Dual regulatory effects of Sheng-Di-Da-Huang decoction on microglial cells in rat models of intracerebral hemorrhage

Two microglia phenotypes, M1 pro-inflammatory and M2 anti-inflammatory phenotypes, exert distinct functions post-intracerebral hemorrhage (post-IH). The M1-to-M2 switch is noted within 7 days, but precise timing remains undetermined. This research sought to examine the specific timing of the M1-to-M2 transition and examine the effect of Sheng-Di-Da-Huang Decoction (SDDHD) on M2 microglia post-IH. Rats were grouped into sham, IH and dose-varied SDDHD treatment cohorts. Rats of IH group had an intrastriatum injection of collagenase IV (0.2 U), while those of sham group were only injected with saline. All rats underwent neurological score assessment and magnetic resonance imaging (MRI) scans at different time points after procedure. The expression markers (iNOS for M1; Arg1, IL-4, and IL-10 for M2) were assessed across days. M1 markers (iNOS) peaked at day 3, whereas M2 markers (Arg1, IL-4 and IL-10) rose progressively, suggesting the M1-to-M2 switch around day 3. SDDHD decreased iNOS expression and elevated Arg1, IL-4 and IL-10 expression, improving neurological outcomes. SDDHD exhibits a bidirectional regulation of microglia, promoting M2 transformation while inhibiting M1, thereby enhancing neurological recovery post-IH.