Cyperus rotundus Extract and Its Active Metabolite α-Cyperone Alleviates Paclitaxel-Induced Neuropathic Pain via the Modulation of the Norepinephrine Pathway

Background: 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 Cyperus rotundus (C. rotundus) extract and its active metabolite, α-cyperone, on paclitaxel-induced neuropathic pain. Methods: The oral administration of C. rotundus 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. Results: 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 C. rotundus extract-treated group. In the locus coeruleus region of the mouse brain, C. rotundus extract administration also reduced the elevated expression of tyrosine hydroxylase induced by paclitaxel. The concentration of α-cyperone in C. rotundus extract was quantified using high-performance liquid chromatography (HPLC). In the group treated with α-cyperone, at levels corresponding to its content in C. rotundus, both cold and mechanical allodynia were effectively prevented. Conclusions: This study suggests that α-cyperone shows potential as a preventive agent for paclitaxel-induced neuropathic pain.