synephrine, a component of Evodiae Fructus, constricts isolated rat aorta via adrenergic and serotonergic receptors.

We investigated the effects of Evodiae Fructus and synephrine, one of the components of Evodiae Fructus, on blood vessels. We found that Evodiae Fructus (1 x 10(-6) - 3 x 10(-4) g/mL) had constrictive effects on rat aorta. The vasoconstrictive effects of Evodiae Fructus were significantly inhibited by pretreatment with prazosin (adrenergic alpha(1)-receptor antagonist), BRL15572 [5-hydroxytryptamine (5-HT)(1D) antagonist], and ketanserin (5-HT(2A) antagonist), but its vasoconstrictive effects were not inhibited by pretreatment with SB216641 (5-HT(1B) antagonist) or propranolol (adrenergic beta-receptor antagonist). These results suggest that Evodiae Fructus constricts rat aorta via adrenergic and serotonergic receptors. We also investigated the constrictive effects of synephrine on blood vessels. The vasoconstrictive effects of synephrine (1 x 10(-7) - 3 x 10(-5) mol/L) were significantly inhibited by pretreatment with prazosin, BRL15572, and ketanserin. However, its constrictive effects were not inhibited by pretreatment with SB216641 and propranolol. The pA(2) values of prazosin or ketanserin were nearly equal between Evodiae Fructus and synephrine. Because the constrictive effects of both Evodiae Fructus and synephrine were exerted via adrenergic alpha(1)-receptors and serotonergic (5-HT(1D) and 5-HT(2A)) receptors, synephrine may be one of the important components in the constrictive effects of Evodiae Fructus.

Effects of the traditional Japanese medicine Tokaku-jyoki-to in rat-models for menopausal hot flash.

AIM OF STUDY: Luteinizing hormone-releasing hormone (LH-RH) has been suggested as an inducer of centrally mediated elevation of skin temperature, and calcitonin gene-related peptide (CGRP) is one of the potent vasodilator neuropeptides that has been suggested as an inducer of peripherally mediated elevation of skin temperature. We investigate the effect of the Japanese herbal medicine Tokaku-jyoki-to using two rat-models for menopausal hot flash. MATERIALS AND METHODS: Tokaku-jyoki-to used in present study was prepared as a spray-dried powder from hot-water extract. Skin temperature was measured by thermister thermometer. Estrogen receptor (ER) binding assay of Tokaku-jyoki-to extract was performed using human recombinant ERalpha or ERbeta. RESULTS: Oral Tokaku-jyoki-to (1000 mg/kg) restored skin temperature rise induced by LH-RH or CGRP in ovariectomized (OVX) rats as well as subcutaneous 17beta-estradiol (0.010 mg/kg) did. Tokaku-jyoki-to did not affect the lower concentration of plasma estradiol and the decreased uterine weight due to ovariectomy, although the hormone replacement of 17beta-estradiol restored them. In estrogen receptor ligand-binding study, Tokaku-jyoki-to extract bound to human ERalpha poorly and did not bound to human ERbeta. CONCLUSIONS: These results suggest that Tokaku-jyoki-to, which appears to contain organ-specific selective estrogen receptor modulator, may be useful for the treatment of hot flashes in patients for whom estrogen replacement therapy is contraindicated as well as menopausal women.

Aqueous extract of Asiasari radix inhibits formalin-induced hyperalgesia via NMDA receptors.

ETHNOPHARMACOLOGICAL RELEVANCE: Asiasari radix is prepared from Asiasarum sieboldii F. Maekawa or Asiasarum heterotropoides F. Maekawa var. mandshuricum F. Maekawa, widely used for treatment of various tussive, inflammatory, allergic diseases and pain. AIM OF STUDY: The antinociceptive effects of Asiasari radix extract (ARE) in mice were examined. MATERIALS AND METHODS: Tail-flick, tail-pressure, hot-plate and formalin tests were used to evaluate its antinociceptive activity. Moreover, N-methyl-D-aspartic acid (NMDA)-induced nociceptive response was also examined. RESULTS: Oral administration of ARE did not affect the responses of the tail-flick, tail-pressure, or hot-plate test or the first phase of the formalin tests, but it dose-dependently decreased the duration of nociceptive behavior in the second phase, as did diclofenac, a non-steroidal anti-inflammatory drug. ARE also inhibited nociceptive behaviors induced by the intrathecal injection of NMDA, although diclofenac did not affect these behaviors. Pretreatment with bicuculline, a GABA(A) antagonist, reduced the antinociceptive effects of ARE on the formalin- or NMDA-induced behaviors. Muscimol, a GABA(A) agonist, exhibited antinociceptive effects in the formalin test and NMDA-induced behaviors in a manner similar to that of ARE. On the other hand, diclofenac significantly inhibited cyclooxygenase (COX)-1 and -2 activities, while ARE did not. CONCLUSION: These results suggest that ARE may inhibit development of hyperalgesia via NMDA receptors based on activation of GABA(A) receptors in the spinal cord.

Goshuyuto, a traditional Japanese medicine, and aqueous extracts of Evodiae Fructus constrict isolated rat aorta via adrenergic and/or serotonergic receptors.

Effects of goshuyuto, a traditional Japanese medicine, on vascular constriction were examined using isolated strips of rat aorta. Goshuyuto (1 x 10(-5) to 1 x 10(-3) g/ml) caused constriction of aorta strips in a dose-dependent manner. The vasoconstrictive effects of goshuyuto were significantly inhibited by pretreatment with prazosin, an adrenergic alpha(1) receptor antagonist. The constrictive effects were partially inhibited by pretreatment with BRL15572, a 5-HT(1D) antagonist, and ketanserin, a 5-HT(2A) antagonist. However, the constrictive effects were not inhibited by pretreatment with SB216641, a 5-HT(1B) antagonist, or propranolol, an adrenergic beta receptor antagonist. In addition, aqueous extracts of Evodiae Fructus, one of the constituent medicinal herbs of goshuyuto, caused constriction of aorta strips strongly, but aqueous extracts of Zizyphi Fructus, Ginseng Radix, and Zingiberis Rhizoma, the other constituents of goshuyuto, did not have much effect on the vascular response of rat aorta strips. Also, synephrine, which is one of the ingredients of Evodiae Fructus, constricted the rat aorta. These results suggest that goshuyuto constricts rat aorta strips and that the mechanisms involve the adrenergic and/or serotonergic receptors. Also, it may be suggested that Evodiae Fructus and synephrine play the important role in the vasoconstrictive effects of goshuyuto on rat aorta strips.

Goshuyuto, a traditional Japanese medicine for migraine, inhibits platelet aggregation in guinea-pig whole blood.

The effects of goshuyuto and chotosan, traditional Japanese medicines, on collagen-induced platelet aggregation were examined using guinea-pig blood. Goshuyuto at the concentration of 1,000 mug/mL inhibited collagen-induced platelet hyper-aggregation to the same degree as aspirin at the concentration of 100 mumol/L, but chotosan did not. Goshuyuto is composed of four medicinal herbs. Of them, aqueous extracts of Evodiae Fructus and Zingiberis Rhizoma inhibited platelet aggregation, but aqueous extracts of Zizyphi Fructus and Ginseng Radix did not. Two components of Zingiberis Rhizoma, 6-shogaol and 6-gingerol, also inhibited platelet aggregation. These results suggest that Evodiae Fructus and Zingiberis Rhizoma may play important roles in the anti-aggregation effects of goshuyuto and that 6-shogaol and 6-gingerol are among the active ingredients. Therefore, goshuyuto may ameliorate migraine by preventing the hyper-aggregation of platelets in migraine with aura.