title: Optimization of combinations of ginsenoside-Rg1, ginsenoside-Rb1, evodiamine and rutaecarpine for effective therapy of mouse migraine.
abstract: Wuzhuyu decoction (WZYD) is a classic traditional Chinese medicine (TCM) formula. It has been extensively used for treating migraine for thousands of years in TCM. Four potential active ingredients from WZYD, ginsenoside-Rg1 (Rg1), ginsenoside-Rb1 (Rb1), evodiamine (Ev) and rutaecarpine (Ru), were found to have positive correlations with pharmacodynamic indicators involving mouse migraine in our previous study. To find a better therapeutic effect on migraine, this research was carried out to optimize the combinations of Rg1, Rb1, Ev and Ru using the uniform design method. The results showed that Rb1 and Ev played key roles in improving the therapeutic effect on mouse migraine by strongly ameliorating pharmacodynamic indicators associated with migraine. They significantly increased the contents of 5-hydroxytryptamine, noradrenaline and dopamine in brain tissues, and reduced the content of nitric oxide in brain tissues and the activities of nitric oxide synthase in both brain tissues and blood serum. The optimal concentrations of Rb1 and Ev were 1057.4 mg/L and 312.5 mg/L, respectively. Rg1 and Ru contributed less to the overall desirability, suggesting that they had reverse effects on some pharmacodynamic indicators of this type of migraine. The verification test demonstrated by the immunohistochemical method that the optimal combination inhibited the expression of c-fos and c-jun in periaqueductal gray of mice, and strongly ameliorated pharmacodynamic indicators. These results suggested that the therapeutic effect of the optimal combination of the four ingredients was strong, and the optimal results were proven to be reliable and accurate.
authors.affiliation: Xuanwu Hospital, Capital Medical University, 45 Changchun St., Beijing, 100053, People's Republic of China.|Beijing Geriatric Medical Research Center, 45 Changchun St., Beijing, 100053, People's Republic of China.
authors.forename: Yanchuan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, No. 10 Xitoutiao, Youanmen, Beijing, 100069, People's Republic of China.
authors.forename: Xueqiang
authors.initials: X
authors.lastname: Pan
authors.affiliation: Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, No. 10 Xitoutiao, Youanmen, Beijing, 100069, People's Republic of China.
authors.forename: Yongsong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, No. 10 Xitoutiao, Youanmen, Beijing, 100069, People's Republic of China.
authors.forename: Xuran
authors.initials: X
authors.lastname: Lu
authors.affiliation: Xuanwu Hospital, Capital Medical University, 45 Changchun St., Beijing, 100053, People's Republic of China.|Beijing Geriatric Medical Research Center, 45 Changchun St., Beijing, 100053, People's Republic of China.
authors.forename: Shida
authors.initials: S
authors.lastname: He
authors.affiliation: Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, No. 10 Xitoutiao, Youanmen, Beijing, 100069, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: He
authors.affiliation: Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, No. 10 Xitoutiao, Youanmen, Beijing, 100069, People's Republic of China. gongmuxin@126.com.
authors.forename: Muxin
authors.initials: M
authors.lastname: Gong
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000627:therapeutic use; D036145:Ginsenosides / Q000008:administration & dosage* / Q000627:therapeutic use; D026121:Indole Alkaloids / Q000008:administration & dosage* / Q000627:therapeutic use; D008516:Medicine, Chinese Traditional; D008813:Mice, Inbred ICR; D008881:Migraine Disorders / Q000188:drug therapy* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D008517:Phytotherapy; D011799:Quinazolines / Q000008:administration & dosage* / Q000627:therapeutic use; D012701:Serotonin / Q000378:metabolism; D052999:Quinazolinones
chemical_list: D004298:Dopamine; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; D026121:Indole Alkaloids; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D009638:Norepinephrine; D011799:Quinazolines; D012701:Serotonin; C442759:ginsenoside Rb1; C028632:rutecarpine; D052999:Quinazolinones; C049639:evodiamine; C035054:ginsenoside Rg1
keywords: Evodiamine; Ginsenoside-Rb1; Ginsenoside-Rg1; Migraine; Rutaecarpine; Uniform design