Association between Go-rei-san administration and blood pressure reduction in neurosurgical inpatients: a retrospective observational study with complementary analyses of AQP4 function

Introduction Go-rei-san (GRS) is a traditional Japanese Kampo medicine commonly prescribed for conditions characterized by fluid imbalance, including edema and headache. Although GRS has traditionally been regarded as having diuretic properties, its clinical effects are not fully accounted for by increased renal water excretion, indicating the involvement of additional mechanisms in the regulation of body fluid homeostasis. Methods A retrospective observational study was conducted in hospitalized neurosurgical patients newly prescribed GRS primarily for the management of edema at Akita University Hospital. Blood pressure, body weight, serum electrolytes (Na, K, Cl), and renal function indices were evaluated at baseline and after three weeks. Subgroup analyses were performed according to concomitant antihypertensive therapy. To investigate underlying mechanisms, in vitro studies using HEK293T cells expressing human aquaporin-4 (hAQP4) assessed osmotic cell volume responses following GRS treatment. Results Systolic blood pressure was significantly reduced at three weeks (127 vs. 118 mmHg, P = 0.001). Serum electrolyte levels remained within normal ranges. Overall renal function remained stable; however, exploratory subgroup analyses revealed increased BUN/Cre ratios under specific conditions, particularly among females receiving concomitant antihypertensive therapy. In vitro, GRS attenuated osmotic cell swelling in hAQP4-expressing HEK293T cells, suggesting an effect on AQP4-related water transport during osmotic stress. Conclusions In neurosurgical inpatients who received GRS primarily for edema, GRS administration was associated with a reduction in systolic blood pressure without clear laboratory evidence of overt diuresis. These preliminary findings represent an exploratory clinical association and support the hypothesis that fluid redistribution, rather than increased renal water excretion alone, may contribute to the observed association. Complementary in vitro findings provide biological plausibility for the involvement of AQP4-related water transport, although the contribution of renal aquaporins and conventional diuretic mechanisms cannot be excluded. This study should be regarded as hypothesis-generating, and prospective controlled studies with larger patient populations are required to validate the proposed mechanism and its clinical significance.