Objective To establish an interpretable deep learning model based on a bidirectional gated recurrent unit (BiGRU) and a temporal attention mechanism to elucidate the dynamic spatiotemporal response mechanisms of the multi-component–multi-target interactions underlying the effects of Buyang Huanwu Decoction (BYHWD) against ischemic stroke (IS). Methods A rat model of middle cerebral artery occlusion (MCAO) was established. Plasma and brain tissue samples were collected at multiple time points after administration. Plasma concentrations of 14 active components of BYHWD were quantified by UPLC–MS/MS, and the expression levels of 15 key targets in brain tissue were determined by ELISA to construct a multi-component–multi-target time series dataset. A BiGRU-based temporal attention network was established using a sliding window strategy, and leave-one-batch-out cross-validation (LOBO-CV) combined with bootstrap resampling was employed to evaluate model performance and stability. The model was further interpreted to identify highly contributive time points, potential key components, and responsive target features. Results The model demonstrated good predictive performance in LOBO-CV, with an R² value greater than 0.80 and a mean squared error (MSE) below 0.20 across all test sets. Temporal attention analysis identified 10 h post-administration as a time point receiving high model attention, with an attention peak value of 0.602 6. Gradient attribution analysis identified paeonol, calycosin, and formononetin as the major driving components, while brain derived neurotrophic factor (BDNF), protein kinase G type II (PKG2), and calmodulin-dependent protein kinase II (CAMK2) were identified as the key responsive targets. Bootstrap resampling showed that the 10 h critical time window was identified with a frequency of 90%, indicating good model stability. Conclusion This study established a BiGRU and temporal attention-based approach for dynamic time series analysis of the multi-component–multi-target actions of BYHWD. The proposed method provides new temporal evidence for elucidating the mechanisms underlying the anti-IS effects of BYHWD and offers a reference for investigating the dynamic pharmacological mechanisms of traditional Chinese medicine formulas.

Buyang Huanwu Decoction  /  ischemic stroke  /  bidirectional gated recurrent unit  /  temporal attention  /  deep learning  /  paeonol  /  calycosin  /  formononetin