在實驗性發燒模式中薑黃素可透過減少下視丘麩胺酸－氫氧自由基－前列腺素E2及循環中腫瘤壞死因子-α而達到解熱作用

Curcumin May Exert Its Antipyresis Via Decreasing Glutamate, Hydroxyl Radicals and Prostaglandin E2 Generation in the Hypothalamus and Circulating Tumor Necrosis Factor-α Production during Experimental Fever Model

證據顯示全身性給予金黃色葡萄球菌腸毒素A（staphylococcal enterotoxin A, SEA）除了可增加循環中的腫瘤壞死因子-α（tumor necrosis factor-α, TNF-α）、介白質-2、干擾素及發燒外，並可在兔子下視丘誘導麩胺酸的產生。目前的研究主要是分析薑黃素是否可透過減少兔子循環中發炎性細胞激素及下視丘麩胺酸、氫氧自由基及前列素E2的產生，而達到解熱的作用。微透析探針經立體定位埋入兔子下視丘前視區，並用來分析麩胺酸、氫氧自由基及前列腺素E2。靜脈給予SEA（30 ng/kg）可增加肛溫及下視丘麩胺酸、氫氧自由基的產生，並伴隨血清中TNF-α的增加。在SEA靜脈注射前一小時腹腔給予薑黃素（5-40 mg/kg）可減少SEA在循環中誘導產生的TNF-α及腦中的麩胺酸、氫氧自由基及前列腺素E2。這些證據顯示全身性給予薑黃素可透過抑制下視丘麩胺酸-氫氧自由基-前列腺素E2途徑及循環中的TNF-α，而達到抑制SEA的發燒。

Evidence has been acculated to suggest that systemic administration of staphylococcal enterotoxin A （SEA）, in addition to elevating circulating levels of tumor necrosis factor-α （TNF-α）, interleukin-2 （IL-2）, and interferon （IFN） as well as fever, induces overproduction of glutamate in the rabbit's hypothalamus. Current study was attempted to assess whether curcumin exerts its antipyresis by reducing circulating pro-inflammatory cytokines and hypothalamic glutamate, hydroxyl radicals and prostaglandin E2 （PGE2） in rabbits. The microdialysis probes were stereotaxically and chronically implanted into the preoptic anterior hypothalamus of rabbit brain for determination of glutamate, hydroxyl radicals, and PGE2 in situ. It was found that intravenous administration of SEA （30 ng/kg） induced increased levels of both core temperature and hypothalamic levels of both glutamate and hydroxyl radicals accompanied by increased plasma levels of TNF-α. Pretreatment with curcumin （5-40 mg/kg, i.p.） one hour before an i.v. dose of SEA significantly reduced the SEA-induced overproduction of circulating TNF-α and brain glutamate, PGE2, and hydroxyl radicals. These results indicate that systemic injection of curcumin may exert its antipyresis by inhibiting the glutamate-hydroxyl radicals-PGE2 pathways in the hypothalamus and circulating TNF-α accumulation during SEA-induced fever.