Park Keun-Tae, Sim Insuk, Lee Jae-Chul, Jin Young-Ho, Kim Woojin
Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 02453, Republic of Korea.
Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02453, Republic of Korea.
Metabolites. 2024 Dec 20;14(12):719. doi: 10.3390/metabo14120719.
Paclitaxel is a widely used anticancer drug for ovarian, lung, breast, and stomach cancers; however, its clinical use is often limited by the side effects of peripheral neuropathy. This study evaluated the effects of () extract and its active metabolite, α-cyperone, on paclitaxel-induced neuropathic pain.
The oral administration of extract at doses of 500 mg/kg and intraperitoneal administration of α-cyperone at doses of 480 and 800 μg/kg prevented both the development of cold and mechanical pain.
The gene and protein expressions of tyrosine hydroxylase and noradrenergic receptors (α1- and α2-adrenergic), which were upregulated by paclitaxel, were significantly downregulated in the extract-treated group. In the locus coeruleus region of the mouse brain, extract administration also reduced the elevated expression of tyrosine hydroxylase induced by paclitaxel. The concentration of α-cyperone in extract was quantified using high-performance liquid chromatography (HPLC). In the group treated with α-cyperone, at levels corresponding to its content in , both cold and mechanical allodynia were effectively prevented.
This study suggests that α-cyperone shows potential as a preventive agent for paclitaxel-induced neuropathic pain.
紫杉醇是一种广泛用于治疗卵巢癌、肺癌、乳腺癌和胃癌的抗癌药物；然而，其临床应用常常受到周围神经病变副作用的限制。本研究评估了（）提取物及其活性代谢物α-香附酮对紫杉醇诱导的神经性疼痛的影响。
口服500mg/kg剂量的提取物以及腹腔注射480和800μg/kg剂量的α-香附酮均可预防冷痛和机械性疼痛的发生。
在提取物治疗组中，由紫杉醇上调的酪氨酸羟化酶和去甲肾上腺素能受体（α1和α2肾上腺素能受体）的基因和蛋白表达均显著下调。在小鼠脑海马蓝斑区域，给予提取物也降低了由紫杉醇诱导的酪氨酸羟化酶的表达升高。使用高效液相色谱法（HPLC）对提取物中α-香附酮的浓度进行了定量。在给予α-香附酮的组中，在与其在提取物中的含量相对应的水平下，冷痛觉过敏和机械性痛觉过敏均得到有效预防。
本研究表明，α-香附酮显示出作为紫杉醇诱导的神经性疼痛预防剂的潜力。
