Mechanistic Evaluation of Abutilon indicum Extract and Syringaldehyde in Ovalbumin-Induced Airway Inflammation Using Computational and Experimental Approaches

Abutilon indicum Linn. is a traditionally used medicinal herb in the treatment of inflammatory diseases. Syringaldehyde (SYD) is a major phytoconstituent of A. indicum.To compare the mast cell stabilizing and anti-asthmatic effects of hydroalcoholic extract of A. indicum (HAEAI) and SYD, and to explore the possible molecular mechanisms. Compound 48/80 (C48/80) induced mesenteric mast cells degranulation in rats was evaluated after 7 days of SYD (25 and 50 mg/kg) and HAEAI (200 and 400 mg/kg). Anti-asthmatic activity was assessed in ovalbumin (OVA)-induced allergic asthma in mice, with SYD and HAEAI administered during the challenge phase. Inflammatory cell counts in blood and bronchoalveolar lavage fluid (BALF) were quantified. BALF Th2 cytokines (IL-4 and IL-13) and serum OVA-specific IgE were measured by ELISA, and lung histopathology was performed. Network pharmacology, molecular docking, and molecular dynamics simulation were used for mechanistic evaluation. SYD and HAEAI showed a substantial effect by inhibiting C48/80-induced degranulation of mast cells (p < 0.0001). In OVA-challenged mice, both treatments decreased inflammatory cell infiltration in BALF and blood, compared with the inducer control group, which showed elevated BALF cytokine levels of IL-4 (98.50 ± 6.56 pg/mL) and IL-13 (159.91 ± 9.56 pg/mL), treatment with HAEAI and SYD significantly reduced these inflammatory markers. HAEAI decreased IL-4 levels to 84.95 ± 3.73 pg/mL at the low dose and 67.20 ± 3.02 pg/mL at the high dose, while SYD reduced IL-4 levels to 66.91 ± 3.88 pg/mL and 55.90 ± 3.32 pg/mL at the low and high doses, respectively. Similarly, HAEAI reduced IL-13 levels to 143.50 ± 6.96 pg/mL at the low dose and 91.83 ± 9.06 pg/mL at the high dose, whereas SYD lowered IL-13 levels to 118.42 ± 4.86 pg/mL and 55.69 ± 3.74 pg/mL at the low and high doses, respectively.In addition, serum OVA-specific IgE levels were markedly reduced in the treatment groups compared with the inducer control group (557.84 ± 3.39 ng/mL). HAEAI reduced IgE levels to 378.44 ± 1.94 ng/mL at the low dose and 180.90 ± 1.30 ng/mL at the high dose. SYD also lowered serum OVA-specific IgE levels to 323.56 ± 1.93 ng/mL and 222.15 ± 1.55 ng/mL at the low and high doses, respectively. These findings indicate that both HAEAI and SYD exert significant anti-allergic effects by suppressing Th2 cytokines and reducing OVA-specific IgE production. and improved lung histopathology. In silico analysis showed a multi-target effect on allergic and inflammatory signalling. Followed by docking, a favourable ligand-protein interaction was observed during simulation. SYD and HAEAI have good mast cell stabilising and antiasthmatics effect, likely mediated through suppression of Th2-induced inflammation and multi-targeting allergic signalling pathways.