Anti-Migraine Effect of the Herbal Combination of Chuanxiong Rhizoma and Cyperi Rhizoma and UPLC-MS/MS Method for the Simultaneous Quantification of the Active Constituents in Rat Serum and Cerebral Cortex

Abstract

Chuanxiong Rhizoma and Cyperi Rhizoma (CRCR), an ancient and classic formula comprised of Chuanxiong Rhizoma and Cyperi Rhizoma in a weight ratio of 1:2, has long been used for curing migraine. This study aimed to explore their anti-migraine effect and active constituents. A nitroglycerin (NTG)-induced migraine model in rats was established to evaluate pharmacological effects. Cerebral blood flow was detected by a laser Doppler perfusion monitor. The levels of endothelin-1 (ET-1), γ-aminobutyric acid (GABA), nitric oxide synthase (NOS), nitric oxide (NO), 5-hydroxytryptamine (5-HT), 5-hydoxyindoleacetic acid (5-HIAA), calcitonin gene-related peptide (CGRP) and β-endorphin (β-EP) were quantified with enzyme-linked immunosorbent assay. CGRP and c-Fos mRNA expression were quantified with quantitative real-time polymerase chain reaction. A UPLC-MS/MS method was developed and validated for the simultaneous quantification of active constituents in rat serum and cerebral cortex. CRCR significantly increased cerebral blood flow, decreased the levels of ET-1, GABA and NOS, and increased the levels of 5-HT, 5-HIAA and β-EP in NTG-induced migraine rats. CGRP levels and CGRP mRNA expression, as well as c-Fos mRNA expression in the brainstem were markedly down-regulated with the treatment of CRCR. After oral administration of CRCR, ferulic acid (FA), senkyunolide A (SA), 3-n-butylphthalide (NBP), Z-ligustilide (LIG), Z-3-butylidenephthalide (BDPH), cyperotundone (CYT), nookatone (NKT) and α-cyperone (CYP) were qualified in rat serum and cerebral cortex. The above results suggested that CRCR showed powerfully therapeutic effects on migraine via increasing the cerebral blood flow, decreasing the expression of CGRP and c-Fos mRNA, and regulating the releasing of ET-1, GABA, NOS, 5-HT, 5-HIAA, CGRP and β-EP in the serum and brainstem, consequently relieving neurogenic inflammation. The active constituents in CRCR for treating migraine were FA, SA, NBP, LIG, BDPH, CYT, NKT and CYP. These findings contributed for the further use of CRCR as a combinational and complementary phytomedicine for migraine treatment.

Effects of Chuanxiong Rhizoma-Cyperi Rhizoma Combination on Migraine in a Murine Model

“…We proved that Chuanxiong Rhizoma-Cyperi Rhizoma combination alleviates the migraine by regulating of increase of vasomotor factors such as CGRP, NOS, NO, ET. These effects are similar to those previously reported by Wu et al [5].…”

“…The use of Chuanxiong Rhizoma-Cyperi Rhizoma combination is first stated in Danxi Xinfa (a comprehensive medical book written by Zhu Zhenheng in 1481) for the alleviation of headache with a syndrome of phlegm syncope and migraine headache [4]. Pharmacological studies have shown that the combination of Chuanxiong Rhizoma and Cyperi Rhizoma can reduce the number of writhing times in dysmenorrhea rat model to varying degrees, can prolong the writhing latency and can reduce the whole blood viscosity of rats [5]. Besides, it can also treat migraines caused by vegetative nerve functional and vasomotor disorders [6].…”

Antiarrhythmic Mechanisms of Chinese Herbal Medicine Dingji Fumai Decoction

“…In our future report, we aim to show the multi-ion channel mechanism of DFD. In addition, with the development of mass spectrometry, multiple constituents of the components of DFD have been analyzed and characterized in recent years [29][30][31][32][33][34]. Modern pharmacological studies have shown that the components of DFD have anti-inflammatory [35][36][37][38][39], antioxidative stress [40][41][42], and myocardial protection [42][43][44][45] effects.…”

Effect of Traditional Chinese Medicine on Long-Term Outcomes of Snakebite in Taiwan

“…In addition, Xiang Fu Chuan Xiong Cha, an ancient formula, composed of Cyperi Rhizoma and Chuanxiong Rhizoma at a 2:1 weight ratio, was used for curing migraines and headaches. A recent animal study demonstrated that Cyperi Rhizoma and Chuanxiong Rhizoma (CRCR) significantly increased cerebral blood flow and decreased several substances involved in neurogenic inflammation, thereby relieving migraines [43]. Fructus Viticis (Man jing zi) is another traditional Chinese medicine that is commonly used for curing migraines and headaches.…”