Abstract
Wuzhuyu decoction (WZYD) has been clinically used to treat migraine effectively since Eastern Han Dynasty of ancient China. However, its antimigrainic ingredients remain unclear. In present study, the antimigrainic ingredients of WZYD were explored and optimized in nitroglycerin-induced migraine rats through correlation analysis of decoction spectra-pharmacological effects and absorption spectra-pharmacological using entropy-weighted partial least squares regression method. The decoction spectra and absorption spectra were obtained through the determination of nine main ingredients in ten kinds of WZYDs and WZYDs' single-pass intestinal perfusion samples using high performance liquid chromatography-diode array detector. The pharmacodynamics indexes related to migraine model rats were detected using high performance liquid chromatography method and kits after oral administration of WZYDs. Then, the key ingredients influencing indexes were achieved through the correlation analysis. And the optimization of key ingredients was acquired through uniform design experiment. The pharmacodynamic verification test was used to clarify the advantages of the optimized sample. The results showed that the final optimized sample, in which the concentrations of rutaecarpine, evodiamine, ginsendside Rb1, 6-gingerol, ginsendside Rg1, rutaevine, and limonin were 0.081, 0.565, 1.455, 0.159, 0.871, 0.178, and 0.009 mg·mL−1, respectively, provided the best comprehensive effect than another optimized sample and the best uniform design sample. Therefore, a new reliable method for rapidly recognizing and optimizing the effective constituents of WZYD treating migraine was established.
Highlights
Migraine is a multifactorial primary headache with a prevalence up to 5% worldwide [1]
After the administration of Wuzhuyu decoction (WZYD), the 5-HT and 5-HIAA contents were significantly increased, and the NE and nitric oxide (NO)-b content was reduced while the NO-p content was still increased
After the administration of uniform design samples (UDSs), the 5-HT and 5-HIAA contents were significantly increased, and the NE content was reduced while the NOp content was still increased, and the NO-b content was increased or decreased
Summary
Migraine is a multifactorial primary headache with a prevalence up to 5% worldwide [1] It was ranked as the seventhhighest cause of disability and third most prevalent disorder [2]. Multiple factors, such as monoamine neurotransmitters and nitric oxide (NO), are involved in migraine [3]. These closely migraine-related indices significantly influence vasoconstriction and vasodilatation [4]. Some patients are inadmissible to use for several side effects Gastroduodenal injuries, such as diarrhea, emesis, and even intestinal perforations, are widely recognized after using nonsteroidal antiinflammatory drugs [6]. Dizziness and coronary vasoconstriction are reported after using triptans [7]
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