Deoxyartemisinin, a compound separated from Artemisinin annua L., shows anti-inflammatory and antiulcer activities. 10-Deoxoartemisinin is a novel compound with a strong antimalarial effect derivatized from artemisinin. Compared to the famous antimalarial natural compound artemisinin, deoxyartemisinin lacks the peroxide bridge structure, while 10-deoxoartemisinin remains this special peroxide bridge group but loses the 10-position keto group. To clarify their pharmacological differences, the absorption, distribution, metabolism, excretion (ADME) properties of artemisinin, deoxyartemisinin, and 10-deoxoartemisinin were first predicted using QikProp software. Also, their pharmacokinetic behaviors in rats were further evaluated by a rapid, sensitive, and specific liquid chromatography–tandem mass spectrometry (LC–MS/MS) method after oral and intravenous administration of each compound, in which deoxyartemisinin and 10-deoxoartemisinin were first evaluated for their pharmacokinetics. All parameters about ADME properties calculated by software met the criteria and the ADME performance order was 10-deoxoartemisinin > deoxyartemisinin > artemisinin. The oral bioavailability of artemisinin was calculated to be 12.2 ± 0.832%, which was about 7 times higher than that of deoxyartemisinin (1.60 ± 0.317%). For 10-deoxoartemisinin, its bioavailability (26.1 ± 7.04%) was superior to artemisinin at a degree of more than twice. Considering their chemical structures, losing the peroxide bridge might decrease the absorption rate of deoxyartemisinin in the gastrointestinal tract, while retaining the peroxide bridge but losing the 10-position ketone might improve the bioavailability of 10-deoxoartemisinin.

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.