Herbal hot compress combined with bianstone warm ironing improves anxiety and cognitive impairment via gut-brain-HPA axis in pubertal mesenteric lymphadenitis rats

Introduction Pediatric mesenteric lymphadenitis (ML) is characterized by persistent intestinal inflammation, intestinal barrier damage and excessive oxidative stress, which can disturb the gut-brain axis, overactivate the hypothalamic-pituitary-adrenal (HPA) axis, and induce anxiety and cognitive disorders in children. Herbal hot compress (HC) and bianstone warm ironing (BS) are clinically used to relieve related symptoms, yet their mechanism linking intestinal oxidative stress and gut barrier function remains insufficiently clarified. This study aimed to investigate combined HC and BS effects on intestinal oxidative stress indicators (MDA, SOD), intestinal barrier markers (DAO, D-lactic acid, LPS), gut-brain-HPA axis function, hippocampal cAMP, neurotransmitter levels, and synaptic plasticity in pubertal ML rats, and verify the cAMP/PKA signaling pathway. Methods Briefly, pubertal rats were randomly divided into six groups. ML was induced by repeated LPS injection (2 mg/kg) once every 3 days for 5 consecutive cycles. After 14 days of intervention, EPM, OFT, and NOR tests evaluated anxiety-like behaviors and cognitive function, while in vivo hippocampal LTP recordings at the Schaffer collateral-CA1 pathway assessed synaptic plasticity, including I/O curves and PPR. Serum samples were collected to detect oxidative stress, intestinal barrier parameters, inflammatory cytokines and HPA hormones; hippocampal neurotransmitters and cAMP were measured via ELISA. Results Model rats exhibited intestinal oxidative injury, barrier dysfunction, gut inflammation, HPA hyperactivity, neurotransmitter imbalance, impaired synaptic plasticity, and obvious anxiety and cognitive deficits. No intergroup differences in I/O curves and PPR were observed across six groups. BS or HC monotherapy partially ameliorated these abnormalities, and HC exerted stronger effects on improving intestinal oxidative stress and gut barrier integrity. Combined HC + BS achieved superior outcomes to single treatments in restoring intestinal redox balance, protecting intestinal barrier and alleviating gut-brain-HPA axis dysfunction. Pretreatment with a PKA antagonist largely abolished these protective effects. Discussion In conclusion, herbal hot compress combined with bianstone warm ironing alleviates anxiety and cognitive impairment in pubertal ML rats by inhibiting intestinal oxidative injury, repairing barrier damage, suppressing inflammation, normalizing HPA axis, restoring neurotransmitter homeostasis and improving hippocampal synaptic plasticity, partially mediated by the cAMP/PKA pathway.