidase and histamine release assays, whereas cytokine expression (IL-4, TNF-α, IL-6, and IL-13) was quantified. GC-MS analysis of the HAEAI identified a wide range of phytomolecules. Plant extract (HAEAI) and phytomolecules were further evaluated using Compound 48/80-induced mast cell degranulation in rat mesentery ex vivo. Compound 48/80 activated mast cells to mediate allergic reactions, and the percentage protection was calculated by counting intact and degranulated mast cells. In silico studies, including molecular docking, ADMET predictions, and toxicity assessments, were performed to evaluate the phytomolecules. Molecular docking revealed that M3IC exhibited a superior glide score (-6.060 kcal/mol) compared to the standard disodium cromoglycate (DSG, -5.483 kcal/mol). The phytomolecules were predicted to be nontoxic with respect to mutagenicity, irritation, and reproductive toxicity. Cytotoxicity results indicated that HAEAI and its phytomolecules (SYD, MC, and M3IC) were cyto-proliferative and nontoxic in RBL-2H3 cells. The positive control, ionomycin, showed 43.34% ± 0.21% cytotoxicity at 7.47 µg/mL, whereas the standard compound DSG was found to be cell-proliferative and nontoxic at 25.61 µg/mL. Both A. indicum L. extract (HAEAI) and its phytomolecules effectively inhibited ionomycin-induced allergic responses, as evidenced by reduced β-hexosaminidase and histamine release, decreased pro-inflammatory cytokines (IL-4, TNF-α), and increased anti-inflammatory cytokines (IL-6 and IL-13). SYD, MC, and M3IC were shown to alleviate ionomycin-induced allergic symptoms, emerging as potential drug candidates for the management of allergic conditions.