## 1 Introduction  
As global temperature has been gradually rising, the issue of pathophysiological responses in living organisms has been raised. Heat stress has been reported to be a critical factor causing hyperthermia, anorexia, weight loss, hypoglycemia, gastric hemorrhage, spermatogenesis dysfunction, heatstroke, and neurological disorders [1, 2]. These symptoms result from systemic metabolic disorders induced by reduced food intake and hormone secretion levels. Physiological responses to stress are regulated by the hypothalamic-pituitary-adrenal (HPA) axis and the sympatho-adrenmedullary system axis [3]. The HPA axis, which includes the autonomic nervous system, plays a crucial role in regulating metabolic dysregulation by thermal stress in response to stressful stimuli, which can self-activate through neurotransmitters [4]. Hormones, such as glucocorticoids and corticosterone, are controlled by the HPA axis and secreted in response to stress, which results in suppression of the systemic immune response and stimulation of pro-inflammatory cytokines [5].  
Geongangbuja-tang decoction (GBT), consisting of the rhizome of _Zingiber officinal_ Roscoe (Zingiberis Rhizoma; ZOR) and daughter root of _Aconitum carmichi_ Debeaux (Aconiti Lateralis Radix Preparata; ALRP), is a representative traditional decoction used to alleviate immune system dysregulation in East Asia. Several reports investigating its pharmacological effects related to stress responses have revealed that GBT activated Na+-K+-ATPase and Ca2+-Mg2+-ATPase transport at cellular levels, resulting in induction of energy metabolism [6]. In addition, activation of energy metabolism by GBT promoted cardioprotective effects by regulating the peroxisome proliferatorator-activated receptor \(\alpha\) (PPAR\(\alpha\))/peroxisome proliferatorator-activated receptor gamma coactivator-1\(\alpha\) (PGC-1\(\alpha\))/sirutin3 pathway [7]. Interestingly, previous studies on ZOR and ALRP have also explored their effects on thermally stressed conditions. ZOR is effective at regulating chicken growth and antioxidant activities under heat stress conditions [8; 9]. In addition, several reports have revealed that ZOR has suppressive effects against systemic inflammatory conditions [10; 11; 12]. For example, oral administration of ZOR promoted antiinflammatory reactions, inhibited the proinflammatory cytokines including interferon-\(\gamma\) and interleukin (IL)-6 in the serum, and blocked the inducible nitric oxide synthase and cyclooxygenase-2 in the liver of mice with lipopolysaccharide-induced hepatic injury [10]. Conversely, ALRP has been shown to suppress decreased rectal temperature and increased serum cortisol levels, expression of PPAR-\(\gamma\), PGC-1\(\alpha\), and uncoupling protein1 under cold stress conditions [13]. Moreover, [PERSON] et al. reported that oral treatment with a processed ALRP increased the activity of Na+-K+-ATPase and Ca2+-Mg2+-ATPase transport in natural killer cells isolated from cold stressed mice [14].  
Based on a previous study, GBT and its constituents are regarded as agents for boosting biological metabolic pathways and suppressing inflammation. However, whether GBT regulates heat stress-induced systemic inflammation mediated by the HPA axis has not been demonstrated. Moreover, its biologically active ingredients against the HPA axis-mediated stress responses remain unclear. In this study, we aimed to explore the thermal-regulatory effects of GBT and to demonstrate its active components. First, we investigated the effects of GBT on the thermal stress-induced behavioral impairment and inflammation in mice. To address its active component, a comparative investigation of ALRP and ZOR on c-fos levels in the heat-stressed mouse hypothalamus was conducted. In addition, we measured the levels of IL-9, IL-13, and prostaglandin E 1 (PGE1), and PGE2 in the serum to evaluate its effects on systemic inflammation induced by heat exposure.